Roche Aktie

[Audio Gap] for today's call, Kindly note that opens being recorded. [Operator Instructions] After the presentation, there will be a question-and-answer session. [Operator Instructions]. One last remark. If you would like to follow the presented slides on your end as well, please feel free to go to roche.com/investors to download the presentation. At this time, it's my pleasure to introduce you to Thomas Schinecker, CEO Roche. Mr. Schinecker, the stage is yours.

Thank you very much, and good morning, and good afternoon, and I'm excited to share our Q3 2026 results with you today with a strong performance yet again, and we made also significant portfolio progress. We had, as mentioned, strong performance year-to-date. Group sales are up 6%, driven by Pharma was 7%. In Q3, in fact, we had a growth of 7% for the group in -- and since we now have actually stabilized currency situation in Swiss francs, the growth was actually plus 8%. And if you then look at U.S. dollars, we're also at plus 7%. So clearly, the exchange rates have stabilized. .

As we called out in the presentation, in Q3, we had a onetime effect in Q3, which is about CHF 180 million or 1 percentage point growth. This is due to a next-generation ERP introduction at [Chugai] in Japan, and this impacted the timings of the shipping. Now let me just say that we had a 2% outperformance versus the consensus, overall or about CHF 360 million and the roughly CHF 180 million means that 1% of the outperformance comes from that. The other percent comes from strong performance in the portfolio.

And let me share that this effect will also then reverse in Q4 2026. Diagnostics growth was 4%, and excluding China, and you're aware of the health care pricing reforms there. Diagnostics grew at plus 6%. And as communicated at half year, we expect full year LOE impact of about CHF 600 million. On the pharma side, we had a very busy quarter in terms of regulatory approvals. We had 4 approvals, U.S. approval for Tecentriq in stage II colon cancer Enspryng [head] and [Kasia] in INS. -- and in the EU, Suspimo received approval for AMD. We filed [fenebrutinib] in RMS and PPMS in U.S., which is under priority review there and spring in both the U.S. and the EU in[indiscernible] . And the Megaport in UME also in the U.S. and the EU. We also reported several positive Phase III readouts. One is the [salamistemo] trial with [LONzUMIO] in second-line follicular lymphoma. As facersen and interim readout showed significantly reduced urea in people with IgAN and the data will be presented tomorrow at ASN.

And we also look forward to sharing this data with health authorities. In Diagnostics, it's worth highlighting a couple of things. One, the rapid response to 2 recent outbreaks. One is Ebola in Congo and the other 1 is cyclospor outbreak in the U.S., where we quickly deployed PCR tests. In urology, we now also received U.S. FDA approval for pTau-217, which is the only market that can be used in the primary setting for Alzheimer's. On the BD front, it was a exceptionally busy quarter. We made a series of deals, and I'll come back later to that. But I just wanted to highlight to both in the obesity space. One is with [Hanmi], first -- potentially first-in-class uricortin-2 analog, which is in Phase I and also with RONA to target T7 with an RNAi and both are promising emerging MOAs in the obesity space and have the potential to improve the overall body composition.

Looking ahead, we have a couple of key milestones still ahead until year-end. One is a trial of Tobii post-CDK HR-positive metastatic breast cancer. And not mentioned on the slide, but of course, we're very much looking forward to our approvals for geodestrant this year in the adjuvant and metastatic setting, the PDUFA dates are November 30 and December 18. And in Diagnostics, we also have a launch coming.

Now let me take you through the next slide. Again, just to reiterate, the growth rate of 6%, driven by Pharma 7%, Diagnostics grew 4% and as mentioned, this is still impacted by the health care pricing reforms. But as you can see, the impact is getting smaller and smaller over time. And so we'll be back to normal than in the near future. Now looking at currencies, we've seen a reversal of the headwinds actually in Q3, and you've also seen that when you look through the slides in Q4. And in fact, in Q3, we had a positive plus 1% currency effect. But what you see here in terms of currency facts still really the impact mostly from Q1.

Now let's move to the next slide. And this shows you yet another quarter of consistent strong growth. And as mentioned before. In Japan, we had a onetime impact in Q3 due to the ERP system implementation. And excluding this, the growth rate for the quarter would be a strong 6%. And as mentioned, this effect will reverse in Q4. Now let's look at the key growth drivers. All segments are growing. And let me start with oncology/hematology. We have strong FESCO conversion from [Perjeta], which continues. The HER2 franchise is going to peak this year with a wrong tail. Tecentriq growth is driven by new indications.

For Alecensa, we have raised the full year outlook to low single-digit growth from flat before. Polivy continued strong uptake in first-line DLBCL and and Colomvi and [Ozumi] continue to grow in later lines in both DLBCL and follicular lymphoma. Hemlibra keeps growing across geographies. And since we don't expect any competitive pressures anymore this year, we are upgrading the outlook to high single-digit growth for the full year versus what we said at the half year, where we still said mid-single-digit growth.

Let me go to a [indiscernible] growing strongly, and there's a strong uptake of the subcut formulation. Teresa will provide more details to that. Again, Avis also had a very strong quarter and is expanding its market leadership position in SMA. Solar continues its strong performance in food allergy. And as expected, we have now in the third quarter, seen the first biosimilar launch Gabe, we're very encouraged by the initial uptake in lupus nephritis in the U.S., and we also look forward to the approval in SLE later this year.

The Bisma in ophthalmology continues to grow well, and we also continue to gain market shares. And I know Teresa will also go into that. In Diagnostics, we had pathology with a strong growth and Core Lab growing despite the China health care pricing reforms and Matt actually will go into that as well.

Now let's look at the highlights of the portfolio. And I like this slide. It's showing that we can launch up to 20 new medicines until the end of this decade, which is up 1 versus what we have said at half year. And the fact that you see a lot of green boxes means that we've seen a lot of positive news over the last quarter. And let me just say that we've added 2 molecules to the slides and had 1 drop off. The 2 that we added is [Temple] in lung cancer, which had very positive Phase III results in second-line small cell lung cancer in Chinese patients, and the data was presented at World Lung.

And then the [indiscernible] in DME. As I mentioned, this now brings us to 20 NMEs with a potential launch by 2030, and we've had great progress across most of those. And let me highlight a couple of those. First, the positive Phase III interim readout for spacers, which I mentioned before, positive Phase II readouts for enesepatide, petrolintide and [indiscernible] -- and based on all this data, we have initiated several Phase III studies. And as mentioned before, fenebrutinib, in MS and the meibordan UME have now been filed.

For Fene look out for the data that we are presenting at MS Toronto this week, Teresa will also cover that. Finally, we've increased the peak sales potential for [diverse] to CHF 3 billion on the back of strong Cresendo 1 data, and we will also present this data this weekend at ESMO. So also please take a look at that.

Now let's have a broader look at our pipeline. Again, a slide that I really enjoy looking at because it shows how the effect is a late-stage pipeline as we implement the bar. In dark blue, you see all of the projects that we have initiated after introduction of the bar on the Y axis, you see the PTS and you see how many projects we have now above 50%. And usually, in the past, above 50% meant a very high success rate for us. And on the -- to the right, on the x-axis, you see the value.

So you see an upward shift in the right-hand shift. And this is exactly that what we actually want to see. Now you may ask yourself what is the little blue dots on the left bottom corner. This is our novel antibiotic and I'm sure you understand why, on the 1 hand, it's important to bring this project forward and the impact it would have in case of a bacterial pandemic, but you also know that how the business model works today with antibiotics, it's hard to reflect that differently than with the dot in the bottom left corner.

On the right-hand side, you see the Phase III readouts this year, which has been a very strong year for us. of Phase III studies were positive. So it means an 88 percentage point success rate. Last year already, we were in line with industry average in terms of Phase III success rate. This year, we're actually ahead -- now 88% is an amazing number. I don't think that this is a long-term rate, but really keeping it at around 80% would be an ideal goal for us. Now moving to the next slide. And this is another way on how we look at our portfolio.

We are very rigorous at applying the bar, which means that as we move assets through the development, we constantly assess these molecules. Currently our fully stand at 60 [indiscernible] , and what I can say is we've almost doubled the portfolio value since '23. So not only do we have more meaningful projects, but I think also we have greater value in terms of potential market impact. And we do expect the number of NMEs to increase because we have a lot of things going on in research, as I will show you in a couple of seconds, but we will also continue our partnering activity.

Talking about partnering. Q3 was a busy year. We closed in total, 6 platform deals -- was a busy quarter, sorry, Q3, we closed into 6 platform deals spanning different drug modalities, for example, ADCs bispecific degraders and elasteric small molecules. And this also in different therapeutic areas. And these collaborations will also fuel our early pipeline in the next years.

Another source of innovation, clearly, to fuel our early pipeline is also the adoption of AI and my team has also shown you at Pharma Day of how we apply AI in drug discovery. And you see that on the right-hand side. And I do believe that this also shows you that we are a front runner when it comes to applying AI in drug discovery. And you can see on the left-hand side from LIGO to LOGO to DevCos -- this is the different phases of our early-stage research and development, a significant increase of molecules over this period of time, and we believe this will continue.

And as a reminder, also, we have a very comprehensive AI strategy that we have rolled out a couple of years ago. And this AI strategy rests on a couple of pillars. One is we call everydayAI constantly training all of our employees on using AI tools to become more productive. And we also monitor the usage of these AI tools in our organization. And we see that 75% of our people are very active AI users. So we feel that it helps us to get more productive. On the reshape side, this is taking the 3 main processes of our organization, service, marketing and sales and R&D. And really reshaping these processes using AI to get faster and more effective and more productive. And what we do is we map that out and we create certain use cases which we then invest in, in order to get to an acceleration.

And we constantly prioritize new use cases so that we are very effective in providing AI tools to accelerate the work that we're doing across these processes. Then the third level is around big ideas. These are the things that can really change the way we do drug discovery or diagnostics, lab in the loop, as you can see on the right-hand side is 1 of those, but also in the diagnostic side using AI in our products. And we have platform initiatives. One of them is deploying the AI factory. One of them is built in Europe.

The other 1 is built in the U.S. So you see that we're making extremely good progress when it comes to AI throughout our organization. Now let me talk about Diagnostics. And we have previously talked about the key platform launches over the last couple of years. mass back and sequencing. Today, I'll dive deeper on the sequencing solution, which delivers unprecedented speed and very high accuracy. It's launched -- it was launched end of June. And as you can see on the right-hand side, has been getting very positive feedback from customers. Now we have a very strong launch momentum here.

At [indiscernible] Day, Matt talked about a target to sell 100 instruments in the first year. Now in the first 90 days or in the first quarter, we've actually achieved 1/3 of that target. So I think the team is doing well here. And the feedback I've visited customers myself has been extraordinary positive.

Now let's wrap up with the outlook. And here, I want to reiterate our guidance that we've also provided both in Diagnostics on the Diagnostics day and on the Pharma Day. You see the diagnostics will continue to contribute well to our growth, not only until the end of the decade, but clearly beyond that. But based on all the positive data readouts we've had -- we also have very good line of sight for growth to the end of the decade and beyond. And we feel that alone with what we have in hand we can continue our very positive trajectory that you've seen over the last couple of years, but also that we can go into the next decade with the same kind of momentum. And this is without additional positive readouts.

Now you've seen yourself on the late-stage slide with the 20 NMEs with the potential launch till 2030. It's very unlikely that this will not turn into a lot of positive readouts. The amount, it's very hard for us to predict at this stage, but there are many potential shots on goals. So we do believe that this will add to significant growth on top of what I just said. And on top of that, we'll continue to do more BD. So I do believe that the growth outlook this year, not only but also next year and the years beyond that is quite positive for Roche. And that there is actually no cliff situation that Roche will run into.

Now with that, let me reiterate the guidance, mid-single-digit sales growth and core EPS growth of high single digits. And we will increase dividends further. Thank you very much. And with that, I hand over to Alan.

Yes. Thanks, Thomas. Great quarter. So hello from my side before I start, thanks to everybody who has really contributed here to this great sales development that we have seen and certainly to the benefit for patients. Sales update, so I will be brief. .

Here's the sales bridge with the growth of 6% in constant currencies. You see year-to-date September left-hand side, 2025 year-to-date September 2026. On the right-hand side. When I lead you through the bridge, I think you see Pharma. And then in addition, the loss of exclusivity impact of minus CHF 355 million in total, a growth of 7% and in constant rates. Let me say the CHF 355 million we think is a good number to support the CHF 600 million negative impact that we have prognosed for the full year 2026, we will have a stronger impact from Actemra in Q4. When you look at Diagnostics, very steady when it comes to growth, excluding China, 6% -- I think also at half year, we had a growth of 6% now the year-to-date with plus 6%.

What you see shrinking is the impact from China. We're now at a minus 13% sales reduction in China compared to last year's same period at half year, we minus 15%. So when you do the math, you will see in Q3, we were at mere minus 9%. So you see really that there is a clear reduction of that negative impact moving forward. When you then look at the currency impact, I think Thomas has alluded to it already. I think we are now at minus 5 percentage points when it comes to sales at half year, we had minus 8 percentage points with the stabilization of currencies in Q3, I think there was also a positive impact on the year-to-date impact.

Good. And let's look a little bit more into this. You see here the growth rates on the left-hand side in concentrate, 6.2%, that's the 6% that I mentioned before. On the right-hand side, you see the growth rate in Swiss francs, 1.4%. This is the 1% that we have mentioned before. And in between, you see the currency movements and I think it is very clear, the major driver here is the U.S. dollar as before. But as I said, I think the impact gets smaller moving forward.

Having said this, here is really our overall projection for the full year. When you take a quick look on the left-hand side, you see that the 2026 average currency rates remain below 2025 for both the U.S. dollar and the euro. So still a negative impact. You see overall exchange rate movements had a negative impact on minus 5 percentage points on the group sales growth in the first 9 months. as mentioned already. And you know our calculation on the right-hand side with the estimate for the impact for the full year 2026.

If we remain and assume that all the currency rates end of September remain constant until the end of the year 2026. We expect an impact on sales of minus 3 percentage points, core operating profit of minus 5 percentage points and core EPS of minus 5 percentage points. That is a slight improvement compared to half year. We had a minus 4%, minus 6%, minus 6% at half year. But what you see is really when you really look at the top line, you have the sales impact. You see in Q3, we had a positive impact in Swiss francs, and we even expect a higher impact in Q4.

So there's a little bit of light at the end of the tunnel, but certainly, currency rates in these days are very volatile. Good. And with that, I think, just to confirm the guidance again, it's my pleasure to hand over to Teresa.

Great. Thank you, Alan. So let's go ahead and get started. So for sales grew by 7% at constant exchange rates, reaching CHF 36.2 billion by the end of September. All of our regions continue to deliver growth. Of note, as Thomas mentioned, Q3 sales in Japan were positively impacted by a timing effect related to the implementation of a new ERP system in the context of a business process transformation.

The size of this impact is roughly about CHF 180 million at constant exchange rates. And excluding this impact, year-to-date pharma sales increased at 6% at CER. As Thomas mentioned, we do expect this impact to fully reverse in Q4. Overall, Pharma volumes were up by 11%. As always, all absolute values and year-over-year growth rates on this graph are presented at constant exchange rates. Until the end of September this year, our top brand, [Solar Hemlibra, OCREVUS Vegas and Polivy] generated roughly CHF 2.1 billion in new sales. I'm going to share the growth dynamics for each of these brands on following slides. So why don't we just go ahead and jump in with oncology.

Oncology sales increased by 1% at constant exchange rates to CHF 11.2 billion, driven by FESGO. So let's start our deep dive with breast cancer and FESGO. The global conversion rate for FESGO has climbed 59%. This is an increase of 5 percentage points over what we shared at half year. It also brings us very close to achieving the previously stated milestone of at least 60% conversion rate at peak.

Moving on to [Kadcyla]. As we expected, we see increasing competitive pressure in the U.S. and the EU, and that is negatively impacting the growth of Kadcyla. But this is probably a good time to reiterate our [HER2] franchise outlook. We continue to expect the [HER2] franchise to peak this year at around CHF 9 billion at constant exchange rates 2024, followed by a steady decline through the end of the decade with a solid tail around CHF 4 billion. Half of that is Fego, around CHF 1 billion for Kadcyla and the rest were Perjeta and Herceptin. Due to the increased competitive pressure, we now project Kadcyla to land a bit lower by a few hundred million.

And to reiterate, we do not foresee a biosimilar in the U.S. for Perretta before 2028 and in the EU before 2027. And nor do we foresee any sort of cliff situation around the [HER2] franchise. The ITOBI launch continues with good momentum, and we expect to see Phase III and [AVO-121] results later this year. And last but certainly not least in breast cancer, duradestrant. We are eagerly awaiting the U.S. approvals for Ladera in November and Avera in December. For Avera, we're also excited about the recent Negan publication highlighting the significantly approved PFS in ER-positive breast cancer.

And for Ladera, we expect the single-arm substudy in combination with bema to read out in Q4. And and subsequently to be presented in an upcoming medical meeting. As a reminder, at Pharma Day, we announced an expansion of our clinical development program in adjuvant ER-positive breast cancer with 2 new studies a Phase III IIS in collaboration with AFT and Natera for MRD guided CKI usage and a Phase I/II in collaboration with Pfizer combining giradustrint with the CDK4tercyclib.

Now let's shift gears into lung cancer, starting -- the new indications continue to drive global growth, led by -- in Forte and small cell. We just added 1 more indication with the U.S. approval of atomic in MMR colon cancer, and this makes Tecentriq, approved adjuvant immunotherapy regimen in this setting, positioning it to become the new standard of care. I also want to confirm our full year outlook of low single-digit growth A quick update for Alecensa based on the continued strong performance, we're increasing the full year outlook from flat to low single-digit growth. And to close in lung in just a few days from now, DVERASIb's positive Crexendo 1 results in second-line non-small cell will be presented in the Presidential Symposium at ESMO. So please do tune in for that.

And with that, let's move on to Hematology. We achieved growth across the entire hematology franchise, resulting in a strong 17% increase at constant exchange rates and CHF 7.1 billion in sales year-to-date. Hemlibra remains the key growth driver. And as you will recall at half year, we increased our full year outlook for HEMLIBRA to mid-single digit. Based on continued strong performance and updates on the competitive environment, I'm happy to share that we once again increased our full year outlook, and we're now projecting that Hemlibra will go at high single digits for the full year.

As a brief reminder at Pharma Day, we presented the upcoming Hemlibra auto-injector. This device has the potential to further expand administration options and enhance patient convenience, and we expect the auto-injector to launch by the end of 2027.

Next up is malignant heme. Polivy has set a new standard of care in first-line deal BCL with continued strong uptake and market share expansion. But you know we're not stopping there. The ongoing Phase III Skyla study for Polivy plus Columbia plus chip and first-line DLBCL will read out in 2027 and has the potential to once again redefine the standard of care Importantly, we are not adding our bispecific on to -- just on to R-CHOP as some of our competitors have done, but we are adding Colombia on to Columbia plus Arch tip the current standard of care in first-line DLBCL -- as highlighted at Pharma Day, that Phase I data was impressive showing promising results for the combination with an ORR of 100% with 0% grade to CRS events.

So in true Roche Spirit, we have raised the bar, and we are once again seeking to raise the bar on ourselves for patients. Let's also highlight the positive Phase III readout of Celestino for Lynsumio and second line plus follicular. Those data reinforce Lesumio's potential. Improve clinical outcomes while offering a tolerable safety profile, simple dosing schedule and outpatient administration. We will submit the data to health authorities and present it at an upcoming medical conference. And to close, let's take a quick look at Gazyva.

So as I've mentioned in previous quarters, increasing competitive pressure in CLL and follicular is negatively impacting Gazyva's performance in the hematological indications. This is happening at the same time as the ongoing launch in immunology, and I will share some updates on that in an upcoming slide. But in short, what we see is that the initial uptake in lupus nephritis is overcompensating for the competitive pressure across the hematological indications. So let me repeat that we will show that sales split by therapeutic area in the future as those data sets mature. So now let's move on to Neurology. The neurology franchise achieved CHF 7.6 billion in sales and a 10% growth at constant exchange rates, September year-to-date.

OCREVUS is driving the overall growth of our neurology franchise. And in turn, OCREVUS global growth is driven by the subcutaneous formulation known as de novo in the U.S. We now have roughly 56,000 patients globally on subcut, and that's about 12,000 more than we had just at half year. And I'll get more on to the subcutaneous update dynamics on the next slide. But before we get there, let me confirm the overall Crius outlook. For 2026, we continue to expect high single-digit growth and our peak sales expectations for the OCREVUS franchise remain at CHF 6 billion by 2029 in constant exchange rates at 2025. This includes CHF 2 billion in incremental sales from OCREVUS subcut, but of course, there's going to be some switching from IV to subcut on top.

And 1 more good piece of news for OCREVUS, we're excited to have received EU approval for OCREVUS in the pediatric setting for patients 10 years on or based on the positive Phase III OpArETA-I/2 studies. And there is more exciting news for our MS franchise. We have successfully achieved U.S. filing for fenebrutinib in both RMS and PPMS. -- the filing used a priority review voucher, or PRV to ensure an expedited review process and enable earlier access for patients. Furthermore, the MS Toronto Medical Conference is currently underway, and we are presenting new data from the fenebrutinib RMS and PPMS studies there, some of which I will highlight on the coming slides.

But first, let me share 2 additional neurology updates. We achieved U.S. and EU filing for spring and Mogad -- the FDA granted priority review and the PDUFA was set for the tenth of January. And as a reminder, we see the Mogad opportunity of summary north of $500 million. We initiated the Phase III prevention trial for trantinumab and preclinical AD. And as you know, the PreVentroN study is enrolling cognitively unimpaired individuals at a high risk of progression to symptomatic Alzheimer's and highlights our ambition to maximize the potential impact of Trane NAD, just like ongoing on Tier 1 and 2 studies in early AD, we see great excitement amongst the medical community and patients for trontinumab, which is leading to strong recruitment in the prevention trial.

So now as promised, let's take a bit of a deeper dive into the MS franchise. And let's start with OCREVUS de novo. So I already mentioned the strong global patient uptake. And you can see very clearly in the graph on the left here. This is based on volume sales across our 50 launch countries and the adoption rate is driven both by conversion from OCREVUS IV to subcut but also and especially by patients naive to OCREVUS, which is, frankly, exactly what we had intended to do.

And for the first time, I also want to share the global OCREVUS IV to subcut conversion. But especially, we can see on the graph on the right, you can see that we've now reached greater than 20% conversion to the subcu formulation. And we expect to continue this to climb. And in fact, today, OCREVUS subcut is the fastest-growing anti-CD20 in the market. And that is really fundamentally the story that these 2 graphs together tell. Subcut has allowed us to expand our MS footprint to new market segments, particularly in the community setting, IV constraints mean that OCREVUS is simply the better fitting option for patients, doctors and health system needs.

And all of this together allows us to continue to grow the OCREVUS market overall. And let's not forget that, again, we are not stopping here. We are further innovating for patients with the development of our on-body injector or -- the OB delivery device has the potential to enable a convenient twice-yearly at-home self-administration. We showcased the device at Pharma Day, and we're expecting our data readouts next year.

So now let's take a closer look at some of the data being presented for fenebrutinib fenebrutinib, as you know, is the first and only BTKI with positive Phase III results in both RMS and PPMS, showing a clear positive effect for both relapsing and progressive biologies. And the additional RNS data currently being presented in MS Tranche are further reinforcing this profile, including acting on markers of progressive disease in the RMS population. Now I don't want to go into too much detail here, but let me quickly cover the highlights of the data on the slide.

On the left, the [indiscernible] 3, which is no evidence of disease activity, results show a 70% reduction of risk for ferabrutinib compared to teriflunomide and in regards to ARR CDP and MRI activity. In the middle, we've compared the total brain volume loss between fetablutinib and tariflutamide patients. Not only is there a clear benefit for fenebrutinib compared to taraflitomide, the patients on fenebrutinib reached a level in line with a brain volume loss rate of healthy adults.

On the right side, you see the continuum improvement -- or the continued improvement for 2 key biomarkers progressive biology for the fenebrutinib arm Chip on for Michael and Serpina I for astrocytes, both show continued improvement for fenebrutinib versus teriflunomide through week 96. And of note, the positive effect of the [Chien] biomarker underscores fenebrutinib ability to cross the blood brain barrier and act on [microglia].

There's 1 more piece of data that I want to highlight in a late-breaking abstract with the oral presentation to follow in the coming days at MS Toronto. Fenebrutinib is showing its therapeutic effect on paramagnetic rim lesion and slowly expanding lesions known as chronic active lesions. In short fenebrutinib demonstrated the first prospective therapeutic effect on chronic active lesions in MS for both RMS and PPMS. And RMS fenebrutinib reduced the volume slowly expanding lesions by up to 30% and reduced accumulation of paramagnetic lesions by 62%, both versus teriflunomide at 96 weeks.

These are exciting and meaningful results that underscore fenebrutinib effect on chronic neuroinflammation in the brain, a primary driver of disability progression in MS. So in summary, we are convinced that fenebrutinib has strong efficacy across relapsing and progressive biologies. And to further underline this, let's take a look at the next slide.

Also at MS Toronto, we presented pooled ARR data from the FENHANCE-1 in 2 trials in RMS. And this slide really speaks for itself, so I can be brief. fenebrutinib achieved an impressive 55.4% relative ARR reduction compared to teriflunomide. makes fenebrutinib the first and only oral to demonstrate an ARR improvement greater than 50% versus an active comparator in RMS. And that puts fenebrutinib firmly in the category of a high efficacy treatment, as you can see here from the review article taken from neurology.

So yes, we are excited about fenebrutinib potential in MS, and we are looking forward to bringing this truly transformative medicine to patients. So now let's move on to Immunology. Our Immunology franchise reached CHF 5 billion, growing 4% at constant exchange rates, with [Solar] being our key growth driver. We now have more than 145 patients treated with XOLAIR for food allergy since launch. That is an increase of 15,000 patients since half year.

As you saw in Q3 and as expected, we saw the first U.S. biosimilar in launch for Xolair. Let me briefly comment on the Q3 performance and the outlook for Xolair. Q3 was impacted by some buying pattern, and we continue to expect around 20% growth at full year. Actemra sales declined by 10% year-to-date, driven by biosimilar impact, as was mentioned earlier. And then moving on to Gazyva, we see continued strong launch uptake in patient share gains in lupus nephritis across early launch countries.

By now, we've treated about 5,000 patients with GAZYVA for lipos nephritis globally. And as mentioned on the hematology side, the uptake in lupus nephritis is more than compensating for the erosion in hematology. One more good piece of news this quarter for GAZYVA, we received U.S. approval for INS. And looking forward, we are anticipating U.S. approvals and both SLE and for Q4.

As Thomas mentioned, when additional highlighted this quarter was certainly the positive Phase III interim data for surfaxercen in a is the antisense umeclide evaluated in this disease and the results show that it has best-in-class potential for selective complement suppression with a clinically meaningful reduction in 24-hour proteinuria. The positive UPCR data will be presented tomorrow at the ASN conference, and we're also planning to share that data globally with health authorities. And of course, the study is still ongoing to determine long-term functional EGFR outcomes. And so with that, let's go on to ophthalmology.

Ophthalmology sales reached CHF 3.3 billion year-to-date, growing 9% at constant exchange rates. Vabysmo is the key driver here, and we continue to see global growth in market share gains. By now, Vabysmo has established itself as the preferred first-line treatment, including in the U.S. We have also reached another milestone with an impressive 1.5 million patients treated globally. One more update for Vabysmo earlier this quarter, at retina, we shared real updated real-world data from the VOYAGER study, which now includes more than 5,000 patients. These results reinforce forbismo's robust effectiveness and durability across previously untreated and treated eyes in AMD DME and RVO. And we are happy to see the strong clinical results for Vabysmo once again replicated in real-world clinical practice.

So let me also reiterate that we expect low double-digit growth for Vabysmo in 2026. And as previously stated, we consider consensus peak sales expectations for Vabysmo around CHF 6 billion is very reasonable, and we're confident that we are on track to achieve this number. Beyond Vabysmo, we had quite a bit of additional news flow in ophthalmology this quarter and spring just achieved its U.S. approval in 10 just last week. Susvimo achieved EU approval in AMD, and we filed the Mickey Bart and UME in both the U.S. and the EU with a PDUFA set for the 23rd of July. And we moved our bispecific VEGF IL-6 due to fab into Phase III in DME. And of note, this includes a head-to-head trial against the Vabysmo, which is frankly something that we are increasingly hearing from ophthalmologists. They want to see trials that use the current standard of care as the comparator, not historical standards of care.

So next up, I will cover our CVRM pipeline. So as you heard at Pharma Day, we continue to develop our CVRM assets at pace. There are quite a few positive readouts in recently announced Phase III trials to cover. So let's start with enasepatide and petrolintide, the foundational building blocks of our CVRM pipeline. I'm going to stay a bit more high level here as we have a more detailed slide on both molecules right after this. So let's just cover the Q3 highlights here. Both enasepatide and petrolentide delivered positive Phase II data in obesity with type 2 diabetes. And for petrolentide, we also presented the FULZURPRI-1 data EASD and initiated the Phase III program consisting of Supreme 3, 4 and 5.

More on the next slide, but first, let's look at the rest of the pipeline, starting with CT 996, our oral GP1. So first of all, we have a new name to unroll a typically broad -- at Pharma Day, we announced positive Phase II data for TFI and obesity. And based on these positive results, we are moving the asset to Phase III with trials to be initiated in the first half of 2027. As Thomas mentioned, we also added 2 new molecules to the CVRM pipeline with partnerships, both in obesity, first UCM 2 analog and Phase 1 via our partnership with Hanmi Pharmaceuticals.

Of note, UC M2 has the potential to simultaneously promote weight loss and preserve lean body mass. And second, an ALK 7 targeting RNI via our RONA Therapeutics partnership -- this asset is preclinical, and we think it's a very exciting new approach in the obesity field directly targeting adipose tissue biology, unlike the incretin-based therapies which target the CNS. I'm looking forward to sharing more on these molecules in the future. But now let's take a closer look at enosepatide and petrolentide.

So you all know that we at Roche have the ambition to become a top 3 player in obesity. And the 2 foundational NMEs that we believe will get us there are edosepatide and petrolintide, both as monotherapies and in combination. So let me highlight not only why we believe in the potential of these assets, but also the significant progress we've made in the last few months. So let's start with needed and asepatide is intentionally designed with a bias GLP-1 GIP agonism, which we believe is key to the strong Phase II results we've seen so far. And obese overweight patients without type 2 diabetes and asepatide did show robust weight loss of up to 22.7% at 48 weeks with no sign of plateau. And importantly, more than 1/4 of treated patients achieved a weight loss of 30% or more at 48 weeks.

Recently, we shared that in obese and overweight patients with type 2 diabetes, a weight loss of 15.5% at 48 weeks was achieved. And again, there were no signals of weight loss plateau after that 48-week mark. And even more even more impressive, however, was the HbA1c reduction in this population. At 48 weeks, enosepatide achieved reductions of up to 2.65%, highlighting its potential for best-in-disease glycemic control.

On the back of these strong Phase II results, we have started a comprehensive Phase III program, 2 trials in obesity and already ongoing. -- and 4 trials in type diabetes glycemia control are being -- are to be initiated in the first half of next year. And this includes a head-to-head trial against tizepatide, underscoring our conviction in anosepatide's best-in-disease potential. And additionally, we're expecting to initiate a CVOT and HFREF trial in the first half of next year.

So now let's turn our attention to Petri. Together with our partner Zealand, we believe that this long-acting Amlin has the potential to redefine the weight management experience, in particular, by delivering double-digit weight loss and improved tolerability compared to current treatment options. Positive Phase II results from SUPREME 1 and 2 studies were announced this year and gave us the confidence to move to Phase III. To pick just 1 highlight. The recent Supreme 2 results show that discontinuations due to GI AEs are very similar between Petri and the placebo arm.

1.9% Patients on petrolintide discontinued treatment due to GI AEs and 1.7% did so on placebo. And this while achieving statistically significant and clinically meaningful weight loss and HbA1c reduction. And we are moving at pace with Petri as well. We initiated all 3 Phase III studies in obesity this quarter, with each of them already having achieved FPI. And 1 of the great things about having both edosepatide and petrolintide in our portfolio is that we can combine them. And so we are doing just that in our upcoming ZYNERGY Phase II trial.

Combining these 2 molecules with their respective strong clinical profiles has the potential to address unmet needs for patients beyond the scope of monotherapy. In particular, for patients needing greater weight loss and/or better glycemic control. And that Phase II trial is expected to initiate later this year. So taken all together, you can see why we are excited to have 2 strong and combinable building blocks in our CVRM pipeline and how they support our ambition to become a top 3 player in obesity.

And with that, let's move to my final 3 slides, a few slides. Here we have the 2026 key pharma news flow, a lot of green check marks, as Tom has noticed earlier, which we love to see. And all of the updates I have already covered on previous slides. So to close things out, let's take a quick look at 2027. This is our expected news flow for next year, which we presented to you for the first time at Pharma day a few weeks ago. When you look at the table, 1 thing is immediately obvious, and that is that 2027 is a year with many key regulatory milestones for us. So our regulatory and launch teams will be exceptionally busy in the months to come to ensure our launch success for our key NMEs and line extensions.

However, let's not forget about the upcoming clinical readouts, which include Phase III data for 2 high-profile NMEs, NX-707 in hemophilia A and a timebar in ulcerative colitis. I'm very much looking forward to next year and to updating you on all the progress that we will achieve across pharma for patients. And with that, let me hand it over to Matt.

Thanks, Teresa. Congrats on the strong quarter. So with that, let's get started on diagnostics. So as you heard from Thomas and Allen, with sales of CHF 10.3 billion, the Diagnostics division grew by plus 4% at constant exchange or plus CHF 388 million compared to September 2025. Now as you also heard earlier, this growth was achieved despite the ongoing impact of health care pricing reforms in China. Excluding the effect of China, the growth of the business was plus 6%, as Alan mentioned. Sales were additionally impacted by CHF 70 million loss of sales due to the weaker respiratory season in the Northern Hemisphere. Despite that, very steady progress in development from the Diagnostics division.

And looking forward to next year, we expect to return to our constant ambition of mid- to high single-digit sales growth. So now let me walk you through the results by our customer areas. Sales in the core lab increased at plus 5%, impacted by the previously mentioned policy impacts in China. Now excluding this effect, Sales in the Core Lab grew at plus 9%. Sales in the molecular lab grew plus 3% with strong growth in transplant at plus 17%. However, this was partially offset by the previously mentioned mild respiratory season that lower testing volumes.

The same affected our near patient care business, which decreased at minus 5%. This was driven by a minus 21% decline in our [COBOsLead] sales but was partially offset by growth in our blood glucose monitoring business at plus 1% following competitive wins. Sales in our pathology lab grew strongly at plus 10% and driven by advanced staining growth of plus 7% and companion diagnostics growth of plus 21%.

So now let's take a geographic view of our performance. In North America, the business grew at plus 9%. In EMEA, the business grew at plus 3%. LatAm grew strongly at plus 12%. Now in APAC, the business declined at minus 4%. As previously mentioned, sales growth was impacted by the health care pricing reform in China. As a result of this, China sales declined at minus 13%. Excluding this effect, APAC grew at plus 6%.

Now you heard a little bit about our groundbreaking AXELIOS sequencing launch. And now I'd like to transition to our portfolio update starting with the AXELIOS sequencing solution, where as you heard, we've experienced strong launch momentum, achieving approximately 1/3 of our instrument placements that we're targeting for the full year within the first quarter of launch. And I would emphasize in order to continue this momentum, it's critical to demonstrate the capability of AXELIOS across the most commonly used applications while at the same time, building out the ecosystem of multi-omic tools and partners to support their use. So I'm going to walk you through the slide from left to right. Starting on the left, I'd like to highlight data from UCSF. This was presented this week in Montreal at the American Site of Human Genetics Conference. This data illustrates the capability of AXELIOS for single cell RNA sequencing in core labs and some of its key advantages. UCSF demonstrated a high correlation between AXELIOS an existing sequencing by synthesis workflows across a broad spectrum of cell populations, as you can see on the chart. But what I would call out is that AXELIOS delivered approximately the same number of reads.

However, these reads were approximately 3x longer consisting of 300 base pairs as opposed to 90 base pairs with the comparator. This enabled deeper isoform resolution. Now finally, UCSF demonstrated the suitability of AXELIOS for its core lab operations across different applications, including 10x single-cell and bulk RNA sequencing. Now if you move to the center of the slide, the second set of data, which was presented by GeneDx again at ASHG, highlights the complementary capabilities of our SPX Duplex high accuracy and SPX Simplex single read longer read modes for whole genome sequencing in rare disease.

Today, GeneDx uses frontline short-read sequencing combined with additional confirmatory testing for certain variants. AXELIOS has the potential to consolidate these workflows onto just a single platform by combining our high-accuracy shorter reads using our duplex mode together with the longer recapability of our Simplex mode. And our SPX duplex mode showed concordance with existing frontline testing for all assessed variants. Furthermore, the longer reads generated by SPX Simplex showed the potential for direct read to have expanded repeats that would normally require additional confirmatory methods.

Now finally, on the far right, I'd like to highlight our collaboration with Twist Biosciences to develop a target enrichment kit for AXELIOS. This collaboration will deliver workflows for different sample types, including cell-free DNA and FFPE tissue samples. Together with our previously announced collaboration such as 10x Genomics and Olink, this will further expand our SPX ecosystem and enable a broader range of applications and workflows. Overall, these examples further demonstrate the capability of AXELIOS across all relevant sequencing applications, together with expanding our ecosystem of partnerships.

So now I'd like to move to our molecular diagnostics infectious disease portfolio and start with the CE Mark for our CobusHDVassay which was announced on July 14. Hepatitis D affects nearly 12 million people globally and severely affects people who already co-infected with HBV virus. Despite being the most severe form of viral hepatitis, testing still relies largely on manual methods or lab developed tests, and there is currently no fully automated molecular IVD solution available for hepatitis D. With Cobos HDV, we're introducing the first high-throughput automated molecular IVD assay for detection and quantification of hepatitis D virus.

Now this will support the identification of infected patients as well as monitor their response to treatment. This is becoming increasingly important as novel therapies for hepatitis D become available. So with this launch, we further strengthened our leading infectious disease portfolio specifically in the highly competitive and valuable hepatitis segment and expand our molecular testing offering in an area of growing clinical relevance. So now I'd like to continue with molecular diagnostics and pick up on something that Thomas mentioned earlier.

I'd like to highlight our rapid outbreak response capability to address public health challenges on a global basis. So within our Tim Mobil organization, we maintain a library of over 15,000 tests predesigns across a wide range of pathogens and more than 3,000 positive control materials. So combined with our strong expertise in oligonucleotide design, we can rapidly develop primary and probe combinations for new pathogens. Now these tests can be rapidly deployed on our light cycler and x800 systems to provide prompt response to emerging public health needs.

Given our global installed base, this is something we can scale very rapidly. A recent example is the Ebola Bundembugo outbreak in the Democratic Republic of Congo, where we developed a PCR test within just 6 days of the virus genome being published. And I would call out that commonly used PCR tests that were available at the time of the outbreak, we're not able to detect the Bundaberg viral clade leading to delays in diagnosis. Our test is able to accurately detect this fire clade and we're actively working to support the response to the outbreak in the DRC.

A second example is the recent U.S. outbreak of cyclosporisis. In August, we announced 2 new PCR RUO tests, 1 specifically targeting cyclospora and another detecting the parasite is part of a multiplex gastrointestinal parasite panel. This provided a key resource to support outbreak surveillance. These examples highlight our leadership in molecular diagnostics and underscore our commitment to support global public health response to emerging infectious diseases.

So to conclude, I'd like to report progress on our key launch list for the Diagnostics division. For the 11 launches here, we've achieved 7 by Q3, and we're making good progress towards the other. I would just call out some of the tremendous launches we've had this year, such as our PTL 217, our Alexis neurofilament live chain and our Alexis TB IGRA assay, all of which have tremendous potential for the growth of our division in the future as well as the ones highlighted by Thomas.

So with that, thank you very much for your attention, and I'll hand it over to Bruno for the Q&A.

Thank you, Matt. And with that, we will start our Q&A session. First questions come from James Gordon from Barclays. .

James Gordon from Barclays. One question on hemo oncology, which was Genmab and AbbVie we announced strong headline data from the DLBCL 2 first-line DLBCL study, and there is a strong benefit at Kenya look like clean side effect profile. So the question was, does that raise the bar for what you hope to see for Colombia plus Bolivia and Sky glo? And the Sky glow delivers on your expectations, how do you think first-line patients will be treated in CL? Is it going to be sort of segmentation by the severity of some disease or something like that, balancing side effects and efficacy?

One question -- second question was on neurology and the slide on AAR benefits in RMS was interesting. -- and I saw the strong benefits that Fanny's got. But then also, how do you think about AI, AR versus CDP benefits, so disability versus relapse rates? Because different agents have different profiles there, it seems. And more broadly in MS, 9 billion peak size for OCREVUS, but what does that assume for the BTKs? And do you still think you can do that even if the BTKs are very good there.

Great. So let's start with Kilian where we think second line DLBCL would do. And I would say, I think we found that data very encouraging for a variety of different reasons. So first of all, let's remember that we've already seen very strong Phase II data for our own combination in this setting. And we do believe that, that Phase II data will translate into Phase III. And although Achille is chemo free, let's just remember, it does actually carry quite a bit of toxicity, including higher rates and severity of hematological toxicity in CRS compared to what we've seen in both Sumo and Star glow. And in addition, it carries a much more cumbersome in regimen. .

So the -- I think we have both a medicine a combination that we believe is going to be very efficacious and much more tolerable and, frankly, easier to give from a community physician perspective. So I think, if anything, the data that we saw actually just raises our confidence in what we're likely to see with our own trials.

When it comes to fenebrutinib, so let's start with your last question first, which is we think there is actually still plenty of room. -- for BTKs in MS. We still have 45% of patients today that are on a low efficacy therapy. And those patients are very ripe for moving over to -- so we continue to believe that we have that $9 billion opportunity for Ocrevus between sub-cut -- and let's not forget, we also have OB coming as well. There's still a lot of opportunity for us with OCREVUS in this space. And then we believe fedabrutinib will ultimately just crack up a whole new market segment very much like subcut did for us. Very much like subcut did for us with the community physicians for OCREVUS.

When we look at fenebrutinib, again, I mean, I think when you look at ARR versus CDP in arms fenebrutinib set a new efficacy bar I mean we have just never seen medicine with efficacy like what we've seen with fenebrutinib. 50% reductions in ARR versus teriflunomide, 70% reductions in brain regions, a clinically meaningful nominal and significant nominally significant improvements in CCD P12, we are definitely in that high efficacy category. And so we believe that fenebrutinib really does represent that best-in-class BTK based on the non-coil binding, the differentiated clinical efficacy that we've seen in Phase I and that dosing really is optimized to reach the concentrations in the blood in CNS that we believe will be clinically meaningful in terms of immune modulation -- so net-net, I think Fani has set a very high efficacy bar. We see benefits in both progression and disability. And we think it is the 1 to beat from an efficacy perspective.

James, can we answer all your questions? .

Yes, you did. I've got a lot more questions, but I'll get back in the queue.

Polight of you.

Then let's move on. Next questions go to Matthew Weston from UBS. .

2 from me, please. The first one, quite simple. Teresa, when should we expect to see first overall survival data from Ladera? Obviously, there are a number of clinicians who are looking at the strength of clinical efficacy data when they look at guidelines and how to integrate [duradestran] into the treatment algorithm and OS is clearly going to make a huge difference to some of the more skeptical docs?

And then the second question, just reflecting on the Pharma Day. It felt like you were more enthusiastic on TL1A combos than perhaps monotherapy. Now maybe I misinterpreted, but if not, when should we think about the real commercial contribution of [Pimkibart] actually having an impact on Roche?

Yes. So great questions, Matt. Thank you. So with Ladera, the next OS cutoff is next year. And we anxiously await that just like everyone else, so more to come. In terms of the TL1A combos, I think we very encouraged by -- we're very excited by what we plan to see with monotherapy data with TLA. I mean, obviously, that's the data that we had with the Phase IIs, which were very impressive. .

So I would expect [indiscernible] to make a meaningful contribution kind of off the bat as we would expect with any new launch in a disease area of this size. I think our excitement around the combos comes from the fact that as with any immunological disease, these diseases are very heterogeneous and complex. And so the reality is in order to get the maximum amount of efficacy benefit, a combination, rational combination likely makes sense. And so I think those are things that we will continue to pursue. But I wouldn't say I am unexcited about the mono opportunity. I think the data that we saw in Phase II was quite compelling and would represent a significant step forward for these patients.

Just to push through now if I'm allowed. OS data, can you give us any indication during the year, first half, second half? I mean, I'd love a month or a week, but -- it's a it's more was the first to Yes, we haven't been more specific than that. No, no, that's great. First half is perfect. .

Yes. Then let's go on. Our next question go to Richard Fosse.

A couple of questions, please. Firstly, just going back to OCREVUS. We've seen competitive pressures from Brian. Just when you think those might and might abate a little bit? And also on novo it does seem at the moment that's more switching, which is obviously good for the LOE, but really not adding incremental potential. So when can we see that actually adding.

And then secondly, just [guradestran], -- we get a lot of discussion and questions around the use of sampling and patient assistance programs in oncology, we don't normally see this. So perhaps you could give us some color of the types of patients how long this will be used for, why it's being useful, the reasons behind it. I think that would help everybody.

Absolutely. So gosh, these are all very good questions, where to start. So let's just take them in order. So with [indiscernible], I mean I think the reality is [indiscernible] is getting inroads because it's using very aggressive contracting strategy as we've talked about this now. for the last couple of quarters. This is something that we believe ultimately is going to be manageable or is ultimately manageable, and it's probably ultimately not super sustainable. If you look at their share of market versus their share of sort of value these are aggressive strategies.

And so I think we do believe that, ultimately, we will be able to we will be able to handle the BMV impact. From a Zunovo standpoint, actually, 50% of starts of Zunovo are naive to OCREVUS. And so we are seeing a significant uptake in the naive population. And this is exactly, as I mentioned before, what we really had hoped to see with Zunovo, OCREVUS was very heavily penetrated into our academic centers into urban centers where IV capacity is very readily available.

But when you look into more rural settings and more community-based treatment where IV capacity is more limited, -- this is a perfect place for OCREVUS Zunovo, and that is where we saw a lot of our initial uptake, and that's where a lot of those new naive patients come from. So I will say, as you do see switching in some of the bigger institutions, patients love the convenience of the 10-minute injection. And so I think you can really you really see a nice pickup on both sides, and that's really what you want both for OCREVUS.

So yes, and it's -- as I mentioned, it's the fastest-growing anti-CD therapy out there right at the moment. So we're quite pleased quite pleased with what we're seeing with OCREVUS Zunovo. Now it might surprise you to learn that I'm not going to reveal all of my launch plans to you on this call. But what I can tell you is that we are very well prepared for ensuring that patients have the ability to access [turadestrant] out of the gate. And that does, in fact, mean that we will do things that are maybe that you've seen more similarly or more familiarly in the immunology settings.

We do anticipate creating what we're -- an access hub program where patients will enroll and where we'll be able to give them assistance as we do in all of our therapeutic areas with maintaining reimbursement. We will have a bridge program. I won't go into specifics on that. But what I can tell you is that when [Jiradestrant] launches, what you can expect from us in terms of how we will report. So of course, you will see sales.

What we will also be able to give you are the total number of patients who are enrolled in the HUB program, and we will provide that to you on a quarterly basis. all patients in the HUB program will have received a prescription. And so it will start to give you a sense of how many patients are actually sort of actively either getting or in the process of getting giredestrant.

So hopefully, that gives you a little bit of a sense of what you can expect in terms of the metrics that we'll be using more publicly to measure the launch. And just to reiterate, we are expecting that kind of hockey stick like uptake. We all know that this is a chronic therapy. These patients stay on therapy for a very long time, 5 years plus. -- so we would expect to see more of a hockey stick like uptake -- and then again, just to reiterate what I said at half year as well.

Consensus is about CHF 500 million to CHF 600 million for grandest next year, and we think that, that's sort of right in line.

Then next question go to Graham Parry from Citi. Graham, please?

So follow-up there on giredestrant as well. So on the coverage program. So just a couple of points or questions there. So when do you expect that to cover Medicare patients as well as commercial? And what sort of percentage of patients do you think will be covered by insurance at launch? And how do you expect that to progress through 2027? Or is that going to be more of a step-up in 2028? Do you need the overall survival data for EMA filing -- and then on the Pharma Day, you suggested about the -- and just now, you suggested the consensus CHF 500 million to CHF 600 million is in line with your internal expectations. But does that include just naive patients? Or are you including switch patients who are already on aromatase inhibitors or have stopped aromatase inhibitor 46 to tolerability issues?

Yes. So maybe just to mix it up, we'll take them in the reverse order this time around. So in terms of who are the patients that we expect to come on initially, so I think it will be a mix. I mean, obviously, the biggest sort of bolus of patients you might expect are patients who have dropped off or are looking to drop off their CDK4/6 is due to tolerability. It's clearly a fairly large group of patients, and we would expect that they're anxiously awaiting the giredestrant launch.

And then you have naive patients as well. who are -- would clearly be very appropriate to start from a monotherapy perspective as they begin their journey. And then over time and as our data sets mature, I think obviously, you're also going to get those patients who who are in need of adjunctive therapy to their CDK46. So net-net, I think, out of the gate, there's actually a significant opportunity within these patients. And as Bruno reminded me before we started today, we have put a ton of Epi data in the appendix of the slide deck. So anything and everything you would ever want to know about the epidemiology of hormone receptor positive breast cancer is all in the appendix. So please take a look at that also for Pharma, the Pharma Day appendix is where it is. There's a ton of great data. So please do take a look.

In terms of overall survival, so we do intend to start our conversations with EMA next year. And in in keeping with our long-standing commitment to make sure that we go to market with the filing packages that we believe are -- have the most the highest likelihood of success to achieve sustainable reimbursement, we would hope to have OS in that package when we begin to talk to our European regulators, which we would expect to do next year. In terms of giredestrant, so I'm not going to get into a ton of details for competitive reasons on exactly what the bridge program will look like.

But clearly, with any new medication, there's always payer challenges and you can rest assured that we have been thinking very strategically about how to ensure that we're able to help as many patients as possible get on therapy as quickly as possible. out of the gate. So again, I won't say more on that, but know that we have put a lot of care to our patient assistance programs for giredestrant at watch.

I think maybe probably what we can add for the bridging programs, I think they are set up for the first 6 to 9 months in this phase when there is still some blocks in place until we have resolved these issues. Any additional questions? All your questions answered? .

That's great. Thanks.

Yes, then let's move on. And we move to Steve Scala from Cowen. Steve? .

Two questions. First for Alan. There are several different 340B reform proposals in the U.S. Should 1 of them be passed? What is the range of possible outcomes for Rush for instance, could it be a material upside for Roche. Secondly, regarding the PD-1 VEGF target, since Roche's Pharma Day, 1 of your peers that had been firmly on the sidelines has completed a big investment. Roche is now 1 of a dwindling group of major oncology companies not involved in this target. Is this Roche's final word on the topic? Or is Roche's view in transition? .

Do you want to?

You can take -- why don't you take the first 1.

I can take the 340B topic. So obviously, none of the proposed rules are yet final. We are looking at them closely and considering what any of them might mean for our business. What I can tell you right now, based on what we know is we would not expect any of them to be material, and they seem very mitigatable from our perspective.

Yes. And to your second question, we're definitely not on the sideline. We have actually internal programs, which look at the bispecifics and trispecifics in this space that also includes. PD-1 MGE. .

Steve, did just answer all your questions?

It does.

Then we move on. The next 1 is Luisa Hector from Berenberg.

Bruno, I have a couple. I'll go to giredestrant again. So maybe just whether you could comment. We're estimating that around half of the eligible patients might be Medicare? I don't know if you can give any color around that. And then the second question really connects to the outlook for R&D spend, but also business development because we can see the high level of success that you've had this year.

So I wonder if that changes your appetite for deals or the focus of the deal, maybe now shooting more early stage since you have such a full late-stage pipeline. And therefore, what does that mean as we think about R&D spend into 2027?

Yes, I can take the second question and you take the first. So I can go with the second let me just quickly give an outlook on R&D spend also for next year and also in terms of what you can expect. So first of all, we do expect that the growth that we have, we can continue our growth trajectory into next year. And I think what we have already committed is that we will at least keep margins stable. I can say that we'll definitely increase margins also next year. .

But of course, this means that also we will have more money flowing into R&D because we have so many trials ongoing. But I just want to reassure you, we will increase margins next year. That's the first thing that I can say. On BD side, I completely agree with you. We have a very full late-stage pipeline. So the pressure that maybe other companies feel we don't feel that pressure. That doesn't mean that we're not open to late-stage opportunities. but they have to make sense. They have to make sense financially. They have to make sense from a scientific perspective.

And clearly, what you have seen -- we've done more early-stage deals also to make sure that we have a full pipeline once we get beyond all those different medicines that will read out. So I think we are in a good position here. And as mentioned before, we have sufficient M&A firepower if we need it or if we want to spend it but we're not in the same pressure situation. And certainly, we will not overspend and will stay at this plant.

Absolutely. And in terms of the insurance breakdown, we have not disclosed that to date. But what I can tell you is that we are actively looking at all types of insurance and again, how we can help ensure that patients get on therapy as quickly as possible. .

Luisa, these answers help?

That's great. .

Then we go on the next 1 and you is Chung Win from RBC Capital. .

Muted. Apologies. I have 2, if that's okay. So just the first one, can you just share us your expectations for the Geri label ahead of that November 30 PDUFA. Do you have any color from the FDA on safety concerns. It does look like the data safety is quite clean. -- but we're just curious if there's any expectations for any warnings, particularly around bradycardia signals we saw in Ladera, -- could that translate to any monitoring requirements.

And then on Xolair, you reiterated the 20% full year growth target. -- we understand the buying patterns in 3Q, but on our calculations, you need close to 40% growth for 4Q to achieve that target. Just what gives you confidence in that trajectory? And in 1Q, you indicated you shouldn't expect any additional Xolair beyond the first beyond the first launch for at least 2 years. Does that guidance still hold?

So in terms of the gradestrant label, we're obviously in active discussions with the FDA right now. So I'm not going to not going to comment on what we believe will be in the label other than to say you should anticipate it would be broadly in line with what we saw in Ladera -- and again, many of the safety events that like QT prolongation, et cetera, that you've seen with other surges, you just simply don't see with with giredestrant. And so again, I think you've seen the data, you've seen the trial design, and we should extrapolate a label.

In terms of Xolair. So -- we do believe that there -- the buying pattern had an impact in Q3. We obviously do now have the first biosimilar that is in market for Xolair in that that will have an impact as well, but we're still quite confident in the around 20% growth that we have been messaging for full year. In terms of additional biosimilars, we expect there could be 1 or 2 additional biosimilars coming in U.S., that's possible, but that is contingent on U.S. approval. So right now, we are staying with the outlook that we had provided earlier, which is, again, the 20% -- around 20% in 2026 and flat in 2027.

Maybe, [Tran], quickly to add. I think we had 2 very strong quarters, beginning of the year, plus 26% and plus 28%. So now the third quarter is a plus 8%. So I think it's doable. And the other thing is, I think the 2 additional potential biosimilars to come next year, they were always back on our mind. So we'll have to see how this plays out. But currently, it stands as a the reason. .

And I think we can say we had plus 20% year-to-date. So I think we need another Q4 with 20% to get to where we want to be. .

Exactly.

Yes. Yes.

Any other questions?

Okay. Then we go on. So next 1 would be Michael Leuchten from Jefferies. Michael, please?

Could I please ask about the Novira study and the CDK4/6 combo study that Teresa flagged -- there seem to be seam studies. Just wondering why and how you'd be able to get those on label if and when they read out? And then a clarification, please, on the bus helpful to confirm the growth outlook for the end of this year, low double-digit dynamics into next year. I think previously you said there's no structural change to the growth profile for Robison. Does this still stand for 2027 if the U.S. growth momentum doesn't come back, and we see a little bit of a sequential flat lining in Europe? .

Yes. So just to confirm with Novara, -- so those those trials are not meant to be label-enabling they're meant to generate safety and some experience data. So -- but they're not anticipated or expected to be label enabling. When it comes to Vabysmo, I think we've been we've been pretty consistent in where we believe the market for Vabysmo heading into the future. I think the U.S. has rebaselined we are expecting to remain in that sort of low single-digit growth for Vabysmo in terms of sales.

It's probably important to note, though, that the volume growth in the U.S. is much higher. There's a contracting effect that kind of takes takes effect there. And then when you look ex U.S., there is actually significant growth for Vabysmo and sort of more opportunity for growth and penetration come outside of the U.S. So I think we remain very confident in that CHF 6 billion census peak sales number and believe we're well on track to achieve that.

Michael, did this answer all your questions. Then next question go to James Quigley from Goldman Sachs. James? .

Thanks, Ken. I've got 2, please. One follow-up on Xolair. Can you give us a rough idea of the split between the immunology and the food allergy indications? -- in terms of sales or proportional or whatever you can give us? And just trying to think about biosimilars as well in terms of -- at what point could the biosimilar start to hit the food allergy indication? Or are there any other exclusivities or protection that you have for that indication?

And the second 1 is on [Taneli]. So what are your plans here for indication expansion -- some of the competitors in China are looking at significantly expanding into a broad set of cancers. -- given the speed of moving out to China, how quickly can you move to establish an early advantage across B7-H3 tumors? And what are the gating factors that you need to overcome here as well?

Great. So let's start with [Tim Pelle]. So I think we shared at Pharma Day that we have -- we have great excitement around [indiscernible] . So obviously, a global Phase III trial in second line is being initiated by the end of the year. The details of that study design, including the comparator that we'll use will be announced in due course. And then we are actively looking at accelerating clinical development with global trials across multiple indications, non-small cell, small cell and in additional tumor types that have that B7-H3 expression in pancreatic as HCC. So we do believe that the data we've seen with Campelli, both in terms of efficacy, tolerability is very compelling.

And so we have plans for a broad development program for that molecule. So stay tuned, and you will definitely hear more. In terms of the breakdown for allergy and food allergy, we have not previously shared that. So I think we're seeing great growth actually also in our chronic erticaria indication as well. So Xolair overall, it continues to grow both in allergy and in food allergy.

I think maybe as a hint, I think since we launched food allergy, all the growth we have seen since then basically was I think whereas the other indications were more flattish, but I think that's how you can calculate it back. Maybe 1 add-on. I think, James, if you go to Pharma Day presentation, I think there you have a full list of what we announced with respect to [Tom Peel] -- so I think we have a Phase III global study in non-small cell lung cancer to be initiated later this year small cell lung cancer, sorry. We have, I think, done a global study in non-small cell lung cancer to initiate first half '27. We have -- we are looking into prostate cancer. We are looking into breast cancer. I think this is already what we have communicated. Any other questions? .

Just in Xolair, whether the biosimilars can attack the food allergy straight away? Or are there any other protections .

Yes, it fully depends on what label they receive. I mean I think with allergy in particular, we would expect some stickiness for continuing patients. So I think this is an area that will be interesting to watch as the biosimilars come into play because, again, you're dealing with allergic patients and conservatism in that population may be higher. And frankly, you're also getting particularly in food allergy, a lot of young patients. So then you also have to convince parents to be comfortable with that as well. .

And biosimilars don't have data in that setting .

Correct. They do not. .

Very good. Then next question go to Justin Smith from Bernstein.

Just a couple on better on, if I can. KOLs, we've spoken to you expressed a bit of concern about whether or not there'd be an antidote -- and then second one, just could you talk a little bit about the challenges of managing the placebo arm given these patients who are receiving frequent treatment so infrequently?

And I'm sorry for what molecule? .

[indiscernible] .

Okay. Sorry. That makes more sense now. So we -- this is something that we actually looked at when we began to design the trials. But ultimately, when you looked at the effect that we were having, we didn't believe that it was necessary at was going to make sense. So I think we're very comfortable in the efficacy and safety profile that we've seen from [Solbestron] through very large Phase II trial populations. And so we're -- I think we're very encouraged by what we've seen so far. And frankly, the rapid with which these trials have enrolled, I think, speak overarchingly to the excitement for for something that has this profile, particularly given the difficulty in controlling these patients over time.

Okay. Then next question go to Peter Verdult from BNP Pariba. .

Pete Dell here, BNP Pariba. -- two, please, 1 on outlook and 1 on obesity strategy. Just Thomas, I totally hear you on Rosol having a plant cliff to deal with, per se, but would like to kick the tires and gauge your early thoughts into next year and whether you would push on the idea that top line growth decelerates from sort of mid- high or mid- to high single digits enjoyed over the last 3 years, something closer to low single digits. And I'm saying that not trying to be difficult, but I get that Jadestone and Fannie will be good launches, but you do have growth pressures or slowdowns on a number of products on list them out, you know what they are.

We've discussed many of them on the call. So that just seems to be pointing to 2027 remain perhaps being a lower on year. So I realize today is not an official guidance platform for next year, but would like appreciate some any thoughts given what you said in your being remarks? And then secondly, for Thomas or Teresa on obesity strategy, given we now see self-pay 50% of U.S. injectable obesity market, 90% of the oral market would Roche have any interest in sort of developing a consumer Rx model longer term where you build a sort of portfolio around your obesity pipeline to include aesthetics or -- and/or men's wellness products. So the question on outlook and obesity strategy.

Yes. So I can take the first question. And I can only say that we are confident that we can maintain a similar momentum that we have. And what I also has said previously is that yes, in terms of margins. We always said that margins will be at least stable. -- but whether I can also commit to even though that we will invest more in R&D. And this investment in R&D that we need on top of all of the efficiency gains that we are putting in place on top of that. We need those investments for all of the clinical trials and all the exciting new molecules that we have. But despite that, we will expand margins next year. .

And in terms of the obesity strategy, so I think we see the evolution of the market, just as you do. Cash pay is certainly going to be a growing part of how monotherapy obesity molecules or medicines are paid for, and we would intend to compete appropriately. .

Okay. Then next question is with Urban Fritsche from ZKB. You're unmuted. .

You're muted. You're still muted.

Sorry it was my fault. Okay. I was now I'm muted. Okay.

Let's maybe quickly go on and then we give a second trial later on. Next question would go to Morgan Stanley Thibaut uterine Thibault?

Just a follow-up on Tampere. Based on the data we've seen CC, the efficacy looks competitive against other BH3 and potentially more favorable on the safety profile regarding the ILDs. Is this the key point of differentiation in your view based on the we've seen so far? And then the second question, just on Xolair for next year. Have you already made price concessions in the U.S. given the do you expect to have a very meaningful price impact next year? And so in that context, can you give us an indication on the direction of Revenue for ear next year if if you have any chance of maintaining this franchise or growing this font next year?

Okay. So for Tampelli, we believe that it's both safety and efficacy. -- that are going to be differentiating for this molecule. I think we've seen it have what we believe to be best-in-class data on both. So I think we're excited about it from both ends. And I'm sorry, I didn't quite hear your question. So is Xolair and and guidance or outlook for next year is...

Just the outlook for Xolair in '27, if you already took a price cut if you're expecting to take a meaningful price cut next year? And just if you can give us an indication on the direction of sales from Xolair next year. .

Sure. So I think I mentioned previously that we would expect Solar to be flattish next year. .

So I think the first biosimilar has launched with a 50% price cut, as you would expect, nothing exceptional there. And I think we are always, as we have been before, not driving the .

The price -- we're not driving the race to the bottom. Yes.

Did this answer your questions? Then we have a final the which is Rama from HSBC. .

I appreciate you expect to sustain current level of growth with operational gearing. -- clearly, -- the Street seems to be getting you down to 4% to 5% top line growth and a bit of margin pressure. I can see that you have an expectation of flat xolair was a street modeling a 9% to 10% decline in '27. What are the other assumptions maybe efficiency on the cost side on AI or R&D phasing or trial phasing costs that we might be missing when we are modeling '27 that we are getting a lower top line growth and a weaker operational gearing.

Yes. Let me just comment on that. And so again, I can just reiterate that we do believe we have good momentum. And this momentum will carry us not only through the end of the decade, but into the next decade. And second, please also keep in mind the other revenue line. So we have a number of income that we get from molecules that have been licensed out, that will give us a certain boost.

That's why I made the comments that I made. -- even though that we stay disciplined in our investment in R&D and MD -- but we know that we also have to invest in the launches. We have to invest in all the trials. We know that we have a certain boost that will help us on the margin.

We have even told the market that we will grow the other revenue line from 3% of sales to 5% of sales until the end of this decade, until 2030. .

So that we are clear. Are you making a specific assumption about or [foglipron] royalties that the market might be getting wrong? Or that's a bit more bullish than what the Street is modeling. .

There are multiple molecules that have been licensed out that will add to growth in that line. And if you just look at the P&L and you assume whatever growth on the sales line, the reality is that any additional growth that will come in that will add to the margin. So I think it's independent, what I said is more or less independent of how exactly successful that will be. But there is just a certain tailwind that we get through that. .

Okay. That is help, right? .

Yes. Perfect. .

Okay. And then I think we have 1 final question. Steve came back. Steve, the final question goes to you. .

So there will be some important competitor BTK data at MS Toronto tomorrow. What specifics in that data would represent a clear win for fenebrutinib? .

answer that. That's a good question.

Do you want to answer that?

I can answer that. I think that fenebrutinib put in quite a high bar in terms of efficacy. And so we have not seen any data on the efficacy side of that other company. So we're going to be very curious to see how their efficacy data looks. .

Okay. I think with that, we will close the call. Thomas, over to you.

Yes, thank you very much, Bruno, and huge thanks to the team. As we mentioned, I think we have a good sales growth this year and good sales momentum. The team and the organization is very disciplined. Also, we have good line of sight for the next couple of years. We have a number of NME launches. I think that Trials showed on her slide, how many approvals we will get in the next months. And this will already carry us to the end of the decade. And on top, we have up to 20 NMEs that we could launch, and there are many more readouts that are going to happen.

So overall, I think we've made significant progress on our pipeline. And also when you look at Phase II success rate, if you look at pipeline value, et cetera. It also shows that as an organization, we've been quite disciplined on cost, and we have arranged and shift money within our organization to make sure that we can fund a lot of these activities. And of course, we are very disciplined also on BD and also in the implementation of AI. So overall, very determined focus and we'll continue to execute and we will deliver.

So it's a pleasure again to provide here our annual update. A lot has happened since last year. And we are really excited how things have worked out. I will not waste a lot of time. Just quickly go through the agenda and housekeeping items.

So let's start with the morning sessions. First speaker, again, will be our Pharma CEO, Teresa Graham, providing an update on the overall Pharma strategy and life cycle options for our rather fresh and well-established on-market portfolio. The second speaker, as you can see, will be Levi Garraway, our CMO and Head of Global Product Development. Levi will provide the R&D excellence KPIs, which we started to share with you 3 years ago and which will allow you to track our progress in that area.

Third presentation then is given by our special guest, Aviv Regev, our Head of Global Product -- our Head of Early Research and Development at Genentech, gRED. And Aviv will talk about our industry-leading adoption of AI in early drug development. And she will also share some KPIs tracking this impact. I think that's at least to my knowledge, an industry first. And the morning session then will close with Alan Hippe, CFO of the Roche Group, providing us an update on financial excellence and digitalization and group finance, all prerequisites for thoughtful asset allocation, which will allow us to optimize our investments and keep innovating for patients.

Following the morning presentations, we have a 30-minutes Q&A with all the speakers of the morning sessions on stage, including Karsten Jung, our Head of GPS; and Wendy Cheung, our Global Therapeutic Area Head for Oncology and Hematology. Afterwards, we are heading into a 50-minutes lunch break. And after lunch, we will continue with the pipeline presentations covering all our therapeutic areas. The first sessions will be -- again, the first session will be given by Levi Garraway covering oncology solid tumors, and you might have seen the exciting news of today. We will announce new trial starts here for giredestrant in the adjuvant breast cancer setting.

Second speaker then will be Matt Hellmann, who just joined us from AstraZeneca, where he led the early oncology development. Matt will be our Global Head of Oncology and Hematology Product Development, and he will take us through the malignant and nonmalignant pipelines. Third speaker is Hideki Garren, our Global Head of NCHFology Product Development. Hideki will provide us an update on our development efforts in Alzheimer's disease and Parkinson's disease, and he will also provide some important Phase II transitions.

Then next, Larry Tsai, our Global Head of Immunology Product Development, who will touch on Gazyva in kidney diseases, the upcoming readout for afimkibart in IBD and of course, on sefaxersen in IgAN, where we had positive top line news out last week. And following Larry, we have Chris Brittain, our Global Head of Ophthalmology Product Development. Chris will provide us an update on NMEs currently filed with the regulators, but also cover some early development efforts. And finally, we will have again Manu Chakravarthy, our Global Head of Cardiovascular, Renal and Metabolism Product Development. Manu just has some intense weeks behind him with the opening of our new research and development center in Boston. He will present one of the highlights of today.

I think for the first time ever, we show a data snippet, which has -- at Pharma Day, which has not been previously presented at a medical conference. I'm talking about the Phase II data for enicepatide in type 2 diabetes, patients with and without obesity, where we had a top line release out last week as well. He will also cover the further development of our oral 996, which we now will take into Phase III development. After a closing remark by Teresa, we will have our second 30 minutes Q&A with all the speakers from the afternoon sessions, including again, Karsten Jung and Wendy Cheung. And the event then will close at 2:40 p.m., but you're invited to stay around for the buffet reception, giving you an additional opportunity to talk to management.

And let me also mention one additional housekeeping item. We have again prepared a short 11-question feedback survey. The link to the survey will be shown to the participants in the webinar 50 minutes before the end of the event. Participants in the room will receive an e-mail with the link to the survey about 1 hour after the event. And we would very much appreciate if you could again give us your feedback as we always strive for improvement.

And with that, it's my great pleasure to hand over to Teresa. Teresa, please.

Good morning, everyone, and welcome to Pharma Day 2026 to everyone who's joining us in the room and online. I wanted to start by just quickly taking a step back and thinking through a little bit the journey that we've been on as a company over the last number of years. So let's start in 2026 -- I'm sorry, 2022, not much of a journey back if we're starting today. 2022 was a tough year for Roche. We had a lot of significant pipeline failures. And that caused us to take a big step back as a management team and actually look at the operations of our business from end to end.

When we came together in 2023, we rolled out a very transparent look about where we were, particularly with our R&D pipeline. And we shared with you the beginnings of R&D excellence and how we intended to invest end-to-end across our entire R&D value chain to ensure that we were able to change the trajectory of where we were headed. In 2024, I stood on stage and I shared with you the One Pharma Strategy, which was our view of where we wanted to play and how we were going to win in an increasingly competitive set of market spaces. And then last year in this room, for the first time, we talked about our ambition to be a top 3 obesity player.

