GlaxoSmithKline Aktie

A warm welcome to this GSK call on our agreement to acquire Nuvalent. My name is Constantin Fest, Investor Relations. I'm delighted to have here today with me Luke Miels, CEO; Nina Mojas, President, Global Product Strategy; Tony Wood, Chief Scientific Officer; Julie Brown, our CFO. Also for the Q&A part of this call, we'll be joined by David Redfern, President, Corporate Development; as well as Mondher Mahjoubi, our Chief Patient Officer. Please go with me to the next Slide 3, for our disclosure statement. Also note our cautionary statement on Slide 4. With this, please turn to Slide 5, and I will hand over to Luke to start this presentation.

Thanks, Constantin. Good morning, and thanks for joining the call at short notice. Look, I'll start here first. As a reminder, this is the framework that we're using to drive value for patients and shareholders. It's got 3 components, so driving top line growth, accelerating late-stage assets and combining this with simplification. And this deal is a disciplined continuation and acceleration of that strategy. Next slide, please. Now we've been following Jim and the team at Nuvalent and their impressive medicinal chemistry work for some time. The deal is a consideration of USD 10.6 billion. It's accretive to EPS in 2029 and is expected to close in Q3 of 2026.

This acquisition critically will bring multiple products. with the 2 lead assets already filed and expected to launch in 2026, immediately impacting top line growth. Next slide, please. So here's the logic for the deal. Simply, it's on strategy and helps us deliver top line growth and accelerate R&D. It accelerates our planned entry into lung via 2 well-defined subpopulations, which have clear unmet needs. Both products work via validated targets and are designed to address these established unmet clinical needs. These are small molecules in oncology.

So, the deal combined with measures to offset costs is accretive to sales and operating profit in 2027 and EPS in 2029. And through discipline, we are maintaining the 70p dividend and the progressive policy. Next slide, please. Finally, just at the start, I would add, this is our type of deal. The difference is that it's a multiproduct deal versus a single asset, single company deal. Zidesamtinib for ROS1 mutations and neladalkib ALK1-driven tumors are the types of products we like. And they're an extension of our BD strategy, which you can see on this slide, which is to acquire external innovation that works via established targets that addresses unmet efficacy or tolerability needs. So with that, I'll hand over to you, Nina.

Thank you, Luke. As Luke mentioned, Nuvalent is a company that has been very successful in developing precision medicine assets with its clinical stage assets focused on specific well-defined patient segments in lung cancer. ALK+ and ROS1+ mutations affect about 3% to 5% of all non-small cell lung cancer patients with about 80% of patients already diagnosed at Stage 3, so metastatic stage. These patients are often younger in their 40s and 50s, unlike typical lung cancer patients who are normally diagnosed in their 70s. These patients are more frequently women and in general, have high rates of central nervous system involvement, so brain metastasis.

What's very characteristic about this specific defined patient population is that they are one of the most engaged lung cancer communities and are actively shaping their treatment. Established treatments have been transformative for these patients, and they frequently remain on ALK and ROS1 tyrosine kinase inhibitor therapy for years. As an example, treatment duration in first-line non-small cell lung cancer patients treated with PD-1s, majority of cancers of patients in non-small cell lung cancer patients. They are treated for approximately 10 months. For EGFR-mutated cancers, patients are treated for up to 2 years. And for ALK+ first-line patients, current median PFS is longer than 7 years and hopefully further increasing.

Next slide, please. Acquisition of Nuvalent is going to strengthen our overall oncology ambition. And specifically, it will accelerate our efforts in lung cancer, supporting both development and commercial efforts for our ongoing Ris-Rez program in lung cancer. After this acquisition, we are looking at a number of milestones from 2 approvals this year, potential approval for ROS1 naive patients next year, ongoing trial in first-line ALK mutated segment and the ongoing trials for the early-stage HER2 asset. On the other hand, GSK's global footprint will maximize the opportunity for Nuvalent portfolio of precision medicine assets.

Next slide, please. We are moving to the ALK-specific segment. Over the past decade, we have seen an improvement in the outcome for ALK+ non-small cell lung cancer patients as innovation focused on solving unmet needs such as blood-brain barrier penetration to address CNS metastases, which I have mentioned before are very frequent in this patient population and then broader coverage of resistance mutations. The current third-generation ALK inhibitor, lorlatinib, recently had 7-year update of its CROWN study, where the median PFS still has not been reached. Despite strong efficacy, unmet need remains as tolerability issues significantly limit potential quality of life and therefore, adoption in first line.

These limitations stem from the lack of selectivity for ALK and involvement of TRK kinase, which Tony will describe in details in a moment. Neladalkib is a next-generation ALK tyrosine kinase inhibitor designed to improve on lorlatinib's profile, sparing TRK engagement with first-line pivotal study ongoing. Next slide, please. So how did this development impact the evolution of treatment practice in ALK+ non-small cell lung cancer space. Most commonly used medicines to treat ALK+ lung cancer are second- and third-generation ALK inhibitors.

Alectinib continues to have a significant use in first line, driven by its acceptable tolerability profile. Despite best-in-disease efficacy, lorlatinib adoption is limited by its tolerability issues, central nervous system events impacting cognition, speech and mood and then metabolic issues like hypercholesterolemia, hypertriglyceridemia requiring co-medications and then significantly weight gain. These issues are attributable to lorlatinib's off-target activity.

And I'll now hand over to Tony to talk more about neladalkib's differentiation and supporting clinical data.

Thank you, Nina. On this slide, you can see the evolution of the -- of the ALK family inhibitors. Neladalkib is a fourth-generation inhibitor, is designed to pair third-generation ALK potency with strong CNS penetration while retaining activity against both single and compound ALK-resistant mutations. This, alongside its Trk-sparing profile, underpins its potential for superior efficacy and tolerability compared to previous generations of inhibitors. Each of these characteristics is critical to maximizing the amount of time a patient can potentially benefit from therapy.

Next slide, please. Okay. Taking a more detailed look, we believe that nela has the potential to be a best-in-class ALK inhibitor as it delivers strong performance against the 3 basic pillars of precision medicine. Firstly, and as you can see on the left-hand side of the slide, it's important to hit the driver of disease hard to control the original tumor. Secondly, and also on the left-hand side of the slide, it's important to address or prevent the emergence of key drivers of disease progression to extend the durability of response. This specifically includes designing molecules, which maintain inhibition in the presence of on-target resistance mutations as well as optimizing for brain penetration to address metastatic disease.

This is illustrated on the right-hand of the slide and is critical because of the high incidence of brain metastases at diagnosis for ALK+ non-small cell lung cancer patients. And thirdly, it's important to address selectivity to avoid off-target adverse events, which can be treatment limiting. You can see this in the selectivity index calculated on the left-hand side of the slide. This is critical to minimize discontinuations and dose reductions and to maximize potential therapeutic benefit while removing barriers to adoption. This differentiation is important as it allows nela to improve on the significant cognitive, psychiatric and metabolic adverse events associated with lorlatinib, which severely impact patient quality of life.

Next slide, please. With these design principles in mind, data from the ALkove-1 study support a best-in-class profile for neladalkib based on cross-trial comparisons. In TKI pretreated patients, nela produces encouraging response rates, including for intracranial disease when compared to lorlatinib. As you can see on the left-hand side of the slide, in the second-line plus setting, a median duration of response is not yet reached. And encouragingly, 60% of patients achieved a duration of response greater than 18 months, which is a meaningful improvement compared to 9.6 months for lorlatinib.

Based on these data, the FDA has granted nela priority review with a target PDUFA date of November 27, 2026. In TKI-naive patients nela produces promising response rates compared to lorlatinib and importantly, shows a 12-month duration of response for more than 90% of patients, exceeding the historical benchmark from lorlatinib in the Phase III CRAM study. A Phase III registrational study for nela in the first-line setting, ALKAZAR, is ongoing and recruiting well.

Next slide, please. ALK+ non-small cell lung cancer patients are typically younger non-smokers who are otherwise fit and healthy. This is a highly motivated and informed patient population and as such, a manageable safety and tolerability profile is a key consideration. Nela spares TRK binding, and this is reflected in its adverse events profile, which shows avoidance of the long-term metabolic and neurological adverse events seen with lorlatinib. Importantly, the liver enzyme elevations seen with nela are typically asymptomatic, transient and manageable through monitoring and dose modifications as is consistent with routine practice for TKIs. Overall, they do not result in increased drug discontinuation rates and compared to other ALK inhibitors.

This is also supported by physician feedback, which highlights a more manageable safety profile for nela compared to the intensive monitoring and caregiver burden associated with lorlatinib's cognitive impairment, mood disorders and metabolic side effects.

Next slide, please. On this slide, you can see the ongoing clinical studies for nela. ALkove-1 is a Phase II study in ALK+ solid tumors with several cohorts. It was designed to have registrational intent of TKI pretreated ALK+ non-small cell lung cancer patients. In 253 TKI pretreated patients, nela delivered a 31% overall response rate and a durable response was 64% and 53% of responders estimated to remain in response at 12 and 18 months, respectively. Notably, 78% of patients had received 2 or more prior ALK TKIs, of which 91% had received prior lorlatinib. So a heavily pretreated population for which no approved therapies have demonstrated meaningful activity.

This pivotal data was presented last week in Chicago at ASCO. As mentioned, based on these data, nela has been granted breakthrough designation with a planned PDUFA date in November of this year. ALK is an ongoing Phase III registrational trial in the first-line setting using the current standard of care alectinib as a control arm. This study is enrolling well.

Now let me hand over to Nina.

Thank you, Tony. We are moving now to the ROS1 space. Consistent with the evolution of ALK TKIs, zidesamtinib is strongly differentiated through its significant improvement on safety profile and strong efficacy compared to previous generations of ROS1 TKIs. Repotrectinib carries notable TRK-driven neurological and metabolic side effects that drive dose discontinuations. Taletrectinib, a third-generation ROS1 TKI improves on tolerability, but still brings meaningful dizziness, GI tox and side effects like diarrhea, nausea and vomiting. Based on the large clinical data sets generated across over 900 patients, zidesamtinib shows a class-leading safety profile.

Its ROS1 selective and Trk-sparing design allows for a differentiated safety profile avoiding the CNS and GI side effects historically associated with the class. Ability to stay on treatment for longer has potential to translate into improved median PFS in first line compared to current treatment options. Back to Tony again.

Thanks, Nina. Next slide, please. As with nela, zidesamtinib has a compelling profile. It's a highly potent Trk-sparing ROS1 inhibitor with broad mutational coverage and improved selectivity profile. Importantly, the G2032R resistant mutation coverage supports durable activity in heavily pretreated patients and improved outcomes in early lines of therapy, including in the TKI naive population. G2032R is a common resistance mutation arising following crizotinib and next-generation TKI treatment.