Today, I want to share with you a simple reality that all of that hard work to build a great pipeline and all of the work that we've done through One Pharma Strategy to build the right capabilities to bring that pipeline into the world only matter fundamentally if we can turn that into patient impact at scale around the world. And so what we're going to talk about today is exactly how we intend to do just that.

So I'm going to start by giving you just a quick snapshot of where we are since last Pharma Day. We're then going to take a quick look at our strategy and how we've really invested from AI to manufacturing at enhancing and building the fundamental things that are going to be required for us to ensure that we can reach as many patients as possible with our incredible pipeline. We're then going to take a look at commercial excellence and exactly what we believe it is going to take to succeed in the therapeutic areas in which we're entering. And finally, we'll close with a look at what you can expect in terms of growth drivers over the next couple of years. So let's dive in.

So we have made significant progress since last Pharma Day. We shared with you at half year that sales remained strong at 6% growth. We're continuing to grow our margin at double -- we're continuing to grow COP at double digits and increasing margin. We've had 10 positive Phase III readouts since last Pharma Day, including, as Bruno mentioned, the sefaxersen results in IgA nephropathy that were positive at interim just last week.

And since last year, we've advanced 6 new promising molecular entities into Phase III, including the decision last week to advance our oral CT-996 into Phase IIIs, which Manu will talk about a little bit later. So tremendous progress on the pipeline. Now of course, that progress didn't just happen. It was the result of very hard work. And I'm not actually going to spend too much time diving into this because you'll hear a whole update on R&D excellence from Levi. But I think it's very clear to see that we have made measurable progress against every part of our R&D engine from the number of best-in-disease medicines that we have to the value of that portfolio to the rapidness with which we're able to advance programs.

Now you can see over time since the introduction of the Bar that the number of programs in our portfolio have gone down. And that's because we systematically removed medicines that we did not believe had the opportunity to be transformative. But the medicines that we have replaced them with are of significantly higher value. We actually have the highest value pipeline that we have ever had at Roche today. And that is because fundamentally, we are focused in areas that we believe can make the biggest impact to global health.

The famous doughnut slide, I think, tells the story really well. And believe it or not, since you last saw it in July, we've actually had a number of really important updates. And the first one is the top line number. We have gone from 19 new NMEs with a potential launch by 2030 to 20, which, as you will recall, was our ambition for the end of the year. Now when we introduced this ambition to you in 2023, it was not a foregone conclusion that we would hit this. And in fact, we had quite a gap. So it's pretty incredible over the last couple of years that we've managed to refresh this pipeline so significantly.

Now let's talk a little bit about the puts and takes within each of these programs. And let's start what's not on this slide anymore, and that's emugrobart. So we recently made the decision to end development of emugrobart, which was our anti-latent myostatin with Chugai's sweeping technology from development in obesity. And this was based on a thoughtful look at the interim GYMINDA results, which just showed us that we did not believe that it was going to have the potential to reach the TPP that we had in place for it. So we have made a decision to discontinue development. We are returning that molecule to Chugai, and Chugai is looking to further development in SMA as well as considering potential out-licensing opportunities.

But there are some exciting updates to this slide in the other direction. So 2 recent additions, Tam-Peli in small cell and non-small cell as well as other solid tumors, which just had some really impressive data presented at World Lung, which we'll discuss later this afternoon, is an incredibly exciting new addition to the portfolio as is our VEGF-IL6 DutaFab in DME, which you'll hear more from Chris about later. I also wanted to be true to my word and let you know that we have updated our divarasib revenue expectations from CHF 1 billion to CHF 2 billion to CHF 2 billion to CHF 3 billion, and that's based on the strength of the Krascendo-1 data, which, as you know, is our Phase III head-to-head against standard of care.

So we are extremely excited about the molecules that we have on this chart and the opportunities that they represent for patients. Now ultimately, what makes that great pipeline possible is strong financial performance. And this performance is clearly driven by our best-in-disease on-market portfolio. So you can see that we've continued to have strong sales performance and continued to increase the margin.

You may notice the sales growth volume in 2026, which drops off a bit. That is largely related to Xofluza and the fact that we had a weak respiratory season at the beginning half of this year and Xofluza clearly is a high sales volume product. But when I have talked to you in prior pharma days about rigor in the science and discipline in the business, this is what discipline in the business looks like. We are carefully considering every investment that we're making, every expense that we're bringing on board to ensure that it's delivering the greatest possible return both to the portfolio and enabling our commercial infrastructure.

And it's because of that strong financial discipline that we believe we have a strong base to grow through the coming years. Now this is a group slide, which you've seen many times. So I'm just going to spend a little bit of time on some of the individual pharma dynamics here. So the on-market portfolio will continue to provide growth right through the end of the decade. We have no patent cliff that we are looking at either up to 2030 or beyond. But we have some exciting things coming into that on-market portfolio, whether that's Gazyva, which is already approved in lupus nephritis and is now getting its other immunological indications improved, the giredestrant launch, which we're expecting by the end of this year and the fenebrutinib launch, which should come early next year. These are exciting new best-in-disease opportunities within our on-market portfolio.

And then by the end of the year 2027, we have the opportunity for 6 more launches, divarasib in second-line non-small cell; vamikibart in UME; Enspryng in 2 new indications, thyroid eye disease and MOGAD, which is actually generating a lot of excitement in the nCHFology community, sefaxersen and of course, the new kid on the block, afimki in UC, where we get data at the end of this year, beginning of next. So we have a tremendous base to build from, and we are incredibly excited about the opportunities that are presented.

But our confidence in this growth outlook is really based on 2 critical things. One is the strength of the pipeline, but the second is our confidence in our ability to deliver that pipeline where it matters, and that's to patients. And how are we going to do that? We do that through the implementation of our strategy. This is how we bring exciting science from the podium to patients. And that journey ultimately begins by making sure that you have the right foundations in place.

When we introduced the One Pharma Strategy, we introduced our 5 target therapeutic areas: oncology, hematology, immunology, CBRM, ophthalmology and nCHFology. These are the 5 therapeutic areas that represent 60% of the cumulative disease burden that our global health care systems are facing. And they are the 5 areas that also represent about 80% of the growth that will happen in the pharmaceutical industry. Currently, within these 5 therapeutic areas, we are focusing on 11 disease areas in an end-to-end way. What this means is that all the way back from early research through commercialization, we want to know that we have a pipeline that will allow us to continue to lead in these areas.

This focus has created a significant momentum in the company because everybody knows where they're going and how they need to get there. Last year, we shared with you the deep dive or the sort of overview of all of these 5 therapeutic areas and what we believe the criteria for success are. NCHFology, immunology, ophthalmology and CDRM are unchanged. But based on the significant movement that we've had this year in our oncology pipeline, we felt it was worth a look at what our aspirations and ambition ought to be in oncology. And I wanted to share that here with you today.

We want to achieve leadership through transformative anchors, and those anchors are things like giredestrant and divarasib. We want to establish and expand our position in key patient segments, and we want to make sure that we're continuing to invest in that next wave of innovation. When you have Matt and Levi up here a little bit later, I hope you will similarly be excited about what you see because we have made a lot of advancements in our oncology pipeline, building off the historical legacy of success that we've had, but with eyes absolutely pinned on the future about where treatment is going and what we need to do to be successful.

But of course, that great science just doesn't magically turn into a great medicine in the clinic. And there are a number of core capabilities that we know we need to invest in to succeed. These capabilities are where I have spent a tremendous amount of my time over the last couple of years, ensuring that we are well positioned in every single core fundamental area that we will need not only to deliver the portfolio of today, but to seamlessly deliver the portfolio of tomorrow.

So let's start with modalities because I think this is one of the more exciting areas for us. So you'll probably think of Roche and Genentech as a biology-driven company. And you're right, that's always been true. But increasingly, we have more modalities at our disposal to make sure that, that biology is exquisitely targeted to the places where it needs to go to deliver the best result in the disease. We currently have 15 different modalities represented in our pipeline, and that comes by leveraging both internal and external strength.

I hope throughout the course of the day, you'll begin to see how all of these modalities actually start playing into our overarching therapeutic area strategies and how they really are positioning us to deliver best-in-disease solutions. Of course, having all of these modalities is one thing, manufacturing them at scale and getting them to patients is quite another. Again, Roche has always had one of the largest, most robust and global footprints of manufacturing of any pharmaceutical company. And we've always been very proud of that. It's been a real competitive advantage for us.

But in order for us to have it remain a competitive advantage in the future, it requires investment and it requires modernization. So of course, we have been looking at things like how do we improve the yield of our existing products. And we've had some great successes in doing that. Our next-generation manufacturing techniques have allowed us to increase the yield of OCREVUS by more than double and increase the yield of Perjeta by 5x.

We are also actively taking advantage of opportunities for innovation across all of the different parts of the manufacturing process. And here's a great example of regulatory innovation, where through the participation in a regulatory pilot, we were able to get simultaneous approval with the FDA and EMA for a tech transfer for Lunsumio. And then through the regulatory reliance program that extended to 14 other countries, which means a line improvement that normally would have taken us 890 days took 240. That's a 73% reduction.

Those kind of improvements are critical in helping to make sure that we can move as fast as possible to get medicines to patients. So that's cool. But what's cooler is what is on the other side of the slide. That is a fully live digital twin of our Holly Springs plant in North Carolina. Working with NVIDIA and their physical scale AI program, we have built the first fully-operational pharmaceutical manufacturing plant using a digital twin. This is helping us ensure that before a single beam was put in place, we knew how that plant was going to operate, how those lines were going to run, where efficiencies could be taken, how we could actually make sure that we were making the best use of every square foot.

This is incredibly exciting because it doesn't stop at Holly Springs. The idea is that we start there, and then we take those learnings and we actually scale them across the entire network. That means any time we need to make a tech transfer, any time we need to move production from one place to another, we know in real time how that's going to work, what we need to do, how we need to do it and how to do it faster. This is an incredible advance. And it just doesn't stop with the physical plant of our network. We're also looking at how we can bring in AI technology to revolutionize all parts of our production, everything from packaging and distribution to final assembly of our medical devices and design excellence across all of the different parts of our manufacturing chain to ensure that we are doing things virtually in a way that allows us to gain scale in the real world.

So this ambition is quite simple from one site to the network to every individual product. Speaking of devices, devices are going to be a critical part of our portfolio going forward. We anticipate the vast majority of our medicines going forward are going to need a device. And so one of the things that we've worked very hard at over the last 24 months is ensuring that we have a scalable platform of devices that will meet every single need we have upcoming in our portfolio. These are the 6 different devices that we have currently moved to a platform model of. These will cover 90% of our future device needs. And this, again, allows us to move much more quickly to ensure that we get cutting-edge devices into the market.

Technology is helping us here as well. So last year, we announced that we were creating a device pilot plant in Basel. Well, that plant is now live. And what you're seeing here is a live working example of a digital workbench where we are in real time, putting together devices and figuring out what's working, what is not working and how that will scale across the actual production lines. This technology will now subsequently be scaled into other parts of our network. But these are tremendous advances that help us be more effective, more efficient and move with much more speed. But having these wonderful devices means they fundamentally need to make it to a patient. And being a commercialization powerhouse is just not simply having differentiated medicines, but it's also making sure that we have a personalized and comprehensive physician and patient experience. And technology is helping us here as well.

So there's sort of 2 sides to the coin when we look at digital excellence in our marketing performance. We look at the creation of materials, but then we look at the dissemination of materials. By using AI in different parts of technology, we've been able to cut our content creation by 50% and reduce the cost of each individual asset by 83%. Those are resources that can go back into the commercial infrastructure and into our pipeline. We then combine that with our AI-enabled Marketing Automation & Revenue Simulation, MARS. I'm sure they worked really hard to make sure that had a really cool acronym. Marketers do that. But MARS actually allows us across every single channel that we use to interact with patients and customers. It allows us to optimize what message, what materials, what creative we're putting where gives us real-time feedback on what's working and what is not working and allows us to create that. This is live and working incredibly well right now in the U.S., and we have plans to scale it globally.

I think what's most important about what I just shared to you, though, is that this isn't just about technology for technology's sake. And I think you're going to hear the same thing from Aviv. Every time we make the decision to deploy a technological solution in our business, we are actively looking at what is the benefit that it is going to create. What efficiency is it going to give us, what speed is it going to give us, what comparative advantage is it's going to give us. And we're working very rigorously across the entire end-to-end value chain to make sure that these incredibly important investments are being used in a thoughtful, ethical and extremely productive way. But none of that matters at all if you don't have the right people working in your organization and pulling that through.

If I had the time, I would love to talk to you about the entire workforce at Roche, all 100,000-plus people who are brilliant, dedicated, committed and excited about the journey that we're on. I suspect you might not stay for that. So instead, we're going to focus on the people who are here in the room today and who are the folks that you're probably going to be interacting with the most. Many of these are new -- are familiar faces to you. But I did want to call out 3 new additions to our team. Wendy, who is our -- wave Wendy, yes. So she's our new GPS Oncology Head. Tanya Monga, who's over there too, wave, Tanya, who's our new NCHFology and Immunology Head in GPS; and Matt, who is our new oncology PD Head.

Now Matt and Tanya have been here a whopping 3 weeks. So be nice. We're going to all be hanging around whether we'll involve them in the Q&A, where they're going to be here at lunch and at the apero later, and they're all excited to meet you. These are the faces who are going to help bring these amazing medicines to patients. In addition to this team here back in Basel, San Francisco and around the world, we have hired hundreds of new people, all of whom are coming to us with the skills and experience that we are going to need in order to bring our pipeline forward.

And while they're not in the room with us today, I also did want to call out a number of the new additions to our early research and development pipeline, including Mark Dawson, who is our new Head of pRED. And I'm sure all of you will have the opportunity to meet with these folks soon.

Now let's switch gears a little bit and talk about execution because a great pipeline and the right infrastructure will help you bring a medicine to market. But alone, they actually won't do the most important thing. And that is to get a medicine to a patient. To do that, you need a robust commercialization engine. And so let's talk a little bit about how we plan to succeed in that all-important last mile. So when we think about commercialization at Roche, we tend to think of it within 3 archetypes: entrench, expand and establish.

Entrench is where we are maximizing positions, leadership positions in our key disease areas. These can be line extensions into adjacent indications. They can be devices, which allow us to increase convenience. But ultimately, it's about commercial excellence and having a fantastic customer experience. Expand is where we are leveraging our existing established disease areas, launching new NMEs and expanding indications. So this allows us to build on our scientific depth and our relationships and drive commercial synergies while we're leveraging the market expertise that we have. And finally, establishing.

And this is where we're entering into new disease areas with the intent of reshaping the current standard of care. This requires capabilities and infrastructure building, but it also allows us to jump off of all of those foundations we already have put in place while we are increasing our market understanding, building those relationships and beginning to tackle those unmet needs. Fundamentally, our commercial execution and our pipeline is about one thing and one thing only. That is about disruption. It is about disrupting the standard of care and bringing new medicines to patients to fundamentally change outcomes and reduce cost from global health care systems.

Now I'm not going to go into too much detail on this slide, but this is how we view our existing portfolio through the entrenched and establish framework. So again, I'm not going to go into this in detail, but we will use it as a guide. So let's jump into entrench, which consists of some of our key on-market growth drivers.

So we'll start with breast cancer. And first, let's take a look at our HER2 franchise. So as we discussed at previous events, we see the HER2 treatment paradigm evolving, and it's going to move away from that one-size-fits-all mindset of the past. Our HER2 franchise is extremely well positioned to remain in a leadership position, and we expect to continue to play a very important part in the treatment of these patients. In particular, Phesgo is expected to remain a key treatment option in the frontline maintenance setting.

You can see on the slide that we continue to increase our Phesgo conversion rate. As always, whenever we add new countries into the mix, we see a little bit of a downturn. That's what you're seeing here. It takes a little bit of time for those countries to come online, and we expect to see those numbers continue to increase. And we expect to end at around 60% or above 60% in global conversion with many countries already in the 80s and 90% from our very earliest launch countries. And while we -- to reiterate our HER2 franchise outlook, which I know we told you many times, but just to ensure that there are no changes, we expect the HER2 franchise to peak at CHF 9 billion this year.

As a reminder, that CHF 9 billion was at 2024 constant exchange rates, followed by a steady decline through the end of the decade with a solid tail of around CHF 4 billion. That includes quite a bit of Phesgo, about CHF 1 billion for Kadcyla and then a little bit of Herceptin and Perjeta. We do not expect a Perjeta biosimilar in the U.S. before 2028, and we do not expect one in CHFope before 2027. And once again, let me just underscore for that our HER2 franchise, we do not expect to see any sort of cliff situation.

Let's move on to one of our cornerstones in NHL and building on leadership in novel combinations. So Polivy is now firmly established as the standard of care in first-line DLBCL with rapidly increasing global patient numbers and firmly taking the lead in patient share. At the same time, we are looking to unlock Columvi and Lunsumio in non-Hodgkin's. Columvi is now the leading bispecific in second-line DLBCL, which is supported by its very well-regarded OS data.

And then, of course, we have the SKYGLO data in combination with Polivy, which has the potential to really change the treatment paradigm one more time. Lunsumio just had positive CELESTIMO data in second-line follicular, and we expect it to continue to be able to help an increasing number of patients as we make that march into earlier lines. Both Columvi and Lunsumio were very specifically designed to treat different kinds of patients. And they have very unique niches that they serve in the market with Columvi serving more aggressive types, whereas Lunsumio is more suited to the community setting. So we very much expect to continue to see great growth in this franchise.

Now let's switch over to hemophilia A. In hemophilia, we have set the standard of care with Hemlibra, but we don't intend to stop there. And let's just be clear, that's actually not a super easy thing to do. 80% of patients on Hemlibra today have 0 bleeds. We have real-world data for over 10 years showing our efficacy and safety. And we have incredible patient penetration, and our patient share continues to grow as we move increasingly into non-inhibitor and older populations. But we're not resting on our laurels. And when you have a chronic condition, convenience becomes something important, and we wanted to make sure that despite all of the options that we have on the market for Hemlibra today, we are continuing to increase the convenience.

And so I'm very excited to say that in 2027, it's stuck in my pocket. We plan to launch the auto-injector. Now this little guy made its first appearance at ISTH in Paris earlier this year in the medical affairs booth where it was so popular, we actually had to station somebody there because people kept prying it off. You will not have to pry it off anything because we have some available over lunch for you to actually interact with, so you can get a sense of how it feels.

This device is designed to ensure optimal therapeutic exposure. It has improved comfort. It's needle -- you can't actually see the needle. There's no visible needle. And of course, it has time-saving administration. But we don't stop there either. We are actively working through the development of the second-generation hemophilia treatment, which I always find hard to say, zemocimig, NXT007, which we think has the opportunity to once again fundamentally change the treatment paradigm for patients with hemophilia A.

So to sum it up, we created a new standard of care in hemophilia. We're improving on to that standard of care, and we're creating the next-generation standard of care. And I would be very remiss if I were to leave this presentation talking about hemophilia and not mention that the Chugai team that was responsible for discovering Hemlibra recently won the prestigious U.S. Lasker Award. So that tells you just how important this molecule has been.

So now let's talk about OCREVUS, which changed the game in MS. It continues to be the #1 anti-CD20 therapy with more than 525,000 patients globally, and we are well regarded within the MS community, ranking #1 amongst MS patient populations. OCREVUS set the standard in MS. But again, we're not stopping there. OCREVUS subcut, ZUNOVO came on to the market, and you can see the current patient count number. It is increasing exponentially. OCREVUS subcut is now the fastest-growing anti-CD20 in the U.S., and that's driven by community practices, which is exactly where we had hoped we would get that entrenchment.

But once again, we're not stopping there. This is the last thing I have in my pocket, I swear. But this is what the OBI looks like, a simple device that you can attach at home and get your OCREVUS treatment twice a year. This is innovation. This is freedom. This is being developed in conjunction with Enable Injections, and we are hopeful that we will be able to have data here in 2027 with our high concentration device, which is just incredibly exciting. So just like for the Hemlibra auto-injector, this is out at lunch as well, if you would like to take a look.

And of course, we can't end the conversation about our on-market drugs without talking about Vabysmo, which has continued to reset the standard of care in retinal disease. The U.S. market has stabilized, and we continue to see branded market share gain. We continue to see significant volume growth in the EU, which is overcompensating for the pricing effects that began at the beginning of this year. In rest of world, we are seeing strong growth driven by market share expansion as all of our newly launched countries come on board. Vabysmo is the market leader in retina, and that is exciting because we do know that it is just a superior product.

But we're not stopping there. We are doing a lot in ophthalmology. It's one of our key focus areas. Chris is going to talk to you quite a bit about this afternoon, but you can see the entry into UME with vamikibart, the data with Enspryng in TED, additional indications for Vabysmo, but also an incredibly exciting pipeline that will allow us to continue to bring revolutionary treatments to patients with eye diseases.

And so now let's move on to expand. Here, you'll find some of our upcoming launches like giredestrant and fenebrutinib. In addition to NMEs, we're also expanding some of our existing medicines into new TAs. I think Enspryng is a great example of that. But let's start where I'm sure a lot of you are interested with giredestrant. So giredestrant, as we know, has the potential to become the new standard of care across a broad spectrum of risk groups in the adjuvant ER breast cancer space. And we see that strong potential for giredestrant to become that new backbone because it helps us overcome the limitations of our existing therapies.

So if you actually look at how we think about the treatment of hormone receptor positive, HER2-negative early breast cancer, you can see that we break out the populations by risk groups. And these groups are largely defined by what we see in our clinical trials. The lidERA population covers quite a number of those, more than what we see with the CDK4s. They're primarily targeted in the high risk and the median risk group, where you see lidERA going all the way through into intermediate risk.

So as we think about what the opportunities are for giredestrant going forward, clearly, patients initiating endocrine therapy monotherapy would be great patients to actually go on giredestrant. Patients who are discontinuing, patients who have discontinued either their AI or their CDK4/6 for tolerability reasons, all really great opportunities for giredestrant off the bat. We are also exploring future combinations with CDKIs. And of course, we will also look into moving into the low-risk patient population.

We are hearing a tremendous amount of excitement on giredestrant from our physicians and from patients. And what gives us additional confidence in the fact that we will be able to disrupt this market significantly is the footprint that we already have in breast cancer. More than 5 million patients have already been treated by a Genentech reverse product. 50% of the physicians who we believe will ultimately prescribe giredestrant, we've already been in contact with. We have a robust plan for how we will think about access in the U.S., including patient assistance programs to clear those initial reimbursement hurdles.

And while it's hard to believe that it's already almost October, breast cancer awareness month is just about to start. And on that same day, we will launch a new patient awareness program to raise patient awareness, there is a new opportunity for them to seek treatment. And what I love about this program is the name. It's about damn time. because it is about damn time that we recognize what these women go through and the difference in the perception of what their treatment is and where they are in their treatment paradigm versus the reality and how giredestrant can help give them a better experience and ultimately better outcomes because that is what it's all about.

Now we do have some exciting new trials to announce for giredestrant, as I'm sure you saw this morning. We obviously have our intermediate to high-risk trial, which we have already talked -- or I'm sorry, we have our all-risk AI intolerant trial, which we've already talked to you about, the all-risk upfront switch. But we also have 2 new trials that are just coming. So today, I'm happy to announce the AFT-70 NAVIGATE study, which is in collaboration with the Alliance Foundation Trials and Natera, which will use MRD-guided diagnostics to personalize treatment based on ctDNA status.

And then just this morning, we announced a combination study with Pfizer CDK4 inhibitor in intermediate to high-risk patients. And this study expands on our ongoing single-arm lidERA studies with abema and ribo to explore giredestrant in combination with CDK4/6s. So you'll hear more about this from Levi in a little bit, but we are confident in the profile that we are launching with lidERA. We know we have the right footprint to make that launch a success, and we're actively putting the things in place to ensure that we'll be able to maximize the success of giredestrant going forward.

So now let's talk a little bit about fenebrutinib. So fenebrutinib, our BTK inhibitor in MS has the potential to be the first high-efficacy oral therapy for both RMS and PPMS. And I think there is one key point that's actually really worth emphasizing here, and that is that MS is a disease that is characterized from relapsing to progressing. And fenebrutinib is the first and only BTK that has positive Phase III data in both settings. And RMS, fenebrutinib achieved the lowest ARR rate seen in Phase III trials to date, paired with consistently positive trends in reducing disability and progression versus teriflunomide.

And in PPMS, it's the first and only medicine to achieve a numerical benefit in cCDP12 in a head-to-head trial against standard, which is OCREVUS. Over the course of the last number of months, we have spent a lot of time talking to our KOLs about what they're looking for in new medications. And one thing is very clear. They are especially interested in therapies that can both prevent relapse and progression. So taken together, we believe that fenebrutinib is extremely well positioned to have a very solid launch and to once again redefine what great treatment means for MS patients.

So let's quickly touch on Enspryng with a differentiated risk-benefit profile in both MOGAD and TED. So this is a great example of how we leverage pathways across our entire portfolio, bringing assets into different pathways based on their mechanisms of action. Now Enspryng, as you know, is an IL-6 inhibitor, and it is maximized for -- it is designed for maximal signal inhibition. And that has turned out to have great efficacy for both MOGAD and thyroid eye disease.

So we are extremely excited that we are going to be able to bring this to you, hopefully, by the beginning -- we have our PDUFA for TED in October, and then we have MOGAD at the beginning of next year. So some very exciting new indications for Enspryng.

And now finally, let's pause with establish because this is where we have some of our most exciting NMEs that we are working on that truly have the opportunity to be disruptive across the largest areas of unmet need in the global landscape. So we all know that Roche has a long history of entering into new disease areas successfully. In the last 10 years, our medicines rewrote the textbooks in MS, hemophilia, SMA and in retinal diseases. In the next 10 years, we intend to do so in a whole new suite of diseases from IBD to Alzheimer's to obesity, type 2 diabetes and hypertension.

So of course, we recognize that these are different types of disease areas that we have been in, in the past. We recognize that the scope and scale of these is different. But that is why we have been investing ahead of our pipeline in our commercialization capabilities to make sure that when these trials read out, we are capable of bringing them to patients around the world who are waiting.

So let's start quickly with trontinemab. Trontinemab has the potential to be a best-in-disease treatment for Alzheimer's, where there is a clear unmet need. And in combination with our diagnostics organization, we believe we can truly revolutionize care here. So for instance, our new Elecsys pTau217 blood test makes diagnosis faster and easier and more reliable and is far less invasive than traditionally used. And let's not forget, and it's kind of surprising to know this, that 3 out of 4 Alzheimer's patients are actually undiagnosed. So there's a huge diagnosis problem with AD. And largely, that's because you don't have great or easy diagnostic solutions. and treatment opportunities have been quite limited. When you have both of those things together, the opportunity to unlock that disease area really reveals itself.

We believe that tronti has the opportunity for true differentiation, both from an efficacy and safety as a next-generation amyloid antibody. The Phase III trial, TRONTIER is now fully enrolled, and that is well ahead of our plan. And that speaks both to our efforts across R&D excellence as well as the extreme excitement from the Alzheimer's community, and we're looking forward to readouts in 2028.

So next is prasi. Prasi has the potential to become the first disease-modifying drug in Parkinson's. Parkinson's wins one of the few remaining white spaces in pharma, where there really aren't a tremendous amount of treatments and the current treatments that are on the market really only provide symptom relief, and that's only temporary symptom relief. So we've taken all of the learnings from our Phase II studies, and we've optimized our Phase III, and we're really excited to see what might happen here. So clearly, PD studies take a little bit longer. We won't see the results of this until 2029, and we continue to think of it as a high-risk, high-reward trial. But it's undeniable that if we were to see results that were positive with this Phase III that we would change the lives of millions of Parkinson's patients.

And then next, afimkibart, which is currently in Phase III trials, both for Crohn's disease and ulcerative colitis. We will get that first UC data expected early next year. Afimkibart has the potential to overcome the efficacy ceiling that we've seen with prior treatments and to have the -- and it comes with a very convenient profile. So we are excited about afimki in UC and Crohn's. However, we know we are also exploring it in other disease areas, which Larry will give you an update on later today.

But this is only our first entry into the IBD space. We also have a number of earlier assets, including a p40/TL1A bispecific and other -- a number of other programs in our early research and development. This is an incredibly deep area of unmet need and one where we have really seen an efficacy ceiling that has been hard to crack. We expect afimki to be the first one to make a run at that. And then hopefully, our pipeline will come in with even more revolutions for patients. And of course, we couldn't end our segment without talking with CVRM and where we are advancing that pipeline.

So last week, as Bruno mentioned, you saw the very strong Phase II results for enicepatide in type 2 diabetes with an HbA1c reduction of 2.65% at 48 weeks. So more of that on in Manu's presentation, but it's clearly something that we're really eager to play out. We are very proud of the Phase III program that we've built. We believe in the last number of years, we've built an industry-leading CVRM portfolio, which includes petrelintide, CT-996 as well as enicepatide and of course, the Phase II combinations of enicepatide and petrelintide.

Beyond this, we're developing pegozafermin for MASH, where it has the potential to be best in these in a new market with a strongly growing growth trajectory. And to round us off, zilebesiran has the potential to boost adherence via twice yearly dosing, offering continuous blood pressure control. And this trial, I have to say, is enrolling like gangbusters, which is a great indication of how excited the HCP community is about it.

So there's lots going on in CVRM. And from 2028 forward, we expect multiple Phase III readouts across the portfolio. So now let's quickly end with our future growth opportunities, and we'll talk quickly with a review of our updated consensus slide. So this is a slide that you're very familiar with seeing. I want to just quickly level set you here on what you're seeing. So the values are based on the post half year 2026 consensus numbers from the sell-side analyst models. The last time we showed this at Q1, we used the full year '25 consensus models. The time frame is still the same from 20 to 30.

So you can see that through consensus models, we see a biosimilar gap of CHF 6.2 billion. And you can also see where the consensus sees our sales growth coming from in that same time period with a CHF 16.3 billion number. Those things compare very favorably. If you look at where our growth is coming from with our on-market portfolio, Vabysmo, [indiscernible] sort of lead the pack here. And then when you look at the pipeline, you see relatively modest numbers in there for quite a number of programs that we're talking about.

And then in terms of potential upside, there are a large number of our programs that aren't even represented in these models yet, which again provide significant additional upside. So this is why we feel very confident that we will continue to grow through the end of the decade and beyond. So this is a new slide for us. We're sharing with you our 2027 key news outlook. And you can see right away from looking at this slide that it is going to be a very busy year from a regulatory perspective. Our launch teams are going to be working on overdrive over the coming year. But we also have a number of important and exciting clinical results coming.

So as I've said in our previous slides, over the course of the last couple of years, we've shared with you a lot of plans. We've talked to you about what we're going to be doing. But what's important to know is that those weren't a vision on a piece of paper. That was a plan in action. All of those actions are paying off. Our pipeline is in a materially different place than it was. Our core capabilities, which were always strong, have been further strengthened and expanded to get ready for our new disease and launch areas. And our commercialization engine is revving up and is ready to go. We are excited to bring these patients the medicines that they need and deserve. And we're going to be thrilled to share with you the results of how that happens, the value that it creates and most importantly, the patient outcomes that it delivers.

And so with that, I'm going to turn it over to Levi. And I'm going to take Bruno's glasses in case he needs them.

Well, thank you, Teresa. Good morning, everyone. It's always a pleasure to be able to describe our progress in R&D performance at Pharma Day. And as Teresa mentioned at the beginning, it's now been over 3 years since we've introduced this enterprise R&D initiative here at Pharma Day. So in addition to updating you on the year-over-year progress, we'll, at various points, comment on progress made since we embarked on this journey back in 2023.

So the R&D Excellence initiative, as you know by now, has 2 overarching objectives. One is to deliver many more transformative medicines by 2030 so that we can easily achieve our pharma ambition of 20 such medicines by the end of the decade. And in the process, we want to achieve top-tier -- top quartile productivity across the biopharma sector.

Now the first big unlock for us emerged when we defined exactly what we mean when we say transformative medicines. And that archetype allowed us to develop an evaluative framework through which we could assess the transformative potential of every asset regardless of where it sat in our end-to-end R&D pipeline, but also regardless of whether it was an internal program or a business development candidate. And so of course, we call this framework the Bar. It has 5 key elements that are shown at the top of this slide.

Now I presented the Bar in detail in the past year, so I'm not going to walk you through each of these elements again today. However, the Bar has arguably become one of the most ubiquitous manifestations of R&D Excellence. Now over the past 3 years, we've implemented, we've fully operationalized the Bar so that it can recursively identify the programs that are worthy of investment and attrit those that don't. And we also reconfigured our governance around the Bar in general, but with a particular emphasis on focusing on those gating experiments that interrogate the crux of programs and also on designing clinical trials, especially late-stage clinical trials that are highly likely to be successful if our underlying hypothesis is correct.

So the ultimate goal here is for our end-to-end pipeline to consist entirely of candidates that either already clear the Bar or have strong potential to do so. So we've now implemented 6 solutions designed to improve our R&D productivity and most importantly, to be on track to achieve that pharma ambition. Three of the solutions are shown on the top, and those are the Bar, reconfigured governance, augmented external innovation. Those are really about boosting the effectiveness of our R&D engine. And then 2 solutions at the bottom, ambitious productivity objectives, evolving our R&D engine. Those were really about making the engine more efficient.

And then lastly, there was a solution that aligned employee and team incentives around this approach. So let's take a look at some of the results that we've seen from application of the Bar. So our clinical pipeline has certainly undergone substantial curation since application of the Bar 3 years ago, and Teresa introduced this, but we're looking at a more detailed look. So the numbers in red indicate attrition and the numbers in green represent additions. And you can see that we've had a lot of both.

Now some of the attrition is the usual ebbs and flows of drug development, but a lot of it resulted directly from the Bar assessment. And similarly, the additions have been quite deliberate and many of those come from business development activity. I'll come back to that later. But you can see that whereas we had over 80 clinical development candidates in 2023, we're down to about 65 candidates today. But of course, the goal here isn't actually to shrink the pipeline. R&D effectiveness requires sufficient shots on goal. So we certainly plan to grow the total number of development candidates again as we go forward. The idea here was to maximize the quality of the pipeline in addition to the quantity of the pipeline.

So now let's take a look at how we're doing in terms of pipeline quality. So we'll start with some very basic metrics, which we think support the premise that we are boosting pipeline quality. So as you can see on the left, the proportion of programs with best-in-disease potential, it was already reasonably good, but we're continuing to increase that percentage. And on the right, you can see that although the total number of clinical pipeline assets went down by 15%, our portfolio value projections have gone up substantially, and they're actually now really at an all-time high since we've been tracking this measure. And in keeping with that, you can see that our average peak sales have gone up by almost 80%. Our total portfolio value has gone up by over 70% since the year-end 2023.

Now here's some data we showed you at Pharma Day last year. So we're looking at a directional plot of team assessed PTS of programs going into pivotal trials on the Y-axis. And then we're looking at adjusted net present value of the new molecular entity on the X-axis. And so the light blue dots show programs that were initiated before implementation of the Bar and the dark blue correspondent program started after initiation of the Bar. And what we showed last year was an upward and rightward shift.

So in other words, we're seeing higher team-assessed probability of technical success and higher adjusted NPV after initiation of the Bar. But now we can add some NMEs that have moved into Phase III since Pharma Day last year. And as you can see, all of them are at or above the threshold that we set for ourselves that we want to see for team-assessed PTS headed into Phase III. Now you could say, well, some of these are not yet mapping all the way to the right on the adjusted NPV side. But as we add additional Phase III trials for new indications, line extensions, as long as those studies continue to have the same reasonably high PTS, the adjusted NPV will increase over time as well.

So overall, application of the Bar and these other governance reconfigurations and other measures, they seem to be having the desired effects of enriching our pipeline with molecules that have transformative potential and with pivotal trials that have a reasonably high likelihood of being successful. Now of course, the ultimate goal is to boost our actual Phase III trial success rates. And as you saw in several of Teresa slides, there's a lot of green checkmarks. So we're still early days, but it does look like we're starting to make progress on that front as well. And in fact, our numbers thus far this year of Phase III successes are tracking above 80%

Now another guiding principle of R&D Excellence from the start was that we would apply the Bar to identify and invest in exciting candidate medicines wherever they might be found, whether they're in our internal pipeline or in the broader biotech ecosystem. And indeed, bringing in great candidates through business development has been a substantial component of R&D Excellence. And the business development efforts have largely in the past several years, involved clinical stage assets, and there are a range of them.

I won't go through all of them, but they start with on the left side, the deal with Alnylam, which brought in zilebesiran that Teresa mentioned, that's our RNAi molecule against angiotensin for hypertension. The deal with Telavant brought us afimkibart. Of course, our acquisition of Carmot brought us enicepatide and also CT-996. You've got the Regor deal that brought us a CDK4/2 inhibitor, and then it goes on and on. Zealand brought us amylin. We acquired 89bio, which now brings us an FGF21 analog for MASH. And then, of course, in the past year, we had MediLink, which brought in the very exciting B7-H3 ADC and of course, a collaboration with Nurix for a BTK degrader.

So what you can see with these is that not only are they really fortifying our pipeline with medicines against foundational targets across multiple therapeutic areas, they've also really boosted the breadth of modalities that are going to be so important to drug these targets, and Teresa mentioned this as well. And there have also been some interesting platform deals, including Poseida, which brought in the allogeneic CAR-T modality.

More recently, we've had deals with DualityBio, which is focusing on novel antibody drug conjugates, Earendil, novel bispecifics. So we've always been active in business development. But this track record shows the results of an intentional strategy to augment our pipeline, and that strategy is anchored in the bar and then it's further shaped by critical choices within specific therapeutic areas and disease areas, as Teresa outlined earlier.

So now let's discuss progress towards our second objective, which is top-tier R&D productivity. And it's often helpful to frame this conversation using our so-called R&D productivity equation. And there are 5 key measures in this equation, the 3 in the numerator, volume, value success rates. Again, it's about R&D effectiveness, the 2 in the denominator, cost and cycle time, about R&D efficiency. And you can see that over the past 3 years, we've made significant progress in each of these measures.

So I've already talked about the sculpting of our clinical pipeline. But in addition to that, 47 assets have progressed into GLP toxicology studies across our 2 early R&D units. And so that should help enhance our early clinical pipeline further over time. Now I've already mentioned the increase in projected average peak sales from clinical stage assets as well as the increases in both team-assessed PTS and actual Phase III success rates.

But looking at the bottom, we've now allocated -- reallocated, I should say, a total of CHF 1.6 billion across the R&D enterprise to more directly support the pharma portfolio. And on average, we've reduced our end-to-end cycle times from lead identification to product launch by approximately 19 months. So that was progress over 3 years, but you can see here that a meaningful proportion of this progress occurred since Pharma Day of last year, whether we're talking about entries into GLP tox or reallocated savings or cycle time compression.

Now let me double-click on the cycle time topic for a moment because 2 years ago, you might remember, we selected 3 programs that we felt were exemplary of transformative opportunities, afimkibart, enicepatide, and trontinemab, and we created a onetime Fast Track Designation. And so that designation unlocked additional resources and front-loading of activities. And actually, each of those Fast Track programs achieved meaningful acceleration as a result. Those are indicated by dots on this slide.

But what we're seeing now is that the learnings from the Fast Track program and the successes that we're seeing are being applied along with other R&D excellence solutions to many other programs that were not part of the original Fast Track group. And so as a result, we're starting to see similarly impressive time savings for those programs as well. And so there are 2 examples shown on this slide, zilebesiran, which Teresa mentioned, and prasinezumab. And moreover, really a significant number of our recent Phase III trial starts are enrolling ahead of expectations. And this is exactly what we hoped to achieve as a side benefit of the Fast Track Designation.

So it illustrates how R&D Excellence is allowing productivity gains to impact multiple pipeline assets. Now there are multiple other efficiency-oriented initiatives stemming from R&D Excellence that I don't have time to describe today. But I will mention one very important effort that's currently ongoing, which involves the identification of many workflows across the entire drug development continuum. Now obviously, this has to be done thoughtfully because we're in a highly regulated environment with drug development, the regulatory requirements, but we are making good progress, and we certainly have high hopes for the potential impact of this on R&D performance.

So this is something we look forward to describing in much more detail at a later date. Now our enterprise R&D footprint in pharma is now nicely aligned with the critical existing and -- sorry, emerging global biomedical ecosystems. You can see this in the U.S., in CHFope and of course, China. Now recently, we had -- I think Bruno mentioned this, we had the grand opening of our Boston Innovation Center. That's going to focus specifically in CVRM, but also on applications of AI and ML and drug development.

Now in a moment, Aviv will describe applications of AI on the drug discovery side. And to support the expanding applications of AI really across the R&D continuum, we're doing a number of things, including building in-house data centers in both the U.S. and CHFope that together will house more than 3,500 NVIDIA Blackwell GPUs. So in conclusion, 3 years into R&D Excellence. Most of our proposed solutions have been fully implemented. Application of the Bar is allowing us to assemble a pipeline of assets with transformative potential, and our R&D engine is also becoming more efficient.

So our pharma ambition for the current decade is to launch 20 transformative medicines by 2030. We're more than halfway there -- or we're halfway there with the potential for 2 more approvals in the foreseeable future. And in our clinical pipeline, as Teresa mentioned, we have up to 20 NMEs that could potentially launch by 2030. And what's nice is these clinical candidates are distributed well across our 5 therapeutic areas, and you'll hear a lot more about that after lunch, of course. And as I mentioned, our portfolio value projections are at an all-time high.

And yet, as Alan will point out later, our ongoing financial discipline keeps us well positioned to do more deals exciting -- if and when exciting opportunities emerge. Now we're not done. There's actually a lot of work ahead to turn these pipeline molecules into medicines, transformative medicines and then to achieve sustainable top-tier R&D productivity. But we do believe that the evidence that we're seeing shows that we're on the right path.

So with that, I'll turn it over to Aviv, who will tell you about our drug discovery efforts and how AI is boosting those.

Thanks, Levi. So these transformative medicines, the ones that -- these transformative medicines, the ones that Teresa described, like giredestrant or fenebrutinib or Ocrevus or divarasib, they're really amazing. We know that because we discovered and we developed them. But we also know that discovering and developing these transformative medicines remains really, really hard. And it's not just the case in Genentech and Roche, and it's not just about one thing.

Every step in making medicines is hard. And all the steps have to align. It has to be the right target and the right medicine and the dose and the patients. And all these things are not just hard in the sense that they're time-consuming. Most of the time, they actually end up not succeeding. And that, of course, begs the question, why? Well, there's actually 4 specific ways in which biology and medicine are hard.

The first one is that all the numbers are huge. They're bigger than the number of patients or cells on the planet or the atoms in the universe. The second is that the system spans many scales from atoms to patient populations. The third is that we can measure this in many different ways, but not simultaneously. And then finally, everything is super varied. We never do the same thing exactly twice.

That's actually why it's so hard. It's hard to predict and it's hard to generate and to interpret and to execute all this work. So that's why it's hard to make transformative medicines. But very fortunately, all of these are also things that have the properties that make AI really, really relevant. Yes, the space of possibilities is nominally huge, but AI can reveal the true dimensionality. Yes, you have many, many scales and all the transformations are nonlinear, but AI can actually translate between them. Yes, you have these many, many different views, but AI can integrate them. And yes, you can't simply automate it, but agentic AI can operate autonomously.

And so the question is, can AI take something that feels almost intractable and most of the time fails and somehow make it better? So like any difficult problem, people usually argue about what's the most important thing. So some people will say it's all about the AI model. Some people will say, it's all about doing the right experiment or clinical trial. Some people will say, it's all about how you bring together all the data. And of course, they're all right, but they're all a little bit wrong. Each of these is necessary, but on its own, it's not sufficient.

What we need is actually to put these together in what we call the Lab- or the Clinic-in-the-Loop. So you start with an experiment, you collect data, you train a model. We use the model to define the next set of experiments and then we iterate our way through drug discovery and development. Now this is what we've been building in Genentech across the full arc of drug R&D, target discovery, drug discovery through lead identification or LI and lead optimization or LO, preclinical work and clinical trials.

And we've been on this journey for about 6 years now. And roughly speaking, our first 2 to 3 years were really about just building. Then while we continue to always build and iterate, we focused on deep deployment and delivery. And we're just about now reaching that point where you can start describing substantial tangible impact on the research portfolio and now starting into the clinical portfolio, and that's what I'm going to talk about today.

And so building and deploying this requires not just AI models, but many other interconnected investments and innovations. And so we established our science strategy in late 2020. We invested very heavily in internal capabilities, including new top-notch large AI teams. We built a center for large-scale iterative data generation. We consolidated a large computational sciences center of excellence. We established a lot of collaborations with NVIDIA and OpenAI and Recursion and Medra and Anthropic and others, and they span many things. Large-scale data generation, we have one of pharma's largest AI factories, as Levi described to you. And more recently, we started building autonomous AI-driven labs. And over time, impact compounds and grows.

So now we can start to look at where our pipeline stands. So over the last 3 years, our LI entries grew 2.5-fold. And those gradually transitioned to a 75% growth in our LOs and a 50% growth in our internal clinical candidates by the end of 2025, and we absolutely expect these numbers to look substantially bigger by the end of 2026, so this year. This means that the early increase that we saw in LI entries was not just volume. Volume is easy. It was high-quality volume because it became an increase in LO and it's becoming an increase in clinical candidates.

And there's 2 other important things that you should bear in mind. The first one is that this entire shift happens with nominally flat resources, which in real terms actually means a slight decline in resources. So we didn't actually grow these programs by spending more. And also, even though there's much higher volume, especially this 2.5-fold increase in LI, we didn't actually clog our pipeline. In fact, our cycle time in LI roughly halved during the same period of time.

Okay. You can also look at this in a slightly different way. So ultimately, any work on projects should lead to an impact on a portfolio decision. A critical contribution to a decision means that something from AI, an analysis or a prediction or a scaffold or a molecule or a modification was material or decisive. A supportive contribution means that AI and computation had a meaningful impact on our confidence in the decision, along with other things. And an informative contribution means that it was relevant information, but it was more peripheral to the ultimate decision.

So in the past full 3 quarters across all the phases and categories, AI and computation impacted in 1 of these 3 ways, 40% of our decisions and is steadily growing, and about 40% of these contributions were critical. And their nature along the pipeline, though, varies. So in target assessment and in Phase 0, the critical contributions are more common. But in LO, we see the largest impact overall with almost 70% of the decisions.

Okay. And so what I'm going to do with the remainder of my time is actually take you through illustrative examples of what's hiding under the hood that delivers these kinds of impacts that I just shared. I'm going to work step by step through the stages, and I'm going to start with target discovery and assessment, which leads to LI entry. So our increase in high-quality LI portfolio entries is based on a shift in a scientific shift in how we discover targets, and we use this thing that we call AI-enhanced pathobiology maps.

So in this kind of approach, we rely on an input of large-scale, high-resolution data, lab data and human patient data, and that includes a lot of things, genetics and disease atlases and perturbation screens and more, and also our whole trove of historical data. We put these into an AI that allows us to derive this AI-based disease model that we call a pathobiology map. And we also by now have an agentic system that allows our scientists to wade through the models and ultimately helps them generate pipeline targets at this unprecedented scale.

Now lab experiments follow in both large and complex bespoke ones and they can feed back, but that's not enough. Actually, we also needed a new organizational process that would allow us to operate in this way. We weren't used to operating at such volume. And so we established something that we call the TAP teams, which is a cross-functional system that allows us to ensure the target assessment is speedy, that it's guided by experts and that we direct resources in the right way.

Okay. Our first pathobiology map was for IBD, and we queried it originally for targets and target combinations that predicted -- were predicted to break the efficacy ceiling. And the first version of the IBD map was built over a year, essentially, between '23 and '24, and it relied heavily on human genetics and cell data. By now, we're multiple versions downstream. And in the next version, it incorporated a lot of spatial data from the patient's tissues, including from our own clinical trials, AI models that can find multicellular communities and agentic enablement.

And if this first effort took a whole year, just a year later, we built maps for 4 neurology diseases in 6 weeks. And by now, we have maps across most of our key diseases, and we continuously update them, and that's how we get to 2.5-fold growth in AI in 2 years. But the ethos of Lab-in-the-Loop is that you always have to iterate and be better. And for this, we innovate in several ways.

First, a couple of years ago, we leveraged the fact that we have these capabilities now in data generation to launch an initiative that we call foundational datasets for foundation models or FDFM. And in FDFM, we collect datasets not to answer just one biological question, but actually in order to get a better foundation model of the disease overall. And we invest in data collection and partnerships across different pillars, sequence to functions, perturbations with high-resolution readouts, patient tissues from key diseases, clinical genomics. And then we train our foundation model so that they can answer questions beyond the data that was actually measured.

So for example, in the perturbation realm, we can ask questions like in this disease, if I agonize protein X, what would happen to the tissues? Or if I want to shift the tissue from this to that, what should I actually be agonizing? And of course, there's a challenge that's hidden here. And it's the fact that it's actually really hard and it's sometimes completely impossible to really design upfront the most informative set of experiments that would allow us to learn a great model. And this is where something called active learning comes into play.

So I'm using here an illustrative test case where we wanted to learn a model of the impact on the whole cell expression of any of the 180,000 pairs of knockouts that exist in a universe of 600 phenotypically impactful genes in macrophages. So naively, this would require doing 180,000 pairs of perturbations and measuring 18 million cells. Instead, we're initiating just with 700 perturbations, and we let the model learn from them.

And then we perform the next experiment with 600 pairs that the model told us to run. And we compete this against simply choosing 600 random pairs out of the 180,000 in each iteration. So we do it for 3 iterations in this example. It's actually a very hard baseline to beat by computer science theory. And yet the active learning trained models outperforms every iteration, and it actually identifies cell states and gene programs that the baseline never covers.

Third piece is that we need to operate scientifically when there's all these data and tools and models, and there is no one size that fits all. And so this inability to standardize or automate has actually been a massive historical bottleneck. And this is where our agentic system called TargetNexus comes into play. It has access to all our tools and our agents and foundation models and foundational datasets and pathobiology maps and project data and our entire history of decision-making and projects from the past several decades of drug discovery.

And it assesses hypotheses across all the dimensions that are critical for drug discovery pipeline, causal biology, drug discovery, the context of the portfolio as well as the competitive landscape. And we're on track for TargetNexus to be part of 80% of the research portfolio decisions by the end of this year.

Now before I fully turn to the molecule making that comes next, I want to spend a moment on the transition or the interface between target discovery and LI, which can merge through essentially what we call AI-driven phenotypic screens. And so an example of this comes from our work with Recursion in the past few years. So in this example, we started with a very important well-known undruggable pathway in cancer.

We defined the cell state, and we set up a lab system. Then we took 250,000 compounds, small molecules and looked at their effect on the cell image called the cell painting assay, and we did the same also with the whole genome CRISPR screen, and we also took a whole genome screen and looked at the cells gene expression. AI turned these into 2 models, a PhenoMap and a TranscriptoMap, and also put those together and helped us identify not just gene targets, but actual compounds.

And by now, these compounds have passed multiple downstream steps through very high bar validation and discovery cycles, and it discovered both new biology and actually a radically novel mechanism of action that shows on-pathway activity on this undruggable pathway, and we confirmed it in vivo. This mechanism of action is so unusual, that I can absolutely say confidently and with a straight face that we would not have discovered it without AI-powered large-scale phenotypic screens.

Okay. It's great. But even a 250,000 compound phenotypic high-content screen is a lot to run, and there is way bigger universe of molecules out there. So we developed AI for high-content virtual cell screens. First, we trained a foundation model over compound screens with microscopy images or molecular profiles. These are things that were measured in the lab. Then we take a known important target or a compound that we want to optimize and we generate its phenotype experimentally.

And then finally, we run a virtual screen over billions of compounds with our model as an oracle to identify compounds that mimic the same effect. So again, an illustrative example. We use here a model that was trained on a 100,000 compound public screen, and we took one of our own PI3 kinase inhibitors to generate an anchor phenotype. Then we ran a virtual screen for about 4 billion compounds and synthesized 400 compounds selected by the AI out of these virtual hits.

And then we tested those back in the lab in 3 rounds of experiments of increasing specificity, cell morphology they cause, whether FOXO3A moves to the nucleus. And finally, direct biochemical inhibition of the kinase. And the results were really strong. It's not just that these are real hits. These are actually multiple novel scaffolds.

Okay. So with this, let me turn to molecule making. So here, AI, again, impacts every step, from drugability and target assessment, hit generation and expansion in LI, and the optimization cycles of LO. And I'm going to focus especially on small molecules today. I'm going to touch really lightly on biologics, even though we do just as much work there. And the same principles we also apply to peptides, to gene therapies, and to cell therapies.

So to start, AI is really crucial for identifying druggable binding pockets. For example, this is a proprietary model that we call Boltz-Jump, and we see it on the left, and it combines co-folding with AI-based sampling, and it generates a plausible ensemble of protein conformation. Then it supports the design and analysis of experimental data like HDX-NMR. That HDX-NMR guides the refinement of the conformational ensemble. And now we can bring again the pocket-finding algorithm on the refined ensemble to find more druggable pockets and repeat Lab-in-the-Loop.

Then on the right, you have molecular hit finding. Here, we start with a defined pocket already, and then we use other models. We have proprietary generative models like VoxBind that can generate molecular design that just bind into this pocket. We can go back to virtual screens with proprietary oracles like SAGE to score virtual molecules, not just for potency, not just optimizing binding, but also for their ADME properties. And then this approach can give us both acceleration and a new scaffold, which is what we see at the bottom. This is actually a first-in-class immunology target. We did it faster and we got to new scaffolds.

Okay. Then finally, this Lab-in-the-Loop means that we're not just iterating on the molecules, we're actually iterating on the model as well. So we can improve the model architecture over time. So for example, we can use the biochemical and biophysical assay data and all these protein ligand structure data from all these campaigns in order to enhance the model. We improved VoxBind to leverage synthesizability, that's a difficult to say word, and pharmacophore information, and we also gave SAGE a better ADME property calculator.

Now we turn to LO. So here, we can rely on active learning. You've seen active learning before with biology, now with molecules. And that improves the molecules and the model parameters in real time. But by real time, I mean each week. Each week, our models use new experimental results to guide the generation of new small molecule designs. And we also use the new experimental results to update our potency in ADME models.

So when we select a subset of designs for synthesis and experimental testing, we actually balance -- we optimize the balance between improving the molecular properties for the specific project and improving the model performance overall for all projects. And in this example, which is a first-in-class neurology target, we simultaneously are optimizing for multiple properties, and we got both better molecules. These are these green dots that are accumulating on the top right panel. And we're also improving the model, which you can see by the improvement in the area under the ROC in the bottom right.

Okay. So overall, this first-in-class neuro target, same one. AI in hit generation allowed us to look ahead so that when we generate the hits, we don't just think about the binding. We also think about their future ADME properties and other properties that historically we would only get to much later. And then in LO, we used AI to rapidly assess almost 100,000 molecules in less than 35 minutes. And then large-scale compute also allowed us to look to about 1,000 compounds by FEP. And overall, we got not only a 40 -- sorry, a 40-fold potency improvement, but we also, at the same time, optimized the metabolic stability.

Okay. Now as you might imagine, this world of models and tools and data and project context and portfolio context and history is extensive, and it requires a lot of skills to operate through. Very similar to TargetNexus, we also have an agentic system for that. Now it's the project context, the SAR, the design goals, all the proprietary models and tools and data and history and legacy, and lots of skills and one agentic system harness reasoning and orchestration.

Now as I said, I'll be very brief on biologics. I will say the same principles in many methods, analogous methods apply there as well. I'm only going to highlight a couple of areas. So as you recall, when we use these pathobiology maps for target discovery and assessment at scale, it also means that increasingly, we have a lot of targets and a lot of ways to combine them. Now as a result of that, we actually have a growing set of biologics building blocks for the putative targets from our maps. And that means we can go to a lot of bi and multi-specific formats, and we can generate a lot of clinical candidates rapidly.

That's all great, but good clinical candidates also have to have low immunogenicity and good pharmacokinetics. So in this example, which comes from a series of immunology projects, models that were trained on past data help us predict that an arm would have high immunogenicity and poor pharmacokinetics in patients. We then define a broader sequence base that we can explore with actually scaled experiments, which weather the impact of different mutations on another key property that we don't want to compromise, which is affinity. This gives the model sufficient basis to then optimize the sequence again, so it retains the affinity, but it cleans up the immunogenicity and the pharmacogenetics (sic) [ pharmacokinetics ] risk.

And then our antibody engineers and our other scientists work with our internal knowledge marketplace and agent platform, overall called agency, that by now has many, many tools and skills and agents. And in this video, you can see our antibody engineers set a single goal: design me a better antibody. And from there, the agent runs a campaign. It grounds itself in what the lab already knows based on internal data. It processes the candidate designs with internal generative models, and scores each of them against 3 competing properties: binding affinity, immunogenicity and developability.

It delegates the heavier screens to subagents. These designs come back to it. It scores, it optimizes them across many competing antibody properties in one step. And it compresses all the sequential modular analysis into single optimization. And even though I'm a really fast speaker, I can't speak as fast as the video. And the video is slowed down from the actual action of the agent to the speed at which humans read.

So this runs and runs. In the end, it can zip up and send you a report, but why stop at a report? In fact, the agent can also send it to an automated lab for synthesis and cloning. And in this way, you will close the loop between design and experiments. So the agentic world is not limited to the virtual side of the Lab-in-the-Loop. It's becoming a growing part of the physical part, leveraging physical AI and where we have partnerships with companies like Medra and Anthropic to build those kinds of labs.

Okay. Now the ultimate test, of course, is never in research. It's not in the lab. It's in the clinic. And increasingly, this is where our programs are just starting to arrive. So an example is this biologic in oncology, which we believe is a first-in-class opportunity. This novel target was identified for multiple large-scale datasets in 2022, took about 1.5 years to figure it out. And then a molecule had an FPI early this year. LI to DevGo was around 18 months. And AI also helped us reduce the immunogenicity risk like I just showed you.

So this is, of course, not where the effort stops. This is where it really begins when we move to the clinic. But there, we also have to shift from modeling just molecules and cells and tissues to modeling the disease in humans. And this is crucial for interpreting trial results. So we start with a copious data from our own previous clinical trials to train AI models of disease phenotype and progression, which we then use in order to model the patients for the design and interpretation essentially of the next trial.

So for example, and with this, I will close, in geographic atrophy, 3D OCT imaging for more than 2,000 patients from earlier trials allowed us to train AI that predicts lesion growth. Then we use the model to assess what would be the disease progression for patients as they enter the trial, and this allowed us to correct for any baseline differences between the study and the control arm. And this is illustrated here actually with retrospective analysis on the lampalizumab Phase II data. It's painful to even remember this molecule. It was advanced to Phase III years ago. And years ago, those Phase III failed. This is what you see in the top, that's historical unadjusted analysis.

Now AI-based model adjustment, which we can do today, but of course, couldn't have done back then, would have allowed us to stop the program after Phase II. The power that is gained by this AI model is equivalent to a twofold increase in the study size. So we now, of course, use this model prospectively, but why stop there? We also use it to close the loop back to discovery. Based on the unique trial data and the model that we train, we define new progression risk phenotypes for GA, such as the ratio here between 2 features, which we then used in GWAS setting to map new risk loci. And those were not detected in traditional risk studies. And we, of course, add this as new input to our algorithms that construct the pathobiology map and close the biggest circle that we can to new discoveries.

So in sum, what I showed you is that our commitment to -- is essentially our commitment to AI independence in R&D. If you want to maximize the impact, you have to iterate. You need active learning and reinforcement learning and models and agents and experiments, you need it in the lab and you need it in the clinic. And this iteration means that you have to own the learnings and the improvements that AI can develop, you need to own the loop.

We need proprietary AI models, the ability to improve them, not just parameters, but architectures. We need agents and harnesses. We build them based on the best of general purpose AI, but they need to be experts in our domain, and we need to continuously learn from our work. We need a massive AI factory for training and inference. And just as much, we need real world. We need the real world of the lab in the clinic.

AI makes reasoning a commodity. And that actually means that the scarcity becomes lab and clinical reality. And this means multiple data generation streams, all at scale, building for iterations in the wet lab, having autonomous lab capabilities and above all, actually having the same thing: scientists and scientific organizations that are willing to embrace this kind of opportunity, and deliver more and better medicines for patients.

I'll close with this and turn it to Alan.

Yes, tough act to follow. What can I say? Yes, I can guarantee you my presentation is simpler, perhaps a little bit more intuitive, I guess. No, welcome. Thanks for coming, and thanks for being with us. I think really a great pleasure for all of us. Before I start, I would like to thank my colleagues. I think when I remember it well, Pharma Day 2025, the share price was on a different level. I have in mind the [ CHF 271 ]. Things have changed, and they have changed really based on tremendous work and effort.

And you've seen all the opportunities now that arise. So you're worried now because we all know that share price is driven by 2 things, pipeline progress. I think we have delivered that in a very impressive fashion. There's more to do. We all agree to this. Now a little bit on my side is now to give you a comfort on the financial results because we have to bring that together. We have to have pipeline progress on one hand, and we have to have great financial results to drive the share price. So let's see whether I can help with this.

Three points I would like to go through. One is, really, on one hand, scalable automation based on AI implementation, but also on the process transformation we're going through. Aviv, I think, has paved the way into this. I think, really, it takes really a whole system to make an improvement. I think we will improve the business process landscape quite significantly. That's what we're going through. And I would argue, set a platform for AI application. I think that will help us in the foreseeable future.

The second point is capital allocation that I will go through. And last but not least, the project that we all went through with the R&D leads, the cost assessment that we have done on the R&D side, which was very helpful, helped us to find additional funds that we can put into new innovation, but also helps us to mitigate potential R&D cost increases.

So let me start with the AI strategic framework. And I just want to put it into the context of what Roche is doing at the moment on the AI side. We have 3 levers. One is EverydayAI, where we embed AI technologies in our daily work to increase effectiveness. Then we have Reshape. This is what I'm going to talk about. This is where I will focus on today with ASPIRE. It's an ERP program, where you might say, oh, that's an S/4HANA implementation. It's not the case. It's really a complete business process transformation that we're going through.

And then last but not least, the big ideas and the really big ideas you've heard from Aviv already, and you've got an impression what we work on this. What we are really after, you see on the right-hand side, I think value and impact, key element. People and change. Certainly want to improve the tech offering. And then we would like to put that into a context of good policies as we speak.

Good. Let me make a quick comment on ASPIRE. And this is an enterprise-wide business process transformation that we are going through for multiple years now. Major point is we are now in deployment. And I can even say that end of this year, I would argue pharma is basically done, which is certainly very helpful. Why? Because we are building a unified standardized digital backbone for the company as a whole. We will harmonize the master data and the processes onto a single core system, as you can see on the slide, really in the middle.

How do we do that? You see on the left-hand side, we have 11 master end-to-end processes that we are focused on. And to really standardize here, we standardize and harmonize more than 1,000 process activities. These are subprocesses, if you like, in the system. I think really very clearly opens the door very, very well for putting the data into the cloud that we have done already, at least for those affiliates that we have implemented and deployed.

I can also say that we are really co-innovating with some of the players that you see on the slide, predominantly with SAP for cloud solutions. And here, I can mention the [ clinical ] supply management, but I can also mention the batch release tools, where we set the standard in the industry. As said, the status looks good, as you can see on the right-hand side, I think corporate 100% deployed, pharma, 80%, end of this year. And then we have, as a remainder, diagnostics, which will take us about 2 to 3 years until this is done. And then finally, the project is finalized.

A little bit of a deep dive on the status. You see that on the left-hand side, 118 company codes deployed out of 273. That's basically the number of companies, if you like, that Roche has as a group. 950 process activities enabled. What is key to me is the template adherence. It's 98%. That means it's not like that we now customize everything for every affiliate, where really I think we allow really not many exceptions. Sometimes they're necessary, but very, very clearly, what we want to get to, to a harmonized and standardized environment, I think we get to this.

So as said, key is that you did bring data processes and systems together allows you a much better application of AI will trigger gains for the foreseeable future. Will they come through right away? No, they don't. Because you deploy, you have to change the processes, there is change management necessary. You still have workarounds. But then you do the next step, you optimize it, you potentially put AI on top and that delivers the efficiencies moving forward. That's why we say the gains will be realized in 2 to 5 years from now, and it will really be an ongoing process.

Good. With that, I come to capital allocation, switching gears quite a little bit. And let me start really with the cash flow. I think on everybody's mind, and that's what I'm really in love with. You could argue, am I really in love with my wife? I'm really in love with cash flow. That's what I can tell you. We have really here, you know that slide, really the net debt level for the last 5 years. When you look at net debt, in 2021, really CHF 18.2 billion, in 2025, year-end, CHF 16.2 billion. So pretty stable. That's the first takeaway.

So really, I think what happened in between really matters. And what you see is the operating free cash flow, that was really averaged annually CHF 17.4 billion, and that contains CHF 12.9 billion in R&D investment, CHF 3.6 billion in PP&E and CHF 1.14 billion in intangible assets. Then you see the nonoperating free cash flow, with the taxes and the treasury. That's what we have to go through. And then the dividend that you hopefully like with CHF 8 billion per year.

I have to mention it, 39 dividend increases in a row. If this year goes well, and that's how it looks like, we will get to the 40th consecutive dividend increase. When you look at the business development, we deployed on average CHF 4.6 billion annually. And I think that's really a number you should really have on your mind, so roughly CHF 5 billion per year. You see really that we've outlined the business development stuff, so intangible assets because that's already implemented into the operating free cash flow. That's why it is really in this dotted box.

But when we put it together with the M&A activities, CHF 3.2 billion per year, you really get to that roughly CHF 5 billion per year. So what we can say here and take away from that slide, and that's the message, I think the financial flexibility for us is roughly CHF 5 billion to CHF 7 billion to do M&A without increasing the debt level. I think that's really -- that's the message here. And that's what we can really operate from. And even you could say now, oh, Alan, net debt has certainly a liquidity and cash element, which is true. But when you compare then the gross debt level from 2021 to 2025, that is also stable. So my message remains valid here.

When you go to the P&L and when you really go to group sales, core OP and the margin at the very end, and I know you're all big fans of the margin. First, I have to say for the sake of completeness, yes, we have here the development in constant rates, but we also have it in Swiss francs. So you have both views here. Very clearly, operating performance is measured in constant rates. Let me emphasize this.

So let's start with the sales growth. And you see really, as we came out of that period where we lost exclusivity on Avastin, Herceptin and Rituxan. And then certainly, we went out of the COVID period, I think really the increase in sales, 7% in CER in '24 and 7% in 2025. When you then look at the core operating profit growth, I think it's quite striking that we had in 2025, a growth of 14% and in 2020 -- sorry, in 2024, 14%, 2025 of 13%. And I think that really exemplifies what Levi has said, the cost discipline that we have applied all over, but also in R&D. So very clearly, I think, a fantastic achievement.

And with that, certainly, the margin moved. The margin moved in 2024 by 2.1 percentage points, and in 2025 by 1.9 percentage points. Yes, I know you're not super interested about the past, you're more interested about the future. So let me say very clearly, we will defend the margin. And if the margin were moving, it will move upwards. Certainly, this is supported by the fact that other revenue becomes more meaningful for us.

As said, at half year, from roughly 3% on sales in 2026, it will go to roughly 5% on sales in 2030. And certainly, that gives us more financial flexibility. You see, very shy on the bottom, there are blue boxes. I think they support the long-term trends that you have seen in sales, plus 5% per year, that's the CAGR. Core operating profit plus 6% from 2011 to 2025, and a margin increase of 6.4 percentage points in that long-term time frame. So really, you see very sustainable development in Roche when it comes to the P&L. And as said, if the margin moves, it moves upwards.

With that, let's talk about something which is balance sheet-like, I would say. This is really now R&D plus CapEx. And why do I have -- what did I chose this, let's say, that setup? Because you all know we have committed $50 billion of investment to the U.S., which is in the middle of that slide. And that's why I'm going to start with from this $50 billion contains $35 billion of R&D investment, well, really, R&D expenses, so 5x $7 billion, I think -- and it contains $15 billion in CapEx. So is that something which is, let's say, stretching our limits? I wouldn't say so. That is anyway something we had in mind and what we wanted to invest.

Levi talked about the R&D center. Teresa talked about Holly Springs. I think there are quite some investments we're going through. When you look at the slide in totality, you see that we are pretty balanced with our investments. You see the U.S. in total, CHF 64 billion in the last 10 years. You see Europe with CHF 67 billion in the last 10 years of investment, and you see Asia with CHF 21 billion.

As we did a significant cycle of investments in Europe and also in Switzerland, we're now coming through a cycle in the U.S. So really, this is really well timed, if you like, and it was relatively easy for us to commit to the $50 billion investment in the U.S. as we are now going out of the investment cycle in Europe and into the investment cycle in the U.S. Certainly, Asia will play a role as well. But very clearly, I think you have a very balanced footprint, and we have further investment into innovation in the U.S.

When you look really at manufacturing, just to support what Teresa has said, because I got a lot of questions about, Alan, you're investing now so much money into manufacturing and the peptide plants and all of that, how is that playing out? Also here, really building on what Teresa has outlined already, when you look really on the left-hand side, and you see really the biologics network optimization since the loss of exclusivity for Avastin, Herceptin and Rituxan. And you see that we achieved a volume growth of 117% since 2018. And in the same time period, really COGS and period costs just rose 19%.

What I would like to emphasize is really the efficiencies that we got out of the system. And don't forget, this is already a period where we brought multiple modalities into the game. This is not the simple setup that we had in the past. This is already quite a complex setup, but it also shows there are significant productivity gains that we can work on. And I would argue we will do the same for the peptide manufacturing. I see on the right-hand side, peptide manufacturing strategy, very clearly will be built on CDMOs on one hand, in-house production on the other hand, very clearly. So I think really, we're comfortable with what we're going to, and you will see a very efficient production landscape moving forward.

Good. My last point is about efficiency in R&D. And let me outline here the pleasure. It has been -- I know it's a cumbersome project when you do a cost analysis and cost assessment. But at the very end, I think really we did it for patients, and we did it really for the sake of innovation because all the funds that we freed up, we reinvest in R&D. So don't think it will fall to the bottom line. It won't. So very clearly.

I think really what you see on the next slide is really, well, all the numbers that you have seen already, but they're split between the one-offs and then the recurring savings that we have achieved. The one-offs are very clearly driven by the portfolio optimization. These are the programs that we have stopped. This is where we applied the bar. I think -- and you see really these savings are significant for the time being. Certainly, they will slow down because, well, as we -- as you know, the pipeline has already achieved a much higher quality level than we have had before.

On the right-hand side, you see really the recurring savings. And what they're driven by, I will explain on the next slide. What is important, though, is that this will last until 2030. And these are just the measures that we have identified so far. And as you can see, that amounts to roughly CHF 2 billion, CHF 1.9 billion, that we would like to realize until 2030, and will certainly help us to keep the R&D cost increases in check.

So what's the -- what is that containing? What's in there? 184 initiatives identified in this, I would even say, historical activity. Let me go through them. I think best-fit operating model, 71 initiatives. This is about rightsizing organizational structures, aligning capacity to what we are really doing in the pipeline, efficient processes, that's what I've talked about, automation, standardization plays a major role here. But at the same time, it's also going against the overheads. It's not like that you just have overhead in headquarter, we also have overhead in R&D, and that's something we discussed quite well.

Then the best-cost footprint, I think there are opportunities to put really certain activities into low cost. And then the vendor and demand management, and let me emphasize demand management. I think really here, it's about drive next level sourcing initiatives through strengthened demand management and certainly vendor reduction. This vendor management comes so humbly along with the 29 initiatives, I can say these account for more than 50% of the savings that we have extracted out of this. So as said, we will reallocate these funds in the portfolio. And what we have done so far is explained on my next slide.

And you see that in that colored bar. Now certainly, all the savings altogether, roughly CHF 2 billion. And what you see is that CHF 1.1 billion went directly into the funding of development of external NMEs. I think Levi pointed to this. I think we did quite some transactions. Certainly, they trigger costs in R&D. We cover that. CVRM, I think, is a very prominent candidate here.

Then CHF 400 million was used to accelerate fast-track NMEs, trontinemab, enicepatide, afimkibart and giredestrant, just to name a few. And then CHF 500 million were invested in future capabilities like Lab-in-the-Loop, what Aviv talked about. So very clearly, I think we were able to put this money into better NPV projects. And as you've seen, I think the pipeline has really pivoted into a much better value frame. And yes, we won't stop with that.

With this, thanks for your attention, and it's my pleasure now to call my colleagues on stage to go for the first Q&A session. Thanks. I assume this applause goes for everybody who has presented so far. Oh no, surely not.

We'll start from the front row to the back. And just to remind you, please stick to the topics we have touched in the morning session. If you have pipeline questions, they will get in that airtime in the afternoon. [Operator Instructions] Let's start over there, ladies first. Luisa?

Luisa Hector from Berenberg. I feel like we've entrenched here to make it efficient for you. I have a really -- hopefully, the easy question is, do you expect an FDA Advisory Committee meeting for giredestrant? And then I have the bigger picture, trying to pull everything together, and it was really, really fabulous presentations. And I think eventually, my question is, when do drugs declare themselves? And will AI change this?

And here, I'm thinking about the value unlock. Is it Phase II, Phase III data? Is it actually eventually a little bit more on the commercial launch side? And I'm bringing into this, you've got the bar charts with the pipeline value increasing over time. But everything we've seen in that is largely, kind of, the assets pre the bar perhaps. So we've had the data on the SERD, the KRAS where you've raised your peak sales.

So we're looking at it a little bit now pre-bar with some post-bar in the mix, but also perhaps pre-AI. So when do you feel that drugs declare themselves? How might this change? And what is your level of confidence in that valuation of the pipeline today and how we should think about it when we meet again in a few years' time? Sorry, big question.

Wendy, do you want to answer the gire question?

Absolutely. Thank you for the great question. For giredestrant, we're on track with FDA discussions right now, and we're definitely expecting our PDUFA by November and December. So no AdCom.

No expectation. I think drug declaring sounds like an Aviv question.

I will at least start. I think, first of all, you're absolutely right. There is a lag time in this industry. It's just baked in. So whatever you're seeing from one part, you can draw a conclusion on any of the others and vice versa. The giredestrant was made as a molecule in the days before what we call modern AI. Having said that, machine learning methods were used way back then in the 2010s as well. So it's not without any computational contribution to it. That has existed for much longer. But you can draw a conclusion from that backwards into the things you saw there.

I think at first, these molecules will have to prove themselves in Phase I and Phase II trials before you could say it really worked, right? Because -- and you need more than one. The fact that one succeeded is that one succeeded. You need a certain volume of them in order to draw a statistical conclusion.

But I think it is not unlikely that someday down the road and that day is not now, you would be able to say, my confidence in things starts earlier than it has before. The better the predictive modeling, the more derisking you can do early, the higher your confidence in something becomes in this world where AI helps us predict better.

Today, we can't really predict that well, which is why we only believe things after 2 Phase IIIs or after 1 Phase III, depending on the indication. If we could predict better, we might be able to pull that earlier. It's not today. That's very important to understand. And it's not just about us. The data is not out there in the world yet to make that assessment.

I mean, I think Levi is always fond of saying at the end of the day. You can say it. I shouldn't say it for you. You still have to put it in a patient, right? You still have to put it in a patient, you still have to see if it works. And so you don't ever quite get past that.

Just to be clear, what I said was not you would be able to know that in research. It would be you might be able to have more confidence from less clinical data, but even then you would still have to run through all the trials. One should have humility with AI as well as with anything, the human body is an incredibly complex system on which we have very little data relative to its complexity. So I said the first problem we have is the big numbers problem. And so we have to be careful at overextending our confidence in AI as well.

We can move on to the next set of questions, Sachin.

Yes. Sachin Jain, Bank of America. I'll kick off with another big picture question for you, Aviv. So it's a great presentation, but I just have a really simple question. So could you perhaps pull out 2 or 3 points where you think what you're doing is different to competition? It's very hard for us to assess how that is different. So that's a big picture.

And then the second one is for Teresa on the giredestrant sort of launch dynamic slide. Could you just provide a bit more color on the patient assistance program? So in a recent topic of debate as to how much free drug you're going to put into the system and how we should think about that from a sales curve perspective. It's unusual to have heard that in oncology. So why you're doing that would be interested in.

And then 2 questions you may or may not want to comment on, pricing. Astra recently launched roughly $300,000 per year. Is that a rough proxy? And then on regulatory, are you confident you can avoid the ECG monitoring also?

I'm sorry, can you repeat the last one?

ECG monitoring, never seen for the competition.

I'll start, it gives her time to write. First of all, with the disclaimer, we -- I cannot tell more than you can what happens in companies behind closed doors. And in particular, I would emphasize that for the research domain on which we usually know the least. On the development domain, we know more. So this is my perspective. I believe it's correct, but it's based on this lack of basic knowledge that all of us share. And I would believe that it is in 3 different ways.

The first is actually the piece that I focused a lot in the first part of the examples, which is the biological piece. We do know that PTS critically, critically determines that actual PTS, the one that is about the results in Phase II and in Phase III, it depends on the target. If we are in the territory of first-in-class targets, we really don't know until much later whether we bet on the right horse.

And I believe that our investment in that, not just quantitatively, but also the style of approaches that we brought, both the experimental approaches and the computational approaches that go with them, and that iteration between them is definite. I believe it is definitely beyond the competition. In many of these areas, we are more innovative than the academic world is innovative in this domain. So that is one.

The second one is the algorithmic investment. Many, many -- I believe many of the peers do not really invest in the wrong algorithms. They either use algorithms that are in the public domains or ones that you acquire from another party, either through a partnership or as a piece of software that you acquire.

Now we do partner and acquire software, everyone does, but we develop also our own algorithms. And this is particularly critical because of the 2 points that I made that you have to update parameters and you have to modify architectures. And both of these things need to happen. We really do not know where this whole thing is going to plateau, but it hasn't plateaued just yet. So that is the second consideration.

And then the third one, which is the point that I made at the very end is that I deeply believe that you have to own the loop and the agentic world that we live in now, which was not a surprise for us. You can even see out in the public domain, we released some of the absolute first autonomous agents for the biological domain. And that is a learning system.

So if you use a system from the outside world through a partner, a piece of software that you acquire and so on, you can absolutely use it, but you can't improve it with your own knowledge. And that loop of improvement is absolutely critical. You also have limitations on what you would agree to show, with especially if you don't have 0 data retention, which is a problem, as you know, today in the AI world.

If you do not have ZDR, would you actually let another party see your history of portfolio decisions? Probably not. And if you want to then advance it with every portfolio decision, with every scientist that interact with it, with every shred of information that comes out of your lab, you have to own that. And I think our early investment in that is now bearing fruit for this purpose. So these would be my top 3.

Yes. And we invited Wendy to join us because her team is actually leading the giredestrant launch, and we thought there might be 1 or 2 questions about that. So I'll let her take that, and I'll pile on if needed.

Sounds good, Teresa. So getting back to your question in terms of how we think about the patient assistance program. But taking that back from one step further, right, in terms of how we ensure that we are product ready, right? So definitely, from a launch perspective, we do ensure that, a, supply chain, we're already given the demand that we're hearing from many of our clinicians, our clinical community as well as our patients. We're definitely ready for that. And given that this is a Part D drug, we do anticipate that we're going to have to see some of that payers block as we work through and hence, patient assistance program becomes key.

Yes. And that's actually pretty typical in a launch like this, actually.

Now on top of that, Teresa has also mentioned in terms of how we also build upon this launch. And I can tell you that I can't tell you how excited we are. We're all ready for this really -- the biggest opportunity for us at Roche. And when we see in terms of, a, the clinical community, the excitement that we have. We are building from a market readiness perspective, a, the disease awareness campaign that Teresa has talked about, it's about damn time, and that will be coming out live in the next couple days right at the time of Breast Cancer Awareness Week.

In addition, in terms of getting our clinical community ready, not only are we focusing on academic centers, we're also focusing on where the clinical practices are. And this is where majority of our early breast cancer patients reside. That is exceptionally critical as this is our first and only oral SERD that has been launched within the last 25 years, so exceptional opportunity.

I do wanted to mention that as we think about launches, it's very rare that you launch both in adjuvant and metastatic setting at once. In fact, I don't actually remember in my history overall when we look at oncology products that whether there has been any others right? So with this uniqueness, we are definitely ensuring that, a, the clinical community are heavily working with us to understand the patient segments, where we can truly offer benefits for patients as well as really building up the next level of evidence, as you will hear from Levi and also throughout the program as well.

Finally, our team is definitely ready. We're definitely investing quite a bit in terms of hiring, training and getting ready for our launch coming up in November and December. But not only is the giredestrant team being the ambassadors, everyone within here, together with the panel here are the ambassadors for giredestrant as we prepare for our launch. So we're all ready.

And pricing, we won't comment on. And monitoring.

Monitoring. So we've seen no evidence of QTc prolongation, so either as a monotherapy or in combination. So we don't expect any monitoring requirements.

Richard? Just to the first row, I think they can hand on for me.

Richard Vosser, JPMorgan. Maybe just one extra question for Aviv. Just you obviously highlighted the 1% to 2% probability that's there in the past and the complexity of human biology. So just thoughts on where that could go from the early experience that you've got in the research side, where could you take the probability?

Yes, I'll actually reflect slightly historically. So a couple of years ago, I was at JPMorgan, and I did a panel in some investor thing, Bruno might actually remember what it was. And we did it together with -- this was a public event. Did it together with a colleague who is the CEO of Generate, and we're all sitting there and mumbling the usual things, and we're actually in violent agreement because at that time, we still both believed very strongly that the impact on this biology piece is actually going to take some time. And that the impact first will be molecules.

And that -- I don't believe that anymore. And the reason for that is that I think that we have access now in the biology of the human and that the models are also a lot better than we thought they could become. And so the areas that we really see a benefit from is from the worlds are coming together. It might be also an add to the answer before, it's not just those 3 things. It's the fact that we're soup to nuts. We're an end-to-end organization. We're a big company. That is a big advantage in the days of AI. And so we can do discovery work, but we have data from our clinical trials.

And so this ability to be tied in to the ultimate clinical impact and have the layered information, all the levels of organization, from the atoms of the molecule all the way to the full patient, and have tissue from that patient and clinical imaging from that patient and peripheral biomarkers from the patient, and so on, allows us now to build models that are essentially like these massive translators.

And so even though on any given patient, we might not know everything, we start filling in the blanks and then the models become a lot more performant. It's far from a simple problem, and it's far from fully solved, but I do think its trajectory is better and faster than I thought 2 years ago.

Maybe just one more question. Just on the digital twin on the gross impact on the gross margin. So something that might be easier for AI models to help with just on that side of things, how can we think about the improvement in the gross margin going forward from that to 2030?

Should I?

Yes, sure. Go ahead.

Yes. Look, I think gross margin always was hovering around 80%. To be honest, I'm not in a position to say it will improve significantly with Holly Springs. I think we build Holly Springs as we move. Then we will optimize it. We will see where it goes. I think -- but am I -- how should I say it, am I concerned about the 80%? No, I'm not. I think we have hovered around this. Can we stabilize that? I guess that's the case.

Yes. I mean those efficiencies are real.

James, please.

James Gordon from Barclays. A couple more on giredestrant and one on fenebrutinib as well, please. So on giredestrant, I heard the comments about disrupting the breast cancer market. And also I've heard some comments about physicians liking longer-term data. So are there any good, like, analogs to think about what the launch might look like next year?

I think consensus is about CHF 0.4 billion. Is that something that's plausible in terms of how the launch might go? And how do you think about the merits of upfront use versus switching? Because you've got upfront use in lidERA, but then there's CAMBRIA-1 and EMBER-4 potentially coming fairly soon from Astra-Lilly. So might it appeal to you something where you switch first before doing upfront?

And then just the funny one quickly was that you've taken your target across both types of MS to more than CHF 3 billion. But how are you thinking about the product potential in RMS versus PMS? I know we've got some data coming up from another BTK next month from Novartis. Sounds like maybe they would look a bit better on disability, but maybe not quite so good or bad year adjusted on relapse rate. So what really matters? Is it the relapse rate or the disability? How have you thought about that?

I mean, both matter and both matter a lot actually. And so when you think about what a good drug looks like in MS, it has to deal with progression and disability. And I think that's where fenebrutinib, frankly, really shines. And so I think we are very confident in -- I'm just trying to think of a word that was other than excited because I used excited a lot today.

But we're very confident in the uptake in fenebrutinib. I think the clinical data were outstanding. I mean at above 50%, you just don't see that. The head-to-head against Ocrevus in PMS, again, PPMS. I mean that's practice-changing data. I think the consensus right now is hovering at like CHF 1 billion for fenebrutinib. We could get that in PPMS alone. So I think we're quite confident in the uptake for fenebrutinib.

Teresa, if I just may. As we showed before on the slide, the RMS data, 51% and 59% reduction in ARR. It's clearly the best of class that we have right now. And that matters a lot, especially for the early trial of the patients. And there is a huge opportunity to market. There's about 1/3 of the patients who are currently undertreated or not treated. So that's a huge opportunity for fenebrutinib.

But then on the PPMS side, so the progressive side, that's the other part of the equation. So patients who continue to progress or are over time progressing even under treatment, there's an opportunity there. So I almost can say on both sides of the equation, there's a huge opportunity for fenebrutinib. And we have to say, what other data has come out, we don't know them today. But we are very confident on our own data, that's a best-in-class BTK.

Absolutely. And then turning over to giredestrant, right, as we're looking at where we believe the consensus is on year 1 is very consistent where we think it is. When you think about the source of business in terms of looking at overall, right, we definitely believe that both the initial new patients versus those that are switching are both equally available for this. And if we're looking at across the segments where there are significant discontinuation rates for CDK4/6, tolerability becomes key especially for patients that you're looking at a long-term treatment.

So I think net-net, if you look at where the source of business is, we do believe that overall, it can be either/or, right? It doesn't preclude us from those that are newly diagnosed patients equally for the simplicity and the tolerability profile that giredestrant will offer through lidERA.

And maybe just to put a finer point on the trajectory of the curves, we expect it to look a little bit like a hockey stick. And I think the consensus estimates that we've seen are around CHF 600 million for next year, and that sounds -- we're comfortable with that.

Matthew, please?

It's Matthew Weston from UBS. Two questions, if I can. Teresa, in your comments, you mentioned that the trontinemab study is recruiting faster than you expected, but you never bring that 2028 readout date forward. What's the likelihood that we see data in 2027? It's just not possible.

And then on giredestrant, there's a big debate amongst investors as to whether or not Roche would do better on its own in early breast cancer with the launch that you are planning or whether or not the entry of competitors into early breast cancer with their data could grow the market in totality. And while you'll have a smaller share, there could be a bigger slice. So Teresa or the team, which would you prefer? Would you prefer to be there on your own for 3 years in early breast? Or would you rather have a competitor driving that market growth for SERDs?

So if you don't mind, I'd like to take that. I would rather be on my own, and I would rather drive it myself because I actually think we have a really phenomenal medicine that is clearly more targeted, more potent, combinable. It is a really impressive medicine. And I think once physicians get it in their hands and more importantly, once patients begin to experience what it can do for them, I think we will be able to expand that market ourselves. That's just me. And no, on tronti, I think we're still in 2028. But nice try. I like that. I like the optimism. You can join the R&D excellence team.

Yes. We're still not able to bend the laws of Einstein in time. It takes a certain amount of 18 months. We can't...

I think the margin would definitely go up if we could do that.

Maybe we do 2 more. One question each, please, for you, Graham and then James. And then I think we have to go to launch.

Graham Parry from Citi. So sorry, another one on giredestrant. So in terms of the cost and the margin impact into next year. So if you think about the launch costs with awareness programs and potentially free drug, is that going to be an incremental positive to margin next year or negative there? So a question for Alan there.

And then you also talked about the aromatase inhibitor population being switchable. So what percentage of that population do you think just doesn't do well on aromatase inhibitors and could be looking to switch? And how does that vary across community versus the academic center populations that you'd see? And then last one's on divarasib. Do you include adjuvant in your updated peak sales potential?

On the margin side? Yes, I think I've said everything about the margin already, I think. Defending the margin, either we stabilize it or it goes up, I mentioned the point about other revenue. I think we have a couple of things that are playing for us. So that's helpful. Honestly, I think nothing more to say at this stage. Is there a possibility for an increasing margin? Yes, there is, as we all know. But as we have a lot of investments on the other hand that we want to make and that we have to make. But very clearly, I think the probability for a margin improvement has increased.

And we've accounted for all of those costs in our launch planning. So nothing new there.

And I'll take the giredestrant and divarasib question then. For giredestrant, I think to your point, the different segments across academic and community might look different as well as across risk patient groups as well, right? So when we're looking across, we definitely believe that majority of the patients that will be switching initially will like -- or to be -- to switch over likely will be in the intermediate and as well as the median patient populations, right? Whereby, a, there's such -- there's high unmet need in the intermediate patient population whereby CDK4/6s are not available and where also the tolerability profile becomes important and as well as the clinical profile for sure.

I do believe that as we work towards really entrenching into the community, this is where the significant uptick will be because that's where the majority of these early breast cancer patients are lying. And then when it comes to divarasib, your question in terms of where there the expansion is coming from, definitely the data coming from K1.

And please come to ESMO to join us. We are in plenary session on the first session there, right? So the data itself really showcased in terms of the best-in-class opportunity for us, and that strengthens in terms of our confidence as we unlock primarily into the frontline patient population. Adjuvant is currently included as well.

I'll just make one more addition on your giredestrant. So after the break, we'll talk more about some of the trials that are ongoing to look at this, in particular, the question of even aromatase inhibitor and side effects that cause patients to go off aromatase inhibitors. I'm actually surprised at how often that can happen. And as you know, in lidERA, our disintegration (sic) [ discontinuation ] rates are even lower than the control arm. So we'll talk more about that after the break.

Yes. I mean I think we just cannot underscore how important tolerability is in this patient population, and it is why you tend to see such poor outcomes because patients don't stay on their treatment. And I think this is why we believe that giredestrant is going to be such a game changer.

So the final question goes then to James. One question, please.

James Quigley from Goldman Sachs. So I've got one for Aviv on AI in target discovery. So how confident are you that the novel target discovery platform -- how confident are you in the novel target discovery from the AI platform? Have you done any back testing to see whether for established targets, AI gets to -- highly established targets, AI gets to the same place? And also how important is the diagnostics business in terms of helping with data generation in your models?

Okay. So I'll start by saying what I also said in the answer to the first question, we will really only know for novel targets when we're in the clinic. We can't tell before then with any confidence, and we shouldn't. That's risky. And we shouldn't. At the same time, our pathobiology maps, these disease models, they're not just about novel targets. Sometimes the target is established and it's about the combination. Sometimes it's about figuring out the right patient population to go after, the indication selection. There's many, many things beyond novel targets, although there's -- they are absolutely part of the game. They're not the only part.

In addition, you often have a lot of targets that you would think are independent from each other in the traditional way in which people have worked, which lead to a lot of failure, not because the target itself is not meaningful, but because that unmet need has actually already been met. You just don't realize it was met by something else that is already in the pharmacopia. So being able to put targets into programs that operate together that can be distributed across multiple different kinds of cells and know how to choose and combine between them is just as important as completely novel targets, meaning the gene name was never known before.

To the second part of your question, which is about -- and a critical piece of that is we would spend a lot of time, not just we, Genentech, anyone would have spend a lot of time on doing a lot of work to even get a target like that to enter at LI. And all that time is resources and money and opportunity cost that is happening. Now that gets shrunk and you get to assess things really quickly, run them through discovery really quickly. And in fact, you have to be very innovative in the clinic at how to assess them really quickly in the clinic because you will have a lot higher volume.

Next, to your question about doing a retro essentially. The challenge with retro is that the base AI models that you use today are all contaminated by your prior knowledge. You can withhold from them Genentech's own prior knowledge, so you can play out on targets that we tried out and no one in the world knows about. But the moment that they show themselves out in papers, presentations, conference abstracts, whatever, forget about it during the other day.

In fact, just this morning, there was a story like that on another thing that people thought was a big discovery by AI. And oh, maybe in fact, you've got to see some human researchers using it along the way. That's not unusual. What we can do is that we can do a lot of assessments based on the history of our past decision-making. We have a lot of programs, like everyone in this profession, have a lot of programs that never made it. They didn't even make it out of research, forget about getting to.

And so that is actually a closed garden that models have never seen that the knowledge is only ours. And when we optimize TargetNexus, that agentic system that I showed, when we optimized it, that was a useful source of information for us, but only up to a point. You can only retro so much. So time will tell on novel target discovery. We have to balance between novel targets and existing ones, but even this balancing act is something that AI helps us do better.

Excellent. I think with that, we will close the morning session. We'll have 40 minutes for lunch, and then we'll meet again at 12:30.

[Break]

All right. Good afternoon, everyone. I hope that the conversations over lunch were fruitful. So as you heard at the introduction, this year, our oncology hematology presentations will be a dual act. We're thrilled that Matt Hellman has joined us earlier this month as Head of Oncology and Hematology Product Development. So Matt will cover the hematology side of the pipeline, and I'll start off by walking us through highlights of our solid tumor pipeline.

So let me start with an overview of the progress that we've made in both oncology and hematology over the last year. So on the left, you can see, you're reminded again, our 5 Phase III readouts that we've had since the last Pharma Day, all of which were positive. And those include 2 NMEs that have best-in-class potential giredestrant, of course, adjuvant HR-positive breast cancer and divarasib in the second-line KRAS G12C-mut lung cancer. Now on the hematology side, we also recently announced a positive trial for Lunsumio in second-line follicular lymphoma, and Matt will cover that in his section.

Now in addition to those Phase III trials, we've also advanced 2 oncology NMEs into Phase III in the last year. We'll be starting Phase III trials with Tam-Peli, our B7-H3 ADC small cell lung cancer. And then there's the bexobrutideg Phase III trial. That's our BTK degrader that's being done in collaboration with Nurix and it started enrolling patients last summer. So we, of course, continue to apply the bar, as I discussed this morning before lunch. And when you look at the 28 oncology and hematology NMEs in clinical development, over 70% have first-in-class and/or best-in-class potential.

And this bar application, of course, continues to go for our business development decisions. On the right side of the slide, we just remind you of the oncology deals we've done over the course of the year, and this includes a range of both asset and platform-based collaborations. So overall, good progress in fortifying and in progressing our oncology and hematology pipeline. So here's the solid tumor portion of our pipeline. And as has always been the case, we strive to ensure that our pipeline is sufficiently diverse in terms of both foundational targets in oncology and the breadth of modalities needed to drug those targets effectively.

And indeed, you can see a broad spectrum of modalities that are represented from small molecules and protein degraders through bispecific antibodies, next-generation ADCs, et cetera. So now, we'll go through a few of our solid tumor pipeline highlights. So let's start with breast cancer. We already talked a lot about it. But in recent years, we've expanded our scope, which historically was in HER2-positive breast cancer and to include hormone receptor-positive breast cancer, and those indications represent 70% of patients with the disease.

And for a long time, the therapeutic attention in the field has focused on a few specific foundational targets, in particular, that drive tumor progression. And those are the estrogen receptor itself, the PI3 kinase inhibitor -- the PI3 kinase pathway in general and the PI3 kinase alpha subunit in particular, which, of course, is mutated in up to 40% of ER-positive cases. And then there are the cyclin-dependent kinases.

So those are, of course, a big focus for us, but we also continue to address unmet needs of people with metastatic HER2-positive breast cancer, especially those who develop brain metastases, and we have a potent and brain-penetrant HER2 tyrosine kinase inhibitor for that purpose. So for the past several years at Pharma Day, we presented the biochemical and clinical case that giredestrant can be a differentiated oral SERD.

So giredestrant, as you know, suppresses the estrogen receptor activity, first by immobilizing the receptor protein, which prevents it from accessing chromatin and then subsequently, the estrogen receptor is degraded as a result. So this mechanism can produce a deep and sustained ER inhibition. And moreover, compared to other SERDs out there, giredestrant comes with the highest potency and the highest target coverage at therapeutic doses.

And what we mean by target coverage is, this is a composite measure of drug concentration, receptor occupancy and receptor degradation in human cells and tissues. So giredestrant has now shown positive Phase III results in both the adjuvant and the metastatic settings, and we'll start with the lidERA trial on the left. This was the first time that an oral SERD had shown positive Phase III results in the adjuvant setting. We had a 30% reduction in recurrence or death at the interim analysis.

And although the overall survival assessment was not yet mature, it was trending in a positive direction with a hazard ratio of 0.79 at 32 months. And so this magnitude of benefit puts giredestrant firmly in the range that's been observed for the combination of endocrine therapy and CDK inhibitor combinations. But unlike those CDK4/6 inhibitor combinations, giredestrant comes with a -- quite a favorable safety profile, as we discussed this morning. In fact, its discontinuation rates are even lower than those that are observed with standard of care endocrine therapy.

And a lot of patients discontinue the CDK endocrine therapy combo, 30% to 50% of patients discontinue because of toxicity. And then that discontinuation, of course, can lead to reduced efficacy. So giredestrant was filed with the priority review voucher in the U.S., and we expect a decision from the FDA in a couple of months.

Now the evERA trial, which is shown on the right, this was our positive Phase III study in the metastatic post-CDK inhibitor setting. And as we showed at ESMO last year, giredestrant conferred PFS improvements in both the ESR1 mutant population and the intention-to-treat setting. So giredestrant is also undergoing regulatory review in this setting with a PDUFA date in December.

So now we'll talk a little bit about how we're expanding our evidence generation program for giredestrant across several patient segments because this has come up a lot already, and I'm sure will come up in the Q&A later this afternoon. So on the left of this slide, you can see the studies that we've added in the adjuvant setting. So one of them is called the [indiscernible] trial. This trial looks at how well people adhere to giredestrant monotherapy and in particular, if they can avoid premature discontinuation due to the common side effects of standard of care endocrine therapy.

And this also will assess the feasibility of switching to giredestrant monotherapy after completing a CDK inhibitor-based treatment. And then a second Phase IIIb trial is called the novERA trial. So this trial looks at adherence and tolerability of giredestrant in patients who are forced to discontinue aromatase inhibitors because of those side effects. So aromatase inhibitors, there are often musculoskeletal and other adverse effects.

So sometimes patients don't stay on therapy. In fact, as many as 1/3 of patients may come off of their aromatase inhibitor at some point before they've completed the course of therapy. So this is really important to see if giredestrant can improve those kinds of outcomes and patient experiences really across the entire early breast cancer risk spectrum.

So those 2 trials were announced previously, but we're now adding 2 more studies in the adjuvant setting. One, as was mentioned this morning, is a study in collaboration with Pfizer. So in that study, we'll look at giredestrant in combination with atirmociclib. So this is not the existing CDK inhibitor. This is a first-in-class CDK4 selective inhibitor. And the idea here is that dialing out CDK6 activity could offer the potential to reduce toxicities associated with the current generation of CDK inhibitors.

And then, of course, with giredestrant, you could imagine a best-in-class type combination. So the Phase I portion, which is obviously to confirm that they can be given together safely, that will start in Q4 of this year. And we anticipate a quick pivot to Phase III if all goes smoothly. And finally, we expect to initiate a study that's sponsored by the Alliance Foundation Trials, the AFT cooperative group. And so this is a U.S.-based cooperative group. And this will also be done in collaboration with Natera.

So the idea here is to use ctDNA-guided optimization for endocrine therapy. So we've already mentioned several times, 30% to 50% of patients who are eligible for the current standard of care, which is a combination with CDK inhibitors, they discontinue because of adverse events. But more generally, approximately 90% of adjuvant breast cancer patients are ctDNA negative at the point that they would start treatment.

So the idea of this study is to see -- so if you have a patient who is maybe intermediate or high risk, but they are ctDNA negative, the question is, can they start on giredestrant monotherapy and you would only add a CDK inhibitor for the subset of patients who become ctDNA positive. And so the question is, is that kind of approach non-inferior to standard of care CDK-based combination. So this -- as you can see, we've already got a robust evidence generation effort across the entire early breast cancer spectrum.

Now in the metastatic cancer setting, we still have additional opportunities in the frontline despite the unsuccessful persevERA trial. We have the pionERA study, which is in the endocrine therapy resistant population. That population, by the way, constitutes about 40% of the frontline metastatic ER-positive population. And then we have the heredERA study, which is looking at giredestrant in combination with Phesgo in metastatic triple-positive breast cancer.

Now based on the learnings from both the persevERA and the evERA trials, we've adjusted the required number of events in both of these trials, both pionERA and heredERA. The idea is to increase statistical power for both of these studies. So now we expect these trials to read out in 2028. So we moved them to 2028. And then finally, on the early clinical development side, we're exploring giredestrant in combination with our own CDK4/2 inhibitor and more on that in a moment.

But now let's move to our PI3-kinase inhibitor, Itovebi. So we've, for a number of years, also been bullish about Itovebi here in Pharma Day. And as a reminder, it turned out in preclinical studies that not only is Itovebi a potent and selective inhibitor of PI3-kinase alpha as shown on the left, but the molecule also catalyzes the degradation of alpha, PI3-kinase. So that observation gave rise to the hypothesis that selective degradation of mutant PI3 kinase could produce a highly robust therapeutic effect, and we certainly saw that.

We saw strong clinical results in the INAVO120 study, aromatase inhibitor resistant could be seen in breast cancer, but the hazard ratio there for PFS was 0.43. And then as shown in the middle, there was a 7-month overall survival benefit observed. And discontinuation rates due to adverse events with the Itovebi regimen was -- they were reasonably low at less than 7%. So now we're awaiting the results of INAVO121. So that's a study in the post-CDK4/6 setting, which compares Itovebi plus fulvestrant head-to-head against alpelisib plus fulvestrant in the post-CDK setting.

And then in 2027, we expect INAVO122 to read out, which looks at Itovebi in combination with Phesgo in the HER2 PIK3CA-mutant setting. And then beyond that, we'll see INAVO123, which is the endocrine therapy sensitive population looking at the triple combination of Itovebi, the endocrine therapy and PTK inhibitor. And we expect in the future to go even earlier if everything works out that we have a Phase II trial, which is called neoTOV, which is the same triplet in the early breast cancer subpopulation that has PIK3CA mutations.

So Itovebi a lot happening. We also are exploring Itovebi in giredestrant combinations and other indications. And we also have an interesting castrate-resistant prostate cancer of Phase III trial, which we disclosed earlier this year. This is actually in PIK3CA wild-type patients, but it's based on a potential new efficacy biomarker. Okay, a few words about our CDK4/2 inhibitor, which is called GDC-4198. We in-licensed this molecule from Regor Therapeutics, and it's currently in early clinical development.

There's evidence from multiple sources that suggests that CDK2 cell cycle activity may provide an important mechanism of resistance to the current generation CDK4/6 inhibitors. And GDC-4198, so on the one hand, it's highly potent against CDK4, but it also exhibits substantial activity against CDK2. And on the waterfall plot on the right side of the slide, you can see that we've seen intriguing preliminary activity in the post-CDK setting.

So we're now looking at GDC-4198 in combination with giredestrant compared head-to-head with atirmociclib in combination with giredestrant in a post-CDK population. That study is called MoonROSE, and it recently enrolled its first patient in sort of -- in the Phase II stage. So we'll close out the breast cancer section with work that's ongoing in the HER2-positive setting. And unfortunately, despite a lot of advances in this segment of breast cancer, it's still the case that 30% to 50% of patients with metastatic HER2-positive disease go on to develop brain metastases.

So ZN-1041 is a highly selective brain-penetrant HER2 TKI. Unlike other HER2 TKIs, ZN-1041 is not a substrate for efflux transporters that's shown on the left side of this slide. And this may account for as high retention in the central nervous system. Now previously, we have described high response rates for ZN-1041 in combination with Xeloda and Herceptin in a China-only study. But at ASCO last year, we also shared results from the global patient population, and some of those data are shown on the right of the slide.

And these are heavily pretreated patients who were given ZN-1041 in combination with either T-DXd or Phesgo. Both combinations were feasible. They were well tolerated, and there was some encouraging, albeit early clinical activity. So ZN-1041 is now being studied head-to-head versus standard of care in a seamless Phase II/III design, which is recruiting very quickly.

So now we'll switch gears to our KRAS portfolio. And there's certainly been a lot of exciting innovation in the KRAS space, therapeutics targeting mutant KRAS, RAS(ON)-based mechanisms. But it's also the place that toxicity, combinability, progression to resistance, these all remain important barriers that we need to overcome. So across really all of our R&D units at Roche, Genentech and Chugai, we're building a pipeline of RAS inhibitors that encompass several different mechanisms of action and modalities.

And the goal here is to be able to deploy best-in-class molecules and novel combinations that could produce additional efficacy and tolerability improvements in the future. Now divarasib is our most advanced KRAS asset. We continue to see divarasib as a potential best-in-class G12C inhibitor. Certainly, divarasib compares favorably to the marketed KRAS G12C inhibitors starting in laboratory experiments, particularly when you look at potency and selectivity, that's shown on the left side of the slide.

And these same preclinical characteristics were borne out clinically in the Phase III KRASCENDO 1 study. So that's shown schematically in the middle of the slide. There, divarasib showed superior efficacy compared to the approved G12C inhibitors, including an overall survival benefit that already was positive at the -- its interim analysis. So the full data set will actually be presented during the presidential symposium at ESMO next month.

The next divarasib study to read out will be KRASCENDO 2 in frontline metastatic non-small cell lung cancer. And as a reminder, we presented highly encouraging Phase II data from the KRASCENDO 170 study, which are shown on the right side of the slide. So those were presented at ASCO back in June, and they reinforce the potential for divarasib to perform in this setting.

So I'll conclude the solid tumor oncology portion of this talk with a few words about Tam-Peli, which is our next-generation B7-H3 antibody drug conjugate, that we recently in-licensed from MediLink for ex-China development. And this ADC was developed on a MediLink platform, which is -- which basically leverages a dual release payload technology. So the linker is hydrophilic and it's plasma stable. So the release of the payload is minimized in the circulation.

And this is important because this has been a reason postulated for many of the current generation ADCs having more toxicity than we would like. And so improving that safety profile is critical, especially when we're thinking about combinations and moving to earlier lines. So Tam-Peli also carries a potent TOPO1 payload and the drug-to-antibody ratio, the DAR is 8 in Tam-Peli. And Finally, the target B7-H3 is actually expressed across a spectrum of tumors. And on the other hand, the expression of B7-H3 in healthy tissue is much more limited.

So this pattern of expression may offer opportunities to go after multiple indications outside of small cell lung cancer and lung cancer, et cetera. So we'll soon be starting global Phase III studies in small cell lung cancer, and we expect to expand to other indications soon thereafter. So these are the Phase III results from a Chinese population in the second-line small cell lung cancer context. These were presented at World Lung earlier this month, and you can see Tam-Peli confirmed actually significant improvement in both PFS and OS. It's the OS results that we're showing on the left of this slide.

And in keeping with this dual release linker payload design, the Tam-Peli safety profile is also encouraging. So that's what we're looking at on the right side of this slide. So first of all, Tam-Peli had a lower rate of Grade 3 or greater adverse events compared to the topotecan control arm. And then when you look specifically at interstitial lung disease rates, which is a very important toxicity concern in this setting, we saw 0 grade 4 or 5 events, less than 1% grade 3 events and a 4.9% overall ILD event rate in the Tam-Peli arm.

So broadly speaking, these ILD rates appear lower than what has been seen with other B7-H3 ADCs in small cell lung cancer despite the fact that patients that were enrolled in this trial seem to be more sick in general than some of the other trials. So overall, Tam-Peli is showing excellent efficacy and at least competitive safety, and this certainly offers promise as we move into other pivotal indications. So this wraps up the solid tumor section.

And now it's my pleasure to turn it over to Matt Hellman to take us through the hematology pipeline.

Kind introduction here. As others have mentioned, I have just recently joined Roche Genentech, and it's a real pleasure to be here. I hope you've heard so far why this moment is so important and exciting for our portfolio. And these are the sorts of things that really attracted me to join Roche Genentech in the first place. I think it has a really uncommon pairing. There's this long scientific legacy and an incredible long-term horizon for investment.

And those 2 things together, which don't often come together, offer an opportunity to build on these learning loops. You heard the concept of recursion, but this is happening in our portfolio, where we're constantly creating breakthroughs and then trying to beat that over again. Those are the sorts of things that drive me, and I think why Roche Genentech is so well suited to succeed in this moment.

And hematology is one of those clearest examples across our portfolio. And so I want to spend a little bit of time telling you about why this is so exciting. It's not just a concept also. This is real execution and action. With the track record of portfolio delivery, you can see where we have 30 years of bringing new molecules, new targets, new modalities into the clinic. So that track record is something we're incredibly proud of and eager to build on.

And you can see on the right, some really clear direction in terms of the key priorities within hematology with very focused efforts in non-Hodgkin's lymphoma, CLL as well as multiple myeloma, and I'll return to nonmalignant hematology at the end as well. And so if the first slide gives you a sense of where we're headed and our key disease focuses, I also want to take a step back and talk a little bit about the how.

What are the elements that inform what success is going to look like in hematology. And so as we reflect on some of the macro trends in hematology, I think there's 4 big ones that we should focus on. The first is novel modalities. Hematology is a space where new modalities often begin, whether those are antibodies or ADCs, cell therapy. And I'll tell you a little bit about Bexdeg is the next one of a protein degrader, where new modalities begin in hematology.

The second key theme, and this is a place that has been absolutely defined in hematology is Combinations. Multidrug combinations beginning from the earliest stages of chemotherapy use in children with leukemia, we're absolutely transformative, building regimens together to be able to achieve curative potential is actually the bedrock of hematology. And that model has been exported to other diseases. So it's a place in which hematology really shines.

But those 2 things together, new modalities with combinations also bring us to the third thing, which is curative potential. Hematology is a place where words like cure, normalization. They're not just aspirations, they're real ambitions. It's what's in our reach. And so there are some examples throughout our portfolio of where we're really pushing the bar towards achieving something remarkable for patients.

And the fourth element is the patient experience. This is a disease where things like outpatient experience, the auto-injector, low toxicity, getting drugs to where they actually need to be for patients can absolutely be life-changing. And so with that, I want to turn a little bit to our portfolio here. I hope you'll see, just like in the solid tumor portfolio, a real breadth of modality and targets, but also a longitudinal investment over time that represents our sustained commitment to hematology.

But I want to then deep dive a little bit into some of the places where we think we're most poised to change practice in the near term. So speaking of practice changing, let me double-click in non-Hodgkin's lymphoma. This is a setting where that pairing I mentioned, that sort of legacy with ambition really comes to life with CD20 targeting. So starting with DLBCL on the top. Just a few years ago, the POLARIX study established a new frontline standard of care for the first time in 20 years that there had been a new standard of care.

And we're aiming to push that bar even higher with SKYGLO, which I'll talk a little bit more about in the next slide. But we're also adding a new slide, EVERGLO, to this armamentarium to target on the elderly and unfit patients with a chemo-free study. In the middle, you'll see mantle cell lymphoma where we have pivotal data planned for 2027. And then at the bottom is follicular lymphoma, where we're moving Lunsumio-based regimens earlier.

And Levi had already mentioned the CELESTIMO study that read out just a few weeks ago, and we're excited to present later this year. But I hope to give you an overall flavor that this is a true franchise strategy for NHL, where we're building on anchors, we're putting complementary pieces together and aiming to move to the earlier lines to be able to improve -- improve outcomes for patients. So we've talked a little bit about the STARGLO study already -- SKYGLO study, excuse me. And DLBCL is a place of key leadership for us. So I wanted to spend this extra moment here.

On the left, you can see that progressive recursive increase in the standard of care. We've established new regimens by adding Polivy to the current standards and establishing a new frontline standard of care with Polivy R-CHP in 2023. And now with SKYGLO, we're aiming to raise that bar again by adding Columvi on top of that backbone. And on the right, you can see why we're so excited to do that, why this Phase Ib data gives us so much confidence, 100% response rate, 96% complete metabolic response rates and meanwhile, having a differentiated safety profile.

These are the sorts of things that allow us to be able to achieve outpatient administration and be able to continue to build the next standard of care in the years to come. I think there's 3 key proof points for SKYGLO. We're building on the single best standard of care with excellent efficacy and a differentiated safety profile that's enabling us to give a fully outpatient treatment, and we're excited as this is one of the key readouts for next year that you saw on Teresa's slide for the news flow to be excited about next year.

I'm turning now to Lunsumio, which is an intentionally advanced differentiated CD20 bispecific. It has a safety and administration profile that allows us to get TCE therapy to match the right patient in the right treatment settings. And there's 2 key diseases where we think that, that can really matter. On the right, you see second-line DLBCL where our SUNMO study showed a substantial improvement in progression-free survival, a hazard ratio of 0.41.

And this is offering a chemo-free, fixed duration, short-length regimen with also a very low rate of Grade 2 CRS, which allows us to give the optimal profile for this disease setting. And this is one where we filed and we're expecting a PDUFA date in February. On the other side, you'll see the CELESTIMO study, which I mentioned just read out 2 weeks ago, and we're excited to share that data later this year, hopefully. And this is another place where the indolence of follicular lymphoma is so important to be able to match the right drug with the right patients. CELESTIMO is distinctly more convenient, offering a fixed duration, far fewer steroid premedication and a simpler strategy for treatment with fewer injections and infusions.

But I hope across both studies, you'll feel this common thread, efficacy plus making TC therapy practical for patients. Levi had addressed the Bexdeg that we're so excited to have collaborated with Nurix earlier this year. And I want to tell you a little bit why we're so excited about it. CLL, obviously, is a place where we're proud to have leadership here, but the disease has been really transformed by BTK inhibitors over the last decade. But there is a real unmet need here, the clinical resistance problem.

About 70% of patients develop mutations in the BTK protein that limits the efficacy of the current BTK inhibitors. And so Bexdeg is trying to do something fundamentally different. It's a protein degrader. And so the ability to not just be sort of a cork in the bottle, but actually fundamentally degrade the protein allows us to circumvent those resistance mechanisms, both in wild-type and mutants and to be able to provide differentiated efficacy.

And so just to illustrate that, I want to bring your attention to that heat map on the left there because across the top, you'll see Bexdeg with all green. And that's showing high potency against all those forms of resistance, both wild-type as well as resistance mutations in CLL. And you'll see as you look down the rows, you see much more varied efficacy, and that's the covalent and non-covalent inhibitors in the marketplace, and you can see where those resistance mutations really matter.

But it's not just the resistance and the efficacy that differentiates us. I think even within the protein degrader class, we have differentiated selectivity, which you can see in the middle plot, which we hope will give us a differentiated safety profile. Similar to the other slides, this isn't just a concept. This is where real data and action gives us confidence. And what you can see on the right is data from our earlier phase studies that highlights just how potent this mechanism can be. We've seen 83% response rates, 22 months of progression-free survival. And all of this is across both wild-type and mutant disease.

You see the mutations along the sort of yellow bar on the bottom as well as CNS disease, which is in the green black asterisks at the top. So these 3 key features, we think can drive our enthusiasm is broad, deep, durable efficacy, differentiated selectivity that can give us differentiated safety as well as CNS activity. These are the sorts of things that we think are going to define the next big leaps in CLL. And to deliver that, we've already begun the Phase III DAYBreak 306 in second-line CLL, and we have additional combinations coming as we move towards first line.

I'm going to turn now to cevostamab, which I'll go through some data that we presented just last week at IMS. In multiple myeloma, this is a disease that has been really transformed by targets like BCMA. But what we hear from clinicians is that in the field, what they really need is differentiated targets, new targets to be able to raise the bar further. And that's exactly the story with cevostamab. It's a first-in-class bispecific targeting FcRH5. And this target is different in that it's expressed across nearly all myeloma cells, but it's independent of GPRC5D as well as BCMA.

And that differentiated expression profile appears to yield a differentiated safety profile such that in comparison with BCMA, we are not seeing that same degree of severe infection rates, and we are also seeing importantly the return of humoral immunity without continuous IVIg. And in comparison with the GPRC5Ds, we're not seeing that characteristic on-target off-tumor toxicity that affects the skin, hair, taste, et cetera.

And so again, this is not just another drug in this otherwise crowded market, but really purposely orthogonal target that's new and is ideally suited for combinations to come. And so you can see -- excuse me, I went too far. You can see that data that we presented just last week at IMS with, I think, a lot of clinical enthusiasm. This CAMA-1 data showed a response rate with cevostamab plus Pom-dex of 86%, deep responses, durability with a median progression-free survival that was not met at 20 months of follow-up and importantly, a difference in that safety profile, as I mentioned, 17% Grade 3 infections compared to much more than that with some of the targets that are already on the market and the return of humoral immunity.

So consistent with the enthusiasm that we've heard from clinicians as we presented this data last week, we're excited to move this forward and the Phase III CEVOLUTION study is already ongoing, and we have other combinations to come as we move into earlier lines of therapy. So I want to end here and talk about hemophilia. This is a place where it's one of the clearest examples of that Roche innovation, where we've already trained patients' lives, and we're looking to do it yet again to push that bar higher.

On the left, you'll see a little bit of the time line of where innovation has come in hemophilia that has been nothing short of life changing. For decades, treatment with patients with hemophilia meant recombinant Factor VIII, and that required intravenous infusions multiple times a week. You can imagine how burdensome that is, especially for children who are suffering with hemophilia. And especially with that the short half-life of the recombinant factor, it left them naturally vulnerable to bleeds in between those trough cycles.

Hemlibra came along and fundamentally changed that paradigm, replacing frequent IV therapy with a subcu. And many of you saw the auto-injectors come. This has enabled a very different life for patients, 80% of them experiencing 0 treated bleeds. And as Teresa mentioned, this impact was awarded the Lasker award just this year, which we're really proud of and the auto-injectors coming. But like so many of the stories you've heard so far, we're not stopping there.

Our ambition is to move even more patients into that bleed-free life and achieve something that qualitatively is different, something that hasn't been achieved before, which is hemostatic normalization. And I'll go through that a little bit in the next slide, but that's our goal with NXT007. And as you can see there, we've already moved this into Phase IIIs, 3 Phase IIIs actually, in fact, and this is another one of the key news flows that we'll hope for in 2027.

But to tell you a little bit about why we're so excited with this molecule, zemocimig, it is that we recognize that Hemlibra's efficacy has been transformative. But what it does often is to move patients with severe hemophilia into a milder phenotype. Zemocimig is designed to close the gap towards normalization. And on the left there, you can see the molecule and some very specific antibody engineering went into engineering a molecule that's 30x more potent than Hemlibra while also being able to deliver a molecule that can be given as an injection subcu infrequently about once a month.

And this is, again, towards achieving that bar of normalization. Much like many of the other molecules, the data backs this up. And I want to spend just a moment explaining this middle plot because it's precisely what we're after in terms of normalization. What you'll see in the middle are 2 horizontal lines that are dotted. That represents the lower and upper limit of normal for patients that do not have hemophilia, the thrombin generation that they experience as a "normal" person.

And what you can see in the purple and green is the pharmacodynamic effects of zemocimig in patients with hemophilia smack in the middle of the normal range. These are patients with and without hemophilia sitting right next to each other in pharmacodynamic terms. And that's translating clinically. As you can see in the bar chart all the way to the right, we're pushing the boundary even higher for bleed-free life now into the 90s. And so hemostatic normalization gives us the opportunity to achieve something very different than what's been experienced thus far, while simultaneously maintaining an excellent safety profile where we've seen no thrombotic events, no TMA thus far.

So, as I mentioned, we have 3 Phase III studies that are already underway. ZEBRHA-2, in particular, I want to point out is the first and only Phase III study that's going head-to-head against Hemlibra and giving us that opportunity to demonstrate how we're continuing to push the bar higher, and we'll look forward to data later next year.

So as I close, I hope what I've given you a sense for across these stories in hematology is that spirit and track record of continuing to push the bar higher. These are precisely the things that drew me to Roche in the first place. I'm so excited to tell you more as these years go of the progress towards that. But of course, it's not just in hematology, oncology, that spirit is characteristic to Roche. And so I know you'll hear more of that across the TAs to come.

And so with that, I'm going to pass the baton to Hideki, who's leading neurology to tell you about exciting things there next. Thank you.

Okay. Thanks, Matt. So I'm really excited to present to you our progress, our rapid progress in neurology at Roche. So Roche -- at Roche, we are the industry leaders in neurology, both in our on-market portfolio and our R&D pipeline. And how do we get there and how are we going to sustain that #1 position? We we're going to focus on the critical capabilities as shown on the left-hand side of this slide.

We have some unique therapeutic modalities, including Brainshuttle, which we're using in both Alzheimer's disease as well as in multiple sclerosis. We, in neurology, have a unique and productive collaboration with our diagnostic colleagues. And there, we have developed -- the diagnostic colleagues have developed a blood-based biomarker for Alzheimer's disease, which allows rapid identification of Alzheimer's patients as well as -- now for the first time, we're talking about preventing neurologic disease before it even happens in Alzheimer's disease.

So we're able to identify patients with this blood-based biomarker who are at risk of developing Alzheimer's disease, but otherwise completely normal. So we've begun a Phase III study in this population of patients called PrevenTRON. And finally, we continue to focus on our end-to-end disease areas, Alzheimer's disease and multiple sclerosis as well as in select breakthrough indications like Parkinson's disease, where today, there are no disease-modifying treatments available.

With these capabilities, we have built this pipeline, which is advanced from what you saw last year. I will highlight a few of these. First of all, as you heard this morning, we have filed for registration fenebrutinib for PPMS and relapsing MS. We have a number of Phase III readouts toward the end of this decade. And then next year, in 2027, we expect to readout for Enspryng in autoimmune encephalitis. The Phase II part of the pipeline has really advanced with multiple molecules for multiple sclerosis, Alzheimer's disease and Parkinson's disease. So compared to last year, the pipeline has become much more robust and diverse.

Let's dive a little bit deeper into fenebrutinib, which is our unique oral non-covalent reversible and very deeply penetrating BTK inhibitor now with impressive Phase III results. As announced earlier this year, and as you heard this morning, fenebrutinib is the only BTK inhibitor with positive results across relapsing MS and primary progressive MS.

And fenebrutinib was designed to address both the relapsing and progressive part of the biology of multiple sclerosis by targeting both B cells and macrophage microglia in the brain. In fact, if you look at the graph on the right, we've shown that fenebrutinib can decrease the activation of microglia by the concentration of IC90 greater than 90%. So in other words, we have near total inhibition of B cells microglia in the CNS.

Now I want to show you the relapsed CNS data that we've been talking about so much this morning with our Phase III trials of FENhance 1 and FENhance 2 in relapsing MS. And it's important to remember that in this study, the active comparator was teriflunomide, which by itself has effect on relapses as well as disability progression. And as you heard, we have a 51% and 58.5% reduction in relapses in this study. And in fact, the relapse rate that's shown here is the lowest ever reported for any Phase III study, and it translates to about one relapse every 17 years for the patient. It's really profound activity.

In the middle panel, you see a profound reduction in new lesions within the brain of 76% and 82%. And finally, in the right panel, we see a reduction in disability progression in the composite measure, cCDP. And in fact, when we pull the data from the 2 studies, we see nominal significance in reduction in disability progression. So again, this is over and above the active molecule, the active comparator, which is teriflunomide, which already shows a reduction in disability progression.

There's a recent publication in neurology that classify all the available treatments for multiple sclerosis into high efficacy, moderate efficacy and low efficacy based on relapse rate reduction. And based on this classification, fenebrutinib would fit into the high efficacy category. In fact, this will be the first and only molecule -- oral molecule to go into that category.

Turning to the PPMS study. Fenebrutinib is the only BTK inhibitor with positive results in PPMS. And again, we use an active comparator, Ocrevus, which by itself is a high efficacy treatment for MS and by itself showed a 24% reduction in disability progression in our Phase III study. So over and above that, we have fenebrutinib, which, first of all, met its primary endpoint of noninferiority to Ocrevus and in fact, showed a 12% reduction in disability progression in this study.

So with these results of effect of disability progression in PPMS as well as what I just showed you with RMS, we now have a molecule that has improvements in disease progression throughout the spectrum of multiple sclerosis. And therefore, we conclude that fenebrutinib effectively targets the underlying common disease biology of disability progression throughout the entire MS spectrum. Our MS strategy does not stop with fenebrutinib, and we have a leading early-stage pipeline with multiple next-generation approaches, including on the left, a brain anti-CD20, which is moving towards CD20, which is moving to our Phase II, sorry.

And on the right, we have an oral MAGL inhibitor, which is designed to enhance neuroprotection as well as to reduce neuroinflammation. And this now is in the Phase II study in combination with Ocrevus. As you heard this morning, with Enspryng, we had fantastic results on a disease called MOGAD, and I have now the pleasure to show you the actual results. MOGAD is a relapsing autoimmune disease where patients experience relapsing visual loss, cognitive decline as well as loss of ambulation. And today, there are no treatments available for this disease.

On the right panel is our Phase III results in a study called METEOROID, where we see reduction in time to relapse versus placebo of 68%. And this is highly significant. And not only in the primary endpoint, but in multiple secondary endpoints, including annualized relapse rates, MRI lesions and rescue therapy use, we hit significance in all these secondary endpoints. This was filed in FDA as well as EMA and FDA, we achieved priority review with a PDUFA date expected early next year.

Let's move to our Alzheimer's portfolio. Despite 2 treatments, as you know, approved for Alzheimer's disease, 2 anti-Abeta approved for Alzheimer's disease, there's a tremendous unmet medical need. We need better diagnosis of Alzheimer's. We need greater clinical benefit and efficacy. We need improved safety as well as we need improved dosing and administration. And with trontinemab, our Brainshuttle-coupled anti-Abeta, we believe we can achieve all of these, and I'll show you some data that suggests that.

As you heard this morning, our Phase III studies in trontinemab called TRONTIER 1 and 2 in early Alzheimer's disease has fully enrolled, and now we expect data in first half of 2028. And just to be clear, answering the question from this morning, the study is designed to set there's a 6- to 18-month dosing period for the last patient in. And that's why that 2028 date cannot come any earlier. And as I mentioned, we have started a PrevenTRON trial study, a prevention of Alzheimer's disease study in Phase III as well.

Trontinemab is connected to the Brainshuttle, which allows not only deep blood-brain barrier penetration, but also broad penetration throughout the brain. And that's shown in this mouse graph on the far right, comparing a non-Brainshuttle version to a Brainshuttle version, Brainshuttle- coupled version, which you see the green fluorescent highlighting throughout the brain. In our Phase II study, we've already shown best-in-disease plaque removal.

Now on the left-hand side, you see that 92% were below the amyloid positivity level at 28 weeks. And only that all patients, 100% of patients had amyloid reduction. In other words, there were no nonresponders to trontinemab in this Phase II study. On the right panel, open-label extension patients continue to show persistent reduction in amyloid for at least 1 year. Further, we see profound effect on fluid biomarkers, including pTau217 and GFAP. And in exploratory efficacy outcome, clinical efficacy outcome, despite the small sample size and the short duration of this Phase II study up to 6 months, we see encouraging clinical efficacy signals with less decline in 2 measures of cognition, CDR Sum of Boxes and Mini-Mental State Examination.

Further in this Phase II study, there are indications that we have potentially a best-in-class safety profile with really low ARIA-E. And why might this be? And we think it's related to the Brainshuttle. And on the middle panel, which is the mouse brain, with a Brainshuttle coupled monoclonal antibody targets the amyloid plaques, as you see in yellow, whereas if you don't have a Brainshuttle-coupled amyloid, targets amyloid within the blood vessels. And so we believe that because of the Brainshuttle allows the molecule to bypass the vasculature and therefore, reduce the amount of blood-brain barrier leakage and therefore, reduce the amount of brain swelling or ARIA-E.

In fact, that's what you see in the right table, which is from the Phase II study during the double-blind period, if you look at the far right column, 3.6 mg per kg dose, which is the dose we're taking into Phase III, there's only one case of ARIA-E, and there was an asymptomatic case within the Phase II study. So in summary, trontinemab has potential for best-in-class amyloid reduction, efficacy on cognition markers as well as safety.

Switching to the early pipeline in Alzheimer's disease, there is an exciting molecule called GSM or gamma-secretase modulator. This is a highly selective oral modulator gamma secretase, which has first-in-class potential in Alzheimer's disease. It alters APP or amyloid precursor protein and inhibits Abeta aggregation. In a Phase I dose escalation study on the right, we've seen encouraging biomarker results with dose-dependent reduction of the pathogenic Abeta 42 species up to 70%, an increase in the non-pathogenic shorter Abeta 37. And so we started a Phase IIa study in early Alzheimer's disease with data expected next year in 2027.

Another exciting molecule in the early-stage pipeline is an NLRP3 inhibitor. NLRP3 forms part of the inflammasome complex. And in Alzheimer's disease, this complex is a link between Abeta aggregation and Tau pathology. On the right-hand side, with another NLRP3 inhibitor, we show in a Phase I study in Parkinson's disease, a reduction in an important biomarker, CSF IL-18, which is associated with inflammation as well as downstream neurodegeneration, and you see a reduction in this Phase I study. Therefore, we started Phase II studies in both Alzheimer's disease and Parkinson's disease with this molecule.

I'll end with one slide update on prasinezumab, which is our anti-alpha-synuclein monoclonal antibody for Parkinson's disease, where, again, there are no disease-modifying treatments available today. As you recall, in the right-hand panel, we went to Phase III based on the Phase IIb PADOVA results, where in the L-DOPA subgroup, we saw a 16-week reduction in the progression of motor symptoms, as you can see on the right-hand graph. I'm pleased to report that the Phase III study called PARAISO has been rapidly enrolling, and so we expect data toward the end of this decade.

So with that, let me turn it over to Larry Tsai to talk about our exciting immunology portfolio.

Thanks so much, Hideki. Hi, everybody. How is everybody's jet lag doing? It's just about time for me to be waking up in San Francisco. So actually, this is pretty good timing for me. And so I'm Larry Tsai. I'm the Global Head of Product Development for Immunology, and I'm super happy to be here to give you a quick update on what's going on in Roche Immunology from the standpoint of our strategy and our pipeline. So hopefully, you're aware that Roche has a long legacy of innovation in immunology, including the first anti-CD20, the first anti-IgE and the first anti-IL-6, all of which continue to benefit patients to this very day.

We're very, very proud of this legacy. And so our immunology strategy aims to build on this by focusing on 4 strategic components. First of all, optimizing validated and novel pathways that are relevant to immune-mediated diseases. Second, developing rational combinations, including bispecifics to lift the efficacy ceiling for complex immune-mediated diseases. Third, using biomarkers to break down heterogeneity and identify endotypes that are more likely to benefit from treatment. And fourth, for selected autoimmune diseases, seeking functional cures through deeper or more targeted B-cell depletion to reset the immune system.

Our strategy centers around 2 end-to-end diseases, chronic obstructive pulmonary disease and inflammatory bowel disease, while also recognizing opportunities for breakthrough innovation in other immunologically mediated diseases because as I like to say, the immune system doesn't recognize anatomic boundaries. And so sometimes you really just need to follow the science to wherever the most potential patient impact is. And as you can see, our immunology clinical stage pipeline reflects our focus both on end-to-end and breakthrough innovation diseases. I'm not going to have time today to cover all of the programs that are on this slide, obviously.

But before I take a deeper dive into just a few of them, I want to briefly call your attention to our COPD pipeline, which targets both inflammation and muco-obstruction, which are 2 distinct pathobiological drivers of the disease. We are particularly excited about some of our next-generation bispecific molecules, including our IL-33xTSLP program in Phase I, which combines 2 foundational validated pathways in order to raise the efficacy ceiling across the entire range of COPD subtypes.

Now one breakthrough innovation area that we are highlighting again this year at Pharma Day is immune-mediated kidney diseases, which are the third most common cause of end-stage kidney disease. Chronic kidney disease or CKD, including end-stage kidney disease, affects about 1 in 10 people worldwide. It's associated with high morbidity and mortality, and it's even predicted to become the fifth leading cause of death globally by 2040. About 25% of lupus patients, about 50% of IgA nephropathy patients and about 30% of membranous nephropathy patients, all immune-mediated kidney diseases will develop end-stage kidney disease. And our pipeline in immune-mediated kidney diseases continues to expand now with multiple programs in lupus nephritis, membranous nephropathy, idiopathic nephrotic syndrome, hemolytic uremic syndrome and IgA nephropathy.

So it really has been a banner year for Gazyva, which received FDA approval for lupus nephritis shortly after Pharma Day last year. And since then has notched 3 additional registrational study wins in extrarenal lupus, membranous nephropathy and idiopathic nephrotic syndrome. Gazyva is, of course, our higher potency next-generation type 2 anti-CD20 that's engineered to be less dependent on complement-mediated cytotoxicity. That makes it better suited to diseases which are characterized by depletion of complement like severe lupus. Building on our experience with earlier generation anti-CD20s, Gazyva tested the hypothesis that deeper B-cell depletion, particularly at the tissue level, could raise the efficacy ceiling in diseases like lupus and immune-mediated kidney diseases. And of course, the whole emerging field of immune reset is actually based on the hypothesis that even deeper B-cell depletion can restore the immune system to a naive state resulting in a functional cure. And our own pipeline, including Lunsumio and cevostamab, continues to test this hypothesis.

So turning back to SLE -- sorry, not expecting on the slides. Okay. Well, turning back to SLE. So SLE affects 3.4 million people worldwide. Many of them are women of childbearing age. Many of them are actually women of color. And lupus can actually affect almost every organ system in the body, including the kidneys. In its most severe form, lupus nephritis actually affects about 50% of lupus patients, about 1/3 of them will actually go on to develop end-stage kidney disease. And actually, lupus nephritis itself is associated with high mortality, about 6x above the normal patient population.

So in the ALLEGORY Phase III study, Gazyva met the primary endpoint with showing a 4-point improvement in the SRI-4 index -- I'm sorry, showing a statistically significant improvement in the SRI-4 at 52 weeks with a clinically meaningful treatment difference of 23.1%. And additionally, Gazyva demonstrated statistically significant and robust efficacy over placebo across all secondary endpoints, including a 20% treatment difference on the DORIS remission score. So you can see that 33.8% of patients actually had complete improvement of their symptoms with Gazyva compared to only 13.8% with placebo. And so this was submitted then for -- to the FDA and to the EMA, and we are expecting approval before the end of the year.

Okay. But the Gazyva hit rate continues with membranous nephropathy. Membranous nephropathy is the most common cause of nephrotic syndrome in adults without diabetes and up to 30% of patients with membranous nephropathy will progress to kidney failure. In the MAJESTY Phase III study, Gazyva met the primary endpoint, demonstrating a 31% increase in complete remission compared with standard of care tacrolimus at week 104. Priority review was granted for Gazyva in membranous nephropathy with approval expected also before the end of the year. Hot off the presses, FDA approval was granted last week for Gazyva in idiopathic nephrotic syndrome, making it the first approved targeted therapy and the first drug of any kind approved for INS since prednisone was approved 70 years ago in 1956. It's been a long time.

The approval is based on the INShore Phase III study, which showed a 23% increase in sustained complete remission at week 52 for Gazyva versus standard of care of mycophenolate. INS, if you don't know much about it, is the most common primary kidney disease in children. 70% of patients cannot taper off of steroids, which are the current standard of care and of course, are associated with major side effects. Gazyva can potentially reduce the need for steroids in these patients, which is highly impactful, particularly for developing children and makes us super, super excited about this approval. With these 4 indications, Gazyva will be well positioned to become the treatment of choice in immune-mediated kidney disease.

But the good news goes beyond Gazyva as we announced last week, sefaxersen is the first antisense oligonucleotide with a positive Phase III study reported now in IgA nephropathy. Sefaxersen targets factor B production in the liver for selective complement suppression and because high factor B levels are associated with IgA nephropathy and are part of the pathobiology, sefaxersen treats IgA nephropathy by inhibiting factor B mRNA translation. In the Phase III IMAgINATION study, sefaxersen met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in urine protein creatinine ratio compared with placebo at week 37 in a prespecified interim analysis. UPCR is, of course, an indicator of early response. That's an accepted surrogate for long-term kidney function, and the data will be discussed with global health authorities and presented at an upcoming medical conference.

A little bit more about IgA nephropathy. IgA nephropathy is a major cause of chronic kidney disease worldwide. It's actually the most common primary glomerul nephropathy (sic) [ glomerulonephritis ]. And about 50% to 60% of patients with the disease remain uncontrolled even on advanced therapies. That's -- and about half of those of them will progress to kidney failure. As a result, there's increasing emphasis on early diagnosis and more aggressive treatment. The current treatment algorithm stratifies patients based upon UPCR with higher-risk patients receiving advanced therapies. Sefaxersen has best-in-class potential amongst the complement inhibitors, which are targeted to patients with more active inflammation at baseline or who are inadequately controlled on the therapies, which again represents 50% to 60% of patients. Sefaxersen actually also uniquely offers convenient subcu at-home monthly dosing, which may improve patient adherence.

Okay. We'll switch gears now for an update on afimkibart. Afimkibart is our anti-TL1A antibody being tested in inflammatory bowel disease as well as MASH and rheumatoid arthritis. TL1A, of course, sits upstream of and amplifies a range of inflammatory and tissue remodeling pathways. And thus, we believe in the potential of afimkibart to be a pan-immunology pipeline in a molecule. I'll give you an update on our IBD studies in just a moment, but first, a few updates on other indications. First, atopic dermatitis, where unfortunately, the VELARITE Phase II study did not meet the primary endpoint and thus, development activities in atopic dermatitis have been discontinued for afimkibart. Afimkibart was well tolerated with no new safety signals. And we, of course, know that TL1A biology is disease-specific with different underlying pathobiological drivers. Therefore, we do not believe that the atopic dermatitis results can be extrapolated to other diseases, and we remain confident in the potential of afimkibart to address a wide range of immune-mediated and fibrotic diseases.

Turning to rheumatoid arthritis. Enrollment in the dRAvite Phase II study is on track. A competitor Phase II study recently demonstrated activity in rheumatoid arthritis, but insufficient efficacy to support continued development. Now that was obviously a different molecule. So the read-through to afimkibart is unclear. But it's also worth noting that dRAvite, the afimkibart Phase II study is studying a more refractory patient population where there may be more potential benefit. Top line data are expected in 2027. And then quickly turning to MASH, the FIBROLITE Phase I study completed enrollment in 2025 and is expected to read out later this year.

Okay. A few words about IBD. IBD remains an end-to-end disease within our immunology strategy. 8 million people worldwide suffer from IBD. And although there have been significant advances in treatment over the past decade, the efficacy ceiling remains low. Only about 40% of patients respond to therapy upfront, only about 20% achieve longer-term remission. And even of those 20%, about 40% ultimately lose their response. Our AMETRINE-1 and AMETRINE-2 Phase III studies in ulcerative colitis are now fully enrolled with top line results expected in 2027. In addition, we are preparing to initiate a third Phase III study with an all subcutaneous induction and maintenance regimen. We believe that IBD patients and physicians want more choices when it comes to route of administration and care setting for delivery. And so offering both IV and subcu induction regimens offers maximum flexibility to personalize the approach and to minimize the overall treatment burden.

Turning to Crohn's disease for a moment, enrollment in the SIBERITE Phase III studies is also on track. And because IBD is an end-to-end disease, we're continuing to progress our early-stage pipeline of bispecifics built on an anti-TL1A backbone combined with other validated targets, including IL-23. Our SUNCREST Phase IIb study in ulcerative colitis for our p40xTL1A bispecific that was mentioned earlier this morning continues to enroll with data expected in 2027. Now this molecule combines 2 validated foundational and orthogonal pathways. And thus, we are excited by the potential of this molecule to break through that efficacy ceiling that I talked about. And this is only one example of several bi and multi-specific antibodies and oral therapies that we have in development as part of our longer-term IBD strategy. So that's a bit of a whirlwind, but hopefully, I've given you a sense of all the things that are to be excited about in 2026 and 2027 and beyond in Roche Immunology.

And with that, I'm going to hand the stage over to Chris to tell us what's going on in ophthalmology.

Okay. Good afternoon, everybody. So ophthalmology is generally considered within the 5 TAs to be -- probably one of the smallest, I understand that. However, as you saw from Teresa this morning, we have the highest growth rate over the next 10 years, well over 30%. So there's really a big opportunity. And we've seen in the last few years, we tend to punch a little bit above our weight with Vabysmo, not only in impact on health care systems, but really in improving vision for individual patients. So I'm really excited about the next 10 minutes just to talk you through a little bit about our pipeline and the progress that we're making towards our vision of preventing vision loss and restoring vision in those for whom prevention is too late.

So how are we going to achieve this? Again, fairly similar slide that you've seen with our other TAs. I'm going to talk a little bit in more detail about these first 2 approaches in the next couple of slides. So just briefly, we have approaches to address novel mechanisms of action and new indications addressing multiple disease pathways using multispecifics. We have an extended durability approach. So we strongly believe that there is going to continue to be an important opportunity to treat patients with extended durability therapies. There remains an unmet need there because of the amount of injections in clinics that are required for the current therapies. Susvimo is a good example, and I'll talk a little bit about the upcoming VELODROME study, which looks at 9 monthly dosing intervals.

And then as Aviv mentioned this morning, the importance of digital large volumes of data and our end-to-end collaborations there across the company. So specifically, super exciting. We've talked over the years about the millions of images that we capture in-house, the tens of thousands of patients worth of clinical data, genetics data. We talk about the thousands of biological samples that we can take. We've already been able to reverse translate some of those to identify new targets in our retinal diseases. And as Aviv also highlighted, we've used those to develop algorithms and specifically the geographic atrophy algorithm, which has enabled us to identify up to -- or to predict up to 50% of the future progression over the next year of patients who develop geographic atrophy.