Once more, high TRK selectivity allows for CNS activity, which is demonstrated in patients who received more than 1 prior brain penetrant TKI as well as in the naive population. Overall, this profile translates to a low rate of serious or severe CNS events with significant improvements in problematic adverse events associated with earlier generation TKIs, including dizziness and GI toxicity. Next slide, please. Moving on to the clinical setting and looking at cross-trial comparison to [existing data], you can see a substantially improved duration of response in both heavily pretreated and TKI-naive patients as evaluated in the ARROS-1 study. Based on these data, the FDA has granted zidesamtinib breakthrough designation with a target PDUFA date of September 18, 2026, in TKI pretreated patients.

These data support best-in-class efficacy with comparable response rates and response durations exceeding that of taletrectinib in both the TKI pretreated and naive settings. Next slide, please. Finally, this slide shows a summary of the ongoing studies. The ARROS -1 Phase II study recruited patients with ROS1 positive solid tumors with a specific cohort focused on ROS1-positive non-small cell lung cancer, including those previously treated with TKI inhibitors as well as TKI-naive patients. As mentioned, clinical efficacy supports a best-in-class profile. And importantly, this extends to safety where zidesamtinib demonstrates considerable improvements in rates of dizziness, GI and liver toxicity that is seen with previous generation TKIs.

The pretreated indication carries an orphan drug designation with an upcoming PDUFA date in September, while filing of a supplementary NDA for the TKI-naive setting is planned in the second half of 2026.

I'll now hand over to Julie.

Thank you, Tony. So to summarize, the acquisition of Nuvalent includes 2 launch-ready best-in-class -- potential best-in-class assets with blockbuster potential with PDUFA dates later this year and will further strengthen our oncology portfolio, building on our exciting development pipeline, which includes Ris-Rez, our ADC for lung cancer. I will now cover 3 main areas, and all my commentary will refer to core results at constant rates. So first, the transaction details. We have agreed a purchase price of $124 per share, a 40% premium to yesterday's closing price and a 26% premium to the 30-day VWAP, equating to an aggregate consideration of $10.6 billion or net of cash, $9.4 billion, which is GBP 7.1 billion.

We will commence a tender offer for the shares within the next 10 business days, and subject to regulatory approval, we anticipate closing the deal in Q3. Second, the financial impact. We expect the acquisition to support GSK's revenue growth from 2027 onwards and be incremental to our existing ambition for sales of more than GBP 40 billion by 2031 and to strengthen sales, operating profit and margin through the dolutegravir loss of exclusivity period.

We expect the deal to be accretive to operating profit in 2027 and earnings per share in 2029 onwards, inclusive of synergies and reprioritization. Assuming completion in Q3, we expect a low single-digit dilution to EPS in full year '26 to 2028, but remain confident in our current 2026 guidance range for earnings per share growth of 7% to 9%. Third, capital allocation and the balance sheet. This transaction is aligned with our investor growth priorities and BD strategy. Our capital allocation priorities remain unchanged. Post the transaction, we will retain our strong investment-grade balance sheet with no impact expected on our credit rating. We remain committed to our dividend of 70p this year and our progressive dividend policy. And lastly, the transaction will be funded from existing and new debt facilities and existing cash resources.

And with that, I'll hand back to Luke.

Thanks, Julie. So to summarize, we think this deal is a strong strategic fit for GSK, and it represents a continuation and acceleration of our strategy. We get 2 potential best-in-class products that can launch this year, driving growth and operating profit in 2027. And as you've just heard from Julie, we have applied financial discipline to ensure that we manage the cost of the deal and that we've recommitted to the dividend and the progressive policy. So with that, let's turn it over to Q&A, please.

Thank you. With this, we're ready for Q&A. [Operator Instructions] The first question comes from Matthew Weston.

It's about the split of the value or the potential, I should say, by asset. So I think consensus has 2 billion peak approximately for Nuvalent, but that's heavily skewed to ALK over ROS1. I'd be very interested in your view on the relative contribution of [zidesamtinib] versus nela. And then also about the speed of launch. I think [zidesamtinib] has an expanded access program with over 500 patients on it. Does that mean that we should expect a rapid launch on approval as we convert those patients to commercial drug?

Thanks, Matthew. So I'll answer the second one and then maybe, Nina, if you want to characterize that without too much color because we'd like you to do your work on your own modeling, Matthew, but I appreciate the question. I mean the speed of launch, absolutely, and that's -- if you look at our heritage working with Sierra and other biotechs that we've acquired, this is a very important component. We're already planning to pivot and execute that launch, and we're in a good place.

The access program, the recruitment for the programs, the first-line ones are very strong. So again, it's a targeted population we can wrap that up. And it was something that we were going to do for B7-H3 anyway. So thanks for that question. And Nina, the split of the asset and $2 billion, Matthew, I assume, again, we won't comment on that, but it's obviously not the time frame that we're looking at over the life of the deal.

Yes. I was just going to mention the $2 billion. I'm not sure that's the peak reference to peak sales, which are clearly higher than that. The -- in terms of value split on sales, I would say ROS space is probably between 1/4 to 1/3 of the total value.

Next question comes from Sarita Kapila.

Just on nela and in the TKI naive cohort that you have in your original data, are you actively discussing with the FDA whether a frontline label expansion is possible? Or will we have to wait for the ALKAZAR Phase III PFS readout for approval in the earlier line setting? And then if I could just squeeze in another one, please. Are you sure that doing a head-to-head in the frontline setting versus alectinib is the right comp, particularly when we've seen 7-year PFS data for lorlatinib from the CROWN study?

Thanks, Sarita. We certainly have looked at those questions in depth. Tony, did you want to cover the first 2? And then maybe Mondher, if you can comment on the standard of care -- on the second question, Nina, feel free to jump in.

Yes. And look, I'm obviously not going to get into the details of regulatory interactions, and it's a little early in terms of the Phase III study. The points you raised are all ones that we have taken into consideration, and we very much see this molecule as being one which has the credentials that will support a first-line indication.

Just to add actually, today, the standard of care in terms of market penetration is still alectinib with almost 45% market share and tells you about how important it is for us to pick the right control arm. Just as a reminder, lorlatinib Phase III trial, the CROWN data that were presented at ASCO used crizotinib as a control arm. So very low bar in the third-generation TKI. So the fact that we are choosing alectinib, I think it's the right thing to do. Having said that, I believe the community will certainly look at other setting of the disease and also other options to have head-to-head data with lorlatinib to try to figure out actually the best benefit/risk ratio.

Thanks Mondher. Nina, do you want to?

Yes, I just realized that we didn't answer Matthew's question on early access program and the number of patients. Yes, actually, Nuvalent did a great job with early access program for both assets, and there are hundreds of patients on early access program, which gave us confidence for multiple reasons because feedback from the physicians who have hands-on experience with actually all TKIs in this space, and we're able to compare the experience of patients and the physicians was a really tremendous benefit. When we launch the drug, the assets, we do expect early access patients to be transitioned to commercial source.

Actually, that's an important point, Sarita. Because there's such broad experience and empirical experience with both of these products, we were able to do a massive amount of due diligence, frankly. So we had over 300 interactions, quantitative, qualitative, in-person interviews, online interviews with physicians, a large proportion of whom have direct experience utilizing these drugs in these subpopulations. So again, that's what's behind the confidence and why we think there's a pathway there. We've also spent a lot of time characterizing the profile of lorlatinib in particular, and have some insights there that we will disclose at a future date. Next question, please.

Next question comes from Kerry Holford.

One for Julie, please, for the financials in the context of the accretion that you cite from next year for revenues and profits and EPS from '29, you referred to synergies and reprioritization. So just intrigued to hear what that involves both in terms of the deal, but perhaps also internally, anything additional to add there?

Thank you very much, Kerry. So as Luke mentioned, obviously, we wanted to be very disciplined about the way we approach the deal generally, appreciating that this was going to be on the face of it dilutive to shareholders. So taking each of those in turn, and I've worked very, very closely with Tony and his team on this, -- the first one is relating to synergies on the integration. We expect some synergies through SG&A, and then we also expect synergies in R&D, including through the discovery portfolio and integration and also contracting synergies for activities such as CMC and clinical study design.

This is exactly what we found with other deals that we've embarked on recently. And then the second thing relates to the just prioritization in the business generally across all areas together within R&D. And as far as we're concerned in R&D, approximately twice a year, we do a very thorough review of the portfolio. We are constantly assessing the internal portfolio and reprioritizing assets to really optimize the return on investment and the probability of technical and regulatory success. So net-net, we believe we've been very responsible in terms of exercising discipline around the dilutive impact of the deal.

Next question comes from Emmanuel Papadakis.

It was just a follow-up on ALKAZAR. I'm not sure if I -- apologies if I missed it. Is the frontline approval predicated on PFS readout? Or is there any scenario in which you could get that approval sooner? And maybe a quick question on ROS1. Back in the day, the original commercial optimism around that landscape is predicated on better diagnosis, unlocking clinical and commercial opportunity that hasn't really happened. Do you harbor any greater hopes for a diagnostic transformation, unlocking the patient opportunity there?

Sure. Thanks, Emmanuel. Nina, do you want to cover the second question? -- then Tony? A quick one.

Yes, the frontline study is based on PFS.

Do you hear that, Emmanuel? PFS. And Nina, on the ROS1 testing and opportunity.

Again, both ROS and ALK are now standard part of testing. It's part of the panels that are done on lung cancer tissue samples when -- at the diagnosis. That's probably less of a barrier. But as we have seen, the product profile so far actually had significant limitations.

And Nina, do you mind expanding on this? Because I think the more you look at these products and particularly you look at these subpopulations with these particular mutations, what we found is a very interesting relationship in terms of innovation price, small molecule, -- you've got a defined population, but you've got these very, very long tails, which the better tolerated profile that you can get, you're more able to sustain this. So the mathematics start to look very, very interesting. But you really have to stop and look at it and just work your way through it, which is what we've spent a long time doing. So Nina, do you mind expand on that?

Yes. So again, to repeat what Luke said, there are a small number of patients, that's definitely true. But if you look at the totality of non-small cell lung cancer in terms of value, it's disproportionately higher because for each patient that you start on ALK or very likely in the future on ROS, you have a multiple duration of therapy for these patients. So CROWN data update 7 years, PFS rate at 7 years is still 55%. So median has not still been reached. It's very likely that, that tail will continue at 50% or above 50%. And these are metastatic patients. They are not stopping their treatment.

It's very difficult for mutation-driven cancer to stop treatment because what we have experienced from all these TKI areas, so EGFR ALK as well as soon as patient stops therapy, the cancer usually comes back. So in terms of value, they are proportionately significantly bigger than what the number of patients would indicate.

I would just add, as Luke mentioned, we spoke to probably about 300 or had interactions with about 300 physicians. Very positive thing is that they had hands-on experience and they could compare the effects of all these TKIs. I will share some of the comments that were made. One is lorlatinib is a drug that everybody loves to hate. But because of the efficacy, it's frequently the first drug that they will offer to their patients. What comes with the use of lorlatinib is CNS-related side effects. So serious conversations with the patient, with patient cares because they have to be aware of these side effects that go into a psychiatric area.

So one of the physicians said using lorlatinib, I became both a psychiatrists and metabolic expert. One of them mentioned that he became a target for sales reps that sell GLP-1s because the patients gain weight, and these are younger patients, it's very relevant for them. One of them described a patient who was a younger woman. Her income was coming from being an influencer on social media. And after gaining weight, she actually stopped therapy and progressed. So these are all issues that you need to address over the years while you're treating patients.

And therefore, it was a very, very clear feedback that tolerability is the main barrier. While we were doing due diligence, just a comment between ROS1 and ALK. -- while we were doing due diligence, I have to say ROS1 space was probably what physicians refer to as slam dunk. There is no way that they would not use this drug over other inhibitors ROS1 inhibitors. So there, our confidence is actually very high that this is going to be the best in disease, best-in-class drug.

Thanks, Nina. And we can expand on that. Again, we've been spending a lot of time on this before breaking cover. And have really been very thoughtful and rigorous in profiling these assets and the team that's developed them.

Next question comes from Sachin.

I'm on dial-in apologies. So 2 quick questions, please. One, just big picture for you, Luke. This is one of the largest deals Glaxo has done in a while and is focused on launch assets versus mid-stage, early-stage pipeline for '29, '30. So just what's driven that, in inverted commas, strategic shift? I know you frame is consistent.

And then second one for Nina, a follow-on to prior. So thank you for giving the split on ROS versus ALK. I wonder if you could just give us a bit of color on second line versus frontline across both, acknowledging that frontline is bigger. So 2-part question. One, how comfortable are you with consensus on the launch in later lines before frontline comes through? And then how much of the deal valuation is frontline out where there's some perceived risk around that data delivering differentiation?

Thanks, Sachin. So I'll answer the first one, and then we'll go to Nina. Look, I think -- and that's what I tried to outline with that slide in my introduction. We have a methodology to our BD. We like validated targets because essentially, the clinical scientific components are heavily derisked. And then we're really relying on our regulatory clinical execution and commercial launch capability, which, again, we have to validate it every quarter, but I think the -- it would be fair to say there's a high degree of -- a strong track record there.

What we had with Nuvalent was unusual. Basically, it was a little bit like London buses session, right? Suddenly, 2 or 3 come along at once. And each one of these products, we would have acquired as a separate deal. We just had the attractive element of having them all embedded in a single company. And importantly, this was very much a bottom-up driven deal. Some deals have driven top down. I might come to the office and say, I really like this company, let's go for it. This was very much a deal that was driven by Chris Sheldon, who you all know from his previous time at AstraZeneca. We had the individual involved in designing Tagrisso on the team.

There was a number of other AstraZeneca and [indiscernible]. I'm sitting next to Tony, who was deeply involved in lorlatinib's design. And so this built momentum inside the organization over quite a long time. And in the end, we reached the conclusion that this was a really smart deal to do and it was a good use of our shareholders' capital. And again, if you take the components apart, it's more consistent with what we've done before. But also there's attraction in critical mass because essentially, we're pulling forward our entry into lung, but in discrete populations to build our credibility there, which positions us very well for B7-H3.

So there's a method to this, but also critically, as we've said, there's financial discipline here to maintain capacity for future accretive deals. But this was just too attractive to let pass by. Nina, over to you.

Yes. And Sachin, I'm not sure I fully understood your question. So I will try and maybe either you need to help me or my colleagues. So first and second line, ROS1, as I think we communicated, second line has been filed. PDUFA date is in September this year. In ROS space, all -- this is really ultra-orphan indication. So a number of patients is very small. All the assets are approved on single-arm studies. Second line -- so the first line is -- filing is expected in the second half of this year, so approval next year.

Again, this is extension or additional -- based on the additional data from TKI-naive patients from the ongoing study. As I mentioned, there is a very, very clear feedback that this is going to be easily standard of care in the ROS space. I'm not sure I fully -- was there a question on ALK as well for.

Maybe reframe the question. So 2 parts. One, are you comfortable with consensus on launch in the later lines across both ROS and ALK in the next couple of years versus yourself framing upside to peak midterm? And then the second was how much of the deal valuation is on front line out for that data '28, '29? And how do you assess the risk around differentiation delivery?

Yes. So Sachin, pretty confident, again, to a previous question about number of patients on early access program and the extent of experience that physicians community had so far. So I would say, again, not going to guide on the year annual sales, but we are quite confident that consensus is not too optimistic or unrealistic. And then the value of first-line ALK, yes, clearly, first-line ALK carries majority of the value of the deal, no doubt.

You are looking at the highest number of patients with the highest duration of therapy. Based on the data that we have seen and the profile of the drug, we actually have very little doubt that this would not be successful. Question is time, which also we actually have a pretty good idea when it's happening because the recruitment in the study is actually going exceptionally well.

And Sachin, I would say, look, 3 things to consider in the context of confidence in the duration of response data in the first-line setting. And this is not only true for nela, but also in the ROS1 setting. If you look at the improved resistance profile, that is important in maintaining response because it prevents the emergence of compound resistant mutations as well as taking care of already existing cases.

Obviously, tolerability plays into that as well and in particular, in the context of dose reductions or dose holds. Nela has a very favorable profile in that context and also in the context of when reductions are necessary, what we see is mostly only single step-down reductions in the case of nela and its intrinsic properties, its PK favor a more reliable outcome in that context. And in case anyone is going to ask me the question, we've looked into the impact of dose reductions and holds on the efficacy, and we can see very little to suggest that there's any significant impact there. So it's a combination of features underpinned by the profile of the molecule, which gives us confidence in duration of response.

I can't resist jump in. And Sachin, you may remember this. 10 years ago, I think a few people believe that EGFR market will become what it is today. And actually, second and third generation of drugs have turned this disease into a chronic one. I think we have with ROS1 and the opportunity to turn those metastatic patients to really a patient who can live with their cancer for many, many, many years. And the key word here is really tolerability. I think we know that second and of course, third generation and this asset hit the target hard, have a broad coverage of the different driver mutation, penetrate the CNS, has definitely a very good efficacy in terms of tumor shrinkage, but the key word is tolerability and durability.

And I think what we have seen so far in the Phase I/II and the momentum that Nina described around clinical trial and expanded access program from the community of oncologists, but also from patients is telling us that this is the right drug for them to stay longer on treatment, even in second line, but definitely more in first line in order to live with this disease more than 10 years. Of course, everyone is excited about the CROWN. But remember, I mean, half of the patients stop their treatment already. And we know what will happen for this patient when you stop treatment.

Next question comes from [Victor].

And so maybe starting with the comment we've made on ALKAZAR. So you've mentioned that recruitment was progressing well and that you have good visibility on completion. So can we ask whether there is an interim analysis planned on ALKAZAR? And what would be the trigger for that potential interim analysis? And then on Nela's hepatic toxicity signal, can you walk us through how you think about managing this signal in clinical practice and why you believe it won't ultimately undermine its tolerability advantage?

And maybe last one for Julie. You've indicated low single-digit EPS dilution for 2026, but guidance for 7% to 9% remains unchanged. So can you just help us reconcile this?

Great. Thanks, Victor. So Tony, do you want to cover the interim? Mondher, you cover clinical consequences and management of nela, which we've learned a lot about and Julie last on that question.

Look, obviously, I'm not going to get into the details of the ALKAZAR study. But yes, an interim is planned, and you can get a clue from that if you look at the landmarks from the Phase III CROWN study.

Right. And Mondher, we've seen the full data set?

Yes. So maybe a quick reminder that one of the challenges that we have seen with third-generation ALK inhibitors is essentially the off-target side effects and the fact that inhibiting the tyrosine-related kinase, there are 3 of them. And actually, the A, B and C, the B is the one that basically is driving the whole CNS side effects. And now actually, it's really disturbing because not only we have somnolence, we have cognitive effect, we have really even mood transformation that basically prompt patients and physicians to stop treatment.

This is the most critical actually side effects. Of course, there are other side effects, in particular, peripheral neuropathy that occur in more than 34% of the patients that sometimes actually are of Grade 3 and 4. These type of side effects are leading to the discontinuation. What we have seen in the 1,500 patients treated so far, both in clinical trial and expanded access program with nela is basically no side effects of this type.

The only thing that was noticed is an elevation of transaminase that is truly asymptomatic. There was no hepatic failure. There is no fatal events. It's only biochemical asymptomatic elevation of transaminase that can be monitored very easily. Physician -- oncologists are used to this because it's not the first time that we have this in tyrosine kinase inhibitors. And the approach is to stop treatment for a while, test until it goes back and then rechallenge with a slight dose reduction. And we have seen that patient can completely be rechallenged without any compromise with the efficacy.

And I will just add that other ALK inhibitors have the same monitoring for liver enzyme elevation already as part of their management clinical practice and the label. So we don't expect that this is going to come as a surprise to the physicians because that's exactly what they are doing with other ALK inhibitors already.

Great. And Julie?

Yes. Thank you very much for the question. So obviously, the EPS is affected mostly by the interest that comes through together with the Nuvalent profile in its own right. And we are assuming for '26 that we've got a Q3 completion of the deal. And clearly, when we've guided, we've guided an EPS range of 7% to 9%. So it does mean that we move within that range to manage the dilution, but we stay within the range on a net basis.

Thanks Julie. and thanks [Victor].

Next question comes from [David Evans].

So just a question, if you could just clarify or give us some more information on the level of discontinuations that you see in the ALK space. I thought your slide said that on lorlatinib, well, only 7% discontinuations versus 5% on nela. Is that a like-for-like comparison? It doesn't quite seem to stack up with your sort of commentary about wildly different tolerability profile. So just anything in the lorlatinib proposition, if you could just flesh out much less well tolerated in theory than those figures would indicate.

Yes. Sure, David. Thanks for your question. I mean these are distinctly different profiles. Tony, do you want to cover that and Nina add any market commentary, physician commentary?