Now we came into a little bit of a paradox as Aviv was talking through that, describing if we had this algorithm, we wouldn't have done the Phase III study. But then if we hadn't done the Phase III study, we wouldn't have got the algorithm. So I was a little bit confused. But I think it's important that we have the algorithm because it really enables us to identify these patients who are going to progress, which enables us to actually either halve the sample size of our trials because of the additional power or we can just accept the additional power and have a higher PTS for our studies.

So going into how we're going to -- how we take our approach to looking at novel mechanisms of action within retinal diseases. We actually take a very thoughtful step-wise methodical approach, looking at these what we've described as hallmarks of diseases, so angiogenesis, inflammation, ischemia and fibrosis. Starting with angiogenesis over the last few years, obviously, we've taken VEGF. We've added the Ang-2. Vabysmo has been extremely successful. You heard from Teresa, the #1 prescribed therapy in many countries around the world for both diabetic macular edema and neovascular AMD. We're continuing on the angiogenesis pathway. We now have a WNT asset in clinic, which is really exciting.

The second hallmark of disease, which we're looking at is inflammation, and I'll be talking a little bit more about this shortly. But we've taken again a very stepwise approach. We have Vamikibart in clinic, has been filed in multiple countries for uveitic macular edema. You've heard Teresa talking already this morning, and I'll mention it again shortly, that the VEGFxIL6 bispecific is in -- is entering Phase III. And we also have our trispecific antibody, which is in clinic. Further down the pipeline, we're addressing ischemia, which many of you will recall, we have a partnership through SEMAthera with a semaphorin target. And then even earlier in the pipeline, we continue to look at fibrosis.

Now looking at durability, the port delivery platform, again, I was secretly hoping that Teresa, for those of you are watching this morning, she pulled 2 devices out of her pocket. I was hoping she was going to pull a third, which is the port delivery system, but it's the size of a grain of rice. So it wouldn't have made much of a visual impact, but it certainly makes a great vision impact. And the reason I say that is because we actually now have 7 years of clinical data from this particular molecule from this particular approach, which is called Susvimo. And also, we have nearly over 95% of patients can go on a fixed 6 monthly treatment interval with Susvimo. So it's really a great asset and the port delivery platform can be used in many ways. We've recently gotten European approval also for Susvimo. In addition, we have Australian approval for Susvimo.

Now this is a unique platform. It's the first and only approved surgically implanted long-acting treatment for retinal vascular disorders. And importantly, it can be used for multiple additional assets. Specifically, we'll talk a little bit about the VEGFxIL6, which can also go in the port in the future. Early next year, we'll be releasing data from VELODROME, which is looking at fixed 9 monthly treatment intervals. So really continuing to shift the treatment durability paradigm.

And this is where we are with our ophthalmology pipeline. Three things I wanted to kind of share with you. Number one, we continue to replenish our Phase I assets. Number two, you'll see here in Phase II, and I'll talk about this in a subsequent slide, we have now entered Phase II with a complement factor B small interfering RNA in geographic atrophy. Number three, just to reiterate, we've entered Phase III with our VEGFxIL6 bispecific in diabetic macular edema. So looking at VEGFxIL6 specifically, again, this is one of our key hallmarks of disease targeting inflammation. As a reminder, IL-6 targets not just inflammation, but it targets leukocyte adhesion and chemotaxis, blood retina breakdown, blood retinal barrier breakdown, angiogenesis and it upregulates VEGF, which means it has a role in multiple diseases, including uveitis, retinal diseases and thyroid eye disease.

And as you can see on the right side here, we've filed and are eagerly awaiting within the next 2 to 3 weeks, the result of the Enspryng filing for thyroid eye disease in the U.S. with a PDUFA date on 15th of October, as you recall, that received priority review. So we're anticipating that. Vamikibart has been filed for uveitic macular edema in the U.S., EU -- and EU. And we've mentioned the VEGFxIL6 bispecific, but also we now have the trispecific antibody in clinic.

Looking at Vamikibart, just as a reminder, really, this is one of the most frequent causes of vision. Uveitic macular edema is one of the most frequent causes of vision loss in patients with uveitis, which is affecting patients, majority of whom are of working age. And despite immunomodulatory therapies, UME persists in about 40% of these patients and the current standards of care are steroids, both systemic and intraocular, which have severe side effects, including cataract, raised intraocular pressure. And if that continues, then patients develop glaucoma and sometimes require glaucoma filtration surgery.

On the right-hand side, you can see the pooled data from SANDCAT and MEERKAT, which is our 2 Phase III studies from last year, which demonstrate clear rapid improvements in vision of about nearly 11 letters. Importantly, the therapy was well tolerated with a low incidence of these important adverse events, including low rates of intraocular inflammation, low rates of IOP and low rates of cataract. We'll be presenting 52-week data in the next 2 to 3 weeks at American Academy of Ophthalmology.

The VEGFIL-VEGFxIL6 bispecific. This, as a reminder, is, as I said, just entering Phase III now, is compatible with the port delivery platform. And the decision was based on a number of elements here. Number one, on the right-hand side, you'll see the BARDENAS study, which showed that for Vamikibart, so IL-6 plus ranibizumab was superior to ranibizumab alone, so a 3.6 letter difference. And if you look at the bottom, in terms of the -- one of the regulatory endpoints, which is 15 letter gainers, you'll see that 44.7% of patients had 15 letter gainers on the combination versus 28% when given anti-VEGF alone. So we took the visual acuity superiority in addition to the Phase Ib, where we looked at some safety data, and that gave us the confidence to move the VEGFxIL6 into Phase III.

Now I just want to add an additional point here, which is how we're looking at our Phase III. You'll have heard for those of you who follow ophthalmology, which I hope is almost all of you, we see many companies talking about how exciting their products are, how much better they're going to be than Vabysmo. And then they go and compare their products with monthly ranibizumab anti-VEGF monotherapy or 8-weekly aflibercept, so 8-weekly anti-VEGF monotherapy. So -- which suggests to me that they don't have the confidence that their products are actually better than Vabysmo. We will be comparing our VEGFxIL6 bispecific with Vabysmo because we believe it's the best comparator, and we have the confidence. And so we're very much looking forward to these studies starting. I think this gives patients the best option because we're really into transformational therapies.

Moving on to Enspryng in thyroid eye disease. Hideki and others have spoken a little bit about the mechanism of action. This is just to highlight the disease as a reminder, it's a complex inflammatory autoimmune disease that affects 80% of patients actually of females with a median age of 43, so working age. Current treatments, which are approved globally, are therefore just to highlight the kind of the adverse events, which are particularly impactful, therefore, hyperglycemia, menstrual disorders, hearing loss and teratogenicity. And therefore, our data, which suggests in SatraGO-1 and SatraGO-2, which has the primary endpoint of improvement in proptosis, which is how far the eyeball sticks out as a relation to activity of disease. So about 50 -- just a little bit over 50% of patients improved their proptosis rate.

In the active arm and when you look at combined active and inactive patients, this was also consistent, and we see consistency of treatment effect in many other secondary endpoints, including the clinical activity score. Then on the right-hand side, if you look at the adverse events, really important to note, we saw no events of hearing loss and no events of hyperglycemia and just a low rate of neutropenia. So really well-differentiated product in terms of safety.

And then my final slide, I mentioned that we're moving into a Phase II in patients with geographic atrophy. We did actually have a complement factor B inhibitor about a couple of years ago in the GOLDEN study, where we saw with a 70% complement factor B knockdown and a 35% PD effective alternative pathway activity inhibition, we saw a small but non-statistically significant effect on GA lesion growth. We, therefore, decided to acquire this asset, which is a small interfering RNA. And as you can see on the right-hand side, it really knocks down CFB and the alternative pathway by about 100%, at least out to 3 months.

The unmet need in geographic atrophy, just as a reminder, it really remains very robust. The only 2 approved therapies are approved only in very, very small number of countries. And the treatment burden is great. So it's injected every 1 to 2 months. And the visual function benefits have not been demonstrated by those approved products. So we really see this as a great opportunity to make a difference, and this is entering Phase II.

And with that, I'm delighted to hand over to my colleague, Manu Chakravarthy, to talk us through our CVRM portfolio. Thanks, Manu.

Good afternoon. I just wanted to thank my colleagues for a wonderful presentation of all the other therapeutic areas. I'm happy to close this out this session with CVRM. So I think for this audience, I think everybody understands the burden and the challenge and the opportunities that we're facing, right? So the reason why we are in CVRM is because this is going to be probably one of the largest burdens of humanity. Over the next 25 years or so, 2 out of 3 people in the world will experience at least one, what is called a CVRM disease. And CVRM disease is indicated on the left there, as you can see, ranges from MASH to diabetes, to obesity, to heart failure, stroke, even Alzheimer's to some extent. So it really is a multi-organ interconnected web of diseases that we're really trying to understand how do we actually grapple.

No doubt that current modern therapies have made a significant impact, right? So if you actually look at the state-of-the-art incretin therapies, we see very promising results in terms of end organ benefits like improvements in heart failure, improvements in CVD, et cetera. But still, even with all of that, 1 out of 5 people that are treated with the state-of-the-art incretin will experience a heart attack. 40% of people will still have residual inflammation markers and 6% to 8% of residual cardiovascular or cardiorenal events still persist even after therapy. So what all this means is that our current evolution, at least the way that we approach it at Roche, is that we're moving from a purely adipose-centric view to an adiposity independent view of the interconnected web of CVRM.

So this is the way that we've been trying to approach how we think about designing our pipeline. This is the way that we've been thinking about how we want to actually think about the modalities that we want to bring forward. And so in terms of our capabilities that we want to actually bring to bear to address this incredible complexity, the heterogeneity, the market segmentation that will no doubt be there is to really position ourselves by building out a pipeline that is really focused on the next generation of molecules across the broad swath of mechanisms because we know that this is heterogeneous. We know this is interconnected. And also, as you heard from Aviv today, we actually have to go deep in research to really build out the foundational pathobiology of how these diseases actually work. And so we are making investments there to understand both the adipose dependent and adipose-independent mechanisms using a diverse set of modalities, and that's going to be really key to address this heterogeneity.

And like you've heard from my other colleagues, combinations are going to be still relevant here, too. It would be really fascinating to think that you could address one very complicated disease with one target. And so bringing in combinations, both within our own portfolio as well as within our wonderfully rich cross therapeutic area portfolio becomes very important. And that's -- I would submit that Roche is very well equipped and positioned for doing that. And then finally, I think you've heard several times mentioned today this very unique partnership with Roche Diagnostics. Dia and pharma reside under the same roof. And just like neuroscience, CVRM is another poster child where diagnostics can really make a big impact. And I can give you one example with MASH, for example, but there are many, including in diabetes, cardiovascular disease and other areas where pharma-dia interface is going to make a big difference.

So when we bring all of these capabilities to bear with the complexity of the biology that I just very briefly outlined, what we have then is a pipeline that we're really excited to showcase the progress over the last 12 months or so. So when I was here last year, I showed you all of the light blue lines where we were just entering into Phase II. We're starting to read some data in Phase II for enicepatide. I'll show you some data on how those results actually turned out. And then happy to report that based off of those results, now we're able to make advances of that program into Phase III. As you heard from Teresa this morning, we've also announced or made the decision, I should say, to advance our oral GLP-1 agonist into Phase III. We continue to make good progress in petrelintide, and that has been advanced to Phase III.

And then for zilebesiran that you've heard a little bit about and I'll show you some more emerging data, very exciting, continues to build the case for why this is so important despite the fact that there are other hypertensive agents, but there isn't one that gives you this level of control. And we are in the midst of our ZYNERGY trial now and it's going really well. And then, of course, pegozafermin, we continue to make good progress. And then finally, we're also able to bring in 2 additional assets into the portfolio, NLRP3 inhibitor for ASCVD. And then a very exciting new target called urocortin-2 that we're doing in partnership with Hanmi for obesity and type 2 diabetes with a particular focus on body composition.

So let's kind of dive into a couple of key areas just to give you the actual data and the feel for why we're so excited about this portfolio. So we can start with enicepatide. So again, you'll recall that one of the unique aspects of this molecule that to the best of our knowledge, is not being replicated by other molecules, is a dual biased signaling property where both receptors, GLP-1 and GIP are fully biased. When we talk about biased, we're referring to, of course, the signal transduction mechanism. So on the left of this graph on the left there is an example of an unbiased ligand. And one example of such a ligand is semaglutide, for example. It activates both the cAMP pathway and the beta-arrestin pathway. Beta-arrestin is the off switch. And when beta-arrestin gets recruited, then the receptor gets internalized and turns off the signal.

So what we had hypothesized was that by removing the off signal, could you keep the receptor in the on state longer, prevent this desensitization and therefore, enhance signaling and therefore, enhance efficacy. Our preclinical data certainly supports that. Our early Phase I data supported that. And then in the couple of slides I'm going to show you, I think we're starting to see this translate into large Phase IIb studies as well. Now of course, Phase III will be the final arbiter, of course, but it's very gratifying to see the translation from cells to animals to early studies to now potentially hopefully late-stage studies as well.

So let me start with the data from the 103 study. So some of you have already seen this since we had presented this at the ADA. Just to again recap, this is about 450 or so subjects randomized to 5 different arms, ranging from 4 mg all the way to 24 mg with the placebo. And what you can see there on the left is the weight loss -- percentage of weight loss over 48 weeks. The thing that strikes at least us anyway is the fact that the 24-milligram dose arm continues its steady downward decline on a linear trajectory without a plateau. The number that you see at 48 weeks, 22.7%, is the number typically seen by other molecules at 72 weeks or 80 weeks. Now of course, we recognize this is a Phase II study, and we have to do the Phase III, which we're very excited that we've already initiated. It's called Enith-1 and Enith-2, and both have been recruiting extremely well. This trajectory, of course, we anticipate will continue furthermore. And then potentially, it has the chance to be best-in-class.

The other number there that's very important to focus on is the proportion of people achieving the critical target weight losses. So typically, for organ benefits, 20% or more is considered to be the number. So if you look at the proportion of people achieving 20% or more, that's nearly half the population at the 24-milligram dose. And what was more remarkable is that more than 1/4 of people achieved 30% or more in less than a year. So that's, again, another reason why we believe this has the potential to be best-in-class. And of course, again, we await the results of the Phase III studies, and those studies have been going really well. So some of this data and additional subsets of this data, secondary analyses, exploratory analyses will all be presented actually this week in Milan at the EASD and where we will talk about the incredible impact of enicepatide on blood pressure, on inflammation markers, on blood volume and several other critical patient-related outcomes as well.

Now Teresa indicated a really fascinating result this morning, and I'm happy to give you the actual data behind that number, which is 2.65%. So that number, of course, refers to the hemoglobin A1c reduction that we saw in what we call the 104 study. So the 104 study was almost an identical study to the 103, which is about, again, 450 or so subjects, 5 arms and randomized to enicepatide versus placebo. And here, what I'm showing you is just the top line results, largely because we want to actually preserve some of that data for a medical conference that's coming up. But the bottom line is this. So what you see is that compared to placebo, there's a very steep and downward decline in hemoglobin A1c, which is reaching a value of around 2.65% in 48 weeks.

What was even more remarkable, and again, as an endocrinologist, having treated many of these patients, what we see typically is uncontrolled patients. So patients who actually have a hard time getting their blood sugar control despite being on 2, 3, sometimes even 4 anti-hyperglycemic medicines. And then if you ask the question, what proportion of people achieved good glycemic control. It's about 90% of people reach 6.5% or less, which is the threshold that the ADA has set to be nondiabetic. And if you ask the question, what proportion of people are actually normoglycemic even a higher bar, that's 62% of people. And in those people that are poorly controlled, that is A1c greater than 8.5, we saw a number of -- a value of 4.13% decrease in A1c.

Now of course, I'll be the first one to say that cross-trial comparisons are fraught with problems. But I know that you guys will do the comparisons anyway. So we've done it for you here. And so with all the caveats of cross-study comparisons, what we just clearly see here is a set of numbers that gives us the confidence to say that this might be potentially best in disease for glycemic control. It's been a long time since insulin that you could actually reduce blood glucose to these levels without hypoglycemia. And that was a really important metric for us. So when you actually look at the proportion of people that actually discontinue because of AEs or hypoglycemia or any other key issues, it was a staggeringly low number, 2%. In placebo, it was 0%. And there were no Level 2 hypoglycemia. And again, Level 2 is the ADA definition of an objective readout of hypoglycemia. So this is an actual blood measurement. So no Level 2 hypoglycemia and the safety and the tolerability was pretty much in line with what you would expect of an incretin class.

So when you put it all together, what we have now is an agent that we believe warrants a full test head-to-head against enicepatide, at least in glycemic control. So for that reason, we have embarked on a very large program. It ranges from looking at, of course, obesity, type 2 diabetes, glycemic control by itself, which we call the Eni-SPIRE program. And then we're also initiating in parallel in the first half of 2027, 2 large outcome studies in its MACE, which includes the subpopulation of type 1 diabetes, which we believe is actually quite unique. Again, to the best of our knowledge, nobody has ever gone into a cardiovascular outcome study with both type 2 diabetes and type 1 diabetes. So this is quite unique.

And then another unique differentiating factor where we believe that enicepatide could really differentiate is in heart failure with reduced ejection fraction. So again, many of you cover this field well, so you know that most people go into heart failure with preserved ejection fraction. So we've taken a fairly bold step based on all of our data that enicepatide could really have the potential to be first-in-class for this indication. Again, of course, the Phase III trials will dictate that. So in summary, a large program, a broad program, a program that gives us the opportunity to be not only best-in-class, but best in disease with the relevant outcome studies that's necessary to be able to claim something like that.

So now I'm going to transition very quickly to an update on our oral GLP-1 program. So the 996 -- CT-996 is an oral small molecule biased GLP-1 agonist. We've shown you some of the Phase I data. We're actually happy to report that the EASD accepted some more of our Phase I results, which we'll actually be presenting this week. But here, you can see the preview of that. So again, in a small cohort of people with obesity and type 2 diabetes. It's only 4 weeks, but you can see here the very robust reductions in A1c and body weight loss in a relatively short period of time. And when we did a dynamic test like the Mixed-Meal Tolerance Test, the glucose excursion was largely obliterated, meaning that there was no excursion of glucose.

So very, very strong glycemic control effect. The PK supports once-daily dosing, no food effect, which is very important. And then ultimately, when we took all of that data into our Phase II program, which was a very robust study, again, with roughly around 350 to 400 people, tried multiple different doses, different regimens, different titrations. And the data that we've seen so far gives us confidence to advance this program now to Phase III. So that has allowed us to then develop what we call the MetORA program, which is going to be for chronic weight management to start with.

So we'll start with that. Plan is to initiate in the first half of 2027. We have an ongoing Phase IIb study in obesity, overweight and type 2 diabetes, which we're running right now. It's on track, and we will report that data when that comes up.

Moving on to petrelintide. So you all recognize this from the last time that we were here, long-acting amylin partnered with Zealand. And a key thing to focus here on is the biological synergy that we expect with an amylin and an incretin. We know this biology and it's been there for the last 20-plus years. And that gives us the confidence that we can actually see that additivity when we actually combine a GLP-1 GIP with petrelintide. So this would be our triple agonist in some ways when we do this in an FDC. But in the meantime, where we are focused on is to do this in a loose combination study, which we call the ZYNERGY program and the ZYNERGY study where we will dose enicepatide and petrelintide in people with overweight and obesity and look for chronic or weight as the endpoint.

Just as a quick recollection. You know this data from the ADA, 10.7% weight loss with petrelintide monotherapy with a really excellent tolerability profile. So the tolerability profile in these ZUPREME-1 results was essentially unremarkable. So no vomiting, very low cases of nausea, generally considered to be "placebo-like". So the main news here is that now based on all of that data, we've advanced this program. And in fact, actually, you saw the release from Zealand where we've taken this program into Phase III as well.

Moving quickly to zilebesiran. So this is, again, just as a quick reminder, siRNA against angiotensinogen. Angiotensinogen is way upstream of the RAS pathway. This is a different kind of RAS, not the KRAS thing that you heard about, renin angiotensin aldosterone system. And by blocking it very upstream, what the advantage it confers is that there is very little feedback that happens from aldosterone. So this allows for very durable and sustained blood pressure control plus with an siRNA, you can essentially knock down angiotensinogen also to very low levels.

And we've shown all of this data before. But what you haven't seen is the data that we presented at the ESC last month. And what that shows you is this very sustained and especially the reduction of blood pressure at nighttime. And the reason why we want to focus on the nighttime is because amongst all the different parameters that influence cardiovascular mortality, it's how good your blood pressure is during the night that dictates that. So if your blood pressure is very poorly controlled at night, there's a higher risk for cardiovascular mortality. And this, you can see, whether it's in daytime or nighttime, there's a very clear sustained reduction.

So this gives us even further confidence to the ZENITH trial that's ongoing right now. So ZENITH, again, as a quick reminder, 11,000-person cardiovascular outcome study, classical 4-point MACE. Very happy to report that the enrollment is going phenomenally well. As Teresa said, there's tremendous interest from patients, from investigators, all across the board and so we are well on track. And again, looking forward to actually seeing how this all translates to cardiovascular outcomes.

The good news is the meta-analysis indicates to us that for every 5 to 7 millimeters of mercury drop, you increase your relative risk reduction by 10% to 15%. A couple of quick things before I wrap up. Pegozafermin. This is simply to just remind you all that this is our FGF21 analog. There's no new data since 2025. But just to remind us that based on the data that we have currently seen, particularly this middle graph with the population of people that have an F4 at baseline and to see roughly 45% of people actually achieved 1-stage improvement in fibrosis, that was really encouraging. Again, small numbers, totally get it. But it's important to see that signal and the fact that you can actually modulate even at that late stage gives us the confidence that FGF21, especially pegozafermin, can, in fact, be best in disease.

So 2 studies are ongoing, which we call ENLIGHTEN fibrosis and ENLIGHTEN cirrhosis. They're going relatively well. Top line data is expected now in the first half of 2028. Last but not least, just a quick word on urocortin. So as I mentioned to you earlier, one of the key unmet needs that we're also trying to solve for is the improvement of body composition, especially in people who are losing a lot of weight. You'll note that most incretins will cause lean mass loss of around 20% to 25%.

So urocortin-2 is a novel mechanism that has the first-in-class potential to really improve this body composition while also improving insulin sensitivity and other end organ benefits, particularly on the heart. It works on a specific receptor called the CRF2. That selectivity is very important. Hanmi's molecule achieves that selectivity really well. That was one of the key reasons why we were excited about this specific molecule and this mechanism. And then the data on the right just gives you the initial hints. Now of course, this is in preclinical species. But if we were to replicate this data in humans, this will be really exciting.

So what this data tells you is that when you compare urocortin by itself or urocortin to semaglutide and then urocortin plus semaglutide, which is the clear bar, you can see there's more weight loss with the combo. But that weight loss is almost entirely driven by fat mass loss. So the clear bar there on the lower left, that's the fat mass. And then on the right, you can see that the lean mass is not just unchanged, but it's actually increased a little bit. So if that were to actually translate, that would be paradigm shifting. And that is the reason why we focused on Hanmi and another reason why based on the bar requirements that you heard from Teresa, we had to stop emugrobart.

So in conclusion, before I hand it to Teresa to bring this home, what I want to leave you with is that it is imperative that when we think about CVRM diseases that we think about it as an interconnected web. So the goal is here to address both the adiposity drivers as well as the adiposity independent drivers. The goal is also to not just treat but to actually prevent. And we can do that because of our diagnostics capabilities. We can do that because of our general capabilities that we have built together now with trying to bring in combinations of different kinds. And then ultimately, of course, the goal is to reduce the global burden of health, which CVRM diseases constitute nearly 60% of it.

So overall, our focus, again, is to bring the best of internal science, the best of external science and ultimately to develop these transformative therapies. So with that, let me hand it to Teresa to bring us home, and we'll be ready for questions afterwards. Thank you.

All right. Fortunately, we only have one more slide. I hope what you're taking away from today is momentum. Over the course of the last couple of years, we have put a lot of things into motion, whether it's R&D excellence, which looks at completely changing our entire R&D engine, applying the bar to all of our assets, dramatically reshaping our pipeline to our operational excellence, the investments that we're making in order to fuel our future or our commercial excellence. We have a tremendous amount of tailwinds behind us as we head into the next period.

For our on-market portfolio, we're making smart life cycle management investment decisions that will allow us to extend those products and continue to serve additional patients. At the same time, we prepare for the launch of exciting new molecules like giredestrant, fenebrutinib, vamikibart, afimkibart and all of the things that we have coming before the end of 2027.

And then we just spent the afternoon really getting a sense of the tremendous pipeline that follows. As we think about the next couple of years ahead of us, we have a lot to deliver on. But the foundations are strong, the momentum is there. And as I said previously, these are no longer just words on a page. They're not a strategy on a PowerPoint. They're not an ambition to be achieved. These are plans that are in action that we will fulfill for patients. And so with that, I'm going to invite all of my partners in crime back up to the stage to go through our last Q&A.

Very good. I think then we will immediately start with the second Q&A session. And let's just go now a bit in the back and then we come back to the front line. Emmanuel, if you go next.

Emmanuel from Deutsche Bank. A couple of follow-ups on your impressive head-to-head clinical trial plans you announced across various therapeutic categories. So maybe bexobrutideg, you announced you're going to Phase III in second line. It looks like that's head-to-head for fenebrutinib. Is the ultimate plan to go in frontline head-to-head with one of the current standard of care BTKs like fenebrutinib, for example? You announced plans with the VEGF IL6 go head-to-head with Vabysmo DME. Would you plan to do the same in AMD because that's obviously an important setting for that molecule. And then enicepatide, you talked about now being confident enough to go head-to-head in diabetes. Will you also plan to do the same in obesity?

I can start just with the question. As we talked about, the clinical profile of the molecule, I think, gives us a lot of confidence that it can deliver the next generation of what CLL patients need. We're beginning in the refractory population based on the resistance data that we showed in that 86% response rate, but we think that there's much more to come. In terms of the specific design of the Phase III to come, we're not commenting on that right now, but we're building combinations that allow us to get to first line.

I can add to the enicepatide. So yes, so as I indicated, the data certainly warrants us to have that experiment against tirzepatide and glycemic control. We'll await additional data and then decide how the program evolves for other -- beyond diabetes, whether we want to go head-to-head or not. So at this point in time, we're going to look at this from a data perspective.

And maybe I'll obviously cover the DutaFab. We've not made a decision yet to move into nAMD. But if we do, yes, Vabysmo would be the priority comparator.

Let's go in the back to Simon, please.

Simon Baker from Rothschild & Co Redburn. Two, if I may, please. Firstly, on the obesity market, a sort of big picture question. Can you just give us your perspectives on how this market is evolving compared to your expectations when you started on this journey in terms of the mix between oral and injectable the impact of price and the level of pricing and the effect that has on volume, just really seeing how things have changed versus original expectations.

And then moving on to sefaxersen. Could you just give us some more thoughts on how you're going to position that in IgAN that is becoming an increasingly crowded area. So some more thoughts on how that fits in there would be much appreciated.

Teresa, do you want to start with the pricing question?

Yes, sure. I mean, honestly, it's all pretty much in line with the bookends that we had when we made the decision to go into obesity. Some things have moved faster than maybe we anticipated. But I think we sort of always expected that we would get to a more consumer-driven price-sensitive market and one where the shift to orals would eventually occur. So again, I don't think it's anything different than we assumed, maybe a little bit faster, but not all within the bookends.

And we always expected the market fragmented...

Absolutely.

[indiscernible] different mode of actions, different modalities. So we also expect it's going to be over time, not just on big market but subsets of markets. There was the portfolio towards that.

And maybe -- sorry. With regard to sefaxersen, yes, obviously, a lot of progress made in the IgA nephropathy field over the last few years. The APRIL/BAFF inhibitors have gotten, I think, most of the attention. But again, even if you look at the clinical trials of the APRIL/BAFF inhibitors, 50% to 60% of patients are not achieving adequate control based upon current clinical guidelines. So that being the case, we think that there will be an important role for complement inhibitors in the treatment algorithm, including sefaxersen, which again, we think has best-in-class potential as a complement inhibitor. And really, I think the focus will be in terms of first-line therapy on patients who have more active inflammation or at higher risk of progression.

And then second-line therapy, again, there's 50% to 60% of patients who are actually not achieving adequate control. And again, just to point out, sefaxersen has a unique value proposition of being every 4-week subcu at-home administration.

Can we go there to Matt?

Matt Weston from UBS. Two questions for me, please. One in neuroscience and Brainshuttle CD20. I think it's been talked about or certainly alluded about at Roche for a number of years. I'm surprised it's still in Phase I with the anticipation of Phase II. So what's been the challenge? If we had a known mode of action, a known technology, why is it taking so long to move forward?

And then the second question about the impressive Phase III trial package in obesity and diabetes. We all got caught out when one of your competitors had an unexpected dosing schedule in its Phase III trial designs with CagriSema. Can you comment whether or not we should just be expecting plain vanilla acceleration in the Roche Phase III program?

Maybe I can start with that because I'm sure that's on people's minds as well. Yes. So obviously, yes, we are well aware of that. It's a fine balance, right? So you want the flexibility, you want to allow for patients to have some opportunity to titrate themselves, if you can. But all of our studies, all of our programs have had a requirement to get to a top dose. Now how you get to that top dose, there's flexibility in that and adjustments that could be made, but the expectation is that they need to get to a top dose but we're also going to allow for enough time after they get to a top dose to have enough sort of follow-up period on the maintenance dose.

And then finally, I mean, I think one way -- I think we had already alluded to this last year but now we can confirm that we're actually incorporating the open-label extension as part of our designs in our -- certainly in our obesity program. So we're well aware, but we also recognize that it's a balance between what patient preferences are and how you actually recruit patients and keep them in these studies, which are challenging to do because they're all still on placebo.

I can speak to the Brainshuttle CD20. So over time, there's been a careful design of the CDP, and it's definitively moving to Phase II. So Phase II is starting with Brainshuttle CD20. And we have early Phase I data that shows benefit and reduction of B cells in CSF in patients.

Can we give the microphone and have it in the second line.

Graham Parry from Citi. A couple of follow-ups on giredestrant and one on fenebrutinib. So on giredestrant, you talked about aromatase inhibitor discontinuation patients as an opportunity. But what about the in situ patient population who just aren't doing well? Do you see them as switchable? And if so, how many patients do you think that actually represents? Can you talk to the differences in the community versus the KOL settings and where you see the best place to target for this drug on launch?

And then also the time you think it's going to take to get patients on to reimbursement coverage if they're in the patient access program? And then on fenebrutinib, in your FDA prefiling discussions, has the FDA asked for any additional suicidality risk or suicidal ideation data to be submitted during the review cycle?

So maybe I'll start on part of the giredestrant question. The short answer is, certainly, we see an opportunity on the switch front. Actually, one of the Phase IIIb studies that I described will specifically be looking at that, the feasibility of switching for patients who are, in fact, not tolerant and doing well on the CDK-based combination. But also, when we think about the discussions that we've had thus far, we don't comment on detail in FDA discussions, but we don't anticipate any label restrictions around switching. So definitely a live question that will require additional studies, but we don't see any intrinsic barriers to that. But maybe Teresa or Wendy would want to comment on the other side of the question.

Good. I can maybe pick it up in terms of -- I think two aspects and tell me what you're thinking about. First is, a, just thinking about you, we definitely are looking at understanding more in terms of the market size. I think the market size has to be balanced also in terms of what the, I would say, willingness to treat right, relative to the current therapies as well. So this is something that we're currently looking at. In terms of community versus KOL or systemic business, I do think that given our legacy and our leadership in HER2, this is an area that we are intimately familiar with. Unlocking the community is going to be a key challenge for us. I mean, a key opportunity for us when we're thinking about the side effect profile and tolerability that we currently are seeing with AI and as well as CDK4/6.

Last question in terms of patient access, we definitely recognize that it is a -- as we talked about being Part B, patient access will be key in terms of how we ensure that we're bridging, right, from the -- not only from the existing patients, but also from clinical trials and onwards. So we're gained, and we're definitely ready to start.

And I can address your suicidality question for fenebrutinib. So first of all, patient safety is Roche's highest priority. And so we carefully examined the data. And we have submitted a file with FDA, and they did not ask for any additional data. We've had great collaboration with FDA, and we expect acceptance of the file anytime.

James Quigley from Goldman Sachs. I've got 2 questions, one for Manu on enicepatide and one for and one for Hideki on fenebrutinib. So on enicepatide, would you be able to let us know what the placebo response on weight loss, but then also the placebo reduction in HbA1c for those at the baseline and greater than 8.5. And then also what in the data gave you more confidence of moving forward in heart failure with reduced ejection fraction versus competitors looking at preserved ejection fraction?

And then fenebrutinib, would you be able to give us an idea of what the 24-week EDSS progression was as part of the composite primary endpoint. When you look at the fenebrutinib press release, and clearly, we need to see the detailed data first, but how do you think the MS community will think about inconsistent results between the static benefit at 12 weeks versus 24 week on EDSS? For the CD20s, it looks pretty consistent for Ocrevus and Kesimpta. What could this suggest about the quality of the data? Or are there any factors that we need to consider about BTK inhibitors that maybe the progression benefit takes longer to come through on EDSS?

So let's start on the enicepatide. So as I said before, we've tried to deliberately not provide too much data largely because we are -- not because we don't want to share it. It's just that there are embargo rules, as you know, right? And so all I can tell you is that the responses are pretty much of what you've seen in the total population. Nothing surprising. They're all pretty much in line with what you would expect of a placebo. There was no strange behavior of the placebo patients or any of those things. So it was really reassuring with a very clean data set.

In regards to the data that gave us confidence in the rest, there was multiple pieces of data. The first is, of course, our own data from -- which will be presented at EASD actually, is the very significant benefits on plasma volume. That actually is a very important parameter that correlates to how well that people with do. Blood pressure changes, of course, inflammatory markers. And then I think the main thing is really looking at the real-world data sets. So when we look at the collective data sets and that's available and put all of that together with our data, it gives us confidence that we would potentially have a benefit in the HFrEF as well.

The final piece I will tell you, which actually worked out in retrospect in our favor is the AHA has now actually reclassified heart failure as simply HFrEF and HFpEF. There is no system in minimally REF. So that classification actually helps us a lot because the population that we're actually studying is exactly what the AHA definition of reduced ejection fraction. So that gives us even further credence to pursue this indication.

And with respect to your 24-week progression data for fen, ditto to what Manu just said. The data will be upcoming at a forthcoming scientific conference and largely consistent with what I showed today.

Okay. Can we pass the mic to -- Justin, maybe you go first.

Just a quick one for Levi. Justin from Bernstein. On the B7-H3 ADC and the DAR you emphasized the 8. Sorry if this is a bit simplistic, but are you encouraging us to think about sort of Kadcyla HER2? Or is it a completely different way to think about it? Obviously, it's differentiating what you have, but would just love to get your thoughts on how important that ratio is.

So probably there are two aspects that I mentioned, probably the one I mentioned the most because we think it's particularly relevant is the linker, the hydrophilic linker and the ability to prevent leakage of the linker in the circulation that from a side effect profile, that's probably perhaps the most important. And in fact, if you look at the -- obviously, we don't have head-to-head comparison, but it does appear that perhaps that is creating a bit of it.

Now the [indiscernible] could also help in as much that, of course, you're that much better able to deliver the payload into the tumor with that favorable linker situation. But I would say maybe on balance, we might even -- maybe the linker, the integrity of the linker in the circulation that might be even more important from a side effect profile.

James?

Maybe if I can build on the across the [indiscernible] and all the B7-H3 by far, Tam-Peli actually has the highest DAR ratio. Right, in comparison to others. So I think in combination, we're thinking about the hydrophilic linker, we're seeing a really good favorable in terms of tolerability profile, which allows us to combine as well as an efficacy potentially as well.

Great. James Gordon from Barclays. One was also on B7-H3, but also about increasingly fast followers. So I think there's about 10 different B7-H3s in the clinic across companies, and most of them are from Chinese biotech companies. And I heard comments about payload and linker being potentially differentiated. But do you think there is a bit of a risk that you're going to get lots more fast followers, particularly in ADCs going for the same target and the returns are going to be eroded even before the patents go? And does that change how you think about what to take forward or what to license in? But there seems to be certain areas that look like there's been loads of people going for them.

And then the other question is in CVRM, so for obesity orals, at least one of your competitors thinks that the oral market, what's going to be really important for the next wave is to be able to combine multiple oral ingredients. So do you think that's the case? It's not just going to be about oral monotherapy, it's going to be oral combos? And if so, do you need some more oral co-ingredients to go with to go for other cardiovascular comorbidities?

So maybe I'll briefly take the first question. So we often have the discussion about the competitive landscape, but we usually end up with -- if we were to use the competitive landscape for the reason not to do something, we would do very little because there are so many examples that you gave where there are many shots on goal, many companies in China that are coming with fast followers. So that by itself can be a deterrent. What we have to trust is our ability to evaluate the opportunities and look for components that may see a little differentiation. And we think thus far, with Tam-Peli, we're seeing that. But of course, at the end, it will be important to have the data speed, but also execution to be able to execute these trials rapidly, but also high quality.

Yes. On the oral -- and thank you for asking that question. In one of the slides I showed, that is one of our critical parts of our strategy, right? So we don't think it's an either/or injectable oral. The market is highly segmented. The needs are varied and patients have different needs along their long journey. So for that reason, we think that orals are a critical pillar of our strategy, both as monotherapy and certainly, CT-996 can represent that. But we're also -- as part of the other pillar of our strategy that I showed you is combinations.

So combinations can come in the form of the usual suspects like a GIP agonist, for example, could make an oral enicepatide. But also, given the interconnected CVRM web, if you will, having agents that can address other comorbidities while you have an anchor or the foundation of a GLP-1 agonist makes it very attractive. So we believe that both are equally possible. And then the final piece I would just say is that a lot of people worry that, well, does the injectable sort of take away the oral market or vice versa. What we're actually seeing is the opposite. There's a market expansion largely because the orals have actually started to come in. And we anticipate that market size will further increase even more so as more people come into the fold.

And you also might imagine a situation where someone who maybe was a little bit intimidated by a shot is willing to start with a pill, realizes they're getting what they want, but maybe not as much and then is happy to move on to an injection. And so I think you'll also -- that market expansion will also help the injectable category later on.

Kerry Holford at Berenberg. Question for you, Manu, following up on what we just discussed on obesity. Limited time, I think, today spent on petrelintide monotherapy. So just keen to hear your level of excitement around that approach.

And then on that product in particular, do you need all 3 Phase III to file? Or will it just be the traditional obesity and obesity plus diabetes that you feel you need to advance to the regulator? And then finally, just an update on your plans for the Phase IIIb for that molecule.

Sure. So first is, obviously, we're very excited about petrelintide. It's a critical part of what we call a foundational pillar, just like GLP-1 is a foundational pillar and FGF21 is a pillar. Amylin our Pillar 2. So the data that we've seen indicates to us that the experience that people want to have can be varied. Again, it comes back to the heterogeneity and the different needs of patient segments. So for those that are looking to have what we would call a gentler weight loss experience, where they're wanting to lose maybe double-digit weight loss, but with very good tolerability or try something else as a different mechanism, Amylin offers that.

And so having that in our portfolio is absolutely vital, and that is the reason why the program has moved into Phase III. Now do you need those 3 ZUPREME to file because chronic weight management requires you to show both the efficacy in people with and without type 2 diabetes. So even though there are 3 studies, actually the package is for chronic weight management.

And the third one, because we want to file globally, the EMA still has a requirement to show cardiovascular safety. And so the third ZUPREME study is to support that. So again, all of this underscores our excitement for the program that we're moving forward with the monotherapy and it's important that we have that optionality in our portfolio. Now regarding to your other question about -- sorry, can you remind me the...

Phase IIIb.

Yes. So that's under discussion right now. So we'll be able to update you once we have that finalized. But again, the thought here is if we are going to go forward with the mono, we want to ensure that we have the best supportive evidence that we can take forward to develop the mono. So there will be more details to come on the Phase IIIb.

Richard Vosser, JPMorgan. Two, please. One on the TL1A class and your product. Just wondering how differentiated this really is the class to the IL-23, where does it fit within the treatment paradigm?

And then secondly, on SKYGLO, could you talk about whether you've had an interim analysis there for SKYGLO, and how you see the market subdividing between the Polivy combination and the one that your competitor is going for, which excludes Polivy?

So happy to speak about afimkibart first. So obviously, great progress in the IBD field over the past decade or so. But again, still that significant efficacy ceiling that we haven't been able to crack. We do believe that TL1A actually will become standard of care for inflammatory bowel disease. But even as standard of care monotherapy, it may be limited in terms of its ability to crack the overall efficacy ceiling. That's why we're also focused on rational combinations, including that TL1A backbone. In terms of where TL1A as monotherapy will actually sit in the treatment algorithm, our clinical development plan looks both at patients who are advanced therapy naive and who are advanced therapy experienced. And only time and data, I think, will tell exactly where the TL1A fit into the treatment algorithm. But again, we believe that to really smash that efficacy ceiling, we're looking ahead to next-generation molecules, including bispecifics based on the TL1A backbone.

In terms of SKYGLO, I can't comment on the interim analysis in particular, but I mentioned how excited we are for the readout next year in '27. And in terms of the competitive positioning, I think you highlighted a key element, which is that the control and the underlying backbone that we're building on is fundamentally different in our study versus competitors. Our belief is that the Columvi, Polivy, R-CHP is the standard and has the best efficacy, as I highlighted in that sort of legacy of progress through DLBCL. It's prescribed as the most common regimen across multiple regions of the world, endorsed by 20 guidelines.

So our belief is that we're building on the best standard against the best standard. There was a question earlier today about sort of how we think about head-to-head comparisons. And I think you see in this study as well as many of the others routinely going up against what is the best standard, and that is maybe relevant to the differentiation question that was brought up before about how do we establish ourselves in a marketplace that's rapidly competitive is by beating the best standard of care and not being vulnerable to questions about whether we've taken an easier route to filing. And so with the clarity of the data we get from SKYGLO, I think we'll be able to be able to have one more standard of care change for DLBCL.

Sachin Jain, Bank of America. A few questions, please. Firstly, on fene. An answer to prior question you said you hadn't had any further questions from the FDA on CNS. Would you have expected those by this stage and the file is not even accepted yet? And any color you can give on the level of comfort FDA has with the different trial baselines on sort of CNS risk that differs your program from the others as an explanation of that suicidality? And then I guess related, we're obviously waiting the competitor data in a few weeks and we'll compare and contrast efficacy. But how do you think the absence or not of monitoring will impact commercial positioning? Obviously they're talking to being approved with that monitoring.

And second one for Larry on the TL1A combination strategy. So very clear on your follow-on molecules. Could you talk to how you might explore 3 combinations that accelerate a combination strategy to build beyond your monotherapy launch? Obviously, a variety of companies, we've got the bispecifics a little bit further ahead than you. Is there anything you can do commercially to accelerate a combination strategy?

And then last quick one for Chris. You talked about active comparators. I don't know whether that was a comment to the Kodiak data just that, but I wonder if you could just comment to that. I know you don't have a lot of time, but any quick comments.

I can take the first question and then hand it over to you for the commercial question on fene. So we don't comment about specific interactions with FDA, but we have had a highly collaborative and really great dialogue with FDA. And like I said, they have the entire file and we expect...

So in terms of the liver monitoring, I mean, in general, it is pretty standard that you get in your label, what you studied in your trial. So if you have liver monitoring in your trial, chances are you're going to have liver monitoring in your label. I think it's important for us to remember that neurologists are very familiar with liver monitoring. They do it all the time. It's something that they have incorporated into their practice. And I think it gives them a high degree of confidence that they're doing the best thing for their patients to keep them safe. So I don't think we see any particular barrier to prescribing by having that liver monitoring. And in fact, I do think it gives physicians comfort.

I can speak just quickly to the TL1A combinations. Obviously, I think in these situations, it's just as important or maybe even more important to get it right as it is to get it fast. We believe that we have a great molecule that's in the lead in our pipeline. We have other molecules as well that are taking similar approaches. We'll see the data in 2027 and look for opportunities to accelerate from there.

And a quick comment on that. On the Kodiak data, very fresh off the press. I think it was coming in as I was speaking. So I'd say my overall impressions, when we compare Vabysmo with aflibercept, Vabysmo consistently drives better than aflibercept. There was -- that data did not exist that I saw in the Kodiak data. So now with nAMD. They have no data in DME, which makes it very challenging to get any product in mass usage in the key markets. So more to come, I think.

And maybe just to add a tiny a little bit of color to that. So I was with a group of physicians 2 weeks ago and a retinal specialists. And what they said overwhelmingly was we need to start studying against the standard of care and that standard of care has changed. And so I think, in particular, in that specialty, there's a lot of drive to actually make sure we're running the trials.

Urban Fritsche from ZKB. First on Alzheimer's. You didn't talk a lot about the impact of the availability of the pTau-217 test on clinical development, but a bit more concrete, did the availability of the test help to accelerate the Phase III patient recruitment for trontinemab? And then also in Alzheimer's, what's your thinking on the combinability of nivegacetor plus trontinemab? I think there is a trial going on combining that with Kisunla, if I'm right.

And then on cardiovascular, did I get it right, the emugrobart discontinuation was quite an opportunistic decision for the urocortin-2 analog. How much of that actually was driven by in-licensing that?

Let me take that second one first. It wasn't. I mean, we evaluate opportunities based off of the science, based off of the needs, what it is that we're trying to solve for. Ultimately, the data from [indiscernible] didn't meet the bar for us. And that study was already well in play even before we even started to even contemplate about urocortin 2. But the way we approach it is to look at it from a disease pathway or a pathobiology perspective, which is what are we really trying to solve for? The thing that we're trying to solve for is the preservation of lean mass while you're preferentially decreasing fat mass.

So what are all the different mechanisms, what are all the different targets that can play in that space is a critical factor for us. And then it has to certainly meet the data standards that we want to have to achieve them. And unfortunately, in the case of emugrobart, it didn't meet that bar. So it was not one or the other or it was entirely driven by the data.

And your question about pTau217 Elecsys biomarker. Yes, absolutely, that has helped in terms of recruiting patients. I didn't highlight in detail, but we have a prescreened study called TRAVELLER. And the pTau217 is a key component of that TRAVELLER prescreening study, and that helped us identify patients to go into early AD, so TRONTIER studies and/or into the PrevenTRON study. So it really has helped in terms of acceleration.

And your question about combination. So we feel that trontinemab is a foundational treatment, and we are looking at potential combinations in the future with trontinemab. And so GSM, nivegacetor could be, but we haven't come to that decision yet, but we're certainly exploring that.

Okay. Maybe, you get the final one, the first one and the final.

Thank you, Bruno. So just a little bit more on giredestrant. Is there any better understanding for the failure in the first line? I know at ASCO, there was not really a clear explanation for that. And I'm asking because I see you're now combining with CDK4 with a competitor. So anything sort of give us confidence around that? And also what the decision-making because I think you had a CDK4 that you've now stopped in Phase I. So the choice to go with a competitor.

And then the final question would be perhaps to. What are the key risks to investing in the new disease areas? And how is Roche mitigating those risks and defending [indiscernible] margin?

So maybe I'll start on the -- so the short answer is there's nothing new to report on the sort of mechanistic explanation for the failure of persevERA. One thing -- so as you know, there was the numeric -- there's a numeric difference, but it wasn't wide enough to hit with the power that we had. There was also the late separation. And so that has led to a hypothesis of why a late separation as opposed to an early separation. And we don't know. Of course, one hypothesis would be maybe ESR1 mutations occurring in the aromatase inhibitor arm, but not in the SERD arm.

So more to come on that. Obviously, we're exploring that. But I would say, if you step back 10,000 feet that there are important differences between the kind of metastatic setting and the early breast cancer setting, namely the tumor burden, the microenvironment. So like, for example, again, we don't know, but I could say when you have a high tumor burden, you already have a lot of resistance mechanisms present, including ESR1 mutations that are kind of latent, whereas in the early setting, you don't actually have that. So you may have an opportunity to reveal selective vulnerabilities of both CDK and hitting the ER in ways that just don't play out in the late setting. So we think there's still equipoise to actually ask the question of the combination in the early stage. So this was one of the reasons to do the study with Pfizer.

Absolutely. And in terms of risks, I mean, the primary risk is always the most theoretical and generic one, and that's making sure that you have a clinically differentiated asset to bring into a new space. If you're going to disrupt, you want to do that with a medicine that's truly going to change the standard of care. And I hope what you've taken away from today is a sense that we really do have a strong belief in those new assets that we're bringing forward that they do have the potential to disrupt.

When you think about scale in terms of manufacturing, commercialization, we've been steadily making those investments over the course of the last couple of years, sort of investing ahead of the pipeline to ensure that the foundations are there when those medicines hit, that we're not hit with a giant cost all at once, very carefully managing our capital investments and our margin. And honestly, we don't need all of them to be successful. And when you look at the sheer breadth of what we have in the portfolio that's already on the market, derisked with meaningful Phase III data, we have a clear path to growth.

So I think when we look at what we have ahead of us with these amazing new assets, I think what we have are a lot of things that give us a lot of confidence that we really will be able to come to market with something that's materially different. And I have a lot of confidence in the manufacturing and commercial engine that we've built to make sure that they ultimately make it to patients.

Excellent. So I think we have the perfect closing remark. And with that, I think we will close the broadcast part of the event. I would like to thank all our speakers for all their dedication and hard work every day to make this company go and in the interest of patients. And I also want to thank a couple of people from my team who have been working for the last weeks to make this event possible.

From the IR team, it's Jan-Philipp Schwarzhans, who worked on the overall strategy and the R&D excellence decks. Jon Bayard, who took care of the group finance deck; [indiscernible], who worked with on Aviv deck on AI and early drug development; Rafal Pawlowski, who was responsible for the oncology deck and managed the overall slide deck Loren Kalm, who was responsible for hematology, neurology, ophthalmology slide deck and also preparing Q&A decks, which needed to be updated constantly as we had a daily news flow, which was very intense for the last couple of weeks. Natalie Chen, who worked on neurology and ophthalmology slide deck and also updated our epidemiology appendix slides. So if you have not spotted them, they are again uploaded on the homepage, the latest and greatest.

Sabine Borngräber and Ada Logiri, they were responsible for the immunology and CVRM decks and also updated the pipeline appendix also uploaded on the homepage. And last but not least, from the IR back office is to call out Melanie Wolf, Beatrice Hau, Eva Losert, Fauael Lloyd for event organization. And I think the people on site here will have another half an hour for the buffet reception. All the management will be around, so they will take additional questions. Thank you.

Ladies and gentlemen, welcome to Roche's Half Year Results Webinar 2026. My name is Henrik, and I'm the technical operator for today's call. Kindly note that the webinar is being recorded. [Operator Instructions] One last remark, if you would like to follow the presented slides on your end as well, please feel free to go to roche.com/investors to download the presentation.

At this time, it's my pleasure to introduce you to Thomas Schinecker, CEO of Roche Group. Mr. Schinecker, the stage is yours.

Thank you very much, and good morning, and good afternoon, everyone. I'm very much excited to share our half year 2026 results with you. We again had a strong performance, and we truly made significant portfolio progress in the second quarter. Now let me take you through this slide. I think the headline says everything: core operating profit growth at plus 10% ahead of sales growth at plus 6%, again increasing our margin, similar to what we have done over the last couple of years, performance driven really by both divisions, both Pharma and Diagnostics. Diagnostics without the China impact is growing 6%. And let me just also reframe the impact of the flu season. The flu season had about a 1% or more than CHF 200 million impact on the group results. So without that, also, we will be growing at 7%.

I already mentioned the strong bottom line performance, with core operating profit plus 10%, core operating margin plus 1.7 points, core EPS plus 9%, very strong performance. We had significant milestones that we have achieved in Q2.

We have 5 U.S. FDA priority reviews in, for example, for Tecentriq, but also in Gazyva, we have made a number of progress in terms of filing, for example, in Enspryng in thyroid eye disease. So overall, extremely good regulatory progress.

On the Pharma readouts, we had 2 positive Phase III results as well. Overall, the Phase III success rate in this year is 80% and with that, significantly above the average of the industry. So I think here also, we are making very good progress. On the business development side, I would highlight 2 that I'm going to also mention later. One is PathAI. The other one is Nurix Therapeutics. On the Diagnostics launches, we've had also a significant amount of launches that I'm also going to go through, and I know Matt is going to go through as well.

We have significant news flow ahead, including Phase III readouts for Itovebi and Lunsumio and potentially a new NME, sefaxersen. So in the pipeline right now, we have 3 new NMEs that we're going to launch, but with sefaxersen, it could be a fourth one. And then some more Phase II readouts. So overall, quite a lot of news flow in the second half of '26. But even more, if you then look at '27, '28, '29, we have really huge amounts of news flow coming with really a lot of potentially very big medicines and also a lot of derisked assets. So we're really, really excited as we look into the next years when it comes to our pipeline.

Again, let me just highlight the all numbers, 6% Pharma, 3% Diagnostics. I already mentioned the impact of the flu season and also the healthcare pricing reforms. So overall, a very good track. Here, you can see the sales growth over the last quarters, and we'll continue to see good uptake in -- also in the rest of the year. And as we move into the end of the decade and into the next decade, as I've shown to you in previous presentations, we believe that we will continue to have a good momentum. And yes, we feel comfortable with where we are at the moment.

Really good growth across the different parts of our portfolio. We have a very diversified portfolio. We have in total 16 blockbusters. We're globally #1 in Diagnostics. We also have very strong market position in many of the areas, like hemophilia, ophthalmology, neurology, oncology, et cetera. And here, you see just some of the news, Vabysmo, where we continue to see good global growth at 6% and market share gains. There is, of course, the U.S. market, which is only growing low single digit, but where we keep gaining market share. Also in the immunology portfolio with Xolair and Gazyva, we have really good progress. And just to point that out, with TL1A, of course, next year, it's a new medicine coming into this portfolio.

On oncology as well, Phesgo conversion ongoing. The HER2 breast cancer franchise will peak in 2026 with a strong tail. Tecentriq, we see accelerated growth driven by new indications. And Alecensa, we expect flat growth for the full year. Continuing with Polivy, continued strong first-line DLBCL uptake. Columvi driven by second-line-plus DLBCL and Lunsumio by third-line follicular lymphoma. Hemlibra, very strong growth in the first half year, double digit. And also in the neurology franchise, we're growing quite well.

So let me talk a little bit about portfolio progress. And portfolio progress is a combination of our own R&D and also bringing in external assets like we've done in the second quarter. We've been quite disciplined when it comes to BD activities. And at the same time, we've built an amazing pipeline in the late stage, but also early stage. So we have a very full pipeline. And I think when you look at the deals that we have done, usually, we were not the highest bidder when we won the deals. So I think this discipline is something that you can count on as we allocate our money that we do it in the right way.

You can see a couple of acquisitions we've done. You see a number of those have already moved into Phase III. The latest one is the BTK degrader in hematology, but potentially also in immunology and neurology. Fenebrutinib is BTK inhibitor. With a degrader, we see even more reduction of the protein, and we believe that this could be a next-generation molecule here with a proven mechanism of action. So we feel this was a very good move for us, especially also because of our strength in hematological cancers and also in immunology and neurology.

And here, usually, when I talk through the slide, you have some red boxes. We had no red box in the second quarter, which really also shows that we've had really good pipeline progress. And just to take you through here, giredestrant, we have filing acceptance by the FDA. We have FDA priority review. We expect to launch towards the end of the year. NXT007 moved into Phase III. This is the next generation of Hemlibra. Feedback has been very positive so far. It's about 30x more potent, but also very safe. I already talked about the BTK degrader. Divarasib, I know Teresa will cover that, very good data. Also cevostamab has continued to progress well as well as the HER2 tyrosine kinase. This is a brain-penetrant molecule for HER2-positive breast cancer, really also addressing one of the biggest unmet needs there is to tackle the brain metastases that are developed in HER2-positive breast cancer. So also very exciting.

And on the obesity side, we've also had interesting data on petrelintide, specifically when it comes to tolerability, placebo-like tolerability. And we know that on current medicines, most of the patients never go to the highest dose. They actually end their dose in the midrange where you would get to the same kind of weight loss, petrelintide. But we also know incretins has a higher level of side effects, and this is really a medicine that's extremely tolerable.

Now let me go to the Diagnostics side and just show you some of the external activities that we've done over the last couple of years. And I would like to pick one from the last years. That one is Stratos, sequencing by expansion technology, which we have acquired in 2020, which is really the basis for the AXELIOS sequencing. And I've always promised that we will deliver, and we did deliver on the sequencing with really a differentiated product. And now Matt will go through that.

In addition, we've done 2 additional acquisitions in more of the oncology space. One is SAGA Diagnostics for ultrasensitive minimal residual disease testing. You know the market cap of some of the companies out there that are working in this space. The really interesting thing about this is not only the really ultra-high sensitivities, but you actually sequence the cancer, and we have AXELIOS. And then you monitor by specific primers, and you do it on digital PCR, which is highly cost effective, and we have a digital PCR system. So we are extremely well positioned here to really scale this on a global level, much better than some of the other players. On PathAI, this is really AI-driven diagnostics, AI-powered diagnostics, specifically in the pathology lab, reading the slides and really improving the diagnostics. And with that, also improving the treatment. And I know Matt will talk about that as well. So really excited about the progress.

And this is just a beautiful slide, 3 major launches. Each of them, even for Pharma terms, would be a blockbuster, really differentiated when it comes to mass spec for sure and sequencing. And if you look at the industry, at times, maybe you have a company having one of such launches, but we had 3 in such a close period of time. It just shows you how productive our R&D is as well as adding new assays. And I just picked 2 out of here. One is the Elecsys pTau217 for Alzheimer's disease, where we have a significant head start versus our other major competitors out there. So really excited that, especially in combination with trontinemab. And you have seen some data just lately that we presented in London on trontinemab, which continues to impress.

And then Elecsys interferon gamma release assay for tuberculosis. This is detecting latent tuberculosis. About 25% of the patients or people in the world actually have latent tuberculosis. These are both really great opportunities in the scale of what you have in diagnostics when it comes to potential sales volume for a test.

Now let me finish with the outlook. Mid-single-digit sales growth, currently growing 6%. Core EPS growth, high single-digit. Core EPS growth, growing 9% currently. And we further will increase dividends in Swiss francs. So I think we're very well on track.

And with that, I hand over to my team, and I want to thank them for all the great work. Alan, Teresa and Matt, thank you very much. So over to you, Alan.

Yes. Thanks, Thomas. I can just extend that and say thanks to, if you like, the whole Roche team for the achievements that we have had, with the fantastic pipeline progress and also the great financial results. So let's dig into that. And let's start with the overview. You see the 6% sales growth, 3% in Dia, as Thomas has said, 6% excluding China, Pharma with 6%, so really doing well. And you look at the Swiss francs, the minus 2%, just for the sake of completeness. In U.S. dollars, we would have grown 8%. Core operating profit up 10%, as Thomas has outlined as well, very good cost containment. I will explain that. Core operating profit to the core net income, we keep the momentum. That means the financial result as well as taxes were not in the way. Nevertheless, I can say stabilizing the tax rate in the first half is a little bit of an outlier, and I will come to that.

And then core net income to core EPS, well, the momentum slows a little bit with the plus 9%, but these are just the outstanding results from Chugai. As you know, we own 60%. So we have to take 40% from the performance away. So I think that brings the core EPS to the plus 9%. IFRS net income, I will explain, plus 6%, still here, a couple of impairments in there. And then the operating free cash flow, plus 21%, plus 2% in Swiss francs, let me outline this. So happy with that number. And then the free cash flow with plus 58% and plus 26% in Swiss francs. This is a timing effect as well. Here, we had some tax payments, or we didn't have the tax payments in the first half that we will have in the second half.

Good. With that, let's go through the sales growth. And you see really, on one hand, the 6% in CER. You see that the currency effect, which is a minus 8 percentage points, which brings us to the minus 2% in Swiss francs. Let me talk about the plus 6% at CER. On one hand, you see Pharma. Excluding LOE, you see the LOE with a minus CHF 244 million came in a little bit better than we all expected. It's also a reason why we updated our outlook for the full year or our additional information for the year and said we expect to lose roughly CHF 600 million due to loss of exclusivity, so a lower number than we had at the beginning of the year. When you put the 2 together, you get to plus 6% in CER. Diagnostics, plus 6% excluding China, minus 15% in China as well. And then you really put it together, and you get to the plus 3% that were mentioned before.

When we go through the P&L, sales is clear, other revenue. Other revenue is increasing by CHF 258 million. There are a couple of elements in it. When I start with Pharma, I think, on one hand, there's a settlement on a royalty claim, which is in here, roughly CHF 70 million. We have in here an expected milestone income from Chugai for Foundayo. That's one element here. And then we have a cross-licensing settlement in Pharma of CHF 126 million. When you put everything together, you get roughly pretty well to the CHF 258 million.

When you look at the cost of sales and the cost of sales, both divisions have grown their costs by 5%, which is quite an achievement because overall, volume has grown by 8%, Pharma by 9% volume growth and Diagnostics by 5% volume growth. And when you look really at the 2 divisions, the cost of sales in Pharma were driven by higher profit share expenses based on higher sales of Xolair and royalty expenses from the increased sales of Ocrevus and Evrysdi. And the cost of sales in Diagnostics were driven by the increased installed instruments, the manufacturing ramp-up of the new launches and then certainly the U.S. tariffs of roughly CHF 43 million.

When we look at R&D, R&D, plus 1%. I think, really here, a lot of cost discipline in the game here. But certainly, I think, also, let's say, quite some investment in key therapeutic areas, like oncology, CVRM and neurology. SG&A has increased by 3%. And let me, on one hand, say, really in Pharma, we had an increase in M&D, so really put money behind our products in marketing and distribution. Admin was really, really flattish. There's even a small saving here. So I think very disciplined approach here as well. And then other operating income and expenses, here, really a lower income from product disposals compared to last year.

Let me make an additional comment about other revenue. I think really, when you look really a little bit at our history and where we stand at the moment, other revenue normally represents roughly 3% of our sales. I think certainly now with the Foundayo element coming in for the next couple of years, we expect that ratio to grow to 5% until the end of that decade.

Good. I think I hope well explained how we get from 6% sales growth to 10% core operating profit growth. So when you look at the margins itself, I think that looks fine. I think, even in Swiss francs, I think, we are able to increase the margin. So as you can see, margin has increased by 1.7 percentage points in constant currencies, and that was driven by strong performance in both divisions, Pharma increasing by 2 percentage points and Dia by 0.6 percentage points. Let me outline here that both divisions benefited from the further centralization of SG&A, especially on the legal side, under corporate. That represented a benefit for Pharma of CHF 105 million in the first half, benefit, and Diagnostics for CHF 24 million, in CER, less costs compared to half year 2025. What does that mean? I'm certainly well aware of the fact that we have said basically it's CHF 300 million for the full year that we're going to shift. I'm not going away from that number. It could be a little bit lower, but we will see a little bit of a ramp-up here of that effect in the second half.

Core net financial results. Core net financial results, improvement of CHF 42 million and surprisingly, in Swiss francs as well as in CER, so the numbers are equal. And you look at the equity securities, I think that's a nice improvement here for the Roche Venture Fund. Net interest income, we had lower cash, so a little bit less compared to last year. Interest expenses, certainly, U.S. dollar helps here with plus CHF 43 million. And then in other, we have the increase in losses from currency results and other effects.

Core tax rate. Well, first of all, I think really it's great that it came in at 17.5%. You see just a very slight increase compared to half year 2025. Let me say here, it's a timing effect. The timing effects that we benefited from came up late. So very clearly, there will be an increased tax rate in the second half. And just to give you additional information here, I'm pretty convinced we will get to around 20%, perhaps a little bit lower for the full year, nevertheless.

Core EPS. When you look at the core EPS and at the bridge, and you see here the 9.3%, which represents a rounded 9% for the core EPS growth we've talked about already, you see operations is the major driver here. Then the product disposals and disposal of subsidiaries, as mentioned before, a decrease of CHF 104 million. The financial income and expense, really positive with CHF 42 million. Then the tax rate, which was pretty much stable. And then all other effects, once again, Chugai with an effect of minus 1.6 percentage points. So really the overperformance, if you like, from Chugai. When you take it out, and that's what we do in the core EPS, where we take the 40% out that we don't own, then you get to this effect.

Non-core and the IFRS income. Yes, you see really core operating profit up 10%, minus 1% in Swiss francs. And then the IFRS net income, up by plus 6%, minus 6% in Swiss francs. And what are the drivers? A little bit less restructuring charges compared to half year 2025. The major difference are the impairments here. Let me outline that we have an explanation for the impairments in Note 9 Intangible Assets in the Interim Consolidated Financial Statements on Page 65, where we really go through it.

Good. When you look at operating cash flow, I think really a great result here with plus 21%, plus 2% in Swiss francs when you really take the whole range of the bars that you have here on the slide. You see really operating profit net of cash adjustments, significant increase. Net working capital is basically effect from payables. On the Pharma side, I think that will wash out. So I think that looks promising. Investments in PP&E, flat. Investments in intangible assets, a little bit less compared to last year. You remember last year, we had Zealand with CHF 1.2 billion cash out. And that leads us to the plus 21%. And then you see the currency effect kicking in, bringing us to the plus 2% in Swiss francs.

Good. When we look here at the margins, I think overall, a great development. Both divisions contributed to what you see really on the left-hand side of that slide and the increase of 21%. So what does that mean for the group net debt development? First of all, you see really that net debt has increased here from end of the year 2025 until end of June 2026, and the increase here is CHF 5.9 billion. Having said this, when you look at gross debt, gross debt is stable. Just to mention this, gross debt is stable. Year-end, it was CHF 31.6 billion. This was not on the slide, that number. And at half year, it was CHF 31.8 billion. So really stable gross debt, which means we have reduced our cash position. I will come to that on the next slide.

When you look really what drove it, I think the operating free cash flow is clear. Then we have really taxes, and the treasury is minus CHF 2.1 billion. And then certainly, the dividend kicks in, as always. I think that's the driver normally for the net debt increase in the first half that we will work against in the second half.

Good balance sheet. I will keep that short. Two things to mention. As I said, cash and marketable securities, I said less cash available. We've paid the dividend. And then the other piece is really the equity. The equity goes down, which is a normal phenomenon for Roche, because we deduct the dividend payment from the equity. And then as the profits come in the second half, we hopefully -- we will not just hope, we will wash that out, and equity will increase.

Good, currency. Yes, interesting. When you really look at half year itself, I've mentioned the currency effects, I think, quite a bit. When you look at year-to-date September, keeping all the currency rates stable at the end of June, we get to minus 5 percentage points. And when you look at full year for sales, core operating profit and core EPS, we get to minus 4 percentage points, minus 6 percentage points and minus 6 percentage points, which is exactly the same prediction that we had in Q1. So the situation is stabilizing a little bit. Let's see what happens, but the volatility is still huge when it comes to currencies.

Good. With that, let's go to my last slide, which is the guidance slide. As said before here, Thomas has made the confirmation already. But let me mention here the LOE impact of roughly CHF 600 million now expected for 2026, which is a reduction to what we had at the beginning of the year 2026. Everything else is confirmed as we had it at the beginning of the year.

And with that, happy to hand over to Teresa.

Great. Thank you, Alan. So let's jump straight into Pharma. So Pharma sales, as Alan and Thomas both mentioned, grew by 6% at constant exchange rates, reaching CHF 23.6 billion at half year. That's 8% in U.S. dollars and minus 1% in Swiss francs. All regions delivered growth with international and Japan growing at double digits. You'll notice that the EU also returned to growth after Q1 was impacted by a number of pricing and one-off effects for specific products. As Alan mentioned, overall Pharma volumes were up by 9%. I'm not going to belabor the P&L too much because Alan made most of the comments that I would have made. Only to reiterate, the core operating profit is up by 10% at constant exchange rates versus that 6% sales increase with the COP margin of 53%. And just to underscore the extreme cost discipline, particularly effective cost management in R&D lending to that.

So now let's jump right into our individual brands. So my usual comment on the graph, all absolute values and year-over-year growth rates here are presented at constant exchange rates. In the first half of the year, our top brands, Xolair, Hemlibra, Ocrevus, Phesgo, Vabysmo and Evrysdi generated roughly CHF 1.4 billion in new sales at constant exchange rates. I'm going to share the details on all growth dynamics for our key brands on the following slides. So let's jump right into oncology.

Oncology sales increased by 1% to CHF 7.4 billion. Phesgo continues to deliver strong growth with the global conversion rate now at 54%. You may notice that this is 1% less than we had in Q1, and this is the dynamic that we normally see. We added 2 more countries into the global conversion metrics this quarter. We would expect that, that will correct itself over time as those countries now come fully online. And to reiterate, we are aiming for at least 60% conversion rate to Phesgo at peak.

Moving to Kadcyla. We are in line with expectations, and we continue to see competitive pressure in the U.S. and the EU. This is also a good time, I think, to reiterate our HER2 franchise outlook. We do expect the HER2 franchise to peak at around CHF 9 billion, and that's CHF 9 billion at 2024 constant exchange rates, just as a reminder, in 2026, followed by a steady decline through the end of the decade, with a solid tail of around CHF 4 billion, primarily Phesgo; around CHF 1 billion for Kadcyla; and a bit of Herceptin plus Perjeta. We do not foresee a biosimilar for the U.S. for Perjeta before 2028 and then the EU before 2027. Let me also confirm again that we do not foresee any cliff situation in the HER2 franchise.

The Itovebi launch is ongoing with good momentum, and we had an exciting Q2 news flow for giredestrant with the PDUFA date for lidERA in adjuvant ER-positive, HER2-negative breast cancer, set for November 30. To briefly remind everyone, for evERA, the PDUFA had already been set for December 18.

Now let's shift gears into lung cancer, starting with Alecensa. As we signaled previously, competitive pressure continues to increase, especially in the EU and the U.S. And therefore, we are, as Thomas mentioned, expecting flat growth through the end of the year. Moving on to Tecentriq. The new indications are driving global growth, especially IMforte in small cell lung cancer. Building on this, we're adding further indications with the successful U.S. approval for IMvigor011 in muscle invasive bladder and have filed ATOMIC in dMMR colon cancer with U.S. and EU regulators. I also want to confirm our full year outlook of low single-digit growth for Tecentriq.

Finally, we are very happy to report the positive outcome of the Krascendo 1 trial of divarasib in second-line plus KRAS G12C positive non-small cell, and let's take a look at that in more detail on this slide. So to reiterate, we recently shared the good news of the positive Phase III Krascendo 1 trial of divarasib in second-line plus KRAS G12C positive non-small cell lung cancer. Importantly, this was a head-to-head study against the currently approved G12C inhibitors, and the results clearly show divarasib's superiority in terms of PFS and OS improvements versus the approved G12C inhibitors. Let's also take note that, that OS statistical significance was already reached at interim, which is very impressive. The divarasib safety profile remained consistent with previous data and was overall manageable. The data will be submitted to health authorities and will be presented at an upcoming congress. So certainly strong results that reinforce our conviction that divarasib has best-in-class potential.