Yes. And the data you've picked are indeed relating to discontinuations associated with tolerance. What's important, though, is to look at the complete picture for treatment discontinuation because as Nina mentioned earlier, with discontinuation and dose reduction, you do see disease return and the data for Lorlatinib at 2 years, I believe, is a 38% progression rate based on the combination of those things. Nina, you want to add anything?

Yes. Again, David, so I think if you look at the discussion that happened at this year's ASCO post CROWN 7 years presentation, I believe there was a slide from the discussant, which something along is the crown the price. or something along that where the focus of the whole discussion was exactly the tolerability profile and is the benefit that comes with such a long PFS actually worth the adverse events that patients are going to. I would probably say if there is an interest to -- for you to talk to some of the physicians who have used the drugs and hear the experience because that probably tells you more than the numbers in the tables.

Great. Thanks, David. And we can certainly do that for anyone who's interested.

Next question comes from [Naresh Chauhan]

Just interested in the ex U.S. development plan, please. 2/3 of Alecensa sales come from outside the U.S. and China is a big part of that. It looks like about 1/3 of the sales. There seem to be no Chinese sites in any of the Nuvalent development program as far as I can see. Can you just help us understand the ex-U.S. development plans, please?

There is a plan to bring Chinese sites. Tony, do you want to.

That's basically it. It is a global plan than just opening Chinese sites.

Thanks for your question. Next one, please.

Next question comes from -- is a follow-up from Matthew Weston.

Lots of dialogues. Can you hear me?

Yes, we can.

Amazing. It's a quick follow-up for Julie. Julie, in your opening comments, you said, I think, that the deal strengthens margins through dolutegravir's LOE. Now I think the previous comments were that margin was going to be flat through the dolutegravir LOE. So does that mean we all need to sharpen our pencils and start taking the margin up?

Or this just gives you incremental confidence that you'll be able to keep those margins flat, particularly because it looks like there may be some incremental pressure in HIV from guideline changes and other things.

Okay. Thank you, Matthew. So just in terms of -- just to recap for everybody, in terms of prior margin guidance, we've said that in '26, we'll be above 31%. And then we've said we will be -- have a stable margin through DTG LOE, which is the '28 to '30 period. What we're referring to when we say the deal strengthens is it will improve. Obviously, it's very accretive to sales during this period as the team have talked about. It's high profitability assets, so it brings through benefits to the profit. And therefore, we would expect the margins during that period to be higher than before the deal. As we know, we've managed the dilutive period to be a very short period with accretion quite quickly. So therefore, it does give us a benefit to profit and margin through the DTG years.

Thanks, Matthew. Appreciate the other questions. We've got time for a couple more if people have them.

Next question comes from Zain.

It's another follow-up for Julie, just on the dilution over the next couple of years of low single digit. I think the color you provided earlier was helpful in terms of the expectation for synergies, and it sounds like there's internal portfolio rationalization goals for CMC costs within Nuvalent that you can potentially unlock to manage at a low single-digit dilution. But just stepping back, I'm still struggling a little bit to fully get that because I think Nuvalent consensus is about $100 million revenues for next year.

OpEx, they've got about $400 million in terms of spend. So what's the key disconnect as you see it? Do you think that the maybe consensus top line is a little bit on the conservative side given your bullishness around zidesamtinib and what the uptake could be there? Or do you think that maybe there's a portion of your R&D effort rationalization that helps you get there that we might not be appreciating?

Thanks, Zain. I mean I think the short answer is it's a combination of those things, but I'm not sure we want to give too much color at this point beyond the commitment. But Julie, feel free to expand if you want.

Yes. I think we've covered it. I mean we wouldn't go into specific projects in the R&D portfolio. And I would emphasize that we're looking at prioritization across the company, not just within R&D, but across the company and driving that hard to be very disciplined, as Luke mentioned. I mean we wouldn't normally also comment on consensus models. But in our view, the R&D cost in consensus models for the target are reasonably high. So I'll just leave it at that.

We have time for one more question, probably also a follow-up, and that is Kerry.

Just a quick one. Anything you could say on the IP for the 2 late-stage assets that you're acquiring here? And just to confirm, you expect both to be exempt from IRA?

Yes. So yes, on IRA because they're orphan and 2040s plus, Nina.

Yes, early 40s.

Thanks, Kerry. Very grateful to everyone joining at short notice. I'll conclude by saying, again, to reinforce, we think this deal is very much the type of transaction that we do. It's a great fit strategically for us. It's consistent with our strategy in lung cancer and actually forms an accelerant for that. And we're getting a number of very, very attractive assets, which, as you've hopefully heard today, have deep exposure amongst the clinical community and patient exposure.

And I think there's a clear pathway for both of them, the late-stage ones to best-in-class as well as some earlier-stage assets like the HER2 and a stable of preclinical medicinal assets, which are also very accretive. And finally, I hope you've seen that we have applied financial discipline here in terms of selecting this transaction, pricing and then integration of it.

So thanks again for your very thoughtful questions at short notice and look forward to following up with you.

It's my pleasure to introduce GSK. We've got Hesham, he's the Head of Oncology R&D at GSK. Exciting times just coming out of ASCO. I guess, Hesham, thank you for joining.

Thank you, Michael.

I guess to start, if you sort of think about GSK's Oncology R&D, what are the 2 or 3 decisions you're most proud of that shaped current portfolio? And is there anything you deliberately stopped doing to focus resources?

Yes. It's interesting because I think one of the first things that I think about just in terms of the journey that GSK has had coming back into oncology is really how the field continues to evolve. During one period of time, probably early on, there was a lot of interest in immuno-oncology and checkpoints as well too. And I think in many ways, if you look across the industry, at times, we may have actually over-indexed on checkpoints.

And I think it's one of the areas that probably as I took on my role, I tried to really strike the right balance of thinking about precision oncology, a focus on what are probably much more well-validated platforms and molecules and a move more towards precision oncology and a bit away from checkpoint exploration. And I think probably, if anything, that was probably the first decision that I think is really important and helping shape at least the oncology portfolio at GSK.

The second really was at a time when I think, maybe early on, there were certainly some mixed feelings about BLENREP, especially after the results of the DREAMM-3 study early on which was the first Phase III study that didn't meet its primary endpoint in a late-line multiple myeloma population. Again, mixed reviews, I think not everyone believed in the asset at the time.

And we kept moving forward with DREAMM-7, DREAMM-8, really optimizing the design of those studies. And ultimately, they really led to successful outcomes, including DREAMM-7, which demonstrated statistically significant PFS and overall survival benefit and DREAMM-8 with a statistically significant improvement in PFS.

The third really is around dostarlimab. I think at the time, if you look at certainly the landscape and opportunities to help differentiate its development program, given how competitive the PD-1, PD-L1 landscape was and identifying opportunities like first-line endometrial cancer, a space where the standard of care hadn't necessarily evolved, and for quite a lengthy period of time, about maybe 15 years or so with platinum-based chemotherapy. A space like, for example, dMMR/MSI-high, locally advanced rectal cancer, where we've seen, at least through the Memorial Sloan experience, 100% clinical complete response rate and initiating a pivotal development program in that space in GI malignancies.

I think those were certainly also decisions that I feel like we're really the right ones to help us start to build the pipeline and then expand. And then probably, I would say like the last one is really business development. A lot of collaboration with Chris Sheldon's team on the BD side, that's really helped enable us access, not only the right technology platforms, but the right assets. And you look at, for example, acquisitions like Sierra Oncology with momelotinib or IDRx with velzatinib as well, too, as another means to complement the pipeline.

So overall, I would say the decisions that I'm really proud of are the ones that, one, really helped us address key unmet needs for patients. Two, helped optimize the probability of success for GSK and its pipeline and rebalanced its risk profile. And then three, this focus on moving towards precision oncology and higher positive outcomes for our assets.

Excellent. And if we stick with BD for a minute and sort of try to link that to internal. So coming out of ASCO, we said it in our note, I think GSK maybe a little bit surprisingly came out as somewhat of a winner out of ASCO for us because we didn't quite expect the IDRx data. And I think what we've seen with other ADCs and PROC, your B7-H4 looks pretty good. Their licensed asset or externally sourced assets. So when you think about that internal versus external mix, what's the ideal mix?

Yes. Michael, it's a really interesting question. I would probably say like all big pharma companies are struggling and grappling with this. I don't know if there is a specific split that I would say is most optimal, right? But what I can say is, I don't think any company could sit here and say, hey, by the way, we are going to source innovation purely from an internal standpoint. Like it's not realistic. It's not possible. Each company has unique strength, unique capabilities.

Like for us, for example, I think our antibody engineering, our small molecule engineering are focused on, for example, functional genomics, immunology, like those are all areas of expertise for GSK. But for us to say, hey, we're going to like -- have like the broadest expertise and the deepest expertise across all areas of platforms, it's not realistic.

And I think we have to really think broadly, like so one, we have to think about where to source the innovation from, right? So historically, it's been much more like from the U.S., from Europe. Now, of course, we're seeing it emerge in Asia and certainly in China as well, too. And the bottom line is making sure that there is an openness towards what can be done externally and what can be accessed externally.

Once you've prioritized like and clearly delineated what you're interested in, and I think to me like that's a like fundamental fact of like what's defining -- what's your strategy? What are your prioritized disease areas? What are your prioritized technologies or platforms? And what are the best out there? Do they exist internally? Do they exist externally? And can you benchmark them in their performance as well, too?

And there's -- to be honest, there's an element of like what are you looking for? Are you looking for first-in-class? Are you looking for best-in-class, right? And then you can think about, is it developed internally and in-house? Or do you try to kind of access an iteration or a best-in-class asset externally as well, too.

But at the end of the day, even now and as we think about discovery research organizations, I think the biopharma space has to really look at it and say, what is the right-sized research organization for this day and age, given where we are and given the open source innovation that exists as well, too, right? Do you have to have an internal presence for a research organization? Of course, you do, right? But at the same point in time, like, does it need to be like tremendously large. I think that's a separate question and very debatable as well, too.

Perfect. And could we maybe briefly try to layer into that sort of the technology angle, everybody talks about AI. There's digital pathology. There's tumor modeling. Like how does that feature into that mix?

Yes. A really important question, Michael. I mean for us, it really starts everything from discovery, right? And I think data and technology go hand in hand. So it's everything from accessing proprietary data sets from either external partners or collaborators or academic institutes to help us with antigen discovery to certainly medicinal chemistry design and how AI/ML can certainly help enable that and is embedded within GSK.