However, this wasn't the only good news for divarasib this quarter. At ASCO, we shared the results from the Phase II Krascendo 170 study in first-line non-small cell. Here, the combination of divarasib plus pembro achieved strong efficacy results across the PD-L1 positive and negative cohorts, and this bodes well for the ongoing Phase III Krascendo 2 study in the same regimen in first-line non-small cell. As you can see on the right side of the slide, we have a broad development program for RAS-targeted molecules. This includes divarasib in first-line, second-line and adjuvant non-small cell, but also a G12D-specific and several pan-mutation assets. So we don't only have one single mechanism of action, but we're bringing in potentially best-in-class molecules and different mechanisms, allowing us to think about unique combinations addressing the efficacy concerns as well as tolerability and combinability. We're extremely excited to see the progress that divarasib has already made, and there is more to come.

So next up, let's move into the hematology franchise. The hematology franchise delivered strong growth of 14% at constant exchange rates, achieving CHF 4.6 billion in sales. Our key growth driver for the franchise remains Hemlibra. We are seeing impressive continued global growth driven by an increasing adoption in non-inhibitor patients and an increasing penetration amongst older adults. Based on the strong performance so far, we're updating our full year growth outlook to mid-single digit from previously low single digit. I should note that this is a conservative projection, which takes into account increasing headwinds later this year due to upcoming competitor launches.

In that context, let me also tease that we're looking forward to sharing more on the in-development Hemlibra auto-injector at Pharma Day in September. A little bit of an aside. We did a demo device at the recent ISTH conference in Paris, and it was so popular that we literally had to position someone at the booth to prevent people from prying it off the wall because people were so eager to get their hands on it. So we're clearly excited to be able to bring you more information on this program and ultimately to bring it to patients.

So next up is malignant heme. Polivy keeps on achieving new milestones in first-line DLBCL with globally expanding market shares and now over 120,000 patients treated globally. That's up from 95,000 patients in Q1 in this setting. For Lunsumio, we achieved U.S. filing for the positive SUNMO data of Lunsumio plus Polivy in second-line plus DLBCL, and that PDUFA date has been set for February 9. Staying on the subject of second-line DLBCL, I wanted to briefly highlight our conviction and the potential for both Lunsumio and Columvi in this setting. Lunsumio SUNMO delivers a best-in-class safety profile with significantly less CRS, making it highly preferred by U.S. clinical advisers for outpatient and community oncology settings due to its manageable profile. Columvi STARGLO is supported by proven survival data with mature long-term follow-up and many advisers regard it as curative. It enjoys a 2-year plus first-mover advantage ex-U.S. and post reimbursement is the standard of care.

So now let's take a look at Gazyva. As I mentioned in our last call, we do see increasing competitive pressure in CLL and follicular lymphoma, impacting Gazyva's performance in hematological indications. This is essentially masking the ongoing Gazyva launch in immunology. However, we have the first early indicators of the launch in lupus nephritis showing a positive impact on overall Gazyva performance. And in fact, we see that Gazyva quarterly growth in countries like the U.S., Germany and the U.K., where lupus nephritis is launched and reimbursed, is ahead of the global average. So more on Gazyva and immunology in the coming slides, but let me repeat, we will show a sales split by therapeutic area in the future as those data sources mature.

Now let's take a look at the newest addition to our hematology pipeline. We recently announced and have now closed our partnership with Nurix Therapeutics to collaborate on the development of bexobrutideg. Bexdeg is a BTK degrader with a best-in-class potential in the BTK-targeted therapy space, so including BTK inhibitors. As you know, BTK, as a target, has been validated for different hematological malignancies, but also in neurology and immunology. More on that later. Importantly, bexdeg is a BTK degrader and via degradation, all functions of BTK are removed. This is unlike existing BTK inhibitors where some function may remain.

Additionally, BTK degradation has been shown to overcome BTK inhibitor resistance mutations. Furthermore, bexdeg has strong data showing it is highly selective and potent against BTK as well as has the ability to cross the blood-brain barrier. Taken altogether, we believe that bexdeg has the potential to deliver best-in-class efficacy, safety and tolerability. Our belief in the best-in-class profile is demonstrated by the recently initiated Phase III in first-line plus CLL, which is running head-to-head versus pirtobrutinib.

Speaking of the development program, we have a broad development program in malignant heme where we're moving at pace together with Nurix. And let me highlight that this includes a basket combination trial where we will explore different combination options in CLL. Additionally, we're planning to investigate bexdeg's potential in MS and CSU in upcoming Phase II trials. In short, a very exciting molecule to be added to the portfolio, and we're looking forward to updating you on the progress going forward.

So now let's move to neurology. Our neurology franchise delivered 9% growth at constant exchange rates, reaching CHF 5 billion in sales. Ocrevus global growth remains strong and the subcutaneous formulation, known as Zunovo in the U.S., is the key growth driver. We now have roughly 44,000 patients on subcut, which is a significant increase versus the roughly 24,000 patients we shared in Q1. And for the U.S., we're excited to see that Zunovo is now the fastest-growing anti-CD20 MS brand, underscoring the strong differentiation of being the only anti-CD20 with every 6-month subcut dosing.

Let me also quickly update the outlook. Beginning of the year, we had provided a 2026 growth outlook for the Ocrevus franchise in the high single-digit to low double-digit range. However, we're currently experiencing some competitive dynamics in the anti-CD20 space that are at the upper end of our previous assumptions. So therefore, we now expect to come in at the lower end of that high single-digit to low double-digit range for the full year growth outlook. However, this does not change our peak sales assumptions, and we continue to be very happy on how we track towards achieving that ambition. As a reminder, our peak sales expectations for the Ocrevus franchise are CHF 9 billion by 2029, and this includes CHF 2 billion in incremental sales from Ocrevus subcut, but there will be, of course, some switching from IV to subcut on top.

In the spirit of teasing Pharma Day topics, we're pleased to see that the development of the on-body injector for the subcut formulation is on track, and we're excited to share more on this subject at Pharma Day. Briefly staying with our MS franchise, I'm sure you are eager to hear more on our fenebrutinib filing efforts. Let me just say that we expect to complete U.S. filing in the coming weeks. And once we have filing acceptance later in Q3, we will confirm this milestone via press release as always.

And finally, we also shared positive updates on trontinemab in Alzheimer's disease at last week's AAIC in London, as Thomas mentioned. This includes long-term data from the Phase I/II study, which continues to underline the strong potential for tronti and the advantages of our Brainshuttle technology, where specifically, this long-term data confirmed the impressive amyloid clearance speed and depth as well as a strong safety profile for tronti. Furthermore, we shared the study design of PrevenTRON, our Phase III study of trontinemab in preclinical AD. PrevenTRON is enrolling cognitively unimpaired individual at high risk of progression to symptomatic AD and highlights our ambition to maximize the potential impact of tronti in Alzheimer's.

Next up is our immunology franchise. Immunology reached CHF 3.3 billion, growing 8% at constant exchange rates with Xolair being our key growth driver. Staying with Xolair, we have reached yet another significant milestone in food allergy, by now more than 130,000 patients have been treated with Xolair for food allergy since launch, a truly impressive number. Our 2026 outlook remains unchanged, and we expect around 20% growth for Xolair. This includes the expected impact of a first biosimilar entering the market in the second half of the year, which is currently projected for September based on our latest knowledge.

Actemra sales declined by 9% at half year, driven by biosimilar impact, as expected. And Gazyva has had a lot of positive news flow this quarter, but we'll cover this in greater detail on the next slide. But before we get there, let me quickly just comment once again on the ongoing launches in lupus nephritis. So as I mentioned on the hematology slide, despite the increased pressure on Gazyva in hematology, we do see strong uptake of the newly launched lupus nephritis indication. As I mentioned, we see Gazyva sales growing faster in those 3 markets where LN is already reimbursed. We see patient shares approaching 10% across those same markets, underpinned by strong early adoption in the hospital setting. We see a real inflection in particular in the U.S.

And in the coming quarters, we expect strong momentum to be driven by 3 New England Journal publications for SLE, lupus nephritis and the INS Phase III results, 2 FDA breakthrough therapy designations and growing lupus nephritis access and inclusion in clinical society guidelines. Taken together, we are confident in realizing the up to a CHF 2 billion opportunity for Gazyva across all of its immunology kidney indications. And finally, I'd like to mention the upcoming Phase III interim readout for sefaxersen in IgAN, which is expected for later in the year.

So now let's take a look at Gazyva in more detail. Starting with the Phase III MAJESTY study in MN, we recently shared at ERA, Gazyva clearly demonstrated superiority over tacrolimus on complete response, as you can see on the graph on the left. Based on the strong results, we believe in Gazyva's potential to become the first approved treatment for MN and therefore, the new standard of care. With that in mind, we're happy to report that we received U.S. and EU -- we achieved U.S. and EU filing in MN. And moreover, the FDA granted breakthrough therapy designation and priority review in this indication with a PDUFA of the 15th of November. As you can see, we have now successfully filed all immunology indications in the U.S. and the EU, and we are looking forward to regulatory decisions in the second half of this year, starting with INS in September. The new indications will further fuel Gazyva's uptake in immunology, and we're extremely excited for the impact that it's going to have on patients.

So up next, let's take a look at ophthalmology. Ophthalmology grew by 6%, achieving CHF 2.1 billion in sales. Vabysmo continues to expand its global market share and position itself as the preferred first-line treatment. This can clearly be seen, for instance, by the fact that more than 60% of U.S. patient starts are naive to treatment. I will spend a little bit more time discussing Vabysmo's growth outlook on the next slide, but here, I also wanted to highlight the positive Phase III POYANG readout in Vabysmo in myopic choroidal neovascularization. This is the potential fourth indication for Vabysmo and while a smaller opportunity is highly relevant for patients, especially in Asia. We are looking forward to discussing next steps with health authorities and data will be shared in an upcoming medical conference.

Moving on to Enspryng, our IL-6, where we are in development for TED, thyroid eye disease. We are excited to not only have achieved U.S. filing, but also to have been granted priority review. This underlines the significant remaining unmet need in TED and Enspryng's potential to provide a much needed additional treatment option for these patients. We're looking forward to the FDA decision by October 15. This leaves us with one more potential new ophthalmology medicine that we plan to file later this year, Vamikibart in UME, and we will, of course, update you once those filings have been completed.

Now as promised, let's take a closer look at Vabysmo growth. Let me start by confirming that we expect continued global market share gains and growth for Vabysmo. Furthermore, and as briefly mentioned on the previous slide, we see that Vabysmo has established itself as the preferred therapy for first-line treatment of AMD and DME. And this is in large part due to the strong and consistent clinical as well as real-world data. This data has shown time and time again that Vabysmo delivers strong anatomic outcomes like drying, paired with high durability across all of its improved indications. And the survey data you see on the left supports how Vabysmo's anatomic outcomes and durability are perceived. The survey comes from ASRS, that's the American Society of Retina Specialists, and is in the 2026 edition of their preferences and trends survey amongst roughly 1,000 retinal specialists in the U.S. and ex-U.S. So this obviously gives us confidence in the global market share gains and growth, but there are some regional dynamics that need to be considered.

In the U.S., we do believe the branded market has now stabilized, though at a lower level than before. We do see this as the new normal and don't expect a full rebound to previous levels, but do expect strong volume growth from here. As Vabysmo is perceived as the most efficacious drug, this will drive sales growth in the low single to mid-single-digit range in the U.S. In the EU, we continue to see strong share expansion across all key markets, and Vabysmo's strong volume growth is overcompensating for price effects in this region. And in the rest of the world, we see significant untapped potential and are encouraged by strong growth momentum across key markets.

In summary, we are expecting low double-digit growth globally for Vabysmo driven by ex U.S. with U.S. growing in the low single to mid-single-digit range for the year. Let me also say that we continue to consider consensus peak sales expectations for Vabysmo of around CHF 6 billion is very reasonable, and we're confident that we're on track to achieve this number.

So now let's move on to CVRM. The CVRM pipeline is making good progress. And following ADA, we hosted an IR call to cover the latest pipeline developments. So let's just focus on what happened in Q2. On petrelintide, we presented positive Phase II ZUPREME-1 data at ADA and shared our Phase III go decision. The data was well received with a lot of excitement about the placebo-like tolerability profile paired with double-digit weight loss that petrelintide demonstrated. We believe in the potential of petrelintide as a monotherapy to provide meaningful weight loss at a level desired by many patients. Combined with the exceptional tolerability that doesn't interrupt the daily life of patients and promotes long-term adherence, a critical factor for sustained health outcomes and chronic weight management, we continue to think this is going to be a very important option for patients. And together with Zealand, we're looking forward to initiating the Phase III in the second half of the year.

On enicepatide, which is formerly known as CT-388, we presented positive Phase II data at ADA, which I will cover in more detail in the next slide. The Phase III trials, ENITH-1 and 2, for enicepatide in obesity are ongoing, and we announced plans to initiate Phase III trials in glycemic control as well as a CVOT. On CT-868, we announced at ADA that we decided to discontinue the development of CT-868 in type 1 diabetes. It's important to note that this decision was entirely unrelated to the safety or tolerability of CT-868. We did have positive Phase II results. But ultimately, we believe we have better options in our portfolio to address the unmet needs for patients with type 1 diabetes. For example, based on the latest data, we believe that enicepatide may have best-in-disease potential for glycemic control. We look forward to sharing the details of our plans in type 1 diabetes at a later stage.

There is a lot of news flow for the remaining of the year, in particular, Phase II results for enicepatide in obesity with type 2, Phase II CT-3 -- sorry, Phase II CT-996 results in obesity, our oral therapy; the Phase II ZUPREME-2 results for petrelintide in obesity with type 2; and finally, the Phase II GYMINDA results for emugrobart plus tirzepatide in obesity. We plan to provide updates for all of these at Pharma Day, upcoming conferences or by top line releases when the data is available.

And let me quickly finish this slide by commenting on further pipeline progress expected to happen in the second half. The Phase II study of ZYNERGY for enicepatide plus petrelintide in obesity is about to be initiated. This study is designed in a comprehensive way so that we can find the ideal combination of the 2 for the best efficacy and tolerability profile. And that is, of course -- and that, of course, is key to select the best fixed-dose combination for the potential Phase III. The decision for Phase III initiation for petrelintide monotherapy in obesity has been formally taken in Q2, and that study is expected to start in the second half. And finally, the Phase III initiation for CT-996 remains scheduled for half 2 following the Phase II readout, which is soon to come.

Now as I mentioned, let's take a closer look at the enicepatide Phase II data presented at ADA. I do believe it is worth reinforcing some of the key insights from the Phase II results that were shared at ADA and in particular, highlight why we're so excited about enicepatide, which we believe has a clearly best-in-class weight loss profile. First, on the left side of the slide, you see the weight loss curves. So clearly, the 24-milligram dose did not reach a weight loss plateau at 48 weeks. Therefore, we see the potential for additional weight loss with longer treatment. That's something we hope to see in the Phase III, which includes longer treatment durations. We have also shared at the ADA IR call that we will explore dose levels higher than 24 milligrams as we've not seen the tolerability ceiling at the highest dose tested.

Secondly, the right hand of the graph shows what percentage of patients achieved what weight loss at a certain dose. What you can see here is that the highest 24 mg dose tested, 48% of patients achieved greater than a 20% weight loss, 38% of patients achieved greater than a 25% weight loss and 26% of patients even achieved a greater than 30% weight loss. Based on these results, we believe that enicepatide has clearly the potential to develop weight loss approaching the efficacy seen with GGG drugs in development and with a tolerability profile in line with that of the dual GLP-1/GIP agonists.

So overall, we are very excited to further develop enicepatide as a monotherapy, but let me also highlight that upcoming Phase II combination trial of enicepatide and petrelintide, combining these 2 molecules with their respective strong clinical profiles and the potential to address unmet needs for patients beyond just the scope of monotherapy, in particular, for patients needing greater weight loss and/or better glycemic control with better tolerability. We have strong conviction in the combined potential of these already individually strong assets, hence, the name of the trial, ZYNERGY. We expect to initiate that trial in the second half of the year.

And now on to my last slide for the day. So as usual, let me close with the 2026 Pharma key news flow. All of the updates here I have already covered on previous slide, but there is one piece that I want to highlight. So far this year, we have achieved 5 FDA priority reviews so far, which is really impressive. And that, of course, helps to speeding up regulatory processes and bringing medicines faster to patients. Just to reiterate, these 5 priority reviews were granted for giredestrant in the adjuvant early breast cancer, Enspryng in TED, Tecentriq ATOMIC in dMMR and MSI-H colon cancer, Gazyva in INS and most recently, Gazyva in MN.

So with that, I am happy to hand it over to Matt.

Thanks a lot, Teresa, and congratulations for the strong half of the year. So with that, good morning, good afternoon, everyone. It's my pleasure to present the half year 2026 Diagnostics division results. So as you heard from Thomas and Alan, with sales of CHF 6.7 billion, the Diagnostics division grew sales at 3% or plus CHF 228 million compared to last year at constant exchange rates. Now this growth was achieved despite the ongoing impact of the healthcare pricing reform in China, which continued to impact sales in 2026. Excluding the effect of the healthcare price reform in China, sales would have grown at plus 6%. Additionally, as you heard from Alan and Thomas, we had the impact of the weak respiratory season in the Northern Hemisphere, which impacted Diagnostics sales by an additional CHF 50 million.

So with that, let me go through the results by customer area. So sales in our largest franchise, the Core Lab, increased 4%. This is impacted by the previously mentioned policy impact in China. Excluding this effect, the Core Lab grew at 8%. Sales in the Molecular Lab grew at plus 3% with -- and I would call it the strong performance of our transplant business, which grew 18%. However, again, this was offset by the previously mentioned mild respiratory season, which lowered the overall testing volumes. And sales in the Near Patient Care business area -- or customer, excuse me -- decreased at minus 5%. This was driven by lower cobas liat sales, again due to the weak respiratory season, but offset partially by growth in our blood glucose monitoring business at plus 3% following competitive wins. Sales in our Pathology Lab grew strongly at plus 11%, mainly driven by advanced staining growth of plus 7% and companion diagnostics growth of plus 24%.

So now allow me to take you through the performance at a regional level. So we saw growth in North America at plus 8%. In EMEA, the business grew at plus 3%. LatAm grew at plus 10%. Now in APAC, the business declined at minus 5%. As previously mentioned, sales growth was impacted by the healthcare price reform in China. And as a result of this, China sales declined at minus 15%. Excluding China, APAC sales grew at plus 6%. Now as you heard in our full year and Q1 earnings calls, we expect a lessened impact of the China price reforms in 2026. And I would call out again that our ambition this year is to grow sales at mid-single digits. Looking forward into 2027, our ambition will be to return to mid- to high single-digit sales growth.

Now I'd like to take you through our P&L line by line. And Alan went through the cost of sales in some detail. And as you mentioned, cost of sales increased 5%, first, driven by the impact of the pricing reform in China, the cost of manufacturing ramp-up for our new launches as well as the tariff impact in the United States. R&D increased at 3% as a result of the increased spend on our innovative systems, including our AXELIOS sequencing solution and our i 601 mass spec. SG&A increased at 3% due to higher distribution costs associated with increased sales volume and also commercial investment into our new launches. As a result, core operating profit on sales of CHF 6.7 billion was CHF 1.2 billion, increasing at plus 6% at constant exchange. As you heard earlier, this was also benefited by CHF 126 million in extraordinary income from patent licensing.

Now I would like to reiterate our ambition from previous calls that while our consistent ambition for Diagnostics is to grow profit faster than sales, our ambition for full year 2026 is to keep our margin broadly stable at constant exchange versus the 14.4% from full year 2025 as we absorb the impact of the healthcare pricing reform in China and the U.S. tariffs. I would also like to mention that in 2026, we again anticipate a negative impact -- or excuse me, we have a negative impact from currency headwinds on our COP margin.

Now I would like to turn to some of the exciting developments in the Diagnostics pipeline. Specifically, I'd like to start with the launch of our AXELIOS 1 sequencing solution, which I'm delighted to report that we launched on June 29. Thomas talked a little bit about our history of M&A, specifically the acquisition of Stratos and how it relates to our development here. I would also frame the discussion by saying that our next -- we view the next-generation sequencing market at around USD 7.3 billion. This was assessed in 2025, and we expect to see it continue to grow, especially as new clinical applications become part of routine use.

I would also like to briefly highlight the performance we achieved with our AXELIOS sequencing solution, as you can see on the left-hand side of this page and why we feel the solution is so highly differentiated. We have 2 run modes utilizing our SBX sequencing by expansion chemistry and our SBX-duplex as well as our SBX-simplex workflow. Now this enables us to achieve flexibility, speed and scalability that is unprecedented and deliver what we feel is a very, I'd say, differentiated cost effectiveness. Now as we previously demonstrated with the technology, we are able to achieve 1.8 terabases of SBX-duplex output in 4 hours of sequencing time. And this is equivalent to around 16 whole human genomes.

I would mention that this is also combined with a high level of accuracy with a Q score of 38, which translates to approximately 99.98% accuracy. Additionally, the simplex mode offers an ultra-high throughput and also longer reads of up to 1,500 bases which can enable isoform detection and structural variants combined with our differentiated price position. And here, I would call out that in 1 4-hour run, we're able to generate 40 billion reads with an average of 175 base pairs, which is an unprecedented amount of data output. I would note that the interest from the market has been consistently high since we unveiled SBX at AGBT in 2025. And our AXELIOS 1 solution is positioned to set a new standard of care in next-generation sequencing for a broad array of applications.

And Thomas mentioned this a bit earlier, how AXELIOS really fits in across our entire vision for oncology. Our strategy in oncology with Diagnostics is to build an end-to-end portfolio that follows the entire patient journey via a combination of internal innovation and purposeful M&A. This is everything from early cancer detection, precise diagnosis of cancer, therapy selection as well as disease monitoring.

So here, I'm delighted to discuss the definitive merger agreement we've signed with PathAI earlier this month, which completes our offering in primary and advanced staining for cancer diagnosis. PathAI is the leading provider of digital pathology Image Management Systems, which enables pathologists to augment their existing IHC or primary, which is H&E staining workflows with AI-powered digital algorithms and tools to automate slide analysis and provide deeper patient insight. The combination of AI-powered digital pathology image management, combined with clinical decision support algorithms will integrate seamlessly with our Ventana solutions and augment our PHC business to increase our leadership position in companion diagnostics.

This solution is wholly complementary to our Ventana business. And by putting these two solutions together, we're going to be even more competitive in this key area of our business. In addition for the pharma side, this will enhance our pharma business with AI solutions that support our clinical trial work as well as enable the introduction of new biomarkers.

So Teresa mentioned briefly AAIC. And now I'd like to switch to our Elecsys pipeline, specifically the launch of our CE mark -- or excuse me, the CE mark we received for Elecsys pTau217 test, which we received on May 12. So Alzheimer's disease is the leading cause of dementia worldwide. We anticipate that it will affect over 80 million people by 2030. However, diagnosis takes approximately 3 years after symptom onset and routine diagnostic methods are either invasive or difficult to access. They involve imaging methodologies that are not readily available and lead to this significant backlog in patient diagnosis.

So with our Elecsys217 assay, we provide a rapid, minimally invasive alternative via a simple routine blood draw. This test is the first blood-based biomarker intended to rule in or rule out Alzheimer's in primary and secondary care settings as a result of the study that we performed. Our assay demonstrated high diagnostic accuracy across health care settings and clinical stages and initially meets the CEOi recommendations for Alzheimer's disease diagnosis. By bringing this test into health care systems worldwide, particularly primary care, we will help physicians to identify Alzheimer's disease earlier, which will facilitate timely intervention and reduce -- and potentially reduce health care costs.

So now I'd like to transition to latent tuberculosis and continue with an update on our Elecsys IGRA TB test, which received CE mark earlier this month. And why this test is important is around the world, approximately 25% of the world's population is estimated to be a carrier of tuberculosis infection. And as a consequence, this is one of the world's largest public health challenges. With Elecsys TB, we enable high throughput testing, automated result generation and a 3-tube workflow, which is superior versus existing systems that are available while maintaining comparable levels of data performance in the clinical setting.

And in the near future, we plan to integrate our cobas ultra solutions to automate the pre-analytical steps, further improving laboratory efficiency for tuberculosis testing, and it will also help facilitate our entry into the high-throughput segments of the market such as the U.S.

This test has the potential to expand global access to latent tuberculosis infection testing and also help advance progress towards the WHO elimination targets. And I would call out here that we have the broadest installed base of immunoassay analyzers anywhere in the world, and we will leverage our installed base to grow and expand with this test.

So to conclude, I would like to report the progress on our key launch list for the Diagnostics division. Of the 11 launches shown here, we've achieved 7 by half-year 2026. We're making good progress on those that remain, and I look forward to updating you on this in future calls.

And with that, I would like to hand it over to Bruno Eschli. Thank you very much.

Thanks, Matt. And let me quickly close here with the next event, which is scheduled for our investor and analyst community. We have Pharma Day coming up at the 28th of September, again, as a live event in London, similar setup as in previous years and a couple of highlights here to call out. In the morning session, we will again cover our pharma strategy and provide an update on our commercialization efforts. We will provide an update on the R&D excellence initiatives on the KPIs we have shown in recent years. And then also have a focus on our cost-saving initiatives and reallocation on the investments.

And then I think a special highlight is we have Aviv Regev joining on the implication of AI and early drug development. We'll take you through all the stages of early drug development and how AI there comes to life and where we stand. And then in the afternoon sessions, with a similar setup like last year, we will take you through the five therapeutic areas with the new area head being present. And until the end of September, we also would expect a couple of additional data points to come in.

And as Teresa mentioned already, we have then the opportunity also to touch on some of the assets of the obesity franchise like 388 or 996 and provide updates on them.

And with that, I think we are done with the presentation, and we'll open the Q&A session.

First questions would go to Graham Parry from Citi.

There's a question on divarasib. You've obviously started now the Krascendo II trial. Primary completion date on clinicaltrials.gov for that is October 2028. I was just wondering though, given the very long PFS that you saw in the Phase II of 19 months, whether you feel there could be separation occurs and an earlier readout on that?

And then secondly, you still have this as a CHF 1 billion to CHF 2 billion peak sales opportunity in your slides despite the strong Phase II data and in Phase and hitting the primary endpoint in the second line as well. Is that now just achievable with the second-line indication? And when would you provide an update on whether you see that as going higher given the strong PFS -- long PFS you're seeing in these studies?

Great. Thanks, Graham. Well, I think Pharma Day is going to be for you. So we will be able to provide an update on the entire divarasib clinical trial program as well as the fact that we are currently now based on the strength of the Krascendo I data, we are reevaluating what we believe peak sales might be. So we're talking with thought leaders, thinking about what our ultimate clinical trial program will look like, and we'll be able to provide you an update at Pharma Day. So for right now, we are confirming CHF 1 billion to CHF 2 billion, but stay tuned.

Graham, did we answer all your questions?

Just the potential for readouts in early readout in 2028.

So I mean, I think we've just initiated the trial. So we'll see how we go. And as always, with an event-driven trial, the data will tell us.

Okay. Then we move on. Next question, go to Simon Baker from Redburn.

Two, if I may. Firstly, I see for Lunsumio, it's entered Phase II for SLE. Just wondering if you could give us your thoughts on Lunsumio in that setting and also the interplay with Gazyva in that space?

And then secondly, on Vabysmo, Teresa, you gave us some color on the dynamics within that market. I just wonder specifically if you could give us an update on any activity you're seeing with respect to patient assistance foundations either by yourself or others and your expectations of that for the rest of the year.

Great. So in terms of Lunsumio for SLE, so SLE is a very heterogeneous and complex disease. And while we saw great results with Gazyva, we do believe there's an opportunity for more benefit for patients. And we think that based on Lunsumio's mechanism of action and its safety profile, we think it could actually be a really great option for patients with SLE. It has very strong B-cell depletion as does Gazyva. So we are curious to see whether or not with a slightly different mechanism, we can actually achieve even greater results for these patients. So stay tuned on Lunsumio, but deeper and deeper B-cell depletion is likely what these patients need -- what these patients need.

In terms of the copay assistance foundation, so again, I will just reiterate that these are charitable donations and they're certainly not meant to drive sales. But I think what we are seeing is that there has not been a recovery to the overall market. We are seeing sort of that 2% to 3% growth in the overall retinal market. We do expect that this is going to be the new normal, and we don't expect to rebound to previous levels.

Okay. Then we go on. Next question go to Sachin Jain from Bank of America.

I've got a few, if I may. So firstly, just another one on lidERA launch. At 1Q, you talked optimistically about launch in discussion by risk group. My question for this quarter is what visibility you have on a bolus of patients that could be fast adopters. That's specifically patients who, over the course of last 3 or 4 years have discontinued CDK4/6 due to toxicity and are back on just an AI. So any sense, firstly, how big that bolus is that could be rapid adopters? And would usage in that switch group be consistent with an expected label?

Second question is Ocrevus. You're calling out competition. I'm guessing that's Briumvi. Wondering if you could just give us a bit more color as to why that's impacting now given it's a launch for a while and why you think it's temporary?

And then just one question for Alan. I think it's the first time you've called out the expected growth in other revenues midterm 3% to 5%. That kind of implies $2 billion growing to about $4 billion. That's all EBIT. So is that a driver of margin expansion? Or is it funding investments within your commentary of margins being stable? I'm just going to dovetail that with Bruno also mentioning an entire cost focus session at the Pharma Day.

Okay. So let's start with giredestrant. So I think it's -- so first of all, Sachin, I think you're spot on to something here, but let's start by sort of looking at what does the treatment of ER-positive, HER2-negative early breast cancer really look like. So there's sort of four risk groups of patients. There's the low-risk patient group, which is between 55% and 60% of patients. There's the intermediate risk group, which is about 10% of patients, the medium risk group, which is between 15% and 20% of patients and then the high-risk group, which is 15% of patients.

We would expect that one of the first places we would gain utilization is patients who just aren't on CDK4/6 inhibitors right now. That's 90% plus of that intermediate group, it's 80% plus of the median risk and 50% plus of the high risk. And so there's a tremendous opportunity within that group that has just never gone on the CDK4/6. But you are right, there's about 50% of patients today who can't tolerate their CDK4/6 treatment. And it's part of the reason that we see such bad outcomes for people with this type of cancer, they just can't tolerate the treatment. And so for those people who either can't tolerate and maybe who have come off and are waiting, we would absolutely see this as a potential patient population, and we wouldn't see this to -- it wouldn't be in conflict with any -- likely with any kind of label.

The switch question or the line of therapy that is not -- the switch question is not usually something that comes up in the label. We are generating, however, switch data. So for patients who are on CDK4/6 today and want to switch, we will generate that data. And we are also generating data for that low-risk population, which is the majority of patients, that 55% to 60%, none of whom are currently on treatment. And then our own combination data is also forthcoming.

So we do believe that when you look at the totality of the giredestrant data that we have in our hands already between lidERA and evERA, we've already got about 80% of the market covered. We're doing trials to cover the rest and sort of really looking at what is the clinical data that we need to make sure that we have the ability to answer all of the physicians' questions in terms of other ways that giredestrant might be utilized. But we do certainly think that there is quite a bit of opportunity for giredestrant.

And in terms of competition with Briumvi, I mean, it's just -- normally, we don't comment on individual competitors. Generally, we're just seeing a higher level of competition in the market. And we certainly believe that based on the clinical attributes of Ocrevus, we are very well positioned to compete. Ocrevus remains the leader in MS with Zunovo as the key growth driver. It is the fastest growth driver in MS. It's the first and only twice yearly MS therapy that's approved in RMS and PPMS. It has over a decade worth of experience. We see that 80% of first-line RMS patients don't experience progression. 90% don't need walking implements.

We're the only high-efficacy therapy that has robust family planning data in hand. And frankly, that outstanding patient convenience with 6 months dosing available as a 10-minute subcut just twice a year. I mean that's an incredible value proposition for patients. So I think in any given situation, you will see a little burst of competitive activity. But at the end of the day, these aren't driven on clinical differentiation. Ocrevus remains the most differentiated product in MS, and we strongly believe in our ability to compete and win for patients who deserve to be on the best therapy.

Yes. Let me take the margin point, Sachin. I think you made a great point. I think very clear once we grow from 3% of sales to 5% of sales, that makes a difference until the end of the decade. There's no doubt about it. I think for the time being, nevertheless, I think we stick to the point to say, either we stabilize the margin or we grow it. I think now things come nicely together. We'll see how that plays out. And yes, I think that gives even more substance to our statement.

Sachin, did we answer your question?

Yes.

Then we move on. Next one in the row is Colin White from UBS.

Colin White from UBS here. Just to go back to Vabysmo. You talked about being confident of the stabilization of the branded market. I was wondering if you could talk about the dynamics related to the reduced Vabysmo growth expectations between charitable funding assistance and the increased use of biosimilars. And if biosimilar market share shift, where -- what percentage of the market do you expect to be biosimilars going forward? And why do you have confidence that the branded market is now stabilizing?

And then just a second question on first-line DLBCL, if I may. There's a big competitor readout for Epkinly coming up in first-line DLBCL. So -- if that study reads out positively, I just wondered what you're thinking about in terms of the impact that might have on Polivy and how it fits in with your own first-line study for your anti-CD20.

Yes. So I mean, let's talk a little bit first about the biosimilar market in ophthalmology. I mean it's just a little bit different than in other places. But where we are seeing biosimilar impact happen, it is impacting sort of directly the molecule that it's replacing. So a biosimilar to Lucentis took Lucentis share, biosimilars for other molecules are taking specifically that share and really impacting that part of the market. You don't really -- we're not really necessarily seeing the bleed over that you might see in other places. We saw 8% growth with Vabysmo in sales, this half, but we saw a 30% increase in volume globally.

So we really do believe that Vabysmo has entrenched itself as the preferred therapy of choice. I think you can very clearly see that from the ASRS data and that where physicians are making a determination for a new patient, the majority of the time that is coming Vabysmo's way. And again, we're not seeing new biosimilars entering the market impacting Vabysmo. We're seeing them impact the originator product that they are the biosimilar of.

The stabilization that comes from just sort of having watched the market over the last 6 months, talking with physicians and seeing how are they running their practice and what they're -- how they're utilizing the resources available to them and their patients. So we do think that 2% to 3% overall growth in retina will accommodate the biosimilar entry, will accommodate other things. But clearly, Vabysmo is continuing to grow in the U.S., and it is continuing to take a disproportionate share of that branded share growth.

With regards to the competitor entry, so they are about a year ahead with first-line DLBCL, but we do see POLARIX being just a much better tolerated regimen in first line. So we wouldn't necessarily expect to see a terrible amount of impact there. POLARIX has well established itself in first-line DLBCL. You meant POLARIX, not Lunsumio because that's really the first-line DLBCL drug.

Colin, did this answer your question? So we also have our own study coming up next year.

Yes.

As you know, SKYGLO.

Yes.

Okay. Then we move on. Next one in the row is Justin Smith from Bernstein.

Just a very quick one on 007. Sorry if this is a bit ignorant. Just any kind of qualitative conviction you can give us as to why 360 patients means you're well powered in that sort of head-to-head versus Hemlibra in Phase III?

Yes. I mean I think we've done the statistical analysis based on what we know about the performance of Hemlibra and what we believe to be true about 007, given, as Thomas mentioned, the incredibly high level of potency, and we feel confident in the design.

Yes. Maybe what I can add here in terms of the time lines, I think for this study, which now has seen the first patient in, we would expect data, I think, at around year-end next year, beginning of the year after. So in '27 and '28, which I think also puts us in a very favorable situation here to bridge to the next generation.

Any additional questions, Justin?

All good.

Thanks, Justin.

Then we move on. And next questions go to Sarita Kapila from Morgan Stanley.

At ASCO, you talked about new indications, sorry, for giredestrant, for the heredERA trial and then evERA trial. Could you quantify how large you think these opportunities are and whether these are upside to the CHF 9 billion peak commentary? And how -- if I can squeeze in, do you see positioning specifically for heredERA of giredestrant in HR-positive, HER2 breast following positive data for Pfizer's Ibrance in the PATINA trial.

If I could just squeeze in a quick follow-up on divarasib. If you're reevaluating peak sales, this is the [ KRAS G12D-C ] how should we think about it versus emerging panRAS agents, including pipeline or programs within your own pipeline?

Yes, absolutely. So when we think -- I'll start with the second question first and then go up to giredestrant. So when you think about KRAS mutations, KRAS mutations are present in about 25% of patients with lung cancer. G12C mutations are present -- they represent 40% of the KRAS mutations, which means you're at about 12%, 13-ish percent of overall non-small cell patients have a KRAS G12C mutation. So the potency, the selectivity, the safety profile of divarasib, we believe, positions it very well in patients with those specific mutations. And I think we've seen that in the 170 data, we're seeing it in Krascendo 1, and it's something that we expect will play out in other trials as well.

So I think because of the very strong specificity for that mutation and the fact that mutation is so prevalent, I think if you have that mutation, you would be more apt to use a therapy that would target that mutation directly. Certainly, there's going to be a place for pan-RAS inhibitors. We have several of them in our pipeline as well, and we look forward to developing them and seeing what their results are for patients. We have a very diverse pipeline here, which is great.

When you talk about the opportunities within -- for giredestrant, as I mentioned previously, between lidERA and evERA, we already have 80% of the ER-positive, HER2-negative market covered. So the other trials that we have in place that are looking at the different aspects of first line in different combinations, those really give us the opportunity to cover pretty much 100% of this patient population. So the peak sales that we've mentioned, they sort of encapsulate the fact that we do have a pretty broad program already in place for giredestrant. But certainly, if some of these other programs came in, that could potentially be upside as well. And as I mentioned, we'll be able to give you a very good and thorough update of what our development plans look like for giredestrant at Pharma Day in just a couple of weeks.

And I mean, the upside on divarasib is also in other cancer types, right, beyond lung cancer. In fact, the RAS is one of the best known or most known and most mutated genes in cancer in different cancer types.

Absolutely.

Did we answer all your questions, Sarita, or your follow-on questions?

Yes.

Okay. Then next questions go to Richard Vosser from JPMorgan.

A couple of questions, please. Just a follow-up on Ocrevus and Zunovo uptake seems very strong and very fast. So you mentioned again the $2 billion for Zunovo. But could this actually be larger and protect more of the franchise from biosimilars? So just thinking about that.

Second question, a follow-up on Vabysmo. I don't think you mentioned pricing impacts. Just wondering about -- we've seen biosimilars to other agents affect pricing in the classes. Obviously, there's very low dose of Avastin here. But are you seeing anything in -- or very low price Avastin, but are you seeing anything there in terms of pricing maybe in the ex U.S. market?

And then one final question, just on other revenues coming back to that. I think there are probably some milestones there in this quarter for some of the new agents. You've got quite a lot of new agents from other companies launching. Just should there be other milestones that we should think about in the next few years that could boost the trajectory from actually the royalties that you're getting in? Just some thoughts there as well.

Yes. Great. Thanks, Richard. So I promised you guys a hockey stick for Ocrevus, Zunovo, and we have delivered the hockey stick. We're well on our way. We do think that as people -- as I mentioned in many other calls previously, as practices and patients get experience with Zunovo, it fits into the practice flow very, very well, and it's intensely convenient for patients.

So is there additional conversion opportunity? Quite probably. I think at the moment, we still feel very confident in our additional $2 billion, understanding that there will be the sort of $2 billion that are just brand new patients to Zunovo, but we would expect that there will be switching as well. So ultimately, that entire pie could look bigger. And certainly, that would provide some additional protection to Ocrevus over time as would the on-body injector, which we're excited to talk more about at Pharma Day.

In terms of Vabysmo, I mean, certainly, we've seen pricing impacts outside the U.S., but those have largely been related to volume because Vabysmo has been doing exceptionally well in generating patient share outside of Europe or inside of Europe.

Alan?

Yes. I think really in general, no, that's the answer. I think there can always be stuff, but that's why we have said we go from 3% to 5%. And I would argue that includes everything.

And it's mostly royalty driven, not milestone driven.

Absolutely...

Just to be very clear. But also, I mean...

There are a couple of milestones...

The majority is royalty by far. But on the Ocrevus side, also, you were talking about switching to Zunovo also to make sure that we can protect the franchise into the next decade as well and beyond. Here, I just want to say that we have a couple of other options in play as well with fenebrutinib, but a number of things that we have in the pipeline where we believe that we can extend that as well. Absolutely.

Richard any additional questions?

No.

And next questions come from James Gordon from Barclays.

James Gordon from Barclays. A couple, please. One with giredestrant and adjuvant and the launch expectations. So at ASCO, there was some mixed discussion feedback lidERA and talk about need for longer-term PFS data and OS and more data versus CDKs. Do you think that view is typical? Could that blunt the initial uptake at all? Or do you think that's atypical? And where are you on ex U.S. regulatory might you need longer-term data there? And I think Bloomberg consensus is about CHF 300 million next year, which doesn't look a lot versus the size of the very big hormone breast cancer market. Are there any sort of roadblocks we should be aware of if we're modeling out the launch? Or is that plausible?

The second question would be fenebrutinib regulatory. So latest confidence on U.S. approvability. I know some investors still have quite big safety and tolerability concerns. But I know you've had a bit more time to have some interactions with regulators. Anything concerning there? And where are you ex U.S.? Any interactions there? I saw fenebrutinib's been EU-approved despite the liver profile. But how are you thinking about timing for ex U.S.?

And then finally was just obesity update. So we've got updates on your GLP-1/GIP and your amylin at ADA. I think you've got your anti-myostatin and your oral GLP-1 imminently, presumably at the Pharma Day or before. So how are you thinking about differentiation? And of the four assets in obesity, which is the one that's most exciting, because you've given similar peak sales estimates for them all. Which is the one we should be most excited about?

James asking me to pick my favorite kid. That's harsh. Wow, okay, there's a lot in there. So in terms of giredestrant adjuvant, I would say that we are spending a lot of time with KOLs and with potential treaters, sort of asking what their confidence is in the data. And I think what we are hearing is that people are excited about having an option. The profile of giredestrant is very attractive to people. We've mentioned this a number of times before, but with CDK4/6 is 50% of patients can't stay on their therapies over time. And that necessarily means that, that leads to worse outcomes when you can't take the medicine that's designed to help you.

The giredestrant tolerability and safety profile just looks much better. And so I think we are increasingly confident that physicians are excited about giredestrant and we'll find a place to use it in their practices fairly easily. So my writing is not great here. So ex U.S., we are currently assembling the data package that we believe will be the most robust data package to allow us to file in Europe and achieve a sustainable reimbursement value. And so that is coming, and we would expect that we fully intend to file in Europe and are just waiting for that data package to mature.

In terms of the consensus numbers, so we don't generally comment on -- specifically on launch projections. But what I will say is that we should remember that this is a chronic therapy. And so while we do expect a strong launch, clearly, the big numbers will build over time as they do with any chronic therapy. We would expect patients will stay on giredestrant for 5 years plus given what we've seen in the market and what the tolerability profile is for giredestrant.

In terms of fenebrutinib regulatory, so as I mentioned, we're well on track to file first in the U.S. We'll use that U.S. package then to springboard off of for other regulatory filings. We are collecting the additional data that we need for the EU. And again, we have every intention of filing. And again, our focus has been on getting the U.S. package ready, and then we'll go from there. While I won't comment on the specifics of any regulatory interactions, we haven't seen anything that would indicate that a filing in the U.S. is going to be at all problematic.

And then in terms of picking my favorite child, that's really, really unfair. I think that what we saw at ADA with just the really impressive weight loss data from enicepatide and the very interesting and positive tolerability profile for petrelintide. I mean if you think of that bell curve that I showed you guys at Pharma Day last year, for the patients who need deep weight loss, we have that. For the people who maybe need that 10% to 15% weight loss with a placebo-like tolerability, we have that. The fixed-dose combination could be a booster for both of those products. I think what we are finding is that the nature of both of these medicines in different ways are making them differentiated and are giving them opportunities to really find a very unique space in obesity in ways that will ultimately really help patients with what they need. And I think that's actually super exciting as we head into our Phase III programs.

Clearly, we'll have the data on the anti-myostatin and CT-996 quickly. I mean having an oral option is, of course, important. So we're excited to see 996. But I would have to say, I don't think I can pick a favorite because I think what I really love about the obesity portfolio that we've built is it's delivering on exactly what I talked to you all about last year at Pharma Day, the ability to build a broad adaptive portfolio that regardless of what a patient's obesity -- where they are in their obesity or health journey, we have a medicine that can help them. And we could help them throughout their entire weight loss journey. And so I'm just really excited about what we've seen in the data as it's come to maturity and increasingly getting excited about bringing the entire portfolio to patients.

Let me add two points, one on giredestrant and one on fenebrutinib also that increases my confidence level in those molecules. You already pointed out the safety profile of giredestrant specifically against CDKs. I would like to point out not only the potency advantage it has versus another SERD, but also the label and safety aspect that it has versus another SERD. So I think from a safety perspective, it is quite differentiated as well.

And then on fenebrutinib, we mentioned that before that the FDA allowed open-label extension for fenebrutinib for initially PPMS patients. And so people that were on the fenebrutinib arm continued, but people who were on the control arm were switched to fenebrutinib. Now the same happened for RMS. So the RMS patients that were on fenebrutinib continue in the open-label extension as well as on the control arm patients moved to fenebrutinib. So I think these are good indicators, I would say. It gives us a certain level of confidence in that. But ultimately, we'll see.

Very good. Any additional questions, James?

I'll leave it there...

Then we move on to the next James. James Quigley from Goldman Sachs.

I have two as well. So again, both for Teresa. So the BTK degrader, from the data you've seen so far, where do you think the asset can be differentiated in cancer indications? Is it efficacy, safety, combinability dosing? It would be interesting to hear there. And then also as you move into immunology, where do you hope to be differentiated on the immunology side? And how quickly do you think you can move there into MS and CSU depending on when you see the data?

And secondly, Gazyva in immunology, I think I asked this last time as well, but when we hear you speak, Teresa, you sound very excited about the opportunity. When you look at the 4 indications, $2 billion, it looks like it might be on the low side. So what is holding you back at the moment in terms of looking at peak sales here? Is there anything in the indication size? Is anything in terms of segmentation that might be holding you back on the potential peak sales for Gazyva?

Great. Okay. A lot of immunology questions. Okay. So bexobrutideg, all of those things, right? I think we're excited about the potential. I think we're excited about the efficacy. I think we're excited about the safety, the tolerability, the combinability. I think we really believe that BTK degrader could be a real game changer in some of these indications, particularly in oncology. And so I think we're very excited to get this into trials and to see where it can go. Now that having been said, for all of those same reasons, having the degrader versus the inhibitor, we could see a really differentiated efficacy profile in immunology.

Immunological diseases are notoriously difficult to tackle. I mean they're -- as I mentioned previously, they're very heterogeneous. And so having a degrader versus an inhibitor, I think we could very well see that incremental efficacy, which in immunological indications can really be quite meaningful. So time will tell. It's a brand-new asset to us. We'll give you a little bit more insight as to what our plans are at Pharma Day, but I think we're really excited to have this partnership with Nurix to be able to bring this molecule forward.

In terms of Gazyva for immunology, a couple of those indications are quite small. So membranous and INS are quite small indications, lupus nephritis, while more sort of on the medium size is also not huge. SLE is clearly a bigger opportunity, but there are some highly entrenched therapies there. So I think it's more just about sort of thinking about where we can actually make inroads. The pricing for Gazyva is also not in the same ballpark, let's say, as some of the other immunological drugs that are out there. So I think that also lends a little bit to what we -- what our peak sales estimates would be just because we're anchored to the oncology pricing. But Gazyva and immunology is going to make a big difference for patients, and I do think it's worth watching, and we do feel quite confident in that up to $2 billion peak sales.

Any additional questions?

That's it. Thank you, Bruno.

Okay. Then next question go to Luisa Hector from Berenberg.

Thank you, Bruno. A couple, please. So I just wanted to check, are you expecting an advisory committee meeting for giredestrant? And then you highlighted your excellent 80% Phase III success rate year-to-date. I just wondered if you can tie that into your latest thoughts on capital allocation. So where are you targeting now? Any future M&A business development and also that kind of relative external versus internal R&D spend given the intensity of your Phase III starts as well? How should we be thinking about those two items?

Well, I'll take the easy question first and then pass off the capital allocation question. So now, we -- because giredestrant received, as you know, priority review. We've been in close conversations with the agency, and we haven't had any indications of an ad board at this time.

Yes. To the second question, so we feel very good where we are at in terms of our pipeline. We've increased the value of our pipeline by 93% versus end of 2022. So we are now at an all-time high in terms of pipeline. We have 19 medicines that we could launch until the end of the decade. So a very full late-stage pipeline. But we are really progressing well in our R&D excellence initiative across all different dimensions. If I just look at the output we have in research, it has significantly increased versus 3 years ago.

If we -- and we also measure for example, also speed of trial recruitment, speed of trial closure, the white spaces between the different phases of development, et cetera, et cetera. And we see a significant progress here as well. Also in terms of reallocation of our resources within R&D, we've now reallocated and brought out efficiencies in our organization of about CHF 1.3 billion, and we could allocate that to all these Phase III trials into other parts of our pipeline. I mean I mentioned one example of that in the past. For example, we negotiated with contracts with CROs. In the past, we were quite fragmented in that. We negotiated new contracts, which gives us a couple of hundred million.

Another one that I already mentioned in the past was Flatiron used to make losses of close to CHF 250 million. We are now profitable with Flatiron. These are all things that we could reallocate in terms of money. So you can see that we are really going after inefficiencies in the organization and making sure that we put money behind the projects. Now that doesn't mean that we don't -- we won't do any more BD or that we don't want to do BD. But we are very disciplined when it comes to BD. We always make very detailed due diligence. We always have material transfer agreements where we really test the molecules in our own hands. These are all things that, I would say, where I've seen other companies lose a bit of discipline in this space. But we don't do that. And maybe it's also because we are not with the back against the wall, and we are not in the same level of pressure as maybe some others.

So you will continue to see us doing deals, but really deals that make sense and also make financial sense and where our team negotiates well. I mentioned that in my presentation. Most of the time when we won the deals, we are not the highest bidder in terms of money, but we bring other things like expertise, to the table, and we are a trusted partner. And I think these are all elements that also are playing in our favor. So you will continue to see that kind of behavior from our side.

Very good. Luisa, your questions answered?

Perfect. Thank you.

Then we have questions coming from Emmanuel Papadakis, Deutsche Bank.

I'll try to be brief. Maybe a follow-up on giredestrant pricing given we're getting a little closer to commercialization. SERDs have launched above $300,000 in metastatic. That seems a little prohibitive for broad adjuvant access. So we've seen examples in the past where you've been prepared to make concessions to ensure that. Could you just give us some latest thoughts on pricing direction, should we see approval at the end of November?

And maybe a follow-up on zemocimig given start -- the official start of the Phase III head-to-head. It looks like Hemlibra can be used discretion the physician in terms of frequency. And if I recall, median ADRs were pretty close to 0. So are you confident in showing superiority on the primary endpoint? Or is this more about showing improvement on secondaries? And perhaps you could also just remind us your latest thoughts on the clinical significance of antidrug antibodies we saw in Phase II.

Yes. Great. So obviously, we won't comment on pricing prior to launch. That's -- we don't ever do that with any of our products. I will say that I think you can expect us to do what we have done in the past, which is to make a reasonable pricing decision based on the clinical benefit that our medicine provides.

In terms of Hemlibra, so we do have a multiple dosing frequency is approved in the label, so Q2 and Q4. So I mean that the patients and physicians can choose what their dosing frequency is. We haven't actually commented on the head-to-head versus whether the head-to-head with Hemlibra is either superiority or inferiority at this point. But we do believe that there is an opportunity for that greater durability and convenience to be very meaningful to patients in the future. So certainly, that can't be the only thing that we bring.

In terms of ADAs in the Phase I/II, the ADAs had no impact on the pharmacokinetic efficacy or safety and didn't have any cross reactions. So at this point, we're not viewing them as clinically meaningful. But obviously, we do continue to monitor.

Emmanuel?

Kind of, thank you.

Good and we move on. Next questions go to Peter Verdult from BNP.

Peter Verdult, BNP Paribas. Just two for Teresa, just back on giredestrant, huge potential, but also Roche's first major launch in a post-MFN world. Now I heard your answer to the last question, so I'm not going to ask you for numbers, Teresa. But could you maybe just remind us what the ballpark U.S. ex U.S. net price difference is for your current on-market breast cancer franchise and how your ex U.S. pricing strategy might evolve for giredestrant in this new environment that the industry is operating in? That's question number one. I realize you're going to go through the specifics, but just want to understand that a little bit better.

And then secondly, on obesity, we share your enthusiasm on 868, but I'm just struggling to see how you're going to differentiate your oral GLP-1 offering given what's currently on the market? And on PET, I'm just struggling to see how you're going to position that asset given data from other amylin targeting compounds who also have good weight loss at lower doses with lower -- with good tolerability. And I just want to understand or do you have a better understanding as to why there was just no dose response seen in the Phase II petrelintide data?

Yes. Great. So in terms of your adjustment, you're right, I won't give you specifics. I can tell you that in general, our U.S. ex U.S. corridors are tighter than maybe some of our competitors have been over time. We've always been quite disciplined about that. As always, when we price a new molecule, we look at three things. We look at what is the clinical value that our medicine brings, what is the ability of systems and patients to pay and what is required in order to continue to return enough value to the company so that we can continue to deliver innovations for patients. And that is the pricing philosophy that we will continue to follow. So stay tuned.

But just to reiterate, it is our intention to bring giredestrant to patients around the world, and we look forward to working with governments to make that happen. In terms of 996, I mean, the data will tell us. So I think we're excited to see the Phase II data to share that. But we remain confident that given the design attributes of CT-996 that we will have a competitive profile and that we'll be able to bring it to market as quickly as possible, when you see the data -- when we are able to share the data when we have it in hand, we'll be able to have a more robust conversation about that.

I mean in terms of petrelintide, again, I just think in every conversation that I had at ADA with thought leaders, there was a real concern for the level of tolerability that patients could really reasonably tolerate over time. 50% of patients don't complete therapy as you would want them to on standard treatments. They don't get to max doses. And so this has always been the promise of the amylin class. And I think we see petrelintide delivering here a very reasonable profile and one that's exciting. And I think it was exciting at ADA for people to think about where this could be used, how it could be used and in the different patient populations we could potentially go into.

So I'm excited about Petri. I think that it actually has the potential to be a really meaningful option for patients. And I think I mentioned this already in my overall comments with the 996 data that will be available later this year. So it will be too much longer before we can have a more robust conversation about why we think 996 might be differentiated.

I think also to add, I think on the missing dose response, which you were asking about petrelintide. I think this phenomenon has been seen before with other gut hormones, and I think we commented on it in the IR call. So there's probably a biology behind, which we don't fully understand. That's all we can say.

Then we move on. Our next question goes to Rajesh Kumar from HSBC.

I got two questions for Teresa actually. I know it's very -- it's next to impossible to predict the future, but if you were to speculate the uptake curve for giredestrant, would that be a very fast uptake in your opinion? Or would that be a more gradual one? And would that differ between U.S. and Europe? That's my first question.

The second question is around obesity. I fully appreciate that your portfolio has something for everyone, and that looks very interesting from a scientific perspective. As we are learning from the current generation of anti-obesity medications, these are subscription models, direct-to-consumer seems to be a much bigger part of the equation. So when you think about the commercialization strategy, are you thinking in terms of efficacy, in terms of product design, in terms of what works for reimbursement channels only? Or are you thinking it from a consumer product design as well? Because in reality, at the moment, about half of the patients in the U.S. seem to be paying out of pocket. And they probably don't want to understand all the scientific gobbledygook we love. They probably want to think through, I want to pay this much. I want to lose this much weight, right?

Tolerability is excellent, but what's the thought process on the commercialization strategy and how that fits within Roche's organization?

Yes. Great. Two good questions. So in terms of the uptake curve, I think I alluded to this a little bit earlier. I mean, as with any chronic therapy, sales build over time, right? So people get on therapy, they stay on therapy and then those curves build over time. So I think there are a number of patients who are out there who are ready for giredestrant and waiting for it. But those really big sales numbers will take some time to generate as we have to build up with adherence and compliance.

We have to build sales up over time. So just to kind of give that a little bit of a framing. And to answer your question, yes, I think we -- as we think about commercialization without going into specifics, we understand that there is a reimbursable market. I mean that's certainly something that enicepatide is probably very well suited for. But we also understand that there is a large direct-to-consumer market, and we are absolutely thinking creatively about how we can reach patients wherever they are accessing their medicines and however they are thinking about managing their health. So just know that we are not approaching this in a traditional Roche way.

Okay. So you think your competitive advantage will not only come from what the product clinical profile is, but in terms of how you commercialize it as well.

I think in the obesity market, those things have to be two halves of a coin or two sides of a coin, right? You have to be able to have the clinical differentiation and you have to be able to show the value from a clinical perspective, but you also have to create a consumer experience that is -- that meets the customer where they're at.

And what skill do you have in the organization to do that in terms of have you hired people around that? Or is it an existing skill or muscle within the organization somewhere?

Yes. So since we have entered into the cardiovascular franchise, we have hired several hundred people from the outside, specifically with the kinds of experiences that we have not had historically. But we also have some great experience to lean on in the diagnostics organization in CVRM that is much more consumer-oriented, and we're certainly taking full advantage of everything that Matt has to offer.

Absolutely. I wanted to actually underline that point. I mean, in diagnostics, we are the leader in this space, and we have a lot of direct access to type 2 diabetics, type 1 diabetics. So a lot of people moving also onto our mySugr platform, et cetera. So we do have a lot of access and know-how in that space. And so I think we're actually quite well positioned. And the feedback that we are getting from KOLs is that they're actually quite excited about having both Pharma and Diagnostics at the table.

Yes, absolutely. It's a real differentiator actually.

Very good. So then we have the final questions here coming from Michael Leuchten from Jefferies, and then we will close the call. Michael?

It doesn't look like that he's on the call anymore. Then with that, I think we are ready to close the call. Over to you, Thomas.

Yes. Thank you very much, and thank you for attending the call today, and thanks to the team. We have great momentum in terms of sales. We have even better momentum in terms of profitability. If you look at the last couple of years, we always delivered what we said. And what you can now see is a significant amount of pipeline progress, pipeline progress that gives us visibility in terms of sales growth for the next years and into the next decade.

But even more exciting is then the pipeline readouts between '27 and '29 that are going to set up really well for future growth into the next decade and beyond. And we'll continue to build on our pipeline and also with internal activities and external activities. And one thing I can say, we will deliver.

So here, I'm delighted to discuss the definitive merger agreement we've signed with PathAI earlier this month, which completes our offering in primary and advanced staining for cancer diagnosis. PathAI is the leading provider of digital pathology Image Management Systems, which enables pathologists to augment their existing IHC or primary, which is H&E staining workflows with AI-powered digital algorithms and tools to automate slide analysis and provide deeper patient insight. The combination of AI-powered digital pathology image management, combined with clinical decision support algorithms will integrate seamlessly with our Ventana solutions and augment our PHC business to increase our leadership position in companion diagnostics.

This solution is wholly complementary to our Ventana business. And by putting these two solutions together, we're going to be even more competitive in this key area of our business. In addition for the pharma side, this will enhance our pharma business with AI solutions that support our clinical trial work as well as enable the introduction of new biomarkers.

So Teresa mentioned briefly AAIC. And now I'd like to switch to our Elecsys pipeline, specifically the launch of our CE mark -- or excuse me, the CE mark we received for Elecsys pTau217 test, which we received on May 12. So Alzheimer's disease is the leading cause of dementia worldwide. We anticipate that it will affect over 80 million people by 2030. However, diagnosis takes approximately 3 years after symptom onset and routine diagnostic methods are either invasive or difficult to access. They involve imaging methodologies that are not readily available and lead to this significant backlog in patient diagnosis.

So with our Elecsys217 assay, we provide a rapid, minimally invasive alternative via a simple routine blood draw. This test is the first blood-based biomarker intended to rule in or rule out Alzheimer's in primary and secondary care settings as a result of the study that we performed. Our assay demonstrated high diagnostic accuracy across health care settings and clinical stages and initially meets the CEOi recommendations for Alzheimer's disease diagnosis. By bringing this test into health care systems worldwide, particularly primary care, we will help physicians to identify Alzheimer's disease earlier, which will facilitate timely intervention and reduce -- and potentially reduce health care costs.

So now I'd like to transition to latent tuberculosis and continue with an update on our Elecsys IGRA TB test, which received CE mark earlier this month. And why this test is important is around the world, approximately 25% of the world's population is estimated to be a carrier of tuberculosis infection. And as a consequence, this is one of the world's largest public health challenges. With Elecsys TB, we enable high throughput testing, automated result generation and a 3-tube workflow, which is superior versus existing systems that are available while maintaining comparable levels of data performance in the clinical setting.

And in the near future, we plan to integrate our Cobas ultra solutions to automate the pre-analytical steps, further improving laboratory efficiency for tuberculosis testing, and it will also help facilitate our entry into the high-throughput segments of the market such as the U.S.

This test has the potential to expand global access to latent tuberculosis infection testing and also help advance progress towards the WHO elimination targets. And I would call out here that we have the broadest installed base of immunoassay analyzers anywhere in the world, and we will leverage our installed base to grow and expand with this test.

So to conclude, I would like to report the progress on our key launch list for the Diagnostics division. Of the 11 launches shown here, we've achieved 7 by half-year 2026. We're making good progress on those that remain, and I look forward to updating you on this in future calls.

And with that, I would like to hand it over to Bruno Eschli. Thank you very much.

Thanks, Matt. And let me quickly close here with the next event, which is scheduled for our investor and analyst community. We have Pharma Day coming up at the 28th of September, again, as a live event in London, similar setup as in previous years and a couple of highlights here to call out. In the morning session, we will again cover our pharma strategy and provide an update on our commercialization efforts. We will provide an update on the R&D excellence initiatives on the KPIs we have shown in recent years. And then also have a focus on our cost-saving initiatives and reallocation on the investments.

And then I think a special highlight is we have Aviv Regev joining on the implication of AI and early drug development. We'll take you through all the stages of early drug development and how AI there comes to life and where we stand. And then in the afternoon sessions, with a similar setup like last year, we will take you through the five therapeutic areas with the new area head being present. And until the end of September, we also would expect a couple of additional data points to come in.

And as Teresa mentioned already, we have then the opportunity also to touch on some of the assets of the obesity franchise like 388 or 996 and provide updates on them.

And with that, I think we are done with the presentation, and we'll open the Q&A session.

First questions would go to Graham Parry from Citi.

There's a question on divarasib. You've obviously started now the Krascendo II trial. Primary completion date on clinicaltrials.gov for that is October 2028. I was just wondering though, given the very long PFS that you saw in the Phase II of 19 months, whether you feel there could be separation occurs and an earlier readout on that?

And then secondly, you still have this as a CHF 1 billion to CHF 2 billion peak sales opportunity in your slides despite the strong Phase II data and in Phase I and hitting the primary endpoint in the second line as well. Is that now just achievable with the second-line indication? And when would you provide an update on whether you see that as going higher given the strong PFS -- long PFS you're seeing in these studies?

Great. Thanks, Graham. Well, I think Pharma Day is going to be for you. So we will be able to provide an update on the entire divarasib clinical trial program as well as the fact that we are currently now based on the strength of the Krascendo I data, we are reevaluating what we believe peak sales might be. So we're talking with thought leaders, thinking about what our ultimate clinical trial program will look like, and we'll be able to provide you an update at Pharma Day. So for right now, we are confirming $1 billion to $2 billion, but stay tuned.

Graham, did we answer all your questions?

Just the potential for readouts in early readout in 2028.

So I mean, I think we've just initiated the trial. So we'll see how we go. And as always, with an event-driven trial, the data will tell us.

Okay. Then we move on. Next question, go to Simon Baker from Redburn.

Two, if I may. Firstly, I see for Lunsumio, it's entered Phase II for SLE. Just wondering if you could give us your thoughts on Lunsumio in that setting and also the interplay with Gazyva in that space?

And then secondly, on Vabysmo, Teresa, you gave us some color on the dynamics within that market. I just wonder specifically if you could give us an update on any activity you're seeing with respect to patient assistance foundations either by yourself or others and your expectations of that for the rest of the year.

Great. So in terms of Lunsumio for SLE, so SLE is a very heterogeneous and complex disease. And while we saw great results with Gazyva, we do believe there's an opportunity for more benefit for patients. And we think that based on Lunsumio's mechanism of action and its safety profile, we think it could actually be a really great option for patients with SLE. It has very strong B-cell depletion as does Gazyva. So we are curious to see whether or not with a slightly different mechanism, we can actually achieve even greater results for these patients. So stay tuned on Lunsumio, but deeper and deeper B-cell depletion is likely what these patients need -- what these patients need.

In terms of the copay assistance foundation, so again, I will just reiterate that these are charitable donations and they're certainly not meant to drive sales. But I think what we are seeing is that there has not been a recovery to the overall market. We are seeing sort of that 2% to 3% growth in the overall retinal market. We do expect that this is going to be the new normal, and we don't expect to rebound to previous levels.

Okay. Then we go on. Next question go to Sachin Jain from Bank of America.

I've got a few, if I may. So firstly, just another one on lidERA launch. At 1Q, you talked optimistically about launch in discussion by risk group. My question for this quarter is what visibility you have on a bolus of patients that could be fast adopters. That's specifically patients who, over the course of last 3 or 4 years have discontinued CDK4/6 due to toxicity and are back on just an AI? So any sense, firstly, how big that bolus is that could be rapid adopters? And would usage in that switch group be consistent with an expected label?

Second question is Ocrevus. You're calling out competition. I'm guessing that's Briumvi. Wondering if you could just give us a bit more color as to why that's impacting now given it's a launch for a while and why you think it's temporary?

And then just one question for Alan. I think it's the first time you've called out the expected growth in other revenues midterm 3% to 5%. That kind of implies $2 billion growing to about $4 billion. That's all EBIT. So is that a driver of margin expansion? Or is it funding investments within your commentary of margins being stable? I'm just going to dovetail that with Bruno also mentioning an entire cost focus session at the Pharma Day.

Okay. So let's start with giredestrant. So I think it's -- so first of all, Sachin, I think you're spot on to something here, but let's start by sort of looking at what does the treatment of ER-positive, HER2-negative early breast cancer really look like. So there's sort of four risk groups of patients. There's the low-risk patient group, which is between 55% and 60% of patients. There's the intermediate risk group, which is about 10% of patients, the medium risk group, which is between 15% and 20% of patients and then the high-risk group, which is 15% of patients.

We would expect that one of the first places we would gain utilization is patients who just aren't on CDK4/6 inhibitors right now. That's 90 % plus of that intermediate group, it's 80% plus of the median risk and 50% plus of the high risk. And so there's a tremendous opportunity within that group that has just never gone on the CDK4/6. But you are right, there's about 50% of patients today who can't tolerate their CDK4/6 treatment. And it's part of the reason that we see such bad outcomes for people with this type of cancer, they just can't tolerate the treatment. And so for those people who either can't tolerate and maybe who have come off and are waiting, we would absolutely see this as a potential patient population, and we wouldn't see this to -- it wouldn't be in conflict with any -- likely with any kind of label.

The switch question or the line of therapy that is not -- the switch question is not usually something that comes up in the label. We are generating, however, switch data. So for patients who are on CDK4/6 today and want to switch, we will generate that data. And we are also generating data for that low-risk population, which is the majority of patients, that 55% to 60%, none of whom are currently on treatment. And then our own combination data is also forthcoming.

So we do believe that when you look at the totality of the giredestrant data that we have in our hands already between lidERA and evERA, we've already got about 80% of the market covered. We're doing trials to cover the rest and sort of really looking at what is the clinical data that we need to make sure that we have the ability to answer all of the physicians' questions in terms of other ways that giredestrant might be utilized. But we do certainly think that there is quite a bit of opportunity for giredestrant.

And in terms of competition with Briumvi, I mean, it's just -- normally, we don't comment on individual competitors. Generally, we're just seeing a higher level of competition in the market. And we certainly believe that based on the clinical attributes of Ocrevus, we are very well positioned to compete. Ocrevus remains the leader in MS with Zunovo as the key growth driver. It is the fastest growth driver in MS. It's the first and only twice yearly MS therapy that's approved in RMS and PPMS. It has over a decade worth of experience. We see that 80% of first-line RMS patients don't experience progression. 90% don't need walking implements.

We're the only high-efficacy therapy that has robust family planning data in hand. And frankly, that outstanding patient convenience with 6 months dosing available as a 10-minute subcut just twice a year. I mean that's an incredible value proposition for patients. So I think in any given situation, you will see a little burst of competitive activity. But at the end of the day, these aren't driven on clinical differentiation. Ocrevus remains the most differentiated product in MS, and we strongly believe in our ability to compete and win for patients who deserve to be on the best therapy.

Yes. Let me take the margin point, Sachin. I think you made a great point. I think very clear once we grow from 3% of sales to 5% of sales, that makes a difference until the end of the decade. There's no doubt about it. I think for the time being, nevertheless, I think we stick to the point to say, either we stabilize the margin or we grow it. I think now things come nicely together. We'll see how that plays out. And yes, I think that gives even more substance to our statement.

Sachin, did we answer your question?

Yes.

Then we move on. Next one in the row is Colin White from UBS.

Colin White from UBS here. Just to go back to Vabysmo. You talked about being confident of the stabilization of the branded market. I was wondering if you could talk about the dynamics related to the reduced Vabysmo growth expectations between charitable funding assistance and the increased use of biosimilars. And if biosimilar market share shift, where -- what percentage of the market do you expect to be biosimilars going forward? And why do you have confidence that the branded market is now stabilizing?

And then just a second question on first-line DLBCL, if I may. There's a big competitor readout for Epkinly coming up in first-line DLBCL. So -- if that study reads out positively, I just wondered what you're thinking about in terms of the impact that might have on Polivy and how it fits in with your own first-line study for your anti-CD20.

Yes. So I mean, let's talk a little bit first about the biosimilar market in ophthalmology. I mean it's just a little bit different than in other places. But where we are seeing biosimilar impact happen, it is impacting sort of directly the molecule that it's replacing. So a biosimilar to Lucentis took Lucentis share, biosimilars for other molecules are taking specifically that share and really impacting that part of the market. You don't really -- we're not really necessarily seeing the bleed over that you might see in other places. We saw 8% growth with Vabysmo in sales, this half, but we saw a 30% increase in volume globally.

So we really do believe that Vabysmo has entrenched itself as the preferred therapy of choice. I think you can very clearly see that from the ASRS data and that where physicians are making a determination for a new patient, the majority of the time that is coming Vabysmo's way. And again, we're not seeing new biosimilars entering the market impacting Vabysmo. We're seeing them impact the originator product that they are the biosimilar of.