Two, basically, and I think to me, this is fundamentally the area that where I try to spend a lot of time is prosecuting and better characterizing disease biology, right? I mean if you think about the challenge that we have in oncology, and I would argue probably across different disease areas is oftentimes, we're only looking at one singular piece of the pharmacology in the context of the biology of the disease without better understanding what's happening around it.

And for us, we focus really right now on building what our foundational models, right? And these foundational models help us get a better understanding of the disease biology in terms of progression, resistance, relevance of different targets and combinations. And at the same point in time, they have to be powered by data. How are they powered by data? They're powered by data that we access externally. So multiomic data, so everything from, of course, clinical outcomes annotated data. to genomic, proteomic, transcriptomic deep immune profiling data, at a tumor microenvironment level, at a spatial level, right?

And at the end of the day, the ability to be able to, again, use AI/ML to generate these biological models is really important. And you also have to keep them up to date because there's new data that's continually emerging as well. And then basically link them to, not only discovery, but also your translational strategy and hypotheses.

For example, we acquired sometime in early 2025, a company called CELLphenomics, and this company focuses on developing novel in vitro model systems. What do they do? They're called organoids. And basically, they try to replicate what happens within a patient's tumor, but outside of the human body. And you're able to, not only do that through the lens of better, for example, replicating what happens in the patient's tumor through unique knowledge, insight and culturing but also be able to visualize it in 3D fashion and collect all of the data that's being developed in this living model system, right? And then see if you can replicate what happens in the organoid from the patient.

And then follow the 2 in parallel to see is the drug predicting, for example, in the organoid what's happening in the patients. And can you predict the resistance mechanisms that are likely to occur, response, lack thereof, et cetera.

So to me, I think fundamentally, like that's equally important. And then finally, maybe the third piece is we're talking about like predictive biomarkers and also diagnostics. Computational pathology is really critical. The ability to be able to once again start looking at biomarkers through a different digital lens and start to move the diagnostic discussions away from just simple testing to more probably slide and AI/ML assessment is also something that we're evaluating and assessing as well too.

Fantastic. So we start talking a little bit more about the ADCs. I guess that -- so to me, the SGO data -- at SGO, you show data for Mo-Rez that look really good and look very clean. So it seems to me that ADCs are still poorly understood, and they're complicated. There's the payload, there's the target, there's the chemistry. It looks like with your B7-H4 that could be quite differentiated. So if I take a step back, what do you think ADCs are still misunderstood? And if I could link the next question into that, how do you decide whether to go single agent or combo with ADCs?

Yes. It's interesting because I know like -- we think back to maybe like 10, 15 years ago. And the only thing that, like, with the first iteration of ADCs that we thought about was, hey, like the therapeutic index, that's the issue that -- like they seem to be really difficult. I think we've moved like beyond that.

And you're absolutely right. Like, I think now, we're looking at ADCs through the lens of like there's 3 different components to them, and they all matter and they matter in different ways. So is it the antigen and not only its expression but also selectivity, of course? Because that matters in terms of on off-target effects. Is it the linker and its stability? And again, because of the toxicity, but also the efficacy as well, too. And also as we think about like things like bystander effect, right?

And is it the payload? Where is it on the spectrum of like potency, toxicity, right? And its mechanism of action because you're also thinking about combinations. What types of synergies could there exist, right? Could it be combinations? I'm just saying like, with like, let's say, DNA damage response agents with, of course, checkpoints and others as well, too. Like does it -- does the payload causing, for example, let's say, DNA damage, elicit an immune response through new antigen or neoantigen generation.

So all 3 components matter. I think we're still following a space where we're trying to optimize dosing, if I may say, because I think it becomes much more important to patients. At the end of the day, we're trying to basically deliver what our targeted chemotherapy to tumor cells. I think the biomarker space is still one that is, I would say, important to consider. I think we've moved beyond target expression. It is no longer a target expression game. It is actually one where we have to think about multivariate biomarkers that incorporate the targets, the linker and the payload and sensitivity to all 3.

And I think there is an element of, we have to think about what's to come in the next 3 to 5 years as these patients start to progress on more commonly used payloads and we identify what the resistance mechanisms are, so novel payloads are going to be equally important as well, too.

Fantastic. And maybe this is unfair, but if I get you to rank B7-H4 versus B7-H3, I think my impression in the past has been B7-H3 was maybe just slightly more interesting asset to you with the data that we've seen, it seems like it's flipped a little bit. Is that a fair interpretation or not?

So I look at the entire portfolio, and I get these questions often like even internally, by the way, like what's your favorite asset? What are you most excited? I'm going to say both of them to me are equally important and for the following reasons. I think you look at B7-H4 and because of its expression profile, it is highly directed towards gynecologic malignancies, broad expression in ovarian, endometrial cancer, a lesser extent, maybe in cervical, a little bit in triple-negative breast and biliary tract cancers. But ovarian and endometrial, very clear, right?

And the way that the ADC is designed as well too. It's a [ dara 6 ], it's cleavable linker, it's a Topo-1 payload and the activity that we've observed, the data that was presented at SGO you alluded to, 62% confirmed response rate in platinum-resistant ovarian cancer, 67% in second-line endometrial cancer, 5 Phase III pivotal studies launched. The drug is active irrespective of H4 expression. And the safety profile, I think, certainly, it's very consistent with that of the Topo-1 payload, just the heme tox, which is quite manageable because of how familiar medical oncologists are with it as well, too, the neutropenia and so forth. And so I think about it through that lens and the drug has got a really interesting efficacy profile.

On the other hand, B7-H3 as well, too. I would say what's unique about it is this broad expression profile of the target. And not only is it expressed across thoracic malignancies, lung, head and neck, GI malignancy, CRC, GU, prostate, bladder and also sarcomas.

But also, I think maybe this is something that's common to both of them. Not only our -- like not only is the target differentially expressed on tumors versus normal tissue. Both B7-H3 and B7-H4 are checkpoints. So there is this like dual role that they have, right, which I think is an area that we're focusing on better characterizing because I think it plays a really important role in how we think about combinations and combining with checkpoint inhibitors as well, too.

And so we're learning a little bit more about that in small-cell lung cancer, where we have a breakthrough therapy designation, but also in osteosarcoma. And we've already initiated a Phase III study in second-line small-cell, but stay tuned. I'm going to say, Michael, for 2 things. One, several more Phase III studies that will be starting with B7-H3 over the next few months. Two, data, multiple data sets from our own development program and from the Hansoh development program that will actually be presented at a key scientific congress in the second half of this year.

Fantastic. One that I didn't have on the list, but I hope you don't mind, just thinking about the combinability. There's data that suggests that Jemperli better than Keytruda in trials. What you just said about the combinability is that ADC approach and ability to bring that out more that you actually have a checkpoint inhibitor that is actually very competitive, but it's just been difficult to do the trials in a conventional way now that the ADCs are there, you can -- that's more enabling to get that through?

Yes. I think it's an interesting question. And I think you're referring to the PERLA data, of course, which is looking at -- it was a Phase II study designed to really just benchmark the clinical activity of dostarlimab to pembro. So dostarlimab plus chemo versus pembro plus chemo in first-line non-small cell lung cancer and what we saw was, at least, again, the study wasn't formally powered for superiority or noninferiority for that matter, but it was just a relative comparison. And what we saw was the response rate were relatively similar and some positive trends for PFS and OS that favored dostarlimab. And I think for us, the key was basically benchmarking the activity of dostarlimab to the market leader in pembro. And I think that was really helpful context for us.

How we think about the B7-H3 and B7-H4 programs? We're thinking about it through the B7-H4, B7-H3 development hat. And so we think where it makes most sense to combine with our already approved PD-1 inhibitor than -- or PD-L1, then we'll do that because, of course, there are clinical, regulatory and certainly commercial considerations.

And the clinical and the regulatory ones involve, of course, investigator use, physician use. They involve having maybe data or not in a given tumor type. They involve what we call contribution of components from a regulatory standpoint and the need to generate that. And then there's the commercial kind of element as well, too, like I said, around uptake and so forth. And where there's opportunities for us to combine with dostarlimab and it makes sense to do that, then we're going to try to do that to help the dostarlimab program out as well, too, from its development strategy.

Now bear in mind, there's 3 pivotal Phase III studies ongoing for dostarlimab. So not only did the Ruby Part I and Part II studies read out positive, but also we have ongoing Phase II pivotal study in locally advanced dMMR/MSI-high rectal cancer. We have a Phase III study in dMMR/MSI-high colon cancer, and we have a Phase III study in locally advanced head and neck post chemoradiotherapy as well. So those components remain ongoing, and I think we're continuing to identify ways to maximize the value of dostarlimab, which has become a blockbuster medicine as well, too, recently.

And then maybe IDRx, which now is a different name, which I always forget. I still call it IDRx.

Velzatinib.

So the data at ASCO looked really interesting certainly in the first-line setting. You've gone into Phase III head-to-head versus Gleevec. That's a punchy trial. It's going to take a little while for that to come through. Should I think about that as the main path to first-line? Or is there a fast forward that could get you there quicker?

Yes. No, I think it's an interesting question. And you're right, you saw the data at ASCO, very encouraging. In second-line confirmed response rate, 38%, unconfirmed 40%, median PFS about approximately 14 months. Well tolerated, I think especially as you look at the second-line data with other agents that have reported data recently as well, too. Like I think probably the Grade 3 event rate is about maybe 30%, 33%. Other agents, it's like 2 drugs, combination regimens, 72% Grade 3 event rate. It's difficult for this patient population that is typically, I would say, more used to well-tolerated, gentler at least treatments like imatinib.

And I think for us, second-line is a starting point. So we've had a Phase III study start in late '25 head-to-head against Sutent in second-line patients. And then we're starting this first-line Phase III study head-to-head against imatinib and again, the ASCO data set, 61% confirmed response rate, 65% unconfirmed response rate. We're very encouraged by it, and we're going to continue to identify ways to accelerate that trial. Let me leave it at that.

Fair enough. I tried. Maybe in the last minute, 2 questions. One, a little while ago, I was sitting somewhere, I think it was in France, and you said look at the ADCs and luckily I did. If I were to ask you, in the next 12 to 18 months, what's the data set that I should be focusing or investors should be focusing at that sort of show that continuity of look at what we've done with the ADCs, look at what we've done with IDRx?

Yes. I'm going to say probably like for B7-H3, multiple data sets coming out over the next 6 to 12 months from our own development program from the Hansoh program, starting with the second half of this year at a key scientific congress. So stay tuned. So I think that's maybe the first one.

I think the second is really more of like continued follow-up from the first-line cohort for velzatinib, which was presented at ASCO, which I think is going to be very helpful.