The stabilization that comes from just sort of having watched the market over the last 6 months, talking with physicians and seeing how are they running their practice and what they're -- how they're utilizing the resources available to them and their patients. So we do think that 2% to 3% overall growth in retina will accommodate the biosimilar entry, will accommodate other things. But clearly, Vabysmo is continuing to grow in the U.S., and it is continuing to take a disproportionate share of that branded share growth.

With regards to the competitor entry, so they are about a year ahead with first-line DLBCL, but we do see POLARIX being just a much better tolerated regimen in first line. So we wouldn't necessarily expect to see a terrible amount of impact there. POLARIX has well established itself in first-line DLBCL. You meant POLARIX, not Lunsumio because that's really the first-line DLBCL drug.

Colin, did this answer your question? So we also have our own study coming up next year.

Yes.

As you know, SKYGLO.

Yes.

Okay. Then we move on. Next one in the row is Justin Smith from Bernstein.

Just a very quick one on 007. Sorry if this is a bit ignorant. Just any kind of qualitative conviction you can give us as to why 360 patients means you're well powered in that sort of head-to-head versus Hemlibra in Phase III?

Yes. I mean I think we've done the statistical analysis based on what we know about the performance of Hemlibra and what we believe to be true about 007, given, as Thomas mentioned, the incredibly high level of potency, and we feel confident in the design.

Yes. Maybe what I can add here in terms of the time lines, I think for this study, which now has seen the first patient in, we would expect data, I think, at around year-end next year, beginning of the year after. So in '27 and '28, which I think also puts us in a very favorable situation here to bridge to the next generation.

Any additional questions, Justin?

All good.

Thanks, Justin.

Then we move on. And next questions go to Sarita Kapila from Morgan Stanley.

At ASCO, you talked about new indications, sorry, for giredestrant, for the heredERA trial and then evERA trial. Could you quantify how large you think these opportunities are and whether these are upside to the CHF 9 billion peak commentary? And how -- if I can squeeze in, do you see positioning specifically for heredERA of giredestrant in HR-positive, HER2 breast following positive data for Pfizer's Ibrance in the PATINA trial.

If I could just squeeze in a quick follow-up on divarasib. If you're reevaluating peak sales, this is the [ KRAS G12D-C ] how should we think about it versus emerging panRAS agents, including pipeline or programs within your own pipeline?

Yes, absolutely. So when we think -- I'll start with the second question first and then go up to giredestrant. So when you think about KRAS mutations, KRAS mutations are present in about 25% of patients with lung cancer. G12C mutations are present -- they represent 40% of the KRAS mutations, which means you're at about 12%, 13-ish percent of overall non-small cell patients have a KRAS G12C mutation. So the potency, the selectivity, the safety profile of divarasib, we believe, positions it very well in patients with those specific mutations. And I think we've seen that in the 170 data, we're seeing it in Krascendo 1, and it's something that we expect will play out in other trials as well.

So I think because of the very strong specificity for that mutation and the fact that mutation is so prevalent, I think if you have that mutation, you would be more apt to use a therapy that would target that mutation directly. Certainly, there's going to be a place for pan-RAS inhibitors. We have several of them in our pipeline as well, and we look forward to developing them and seeing what their results are for patients. We have a very diverse pipeline here, which is great.

When you talk about the opportunities within -- for giredestrant, as I mentioned previously, between lidERA and evERA, we already have 80% of the ER-positive, HER2-negative market covered. So the other trials that we have in place that are looking at the different aspects of first line in different combinations, those really give us the opportunity to cover pretty much 100% of this patient population. So the peak sales that we've mentioned, they sort of encapsulate the fact that we do have a pretty broad program already in place for giredestrant. But certainly, if some of these other programs came in, that could potentially be upside as well. And as I mentioned, we'll be able to give you a very good and thorough update of what our development plans look like for giredestrant at Pharma Day in just a couple of weeks.

And I mean, the upside on divarasib is also in other cancer types, right, beyond lung cancer. In fact, the RAS is one of the best known or most known and most mutated genes in cancer in different cancer types.

Absolutely.

Did we answer all your questions, Sarita, or your follow-on questions?

Yes.

Okay. Then next questions go to Richard Vosser from JPMorgan.

A couple of questions, please. Just a follow-up on Ocrevus and Zunovo uptake seems very strong and very fast. So you mentioned again the $2 billion for Zunovo. But could this actually be larger and protect more of the franchise from biosimilars? So just thinking about that.

Second question, a follow-up on Vabysmo. I don't think you mentioned pricing impacts. Just wondering about -- we've seen biosimilars to other agents affect pricing in the classes. Obviously, there's very low dose of Avastin here. But are you seeing anything in -- or very low price Avastin, but are you seeing anything there in terms of pricing maybe in the ex U.S. market?

And then one final question, just on other revenues coming back to that. I think there are probably some milestones there in this quarter for some of the new agents. You've got quite a lot of new agents from other companies launching. Just should there be other milestones that we should think about in the next few years that could boost the trajectory from actually the royalties that you're getting in? Just some thoughts there as well.

Yes. Great. Thanks, Richard. So I promised you guys a hockey stick for Ocrevus, Zunovo, and we have delivered the hockey stick. We're well on our way. We do think that as people -- as I mentioned in many other calls previously, as practices and patients get experience with Zunovo, it fits into the practice flow very, very well, and it's intensely convenient for patients.

So is there additional conversion opportunity? Quite probably. I think at the moment, we still feel very confident in our additional $2 billion, understanding that there will be the sort of $2 billion that are just brand new patients to Zunovo, but we would expect that there will be switching as well. So ultimately, that entire pie could look bigger. And certainly, that would provide some additional protection to Ocrevus over time as would the on-body injector, which we're excited to talk more about at Pharma Day.

In terms of Vabysmo, I mean, certainly, we've seen pricing impacts outside the U.S., but those have largely been related to volume because Vabysmo has been doing exceptionally well in generating patient share outside of Europe or inside of Europe.

Alan?

Yes. I think really in general, no, that's the answer. I think there can always be stuff, but that's why we have said we go from 3% to 5%. And I would argue that includes everything.

And it's mostly royalty driven, not milestone driven.

Absolutely...

Just to be very clear. But also, I mean...

There are a couple of milestones...

The majority is royalty by far. But on the Ocrevus side, also, you were talking about switching to Zunovo also to make sure that we can protect the franchise into the next decade as well and beyond. Here, I just want to say that we have a couple of other options in play as well with fenebrutinib, but a number of things that we have in the pipeline where we believe that we can extend that as well. Absolutely.

Richard any additional questions?

No.

And next questions come from James Gordon from Barclays.

James Gordon from Barclays. A couple, please. One with giredestrant and adjuvant and the launch expectations. So at ASCO, there was some mixed discussion feedback lidERA and talk about need for longer-term PFS data and OS and more data versus CDKs. Do you think that view is typical? Could that blunt the initial uptake at all? Or do you think that's atypical? And where are you on ex U.S. regulatory might you need longer-term data there? And I think Bloomberg consensus is about CHF 300 million next year, which doesn't look a lot versus the size of the very big hormone breast cancer market. Are there any sort of roadblocks we should be aware of if we're modeling out the launch? Or is that plausible?

The second question would be fenebrutinib regulatory. So latest confidence on U.S. approvability. I know some investors still have quite big safety and tolerability concerns. But I know you've had a bit more time to have some interactions with regulators. Anything concerning there? And where are you ex U.S.? Any interactions there? I saw fenebrutinib's been EU-approved despite the liver profile. But how are you thinking about timing for ex U.S.?

And then finally was just obesity update. So we've got updates on your GLP-1/GIP and your amylin at ADA. I think you've got your anti-myostatin and your oral GLP-1 imminently, presumably at the Pharma Day or before. So how are you thinking about differentiation? And of the four assets in obesity, which is the one that's most exciting, because you've given similar peak sales estimates for them all. Which is the one we should be most excited about?

James asking me to pick my favorite kid. That's harsh. Wow, okay, there's a lot in there. So in terms of giredestrant adjuvant, I would say that we are spending a lot of time with KOLs and with potential treaters, sort of asking what their confidence is in the data. And I think what we are hearing is that people are excited about having an option. The profile of giredestrant is very attractive to people. We've mentioned this a number of times before, but with CDK4/6 is 50% of patients can't stay on their therapies over time. And that necessarily means that, that leads to worse outcomes when you can't take the medicine that's designed to help you.

The giredestrant tolerability and safety profile just looks much better. And so I think we are increasingly confident that physicians are excited about giredestrant and we'll find a place to use it in their practices fairly easily. So my writing is not great here. So ex U.S., we are currently assembling the data package that we believe will be the most robust data package to allow us to file in Europe and achieve a sustainable reimbursement value. And so that is coming, and we would expect that we fully intend to file in Europe and are just waiting for that data package to mature.

In terms of the consensus numbers, so we don't generally comment on -- specifically on launch projections. But what I will say is that we should remember that this is a chronic therapy. And so while we do expect a strong launch, clearly, the big numbers will build over time as they do with any chronic therapy. We would expect patients will stay on giredestrant for 5 years plus given what we've seen in the market and what the tolerability profile is for giredestrant.

In terms of fenebrutinib regulatory, so as I mentioned, we're well on track to file first in the U.S. We'll use that U.S. package then to springboard off of for other regulatory filings. We are collecting the additional data that we need for the EU. And again, we have every intention of filing. And again, our focus has been on getting the U.S. package ready, and then we'll go from there. While I won't comment on the specifics of any regulatory interactions, we haven't seen anything that would indicate that a filing in the U.S. is going to be at all problematic.

And then in terms of picking my favorite child, that's really, really unfair. I think that what we saw at ADA with just the really impressive weight loss data from enicepatide and the very interesting and positive tolerability profile for petrelintide. I mean if you think of that bell curve that I showed you guys at Pharma Day last year, for the patients who need deep weight loss, we have that. For the people who maybe need that 10% to 15% weight loss with a placebo-like tolerability, we have that. The fixed-dose combination could be a booster for both of those products. I think what we are finding is that the nature of both of these medicines in different ways are making them differentiated and are giving them opportunities to really find a very unique space in obesity in ways that will ultimately really help patients with what they need. And I think that's actually super exciting as we head into our Phase III programs.

Clearly, we'll have the data on the anti-myostatin and CT-996 quickly. I mean having an oral option is, of course, important. So we're excited to see 996. But I would have to say, I don't think I can pick a favorite because I think what I really love about the obesity portfolio that we've built is it's delivering on exactly what I talked to you all about last year at Pharma Day, the ability to build a broad adaptive portfolio that regardless of what a patient's obesity -- where they are in their obesity or health journey, we have a medicine that can help them. And we could help them throughout their entire weight loss journey. And so I'm just really excited about what we've seen in the data as it's come to maturity and increasingly getting excited about bringing the entire portfolio to patients.

Let me add two points, one on giredestrant and one on fenebrutinib also that increases my confidence level in those molecules. You already pointed out the safety profile of giredestrant specifically against CDKs. I would like to point out not only the potency advantage it has versus another SERD, but also the label and safety aspect that it has versus another SERD. So I think from a safety perspective, it is quite differentiated as well.

And then on fenebrutinib, we mentioned that before that the FDA allowed open-label extension for fenebrutinib for initially PPMS patients. And so people that were on the fenebrutinib arm continued, but people who were on the control arm were switched to fenebrutinib. Now the same happened for RMS. So the RMS patients that were on fenebrutinib continue in the open-label extension as well as on the control arm patients moved to fenebrutinib. So I think these are good indicators, I would say. It gives us a certain level of confidence in that. But ultimately, we'll see.

Very good. Any additional questions, James?

I'll leave it there...

Then we move on to the next James. James Quigley from Goldman Sachs.

I have two as well. So again, both for Teresa. So the BTK degrader, from the data you've seen so far, where do you think the asset can be differentiated in cancer indications? Is it efficacy, safety, combinability dosing? It would be interesting to hear there. And then also as you move into immunology, where do you hope to be differentiated on the immunology side? And how quickly do you think you can move there into MS and CSU depending on when you see the data?

And secondly, Gazyva in immunology, I think I asked this last time as well, but when we hear you speak, Teresa, you sound very excited about the opportunity. When you look at the 4 indications, $2 billion, it looks like it might be on the low side. So what is holding you back at the moment in terms of looking at peak sales here? Is there anything in the indication size? Is anything in terms of segmentation that might be holding you back on the potential peak sales for Gazyva?

Great. Okay. A lot of immunology questions. Okay. So bexobrutideg, all of those things, right? I think we're excited about the potential. I think we're excited about the efficacy. I think we're excited about the safety, the tolerability, the combinability. I think we really believe that BTK degrader could be a real game changer in some of these indications, particularly in oncology. And so I think we're very excited to get this into trials and to see where it can go. Now that having been said, for all of those same reasons, having the degrader versus the inhibitor, we could see a really differentiated efficacy profile in immunology.

Immunological diseases are notoriously difficult to tackle. I mean they're -- as I mentioned previously, they're very heterogeneous. And so having a degrader versus an inhibitor, I think we could very well see that incremental efficacy, which in immunological indications can really be quite meaningful. So time will tell. It's a brand-new asset to us. We'll give you a little bit more insight as to what our plans are at Pharma Day, but I think we're really excited to have this partnership with Nurix to be able to bring this molecule forward.

In terms of Gazyva for immunology, a couple of those indications are quite small. So membranous and INS are quite small indications, lupus nephritis, while more sort of on the medium size is also not huge. SLE is clearly a bigger opportunity, but there are some highly entrenched therapies there. So I think it's more just about sort of thinking about where we can actually make inroads. The pricing for Gazyva is also not in the same ballpark, let's say, as some of the other immunological drugs that are out there. So I think that also lends a little bit to what we -- what our peak sales estimates would be just because we're anchored to the oncology pricing. But Gazyva and immunology is going to make a big difference for patients, and I do think it's worth watching, and we do feel quite confident in that up to $2 billion peak sales.

Any additional questions?

That's it. Thank you, Bruno.

Okay. Then next question go to Luisa Hector from Berenberg.

Thank you, Bruno. A couple, please. So I just wanted to check, are you expecting an advisory committee meeting for giredestrant? And then you highlighted your excellent 80% Phase III success rate year-to-date. I just wondered if you can tie that into your latest thoughts on capital allocation. So where are you targeting now? Any future M&A business development and also that kind of relative external versus internal R&D spend given the intensity of your Phase III starts as well? How should we be thinking about those two items?

Well, I'll take the easy question first and then pass off the capital allocation question. So now, we -- because giredestrant received, as you know, priority review. We've been in close conversations with the agency, and we haven't had any indications of an ad board at this time.

Yes. To the second question, so we feel very good where we are at in terms of our pipeline. We've increased the value of our pipeline by 93% versus end of 2022. So we are now at an all-time high in terms of pipeline. We have 19 medicines that we could launch until the end of the decade. So a very full late-stage pipeline. But we are really progressing well in our R&D excellence initiative across all different dimensions. If I just look at the output we have in research, it has significantly increased versus 3 years ago.

If we -- and we also measure for example, also speed of trial recruitment, speed of trial closure, the white spaces between the different phases of development, et cetera, et cetera. And we see a significant progress here as well. Also in terms of reallocation of our resources within R&D, we've now reallocated and brought out efficiencies in our organization of about CHF 1.3 billion, and we could allocate that to all these Phase III trials into other parts of our pipeline. I mean I mentioned one example of that in the past. For example, we negotiated with contracts with CROs. In the past, we were quite fragmented in that. We negotiated new contracts, which gives us a couple of hundred million.

Another one that I already mentioned in the past was Flatiron used to make losses of close to CHF 250 million. We are now profitable with Flatiron. These are all things that we could reallocate in terms of money. So you can see that we are really going after inefficiencies in the organization and making sure that we put money behind the projects. Now that doesn't mean that we don't -- we won't do any more BD or that we don't want to do BD. But we are very disciplined when it comes to BD. We always make very detailed due diligence. We always have material transfer agreements where we really test the molecules in our own hands. These are all things that, I would say, where I've seen other companies lose a bit of discipline in this space. But we don't do that. And maybe it's also because we are not with the back against the wall, and we are not in the same level of pressure as maybe some others.

So you will continue to see us doing deals, but really deals that make sense and also make financial sense and where our team negotiates well. I mentioned that in my presentation. Most of the time when we won the deals, we are not the highest bidder in terms of money, but we bring other things like expertise, to the table, and we are a trusted partner. And I think these are all elements that also are playing in our favor. So you will continue to see that kind of behavior from our side.

Very good. Lisa, your questions answered?

Perfect. Thank you.

Then we have questions coming from Emmanuel Papadakis, Deutsche Bank.

I'll try to be brief. Maybe a follow-up on giredestrant pricing given we're getting a little closer to commercialization. SERDs have launched above $300,000 in metastatic. That seems a little prohibitive for broad adjuvant access. So we've seen examples in the past where you've been prepared to make concessions to ensure that. Could you just give us some latest thoughts on pricing direction, should we see approval at the end of November?

And maybe a follow-up on zemocimig given start -- the official start of the Phase III head-to-head. It looks like Hemlibra can be used discretion the physician in terms of frequency. And if I recall, median ADRs were pretty close to 0. So are you confident in showing superiority on the primary endpoint? Or is this more about showing improvement on secondaries? And perhaps you could also just remind us your latest thoughts on the clinical significance of antidrug antibodies we saw in Phase II.

Yes. Great. So obviously, we won't comment on pricing prior to launch. That's -- we don't ever do that with any of our products. I will say that I think you can expect us to do what we have done in the past, which is to make a reasonable pricing decision based on the clinical benefit that our medicine provides.

In terms of Hemlibra, so we do have a multiple dosing frequency is approved in the label, so Q2 and Q4. So I mean that the patients and physicians can choose what their dosing frequency is. We haven't actually commented on the head-to-head versus whether the head-to-head with Hemlibra is either superiority or inferiority at this point. But we do believe that there is an opportunity for that greater durability and convenience to be very meaningful to patients in the future. So certainly, that can't be the only thing that we bring.

In terms of ADAs in the Phase I/II, the ADAs had no impact on the pharmacokinetic efficacy or safety and didn't have any cross reactions. So at this point, we're not viewing them as clinically meaningful. But obviously, we do continue to monitor.

Emmanuel?

Kind of, thank you.

Good and we move on. Next questions go to Peter Verdult from BNP.

Peter Verdult, BNP Paribas. Just two for Teresa, just back on giredestrant, huge potential, but also Roche's first major launch in a post-MFN world. Now I heard your answer to the last question, so I'm not going to ask you for numbers, Teresa. But could you maybe just remind us what the ballpark U.S. ex U.S. net price difference is for your current on-market breast cancer franchise and how your ex U.S. pricing strategy might evolve for giredestrant in this new environment that the industry is operating in? That's question number one. I realize you're going to go through the specifics, but just want to understand that a little bit better.

And then secondly, on obesity, we share your enthusiasm on 868, but I'm just struggling to see how you're going to differentiate your oral GLP-1 offering given what's currently on the market? And on PET, I'm just struggling to see how you're going to position that asset given data from other amylin targeting compounds who also have good weight loss at lower doses with lower -- with good tolerability. And I just want to understand or do you have a better understanding as to why there was just no dose response seen in the Phase II petrelintide data?

Yes. Great. So in terms of your adjustment, you're right, I won't give you specifics. I can tell you that in general, our U.S. ex U.S. corridors are tighter than maybe some of our competitors have been over time. We've always been quite disciplined about that. As always, when we price a new molecule, we look at three things. We look at what is the clinical value that our medicine brings, what is the ability of systems and patients to pay and what is required in order to continue to return enough value to the company so that we can continue to deliver innovations for patients. And that is the pricing philosophy that we will continue to follow. So stay tuned.

But just to reiterate, it is our intention to bring giredestrant to patients around the world, and we look forward to working with governments to make that happen. In terms of 996, I mean, the data will tell us. So I think we're excited to see the Phase II data to share that. But we remain confident that given the design attributes of CT-996 that we will have a competitive profile and that we'll be able to bring it to market as quickly as possible, when you see the data -- when we are able to share the data when we have it in hand, we'll be able to have a more robust conversation about that.

I mean in terms of petrelintide, again, I just think in every conversation that I had at ADA with thought leaders, there was a real concern for the level of tolerability that patients could really reasonably tolerate over time. 50% of patients don't complete therapy as you would want them to on standard treatments. They don't get to max doses. And so this has always been the promise of the amylin class. And I think we see petrelintide delivering here a very reasonable profile and one that's exciting. And I think it was exciting at ADA for people to think about where this could be used, how it could be used and in the different patient populations we could potentially go into.

So I'm excited about Petri. I think that it actually has the potential to be a really meaningful option for patients. And I think I mentioned this already in my overall comments with the 996 data that will be available later this year. So it will be too much longer before we can have a more robust conversation about why we think 996 might be differentiated.

I think also to add, I think on the missing dose response, which you were asking about petrelintide. I think this phenomenon has been seen before with other gut hormones, and I think we commented on it in the IR call. So there's probably a biology behind, which we don't fully understand. That's all we can say.

Then we move on. Our next question goes to Rajesh Kumar from HSBC.

I got two questions for Teresa actually. I know it's very -- it's next to impossible to predict the future, but if you were to speculate the uptake curve for giredestrant, would that be a very fast uptake in your opinion? Or would that be a more gradual one? And would that differ between U.S. and Europe? That's my first question.

The second question is around obesity. I fully appreciate that your portfolio has something for everyone, and that looks very interesting from a scientific perspective. As we are learning from the current generation of anti-obesity medications, these are subscription models, direct-to-consumer seems to be a much bigger part of the equation. So when you think about the commercialization strategy, are you thinking in terms of efficacy, in terms of product design, in terms of what works for reimbursement channels only? Or are you thinking it from a consumer product design as well? Because in reality, at the moment, about half of the patients in the U.S. seem to be paying out of pocket. And they probably don't want to understand all the scientific gobbledygook we love. They probably want to think through, I want to pay this much. I want to lose this much weight, right?

Tolerability is excellent, but what's the thought process on the commercialization strategy and how that fits within Roche's organization?

Yes. Great. Two good questions. So in terms of the uptake curve, I think I alluded to this a little bit earlier. I mean, as with any chronic therapy, sales build over time, right? So people get on therapy, they stay on therapy and then those curves build over time. So I think there are a number of patients who are out there who are ready for giredestrant and waiting for it. But those really big sales numbers will take some time to generate as we have to build up with adherence and compliance.

We have to build sales up over time. So just to kind of give that a little bit of a framing. And to answer your question, yes, I think we -- as we think about commercialization without going into specifics, we understand that there is a reimbursable market. I mean that's certainly something that enicepatide is probably very well suited for. But we also understand that there is a large direct-to-consumer market, and we are absolutely thinking creatively about how we can reach patients wherever they are accessing their medicines and however they are thinking about managing their health. So just know that we are not approaching this in a traditional Roche way.

Okay. So you think your competitive advantage will not only come from what the product clinical profile is, but in terms of how you commercialize it as well.

I think in the obesity market, those things have to be two halves of a coin or two sides of a coin, right? You have to be able to have the clinical differentiation and you have to be able to show the value from a clinical perspective, but you also have to create a consumer experience that is -- that meets the customer where they're at.

And what skill do you have in the organization to do that in terms of have you hired people around that? Or is it an existing skill or muscle within the organization somewhere?

Yes. So since we have entered into the cardiovascular franchise, we have hired several hundred people from the outside, specifically with the kinds of experiences that we have not had historically. But we also have some great experience to lean on in the diagnostics organization in CVRM that is much more consumer-oriented, and we're certainly taking full advantage of everything that Matt has to offer.

Absolutely. I wanted to actually underline that point. I mean, in diagnostics, we are the leader in this space, and we have a lot of direct access to type 2 diabetics, type 1 diabetics. So a lot of people moving also onto our mySugr platform, et cetera. So we do have a lot of access and know-how in that space. And so I think we're actually quite well positioned. And the feedback that we are getting from KOLs is that they're actually quite excited about having both Pharma and Diagnostics at the table.

Yes, absolutely. It's a real differentiator actually.

Very good. So then we have the final questions here coming from Michael Leuchten from Jefferies, and then we will close the call. Michael?

It doesn't look like that he's on the call anymore. Then with that, I think we are ready to close the call. Over to you, Thomas.

Yes. Thank you very much, and thank you for attending the call today, and thanks to the team. We have great momentum in terms of sales. We have even better momentum in terms of profitability. If you look at the last couple of years, we always delivered what we said. And what you can now see is a significant amount of pipeline progress, pipeline progress that gives us visibility in terms of sales growth for the next years and into the next decade.

But even more exciting is then the pipeline readouts between '27 and '29 that are going to set up really well for future growth into the next decade and beyond. And we'll continue to build on our pipeline and also with internal activities and external activities. And one thing I can say, we will deliver.

Welcome to the Roche Virtual ADA investor event. My name is Henrik, and I'm the technical operator for today's call. Kindly note that the webinar is being recorded. [Operator Instructions] At this time, it's my pleasure to introduce you to Bruno Eschli, Head of Investor Relations. Bruno, the stage is yours.

Thanks a lot, Henrik. And could I have the first slide, please? So welcome to our fifth IR call in 2026, covering new Phase II results for enicepatide, previously known as CT-388 and petrelintide in obesity which just got presented at ADA in recent days. Today's call is scheduled for 90 minutes. We have planned for roughly 50 minutes for the presentation and then 40 minutes for Q&A.

Let me quickly take you then through the agenda. Our first speaker today, as you can see, will be Morten Lammert, our Global Therapeutic Area Head Cardiovascular, Renal & Metabolism. Morten will provide a quick update on our overall obesity strategy before our second speaker, Manu Chakravarthy, Senior Vice President and Global Head of Product Development, Cardiovascular, Renal and Metabolism, will take us through the latest from the obesity pipeline, including an update on the study start of a Phase II multi-arm fixed-dose combination study called SYNERGY for enicepatide and petrelintide in obesity plus/minus type 2 diabetes.

Our third speaker, as you can see, will be Ildiko Lingvay, MD, MPH, MSCS and Professor of Medicine in Endocrinology and the lead investigator for CT-388 -- for the CT-388-103 study. Dr. Lingvay will take us through the Phase II enicepatide results in obesity. And finally, we'll have a presentation by Louis J. Aronne, MD, previous Director of the Obesity Society, Founder and Chair Emeritus of the American Board of Obesity Medicine and Professor of Metabolic Research. Dr. Aronne is known to the broader scientific community for his foundational role as a pioneer who helped shift the medical perception of obesity from a just behavioral failure to a biological treatable chronic disease.

He serves as a principal investigator and lead clinical trialist for key anti-obesity trials, including petrelintide, and he will take us through the Phase II ZUPREME-1 petrelintide results in obesity. Following these presentations, we will have our 40 minutes Q&A. And in addition to our 4 presenters, we will be joined for the Q&A by Louis André Villeneuve, our lifecycle leader for enicepatide and by Marisel Salzger, our lifecycle leader for petrelintide. And with that, let me hand over to Morten to get us started. Morten, please.

Thank you, Bruno, and good morning from New Orleans. I'm Morten Lammert. I'm the Global TA Head for CVRM, and I thank you for joining us today. I'll not take a lot of time as I know the true highlights of this call is coming after my presentation. But I would like to take this opportunity to provide you with a high-level overview of our strategic blueprint we are executing to become a leader in CVRM. Obesity is a core focus within our CVRM strategy, driving our ambition to deliver innovative and transformative solutions for patients.

Our ambition is clear. We aim to become a leader in obesity. To achieve this, we are focusing on securing a strong market entry before year 2030 and differentiating our opportunities and offerings through the Roche unique capabilities. We have defined strategic pillars to deliver on this commitment. Firstly, we must deliver the near-term portfolio. We are focused on advancing our late-stage assets into Phase III at speed while preparing for launch of our diverse portfolio.

Then we are expanding and differentiating. We will unlock the potential of combination therapies and iterate on validated mode of actions, while over time, also developing novel treatments with transformative potential. And not only treatments need to be transformative, also the care delivery needs transformation. We are thinking beyond the molecule, leveraging our diagnostic capabilities and ensuring we meet patients where they are in their individual journeys.

Next slide, please. The global obesity pandemic represents a monumental challenge to the individual, to the health care systems and to our societies. If prevention and treatment measures do not improve, the global economic impact of obesity could reach USD 3.5 trillion by 2035. By that time, projection shows that more than half of the global population will be living with either overweight or obesity. Despite this health challenge, the treatment rate is still far below that of other chronic diseases. Data suggests that only 10% to 15% of all the eligible patients in the U.S. are currently treated with a branded anti-obesity medication. And treatment is also initiated too late at a point where the BMI is above 35 and many of them have already established comorbidities.

With new and better treatments, we believe we can shift the curve and treat more people and treat them earlier. This would allow us to not only address severe obesity with obesity-related complications, but also focus on health preservation and early disease -- in the early disease stages.

Next slide, please. To successfully engage the patients earlier, we must go beyond one-size-fits-all treatment paradigms. Our strategy is taking point of departure in the patient-centric insights, shifting to tailored solutions that meet the needs for people with obesity. We have studied how patient needs and decision drivers change as a function of their disease states and their journey. If we are zooming in on the far right column, we focus on patients with obesity Class II or Class III and often with established obesity-related complications.

The treatment of choice deliver maximum efficacy and has demonstrated benefit on the relevant comorbidities to achieve -- willing to accept some side effects of the treatment and discomfort that to get that more and higher potency. Left column are people earlier in the disease journey. They know it would be healthy and good for them to lose pounds, but would most likely not consider themselves as living with a chronic disease. Majority of people in this group are looking for 10% to 15% weight loss that can be achieved in the most gentle and the most convenient way. In other words, they make a trade-off between the efficacy, the convenience and in particular, tolerability relative to the first group.

This is why we need patient-centric approaches that is critical to deliver treatment solution matching the different patient needs. Our go-to-market strategy aligned with these changing needs from specialized care for the high-risk patients to primary care and direct-to-patient approaches for early intervention and for health preservation. Next slide, please. Lastly, we are entering the next era of obesity management and expect continued and significant market growth over the coming decade. In addition to pricing and accessibility, we see 3 main drivers of this continued market growth. If we start from the bottom, a continued inflow of AOM naive patients is driving the market expansion today and will continue to contribute to market growth over time.

AOM experienced users will, over time, become a significant part of the future market. This is not the classical switch patients, but represent the cyclical nature of AOM treatment and the market will require new solutions to reengage those patients who, for one or the other reasons, decided to stop their chronic care. Treatment persistence will continue to improve with very low level -- from the very low level today. Education, disease understanding and improved treatments and maintenance strategies will increase adherence and the long-term use.

This market will continue to be hyper dynamic, and we believe our pipeline is very well positioned to offer the right treatments across a heterogeneous patient population from early intervention to late-stage comorbidity management. With this, I would like to hand over to Manu for a pipeline update. Thank you for your attention.

And thank you, Morten, and a warm welcome on my behalf as well, and good morning and good afternoon. Good morning, certainly from New Orleans. So I'll take you through the pipeline update and give you a little bit more of the progress that we have made since our last time together. So if you go to the next slide, please. So -- over the course of the last 6 months, we've had a significant progress across multiple fronts. And I'll walk you through some of those key developments through this slide. It's a little complex, but I'll walk you through this asset by asset. So the first important advance that we've made in -- since the beginning of the year is to advance zilebesiran, which is our once every 6-month angiotensinogen siRNA for uncontrolled hypertension in a cardiovascular outcome study that we call ZENITH.

It's 11,000-person study, and happy to report that we're making really substantive progress in recruiting that study now, and we're making really good headway there. In terms of enicepatide, which you'll hear a lot about from Professor Lingvay in a second. But again, very happy to report not only the presentation of the 103 study at this conference, but more importantly, the advancement of this program into Phase III, so into chronic weight management with 2 pivotal studies that we call ENITH-1 and ENITH-2, which is in people with and without type 2 diabetes and obesity and overweight.

We also have a fairly comprehensive program, which you'll hear at our next update in terms of how we're developing it for glycemic control for a cardiovascular outcome study. So really a comprehensive package to really position enicepatide as a potential best-in-class dual GLP-1/GIP agonist. In terms of additional progress, pegozafermin, which we have now completed the full integration with 89bio. So the company was acquired in October of 2025. And since then, we've completed the integration. And again, happy to report very good forward progress here with the 2 pivotal studies, which we call ENLIGHTEN fibrosis and ENLIGHTEN cirrhosis, so both progressing quite well. And then petrelintide, which you'll also hear a lot about from Professor Aronne in a second. And we also presented data on the ZUPREME-1 study here in ADA. So that has yielded very exciting results for us.

And those results, along with enicepatide data, give us a lot of confidence to then do a combination study that we call SYNERGY, which I'm going to give you a little bit more of a flavor in a couple of slides. So that's a combination study with enicepatide and petrelintide. So that is to be initiated in the second half of 2026. And we've also made the decision to advance petrelintide monotherapy into Phase III in the second half of 2026. Then we have our oral synthetic molecule, which we call CT-996, which is a GLP-1 receptor agonist, again, anticipated for broad indications, both in obesity, but as well as in type 2 diabetes. So we're in the midst of our Phase II program for both obesity and type 2 diabetes.

We're making good progress there. We anticipate that we will be making a Phase III go decision in second half of this year as well. And then we have our ongoing what we call the GYMINDA study, which is the anti-myostatin plus incretin combination study, which is on track to be reading out its Phase II data also at the end of this year. Then we have acmopatide. So we've made the difficult decision, which is entirely strategic to not advance this program for type 1 diabetes into Phase III. So as you may recall, acmopatide is a once-daily dual GLP-1/GIP agonist that we had developed for type 1 diabetes.

At this conference at the ADA, we presented at a symposium the really good efficacy and safety data. And the results certainly speak for itself, but it was a strategic decision not to advance it into Phase III. Just want to emphasize here that while we are making a decision on a molecule, it doesn't mean that we're not committed to diabetes for both type 2 and type 1. So we remain highly committed. And you can see from our portfolio, there's actually some very interesting choices that could potentially be made to really ask ourselves what's the best molecule, what's the best mechanisms that we can bring to bear to really help people with diabetes, both type 1 and type 2.

And then, of course, we have afimkibart for MASH and then NLRP3 in an earlier stage of a program for cardiovascular disease. So if you go to the next slide then, please. I'll give you a little bit of the quick snapshots on 3 programs. Obviously, we won't have time to go through all of them in detail, but I want to highlight 3 programs, and then we go deeper into the data. So enicepatide is our fully biased dual GLP-1/GIP receptor agonist, and I'll explain a little bit better what that really means in a second with the next slide and what does bias really bring. But on the right, just to emphasize a little bit further what I said in terms of where we are. So we've now completed the full Phase I program, Phase II program for obesity is completed.

We're in the midst of almost nearly completing the type 2 diabetes study, which we call the 104 study. Results are expected in second half of '26. And then all of these 4 Phase III programs that are either started or soon to be started are all underway. So in terms of what is special about this molecule, we thought it might be best to explain it with a little bit more of an animation. So if you go to the next slide, please. This introduces the concept of signaling bias which is really the mechanism of action which provides this molecule.

[Presentation]

So, of course, that signal bias, we've seen the benefits of it in preclinical models, several different studies, as you can see published here, and the evidence continues to accumulate, and we have some early hints of our Phase II data that might support its benefits. And of course, Phase III will be the ultimate proof in the pudding, if you will, of how a signal bias molecule may eventually translate to better efficacy and potentially better tolerability. So now let's move to petrelintide. Just as a quick high-level update here. Again, Dr. Aronne will speak a lot about the results, so I'll not go there. But just suffice to say, in terms of its development program, where we are, -- so again, we've completed our Phase I.

We've completed ZUPREME-1 Phase II, and we're awaiting data from ZUPREME-2, which is the overweight obese type 2 population, and that data is expected at the end of this year. And then as I mentioned in the pipeline update, we've advanced the monotherapy program for Phase III and then excited now to present to you the kind of a study design overview for what the SYNERGY trial is going to look like. So if you go to the next slide then, please. So this might seem a little complicated, but I'll kind of walk you through kind of the core principles of how the study is really designed.

So we wanted to do a comprehensive Phase II program, so where we can study both the mono components and the combo components all in one study so that the end goal coming out of the Phase II is to be able to identify the ideal regimen of the best risk-benefit ratio, if you will, of the best efficacy, best tolerability that then we can take into a streamlined Phase III design so that we don't end up having to do monotherapy in Phase III, if possible.

So you'll see in the bottom 3 rows, arms 4, 5 and 6 really represent placebo, petrelintide monotherapy or enicepatide monotherapy. And then the top 3 rows, #1, 2 and 3 are 3 different regimens, 3 different doses, combinations, if you will, of petrelintide/enicepatide combos that we are studying in a fairly comprehensive manner to identify, as I said, the best ideal combination that we can get to with tolerability and efficacy as the key center pieces. So this is a 40-week study. This is going to be in people with obesity or overweight with at least one comorbidity. And this one is -- this one depicted is not in people with type 2 diabetes.

And so the expectation is that emerging out of this trial, we will have identified the right dose for each and that we will take into a fixed dose combination into the Phase III study. This specific design is not a fixed-dose combination. It's a loose combination. So we're giving 1 injection of petrelintide, 1 injection of enicepatide separately. But once we identify what the right combination is, then we can make a fixed dose.

So this is, again, slated to start in the second half of this year. Now my final update on the pipeline per se is on the next slide, which is our oral molecule, CT-996, if you go to that one, please. So you might recall, again, from our last update that we had, we were in the midst of our Phase I program, which is fairly comprehensive. It included people with and without diabetes. And so what you're seeing on the left there is just a quick refresher of the weight loss that we saw over 48 -- sorry, over 4 weeks in people living with obesity, but no diabetes. And so we saw a weight loss of up to 7.3%. Part of that study also included people with diabetes.

I'm happy to report that, that has now been accepted to the EASD, and we can present the type 2 diabetes cohort there and that will have completed our full package for Phase I. And then we are in the midst of 2 Phase II studies, which are also very comprehensive programs to really do a proper full dose ranging across multiple doses in both people living with obesity and obesity and diabetes. So that's what we call the 2 sort of the Phase II studies and then ultimately making a decision based on those data, whether to take this forward into Phase III towards the end of this year.

And then my final slide before I hand it off is just to kind of recap kind of where we are. So you heard from Morten very nicely that there are many unmet needs, and there is a wide heterogeneity of people living with obesity. And then we need to meet people where they are in their journey because obesity is a chronic disease. It's relapsing and it's heterogeneous. So our approach has been a holistic patient-centered approach really anchored on what are the core unmet needs that we are trying to really satisfy. So you heard about tolerability, you heard about the plateauing. You heard about the weight maintenance challenges, the comorbidities, 2 out of 3 people living with obesity have at least 1 comorbidity.

If you lose too much -- too fast body weight, especially in a vulnerable population, elderly population, muscle loss is a significant concern. So that's an important issue. And then 1 out of 5 people do not respond to an incretin. So having more mechanism of actions to treat such a heterogeneous disease is a must-have. So those are our anchoring pillars. And so when we ask those questions of what can we do in our portfolio to satisfy those pillars, you can see every one of our assets that we have carefully and thoughtfully designed and brought together is there to address those unmet needs.

Again, I'm not going to go through it all again, but just simply to provide this visual to say that the way we have constructed our portfolio is really anchored with patients as our North Star and to ask ourselves, where are we going to make the biggest impact to help our patients. So those are the areas. And it's both in monotherapy and in combination therapies that we can bring our portfolio to bear. And then the final piece I will just emphasize are 2 other things. As Roche, one of the advantages that we have is also the benefit of multiple therapeutic areas.

So not just CVRM, but we also have neuroscience, immunology, oncology, et cetera. And so we know that there are over 200 comorbidities of -- in people living with obesity. So we're also looking at what are our other assets within our other parts of our therapeutic areas that we can bring in combination at the right times. And then the final piece is, of course, the diagnostics and the therapeutics, both residing under the same umbrella, where I think we all can appreciate how important it is to not only diagnose, monitor, but also prognosticate how patients are doing.

And so having a diagnostic arm that works in tandem hand-in-hand with our therapeutics arm is another significant advantage that we see and that we want to bring to bear in its totality to really help patients. So with that, it's my true pleasure to hand it off now to Dr. Lingvay to walk us through some of the core data pieces that we presented actually both today, and we also had a late-breaking poster yesterday. So Dr. Lingvay.

Fantastic. Thank you so much. Hello from New Orleans as well. And it's my honor to present the 103 study results. We can get the next slide. And that's on behalf of a number of co-authors that have worked really hard on this study as well as all the study participants and the study staff that were caring for these patients every day. These are my disclosures and these extensive collaborations with industry, along with my firsthand experience with treating patients with metabolic conditions and extensive research experience have really informed the way I look at the field and the way I think about what's most needed in our field.

Let's move on. So enicepatide, as you've heard, it's a dual signal biased, both GLP and GIP receptor agonist. It's a once-weekly subcutaneous injection, and it's being developed for treatment of obesity, type 2 diabetes and weight-related comorbidities. You might remember that the Phase I trial, which was 24 weeks long, had very impressive results. The highest dose in that trial was 22 milligrams of enicepatide, and it produced reductions in weight of up to 18.9% in people without diabetes living with obesity.

It's -- also its safety and tolerability were very reassuring, which means that this compound moved into Phase II. And this is what we're hearing about today. It's the Phase II study, which was intended to evaluate the efficacy, safety and dose response of enicepatide in participants with overweight, obesity, but without diabetes. Let's move on.

There you go. All right. So this study was a double-blind, placebo-controlled multicenter trial conducted exclusively in the U.S. It enrolled participants -- adult participants between the ages of 18 and 75 and they must have a BMI over 27 with at least 1 weight-related comorbidity or BMI over 30 and no diagnosis of diabetes. Participants that were eligible were randomized to 5 different doses of enicepatide ranging from 4 to 24 or placebo. And the primary endpoint was reduction in weight at week 48.

There were a number of secondary endpoints as well. The important one that I'm going to point out is the proportion of participants with normal glycemia among those who had prediabetes at baseline. Let's move on. This is a study design. And you will see that the lowest dose, the 4 milligrams did not have any titration steps. And then the higher the dose, the more titration steps as it should be. And the highest dose was reached after 4 titration -- 5 titration steps. Of note, which is important when we're also looking at the results is that participants had to come in weekly to the study sites to receive the medication.

This obviously influences the practicalities of getting the medicine and participating in the study. And also in this study, there was flexibility on dose titration, but to some degree, people were able to down titrate or slow down the titration if needed for safety, but they must have been on a minimum of 4 milligram of study medication in order to stay on the medication. And also, there was that point at 27 weeks beyond which titration was not allowed. So whatever dose they were able to titrate up to at that point, that's what they stayed on for the rest of the trial to capture that steady-state effect of respective dosages.

Let's move on. All right. So on the left, I'm showing you the baseline demographics, which are fairly typical for participants in obesity studies. Age is 49, predominantly female participants, BMI of 38 and an A1c that's well in the normal range, but there were 50% of participants who had prediabetes at baseline. I also want to point out that there were a good representation of African-Americans, which gives us confidence of the fact that the study results will be representative of a larger population that will be studied in Phase III and the population specifically that we tend to use these medications in the United States.

On the right, I'm showing you the disposition. And you will see that everybody received -- almost everybody received at least one study medication. And then you will see on the second line, the number of -- the percentage of participants who reached the full dose of the study medication. Remember, by week 27, if they were not able to get to their assigned dose, they could not uptitrate after week 27. So in this context, I'm happy to report that those on the 4-milligram dose achieved 99% of participants got to that dose, 8 milligrams 97% and then in the highest dose, 80% of participants were able to get to that 24-milligram dose.

You will see the study completion that is quite good for the obesity studies. If you followed ADA this year, you would see that there have been struggles in the field with keeping participants in the study. You will see that 34% of participants in placebo stopped the -- I mean stopped participating in the trial and stopped the medication. And that's not unexpected for the field. People now have choices. And if they see that they're not getting the responses that they're looking for, they no longer stay in the study. And also, this number is actually very good for the field as it stands currently.

Among people who received enicepatide, anywhere between 14% and 31% stopped the study medication. And I have to point out that I think this is a small study and the 12-milligram dose had an unusually high discontinuation rate, but it stands out, and I would look at the totality of the data and see that in all the other arms, including the highest dose, the 24-milligram arm had only 19% discontinuations. And if you look on the last line, that's the most important one, how many people actually discontinued due to adverse events. And this is not just GI adverse events, any adverse events. And you see that the discontinuation rate because of adverse events is extremely low.

Let's move on to the study results. There you go. This is the most important slide. So people treated with the highest dose, the 24 milligrams of enicepatide reduced their weight down by 22.7% at the 48-week mark. That represents a placebo-substractive difference of 22.5%. And you would appreciate that, that line is quite steep, still going down. So it's anticipated that with ongoing care and ongoing treatment, people will probably lose quite a bit more than 22% of their body weight.

On the right, I'm showing you the treatment estimate. And with the highest dose of 24 milligrams, the placebo-subtracted weight decrease was 18.3%. I also want to point out that even the lowest dose, the 4 milligram, which was required no titration. It's a one-stop shop, achieved quite meaningful weight loss with a placebo -- I'm sorry, with 6.7% body weight loss by the end of the 48 weeks. Let's move on. So these are important secondary endpoints. On the left is the categorical weight loss data. And you will appreciate that the overwhelming majority achieved 5% body weight loss. When you look all the way to the right-hand side, and it's probably unprecedented to see 30% weight loss category in these graphs.

It's something that we just recently added to our graphs in various -- for various studies because not until long ago, that was not even a number that we would dream of. But 26% of the people treated with the highest dose of enicepatide achieved 30% body weight reduction. That's in the range of bariatric surgery, and that's quite impressive, especially coupled with the on-treatment retention that we have seen in this group. On the right, I'm showing you the number -- the percentage of people who achieved normal glycemia if they had prediabetes at baseline. So you will see at the bottom what number -- what denominator we had for each of these group.

Remember, about 50% of participants had prediabetes at baseline and up to 73% of people just within 48 weeks, they reversed from prediabetes to a normal glycemic state. Let's move on. And these are the side effects. And overall, pretty well tolerated for a GLP-1 receptor agonist. Participants who withdraw due to side effects, I mentioned to you before, it's a pretty low number. But let's look at the participants with any GI adverse events. So that means either they had nausea, constipation, diarrhea or vomiting. And you see those numbers compared to placebo at 28%. These range between 47% and 55% across the various enicepatide treatment groups.

Nausea was 19% in placebo and in the enicepatide groups, it ranged from 33% to 46%. Constipation, around 25% across the various groups, diarrhea around 15% with the highest percentage in the highest group. And then vomiting was quite a good number. I know it's never good for anybody to have vomiting. But compared with other GLP-1s, especially GLP-1s that are able to achieve the amount of weight loss that we have seen in this study, these numbers are quite impressive.

So with the lowest dose, 8% and then the highest dose, 21%. Most of these events were mild to moderate, very few Grade 3 events. There were no grade 4 and 5 events reported. Next, please. All right. So let's conclude. This was the first Phase II trial of enicepatide, and it demonstrated clinically meaningful, very statistically significant dose-dependent weight reductions of up to 22.7% at 48 weeks of treatment.

In the highest dose arm, the 24 milligrams, the percentage of participants achieving 10% and 20% weight reductions was 87% and 47.8%, respectively. Among those with prediabetes, 73% had a reversal to normal glycemia. And then I've shown you that fewer participants actually discontinued treatment in the active groups than in the placebo, underscoring the favorable benefit risk profile. Thank you, and I will pass on back to the team.

Hi. I'm Dr. Louis Aronne, and you've heard my introduction before. I was involved in the development of the -- of this trial, ZUPREME-1, which was presented here at the ADA in New Orleans, where I am across the street. I can see the convention center across the street. I'm looking at it longingly because I haven't been there today for the first time in 5 days. I want to point out that in a different universe, amylin analogs would be the primary drugs for the treatment of obesity. When amylin -- the first amylin analog, which was pramlintide and exenatide, first GLP-1 were approved in 2005, almost simultaneously, we found in using them initially for weight loss that pramlintide and the amylin action seemed a little bit better than the GLP-1s because it had fewer side effects.

It was more tolerable and produced very good weight loss. And we published several papers back then looking at the weight loss. But for reasons that I still can't understand, but I'm sure the industry does, it was not developed for obesity at that point in time and was used for a very narrow indication, which was along with insulin in people with type 1 diabetes. But now we're beginning to see that there are amylin analogs. May I have the next slide, please? And what I'm going to be presenting are the results of the Phase II trial of petrelintide, this new human analog. This study was led by Tim Garvey from the University of Alabama. I was on the steering committee for this trial and helped to develop the treatment paradigm.

Next slide, please. And these are Dr. Garvey's disclosures. Next slide. So you're well aware that obesity is a heterogeneous chronic disease and pharmacotherapy we're seeing makes a lot of sense. Despite many advances in the development of obesity medicines, treatment persistence is the big issue, and it remains low for a number of reasons, including side effect profile. Petrelintide, which has a half-life of 10 days is being developed as a weekly injectable for long-term obesity pharmacotherapy. And the objective of this trial was to compare the efficacy, safety and tolerability of various doses of petrelintide versus placebo in people with obesity or overweight and with complications.

Next slide, please. So here is the trial paradigm. It was a randomized, double-blind, placebo-controlled parallel arm to parallel group, 10-arm trial. Each dose arm had a placebo arm, a matched placebo arm. The baseline characteristics you should note are that there are 485 subjects in total, age 47 years. Women comprised only 53% of this group. And you saw that Dr. Lingvay presented about 68% women. And in many trials of GLP-1s, it's 75% and even higher. This is important because what we have seen with the GLP-1s and perhaps now with other trials of amylin analogs is greater weight loss in women. It's kind of the reverse of what we used to see with diet alone.

And so this may have an impact on the results on the magnitude of the weight loss. The mean BMI was 37, body weight was 107 kilograms and subjects were not to have type 2 diabetes, although they could have prediabetes. The dosing was weekly and it escalated every 4 weeks as the subjects tolerated. The primary endpoints were the percentage change in body weight from baseline to week 28 and the secondary or exploratory endpoints included change in body weight at week 42, change in waist circumference at week 42, change in cardiovascular risk factors and treatment-emergent adverse events. So you can see 42 weeks. The titration went up to week 28 and then the dose remained stable, and then there was a following -- a follow-up of 9 weeks.

Next slide, please. Here is the efficacy estimate for the results. And you see in the pooled placebo arm, 1.7% mean weight loss up to week 42. And the various doses, which you can ask the company about, the apparently lowest dose, dose 1, 8.7%, up to dose 5 was 10.2%, but dose 3 in the middle in pink was 10.7%. That seemed to be the greatest efficacy. So placebo subtracted weight loss of 9% to week 42, but the trend continues to be down.

Next slide, please. If we look at cardiovascular risk factors, and this is a small selection of them, we see that waist circumference, which is a very good summary of where the cardiovascular endpoints are going, ranged from 7.9 to 10.8 centimeters, very good reduction in waist circumference and proportional to the amount of weight that was lost. If we look at C-reactive protein, a key measure of inflammation, it went from a 17% up to a 41% reduction in the various doses. And triglycerides similarly went from a 12% to a 21% reduction over the period of 42 weeks of treatment.

Next slide, please. Now here is the most important slide for this trial, and that is pooled petrelintide versus pooled placebo adverse events. And you can see that in the far left column, they're virtually identical. And this is I don't want to say unprecedented, but we have not seen so few adverse events in a treatment group compared to placebo, at least I haven't. And if we look at serious adverse events, you see that they are identical. This is really, really a striking finding. So that while the magnitude of the weight loss may not be what some people would want, it may just take longer, the safety profile here is quite remarkable, really remarkable.

In the middle, we see the mild, moderate and severe side effects. And you see, again, parity and perhaps fewer severe side effects in the severe group. So there were fewer severe side effects in the treated group versus the pooled placebo group. And finally, in the right column, you see adverse events leading to discontinuation and virtually identical. So a very, very good side effect profile that I think if side effects are an issue for a patient, this would be what I would use.

Next slide, please. Here, we look at selected GI adverse events, and most of them were mild. You could see that over 3/4 were mild, and they were reported during dose escalation. That's typically what we see in our trials is as whenever the dose goes up, you may have an increase in the incidence of adverse events. So we see nausea, 19.6% versus 6.2% in the placebo-treated group. Diarrhea, exactly the same. Constipation, slightly greater in the treated group and vomiting lower, 6.2% versus 3%.

So reduced incidence of vomiting in the petrelintide group. So maybe it's a treatment for vomiting as well, just kidding. Next slide, please. Here, we see the adverse events based on the preferred terms, and this is in those -- which were reported in greater than 5% of participants. You can see on the top line, the nausea numbers, which ranged -- so we see in the placebo group, 6.2% in the petrelintide group ranging from 12.3% to 28%. We see some fatigue, which we often see. Again, clinically, I'm not sure how important that is. Diarrhea, a small increase. Injection site reactions, not many, but there and then constipation. And then the usual side effect profiles that we see in our clinical trials.

The one I'd like to point out at the bottom is vomiting. If you look at vomiting, you see that the numbers ranging from 3% -- from 0 in 2 of the doses to 8.5%. And this variability is undoubtedly because of the small size of this trial. But the point is that these are very, very low numbers in the pooled group, 3% versus 6.2% in the placebo group is very, very exciting to see because vomiting is extremely unpleasant in some cases and is a reason why people drop out of our studies. Next slide, please.

So in summary, in this Phase II dose-finding trial, petrelintide demonstrated statistically significant and clinically meaningful weight reduction across all dose cohorts at both week 28 and through week 42 in a gender-balanced population. And again, I think that if you do the math, there should be significantly greater weight loss if women -- if there are more women and if women respond as they do in GLP-1 trials. The treatment was associated with improvement in cardiovascular risk factors. It was well tolerated with rates of GI adverse events and serious adverse events that were similar to placebo.

And in conclusion, these findings support the potential of petrelintide as an effective and well-tolerated obesity medicine with a distinct mechanism of action, could be added to other compounds, for example. And these properties offer the opportunity to improve longer-term medication persistence because I think the reduced side effect profile is going to be very exciting. So thank you very much. And the Phase III studies are scheduled to initiate in the second half of 2026, and we eagerly await them. Thank you.

Thanks, Dr. Aronne. And with that, we will open the Q&A session.

The first questions go to Graham Parry from Citi.

So firstly, a question for Dr. Lingvay. The 12-milligram group, the CT-388 had a very high 14% dropout rate due to adverse events. It was double what we saw in 24 milligram. Just if you can -- is there any additional data around what explained that? Was there any specific sort of AE that was causing the dropout there? And then secondly, a question for Roche. Are these the dose titration schedules that you'd be looking to use in Phase III monotherapy? And then the last question is when you're talking about looking at fixed dose combinations for Phase III for the combination, is that fixed dose in a single device, so unlike what we've seen with CagriSema, for example, where you have a dual chamber pen.

I guess I can kick it off with my question. And this is a Phase II trial with small numbers of participants. So you would imagine that any sort of occurrence of extra 1 or 2 events will influence the numbers quite significantly. And that's why I said that you need to look at the totality of the data across the 5 treatment arms and look sort of at the trend across them. The 12-milligram group was definitely a little bit odd, but the 14% dropout rate due to adverse event was not any -- due to any specific adverse event. It was just a measuring of this and that. I also want to remind you that these participants had to be at the site every single week to receive their injection. And that does influence your willingness to stay in a trial when so many other external factors might influence your ability to come to the site on a weekly basis.

And I'll take the other questions on the FDC and the titration. So the FDC -- so one of the advantages of petrelintide is that it doesn't fibrillate. And therefore, it is compatible with other peptides. So we are able to take advantage of that property and therefore, provide that into one single cartridge. So it is not a dual chamber device. It's a single chamber device. Both will be in the same cartridge. Regarding titration, so this is an every 4-week titration. But as we learn from the field, and both Dr. Aronne and Dr. Lingvay can add to this, we know that patients will require some degree of flexibility. And so in all of our trials, we have been very thoughtful in terms of providing such flexibility.

So while it's every 4 weeks, there are provisions in the protocol that allow some flexibility to take some time to get to the next dose if they need to. There's a flexibility to down titrate. There's a flexibility to stay on the same dose. And so there's multiple avenues provided to participants to get to their assigned top dose. So flexibility is an important component of it, but the titration is on protocol, it's every 4 weeks.

Graham, did this answer all your questions? Do you have any follow-on questions?

So actually, one follow-on. Just in terms of the combination, why would you be varying the petrelintide dose? I mean it looks like you just took dose 3, which looks like it's already optimized with no vomiting and then varied the CT-388 dose, that would be the sensible way to -- why do you need to vary the petrelintide dose in the Phase III?

So we haven't disclosed all of the doses yet. So when we do that, you'll see the full dose ranging there. So we're going to take a full look at all of the factors now that we have the full data set. But the goal here is really to try to find the optimal balance. As you can imagine, we want to maximize tolerability while also really maximizing efficacy. So I think it's a balance that we will look at.

Very good. Then we move on. Next questions go to James Gordon from Barclays. James, please?

James Gordon from Barclays. The first one was on eni as a monotherapy. So is that you show superior weight loss versus obesity? And I heard the comments about -- and we heard quite a lot of this at the conference about patients in the placebo arm now end up just going and getting themselves GLP-1 therapies anyway, so it makes it harder to show a difference. So would you actually think about then putting an active comparator so you can say you're better than something else and not have this issue all the placebo patients just start medicating with the GLP-1 anyway? And similarly, in terms of differentiation for eni, including as a petre combo, I think Lilly already doing something similar in terms of doing GLP-1/GIP with the amylin and they've already started the trial there. So the thinking on the differentiation there?

Okay. So I can take that. So regarding the head-to-head, again, we're in the middle of getting our clinical development plans all finalized. So as I mentioned to you, we have, of course, a comprehensive chronic weight management program, but we also have a very comprehensive glycemic control program. So in those studies, we anticipate that we will do head-to-head studies. We're fully aware that retaining patients in a placebo-only arm is getting more and more challenging. And you already saw the hints of the data that Dr. Lingvay showed, 34% of people on placebo dropping out. So fully aware, recognizing that as an issue. So head-to-head trials will be part of the package. We are also going to have long-term extensions as part of the package of keeping patients in trials as a way to provide an incentive.

So after they finish their main, what we call the primary intervention period, they will be invited to participate in a long-term extension. So that's part of our program as well. And then in terms of differentiation, I mean, great question, and we spend a lot of time, obviously, thinking about that every day. I think the way to think about it is on multiple fronts, right? So it cannot just be just can we get an extra 2% weight loss? And would that be a differentiator at the end of the day. So we have to think a little bit more broadly.

So I mentioned already 2 of them. One is a package that includes head-to-head, package that includes long-term extension, a package that includes the flexibility of dosing. So we're working on making the devices highly patient friendly, so multi-dose pens, for example. And then ultimately, when we really think about overall differentiation, we have to also think about where -- what are the patient segments that we really want to go to. So one differentiation -- and again, we'll await the 104 study with enicepatide, which is a Phase II study in type 2 diabetes. we believe that the characteristics of the molecule plus the Phase I data that we have seen and all the vast body of evidence that we have in the preclinical space has the potential that enicepatide can have a differentiation of glycemic control.

So again, the key message here is that we're trying to address the heterogeneic needs of patients, and then we have to figure out exactly where that unmet need will be best served by the characteristics of this molecule.

James, may I quickly double check. Was there an initial question from you about the superiority of weight loss seen versus tirzepatide we should comment on? Or was it just a comment?

Well, I guess the question is, do you think that you could be better? Because I think there was a comment before about how you don't plateau or you plateau...

So how do we see the weight loss?

Yes. So mechanistically, and that's why we showed you the bias signaling, right? So what we know from the science and what we've seen very clearly and consistently and now actually supported by other independent investigators have also shown the importance of bias is that when you have that, you will have a chance for a deeper efficacy. Now the trajectory that Dr. Lingvay showed is very enticing, right? I mean you're seeing a very steep decline, 22.7% weight loss at 48 weeks, no evidence of plateau at all. So you could envision that if you take it to 60, 72 or even 80 weeks, you might get more. I mean -- but again, we have to do the study, right? So we're obviously excited about that profile. We have -- we see that as a potential way to differentiate, but we also see other ways of differentiating.

So yes, to answer your question, that is one of the levers where we see there could be a differentiation in terms of weight loss, but we also see differentiation in terms of A1c or in other areas that I just mentioned.

Very good. James, we answered all your questions.

There's plenty of them I could ask, but I'll let someone else have a go.

Yes. Then we move on. Next, please, Luisa Hector from Berenberg.

So I was wondering if you could tell us anything about the relative proportion of fat versus lean mass loss, whether you've got some data when we might see it? And maybe just to follow up on that question on the running the placebo-controlled trials. I see -- I hear you, Manu, you've got your head-to-head, you're thinking about a long-term extension. But in the trials that have already started, so eni, is there anything more you can do other than the long-term extension? Are you able to kind of check whether there's any unapproved use of GLPs happening along the way or anything you can work within that trial if it does happen?

Yes. So I'll start with the first 2. I would definitely invite Dr. Lingvay to provide her perspectives in her own clinic about how she manages that. I mean we're fully aware that there's always going to be add-ons of GLP-1s, and we have prespecific endpoints to try to manage that. So regarding fat versus lean, I mean, of course, that's going to be a body composition analysis that we will have, and we'll present some of that data at upcoming conferences. We don't have the data as yet right now. But yes, we have measured body composition, of course, in both our ZUPREME-1 study and the Study-103.

What other things can we do on the placebo side? I mean, we are going to do everything that we possibly can to retain patients. And I mentioned a couple of key ways of doing this, right? I mean, head-to-head trials, long-term extension, great relationship with sites and investigators that we want to have to educate people that, look, this is a known phenomenon, but that we have to be able to work with the right sites and the right investigators and the right patients.

So I'm not diminishing that it's a challenge, but we do have methods in place that we feel that we can do that. And plus, we've had prespecified analyses within our protocols to try to ensure that we have a way to look at both the truly GLP-1 naive population as well as those populations that may be using a GLP-1. And we recognize that there will be some diminishment of efficacy just because you're adding it on to another GLP-1. So prespecifying it will be helpful and to really get us a good understanding of what this effect will be. But Dr. Lingvay, if you have anything to add, please feel free.

Yes. So just happy to remind people that this is really not because we want to do studies against placebo. It's a regulatory requirement. And we would very much like not to do them against placebo, but not much of a choice in the matter here. Some of the glycemic studies can be done against active comparator in that space, but in the obesity space really, the placebo is a requirement that drives the design of these studies. That being said, I have to be Roche. It's one of the first companies that has these open-label extensions, which are truly meaningful. I'm hopeful that they will change how patients think about participation in the context of them thinking they might be on placebo.

And it's not just a 6 months extension. It's a meaningful extension for everybody, and everybody can go to the maximum tolerated dose. So I'm really, really thinking that this will be a game changer in the field of obesity when we're still required to use placebo. Of course, all the other measures that Manu mentioned, I think they're doing a great job at selecting the sites right, educating the sites and the site staff and making sure that they're fully engaged with their patients, providing the dietary counseling, which is so essential for people to maintain that interest in the study and make the good changes in the life that will help them and benefit them in the long run and then making sure that they're staying through the end and being great supporters of these patients so they can get to that open-label extension phase.

Then next questions come from Sarita Kapila from Morgan Stanley.

So Roche have previously talked to potentially dosing CT-388 above the 24 milligrams tested in Phase II. How much of a barrier is the 20% to 30% vomiting, diarrhea to pushing the dose higher? And for any of the 3 combo regimens, do they include CT-388 exposure above the 24 milligrams? And then just a quick follow-up on the no plateau comment for CT-388. Is it because the 24-milligram arm reached target dose late? So we noticed there were 6 titration steps before reaching 24 milligrams. So how many weeks of actual exposure did the median patient receive to 24 milligrams by week 48?

Yes. So I'll start with this one and invite others as well as needed. So just the last question first. So it was 20 weeks because they finished their titration at week 28 and the endpoint was at 48. So they were at least able to take up to 20 weeks -- between 16 and 20 weeks. So you're right, it's -- could we have gotten more? This is why we feel very optimistic that we will if they were to maintain it around 24 milligrams over a longer period of time.

The other thing I'll try to remind people here is that when we actually looked at very carefully the performance of people at the 24-milligram dose, the tolerability was actually really well tolerated. The challenge was from 12 to 16. And then once they got to the 24, the background rates of nausea, vomiting, constipation, diarrhea generally tended to be very stable and certainly did not increase. So that gives us actually quite a bit of confidence to actually push the dose to higher doses.

So I think this is a great opportunity to emphasize the other comment that the other person made about how else can we differentiate, we can also differentiate by potentially going at a higher dose. And the reason why we are confident that we can go to a higher dose is, again, as I said, the current data set that we currently have. No plateau there. So it means that you can push to a higher dose. Tolerability is actually quite good at 24. And then the final piece, how to ensure that we can get there, and this is still in evolution in terms of our final design elements. But one way is to just be more flexible, take some more time to get to the top dose.

So I'll just remind people that it's not a race to the bottom to get to the lowest weight loss number in the shortest period of time. We want to be really mindful of taking people through that weight loss journey as comfortably as possible. And our properties of the molecule gives us confidence to say that we can do that safely. So more flexibility, slower titration, great tolerability at 24 already that provides us confidence that we can go higher. And what that higher will be, we'll hopefully come back to you all once we have finalized that design to say what that dose is. But we fully anticipate that we will try to get to a higher dose than 24.

Manu, I think there was also the question whether the Phase II combo had already a higher dose included. Sarita, if I got your question right.

Yes, that was right.

So in the SYNERGY study, are we doing a higher dose?

Yes, exactly.

So this -- so the point of the SYNERGY study is to try to maximize both in the current dose ranges that we have actually studied. We believe that with the current doses that we have had between a really nice dose ranging that ZUPREME-1 did, a really nice dose ranging that the Study-103 did, we have plenty of doses there that we feel really confident to be able to say that we can mix and match the right dose combination to maximize the efficacy. And there, I'll just remind people that combination is really designed for people that are really needing that level of weight loss, right?

So greater than 25% of weight loss, where maybe it's the high BMI category with type 2 diabetes or other comorbidities where getting to that degree of weight loss really will be helpful. But we also remind people that there are plenty of people who need only 10%, 15% of weight loss. And maybe there are other parts of our portfolio that can serve that, like petrelintide, as you heard from Dr. Aronne, right? So we have to really think about kind of where we want to use and where do we want to deploy these medicines. And given our portfolio, we're well positioned to do that.

Sarita, did we answer all your questions?

Yes, that was perfect.

And the next one in the queue is James Quigley from Goldman Sachs. James?

I've got 2 questions, please. So firstly, for Dr. Aronne and Dr. Lingvay. ADA, we saw lots of new data from different therapies for CagriSema yesterday and as well. So what are you thinking in terms of positioning for CT-388 and petrelintide? And we're particularly interested in Dr. Aronne, your view on 388 and Dr. Lingvay, your view on where petrelintide could sit. And second one is a sort of clarification/reminder. So on the lack of dose response in ZUPREME-1, what were the reasons for that lack of dose response? Is it also related to imbalance in gender between groups? Are there other factors that are at play there that you've noticed? And apologies if it was on the slides, but which dose is going forward into Phase III for -- which dose level is going forward for the next Phase III for petrelintide?

Would you like us to respond?

Yes, Dr. Aronne, you might want to start.

So I think that enicepatide, the data is fantastic. It looks like it's at least as good as tirzepatide. I think you have to agree the weight loss hits the tirzepatide point of 22.5% weight loss plus/minus, and it's still going down. Is it going to abruptly plateau? I mean that doesn't usually happen. So it could be that the biased signaling is giving greater efficacy. We won't know until we treat people for a longer period of time, but it's at least theoretically possible. But also in looking at the weight loss curve, it is -- I think it is definitely possible. That would be a big differentiator to have a GIP/GLP-1 that is more effective than tirzepatide. That's been kind of an invisible barrier that people have been trying to break through.

You see CagriSema hitting the same number. And this is -- and a triple agonist obviously goes past that, but this would be the first dual agonist that looks like it could go beyond that 22% to 23% weight loss in this type of trial. As far as the petrelintide, I personally think that, that could be one of the reasons we see the 10.7% maximum weight loss is that this is the lowest percent of women in a trial that I've seen for some time. So it is at least theoretically possible that, that will be a difference in that in the next trial, if you do the math, it should be 14% to 16% if the percent of women is what it is in other trials, around 75% and also if the response is the same as it is with the GLP-1s. So we'll just have to see those.

And maybe also the same question then goes to Dr. Lingvay. I think the question was on how do you see petrelintide positioned within the field currently?

Well, I thought Louis is going to take that, but I'm happy to take that because I'm a big fan of petrelintide. I think its safety profile is so compelling that it's going to be the first-line therapy for a lot of people and especially in the primary care field where they don't have the energy, time or just multitasking ability to deal with all of these side effects and the multiple prescriptions and the multiple dose escalations. This is an ideal drug for primary care patients and for really the way more than half of the population that needs weight loss and it needs weight loss in the range of about 10% or so, give or take, while improving their cardiovascular risk. And we've seen that petrelintide does that very nicely.

It improves blood sugar, improves cardiovascular risk factors like blood pressure and lipids and CRP. And therefore, it's really a nice gentle drug to deliver the type of weight loss that most people need. I'm also excited about the potential of exploring and using an amylin-based therapy like petrelintide in people that are older, that are more frail, that perhaps have more false fractures. Many of those people would benefit from weight loss. But currently, we're a little bit timid about intervening with the agents that we currently have because of the risk of muscle wasting and the risk of additional falls and fractures. If the data pans out as we hope it will, there will be a huge population there in the 75-plus age range that would benefit from an intervention that is gentle, that drives the potential of improved bone health and muscle health, that would be such a welcomed asset in that population.

I agree with Dr. Lingvay completely. I also wanted to point out that if you look at the evolution of our field, as time goes on, people are going to be treated earlier and earlier. Right now, we're dealing with a lot of people with very high BMIs because they haven't had any treatment really available that was accessible to them. So there is a big need for extremely effective compounds. But over time, the right way to manage obesity is to treat people when they get to a BMI of 27 or at the maximum 30, and they'll never get to these catastrophic weights. And at that point, think about it, if you had a BMI of 27, let's say, and you were treated with a medicine that had almost no side effects and you got down to 25 or 24, that would be fabulous. That would be a really great outcome. So I think that is ultimately where we're going to be headed. And so a medicine like this is very well suited for that future.

I think there were 2 questions still open. And maybe, Manu, they go to you. One, the lack of a dose response seen with petrelintide, so the plateauing. Any explanation why this is? And then the second question, which dose to be taken in Phase III development?

Yes. So in terms of the doses to be taken for -- in Phase III, we'll be able to get into a little bit more of that detail in a few weeks' time. We're not able to disclose that right now because we're still finalizing some of those protocols, and we need to get some regulatory feedback on the final design. So we are not able to share it for that reason. But based on the data that we've currently seen, we are confident of what those doses can be.

Regarding the lack of dose response, I mean, this is still obviously in speculation territory, right? I mean I think one of the things we do know about amylins as a class is that unlike GLP-1s, which doesn't seem to have kind of essentially a plateau where you get to, it's largely limited by tolerability. It's not limited by efficacy. Here with amylins, we are starting to see there may be ultimately an efficacy plateau as well. And so the study that was done, which is the right study to do, which is a full dose range, gave us that empirical information that gave us that actual clinical data that we needed to see on the 5 doses that we tested, where does the curve fall.

So I think it's a mechanistic sort of difference. A lot of people are used to seeing incretins where you can keep pushing the dose. And as long as you're not tolerability limited, you will get more -- potentially more efficacy. But with amylin as a different class, a different mechanism, we're starting to see that there is, in fact, a plateau with the efficacy. But as Dr. Aronne mentioned, I mean, with all of the different caveats of this trial, 50% female, maybe in retrospect, if it's 42 weeks, perhaps we should have gone a little bit longer, et cetera.

We feel confident that the data that we have puts us in the right position to test this out in the right settings in Phase III. And obviously, in Phase III, we expect the population to kind of resort to the kind of the norm, if you will, where we'll see 65%, 70% of the population to be female. We'll obviously do a longer-term study, and then we'll really see how these doses play out.

James, all answered? Then next in the queue is Richard Vosser from JPMorgan.

Sorry for the background noise. I've got one question just on flexibility. Manu, you mentioned flexibility and the importance of using it going forward. We've seen other companies have trouble with the right flexibility and the lead -- and that leading to lower weight loss than anticipated. So just wondering how you can guard against making sure that the flexibility doesn't impact efficacy too much. And also linked to that, just thinking about tolerability, the tolerability was pretty good with eni, but not maybe quite as good as tirzepatide at the high dose. So just thinking about what else other than the flexibility you might be able to employ to further improve the tolerability there.

Sure. Okay. So you're right, I mean, you have to have the right balance. If you have too much flexibility, you may not get to the top dose. If you have too much rigidity, you might have too much dropouts. And we've seen, again, empirical evidence from 2 separate compounds showing exactly those 2 things. So we have had a lot of learnings in the field. And so we take those learnings seriously and try to provide that into this protocol where we try to achieve that sweet spot, that balance. I can't get into this every little detail, but there are very specific steps in the protocol where we are allowing for certain flexibility, but not so much that they're not getting to their assigned top dose, whatever dose that they're assigned to.

And again, I come back to what I said before, rightsize, right investigators and really try and motivate the participants in a way that we can achieve this. So the benefit that we have is that we've learned a lot from the field. We try to incorporate those learnings. We'll execute on the Phase III, and we feel confident that we'll get to that sweet spot. Now the tolerability part, I mean, I know that a lot of people love comparing studies. But I just, again, caution people. Just look at the study for what it is. Cross-study comparisons are a little bit challenging.

Oftentimes, people compare a Phase I to a Phase III tolerability profile and Phase II to a Phase III, et cetera. This is a Phase II study. And we have to recognize that there are certain vagaries of this study, as Dr. Lingvay mentioned. They were coming in every week to get their injection. When you come to a clinic every week and you get asked how are you doing? Do you have AEs? You're kind of in some ways, sort of prompting the question to some extent. So I think we have to be a little bit careful of not to try to make an apples-to-apples comparison with the Phase II and Phase III. But what I will say is that, as I said before, with the measures that we are putting in place with the type of investigators that we have in our study and the learnings that we have, especially on the flexibility side, we will manage through the tolerability.

And I think the final piece I'll say and I hand it over to Dr. Lingvay is the data, again, speak for itself. Personally, I was actually really concerned about going to 24 milligrams. But I was reassured by the fact that in the Phase Ib, we were able to get there very fast titration, no safety signals. Yes, the tolerability was higher because you're forcing the titration. Then we slowed the titration down in Phase II to every 4 weeks, then we saw almost half to 2/3 less AEs compared to the Phase I. So which tells us that there's nothing here in the molecule that concerns us. We feel that with the learnings that we have, we can institute the measures to get to better tolerability. And I think the final proof is Phase III to Phase III and ultimately a head-to-head comparison. So I would stay away from a Phase II to Phase III comparison. But let me hand it to Dr. Lingvay.

Yes. So actually, I'm pretty passionate about this topic, so I wanted to speak up because there is a difference in priorities that it's emerging strongly between the regulators who are really looking to make sure that the medicines that we're developing are safe for everybody that might potentially use this medication, investors like you guys, which are really just measuring these drugs against who gets to the bottom faster and harder and bigger and then the patients and those who care for the patients who really want the right therapy for the right person.

So we're designing these Phase III trials and Phase II trials with the regulatory requirements in mind, including people with a BMI of 27 and above. But then we're studying these drugs and pushing people to these highest dose drugs expecting 20%, 30%, 35% body weight loss. And the reality is most people, not only they don't need that, they should not get that, and we're hurting them by pushing them there. So yes, to marry all the interests here, we need flexibility in these studies. We need a lot of flexibility because if you don't get the flexibility, you're hurting people who are participating in the study who don't need that much weight loss, who might have side effects, and there's no reason to push them up if they're doing just fine on the lower dose and achieving the goals that they want.

Again, if you would want the race to the lowest, then we need to do studies that only enroll people with BMIs over 40 or people who truly need those amounts of weight loss that the investors are looking for in order to compare these studies against each other. So please don't measure development -- drugs in development by their amount of weight loss. Look at how much of -- how safe these medications are and in the right patient, do they deliver what they need to deliver and make the people healthier. Lowest weight is not our goal. It's really not our goal.

Then let's move on. Next one is from Steve Scala from Cowen. Steve, please.

Two questions. Does Roche have a strategy for monthly dosing of a GLP-1? And for Dr. Aronne and Lingvay, what percent of patients do you believe will be on a monthly product in 3 to 5 years? Is it a small minority? Is it the vast majority? Or is it somewhere in between? And then secondly, on CT-996, you mentioned go/no-go decision by the end of the year. What do you need to see to advance that molecule?

Dr. Aronne and Dr. Lingvay, please start on the monthly.

Well, as far as what percent of people will be on a monthly, I think we still don't have enough data to really determine how tolerable it will be, how effective it will be. I think that there will be big demand for it. I think it's very appealing. It's very exciting to think that we could have that. Will it work? Will the side effect profile -- obviously, giving something weekly will produce a better side effect profile for the same amount of medication for the average drug. So making that transition, we still have to be certain that that's going to be okay, but I think it will.

I'm not sure 3 to 5 years is going to be the time frame where there will be a massive uptake. But over time, I do think that for chronic disease, this significant number of people may switch to monthly. And it's very appealing as a treatment paradigm. I think for clinics, too, like have the patient come in and give them a shot once a month. I mean that could be very good for a chronic problem like this.

And I think there were also like 2 questions to you, Manu. What do we do in terms of our pipeline in terms of developing a monthly solution? And then 996, what does the go/no-go decision depend upon?

Yes. So regarding the monthly dosing, right? So I think the way we look at it is, again, coming back to the patient needs. As I said before in my opening the way we've sort of designed our portfolio is based on really addressing those kinds of heterogeneous needs. Some people, as I said, need oral, some people need injectables. Some people need a weekly, some people need a monthly or maybe even a quarterly. So at this point in time, we are very open to looking at all of them. And part of our strategy has been to sort of see what are the long-term -- I mean, long extension half-life technologies that we would want to really bring to bear.

And whether it's monthly or quarterly, et cetera, we can come back to refining that. But on a strategic level, I mean, I think that optionality is exactly in line with our strategy that Morten laid out, right? So we're never going to say it's an either/or situation because we just are humbled by the fact that obesity is so heterogeneous and there are needs at different stages for the same person actually. So I think we have to be open-minded about where those needs are. But it will always be guided by the same thing, which is if we were to bring a long-acting, is this going to significantly improve their quality of life above and beyond what they're already getting with their weekly or an oral? Is it really safe? Can we put somebody on for that long and be really comfortable with the fact that the safety and the tolerability profile will be good?

What are some of the conmeds that they may be using during that period of time? Because, again, remember, there is polypharmacy in people living with obesity because they have so many comorbidities. So there may be some advantages to having short-acting compounds for certain people, very long-acting compounds. So it's really not that simplistic when we kind of look at it in that way. Regarding 996, I mean, we'll obviously look at all of the things that we all look at when we made the decision for either enicepatide or petrelintide.

It's going to be a same set of very rigorous set of assessments, safety, tolerability, weight loss, glycemic control, cardiometabolic risk factor modification, the full gamut, right? Because what we're trying to do with 996 is to position it also for a broad set of indications, which includes obesity and glycemic control. So I think we have to look at the totality of the data. I can't get into specific numbers of what we need to see, obviously. But suffice to say, it's a rigorous assessment to really make sure that it meets the bar as a way that we define the bar. So you've heard from define what that bar is. And so it has to meet our bars to advance this forward into our Phase III pipeline.

Then we quickly go on. Next one is Simon Baker from Redburn. Simon?

Apologies again for the background noise here. Two, if I may. Firstly, just a question on petrelintide itself. There's been a lot of debate over the conference about the importance or otherwise of bias between the various -- the 3 amylin receptors and calcitonin. I just wonder if you could give us an idea of the relative affinity of petrelintide for those 4 receptors. And then a question for both Dr. Lingvay and Dr. Aronne and picking up on what Dr. Lingvay was saying. There is a clear disconnect between the market demanding ever higher percentage weight loss and clinicians demanding ever lower GI side effects. And it looks like with petrelintide, you may have a product that fits that profile of about 15% weight loss and very low AEs. So a question to both of you. What proportion of your patients would be adequately treated by a drug with that profile?

So I can take the first one and hand it off to both Dr. Aronne and Dr. Lingvay. So as you know from the data that's been presented already in the public domain, petrelintide is what we call a DACRA. So it's a dual amylin and calcitonin receptor agonist. It basically has receptor selectivity for both the amylin-3 and the calcitonin receptor. So at this point in time, I think the data is still premature to know that amylin-1 is superior to amylin-3 or not. Yes, on the surface, it might look like there's more to be had with amylin-1. But again, as I said before, I would caution us to not come into that trap of cross-study comparisons because ZUPREME-1 had baseline characteristics that were quite different. The demographics were different. Duration of therapy was different and so on and so forth.

So I think the jury, at least in my mind, my own personal mind is that it's still out in terms of what is the perfect ratio to have. But I think what we do know from the field is that having some calcitonin can be beneficial largely because it has potential beneficial effects on bone because we use in calcitonin today in clinical practice to treat osteoporosis. We know from preclinical studies that having some calcitonin actually can enhance insulin sensitivity. Now whether all those things will ultimately translate into the clinic with a DACRA or not in terms of those outcomes, yet to be determined, but that's our plan, right? I mean we want to have a robust clinical development program where we can interrogate the bone, body composition, et cetera, right?

So we do believe that, that mechanism lends itself to that. And that's what we're excited by. But I think to over-index on amylin-1 or amylin-3 purely on a cross-study comparison on weight loss, in my own personal opinion, is a little premature. But Dr. Aronne and Dr. Lingvay, you want to answer the second question?

I can jump in real quick because I agree it's a little bit premature to make this forecast. As I alluded to earlier, I'm very excited about an amylin-based product and especially because in primary care for the vast majority of people with no comorbidities and with a moderate amount of weight loss, targeted, this is a good option. Now as far as additional patient populations are going to depend on what sort of data is amylin going to be able to deliver. Will it deliver the data that it prevents fractures and falls and muscle wasting and all the other potential benefits that we're thinking would position this really favorably for an older population, for example. If that's the case, that's really a quite important segment population that would be favorably positioned to receive petrelintide or a similar drug.

There's also a big question of whether this petrelintide or similar agents will have cardiovascular protection on their own without mixing it with a GLP-1 agonist. If they do, I mean, that's really a game changer because now it can position it across a very wide age range and risk range and pretty much everybody with a weight loss need that is below 15%. It's a potential candidate. So I think as an initial phase, it does have a significant potential, especially in primary care and sort of entry-level treatment with first-line therapy for overweight and obesity. Over time, as data gathers and more information is available, it does have the potential for these additional market segments that are well represented.

I agree with Dr. Lingvay. I see older people would be a great one, primary care because of the side effect profile. I would also add people who aren't responding to the other compounds. So because of mechanisms, I imagine, we're seeing a minority -- a small minority of people, but a significant number who don't respond to GLP-1s or even the GLP-1/GIP combination. And I think that with an additional mechanism added, we may get extra weight loss in those people who are refractory. I mean, think about it if it's just 5% of the population, you're talking about millions of people who potentially could benefit from a drug in this class. So I think there's plenty of market for compounds in this category.

Very good. So we have one final person. Actually, it's Graham Parry from Citi coming back with a final question. And then I think we will close the Q&A session. Parry, the final question goes to you. Graham, the final question goes to you.

Actually just a quick follow-up. So on CT-388, you're saying you'd run head-to-head studies in glycemic studies in type 2 diabetes, but I wasn't sure if you said you would or wouldn't run head-to-head in obesity.

Just to clarify, I mean, we are still fully weeding out all of the Phase III and the Phase IIIb plans for the chronic weight management side. So we're not precluding the possibility that we might run it there. But for glycemic control because the standards of care are already pretty established in terms of what your background therapy is going to be, there, it just -- it's much more obvious. And there, back to what Dr. Lingvay had mentioned before, the FDA is actually well aware of the fact that those background therapies for type 2 diabetes have to be studied, right? So that's the reason why those head-to-head studies are a little bit more firmed up for glycemic control.

But for chronic weight management, there's still some uncertainty around can we not have a placebo from what we have understood from the health authorities is that they want to understand the safety profile of these novel therapies on a "clean background." And so it's not that we want to constantly keep doing placebo-controlled studies. I mean, just to be really clear, it's -- we have to meet certain regulatory requirements. And so exactly how those evolve, when they evolve, we will adapt to those. And at that point in time, we may foresee doing head-to-head even in chronic weight management. But it's a little bit more established in glycemic control, and that's why we have more firmed up plans there.

Yes. I think with that, we close the call. Let me thank again for all our presenters for their time and efforts exploring new treatments for obesity patients. Let me also thank the IR team members who worked on the slides and prepared this event. So I have to call out here, Jan Patrick Scharzon and and also Melanie Wolf for the event organization. I hope the event was helpful and provided a timely update on our CVRM franchise. And if there are any remaining questions, then please do not hesitate and reach out to the Roche IR team. We are happy to further help and come back to you. And with that, we'll close the call, and goodbye.

So welcome to our Annual IR Diagnostics Day 2026 here in London. Let me quickly take you through today's agenda. We have today 10 speakers with us who will provide updates on the Roche Group strategy, the diagnostics strategy, the diagnostics business portfolios and priorities, as well as latest overviews on the pipelines of our 4 customer areas, which are core lab, molecular lab, including Foundation Medicine, pathology lab and near patient care.

This year, we will have a special focus on the upcoming global launch of our truly transformative next-generation DNA sequencing technology, which is called AXELIOS, and on the end-to-end oncology ecosystem, which we have partly built already around it. This ecosystem has recently been strengthened by partnerships with Freenome in early cancer detection. And by the recent acquisition of SAGA Diagnostics, a company known for ultrasensitive MRD testing.

In addition, this emerging ecosystem has also been completed, complemented by the most recent acquisition of PathAI. This is the announcement we made just last Friday, which is a company from Boston developing AI-based digital pathology solutions. And taken together, all these approaches will not only help us to revolutionize cancer detection and care, but also they have the promise to contribute in the future to drug development efforts.

Can I have please the agenda slide? So I will take you through the agenda and also the changes we made last minute. As last year, we'll have 2 sessions, as you can see here, 2 presentation sections of 60 minutes each, followed by 20 minutes of Q&A, where we will have [ always the respective ] speakers of the presentation section on stage.

So for the first session, which is scheduled from 1:00 to 2:10, you see this session will be opened by Thomas Schinecker, our CEO of the Group. Thomas will provide us a quick update on the group's strategy and comment on our longer-term ambition. The second presentation will then really open the IR day. It will be by Matt Sause, our CEO for Roche Diagnostics. Matt will provide an overview on the overall vision and strategy for Diagnostics, and he will talk on the future ambition for the Diagnostics division. Third speaker is Palani Kumaresan, our Global Head of Roche Diagnostic Solutions, who will break down for us the strategic priorities of all our 4 customer areas. He will also provide a quick update on the ongoing mass spectrometry launch, one of our key growth drivers for the future.

The final presentation then of the first session, focusing on Roche Information Solutions, will be given to 2 speakers. It will be held by Moritz Hartmann, our Global Head of Roche Information Solutions; and by Andy Beck. Andy is our surprise guest for today, Founder and CEO of -- sitting over there, of PathAI. Moritz will briefly summarize our overall efforts in digitalization, how we strengthen our product development capabilities and also create new product opportunities, whereas Andy Beck will explain to us how AI-based digital pathology will strengthen our product development capabilities, especially in oncology and immunology and also how this approach could contribute to scientific hypothesis generation and ultimately support future drug development efforts.

Following these presentations, we will have a 20-minute Q&A session before having a quick break of 15 minutes, and then we are back at 2:45 p.m. for the second session. Session 2 will be opened by Josh Lauer, our Global Head of Customer Area Molecular Labs. Josh will provide us with the latest and greatest of our truly revolutionary and game-changing AXELIOS sequencing technology. He will highlight the unrivaled versatility of this technology and its potential to future applications by sharing some of the latest data, which we have generated.

Second speaker will then be Daniel Malarek, CEO of Foundation Medicine, which is Foundation Medicine is part of the molecular labs customer area. Then we'll talk to our increasing product offering of FMI in oncology and the unique opportunity, which we have here to integrate Roche Innovation Solutions, whether it's the AXELIOS sequencing, the VENTANA platform or navify Digital Solutions.

Following molecular labs, Laura Apitz, our Head of Pathology Customer Lab area will then cover the fastest-growing customer segment, Pathology Labs. She will drill down and take us through the strategic priorities of this segment. And fourth speaker, as you can see here, then will be Ildiko Amann-Zalan, our Head of R&D Roche Diagnostic Solutions. Ildiko will cover our near patient care portfolio providing latest updates on the early launch days for our CGM solution and for LumiraDx. And finally, we will close the second session again with Olivier Gillieron, our Lifecycle Leader Cardiometabolic and Neurology with an update on [ collab ] assay highlights, which include novel assays in neurology. So that's the NfL assay, but also the pTau217. You might have seen the news this morning. And also some news on the long-awaited update in infectious diseases on our tuberculosis assays.

Following the second session, we'll have then, again, our second 20-minutes Q&A before closing the broadcasted part of the event. Participants on site will have the opportunity to meet all senior management at the closing, upper row. Most management will be around for another 40 minutes.

In terms of housekeeping items. Let me just point out that we again have prepared our short survey to collect your feedback. Participants joining online will be invited to join the survey 10 minutes before the final Q&A ends. A pop-up window with the questions will show up, whereas participants on site will receive an invitation to participate in the survey by e-mail roughly 1 hour after the reception took place.

And with that, before handing over to Thomas, let me thank the speakers again for their time and their continuous efforts in improving the life of patients. And also the IR team and the members who contributed to this event. First to name, Birgit Masjost, who led the -- who's leading Diagnostics within the IR team. Birgit had the overall lead for the event, and she will also moderate both Q&A sessions. And then in addition, I have to call out [indiscernible] for speaker support and slide preparation; [ Julio ] [indiscernible] for speaker support and slide preparation and managing the master deck; [ Rafael Pavlovsky ] for speaker support and slide preparation; and last but not least, Eva Losert; Melanie Wolf, Beatrice Hau and [indiscernible] for event organization.

And with that, it's time to hand over to Thomas for providing us an update on the overall group strategy and the longer-term ambition. Please?

Thank you, Bruno, for the introduction, and it's great to see you all here in London today. As mentioned in the Q1 call, in the future, the idea is that I would attend a pharma day and a diagnostic day always in separate years so that I give attention to both divisions. And of course, this time, there are 2 highlights that I thought I cannot miss, and one is the sequence launch. Something that I know for many years, I've always been asked, when are you going to launch, when are you going to launch? And I always said, we are going to launch, and we will have a very competitive solution. So I'm personally also very excited on that. And also, I'm very excited that we made an agreement with PathAI so that Andy could also attend today. Thanks, Andy, for joining us, and welcome to the Roche family.

Now let me go through and give you a brief group strategy update and then also give you an outlook on growth for the group over the next years and into the next decade. On the group strategy side, you've seen the strategy house before the 10-year ambition. So where do we want to be in the next 10 years. But also the different elements of our strategy using AI, digital health, sustainability, people and culture and then diagnostics and pharma. Good thing is not only did we complete the strategy house to really define the direction of the company, we are also making superb progress when it comes to implementation. And let me just go through a couple of things.

First, on the 10-year ambitions, 10-year ambitions on the pharma side, it's about delivering 20 transformative medicines by the end of the decade. And here, we've made superb progress. Not only do we have now 66% of our portfolio with best-in-disease potential. But also, we have increased average peak year sales of our pipeline per project by 67% and a total pipeline value by 63%. So we have a higher pipeline value than ever before in our company. And if you look at the readouts that are going to come over the next couple of years, with up to 19 medicines that could launch by the end of the decade. This is a very strong late-stage pipeline.

But not only have we accelerated what we did in late stage, we also did that in research. If you look at lead identification and optimization, if you look back 3 years ago, we had around 50 of those every year. We have doubled that output. And clearly, AI plays a role in here as well. On the Diagnostics side, it's also about doubling our output on R&D and reaching more patients. Just a couple of numbers that really underline that.

First, if you look at the industry, how many FDA approvals that were in the last 6 years. Roche Diagnostics has more than 50% of those diagnostics approvals. And certainly, we are not spending more than 50% of the industry's budget. So clearly, we have a very productive R&D. And you can also see that we have 3 instrument launches, 3 instrument launches with blockbuster potential, CGM, mass spec, and now coming next generation sequencing. Again, something that I don't think any other diagnostics company has in such a short period of time. Also, we keep filling our menu with additional tests and digital solutions that augments and differentiate us from our competitors. So clearly making a lot of progress here.

Now let me also recap the group strategy and where do we want to go and what are we going to focus on. And you have seen this slide before. So these are the major trends that we see in health care and how we respond to those major trends. Clearly, there are 3 therapeutic areas: oncology, neurology and CVRM that are contributing to more than 50% of the global disease burden. And you'll see the same later on the pharma slide. Especially in situations with health care systems are really in tight budget situations, health care systems will continue to prioritize areas where they can have the biggest impact with the money that they have to spend. So for us, it's important to prioritize the diseases with the highest societal burden. And clearly, have differentiated medicines, transformative medicines. And this is also where then you can address higher patient populations or larger patient populations.

As mentioned already, health care costs continue to grow faster than GDP. So we have to provide solutions that improve outcomes. At the same time, reduce cost of care. Hemlibra being a good example. It improves the life patients with hemophilia A, but also reduces hospitalization with that cost of the system. So we have to write these kind of solutions in order to address this trend.

But what else do health care systems do in order to address the trend? One is decentralization of care, meaning that people that go to the hospital today in the future will be treated in the outpatient setting, meaning primary care or sometimes in at home. So for that, we need decentralized solutions, both in diagnostics and in pharma. Diagnostics, for example, solutions like Lumira where you can do testing in the GP segment as well at the low cost. But also in the diagnostics -- on the pharma side with drug delivery systems. So people can actually take the medicine at home or in a GP setting and don't have to go in the hospital and drive cost in the system. Plus for the patient, it's also a better experience because who wants to be going to the hospital all the time, it's better to do it in your home. Also, what you will see is a trend towards early detection, monitoring and intervention.

Bruno mentioned Freenome for early cancer detection. We also mentioned SAGA for minimal residual disease testing. Again, tests that detect disease early, so you can intervene early and reduce costs in the system and prove the chance for the patients. Of course, access to health care is still a challenge. More than 50% of the world does not even have access to basic care. This is a big opportunity to reach more patients. And then there are transformative technologies, AI being one of them that we have to be at the frontier of because they are going to change the way we either discover medicines or treat patients or even diagnose patients.

That's why we have this group strategy around convention, stopping and curing diseases so that people don't only live longer, they live longer in a healthy way. So not only lifespan, but health span. And the combination of diagnostics and pharma plays a significant role here because you need a diagnosis in order to have the right treatment. You need an early diagnosis to have a high chance for cure, clearly focusing on the diseases that drive the highest societal burden and the highest cost to the health care system and really innovating a long patient journey to improve care for these diseases and meeting where patients are, where they are, and not only in the hospital, but even in the home setting.

So this is around prevention, identifying these patients early for diagnosis, making sure we have an early treatment like with giredestrant in the adjuvant setting where you have a higher chance for cure, stopping the progression of disease or even moving towards cure, as we do, for example, with CAR T cells where you can reset the immune system for certain autoimmune diseases.

Now let me give you an update also on our progress on AI and data. As we implemented our AI strategy in the company, we implemented in 3 levels. First level we call EverydayAI. And And EverydayAI means we've trained 100,000 people on AI, and almost everyone completed it. And if we monitor it now, we can see that 75% of our people now use AI in their everyday work. And this is really using off-the-shelf tools to make them more productive. As we go into the next round of training, we'll also introduce agentic AI, so people continue to get trained, so that we can use these tools to improve the productivity in our company.

The second level of AI is what we call reshape. So basically, we have 3 main processes in the organization. One is service. The other one is marketing and sales, and the third one is R&D. And we can use AI tools across the entire process to shape, reshape and redefine the process and also accelerate the process using AI tools in different steps of the way in order to become more efficient and more productive as a company faster and also create more output. For example, if we generate kind of protocol -- study protocols, we can use AI to generate the protocols. Clearly, this reduces the amount of time that people need to write those protocols, and we can become much more efficient. So we do that along the entire journey.

The third level is really around the big ideas. What are the areas of disruptive potential. And AI can have disruptive potential in research in pharma. What we call Lab-in-a-Loop, basically, you use different AI tools to generate drug targets. You make those and then you test them in the wet lab, you feed back the data and you constantly update your model, you train your models. These are proprietary models that our people have developed in order to accelerate drug discovery to find more targets, become more efficient. For example, we've now embedded AI tools in 100% of large molecule drug discovery programs. And we have more than doubled target entry using AI, and we also can accelerate, as you can see here, we have 3 DevGo accelerations.

Another area that we can see as big ideas is digital pathology and using AI in pathology is one of the areas we'll talk about later as well. Yes, one area, as I mentioned, is digital pathology, and PathAI is clearly taking us into the next era here as well, bringing in the leader in this space to really accelerate our activities. But our activities in AI haven't just started with the acquisition of PathAI, it started much earlier.

Back in 2016, when we did the first collaboration with NVIDIA. And why did we do that in sequencing because we knew as we were developing the sequencer, we need to have chips that are able to handle the amount of data that we produce on the sequencer. The sequencer today, and it's only the start because we're going to improve further on that, the amount of data it needs to handle is 3 high-definition movies per second. There was no computer chip in the past that could be able to do that. That's why we needed to work with NVIDIA. And the speed will even go up further. And this is all computing that actually happens on the chip.

And then as you can see, 2019, for example, it was the first time that an AI algorithm outperformed the radiologists. It was already clear that time that imaging was one of the areas where AI would really play a significant role, and that's why also the acquisition of PathAI. You probably remember also the protein structure prediction by AlphaFold. So you can see a lot of progress that has been made, and we have invested in AI in that time period. And now expanded back in 2023, our collaboration with NVIDIA on the drug discovery.

This has now led to us also investing more into own chips and on-premise infrastructure. With that, we now have the highest compute power in the pharma industry. And we need that as we continue to build our models and co-train our models, feed the models with more data. We need that compute power in order to be able to leverage AI throughout our R&D. Also, we are a founding member of the SAIL Foundation. So this is a shared license agreement with companies like Anthropic, Microsoft or IBM.

Now we already talked about digital health and PathAI clearly playing a role here. There is a strong synergy to both diagnostics and pharma. Clearly on the diagnostics side because the cancer cases keep rising. The complexity of diagnostics keeps rising because there are just more markets that you can look at. And actually, the number of pathologists is actually decreasing. So how do you generate better diagnosis? It's using AI. Clearly, a strong synergy with the Diagnostics business with our advanced staining business with our PHC business in diagnostics. But also on the pharma side, leveraging those tools in research, increasing our speed in research, increasing our PTS in research as well. But Andy and Moritz will talk more about that as well.

Now let me briefly dive into the area of sustainability, also an area where we've made significant progress, and where also Roche is a front-runner. Just to give you a couple of examples here. On the one hand, on environment; the other hand, on access and innovation. In environment, since last year, we have 100% of all our sites globally now on sustainable energy, 100% of our sites. We've reduced water consumption by 10% last year, 26% since 2020. And if you look at greenhouse gas emission alone last year, we reduced it by 34%. We've now reduced it by 78% since 2004. And our goal is not to have a net zero. Our goal is to have a real zero in terms of greenhouse gas emissions.

If you look at access and innovation, just last year, again, we claimed #1 spot in the Global Patient Reputation Survey. This is done by patient organizations, and they rank pharma companies based on how we are to work with. We have global impact in diagnostics, 31 billion tests. That's more than 3 tests, 3 to 4 tests per inhabitant in the world. We've also invested in antimicrobial resistance with the first antibiotic in 50 years. So again, something where we contribute to society. Also in Africa, working together with different foundations to address the AIDS crisis and also expanding that into other areas such as cervical cancer screening. Again, significant progress in the area of sustainability, also making sure we take our responsibility here very seriously.

Now let me talk about people and culture because at the end of the day, we can only do what we do if we have the right people and the right culture in the organization. We have a highly motivated organization. 3 years ago, we talked about a high-performing organization. Now when I see some companies talking about culture in the organization, they also start to talk about high-performing organization. I just want to say, we've been talking about that for 3 years now. And not only did we talk about it, we've done substantial changes in the organization.

For example, the way we give incentives. We make sure that we have a strong differentiation between high performance and low performance in the organization. 3 years ago, we changed our bonus system. What do I mean by that? 3 years ago, we changed that people who are low performers, so greater contribution needed, would not benefit from company multipliers. So they would be capped in their bonus. So there is a significant differentiation to those people who have shown great performance. And what we've done is we created IMPACT Award to spot awards for those people who have really shown tremendous performance, again, shifting money from low performance to high performance.

If I look at our turnover rates, we have pretty much lowest turnover rate in the industry. But then if I look at the turnover rate between the different populations in our people, so between greater contribution needed, valuable and high performance, we have ultra low turnover in high performance and valuable performance. And because of the incentive schemes that we introduced, we have significantly increased the turnover rate in the low performance groups. So in the high performance, in the very, very low single digit. In the low performance, we are 35% to 37% turnover. That's exactly what we want because we want to make sure that we reward high performance in the organization. And with that, you change the culture in the organization to drive this kind of high performance. And we also don't want to make it comfortable for those people who don't deliver the performance.

And part of high performance is also leadership. So we've invested significantly over the last 3 years in leadership training of our people because at the end, people leaders also need to make sure that their teams perform in a very high way. They need to drive accountability. They need to create clear expectations, and they also need to make sure that we focus on efficient decision-making. We've also trained the organization more on different skill development areas because we feel that's also important in order for an organization to be a high-performing organization.

Now what does that translate to? At the same time, as we move into the shift of a high-performing organization, where we are on the journey already for years, we have excellent scores in terms of employee engagement. Just on Monday, we sent out the results of the employee satisfaction survey that we did over the last 3 weeks. And if you look at it, we have 82, and it's plus 3% higher than what we had 3 years ago. At the same time, if you look at the global benchmark, we are 12 points above the global benchmark. And 1 year ago, we were only 8 points above the global benchmark. So we increased the satisfaction of our employees while at the same time in the industry, the satisfaction dropped by 3 points. We are also externally recognized as one of the best employers by LinkedIn, but also by the Science magazine being #8 and #1 spot across all different pharma companies.

And we just put together a couple of quotes. So these are not quotes from our internal employee survey, these are actually quotes from external sites where employees give kind of a sentiment on what's happening in the company. And you clearly can see that we have a strong shift into faster decision-making, strong accountability, stronger link from incentives to achievements. Clearly, in terms of speed, more science rigor, more debates. And this is exactly the cultural shift that we wanted to make 3 years ago. And you can see that it has happened. And this happened while the satisfaction has gone up. And while we still do the changes that are necessary. And you may have seen that in some of our past presentations. We have cut about 1 billion cost out of the system in R&D that we have reallocated in the project, 1 billion, and that's about sourcing. This is about using AI to accelerate.

But it's also, for example, to give you one very concrete example, 3 years ago, Flatiron lost about 250 million a year. This first quarter, Flatiron is positive in profitability. So we've made a significant turnaround in that business, while at the same time, growing high teens. And that's exactly what we need to do. We need to become very, very productive to make sure that our money goes to the areas where it has the highest impact and where it creates speed in the system. And what I like, if I now see a progress in different parts of our R&D, I get e-mails from people in the organization. Oh, we just broke another record in how fast we recruited here. We broke another record how quickly we went to filing. We broke another record, and this is exactly this mentality that I want in the organization that people take pride in achieving the speed that we need in order to be competitive. And this is exactly the direction that we want to go.

Now let me briefly touch on the pharma strategy as well. And you have seen this slide before. This is why we're focusing on these 5 therapeutic areas. The 3 that I mentioned before, cardiovascular metabolism, oncology, neurology, making up about 50% of the global disease burden. If you add immunology, which plays a role in multiple disease areas anyway, and ophthalmology, you are at about 60% of the global disease burden. And these are the areas that actually grow. So we are focusing on the areas of growth and where we can reach as many patients as possible and where we can make a difference. At the end, this translates into the market. This is the size of the market. That's why we're focusing on it.

And if you see the progress that we have made in the pipeline, I already mentioned that we are at an all-time high when it comes to the value of our pipeline, a 63% increase versus 2022. At the same time, we have less volume. Now the volume will continue to increase again, but the point is we can't do everything at the same speed. We need to fast track certain programs so we had to have more money available for programs where we need to go extra fast. Trontinemab being a great example for Alzheimer's, for brain [indiscernible] antibody because it's one of the biggest opportunities we have with a clear differentiation. So we fast track those programs.

At the same time, I already mentioned, we need to become highly productive and efficient, and that's why we work on constant reallocation of R&D resources. Just because we don't announce like other companies, 8,000 or 9,000 people reductions, doesn't mean that we are not working very hard on productivity. We just do it in a very calm way and not in a very, I would say, that outspoken way. What we also introduced is this organizational -- we changed the setup in terms of end-to-end accountability across our entire R&D and also introducing business and scientific Boards. And these are important because these are the challenge Boards.

And what it translates to, you can see here, if you look at this on value and PTS, in dark blue, you can see those projects that have gone into late stage, significantly higher value, significantly higher PTS. In fact, if I look in the past, usually the PTS protection of our people was always correct. So when our people protected PTS is above 50%, usually, that meant that, that trial was successful. If you look at the average PTS right now that we have in the pipeline, it's around 70%. So clearly, a significant progress, not only in terms of value, but also in terms of PTS.

Diagnostics, I will not go into. I will let the Dia team handle that because I know you're going to be in very good hands with them. So I look forward to listening into that as well. Now let me finish with giving you a growth outlook. You've seen this slide before, consistent, strong delivery of growth, 5%, 8%, 5% sales, 8% in core EPS. In fact, if you look at the last 2 years and 3 quarters, in fact, we had an average growth of around 8%. So significant delivery. And I can say we've actually really delivered. And we delivered in this time period when we actually had the cliff of MabThera, Herceptin and Avastin as well. So we continue to grow and we also continue to grow through digesting also the COVID sales.

And if I look forward, between '27 and 2030, we have 19 medicines that could reach patients, 19 Phase III readouts. This is a very full pipeline that we have. And so we have a lot of trials now ongoing in the late stage. And in Diagnostics as well, we have strong pipeline, and we have already launched a number of blockbuster products, CGM, mass spec, very soon, the sequencer, but we also have a number of assays that are going to be very important for our menu. Lp(a)., I know this is also a big target right now in pharma. But also if you look at pTau217, you saw the press release on that for Alzheimer's NfL to look at the progression in multiple sclerosis and the interferon gamma release assay for TB is also one that people are really looking forward to.

Now you've seen this slide before. And what does that translate to in terms of the growth outlook for our company? Diagnostics, as you can see on the bottom, we'll continue to drive growth. It will be growth in the mid- to high single digits over the long term and corp growth ahead of sales. If you look at the pharma portfolio, and here is a big change to what we showed you in September. In September, we said the on-market portfolio and the data we have in hand is going to deliver growth until 2028. And then the on-market portfolio will compensate for any generic version.

Now given all the positive readouts we had in the last 6 months, 4 positive Phase IIIs of Gazyva in a row, the data on giredestrant adjuvant, which is a significant opportunity, adjuvant is more than 70% of the market for [indiscernible]. And also the fenebrutinib data, you see that we will no longer have a situation even with what we have in hand where we are not going to grow. We will continue our good growth momentum, not only until the end of the year, end of the decade, but beyond. We'll continue a strong growth momentum.

And with all the medicines that we have in the pipeline that are going to read out in the next 3 years, this will add on top, BD will add on top. So we can be confident about the growth momentum that we have and that we will continue to have. And if you compare that to the consensus, you can see on the left-hand side, the biosimilar gap that's expected if you take all of the different analyst numbers together, it's about 6.7 billion over a 5-year period. And then you see in the middle, the growth on the on-market portfolio and what's in the pipeline. In many of those areas, we already have the data in hand, giredestrant. Gazyva is a significant opportunity with the different -- in lupus nephritis or SLE, for example.

So if we then go through the list, personally, I would say there is upside potential, and there's definitely more potential for the upside than for the downside. And there are many things that are not uncovered by the models today. So there is the opportunity to drive growth into the future here as well. And let me just say, as I hand over to Matt, we have delivered in terms of what we have said 3 years ago in terms of growth, in terms of pipeline rejuvenation. Our outlook has fundamentally changed given all the positive readouts that we have seen, and we have a very full pipeline in pharma and in diagnostics that are going to drive growth also beyond the decade.

Thank you very much. And now I hand over to Matt.

All right. So welcome, everyone, to Dia Day 2026. So on behalf of myself, and all of our colleagues, we're really looking forward to giving you insight into the diagnostics strategy, our rich pipeline of innovation. You got a bit of a preview there from Thomas, and some of the innovative diagnostics solutions that are going to have a big impact on health care around the world and propel our business to that diagnostics financial ambition, which you just heard from Thomas. And so with that, let's get started.

So anchoring ourselves first with the strategy. The strategy has been unchanged for the last 6 years, and it consists of 3 key pillars. The first, we will continue to innovate and deliver high medical value diagnostic solutions. Second, we will deliver clinical decision support tools, and you're going to hear more about this from Moritz and Andy, to improve clinical decision-making. And then third, we combine these into solutions that span across the entire care journey and give patients and caregivers the tools to better navigate chronic conditions and diseases. And this also creates competitive differentiation from us against other diagnostics companies.

So how do we translate that into ambitious goals for the organization? So we are #1 in vitro diagnostics, and we have a goal to expand our position as the leader in the clinical lab. Second, we have the goal to become a leader in decentralized testing. You heard quite a bit from Thomas about why we feel that's an important area for us to remain focused as an organization. The third is to differentiate ourselves from our competition by offering comprehensive solutions across the highest disease burden areas. And the fourth, to deliver these in a way that help patients and caregivers better navigate the entire disease continuum in a way that delivers better outcomes for patients and society. A great example of this is our ecosystem we're building in oncology and neurology.

So now I'd like to explain a bit about how we are organized as Roche Diagnostics, which is centered around our customers. So going from left to right on the slide, starting with the core lab, this is the biggest business unit within Diagnostics and is focused on routine laboratory operations. The heart of this is our leading serum work area, which includes clinical chemistry and immunochemistry testing. I will also highlight that this includes the new mass spec system, which you're going to hear more about from Palani.

Molecular lab, covers both molecular diagnostics and sequencing. This consists of our mid- to high-throughput PCR systems, syndromic panel testing as well as the forthcoming AXELIOS sequencing solution, and Josh is going to take you through that.

Our pathology lab is centered around cancer diagnosis and companion diagnostics. So this includes our leading advanced and primary staining business as well as our digital pathology and personalized health care portfolio. Laura is here from VENTANA, and she's going to take you through that as well. And also, you'll hear about this from Andy.

Now near patient care provides solutions for decentralized and acute health care settings. This includes diabetes management, which is our largest segment as well as if you look at our LumiraDx, molecular, immunochemistry and clinical chemistry, and I'll cover that a bit later, but you'll hear more in depth from Ildiko, who's our Head of R&D for Diagnostics in her section.

So lastly, our precision oncology subsidiary, Foundation Medicine, which delivers comprehensive tests for oncology including our recent definitive merger agreement for minimal residual disease provider, SAGA Diagnostics. And I would call out that integrated across all of these, we integrate these lab solutions with digital products and solutions across the lab and the clinical settings to enhance their value to health care providers, and I would also call it this improves our competitive position against other diagnostics providers.

So now I'd like to talk a little bit about the size of these customer areas. The first is the core lab, as I mentioned, our biggest business unit. This is a CHF 40 billion segment. Now it's growing at 3%. Again, we hold the #1 position here. But as we expand with solutions like mass spec, we feel we can grow the segment in the future.

The second, the molecular lab, PCR valued at CHF 9 billion and sequencing valued at CHF 7 billion. We are #1 in the laboratory molecular diagnostics based market. This is growing at 4%. And as I mentioned earlier, we are going to very ambitiously enter the sequencing space, which is growing at 7%. Here, we see a lot of opportunity for growth, especially as testing moves more in the direction of the clinical space. In the pathology lab, we are the #1 provider for precision oncology diagnostics, and this is a market growing strongly at 8%.

Lastly, for near patient care, the market is growing at 3%, but what I really want to call it is one of the fastest-growing segments within that, which is continuous glucose monitoring, which is growing at 14%. And again, you'll hear more about this from Ildiko.

So given the growth dynamics in the in vitro diagnostics market, and as you heard, our ambition to grow above the market with mid- to high single-digit growth. Our focus is on the highest growth segments in the diagnostics market to drive our business above market levels. So we will do this by focusing on the diseases with the highest burden on global health. And if you look collectively across our areas of focus, these represent 60% of the global health burden. So I'll discuss some of the drivers that we expect to continue to accelerate testing in these areas.

Starting with oncology. Here, mortality is expected to increase 50% by 2040, and we expect testing to be driven by a significant rise in early blood-based cancer screening, precision oncology testing and the rise in minimal residual disease testing, and this is driven by its incorporation in early cancer regimens as well as the availability of those early-stage treatments.

Second, neurology, where mortality is going to increase by 67% by 2040. And as an example, people living with Alzheimer's is going to reach 50 million people by 2030, the majority of which are never diagnosed. We expect testing to be driven by the approval and access of new disease-modifying therapies that require early detection and therapy initiation, but also combined with the availability of these new early blood-based biomarkers.

So third, cardiometabolic mortality will grow by 40% by 2040. Here, we expect testing to be driven by rising prevalence of type 2 diabetes and decentralization and growth of consumer-based testing.

Lastly, infectious disease mortality will increase 29%. And here, we expect the growth to -- or this mortality and the testing to increase driven by the growth of STI testing as well as syndromic-based panel testing. And here, this is where our strategic investment and acquisition of GenMark is going to be a key part of this, an area where we're going to continue to expand our menu.

So now I'd like to talk how we're going to achieve each of these goals, and I'm going to start with how we plan to expand our #1 position in the clinical laboratory. So if you look at this slide and break it into the left and the right side of the slide, our strategy here is very clear. We will continue to invest in delivering innovative solutions in the areas where we lead. We will not be complacent with our leadership position, and we plan to deliver innovation in our core areas of strength. And the key examples are really on the slide.

So first, cobas ultra. Here, we will combine preanalytics and analytics and deliver high capacity together with intelligent sample handling. Our smart e benchtop immunoassay platform, which we'll launch this year, this is going to be critical to enable our market capture of [ TB IGRA ] as we decentralize out into smaller customers. Our next-generation molecular work area, which will replace our industry-leading 58, 68 and 8800 with the next-generation molecular solution. And in the same theme, we're building an advanced staining fully automated next-generation solution for the pathology lab, which will replace our leading benchmark ULTRA Plus platform.

Now while we continue our growth in the areas where we're strong, we also plan to disrupt the market with innovative solutions that we will launch with the scale that only Roche Diagnostics can bring to the market. And here, I will call out our i 601, the industry's first fully automated clinical mass spec solution. Again, Palani will cover this, but we are seeing really strong excitement from our customers. Some of our customers have even put out press releases when they've acquired the system, and we're seeing very strong interest from the market.

I'd say the same theme with our soon to launch AXELIOS sequencing solution, which will bring unprecedented throughput and flexibility combined with high accuracy. And then I would also say beyond platforms, and I spoke with some of you at the break about this, we'll continue to innovate on our digital solutions as well as our chemistries. So an example here on the slide on the bottom, you'll see our protein to DNA workflows that will enable detection of extremely low amounts of proteins. This is critical for early detection of neurological illnesses as well as cancer. And a second example, well detailed by our definitive merger agreement with PathAI is our importance of AI enhanced digital pathology as a significant area of focus.

So with that, I'd also like to talk about how we plan to become a leader in decentralized testing. So if you look at this slide, you can see the different settings where decentralized testing is utilized from the emergency room and moving out farther away from the hospital to GPs, pharmacies and then even consumer and patient-based testing. And then you can see on the left-hand side, infectious diseases, cardiometabolic and diabetes. These are the conditions where an answer is critical to know right away that are most amenable to these kind of point-of-care testing modalities. And here, what I would call out is that we're going to cover every major point-of-care segment with our solutions in our pipeline and that we have been very intentional about how we built a portfolio that enables us to compete in terms of quality and our cost position, and Ildiko will take you through this as well.

So for the last 2 goals, I will combine them in a single section, how we differentiate ourselves through high medical value solutions and comprehensive disease management. But first, I want to really level set on how we define the different stages in the diagnostics patient journey. So first, on the far left, early detection. This applies to screening tests, which enable health care systems to move to preventive care model, reducing global health burden. Again, as Thomas mentioned, our investment in Freenome, having that option space in early cancer detection. We have a strong level of interest in early cancer screening, but screening more broadly.

Precision diagnosis, this refers to testing that provides precise characterization or disease and enables appropriate patient management. Therapy selection, solutions that enable optimal patient management and therapy selection. A great example is the CGP product delivered by Foundation Medicine. And then disease monitoring. This refers to longitudinal testing solutions and digital tools that enable patients and physicians to manage chronic conditions. An example here is our Diabetes Care business, for example, our CGM. So this is how we divide up how we view the diagnostics patient journey and where we build specific solutions.

So now I'd like to start by walking you through our 4 key disease areas where we see the opportunity for diagnostics as well as the growth potential in each of these segments. And we give an outlook for the segment growth to 2030. You'll hear in detail from the team about our solutions that we're developing for each of these segments.

So I'll start with the segment that has high unmet medical need and where we're investing significantly as Roche to develop best-in-class diagnostics. Early detection for oncology is experiencing significant growth. You see this in the 35% compound annual growth rate for multi-cancer early detection, which is driving this segment to CHF 5.3 billion opportunity by 2030. We feel we have a strong position and optionality in this space given our partnership with Freenome.

Therapy selection for oncology is a CHF 17 billion opportunity, growing at 9%. And here, we see growing demand for targeted companion diagnostics, digital pathology solutions as well as comprehensive genomic profiling, all of which are an area of significant investment for Roche Diagnostics.

Lastly, disease monitoring is also projected to grow at 32% to CHF 5 billion. This is driven by uptake of minimal residual disease testing. Here, our FMI portfolio and AXELIOS solutions will play a key role, especially with the recent acquisition of SAGA Diagnostics.

And so you heard Bruno mention this at the start. But just to be really clear, in oncology, we have built a unique set of assets that span the entire continuum of testing and uniquely position us versus other competitors to lead in this exciting space. So you'll hear detail from the team in their sections, but at a high level, what I want to point out is our industry-leading portfolio of assets.

First, I would highlight, we have the full complement of IVD technologies to enable leadership of lab-based oncology testing. And I would really emphasize that our AXELIOS technology platform is key to drive the future of molecular-based oncology testing together with our digitally enabled IHC VENTANA business, where you see the strong synergy between VENTANA and PathAI. We're also well positioned to compete in the precision laboratory business with our Foundation Medicine organization, especially with the soon-to-be finalized addition of SAGA Diagnostics to deliver on the opportunity in minimal residual disease testing. But we've also, as mentioned previously, built a strong position in option space in early cancer detection with our partnership with Freenome.

All together, we have built a full end-to-end oncology portfolio that will enable us to shape the future of the oncology testing in the market in a way that no other company can. And the team will take you through the details in their presentations. But I'm very excited about how we've pulled this together and built a leading position from end to end in one of the most critical opportunity spaces in diagnostics.

So now you heard about this earlier, but I also want to take the opportunity to really highlight a key part of our oncology strategy, which is the recently announced definitive merger agreement with the PathAI team. So PathAI, as you heard, is the leading provider of digital pathology image management systems. And again, this really enables pathologists to augment existing immunohistochemical or primary staining workflows with AI-powered digital insights to improve patient management. And what I really want to call out here is this business is entirely complementary to our VENTANA business. It also has high levels of complementarity to our pharma services business, both in the pathology space, but also at FMI. It gives us the ability to engage earlier with pharma companies to build companion diagnostics programs and it provides that seamless complementarity again with our VENTANA business. This is going to position us strongly for the future. You're going to hear more about this from their CEO, Andy Beck; as well as our Head of RIS, Moritz Hartmann, but this is a key part of our oncology strategy.

So with that, I'd like to continue to neurology, which is the disease area undergoing rapid growth, again, to our aging society. And I will start with early detection, which represents a CHF 480 million opportunity by 2030. And this is going to be driven again by the availability and proliferation of blood-based biomarkers. So Olivier will talk about this in his section. But here, I would call it that we've just announced today the first CE mark for pTau217 blood-based rule in, rule out with an intended use in primary care.

One of the biggest barriers to diagnosis of Alzheimer's is the referral into secondary care, the availability of imaging and lumbar puncture based CSF test. And by having an intended use in primary care, we have a meaningful competitive differentiation against other test providers.

Now therapy selection is projected to grow at 17%. And here, we mostly focus on optimizing selecting patients for side effect profiles based on their ApoE4 status. But we also see an opportunity, and Thomas mentioned this earlier, for looking at disease progression as disease-modifying therapies enter the clinic, the need to understand progression and optimize patient therapy will increase. So here, I would call out our neurofilament light chain assay, which also received CE Mark in the first quarter, which is able to detect neuro inflammation and be able to help physicians better optimize treatment for patients with multiple sclerosis.

So now I'd like to continue with cardiometabolic testing, a segment where we are the market leader. Early detection is a significant market, valued at CHF 6.9 billion by 2030 and one where we are making significant investment, both with our core lab and near patient care portfolios. In early detection, we focus on earlier risk stratification in triage through novel biomarkers and integrated digital and diagnostic solutions.

Acute diagnosis of cardiovascular disease is at CHF 4.2 billion opportunity. And here, we feel that we have a focus on precision diagnosis of cardiovascular diseases with biomarkers such as troponin, which we plan to augment with new and novel biomarkers to improve the diagnosis of myocardial infarction. And here, I would also call, as you heard, Lp(a), while not really for the acute setting, is a test that is really exploding in terms of its utilization. And these are the kind of tests we will also use to augment our cardiovascular portfolio.

So cardiovascular disease monitoring is one of the largest opportunities in med tech overall. And this is primarily driven by glucose monitoring for people with diabetes. This segment is experiencing strong growth, driven by the explosion of continuous glucose monitoring, again, growing at 14%. This is a key market where we plan to expand.

So on that topic, I would like to transition to our Accu-Chek SmartGuide CGM. This is our AI-powered CGM solution that will help people living with diabetes manage their condition by addressing one of the biggest challenges that people living with this disease face, which is uncertainty. The algorithms we provide, such as our glucose predict and night low predict address the concerns people with diabetes have around how their glucose values may affect them, especially during sleep. We are developing future algorithms around therapy initiation as well as diet and exercise. And, and you'll hear about this from Ildiko, a next-generation sensor that will add to this portfolio of tools to enable people with diabetes to live their lives as they choose rather than centered around their disease. We're excited about our progress here in one of the largest and fastest-growing segments in med tech, and you'll hear more about this from Moritz and Ildiko.

So now coming to our final disease area, infectious disease. Here, diagnosis is a very large segment, predicted 2030 market value is CHF 25 billion. And this is really driven by segments such as sexually transmitted infections, where you saw from Thomas slide, are BV/CV, and we are continuing to expand our menu there, and syndromic panel testing as well as screening for diseases such as latent tuberculosis, which we will cover today as well. All of these are areas of significant focus and investment for Roche Diagnostics.

Disease monitoring here is a CHF 1.6 billion opportunity and one where Roche has and will continue to have a significant presence. This is driven by quantitative testing for patient viral load, and this is an area where I would say we've really shaped and built the market over several decades.

So now I'd like to summarize. So we gave really where we are going to be focused, how we're going to win, and I'd like to summarize that with our financial ambition. We are the leader in in vitro diagnostic testing, and we have a clear strategy to stay ahead of our competition and outgrow the market by focusing on the highest growth segments with differentiated solutions. You heard about the AXELIOS solution, which has a differentiated value proposition, and will make a profound impact on the sequencing market for years to come. And this will lead us to a mid- to high single digit -- mid- to high single-digit growth.

For core operating profit, you heard from Thomas, we will grow our profit faster than our sales. This is going to come from the profit contribution of our core business as well as our new launches as well combined with continued operational excellence. So mid- to high single-digit growth with profit growth faster than sales.

And so now to get into our portfolio, I'd like to hand it over to our Head of Roche Diagnostic Solutions, Palani Kumaresan. So thank you very much.

Thank you, Matt. A warm welcome from my side as well to everyone in the room and also those who are joining virtually. I'll try to keep us moving faster because we do want to keep the time for Q&A with you guys. I know many of you have many questions. I'll spend the next few minutes going through the Roche Diagnostic Solutions pipeline. So let me get started. Matt very nicely already laid out the 4 customer areas that are within Roche Diagnostic Solutions. The important point I will mention additionally here is these customer areas very nicely mirror how our customers are set up in the markets.

Now one of the core elements of our Diagnostics business is instrument placements. And so I wanted to start out also showing you how our instrument placements have grown over the course of 2025. These are some key instruments across the 3 lab-based customer areas. You can see very nice double-digit growth. And as we look to the future, this is in one slide gives you a holistic view of some of the key instruments and platforms that are going to be hitting the market in the coming years. '26, obviously, AXELIOS is an important focus, but also cobas smart e. I will spend a little bit of time talking about that for immunoassays. Over the next 3 years, '27 through '29, important additions to part of our automation portfolio, but also our near patient care portfolio. And then as we go into 2030, early part of next decade, Matt already mentioned, next-gen advanced staining, next-gen molecular work area and continue to build on our automation portfolio.

Now going hand in hand with our instruments is a very rich pipeline of tests. And this is, again, a holistic view on one slide. Over 140 new tests that we'll be looking to launch across the 4 disease areas with highest disease burden that match share, but also across some other areas that you see in the bottom. On the right-hand side, some examples, some of them are highlighted in red dotted lines. And the team after the break will get into the details of many of these tests.

So for the remainder of my presentation, what I'll do is I will very briefly, for each of the 4 customer areas, share with you the 5-year strategic priorities and then some key highlights, portfolio highlights. So let's start with Core Lab. Here are 3 important strategic priorities, evolve our next-generation systems portfolio. So I'm here mainly talking about mass spectrometry and also our cobas smart e. Develop integrated lab automation offering. Here, the centerpiece is going to be cobas ULTRA, and I'll say a little bit more about it in a bit. And then continued menu expansion with focus on high medical value assays, particular focus on neurology and infectious diseases, which we will, of course, get into more later on.

So mass spec, I wanted to give you an update here for some of you who might be a little bit new to this segment. CHF 3 billion segment, largely manual, labor-intensive and laboratory developed tests. With the introduction of our fully automated IVD solution a little over a year back, we've had some very positive feedback from customers. Performance, they really like. They absolutely like the end-to-end automation as well as the robustness of the instrument as it has come into the market. We have had placements across influential labs in Asia, in Europe as well as in North America with LabCorp.

Now by the end of this year, we are targeting a total installed base of 100 instruments. We have 39 assays that are launched in CE mark countries, and we look to continue to grow this menu. Now talking about growing the menu, I wanted to quickly share on this slide, how is the menu coming along. Top of the slide, you can see the 39 tests that we have launched in CE mark countries. These are focused on steroids, vitamin D, and therapeutic drug monitoring. So we are talking about immunosuppressive drugs, antibiotics and antiepileptics.

Going into 2026, we are looking at launching 4 more tests in CE mark countries. Now U.S. is the single biggest market for i 601. Here, we have already approval for the instrument along with vitamin D and 6 steroids tests in a CLIA exempt setting. And we are actively working with the FDA to bring the rest of the test that you see in the upper half through a 510(k) process towards the end of this year and then going into next year. Simultaneously in development, we are already working on the next wave of mass spec tests, and that would be primarily drugs of abuse testing.

Let's switch to cobas smart e. This is a low throughput stand-alone immunoanalyzer targeting low-volume labs. So low volume labs for immunoassays is around a CHF 1 billion market, growing at around 5% CAGR. Now in this market, we have had cobas e 411, and we have a very healthy installed base, over 18,000 installations, and this is going to be a successor to e 411. On the left-hand side, you can see some key highlights of this instrument.

One important call out, it will use the same [ reagent cartridge ] as it's used in our other immunoassay platforms, the e 402 as well as the e 801 that is -- that are widely available in the market. And this is something that is really liked by our customers to have the family concept. You can see on the bottom right, some key advantages of this platform. It's a benchtop, built very robust for remote settings with limited maintenance requirements. And we are looking to launch this and see more countries towards the end of this year and then subsequently in other markets, and it will have the full menu of immuno tests that we have on our other platforms like e 402 and e 801.

Now on automation. Here, I mentioned earlier about cobas ultra. And here, we are taking a very systematic approach to bring a series of innovations to the market. This year, we will have control launch of cobas ultra preanalytical system. This is the successor to our highly successful p512 and p612 pre-analytics solutions in the market. Next year, we will bring some important modules to this, like the centrification, which is very important for our customers, but also by directional movement of tubes, cobas ultra dual transport, and mobile robots to allow for automation across islands of analyzers in the lab.

And then working towards our omni transport. This is the ultra-high throughput, 2-dimensional single-tube transport that we are working on with our partners, Hitachi, and we will also bring modular pre and post analytics systems and analytics capabilities.

So what does this all mean? First of all, high level of modularity means our customers only pay for the hardware that they really need. Two, flexibility, space efficiency, it can really work with limited space, lab space, which is an important worry for a lot of our customers. And industry-first ultra-high throughput movement of tubes across different analyzers.

Now before I move on to molecular lab, I did want to very briefly talk about the neurology menu, especially on Alzheimer's. I won't go into the details here because you will later hear from Olivier a very nice data on phosphorylated-tau 217. But what I wanted to emphasize is we are taking a very systematic approach to introducing several different assets leading up to now phosphorylated-tau 217, and we will continue to increase or improve on a build on additional intended users and additional tests coming into the market in the future.

Now moving on to molecular lab, 2 important strategic priorities. On the PCR side, we want to continue to build a menu of tests, primarily looking at sexually transmitted infections, GI, gastrointestinal infections, also hospital-acquired infections on that ecosystem of PCR instruments we have. And on the sequencing side, of course, launched our AXELIOS sequencer.

Now on this slide, you can see that entire ecosystem of PCR platforms that we have in the market. Very briefly, on the left-hand side, we have our high-volume fully automated IVD solutions. 58, 68, 8800. Also the preanalytics solution, cobas prime. For point-of-care testing, this is, of course, liat. On the right-hand side, the open molecular solutions are two, we are talking about digital light cycler and life cycle pro, where we have a broad menu of research use only and IVD test from our TIB Molbiol side of our business, and syndromic panel on ePlex platform from GenMark.

Now Josh will later tell you how that menu is evolving on these platforms. But I also wanted to shine a quick light on donor screening, which is an important part of our PCR portfolio. And this is essentially blood testing for blood donations as well as for plasma fractionation. Together, the serology and nucleic acid testing, NAT is around CHF 1.8 billion market. On the NAT side, we see a good growth based on a few factors. There's adoption of NAT in many NAT naive countries, which still only perform serology testing. We see increasing testing of emerging pathogens. A good example of this is testing for malaria, and increased demand for plasma-derived medicinal products.

While there are many differentiating factors to our portfolio. The most important call out is this end-to-end integrated solution across serology and nucleic acid testing using our automation solutions as well. And towards this, we are introducing some additional solutions. So you see cobas SynergyPlus, which will allow for automated blood pooling, which is a common practice in many countries that are performing NAT testing. And also last month, we launched a multiplex test, MPX-E, which is bringing hepatitis E virus into our already multiplex assay for HIV 1, 2, HBV and HCV. And this allows for essentially workflow simplification for our customers because they don't have to perform a separate [ HEV ] test. So this is a great business for us, very robust, and we continue to maintain a good presence in this market.

Now on AXELIOS. I wanted to mention only a couple of points. Now last year, we introduced the technology at AGBT in February. And since then, we have systematically worked with early access sites like Hartwig in Europe, like Broad Clinical Labs in the U.S. and so on, to systematically demonstrate many of the applications that you see on the left-hand side. And as we get closer to launch in the summer of this year, we will be coming out with application notes that will lay out for our customers, future customers how to realize these applications in their own labs.

Now last month, we brought together a few hundred prospective customers from the U.S. and in Europe. And we had really tremendously positive feedback from the customers, both around speed, throughput, accuracy, the flexibility and of course, the pricing, the $0.06 per million repricing. And Josh will definitely get into a lot of the details here because we know that you're very much looking forward to hearing more about this.

Let me switch gears. Go to pathology lab, 3 important strategic priorities. Strengthening our advanced staining core business, both in histology and cytology. Driving digital pathology adoption. And here, of course, a definitive merger agreement with PathAI will play an important role. And then continue to build our assay menu, the test menu. And here, our pharma partnerships play a very important role, and I'll talk to you a little bit about that.

So how does advanced staining feature? Now here, we have the largest installed base of our advanced staining platform, Benchmark ULTRA and ULTRA PLUS, which is the core of our business. But you see we have primary staining, special staining platforms to go hand in hand as well as our digital pathology scanners. And when it comes to digital solutions that you see in the bottom, we have important solutions for lab automation. And then PathAI's AI site will become an important part of our digital offering for image management solutions.

Now as we look to the future, our next-generation advanced staining platform that we are developing with Hitachi, which will be a successor to Benchmark ULTRA PLUS, that will be important, end-to-end workflow automation here is not only software automation. We're also talking about bringing some clever hardware in the form of mobile robotics, flexible robotics and so on into the pathology lab as well. And then the AI-driven ecosystem, again, PathAI will be a key underpinning for this.

On the assay side, something that is quite remarkable is we have a menu of over 250 immunohistochemistry and in situ hybridization test on our advanced staining platform, and we continue to bring more innovation. We are looking at brightfield multiplexing tests, digital pathology algorithms. But what I wanted to point out actually is on the right-hand side, our personalized health care services business. Stand-alone, this is a great business for us. We have right now over 85 plus pharma partnerships, over 150 ongoing in vitro diagnostics programs. And what this enables us is having -- continuing to build this menu allows us to drive the placement of our instrument. And as we place more instruments in the market, we drive more access to all of these tests. And this is something that our pharma partners really like because they want to have broad access to the companion diagnostic test to make sure that the drugs can be really available to patients all over the world. So not only it's a great stand-alone business for us, it's also synergistically works very nicely with our core business.

Now to close out, I want to show you a couple of slides on near patient care. Key strategic priorities, building a leading portfolio in clinical chemistry and immunochemistry across hospital, decentralized and close to patient setting. Strengthening our position in molecular point of care through systematic menu expansion on liat. Here, the important focus is on sexually transmitted infections. And then deliver a competitive CGM solution.

Now Matt already showed the 6 platforms that form the base for our near patient care portfolio. I wanted to do one more click, share some key launches that are coming up, and then Ildiko will go into the details of some of these.

cobas sense is essentially our benchtop immunoanalyzer bringing lab-like performance in an emergency room setting, particularly for cardiac markers like high-sensitive troponin T. cobas vital is our next-generation blood gas and electrolyte platform. This builds on [ B1, 2 , 3, ] it will bring some unique algorithms like venous to arterial conversion but also significant sustainability and cost benefits. cobas pulse is a handheld hospital blood glucose monitor. We've had very nice growth in installed base since the launch in EMEA, LatAm countries over 24,000 placements. It also brings in a nice integration of third-party apps into this handheld device in a hospital point-of-care setting, and we're looking to launch it in the U.S. later this year.

cobas liat later this year, the lesion panel for Herpes simplex virus, [indiscernible] virus, which causes shingles and syphilis, also with mPOX. And then following that launch of Trichomonas and Candida vaginitis, again, really rounding off our STI menu.

LumiraDx, our focus is on menu that would really drive its adoption in highly decentralized setting. And this is where we are looking at the lipids panel, but also the next generation of HbA1c. And when it comes to Accu-Check SmartGuide with our current generation in the platform getting factory calibration, and pediatric claim is a big focus. And then we are also simultaneously working on the second-generation patch, both of which actually Ildiko will later show you how do these patches look.

With that said, I want to close out my section. And I'll hand it over to Moritz and Andy to talk through the Roche Information Solutions portfolio. And then after the break, we'll come back and we'll double click into some of the key parts of the Roche Diagnostic Solutions portfolio. So thank you for your attention. And Moritz, over to you.

Thanks, Palani. Yes. Thanks, Palani, and welcome as well from my side for being here today. I want to highlight on how our Digital Solutions portfolio and pipeline plays a strategic role in driving value for our customers and for Roche. I will talk specifically about how we're using AI to even elevate that value further. And of course, a good portion of this section will focus on the exciting opportunity with PathAI.

Our ambition is to transform diagnostics with data and digital solutions, moving from our strengths in the central lab towards decentralized care. We have 3 main value propositions across our digital portfolio and pipeline. The foundation for us is the connected lab, where our diagnostics insights portfolio delivers operational excellence to labs. We're making very strong progress in this segment where we have already converted our industry-leading analyzer footprint into the largest connected digital software footprint globally.

Building on this foundation, we're expanding our offering into our second value proposition, the informed clinician. This is where our solutions for clinical workflows and clinical decision-making drive faster and earlier diagnosis and better patient outcomes.

In our third value proposition, we're providing solutions for patients living with chronic diseases such as diabetes to better engage, control and manage their diseases.

Digital solutions contribute in 2 ways to accelerate the overall diagnostics value creation. First, our digital solutions drive important differentiation of our core diagnostics offering. This increases our win rates and actually drives longer customer lifetime value, including through our industry-leading portfolio of data security solutions. With our clinical support solutions and our patient-facing solutions, we're focusing on additional value streams, utilizing our market-leading strength and capabilities. This is why our digital solutions here are either FDA approved or CE marked, which is a very important and much appreciated differentiation factor for our customers. We're also seeing progress with reimbursement and adoption. Recently, the first European country has included an innovative algorithm and reimbursement, and an Asian country has included the same algorithm in their national guidelines.

Let's move on to how we utilize AI to transform the laboratory space. Here, our focus is to turn a fragmented, highly customized, but inflexible software landscape into an AI-native lab operating system environment, essentially doing for lab software what we have done with the [ same ] work area. We're approaching this in 3 phases. Phase I, which we plan to make available at the end of this year. We will build a native AI foundation using operational data. This will allow us to optimize workflows such as better demand forecasting or quality control and normally, detection.

In Phase II, we will build lab clinical intelligence by adding lab results to our trained LLM, and enabling use cases such as the interpretation of test trends or correlation between lab performance and outcomes.

And in the third phase, we will really create a holistic precision engine by now adding selected EMR data to this LLM, which will bring context aware reasoning across the entire patient workflow.

As you can see, we're executing on our digital strategy and our broad digital solutions portfolio and pipeline demonstrates our commitment. In the following presentations, you will hear more about our digital solutions that are very closely linked to other parts of the portfolio. Those highlighted in red here. The navify clinical hub, which complements our FMI offering or the Accu-Chek Care platform, and our leading customer experience, mySugr, which is now part of our CGM solution.

For now, I would like to share more on the exciting news we shared with PathAI. And as Matt already highlighted, the digital pathology market outlook is very strong. While the PathAI transaction is currently subject to regulatory approvals, we're excited by the potential to augment our offering in digital pathology by complementing the scanners and actually the full portfolio of pathology and also our algorithm offering. We will enhance the workflows with a next-generation AI-centric image management system, and we're turning -- and when turning towards pharma and our biopharma customers, we have the potential to build on our already existing successful partnerships in developing companion diagnostics algos. Finally, we will be able to provide a strong portfolio of AI services for biopharma customers with clinical trial efficiency and biomarker discovery.

With that, I'm very happy to welcome Andy back on stage, CEO of PathAI, who is our guest speaker for today and to walk you through more details of that. Andy?

Great. Thanks, Moritz. Thank you. Great. Well, it's my pleasure to introduce you to PathAI. Our mission since founding the company 10 years ago is improving patient outcomes with AI-powered pathology. From the beginning, we've been focused on technical leadership in AI as well as software engineering and medical leadership really focused on developing this technology for applications in pathology. We're also very focused on discovery, science as well as clinical and regulatory validation, and I'll provide a couple of examples of those today.

A key focus of our strategy from the beginning and where we see tremendous synergy with Roche is we're very focused on having one foot in biopharma and one in diagnostics and using those to strengthen each other, as Palani mentioned, with this virtuous flywheel where if we make discoveries in biopharma and we're already widely distributing diagnostics, we can then scale and distribute those insights globally.

And lastly, we're very well positioned early in a market that is just starting to inflect now. Today, the minority of pathology is digital. We expect in 10 years, it will be absolutely routine that pathology is done digital and with the assistance of AI. So we're aiming to build the operating system for precision pathology to power patient diagnosis and drug development at a global scale. And we have these 2 synergistic customer segments, both supported by one underlying AI flywheel.

For clinical diagnosis, we support the pathology lab by building tools, a broad menu of tools to cover the full spectrum of needs in the lab with the overall value proposition that digital and AI will drive increased accuracy, increased efficiency and increased access to precision AI tools to enable patients to get accurate diagnoses and to be recommended the right therapies.

The work in biopharma is very focused on how we can best use AI-powered pathology to serve 2 of the major value drivers within pharma, which is increasing the probability of technical success in clinical development programs, generating new pathologic insights in the mechanisms of response and resistance, and then with this synergistic flywheel, how can we use AI-powered digital pathology to not only increase the probability of success of the trial, but also to accelerate time to peak sales and even increase the amount of peak sales.