And then the third, continued data maturity for the B7-H4 data across ovarian and endometrial as well, too. And then finally, maybe just one more point to put out there for BLENREP. Interesting data that was presented from DREAMM-9 at ASCO, looking quadruplets. But also interesting data that was presented a few months ago by Evangelos Terpos from Greece, there was a Phase I study that he was conducting called the TERPOS trial, as we call it, looking at the triplet of BLENREP in combination with RD. And the data from that actually was -- or has been presented across ASH, EHA, a few times.

What was interesting is at a recent meeting called EMN which is a European myeloma network meeting. He presented some interesting data. It was actually some modeling work that he did. And the modeling work looks at the data from his study, the first-line study newly diagnosed the triplet regimen, which is in DREAMM-10, head-to-head against the MAIA regimen, daratumumab.

And it looks at across different dose levels, 2.5, 1.9, 1.4, all 3 - just all 3 regimens. It projects what the median PFS could look like based on the extent to follow-up he has right now. And the modeling projects that across all 3 doses, the median PFS would be about 115 months across the 1.9 milligram dose specifically, which is the dose that is being used in DREAMM-10. It's about 100 months.

So imagine, we know that quadruplet CD38-based quadruplets are delivering about maybe 90 months PFS. Well, imagine if you could deliver 100 months with a triplet with a better tolerability profile in these newly diagnosed transplant ineligible patient segments.

So I'll leave you with that and say that we're going to continue, of course, as I alluded to earlier, to think about business development opportunities. We've done a lot on the research, the discovery side. And I think at the end of the day, for us, as we think about things that complement the portfolio, they have to fit into this framework of: one, address a key unmet need just based on the pharmacology and the mechanism of action. Two, align to key prioritized tumor types where we have strong capabilities. Three, there's preliminary clinical data that's indicative of a high probability of technical success. And then four, of course, bring the right value proposition for the organization and complementarity with existing assets.

Fantastic. And then final question, and maybe the answer to this is, hey, I'm the R&D guy. But if I look at guidance or ambition for the company, 2031 in revenues is GBP 40 billion. The GAAP to consensus is GBP 5 billion. And so far, the answer has been the biggest gap between GSK's expectations and the market is like 50%, that's BLENREP. If I look at what you've got with 7-H4 with IDRx, Jemperli data, these data coming through that there's a lot going on. It's -- I don't need that much out of BLENREP to get to a more ambitious outlook.

Yes. I mean, Michael, I love your view like that. So I think what we need is for everyone to embrace that, that's really the key. And you're right. We just talked about all this data across velzatinib, H3, H4, dostarlimab and let alone, of course, momelotinib, which is growing quite well. Yes, I think there's a lot of potential. I mean, there's a slide that Emma presented probably sometime in early 2025, that looks at, for example, the contributions that specialty medicines would be making to the long-term growth of the organization. And I think when you look at, for example, oncology, it's expected to be significantly contributing by 2031 as well, too, and 2034. So you're right, I think there is a reason to believe, I guess, maybe is the best way to put it.

Fantastic. Hesham Abdullah, thank you very much.

Thank you very much.

Dear ladies and gentlemen, welcome to this GSK EASL presentation on Bepirovirsen B-Well 1 & 2 pivotal phase III studies. My name is Constantin from IR. I'm also joined by Nick from IR, and I'm delighted to introduce the following speakers for today's call: Nina Mojas, President, Global Product Strategy; Professor Seng Gee Lim, Director of Hepatology, National University Health System, Singapore; Kaivan Khavandi, SVP, R&D, Head of Respiratory, Immunology and Inflammation, Head of Translational Development and Sciences; Melanie Paff, Vice President, Medicine Development Lead Hepatitis B Programme; and Pedro Zarazaga, SVP, Global Product Strategy, Specialty.

Please note on the next slide, our cautionary statements. Also note that during this presentation, we will also make the slides available.

With this, I'd like to hand over to Nina to kick us off. Over to you, Nina.

Great. Thank you, Constantin, and greetings from Barcelona. Thank you. So chronic hepatitis B remains a large lifelong infection largely untreated at the moment. Majority of the infections happen vertically, so from mother to child at birth or in early childhood. And as you can see, about 95% of these infections lead to chronic hepatitis B. At the moment, the standard of care in hepatitis C varies globally, but nucleoside analogues are the backbone and the benefit of nucleoside analogues is the suppression of hepatitis B virus DNA. These treatments do very rarely achieve -- functional cure. They are also lifelong therapies with no defined endpoint.

The unmet need in hepatitis B is durable loss of hepatitis B surface antigen. And with the full suppression of hepatitis B DNA, this is referred to as functional cure. Receiving functional cure will transform hepatitis B treatment into finite treatment, which is highly desirable and at this point, not available. Next slide, please. Nucleoside analogues and the impact and current standard of care. As you can see on the slide, nucleoside analogues do lead to complete suppression of DNA and the benefit of that is significant 41% reduction in hepatocellular carcinoma. For those patients who are treated with nucleoside analogue in this study, if they achieve so-called functional cure, the reduction of the risk of hepatocellular carcinoma goes further down by 76%.

Next slide, please. When we look at the opportunity, as I mentioned, this is highly undertreated disease. You can see the global gap between number of infected individuals, number of diagnosed individuals and those who are currently on treatment. U.S. and China, we are looking at about 120,000 in the U.S. and about 6 million treated patients at the moment, of which in both regions, about 70% are hepatitis B surface antigen below 3,000. In the U.S., standard of care are nucleoside analogues. Patients who are treated are largely patients who originate from immigrant backgrounds, so originating in Africa and Asia. In China, hepatitis B is very high national health priority. In China specifically, nucleoside analogues are used in addition to interferon.

Next slide. Looking at 3 key markets for us, thinking about bepi, about 80% of the opportunity are between United States, China and Japan. All these geographies have accelerated regulatory processes, breakthrough designation in the U.S. We are expecting approval in October, PDUFA 26th of October. The market in the U.S. is highly concentrated in 5 states where -- that are marked by high immigration. So we are looking at states like California, New York, Texas, Florida and New Jersey. Patients who are treated are highly motivated. They have access to treatment and are very much willing to look for finite treatment. In China, you have seen our announcement that we have signed a collaboration with Sino Pharma.

Sino is market leader in hepatology in China with very broad commercial footprint with access to more than 5,000 medical centers. Japan, SENKU designation as well. We are looking at accelerated review period. Again, Japan is second market in terms of number of treated patients with very high government incentives for treatment.

And with this, I will pass on to Professor Lim to walk us through B-Well 1 & 2.

Thank you very much, Nina.

So I'm going to go through the presentation that I did this morning for the EASL conference and excuse my voice, I've got a bit of laryngitis. So the title of the talk was -- can we go back one slide, clinically meaningful rates of functional cure in virologically suppressed patients with chronic hepatitis B infection, treated with bepirovirsen in Phase -- B-Well Phase III clinical trials. Next slide, please. I think Nina has already covered that chronic hepatitis B infects more than 240 million people and causes more than 1 million deaths annually.

It actually is the most common cause of hepatocellular carcinoma globally. Functional cure is now the new treatment goal of chronic hepatitis B, and that's defined as shown in the slide, more than 24 weeks of sustained HBV DNA below the lower limit of quantification and HBsAg loss after finite therapy with or without anti-HBs. Bepirovirsen is an antisense oligonucleotide that targets all the HBV transcripts, reducing HBV DNA and HBsAg levels. And this is the first therapy in global Phase III trials with functional cure as a primary outcome. So here, I'm going to show you the primary efficacy and safety results of the trials.

Next slide, please. The objectives of the B-Well 1 and B-Well 2 studies are shown here. The primary objective was evaluated at week 72, which is the functional cure rate in those with a baseline HBsAg level below 3,000. And the key secondary outcome was also evaluated at week 72. This is a functional cure rate in those with a baseline HBsAg level below 1,000. In addition, also was assessed the sustained HBV DNA below LLOQ off all HBV treatments in those with HBsAg levels below 3,000 and below 1,000.

Next slide. So B-Well 1 and B-Well 2 were replicate studies, which are identical in study design. So patients could be enrolled in -- the studies they had chronic hepatitis B or on stable nucleoside analogues had HBsAg levels between 100 and 3,000 had DNA suppressed below 90 IU/mL, had ALT levels below 2x upper limit of normal, did not have cirrhosis or did not have interferon therapy more than 12 months. Upon enrollment, patients were stratified by HBsAg levels above or below 1,000 and were randomized 2:1 to receive bepirovirsen or placebo as 2 loading doses followed by weekly injections for 24 weeks on the background of nucleoside analogue therapy.

Upon completion of treatment, they were followed up for an additional 24 weeks on nucleoside analogue therapy after which they were assessed at week 48 for eligibility to discontinue nucleoside analogues. The eligibility criteria is shown in this slide. They had to have DNA less than LLOQ and HBsAg not detected between week 24 and week 46. ALT had a bit below 2x upper limit normal and had to be HBeAg negative. Those who were eligible to discontinue nucleosides then stopped therapy and were monitored for 24 weeks, after which they were evaluated for functional cure at week 72, which is the primary outcome of the study.

Next slide, please. The baseline characteristics were similar across groups. Average age was around 50 years. They were predominantly male, mainly Asian. The mean HBsAg level was between 900 and 950. Patients with HBsAg below 1,000 comprise 60% to 65% of patients. And most of these patients were HBeAg negative, only 8% were e-antigen positive. Next slide, please. This is the primary outcome. Functional cure was achieved in 19% of bepirovirsen recipients and no placebo recipients shown in the pooled study results on the right-hand side.

Next slide, please. For the key secondary outcome for HBsAg levels below 1,000, slight differences in B-Well 1 and 2, the pooled results showed a 26% functional cure rate in bepirovirsen-treated patients and none in the placebo. Next slide, please. This treatment effect was seen across all regions, this regardless of HBsAg level. There were minor differences in efficacy rates between different regions, largely due to differences in baseline characteristics between study populations in those countries.

Next slide, please. The key secondary outcome of HBV DNA below LLOQ off all HBV treatments was seen in 23% of bepirovirsen treated recipients and none in the placebo. This 23% constituted 19% of patients had functional cure and 4% additional patients who had DNA below LLOQ but did not achieve functional cure and none in the placebo group. Next slide, please. Sustained HBV DNA below LLOQ off all HBV treatments was seen in patients with HBsAg levels below 1,000 IU/mL. There were slight differences in B-Well 1 and B-Well 2. The pooled results showed a 31% DNA below LLOQ comprising 26% of patients with functional cure and 5% of patients who had DNA below LLOQ who did not have functional cure and none in the placebo group.

Next slide, please. This is the patient disposition of all patients in the B-Well 1 and B-Well 2 studies. I would point you to the pie chart on the right-hand side. I've already shown you 19% of patients achieved functional cure, but an additional 30% of patients achieved HBsAg levels below 100 IU/mL without functional cure. And these comprise 12% of patients with HBsAg levels below between 100 -- between 10 and 100 IU/mL and 18% of patients with HBsAg levels below 10 IU/mL.

HBsAg levels below 100 IU/mL are thought to be clinically significant because these patients may have a future possibility of HBsAg loss. Next slide, please. This is the on-treatment safety profile, which is consistent across B-Well 1 and B-Well 2, and I will point you to the pooled results on the right-hand columns in blue are the bepirovirsen results show that AEs, meaning the permanent discontinuation study treatment constituted only 3% of patients and SAEs related to study treatment only constituted 2% of patients. There were no fatalities and no fatal SAEs related to study treatment. Next slide, please. treatment AEs reported in more than 10% of patients is shown here. Most of these were injection site reactions comprising injection site erythema, pain, pruritus, or bruising.

There were also safety signals in ALT [indiscernible] increase and platelet count decrease. Participants had permanent discontinuation or liver-related events. However, 2 of these 4 patients actually achieved functional cure as well. Transient ALT increases after bepirovirsen initiation were associated with HBsAg reduction. There were platelet and eGFR declines, but these resolved once treatment was completed or paused and there were no clinically significant bleeding events attributed to bepirovirsen. Clinically significant changes in eGFR were not associated with markers of renal injury.

Next slide, please. So to conclude, functional cure rates of 19% treated with bepirovirsen among those with a baseline level of 3,000 IU/mL and 26% in bepirovirsen-treated patients among those with baseline HBsAg levels of 1,000 IU/mL was achieved and none was placebo. In addition, sustained HBV DNA below LLOQ off all HBV treatment seen 23% of bepirovirsen-treated patients in those with a baseline level of HBsAg below 3,000 IU/mL and 31% of patients with a baseline level below 1,000 IU/mL and none with placebo.

So bepirovirsen is a first-in-class 24-week finite therapy achieving functional cure in virologically suppressed patients with chronic hepatitis B infection with an acceptable safety profile. And this will definitely change the landscape of chronic hepatitis B treatment for the future. So you can access the full paper in the New England Journal of Medicine from today. Thank you...

Thank you, Professor Lim. My name is Kaivan Khavandi. I lead Specialty R&D at GSK, and I'm joined by Dr. Melanie Paff from R&D, who's the Medicine Development Leader for bepirovirsen. Next slide, please. The key point that's important to consider for a moment is the clinical impact these data show bepi could have. When we think about clinical importance, we typically consider the target value for an effect size and how this translates to improvements that matter for patients.

This is sometimes conflated with the proportion of patients who respond to therapy when exposed. And so I wanted to cover both. It's now accepted that functional cure is the very highest bar of efficacy to aim for in this disease. It's the single greatest predictor for prevention of hard endpoints, hepatocellular carcinoma and mortality. As the term suggests, this allows patients to come off all treatments with a finite management, and you'll appreciate that curative intent is a rare goal for a medicine in any portfolio.

So there's clearly no question of the clinical importance of functional cure, and this is reflected in management guidelines and regulatory processes. It also comes with a high burden of proof to demonstrate this in an [ RCT, ] as shown in this slide, requires undetectable DNA and loss of surface antigen once off all treatments for 6 months within a study. Bpi met this high bar in the B-Well studies. The comparative arm emphasizes this high bar, which we labeled in the presentation as placebo, but which actually represents the standard of care, nucleoside -- tide animal treatments for 48 weeks before coming off treatment compared to a similar group who received bepi for the first 24 weeks.

So it's 48 weeks of active treatments with NAs that we refer to as the placebo group. And in that comparator group, you see 0% achieved the primary endpoint of functional cure in the ITT population, those with surface antigen of 3,000 or less. Further, 0% achieved functional cure in those with baseline surface antigen of less than 1,000. And finally, 0% achieved response to HBV DNA at the lower limit of quantification at 72 weeks. So 0 is all around for the comparator arm, which is the standard of care. In comparison, in the ITT group, bepi achieved 19% cure. In the prespecified population with surface antigen less than 1,000, bepi achieved 26% functional cure. If we relate this to real-world numbers, the majority of the treated population with chronic hepatitis B have surface antigen less than 3,000 and over 40% have surface antigen less than 1,000.

And then when we consider the pie chart that Professor Lim presented, an additional 30% of patients achieved surface antigen levels below 100 bepi, a threshold reduction now accepted in guidelines as partial cure on the basis of the strong longitudinal data that shows protection from hard endpoints and which standard of care is poor at achieving. That allows us to appreciate the breadth of benefit across patient groups. So 1 in 5 and 1 in 4 patients achieved the highest bar of efficacy cure depending on baseline surface antigen levels in the most commonly treated patient groups and 1 in 2 patients received a response expected to predict protection from long-term outcomes by achieving surface antigen less than 100 IU/mL.

These data are clearly recognized and reflected in the impressive regulatory breakthrough and priority review designations achieved in filings across multiple authorities. Now if we go to the next slide, I'd like to take a moment to consider that this is a monotherapy. And so it's quite remarkable that a single product can confer such protection. How can it do that? Well, it's a single therapy, but it unlocks a 3-pronged efficacy benefit. And it does this in a large part because bepi targets a highly conserved region across all HBV genotypes and present across all HBV RNAs. As such, it targets protein-coding RNAs pcRNAs that stop translation of HBe antigen. It targets pre-genomic RNA, pgRNA, which prevents the translation of HBV polymerase and correlated proteins, knocking down HBV DNA.

And of course, the RNAs that translate HBV surface proteins or antigens, which really stops this latent substrate that's responsible for reactivation and relapse when, for example, the immune system is tested. And last but not least, it directly acts as an innate immune stimulator, which when combined with the strain that residual HBV antigen burden places on T cells, prevents the immune exhaustion that's problematic in hepatitis B. This gives the system a chance to recover and therefore, sustain the durable clearances that we observe. From a portfolio and competitive perspective, the efficacy of bepi truly resets the bar when we consider what could add meaningful benefit beyond bepi. And you'll appreciate it's not typical to have a first-in-class programme for a major public health challenge with a finite and curative solution.

For this reason, we see the hep B portfolio positioned with bepi as the anchor. And to this end, Mel will later cover one such programme that does offer real promise alongside bepirovirsen in those with surface antigen levels not studied in B-Well. But first, Mel will help put these data in the context of standard of care and clinical management of these patients.

Thank you, Kaivan.

So I want to talk a little bit about the established standard of care that we have in hepatitis B now. And you'll note that both nucleoside analogues, which are used around the world and pegylated interferon, which is primarily used in China, neither of these drugs were designed for functional cure. So nucleoside analogues were specifically designed to stop viral replication. So it's not surprising that the functional cure rate is extremely low. And as Kaivan stated, in our trial after 6 months of therapy, you can see that the functional cure rate in the placebo or the nucleoside analogue comparator was 0% in our trial. pegylated interferon on the other hand, is primarily used in China, and it's a treatment for 144 weeks for HBsAg loss.

Now it has a fairly low functional cure rate, around 2% to 8%. The issue that you have with pegylated interferon is the unfavorable safety profile and the limited tolerability. So patients have a problem staying on this drug because it basically makes you feel like you have flu-like symptoms. So there's quite high dropout rate and compliance is a problem. And we contrast that to what is the expectation of a standard for tomorrow. So clearly, we're looking for functional cure as the gold standard. We're looking for a finite duration of therapy. Patients don't want to be on nucleoside analogue for the rest of their lives. We're looking to lower that risk of cirrhosis and liver cancer and all of the associated reduction in morbidity and mortality.

We're looking for a larger eligible patient population. And I think it's really important for us to point out the burden that these patients walk around with the psychosocial burden of having this chronic infection and the lifelong medication. So if we could go to the next slide, please. In addition to the information that Nina shared earlier, I want to point you to an analysis that was recently reported this past year that looked at the clinical outcomes of surface antigen loss. So this was a retrospective cohort study using an electronic medical record database over a 7-year period, and it showed significant association between HBsAg loss and the reduction in the risk of liver cancer and even all-cause mortality. So 89% reduced risk for liver cancer and 62% reduced risk for all-cause mortality.

Next slide, please. One of the questions that we get a lot is what about the ongoing development? What is GSK interested in from hep B from a portfolio perspective? And we'd like to draw your attention today to another study that we have going on right now in Phase IIb with an siRNA that was in-licensed from Janssen. In this particular study, you can see from the graph, we're looking to expand the patient population to all treated patients, 100% of treated patients, not just the 70% of patients that are below 3,000. Dap, tom or siRNAs are classically shown a very strong and robust response to lower even very high levels of HBsAg to a low level.

Unfortunately, by themselves, they don't seem to be able to achieve functional cure. However, what these siRNAs can do is bring the HBsAg down to a sweet spot where we know bepi works best. So our intention with the B-United study is to test 6 months of Dap/tom therapy, allowing the HBsAg to come down to this low level, then following that with 6 months of bepi, again, to achieve functional cure on the backbone of nucleoside analogue treatment. After week 48, those patients will continue on their nucleoside analogue for another 6 months. And those that are available to cessate, their nucleoside analogue will then stop and functional cure rate will be called at week 96.

So we're very excited about the study. It has the potential to show both the increase in functional cure rate overall as well as opening up a treatment for functional cure to patients that now have no ability to get functional cure. So we're very excited about this. Can we go to the next slide? So I think in summary, what we've shown today is that bepi is clearly a clinically significant functional cure medicine. It's achievable, it's durable, and we additionally have almost half of the patients who receive a clear medical benefit after one year of treatment. What we want to do is to think about the things that we have heard today around the EASL conference. Physicians that we've talked to and that you've seen in print have said things like transformational, generational change in treatment, historic. The editorial from the New England Journal said remarkable results.

I think this also reflects the innovation that we've seen by regulators and their recognition of that innovation. And you can see both in the U.S., China, Japan, we have things like Fast Track priority review, breakthrough, SENKU designation. It's not a regular occurrence that you get this across so many regulators. And I think it's a recognition of the innovation that we bring. So we'll stop here and then move to question and answers.

Thank you very much, Mel. With this, we are ready to take your questions. [Operator Instructions] First question comes from Peter Verdult.