So to give you one example of this from our work in translational research, where we aim to unlock insights from whole slide images to drive advances in drug development. I'll focus on our PathExplore and IHC Explore products because I think they very nicely highlight these concepts. These are our products focused on exploratory translational research in oncology. So if you look at these 2 images on the left side of both of these panels, the one on the left is the H&E, which is the standard stain in pathology. It's been used for 150 years. If the pathologists were to look at that, they could easily say this is cancer. But what would be impossible for them to do would be to provide a single cell dissection and enumeration of every cell within the image as well as characteristics of the tumor and the tumor microenvironment.

With our AI-powered system, we can provide not only the -- support the diagnosis, but also provide this rich quantitative feature set, which can then inform studies into insights of pathologic mechanisms of resistance and response to therapies.

We do something very similar with our IHC Explore product, which is deployed on the core biomarker methodology in tissue pathology, IHC, except in addition to identifying every single cell within the image, we can also assess whether that cell is expressing a drug target of interest, which is valuable across oncology, but in particular, in immuno-oncology and to support studies of antibody drug conjugates.

We've been partnering since 2024 with Roche Diagnostics, a leader in tissue-based companion diagnostics. And the partnership is really focused on going from potentially finding a signal using an exploratory tool like IHC Explore, but how do we plug that into Roche's industry-leading platform for turning insights, turning signals into potentially regulated diagnostics not only to support registrational trials, but also to support global commercialization.

And I'd like to provide one case study of work led by our colleagues at Genentech that was presented as an oral presentation at the AACR meeting in 2023 that really, I think, highlights the power of the information that currently is hidden within these H&E images, which are literally created on every single patient in major therapeutic areas like oncology, inflammatory bowel disease and MASH.

So the investigators from Genentech wanted to answer a question. They said, if we applied deep learning power technology to a large set of H&E images from the OAK trial, could we identify a novel patient population who may show the best response to anti-PD-L1 therapy? And then beyond that after finding potentially this population, could this generate new insights into the pathologic mechanisms of response and resistance? And lastly, could there even be a world where identifying this new population in the future could expand the population of patients eligible for immunotherapy?

And what I want to highlight in this Kaplan-Meier curve on the left is this very top curve of the patients who are showing the best response to immunotherapy had a signature, which these investigators characterized as CP1 signature. So this is the population that showed the best responsiveness to anti-PD-L1 therapy. And when they looked into what was driving the signature, there's a very clear biological signal, which was increased lymphocytes and increased plasma cells with decreased fibroblast, was really the sort of cellular [indiscernible] that caused or influenced the environment to make patients most responsive to this therapy. So that's a new biological insight and a new population showing best response to this therapy.

And then they ask the question, is this only in [ all-comers ] or in the overall population as indicated on the left? Or would this even work within the PD-L1 negative population? And they found interestingly that the CP1 low population also showed strong response to anti-PD-L1 therapy even if they were PD-L1 IHC negative. So this is a new biological insight, potentially new prognostic signature, but also potentially a new strategy for increasing market for immunotherapy beyond just PD-L1 IHC.

So that was the biomarker discovery cohort. Because Genentech had digitized so many of their clinical trials, they were then able to validate this finding on a held out data set, which was IMpower150. And they found very similar response where overall strong predictive effect. And even within the PD-L1 negative population, the hazard ratio for the anti-PD-L1 containing regimen was 0.56 compared to about 0.7 in the intent to treat or a biomarker valuable population or much higher within the CP1 high population. So this is just an example of all the data that we have access to, but there are many insights to be discovered.

And this is one example of PathExplore applied to oncology. We also have a rich algorithm menu in liver, IBD, inflammatory bowel disease, as well as a number of different products for the clinical lab. And 2 that I'll quickly highlight is our PathAssist Derm product, which obtained FDA breakthrough device designation in Q1 of this year, and our AIM-MASH AI Assist, which is for use in registrational trials in MASH, which obtained both EMA and FDA biomarker qualification in 2025, which is the first AI algorithm to be qualified by both the EMA and the FDA for use in MASH trials.

On our clinical side of our business, the distribution of our platform is really driven by AISight Dx, which you've heard is a best-in-class digital pathology imaging management system to support diagnosis, collaboration as well as access to AI tools. This received CE-IVDR and FDA clearance last year as well as was the first digital pathology image management system that obtained a predetermined change control plan to enable us to rapidly expand the label and add new scanners and new monitors as needed.

So in summary, we expect that although the minority of pathology today is digital and utilizes AI by 2035, this will be completely routine. This will be driven by overall increased digitization as well as the massive increases of AI that we're already seeing today. But you can only imagine where it will be 10 years from now. Because of that AI-powered CDx, we expect we'll accompany most new approvals.

AI will be run in every single slide, driving increases in both quality and efficiency. This will also enable the generation of massive real-world data sets from billions of slides that can drive R&D decisions, regulatory decisions as well as policy decisions. And we're really -- our mission is really, how do we lead this over the next decade, enabling AI -- native AI slide to become the operating system for pathology, to leverage the tremendous synergies we see with Roche, to generate data at scale from many different areas where we're already synergistic, that you already heard, including FMI, VENTANA, as well as the new NVIDIA AI factory to enable data at scale in frontier AI to accelerate precision medicine. We have ambitions to develop the broadest IVD approved menu in the industry and to continue to focus on pathologists-led innovation to ensure that we're focusing on the products that matter most to physicians as well as to patients.

I just want to end by thanking everyone for their attention. I'm super thankful for the Roche team for their amazing partnership as well as for including me today. And then I truly believe that this partnership will enable us to realize our mission of improving patient outcomes with AI-powered pathology at unprecedented scale and speed.

And with that, I'll hand it over to Birgit to lead Q&A. So thank you.

Hello, everyone, and a very warm welcome from my side as well. So my name is Birgit Masjost, and I'm leading the Diagnostics IR team. And I welcome the speakers from the first session on stage now for the Q&A. I will be moderating the Q&A, and I would very much invite you to raise your hands if you have questions. And for the people who are joining online, please enter your questions in the Q&A tool. Also, I would really like to ask you to restrict your questions on the topics that have been presented today, so mainly focusing on the Diagnostics division.

Yes. And I see Matthew has his hands up. So Matthew, first question goes to you.

It's Matthew Weston from UBS. Thomas, in your opening comments, you talked about your confidence in increasing growth in pharma. But we haven't talked about the financial implications of all of the diagnostics growth opportunities that you've laid out today, Matt.

So I don't know if you can help frame that in terms how you see the midterm growth outlook. Do you see it accelerating, particularly with the new acquisitions? And when we get back to our desks, get our models out, what are the growth numbers putting in? What's the profitability we should be putting in when we take everything we've learned today in terms of real financial performance?

Yes. Great question. And so if you think about our ambition, which is mid- to high single digit, we know that we still have this headwind that we're working through on China. And I think as we get through this really in the next -- we say next year, we expect it to stabilize and then return to growth afterwards, I think then we can really have an assessment of if we want to take that ambition up. But I think at the moment, we want to keep it at that mid- to high single digit as we digest this headwind. But I think absolutely, we expect to see significant tailwind coming from these acquisitions and the new launches. But I think we want to make sure that we have the right baseline to set. But so for the moment, we'd say our ambition is mid- to high single digit.

And again, on the -- you said on the margin, profit will grow faster than sales. And what that means is we will consistently improve the margin over time. That would be how we would frame it.

Okay. Next question goes to Peter Verdult.

Peter Verdult, BNP. Could I ask a question just to you, [indiscernible] on margins? And then hand over to my esteemed med tech colleagues for some deep dive on diagnostics. But for me on the margin, it's just what's the real driver there? Is it mix? Is it SG&A leverage? Is it R&D efficiency? Is it a little bit of everything? But just a little bit more about growing faster than sales, what's the key driver? And then just with oil, and it's topical with oil, looking likely that it's going to be sustained above $100. Some of your peers are talking about 100 basis points of headwind from that. I know it's not a big deal for pharma, Thomas, but maybe a bit more for Diagnostics. Anything you can say about that would be helpful.

Yes. So all of those factors are factored in our financial ambition, but to talk about margins. So again, we are -- we have had and we've had since last year a focused operational improvement program. That's how we worked to stabilize last year. And I would say that's something we're continuing this year. And at the same time, we're also investing in our launches. And a big part of that operational efficiency was to make sure we have the space in our P&L to invest in our launches, which are going to drive future profitability. That's how we're going to get to that profit growing faster than sales. And so we think mid- to high single digit on sales, then you would assume mid- to high to high growth on profit. And that's how we're going to continue to -- that's how we're going to increase the margin over time.

And you mentioned some of these headwinds this year. I mean that's all factored into our ambition this year, which I think we talked about at the start of the year, which is to broadly stabilize the margin this year, and that's where we want to get to, recognizing there are these headwinds but they are something that we factored in when we talk about ambition.

And let me just bring it back to the group level. If you look at group, the last 2 years, we grew profitability by 13% and 14% incorporating profit. So you see we have increased margins on the group level in the last 2 years. And our commitment is to keep margins at least stable going forward. So I think this is a very strong commitment on a group level, and we guide on a group level.

May I follow up with product-specific one on AXELIOS. You noted it as a key part of your midterm sales target for a market that's not necessarily the largest one you're addressing on the diagnostics front. Could you give us a feeling of your market share expectations here? [indiscernible] you're going for, for number one. And secondly, on TB, just a clarification. On the U.S. launch here, should we think it comes along with your full ultra automation upgrade, around [ 2028 plus, ] or is prior to that possible as well?

So maybe I'll take the AXELIOS question, and I think Palani is ideally suited to address the TB IGRA. So I would say we've had -- and I also want to not get ahead of Josh's presentation, you've seen the data, but we've had really great response from the market and from customers. We've seen tremendous interest in the truly differentiated chemistry, which is a move away from sequencing by synthesis to sequencing by expansion, which is fundamentally different. And I think that's been really received a warm welcome from the market.

We're not going to give you our market share ambitions specifically, although we will talk about how we feel the reception from the market is, again, it's encapsulated in our divisional ambition, which is mid- to high single-digit growth, which again is to address Matt's question, we'll be addressing as we get through the China topic. But we do expect this to be an accelerant on our growth and we do expect to be able to capture significant market share and we're very confident, especially with this ecosystem of assets we're building around sequencing to offer full solutions, especially as sequencing becomes more entrenched in the clinical space. We feel we'll be meaningfully differentiated on the technology, but also on the application side and on the channel when you think about things like Foundation Medicine.

I think what we can say is what we had on the slide, it's a blockbuster potential. So that's 1 billion plus. We don't give you exact time line, but I think that's a substantial growth opportunity. And as Josh will talk about, I mean we already have the first orders. So you can see that the excitement is very high.

And I would add that those are orders from around the world. The interest is truly global for this solution.

Quickly on TB. Look, the clinical trials in the U.S. are coming along nicely. We're also having good conversations with the FDA. We see the performance of -- I mean we also have readouts ex U.S. as well, the positive person agreement, negative person agreement at parity with standard of care.

In terms of automation, there are 2 elements to it. One is the front-end automation and then there is the readout. On the readout side, from the get-go, we have a broad installed base of our Elecsys platform. Throughput-wise, super high throughput compared to anything that's in the market today. So 100 tests per hour with a single module of e 801, 400 tests per hour if you combine 4 modules.

Now on the front-end side, where you do the incubation of the tubes. Here, we will start out working with, of course, third-party liquid handler automators. And many of these labs already have those. So we'll make sure that our setup works with that. But we, of course, in our cobas ultra road map that I shared with you we will, of course, also try to bring in elegantly the front-end automation as well in the coming years.

So we feel very good about the automation from the get-go, good automation, bringing some important workflow improvements off the gate on the reading side. And then on the front end, we will, of course, work with third parties and build out in our own automation platform.

Okay. I think next question goes to Dan Brennan from Cowen.

Terrific. Just on maybe on AXELIOS, maybe a 2-parter since you did mention orders, I would just ask you, can you share what you think a successful launch would look like in terms of year 1 placements? And then just on the clinical opportunity there, how will Roche seek to leverage your global diagnostic leadership position to help AXELIOS penetrate diagnostic labs? Kind of where do you see the best opportunity there? And what does early interest look like?

Sure. So I would say for that, if you talk about our global network, we're present in over 100 countries. And what we've seen is some of these early orders, again, like I said, are coming from those countries because we already have that channel in place. And that really gives us a significant advantage in terms of infrastructure to drive the testing.

Now what would a successful first year look like, I think we would ideally want to place 100 of these systems in the first year with thereabouts. But I think what we've seen is a real tremendous positive reception from the market, and we're going to drive that.

Okay. Next question goes to, I think it's Graham, right? Yes, from Citi.

Graham Parry from Citi. So a question on Core Lab 5-year CAGR on Slide 38. That's now showing at 3%, it was 4% this time last year. Just to see if you can help us understand what's driving the change there, is that China or something else?

And then a question for Thomas on pharma margins. You guide to at least stable core operating profit margin. But can we dream a little bit more when we look at things like giredestrant, a wholly owned small molecule product with significant potential there? So what's holding you back from being more optimistic there?

And then thirdly, what -- with PathAI, how inhibited will be PathAI be with third-party contracts with other pharma companies post acquisition?

I'll take the first part. I think definitely, Thomas will take the second. And then maybe Andy. So you hit it. I think you answered your question. China is probably the second biggest global market for immunoassay testing and with the reduction in reimbursement and health care reform, that's dropped the size of that market, and that's the impact on CAGR.

Yes. So to your question, I mean, for the last 3 years, we always said the same. We said that keep margins at least stable. Now if I look back the last 3 years, we always grew margins faster than profit. So profit faster than sales or we increase margins. So I guess what I'm saying is future looking, we will say in the long term that in terms of guidance. If we change the guidance for that year like we did this year. This year, again, if we say we will grow core EPS faster than sales, then we will say that in the beginning of the year. That gives us, a, the flexibility to make the right investments that we need to make, and b, it also gives us the flexibility to be positive in terms of guidance and not already give out a guidance like that right now.

Sure. And on the pharma question, so Roche has a tremendous history with PhDS as well as FMI for building strong relationships with pharma and really driving value for pharma partners. So far, we've been operating as an independent company, but also building a strong portfolio of projects and partners within pharma. In 2024, we signed an AI-powered CDx agreement with VENTANA. So each jsite has tremendous experience supporting pharma, and I would expect that putting us together would even increase the ability of us to drive value with pharma partners.

Okay. Next question goes to Urban Fritsche from ZKB.

Yes. Question on Alzheimer's, pTau217. So how do you envision the implementation of the test in primary care? Will this become a routine test, which patients will do like annually with their health check? Or will it be more on when you suspect some symptoms already?

I mean I can take a -- give a quick answer. But of course, after the break, Olivier will go into more details. Right now, it's still indicated in symptomatic patients. So patients who are showing up with signs and symptoms of dementia. And typically, they show up in a primary care setting before they are then sent over to a secondary care setting. And this is where one of the key strengths of the data that later on, Olivier will be showing is we have shown very good performance for both rule in and rule out, not only in a secondary care setting, which is where many of the others are starting, but also in a primary care setting.

To your point, it's to have an annual kind of test, that's in a more preclinical asymptomatic population. That is not the case at this point in time. No one has a solution for that. That's a pretty tough problem, but that is something that we will absolutely continue to work towards. But right now, it's individuals who are coming in with signs and symptoms of dementia. And here using a simple blood test, we can triage them instead of going through a cerebrospinal fluid test or a PET-CT scan or so on.

Okay. Next question goes to David Westenberg from Piper.

So first, just for Matt, you talked about growing faster than the overall market. First of all, that's hard to do, given the size of the portfolio. Just kind of curious about how you're benchmarking that. There's life science tools growth rate. There's diagnostics growth rate. You're all over the entire diagnostic market. So can you just give us a flavor for that benchmark? Does that -- just one growth rate overall or just versus all the other ones?

And second one for Palani, I'd love to see all that innovation. Can you talk about maybe the trade-off between getting things perfect and getting things out on time. New innovation is always hard. There's always software, other kinds of things that you get in the hands of customers and they go, "Oh, you know what, here's a fix and whatnot." So just how you're thinking about that dynamic?

Yes. So starting with your question, the overall IVD market, I mean IVD, we're not talking about life science tools, is growing at a little bit above 3%. So if you say we're growing mid- to high single digit, that could be as much as double the market rate or 5%, at least [ 66% ] above the market rate. So I think we're significantly outgrowing the market. And I would say, yes, that is challenging, but it's something that we've done, and we will continue to do. But again, I'm referring to the clinical IVD marketplace, not the broader life science tools market.

It's a great question. This is something that we think about all the time. And I was just wondering, maybe I'll give you 2 examples how we try to balance this. So let's take the example of Alzheimer's disease. And here, there are some key assets where we feel we absolutely have to take the lead and generate the clinical evidence. And that's what we are doing with Phospho-Tau 217, Phospho-Tau 181 and so on and so forth.

But we also have the neuro toolkit where we have a range of early biomarkers that haven't been validated yet. These are research use only. And here, we make them available to many of our customers who then can use them to do their own research. They can use that to do research with their biopharma partners and so on and so forth.

So we are striking that balance on certain assets, we feel we absolutely have to take the lead and drive it because that's how we bring medical value. And in other cases, where there is not enough evidence, we work with our customers for them to allow them to generate the evidence.

The second example will be with AXELIOS as well. I mean there are so many different workflows that we can be looking at. And as we are having conversations with customers, they're coming up with their own ideas because now their gears are turning around a completely new chemistry and a new technology. So we will introduce many of the application notes and workflows, but there will be many more that customers will develop. We will hand it over to them. And we will, of course, support them with -- on the library prep side as well as on the bioinformatics side.

So that's how we are trying to strike the balance in many of these cases where we feel like, okay, certain things we have to own and drive to capture the value. And in other cases, we feel there will be other brilliant minds who will be able to essentially generate value.

Okay. Thank you very much. I think we have to close the first Q&A session now. There will be an opportunity to ask more questions in the second Q&A session after the second set of presentations. And for now, we are doing a break. And I would like to ask everybody to reconvene here at about 5 minutes to 3:00. So thank you very much for your attention so far.

[Break]

All right. Welcome back, everyone, from the break. I hope you managed to squeeze in some coffee and bio breaks. My name is Josh Lauer, and I'm the Global Head of the Molecular Labs Customer Area. Today, I'll be very excited to give you a brief overview of our strategic priorities in PCR. But then, of course, I'll spend most of my time expanding on our recent upcoming launch with AXELIOS.

As Palani mentioned, our strength and leadership in PCR really stems from our core position in higher-volume automated platforms that sit in the central lab. This is where our leadership position exists in infectious diseases and in blood screening. But that's only part of our broader PCR ecosystem. Our platform portfolio extends beyond these automated platforms and into syndromic testing, digital PCR and open molecular systems. This broad portfolio helps us cover the entire continuum of testing and enables us to deliver the right assays to the right platform for the right use case.

Speaking of those assays, we are continually investing to expand our menu across this portfolio with over 16 assays planned for launch over the next 3 years. These assays not only generate value for patients, they accrue increasing value to our lab customers who are able to consolidate testing on to single platforms over time.

To highlight a few assays. I would say this year, we will extend our leadership in the blood screening franchise with the launch of a multiplex assay that includes hepatitis E. We will also gain increasing share in the fastest-growing segment of sexually transmitted diseases with the launch of our BV/CV assay. And over the next couple of years, we will launch a variety of products, including completing our syndromic testing menu, completing our STI testing menu, launching panels and gastrointestinal diseases and respiratory and offering new solutions for self-sampling or home sampling, which can expand the market for PCR into decentralized settings.

Now one assay in particular that I'd like to dive a little deeper on is a key launch in the next couple of months will be our hepatitis D assay. Hepatitis D is an important disease that affects over 12 million people around the world. And unfortunately, the chronic forms of hepatitis D lead to liver cirrhosis and liver cancer, which are 2 horrible diseases. We're excited about this assay because it's the first fully automated test to diagnose hepatitis D infections via RNA. And it fits into a very clear diagnostic pathway.

We have 2 forms of testing for this that we envision. The first is, of course, existing guidelines to test patients who have chronic hepatitis B infections for hepatitis D. The second is a growing opportunity to monitor the effectiveness of new therapies for hepatitis D. And so we see this as a growing opportunity over time. We think it's a great example of extending our leadership position in virology to gain increasing share in PCR.

Of course, while we are excited to continue investing in PCR leadership, most of what we want to talk about today is how we're expanding into a new category of sequencing with the AXELIOS platform. As mentioned before, this is a generational technology, and we couldn't be more excited about the positive reception we're hearing from the market about this. We don't have the instruments here today. So we just have them on screens everywhere. If you weren't here last year, I hope you had the opportunity to watch some of the webinars or conferences where we've explained to the SBX technology in more detail. But at a high level, I would say there are 3 components of the system, each which highlight the differentiation of our architecture.

The first is the synthesis instrument, which turns a DNA molecule into an Xpandomer. This makes single molecule sequencing at scale possible for the first time because it improves the signal-to-noise ratio. The second instrument is the sequencing instrument, which runs those Xpandomers through an 8 million well reusable CMOS array, which provides incredible data rates. And the third is the analysis module, which, while we don't talk about it as much, is a critical component of this end-to-end architecture. It is essentially a high-performance compute stack, which is able to keep up with the data rates of the sensor module, processing all this sequencing data in real time.

Before I jump into more on the workflow, we've recently held workshops with hundreds of customers in the U.S. and Europe. And I'd love to show you a brief video to hear what they have to say about AXELIOS. Please queue.

[Presentation]

Okay. I love it. One of the themes you often hear customers talk about and you will hear us talk about is speed. That's not the only attribute of this platform, but it is a compelling attribute. So let's look a little bit at how that speed manifests in an end-to-end workflow just to orient us. I'll walk through some of the steps, but the first thing to be aware of is the speed is actually flexible because customers have the ability to load anywhere from 1 to 4 pools onto this instrument. They can tailor the throughput to what they need, and that unlocks economics for different classes of users. Mid throughput users can actually access the same economics as high throughput users. So the workflows themselves are flexible.

But if we start at the left-hand side, library prep is pretty similar to traditional methods. The important thing here is that we've already shown that you can automate this library prep, not only on Roche platforms but on other leading platforms from [ Beckman, Hamilton, ] et cetera. So this is pretty easy. It makes it impossible for users to walk away and not worry about the steps here.

Where the speed really comes in is when you look at the Xpandomer synthesis and the actual sequencing times. These turnaround times are simply much faster than traditional methods. And if you want a benchmark, you can say that if you wanted to load this thing up fully with 4 queued runs, you can generate 64 genomes in less than 2 days when traditional technologies take significantly more than 2 days, 2 days just for the onboard sequencing time alone.

Obviously, we have shown the ability to go much faster. We have amplification-free workflows, such as the one used in the world [indiscernible] for NICU testing to generate a full VCF file from a sample in less than 4 hours. So the platform is fast no matter how you run it. And as we mentioned before, the unsung hero of this is also the high-performance compute, keeping up with all this processing in real time. This is actually a unique aspect of the architecture as well because we don't have to wait for every flowing cycle of nucleotides to complete a read, our reads are read in real time, and we can immediately start processing those on the compute module so that by the time the sequencing run is done, the data processing is almost complete.

One thing that shocked the market a little bit when it comes to the flexibility of our architecture is the fact that we can reuse this sensor module up to 20 times. This is really impressive because it's part of how we unlock the flexible economics for users. It doesn't matter whether you're running or queuing one run because you only have a certain amount of genomes available or you want to queue up to 4 runs because you're a very high throughput lab. Both labs can access the same economics.

Now obviously, as a leader in clinical diagnostics, we're keenly aware of the importance of carryover whenever you're reusing a component like a sensor module. We've already done experiments that show carryover on the AXELIOS system is actually lower than traditional systems. You might wonder why that is. There are several reasons, but one obvious technical reason is that we're not sequencing DNA. DNA is a very robust molecule. And if it's stuck in fluidic systems, it's very easy for carryover to occur. We, on the other hand, are sequencing Xpandomers. These are more delicate molecules, and they're easily cleaned out via our system cleaning cycle. So carryover is not something we are worried about.

Now one of the top things I hear other than speed, speed, speed, is customers are really impressed that a new technology comes right out of the gate, matching or exceeding the accuracy and cost and performance of traditional platforms. That's a rare thing for a new technology to do. And a lot of that performance data that you're seeing is driven by the duplex workflows that we've described.

But one underappreciated attribute of the platform that we're just beginning to explore with the community, and you saw Michael [indiscernible] talk about that. You saw [ Graham Wiley ] talk about that is people are starting to think about new use cases, things they've never been able to do before. And this essentially is leveraging the fact that SBX has longer reads than traditional short-read platforms. If you want SBX style performance and accuracy, simply fold those in half and you get duplex for high intermolecular consensus quality. But if that's not your focus, what if you want longer reads, we can easily generate 500 to 1,000 base payers at a scale no other platform can do. This is useful for things like novel isoform detection. What if you only want cheap reads? We can tune the system down so that if you're only going for short reads, we can generate output that no one has ever seen before on a sequencing platform. These different use cases will unlock new types of applications, and we're only at the beginning of understanding what the community will do with this new technology.

Some stats that we showed at AGBT, which kind of help customers understand what to expect when we launch this summer. On duplex, you're looking at roughly a couple of terabases. This is sufficient to always generate 16 genomes or more at a very high quality, Q38 or higher. Note that those insert sizes are longer than the traditional [indiscernible] 150 as well. This is part of the quality that we're driving. It's not just Q scores. It's also read length from [indiscernible].

On the simplex side, it's just staggering the amount of data that can come here. On the short read side, over 40 billion reads in 4 hours. Just think about that. That's over 10 billion reads an hour. The sequencing world has never seen output like this. If you want the longer reads, you can still get over 10 billion reads in 4 hours, still unheard of.

These statistics are what we use to communicate pricing expectations to the market. We said that SBX and AXELIOS would be competitive with high throughput platforms, and we delivered that with a list price of $150 per genome. This doesn't require any volume-based discounting. Everyone can achieve this pricing. And while it sounds competitive with high throughput platforms, it's actually way more than competitive if you're running smaller throughput. Remember, lower throughput users don't get the headline number economics the other sequencing platforms enable. They have to pay a lot more per genome. And if they're able to access these economics, it's not just competitive, it's transformative for them.

We already talked about how simplex offers economics that we've just never seen before in sequencing, $0.06 per million reads is multiples lower than the nearest competing technology. And we also gave some examples of how you can turn these reads into different application economics. Now panels all vary, so it's hard to baseline. We can't just come up with dollars per genome or dollars per million reads. But we took a commonly used 1.1 megabase panel sequenced at normal depths to achieve kind of clinical grade accuracy that liquid biopsy requires. And we found that you could do that for $25 a sample. This is multiples lower than what you can achieve with other technologies.

Now that breeds certain questions. After AGBT, we got some questions from the analyst community asking, hold on, how does target enrichment really work. Previously, we only showed data on target enrichment using simplex, and there's a good reason for this. In liquid biopsy, the standard practice is to stack up multiple reads with UMIs, or unique molecular identifiers, all technologies form consensus for these needle in a haystack applications. Here, you want more than 2 reads. You want several reads. And so we used UMIs and our ability to generate cheap simplex reads cheaper than anyone else to show this.

This is also useful because the error profile of SBX is largely dominated by random errors. So as you stack up more reads, you can push beyond Q38. We've shown Q50, and we don't even know yet where that ceiling is, but we're very confident that these simplex reads can deliver the kind of accuracy liquid biopsy requires.

But this is not the only way to do target enrichment. It's just the only way we had presented so far. The answer to the question many of you have asked is, yes, it is possible to do target enrichment with duplex. But because of the way the molecular biology works, it will be a different workflow. Essentially, what this will be is a traditional workflow, which uses some PCR mediated steps at the end to extend [ out a hairpin ] and make a duplex construct. This will still enable high intramolecular consensus accuracy for applications where 2 reads are sufficient. So we'll be interested to see how the market adopts these for different clinical level accuracy workflows.

Stepping back, this is our first-gen RUO platform, and we are very honored that the community has been embracing this platform to demonstrate how it can work across all of the highest volume workflows in sequencing and including some new small ones that we hope will expand to be high volume.

For SBX-D, we've already talked about how high accuracy has been demonstrated in germline. In oncology, we've shown fresh frozen tissue. We've shown FFPE. And our partners at Foundation Medicine has shown MRD. This is all great. But we also showed the unique capabilities of duplex and the speed with the world record, as we mentioned before. We think this can be transformative in NICU settings where ultrafast typically means a few days, and the Broad and Boston Children showed that it's possible to do this same day.

I won't go through all of the other applications. But as I mentioned, simplex is -- there's a long tail of applications that we want to explore with the community. Some of the ones we all hear about, single cell, Perturb seq, [ CRISPR ] screens, that's all great. But there's a lot of things being spatial, proteomics, novel isoform detection that we look forward to expanding on in conferences over time.

A few examples in this vein that we showed at AGBT were the partners with proteomic vendors. Olink has been the largest vendor in this field. We were happy to collaborate with them and show the ability of this platform to generate the kind of data they expect. But this was also done with Pixelgen and Alamar. This is only the beginning of our engaging with the sequencing ecosystem.

So that's part of our strategy with this open platform. It's not only going to be Roche solutions. We showed data with Watchmaker and other vendors. We have a partnership with 10X. We will engage with the NGS ecosystem to make sure AXELIOS is usable across all of the solutions that are predominant in the market. We also see the potential for DNA to be a -- sequencing to be a technology beyond DNA and to power multiomics, not just [ methylation, ] but proteomics, spatial transcriptomics, et cetera. And because it's not only important for research, but for our longer-term ambitions for AXELIOS to be a clinical platform, we will focus on end-to-end workflows and bringing our expertise in automation, library prep, et cetera, into the AXELIOS ecosystem.

But we also said this is a generational technology. So it's not enough to just invest in it being an open platform. We intend to invest in the next 20 years of improvements on SBX in the same way traditional platforms have been optimizing over the last 20 years. I won't go into all of these in great detail, but suffice to say, we have the ability to scale this platform up and down, not only deal with short reads but extend read lengths. We intend to continue optimizing the chemistry for accuracy, to extend reuse of the sensor module and to proliferate AXELIOS into a wide, wide variety of applications.

You know, as a leader in clinical diagnostics that we've been investing in sequencing heavily because we believe sequencing will be a very significant platform in clinical diagnostics. It's already becoming one, but we think this is only the beginning of an ongoing trend. So we were very honored that our partners at Foundation Medicine looked at AXELIOS and demonstrated what it can do in one of the largest high accuracy applications out there in liquid biopsy, minimal residual disease.

This was presented at AACR, but essentially what it shows is that AXELIOS was actually able to detect more MRD positive cases than a competing technology, and it actually showed that it was better at doing this in earlier stage disease as well. As I mentioned earlier, Q38 is not a limit here. We're seeing Q50 and higher, and so our limits of detection should be very competitive in this space.

Obviously, MRD is not the only large liquid biopsy opportunity out there. We've already talked several times in this meeting about the partnership with Freenome, but we're very excited to work with them what AXELIOS can do with their multi-cancer early detection platform and to enable decentralized testing with AXELIOS. So these are examples of our strategic intention to make sure we're partnering with the leading labs around the world to make sure that AXELIOS has the content to be a leading clinical genomics platform over time.

With that, I think it's a great opportunity to hand it over to Daniel Malarek, the CEO of Foundation Medicine, and I look forward to answering your questions at the Q&A.

Thank you, Josh. I'm excited to be here to share how Foundation Medicine is going to continue shaping the oncology market moving forward. Now when we talk about oncology care, what we're essentially talking about is a sequence of often irreversible decisions. So what therapy to give when to change course, how aggressively to treat when to monitor and even how to monitor and went to intervene again. And every one of those decisions depends entirely on how quickly and how confidently we can turn complex biology into insight for oncologists.

And this is exactly where Foundation Medicine operates. And what excites me the most is that actually, we're only at the beginning of this year. So let's zoom out a bit. So Josh just ended speaking about screening and early detection, and I'm going to focus on what comes next. So those critical steps where molecular insights really guides therapy selection, therapy management, monitoring and ongoing care.

But let me start by grounding us in who is Foundation Medicine and what have we built? So Foundation Medicine was founded in 2010 out of the Broad Institute with a core belief that cancer is a disease of the genome. And if we can get those genomic insights into the heads of drug developers, if we can get those genomic insights into the hands of oncologists that ultimately, that will lead to better outcomes for patients. And that's exactly what has happened. And over the past 15 years, we've helped define the field of personalized medicine in oncology. So we were the first to launch a comprehensive genomic profiling assay, pioneers and linking genomic data with clinical outcomes at scale, leveraging advanced machine learning early on in genomics, and we continue to invest heavily in AI. We paved the regulatory path for companion diagnostics, all in parallel to paving the path to reimbursement.

Now these milestones didn't just matter for us. They actually shaped the entire industry. And in the process, on the clinical side, we've delivered more than 1.5 million comprehensive genomic profiles to patients. And one thing I want to highlight is our commercial reach. So we built a platform where, over the last 12 months, over 40% of oncologists in the United States have ordered from us. And that is via our portal and that is via our EMR integrations. And that will be a springboard for all our future launches. And that pioneering work has also resulted in extremely valuable data assets, AI solutions, and industry-leading number of publications.

Now on the biopharma side, we're fully embedded in the biopharma drug development ecosystem with more than 100 approved companion diagnostics, and that represents more than the entire rest of the industry combined. So when we talk about Foundation Medicine, what we're talking about is a scaled clinically embedded biopharma connected platform that has shown to create value across the entire oncology ecosystem.

So how does our business work? Well, our business model actually has 2 aspects to it. So the clinical business and the biopharma business. And in the clinical setting, it's our multimodal portfolio that supports decision-making across the entire patient journey, making us a one-stop shop for oncologists. And our customers range from major academic medical centers all the way to the community oncology practices. And what we consistently see is that adoption is still far from where it needs to be. For example, I was recently speaking with one of the largest community oncology practices in the United States, where they treat around 20% of all cancer patients. And they said that in the metastatic setting, only around 50% of their patients are getting a comprehensive genomic profile, that is unacceptable. We agreed that, that number needs to be north of 90%. So there's huge opportunity there.

On the biopharma side, we work with the top 80 biopharma companies and are currently supporting over 300 active clinical trials to date. And our partners not only value our scientific capabilities, but also our regulatory strength. And what do I mean by regulatory strength? Well, it's our ability to execute complex companion diagnostic programs aligned with regulators and ensure that their launches and commercialization goes smoothly. And importantly, these 2 businesses actually reinforce each other.

So insights from clinical practice, feed in to drug development and advances in drug development then, in turn, feed back into clinical care. And like I said, we're still at the beginning of this journey. So if we look at the market, the oncology testing market is one of the fastest-growing markets in diagnostics. If we look across biopharma, clinical therapy selection and clinical monitoring, we expect the market to essentially double over the next 5 years. And this is due to 3 factors. So the first one is we are seeing an explosion of new targeted therapies and actually new targeted modalities being developed that require genomic insights. So everything from bispecifics, trispecifics, ADCs, cyclic peptides, even molecular glues, individual neoantigen therapies. All of these require those genomic insights. So complexity is exploding for oncologists.

The second reason is CGP adoption is going up. especially as these new therapies are being launched that require genomic insights. And then the third is around molecular monitoring. So as clinical evidence builds showing that molecular monitoring is superior to traditional pet and CT scan monitoring, that market is expected to grow rapidly. And there are approximately 50 million people currently living with cancer, and that number is expected to almost double in the next 10 years.

And for any cancer survivor, there are 2 questions that dominate. The first one is, is my therapy working? The second one is when might my cancer return? And being able to answer those questions by a simple blood test has profound implications for patients and for health care systems. So overall, we're moving from the narrow question of what therapy do I give my patient to how do I manage my patient over time? And this is central to where Foundation Medicine is going.

So 3 core differentiators position Foundation Medicine for the next era of growth. Quality, innovation across the patient journey and being Roche powered. And I'm going to now double-click into each of these.

I'm going to start with quality. I'm going to say that not all cancer tests are made equal. So if assays are not engineered to detect and capture difficult alterations, patients will be missed. -- copy number loss is an example of a difficult to detect alteration. And a powerful example that I would like to use is a copy number loss called MTAP law.

So why is MTAP loss so important? Well, it is actually present in around 10% of all cancers and is a critical biomarker in trials that are evaluating MAT2A and PRMT5 inhibitors, which are showing great promise. And in a recent publication by Sarah Cannon Research Institute, when they looked at their own real-world data, comparing 3 major testing laboratories. They actually found that Foundation Medicine detected MTAP loss at rates consistent with published incidents.

The other labs showed detection rates between 40% to 60% lower. Now that difference matters. So missed calls mean miss trial enrollment, delayed drug development and patients who never received potentially life-changing therapies. And our biopharma partners have also recognized this material difference, and that's why we are the clinical trial enrollment assay currently for 15 different MTAP trials. And with another copy number loss, [ T10 ] Loss, FoundationOne CDx is the only FDA-approved tissue NGS test validated to detect a -- copy number loss. This is why quality matters. It matters for patients. And this is why we believe that every patient doesn't just deserve a CGP test, they deserve a Foundation Medicine CGP test.

The second differentiator is innovation. So we're -- we talked about how molecular monitoring is rapidly expanding. So let me talk about 2 exciting new products that we have. So first, let me talk about F1 monitor. So F1 monitor is a liquid only, so no tissue needed assay used in the metastatic setting, to answer a simple question, is this therapy working? And in studies, we detected progression at roughly half the lead time of traditional CT PET scan imaging.

So that means earlier decisions. That means whether to stop an ineffective therapy or it also means that confidence that the therapy is working. And another differentiator of F1 monitor relative to other common tests is that F1 monitor also provides resistance mutations. So if a therapy is not working, the next question the oncologist will have is why isn't it working and F1 monitor also provides that information.

Now to Pathlight MRD, obviously, you've heard around our acquisition of Saga. And once that closes, we're excited to welcome the Pathlight MRD assay into our portfolio. I'm excited about this. I'm excited about it for a number of reasons. So from a clinical perspective, patient impact perspective. Pathlight has just demonstrated the ability to detect recurrence over 13 months before traditional CT PET scan imaging in early-stage breast. That's the first reason.

The second reason, Pathlight is already Medicare approved. So if Medicare covered for early-stage breast, Stage 2 and 3 across all subtypes over 6 years of a patient's journey and 12 time points.

The third reason, it's a best-in-class assay. By best-in-class, what I mean ultrasensitivity, and disruptive turnaround time. And then just as exciting as the assay itself is our plans to decentralize testing. We have the [ Actelios ] platform where we can do the whole genome sequencing tissue baseline, and we have our digital life cycler platform from which we can do the multi-time point testing. And by decentralizing using our own platforms, we can provide access to patients in all settings. So with this portfolio, Foundation Medicine is exceptionally well positioned to scale and become a leader in monitoring.

So the second thing I wanted to talk about on an innovation standpoint is as our biopharma partners develop increasingly complex therapies, we're expanding how we interrogate disease biology. So we have built a platform to understand disease of operationalize insights at scale. This is our [ Flexomic ] platform. And essentially, just how we were integral in turning oncology into the poster child of precision medicine. Our aim is to take those same capabilities and apply it to other disease areas, neurodegenerative, metabolic and autoimmune diseases.

And this is what our Flexomic lab will bring. So for biopharma, this means better target discovery, better patient selection and also derisked development. Now innovation alone cannot make an impact. you have to have delivery at scale. And this is what being powered by Roche actually means.

So we operate actually 3 different models. So the first model is our centralized testing model, where samples come from over 50 countries into our labs based in the U.S. and based in Germany. And Outside the U.S., it's Roche Diagnostics that are commercializing our products. And in Japan, it's true guide.

The second model that we operate as our installation and services model. So this is where we essentially build our lab at our partner sites. And they run the wet lab workflow, the data goes into the cloud. We collect the data. We run it through our analysis pipeline, we generate the report, which essentially means they get FMI quality in their own lab they get all the latest complex biomarkers that we run all in their lab. We have INS sites in the U.K., where we won 50% of the NHS liquid biopsy, tender. We have at the [ Gustav Rose ] Institute in Paris, where they become a hub for liquid biopsy testing in France. And we also have at the University of Zurich Hospital.

And then the last model that we operate is our completely decentralized model, which is based on the Roche AVENIO kits. And these kids have been codeveloped with us, and they run and are powered by our analysis pipeline. And we believe that the future will be always a combination of centralized and decentralized testing. And so our focus is to hit our solutions, which enables us to win overall.

And with these models, it allows us to scale globally while also not compromising on quality. Now being part of Roche goes beyond just the scalability. We are, as you heard, we're an early access site for the AXELIOS sequencer and implementing the AXELIOS sequencer in our clinical workflows has the potential to shorten our turnaround time and improve our cost basis. And over time, once we embed that in our clinical workflows, our plan is also to onboard our installation and services sites, the sites I just mentioned in the U.K., in France and so forth.

So it's exciting to see how Foundation Medicine and Roche together can accelerate the adoption of the AXELIOS platform in the clinical sequencing market. So secondly, we also leverage VENTANA IHC to aid in treatment selection, and we're going to continue expanding our portfolio to be the one-stop shop for multimodal insights.

And the third area and partnership is with our navify colleagues, where I'm very excited to be launching navify clinical hub decision support applications within our Foundation Medicine portal. We talked about the community oncologists. They're treating 20 to 30 patients every single day. They need to be making decisions and have all the insights at their fingertips. And with the applications around clinical trial matching, dynamic NCCN guidelines, which essentially allows them to see where their patient is in the decision-making tree dynamic publication search and AI patient education, we actually make it easy for them. We bring those insights straight to them so that they can make the right decision for their patients. This is how precision medicine becomes routine practice.

So our product road map reflects a deliberate strategy from single test to platforms from snapshots to longitudinal insight from information to decision support. Each initiative essentially builds on assets that we already have, data, scale, regulatory credibility and extends us into new value pools. And that is our approach to disciplined growth.

So in summary, let me close with 3 points. The oncology testing market is poised for strong growth. Foundation Medicine is evolving from helping decide what therapies to give to helping manage patients over time. And together with Roche, we have an unmatched ability to scale. And Foundation Medicine is going to continue shaping the market by turning complex biology into better decisions and better decisions mean better outcomes for patients, better outcomes for health care systems. Thank you very much.

Thank you, Dan. Good afternoon, everyone. I'm Laura Apitz. I'm the Head of Pathology Lab, and I'm going to be sharing with you the most impactful developments that we have going on in pathology. So Helane already mentioned our 3 focus areas is all about automating our core business. It's about digitization, and it's about growing our high medical value menu.

So we have -- we're a strong leader, #1 leader in pathology lab. And you can see we've had double-digit growth, 14%. It's driven by our advanced gaming business, our personalized health care business, as well as our IT and IS systems are over 13,000 installed base globally. I want to call your attention to the innovation section of the slide because I'm just going to be going through our next-generation systems that we have in development a little bit more in our personalized health care business, digital pathology and how that's helping there. And then also, we cover the cervical cancer disease state in pathology as a holistic disease date.

So first, our vision for transforming the pathology lab is really about bringing end-to-end automation to the lab. Pathology is not very automated today, and it really needs a way to integrate patient workflows and make the lab more efficient. We're going to be doing this with our partners, Hitachi, high-tech to bring out our next-generation advanced staining system.

Also, within the next 18 months, we'll bring out task targeted automation with some AI-driven tools that will help labs go to digitalization overall. And so these are some of the ways we'll be bringing more automation and digitization to the lab. When I turn to our multiplexing portfolio, we've been doing multiplexing for some time. You can see that in our pipeline here. But what we're going to bring out uniquely now next year starting with some duplexes is our new [ transluciccroba ] genes. This allows easy access to doing multiplexing.

And the 2 I want to highlight is P40 and TTF1. This is in the lung cancer space, where we'll differentiate non-small cell lung cancer. And then one of them is SOX-10 and KI-67 where you can tell between a melanoma and a bone 9 lymph node. So this is just the first of many multiplexes that will bring out in the companion diagnostics space in the companion digital pathology space as well as some non-going cytology space as well.

So turning to a little bit more to our personalized health care business. This is a growing business. We've been in it for 25 years. We really have a strong footprint here to grow even more. What's growing even more important is these computational pathology algorithms. And you can see we have over projects in our pipeline for these computational algorithms. And this will be significantly enhanced. You've heard a lot today about Path AI. This will really help us grow this area of digital pathology even more.

But I want to call your attention to our TROP-2 franchise, and it really is going to be a franchise. But it will be the very first computational pathology companion diagnostic that will launch in the lung space next year. And so right now, with the RUO, TROP-2, we're really growing that footprint globally. So it sets us up really nicely for those companion diagnostics algorithms. So digital pathology, I'm hugely excited that we have a complete end-to-end offering here.

So you've heard about the best-in-class image management system that we're going to be bringing into the fold pathology centric collaboration is really what this is all about with some AI-driven tools as well. We also have our DP 200 and 600 scanners and we're going to be bringing out improvements next year to these scanners, faster scan speed as well as improving cytology workflows as well. So you can see we're really rounding out our digital pathology platforms to be able to fuel this growth in the future.

Now I'm going to turn to our cervical cancer solutions. So we're on a mission to eliminate cervical cancer. And you know that HPV infection causes most cervical cancers. So it's really about getting access to the important testing. So the first test I want to highlight is our HPV genotyping test. Detecting 14 individual high-risk genotypes. And this is important for screening programs around the world so they can really customize in an evidence-based way how they want to manage their patient populations all over the world.

And with our large installed base of x 800 molecular platforms, we're really able to bring this test everywhere, and we plan to launch this in CE Mark next year. The other area of serval cancer I want to highlight is really our self-collection. So again, it's all about accessing people for testing and getting closer and closer to their homes, so we can get those samples. And so we're going to do that for HPV. You can see our kit design here that we're going to launch next year.

But what's also really unique is we're adding our FCI testing. So all in one, will have HPV, STI testing, and actually a really seamless workflow to bring it into the laboratories for testing with not a lot of manipulation needed. So we're really excited about both the genotyping and, of course, the self-collection to bring access to this important type of testing. So with that, you see we have a really strong pipeline in pathology, still growing growing stronger. And what we're super passionate about is making sure we're reaching beyond the 44 million patients that we reached last year.

So thank you very much for your time. I'm going to hand it over to [ Elliot ] to talk about near patient testing.

Yes. Thank you very much, Laura. It's always impressive to see the many patients that are positively impacted by our pathology solution. A warm welcome also from my side. My name is [ Eriko Amanda ]. I'm heading the Research and Development Department in RDS, and I'm here today to talk about the highlights in near patient care, our updates of our products and any upcoming launch.

As Palani already said, we are up, and we want to establish new patient care as a leader in this space, and we have 3 priorities to do that. One is building a leading portfolio in clinical chemistry and in immunoassays. We want to strengthen our position in molecular point of care, through systematic menu expansion and we want to deliver a competitive CGM solution. You have heard about that a couple of times.

I would like to dig deeper into our strategy and how we want to achieve that. And first of all, I want to concentrate on the disease areas. We are convinced that testing in proximity of patients that are affected by infectious disease cardiometabolic or diabetes will improve the outcome of these patients. And this is why we do point of care in these 3 prioritized disease areas.

Now we want to serve these patients across the whole spectrum of decentralized setting. And as you appreciate from this slide, these settings are very diverse. We have emergency room and intensive care settings. We have GP settings, we have pharmacies, and we have consumer patients. to understanding the needs in these different settings is of essential importance and we will provide tailor-made solutions for each of these settings in order to become a leader in near patient care.

For my presentation, I would like to start on the very right side on the consumer and patient area and then work backwards to the emergency rule. You have already heard about Accu-Check SmartGuide, our CGM solution a couple of times. In the last year, we have made substantial progress with our controlled launch strategy. We are now available in 45 markets.

Last time when we spoke, we were around 4 to 5 markets. This year, we are available in 45 markets. We have launched across EU, Middle East, APAC and Latin America. In the first half of this year, we have also achieved very important milestones. We continue to ramp up our manufacturing facilities. And we had a full rollout of my sugar as part of the Accu-Check SmartGuide CGM solution. I will talk about both of these points in a minute.

In the next half of the year, we aim for regulatory approval for factory calibration to avoid the first finger prick and first use, and we will broaden our geographical market deployment. Now it's very important that the foundation of our market penetration are our 11th state-of-the-art manufacturing facilities that we have built up over the last couple of months and years.

And these are highly automated, state-of-the-art manufacturing centers. We have built here on our long-lasting know-how that we have in diabetes care for more than 30, 40 years we are in this field. And in order to give you an impression how these manufacturing lines are built up and what they do every day for us, I would like to show you a short video.

[Presentation]

Now with this, we really want to highlight that we are focused on investing in a solid base for our CGN solution and making it available globally. The other highlight and milestone we have achieved over the last couple of months was really the combination of the Accu-Check SmartGuide predict the app, where we have AI-enabled algorithm, for example, for the 2-hour glucose forecasting or the night low prediction, together with our MySugar ecosystem where we have a download of more than 7 million users.

And this combination really provides a scalable digital ecosystem for our diabetes customers. We can, with that accelerate PGM to CGM conversion, and we will also improve clinical outcome. For the future, this means that we integrate data and insights from multiple smart devices and health platforms.

Now moving over to our customers. Up to now, we have focused very much on the multiple daily injection patients. But as a matter of fact, Diabetes Care in Roche has a legacy. We have already more than 30 million BGM users that use our blood glucose monitoring platform. 11 million of them in insulin users and 20 million of them in non-insulin users. And our strategy will be to upgrade those Roche customer base from BGM to CGM by leveraging reimbursement availability. We will also partner with third-party systems and integrate their devices.

For the non-insulin users, we will offer intermittent -- of BGM and CGM via MySugar together and learn user insight. So this is very important because most of the customers that today are not yet on England, but earlier or later end up as an insulin users. And to give them already the opportunity to use the CGM early on will help them to learn how their exercise, how diet is impacting their blood sugars.

And last but not least, we also connect our portfolio with Roche Pharma. And this is really also a nice synergy between the 2 divisions. Now as you already heard, we are constantly improving our device, and we are also listening to our customers. And we have also an evolution in our pipeline from a first generation to next generation. As you can see here, the next generation, the inserter will be much smaller. We will exchange the battery. We will have also less manufacturing step.

But most importantly, if you look at the current size of the CGM solution today, it is like that. And the new one will be like that. And I hope you appreciate the difference in the size that all will actually improve the varying comfort for our customers.

Now with that, I can say that all over, we are absolutely on our way to provide our patients, our strategic intent of a very competitive solution. Now moving on to our next segment, and that is the GP setting. And you heard from Thomas that primary gets more and more important because more of the health care will be decentralized.

And here, in 2024, we made a very important acquisition with LumiraDX. And that platform is really remarkable. We have shown it last year, it's a portable platform that has less than 1 kilogram. And the technology as such, provides multimodality. So you can measure immuno-asset clinical chemistry as well as [ cabilation ] assets and potentially in the future, also molecular assays. It provides multiplexing capabilities. Those 3 assays can be done at the same time. And it also, in addition, comes at room temperature. As you can see, I like to wear this parts here in my pocket because it's always nice to have point of care test with you. It also has finger-pricking capability. So you only need 1 drop of blood for this platform.

In fact, last but not least, is really tailor-made for the GP setting. So since we acquired LumiraDx, we have made commercial available this platform in more than 43 countries, and we have approval in more than 75 countries.

I also want to highlight a couple of commercial wins that we have, for example, in -- and whereas we have a pilot currently running with CRP testing, to fight against AMR, and that is government backed. We have a pharma partnership in India where we test anti-proBNP for cardiac risk. And here, the main differentiator was really the finger pricking capability for anti-proBNP on this device. So really a real platform. We are also investing heavily in alignment with our disease area strategy, we will make it IVD compliant, and we also have an update for our HVAC.

And for 2028 onwards, we will add further tests like the lipid panel and also further tests in infectious disease and inflammation. Moving on to the next big segment. This is a molecular point-of-care segment, which has a market size of EUR 2.65 million. We are participating in this market segment with our [ Pubali ] platform, which is well established and which provides lab-like PCR quality at the point of care.

As you can see here, we have already a pretty broad spectrum and menu there. We are adding now it's actually transmitted disease sales like we have last year with CTMG or the -- panel. What I would like to point out that we address with these platforms, always gaps that are existing in care where this rapid diagnosis is essential. For example, we will now or have already launched the water deli test which is super important for newborns for small babies and elderly.

And here, the decision is an antibiotic is necessary or not is a very important one and needs to be taken rapidly. And again, the lead platform helps in this regard. And talking about lab-like performance, I'm super pleased and happy and privileged to announced the launch of the Cobas Sense instrument and the high-sensitive troponin T in 2027.

We have talked about this platform a couple of times. Today, I would like to provide you the correlation between the Cobas Sense high sensitive troponin T essay and our fifth generation. This is the newest generation of our KOALA platform, the Alexis platform.

And as you will appreciate, this is an almost perfect curve. There is a correlation curve of 0.995 between these 2 assays. This means it's really lead like performance. And it's not only true that this is across the whole curve, but it's, in particular, in this very low range where you need this high sensitivity in order to make this important decision if a patient has a [ myocalli infection ] or not.

Now this supports us energization and enables interoperability between lab and point of care. It also overcome the barriers that we have in the emergency room because up to now, it was always perceived that point of care is not sensitive enough. Now with that, we can help our customers and our positions to reduce the amount of patients in the emergency room because the decisions of if a patient has [ mytocyinfaction ] or not can be done with certainty.

We will also add additional assays additional cardiac assets on the Cobas Sense like NT-proBNP and -- for patients that present in the emergency room with shortness of press or test pain. So a very nice and comprehensive platform that we will bring on the market in 2027 with lab like performance and talking about lab-like performance, it's my pleasure to introduce Olivier to you who will talk about the exciting portfolio that we have in KOALA. Thank you very much for your attention

Yes. I think it's indeed great to see that like performance at the point of care. So my name is Olivier Gillieron. I'm the life cycle leader -- and Neurology, and I'm pleased to be here to provide the overview of the call up assay highlights. In CoLab, our goal is to continuously expand our menu across our 4 key disease states, which are oncology, neurology, cardiotabolic and infectious releases.

Within 24 months, we have actually been able to deliver 10 new solutions to the market, which is peaking literally in this quarter with the introduction of the NFL has post 17 test in neurology as well as our aged solution in infectious diseases. I will focus on these 3 solutions in my presentation today.

So let's start with infectious diseases. As mentioned by Paul earlier, our goal is really to provide a high-quality comprehensive testing menu in infectious diseases. End of last year, we launched our antigen tab, followed by the IgM test earlier this year and the IgG coming later this year.

In 2027, we plan to launch the Lyme IgG and IgM assays with more menu coming further down the road, as you can see on the right side. Now the highlights for this year is indeed our IGRA TB assay. And before I get into specifics, let me give you a bit of disease context.

Tubecolosis is the dealers infectious disease around the world. As you can see on the left side, there are more than 10 million new active cases globally in 2024. At the same time, if we move to the right, up to 25% of the global population may have a latent to the closest infection. This is why it is important to [ test folate ] in TB, not only in high prevalence countries but especially in high-risk populations. And this is where both the tubercolosis skin test and the interferon gamma release assay blood-based are established in clinical routine.

As of today, there are approximately 13 million tests of IGRA TB, which are run on an annual basis globally. Now I'm excited to share that next month, we plan to launch our Alexis Aggregate assay in -- acceptance CE mark. We have validated the test in close to 2,000 patients and we plan to present the results at the ESM Congress in Verona next month.

As there is no gold standard in aggressor testing, we compared our solution to the current standard of care. And I'm happy to share that we have reached our end point and we have a strong performance, which is on par with the standard of care, and you see the PPA of 91.1% and the NPA of 94.6%. We will offer our IGRA TB test on all our second-generation electric platforms as Palani elaborated on it, if you look at our -- which is our high throughput platform, this will enable a throughput of up to 400 IGRA TB samples per hour.

The pets will also be available under [ E42 ] and on the Smart E, which is our solution from our decentralized settings appended by Palani earlier today. We do plan to further differentiate our solution by automating the prenatal steps, and we'll do this on our next-generation Cobas Ultra automation platform.

So with that, we're in a strong position to scale testing into the markets. As you can see on the left, we can leverage more than 48,000 electric instruments as well as our direct presence in more than 150 countries to drive access to latent TB testing. As you can see on the right, the market will evolve into a highly attractive above [ CHF 1 billion ] segment by 2034. And our goal is clearly to capture a significant share and become a leader in IGRA TB testing.

Now let's shift gears and move into neurology. Neurological conditions constitute a significant health and socioeconomic challenge around the world. In Alzheimer's disease, 75% of the patients are undiagnosed. It takes 3.5 years to get a formal diagnosis of the disease. At the same time, 98% of the patients are untreated. If we move into multiple sclerosis, 40% of patients are untreated and [ 35% ] are on low-efficacy treatments despite the availability of highly potent anti-CD20 treatment. So clearly, there is a significant opportunity to leverage diagnostic solutions to shape here pathways and drive access to these novel disease-modifying therapies.

So let me start with multicrosis. I'm happy to share that we have obtained CE Mark for our Alexis neurofilament light test, reflects neuroinflammation in patients with relapsing remitting multiple sclerosis. It is important to highlight that we have established specific NFL healthy reference ranges to support clinical interpretation as NFL values increase with age. In combination with MRI and other clinical data, NFL supports clinicians to monitor disease activity and guide treatment decisions. towards high efficacy treatments, such as [ Ocrevus and fenebrutinib ] moving forward.

Now moving to Alzheimer's disease. Our goal is to drive the early detection of amyloid pathology and therefore, again, access to treatment. In the meantime, we have a total of 7 diagnostic solutions along the patient journey. We have our success ratios, which are used for the -- diagnosis of amyloid pathology.

Last year, we introduced our [ Phosphate ] 11 solution, which is the first blood-based biomarker specifically approved in the primary care setting, which is ruling out amyloid pathology. And early this year, we introduced our up report test, which is a test which is able to discriminate between [ ApoE4 ] carriers and noncarriers.

Now the highlight is clearly our phosphate 17 solution as we have shared earlier today, we have obtained the CE mark, and I will speak to it on our next slide. We are also further expanding our solutions elongation journey. We're looking at digital -- streaming solutions on left side of the patient journey. At the role of pTau217 also in the positively unimpaired population and we are also developing new biomarkers for other pathologies and disease mechanisms as well as treatment monitoring.

Now let's speak about pTau217. I'm really excited about the launch of this test. It has the potential to redefine the standard of care. We have validated the solution in a real-world cohort spanning across care settings, so both primary care and secondary care, but also different clinical stages. Now let me guide you through the results on the right side. So in the middle, you can see that illustration. You can see that we have established 2 cutoffs, and it's important to highlight these cutoffs are consistent and valid in both primary care and secondary care. The 2 -- classified patients into positive, high likely -- pathology, negative, low like use of amyloid pathology and intermediate where patients should be considered for further testing.

Now let's double-click on the performance. I'm really excited about the sensitivities and specificities in both secondary care and primary care. They're all above 93%. If we look at the performance in secondary care, you can see that both NPV and PPV are above 90%. And moving into primary care, the NPV is at 98.6%, and the PPV despite low prevalence is at a remarkable close to 80%. And finally, looking at the patients in the intermediate zone, we have less than 20% in basically that specific zone.

So with this performance, we're actually taking off all performance criteria of the COO guidelines for -- markers, both in secondary care and in primary care. And with that, we really believe that we have a robust best-in-class [ photocatventin ] assay, which will enable clinicians to rapidly unsafely triage and diagnose patients with signs and symptoms of cognitive decline.

Now with the addition of NFL and pTau217, we have the broadest on-market IBD portfolio. We're also further expanding our early pipeline by closely collaborating with academic centers and pharmaceutical companies and by leveraging our newer toolkits. Our goal is to add 5 to 10 new robust assays or researches only tests in specific diseases where we focus on, which are Alzheimer's disease, Parkinson's disease and multiple sclerosis. So let me close with our ambition.

On one hand, we continue to drive the early biomarker innovation. At the same time, we continue to collaborate closely with pharma companies to drive that innovation. But then we're really ready now to scale these tests into the geographies. We have the broadest menu on market, we can leverage our large installed base. And as you can see on the right side, specifically for the Alzheimer's disease market, this market is expected to quadruple in the next 10 years. And our clear ambition is to be the global leader in this field shaping their pathways and making an impact on patients, families and society.

So thanks a lot for your attention. And yes, with this, I would like to hand over to Birgit for the second Q&A and my colleagues on stage.

Okay. Thank you very much, Olivier, and I would like to ask the speakers from the second set of presentations to join me here on stage for the Q&A, including an Palani and Matt.

Okay. Happy to take your questions now. First question goes to Richard Vosser from JPMorgan.

One question on the adoption of molecular testing. There was a about a week or 2 ago, which was trying to adopt earlier molecular testing rather than radiographic progression testing and the regulators pretty much didn't like it. I didn't have enough clinical data of the proof. So pharma companies are probably not going to do the trials that the regulators seem to want. So how do you get adoption of earlier testing, particularly in the metastatic space. So just your thoughts there. And then secondly, on -- testing. What evidence have you seen that the integration of the QTS that are able to differentiate between patients allowing better treatment algorithms, just thoughts there.

I can start on the first one. So the importance of designing your studies in a way that will resonate also with regulators is incredibly important. And I think that's one aspect of it, where we feel that it was a step back in a specific case, but not a setback overall. And molecular guided MRD testing is something that will continue to evolve and that evidence will continue to build.

I think the second point is that pharma companies are also looking for surrogate endpoints to their studies. And this is where ultrasensitive MRD assays will provide that for them. So that evidence is going to build with time. We just have to also work very closely with our pharma partners in developing the advance.

Then I can take the TROP2. Thanks for the question. I think it's very similar to what Dan just said. I mean, evidence is going to build on how these computational pathology algorithms can really help differentiate and detect therapy for TROP2. So obviously, there's evidence, early evidence that it can do that, but we're really waiting for next year, and those important for readouts to see what the true impact is going to be.

Okay. Good. The question goes to Subbu Nambi from Guggenheim I actually have 2 questions on foundation. How has the growth profile of Foundation Medicine evolved relative to peers over the past few years, especially in therapy selection. And it seems like you were lagging for a few years for do you agree? And is that improving as your focus and strategy have evolved. Second, how important is moving foundation content to AXELIOS pursuant to generating above-average growth relative to peers?

Okay. So on the first question, even today, when talking to clinicians, when talking to pharma companies, we are viewed as the best-in-class and that's without doubt. You can go to any ASCO meeting, you can go to ESMO meeting, you can talk to our biopartners, and that's something that we're confident in and they see the quality that we provide. So there, from that perspective, that quality differentiator still stands. I think the second aspect, which is incredibly important is our ability to scale. And that is something that we have unprecedented reach with the Roche partnership. So our reputation has grown, especially outside the U.S. and that's something that we're extremely happy with.

The second question was around, correct me from AXELIOS and inclusion in our clinical workflows. This is something that we're extremely excited about because the potential that AXELIOS provides us is better turnaround times and a lower cost base. And with that, we also feel that the capabilities of the system will also enhance our offerings to our biopharma partners and enable us to further differentiate not only the competition, but also further enhance our own internal developments and what we're able to provide in terms of services for our biopharma partners. So overall, we're very excited about the platform.

Okay. Next question goes to David Evans from Kepler Cheuvreux.

Yes. So maybe for Matt, but just of all of the product launches and innovations and assays we've heard about, which ones do you hope may have the biggest, most visible impact on Rpieoche agnostic sales growth. I mean I assume that AXELIOS would be the biggest single one, but is that like quite a distance. Is there any uptick likely from Gen 2 of Accu-Check or next wave of mass spec launches or equally assays like the Alzheimer's diagnostics seems to be a very big opportunity.

Yes. So I would frame again, back to our financial ambition to mid- to high single digit. I think in order to the kind of growth we expect, which is well above market. We need all of our launches to contribute. So I think they're all extremely exciting. And I think each of them, if I'm being super direct has an extremely, I'd say, exciting aspects to them. This Axelios is really going to be the core of that backbone that we use to drive oncology and it also gives us an opportunity again to really engage in the translational space. So that's exciting. The mass back again, is the first fully automated, fully standardized with an IVD menu mass spec system and we see there is an opportunity to grow our biggest business unit, which is the core lab.

And then if you look at CGM, we had for several years decline in our blood glucose monitoring business. Now we have an opportunity to really revitalize that franchise, bring in a state-of-the-art technology, combine it with our AI capabilities and return that to growth. So all of those together I think, are going to be what drives -- so it would be impossible for me to pick one from that group. But thank you for the question.

Next question goes to Tycho Peterson from Jefferies.

Maybe just a follow-up on the content strategy for AXELIOS. Saga had their own road map, Curious how you're thinking about some of their other indications, lung, head and neck, ovarian, some items I've talked about in their pipeline. And then maybe timing on Freno, converting over in your view? And then lastly, how are you thinking about the willingness of the community hospitals to embrace sequencing in-house? I mean, is this mainly for the -- medical centers for the next few years? Or -- when do you see that transition on the community side?

From the Saga perspective, so they have also launched their -- so we have both indications, breast CRC right now. They have studies in ovarian, and we will further invest in driving clinical evidence in other indications. We're immediately looking into lung and so forth. More than that, I'm not going to comment because the deal hasn't closed, so we need to wait for it to close and then we will put a robust clinical development strategy in place for the Saga acquisition. We're really excited about the capabilities of the assay.

Okay. So I'll just say for Freenome, that's an easy one. As we publicly disclose, they're going to evaluate the AXELIOS sequencer. And so then how that's going to be incorporated in their workflows is going to depend on how that shapes out.

Maybe then the third part, you asked about community settings. Here, I think we have some surrogate for this. Obviously, Foundation Medicine has a lens into serving these different populations. But there is, as Dan described, a lot of demand for some centers to want to bring testing in-house, and that can be for a variety of reasons.

But often, this reimbursement and the ability of some of these community oncology practices to tap into that. The real question is, do you deliver a solution that's capable and economic for them to run and capitalize on that opportunity. We don't see any reason why we can't do that. So sure, AMCs and researchers might drive early momentum, but our view is, over time, as Dan said, these can be both centralized and decentralized solutions.

Okay. Next question goes to Kyle Mikson from Canaccord.

A couple of questions. So on the -- some diagnostic growth drivers in Alzheimer's and neurology. Any interest or appetite to combine markers here like pTau217 and NFL or maybe even more. And the MSD, you kind of referenced this 35% CAGR. Is that international as well as U.S. It's obviously different markets. We have trial kind of read out recently. And then just separately, just taking us back your thoughts on profitability in the NGS AXELIOS kind of segment Obviously, if there is operating profit dilution, it's a smaller segment, not going to really affect the full company, but you could -- pricing headwinds in that industry. How do you think about going the $1 billion? And if it's a blockbuster product, could you -- that building the revenue on $1 billion in expenses? Or could it take more?

So we'll start with the neurology questions. So first of all, I mean, as of today, the stand-alone or pTau217 performs best. But I think the field will indeed move into an approach where multiple biomarkers will be combined and where potentially better evidence is generated. Maybe also for very specific use cases is obviously NFL or also GFAB -- biomarkers, which may add a certain components to the fossil tows -- so I think moving forward and also thinking long term, we will see certainly a combination of biomarkers where, again, we may integrate with more patient-related data into algorithms. So that is probably the future.

On the market potential per se, so it's -- we outlined a global market potential, but you are absolutely right. At the moment, it's certainly in the U.S. market, which is the growing market based on the acceptance of disease modifying therapies. Thinking about the future, we see the growth actually across all geographies. And it's clearly also our goal to have solutions basically for all geographies, including, for example, also China as an important future market.

And I believe you also said MSED. So for them said, yes, that's a global number. But again, it's early days, and I think the potential is that it could be higher, but I think that's a number we feel comfortable with. And then, Josh, I think you can take the profitability

Yes, for sequencing, I see no reason why even blockbuster scale sequencing can't be massively profitable. Molecular diagnostics in general are high-profit diagnostics. I think if you look at the field, you can look at public companies that are out there and their margins. We have every technical entitlement to be just as cost efficient, if not more, than all the solutions that are out there. And I say that based on our technology today, let alone on where we can take it over time, we think 2 things will happen. One is our technology will scale, and we will remain competitive and profitable. And two is the focus of cost is going to shift a bit. We're already seeing potentially diminishing returns on if you get the cost per genome for a certain amount, the costs are elsewhere. They're in library prep, they're in sample collection, they're in other things. So it's not obvious where this will go, but we'll be profitable no matter where it goes.

And what Josh said is assuming we will also continue to maintain the same type of R&D investments as well.

Okay. Next question, we'll go to Doug Schenkel from Wolfe.

You've done a really nice job today demonstrating progress across the portfolio and outlining strategic priorities for the next several years. A lot of this progress has come via organic efforts. It does feel like -- and I haven't gone back and pressure tested this observation, but it does feel like there's more contributions that you're highlighting today from partnerships, investments and acquisitions. Amongst those, I think, of Saga and Foundation and Freenome amongst others. So with that in mind, really a 3-part question. One, over the next 5 to 10 years, what's your expectation for organic versus inorganic development? Two, what's the criteria we should expect you to use? I'm thinking of things like size, growth profile, when and why? And then maybe a little bit redundant, but the third part is, does this criteria differ by diagnostic subsector or even geography based on the geopolitical, regulatory and market backdrop?

Yes. So that's a great question. And what I would maybe start by saying is if you look at what we highlighted today, which is Foundation, which has been part of Roche for a while, but Saga and PathAI, these are 2 particular organizations that fulfilled a very key part of our overarching strategy that we've had. and that being the integration of high medical value diagnostics with clinical decision support tools, very on strategy and in an area where it's very clear that these are going to be growth drivers. And what I would say when we look at and we look at everything, we're the largest IVD company in the world, and that limits a lot of our optionality for inorganic growth.

But in this case, what we saw was, and we showed our key areas of focus, these were key drivers. I mean we know that MRD is going to be one of the biggest drivers of the diagnostics industry in the years to come. We saw an optionality that very much fit with our technology stack and our strategy. So it was a smart bolt-on. And with PathAI, the absolute complementary nature of that to our VENTANA business also made sense and the fact it was very much aligned with our strategy. So that's the way we're going to look at it. But again, we will be somewhat limited by our size and our scope, our scale, excuse me, because we are the biggest IVD company. I hope that answers your question.

Okay. I think one more, and then we need to close the Q&A session. So without question. So...

I mean PAMA has been pushed for about 6 years now. I just want to get a feeling of whether you think PAMA or a version of it through the Results Act gets enforced from next year. And in general, I mean, the U.S. reimbursement environment, do you see it getting worse from here given what seems like a 6-year break?