We also checked in with Professor [ Wong ] at Stanford earlier today, who's also at EASL. He definitely thinks the data is exciting, but he did say it's not groundbreaking. So a couple of follow-on questions. He -- on the presentation talked about an applicable population as defined by B-Well is about 70%. He was saying that in that -- the B-Well study probably only represents 30% to max 50% of treated patients. So I just want to square the circle there. That's a clarification.

My real question is the interesting stuff. I mean the sequencing in the combination study with siRNA is definitely interesting. But what about some of the other questions from B-Well? So the one I'm really interested in, in the trial design, patients were allowed to stop their nucleoside therapy. And I think that finite treatment is a real sort of selling point. So within B-Well, can you tell us how the patients that stopped their [ Nucleoside analogues ] after 48 weeks, how did they do to those that continued? So that would be my one question.

So patients were eligible to stop treatment. They had HBV DNA negative and HBsAg was undetectable, ALT was below 2x upper limit of normal, and they were HBeAg negative. So they had to fill all those criteria for them to stop Nucleoside analogues therapy. So in other words, they already had HBsAg loss. Does that answer your question?

Peter, I assume this has answered your question. If not, raise your hand again, and we can have a follow-up. With this, we...

Sorry, I was muted.

Yes. And I'm happy to address also the treated population. So the average that we have shown you today, meaning 68% of the treated population is less than 3,000 and 45% is less than 1,000 is the average across the 5 major markets, meaning U.S., China, Japan, EU5 and Germany. But there is variability from market to market. So for instance, in the less than 3,000 population, the average across those markets is 68%; however, Germany is a little bit lower at 54% and Japan is a little higher at 86%. So what we're providing is the average.

Can I just follow up on that issue about whether this is breakthrough or not breakthrough, which I think is a matter of opinion. But I think the breakthrough part is the fact that 90% of patients achieved functional cure. That's never been achieved in any treatment programme before. Nucleos(t)ide analogue for interferon. So if you don't call that breakthrough, I'm not sure what else you call it.

Next question comes from Sachin Jain.

I've got a question around testing and monitoring. The editorial calls out need for stringent safety monitoring referencing every 1 to 2 weeks. So I just wanted to clarify the safety monitoring requirements in the study, what do you expect from the label and how onerous that will be? And then around HB surface antigen testing, obviously, approvals in October, minority of patients are currently tested in the U.S. is our feedback. How quickly do you think that can mobilize post approval?

So let me take the question on safety monitoring. So patients were injected weekly. So they were obviously monitored weekly for safety features. I think the 2 safety features that were important, the ALT rise. And I showed you in the -- I didn't show you in the presentation, but ALT abnormality was seen in about 45% of patients. ALT more than 10x was seen in 6% of patients and 20x was seen in, I think, 1% of patients. However, if you had an ALT rise more than 3x baseline, you had an 85% chance of getting a cure or HBsAg loss. If you had ALT less than 3x baseline, then your chance of getting HBsAg loss was only 35%.

So it seems that the ALT rise is associated with efficacy. There were no drug-related liver injury problems that were called. So from the ALT viewpoint, it seems to be an efficacy feature. As far as the other safety issues is concerned, they comprise 3 issues: thrombocytopenia, renal function abnormalities and complement abnormalities. These 3 features are actually features of class effect of antisense. They're not related specifically to bepirovirsen. Thankfully, all these features resolved once bepirovirsen was stopped and including the renal function and the thrombocytopenia and the complement activation process, none of them were clinically significant.

There were no bleeding effects and renal abnormalities resolved once the bepirovirsen treatment was discontinued or paused. And also, there was no markers of renal injury that were related, particularly things like proteinuria. So I think safety monitoring needs to continue. But as far as the long-term safety is concerned, it seems to be a transient effect related to study treatment.

And maybe I can address the difference between a clinical trial in real world setting. When you go into especially a Phase III clinical trial, you don't know the outcome. So of course, we're going to measure and we're going to monitor more than you would in a normal setting once you know the outcome. So I wouldn't be concerned about the clinical trial monitoring that takes place right now. Now as we submit this data to regulators around the world, the regulators will decide what monitoring should or should not be in place. And in my experience as a drug developer, that may be a little different from region to region, but they will approve what is appropriate for the safety and efficacy for patients.

As far as HBsAg antigen testing goes, you are correct that quantitative HBsAg antigen is used primarily outside of the United States. However, quantitative HBsAg antigen is readily available inside the United States as a laboratory developed test. We use laboratory drive tests all the time. That's not a problem. It's available on Epic. You can order it, you can get it. And I think one of the things that we are going to see much like you do in many diseases, the patient wants to know whether the medication is working.

And this quantitative test is going to be able to give them that immediate feedback of how they're doing on therapy, which is going to provide extra motivation and compliance for them to finish the full 6 months of therapy. So I think what's going to happen in the future in the U.S., now that we have a reason to use quantitative HBsAg, you're going to see a significant uptick in that.

Yes. Sachin, I would just add on the testing. Testing in the U.S. is available. This is not some kind of novel test that is not available. And just from the execution perspective going into the launch, it's clearly our priority to make sure that physicians, whenever they want to use it, will be able to use it. It's just that the testing so far did not -- was not needed for diagnosis, treatment or anything like that. And therefore, it's used less or less available. But going forward, this is something that from the commercial execution perspective, it's a priority, and this is going to be changed.

Next question comes from Graham Parry.

I was just going to follow up on the testing question. So can you just confirm the frequency of testing -- of liver testing during the trial and why you think the regulator wouldn't require you to have the same level of testing because that may have masked additional ALT elevation. And then on commercial strategy, can you just talk us through how you're thinking about pricing commercial strategy just given the very large number of untreated patients, both across the U.S. and China. But just given the large numbers of untreated patients and even undiagnosed patients, can you just talk us through how to access that and how you think about pricing?

So I'm happy to take the testing question. I think what will happen, again, discussing the ALT, the platelet, the EGFR, I suspect what will happen around the world is that we will want to monitor those patients on a weekly basis for the first 12 weeks, and then it will loosen from there on out. But again, as I said, we can't really comment on exactly what the monitoring profile will be because the regulators will decide that on a country-by-country basis.

I'm going to make a quick point to put the safety data in context. Isolated ALT increases within the range of the fold increases in question without associated increases in bilirubin or evidence of liver injury. And in this setting, it tracks with efficacy and it's all mechanism. So you've got a boost in immune competence. It clears infected hepatocytes and you have an associated increase in ALT, which for those of you who are familiar, will remind you perhaps of the eGFR dip you get with SGLT2s, which is a marker of benefit and efficacy. But finally, I think the adverse events should be put in the context of a finite treatment, where if any effects are resolvable or reversible, that's a very favorable setting for benefit versus risk.

I will touch base on pricing. So our approach here is to access patients who are on treatment, who are being treated, who have desired to be treated, who are willing to go through it for whom physicians will recommend treatment. At the moment, our initial commercial approach is not focusing on going after all pool of diagnosed and let alone those who are infected but not diagnosed. So from that perspective, I think we mentioned before in terms of pricing for the U.S., we are looking at a price range that is similar to hep C space that we have seen. And so far, we have a very clear understanding that this is very acceptable price level from the payers in the U.S.

Next question comes from Ben Jackson.

I guess, can I ask for some further color on this 30% of patients that are achieving the antigen levels below 100 without the functional cure. You've made reference to the current antigen testing frequency in different regions. Does this mean that this kind of supportive data is more impactful in different regions, particularly ex U.S.? And how meaningfully could this mean that uptake is diverges between different regions as a result of that data?

Just to get some clarification, you're asking about HBsAg levels below 3,000?

Below 100 to be clear. And how meaningful is that data? And is there a disparity by region about how important that data is?

I see in terms of the effect of bepirovirsen, I think we don't know whether bepirovirsen treated patients with HBsAg levels below 100 are the same as nucleoside analogues treated below 100. So we'll need some long-term follow-up to determine whether that's the case. However, these patients are all of nucleoside analogue therapy. And after 6 months of nucleoside analogue therapy, they seem to have HBsAg levels below 100. So that's definitely a good sign. Some of these patients will continue to have HBsAg loss. So I think there's definitely a beneficial effect of patients below 100 IU/mL. Whether there's any regional specific differences, not as far as I know.

I think across the regions and across clinical studies, the 100 IU/mL cutoff seems to be holding on quite well.

I'd like to also point out from an R&D perspective, when we were designing this clinical trial, you'll note that the inclusion criteria only allowed patients to come in that were greater than 100. There was a reason for that. Patients who have less than 100 more naturally have a chance over several years to achieve functional cure, and we were concerned that, that would overly bias the outcome. So I think that in itself is evidence of this effect.

Just one final point that both the EASL and the AASLD guidelines were updated in the last 18 months, acknowledge that surface antigen less than 100 represents partial cure and is clinically important as a treatment goal.

Our next question comes from Zain Ebrahim.

So my question is on the efficacy and the potential breadth of label that you might receive given that -- so the ITT population efficacy looks really good at 19% functional cure rate and then in the less than 1,000 is 26%. But in that intermediate sort of patient subgroup, so 1,000 to 3,000 international units per milliliter, the functional cure rate was about 5%, 10% or 7% pooled. So just your thoughts on whether the data set you have, you think is sufficient to get a broad label covering the ITT population or whether that might be more focused on that less than 1,000 unit subgroup or and whether -- and even if you have a sort of broader label, how uptake could look?

Yes. Thank you for the question. I believe that what we'll see in this population, and this is the biology of the virus and the biology of the disease. As you go from 3,000 down to 100, it is a continuum of efficacy. So the lower the HBsAg has been seen as probably the strongest predictor of response. So what we want to be able to say about this is that when we designed the clinical trial, we specifically stratified on 1,000. But that 1,000 to 3,000 group will contain people who are 1,050, and it will contain people that are 2,998.

So it will be up to the physician to have a discussion with their individual patient as to whether the risk benefit of this drug is available. And I suspect from the feedback that we have heard from patients, a 7% functional cure is about what you see with pegylated interferon. And if you had a finite therapy that gave 7%, patients would be highly motivated to take that.

I see we have one more question in the queue. Zach, please go ahead.

This is Zach Dunn on for Seamus Fernandez from Guggenheim. Appreciate the question. So I guess I want to follow up on the 1,000 to 3,000 group because then at least based on the China functional cure rates, you're kind of falling in that peg interferon level.

So I guess when you compare then the side effects, can you provide any maybe qualitative color on those Grade 3 adverse events? Are they evenly split between the 2 groups? And then yes, if we can just kind of hear a little bit more on the risk benefit in this 1,000 to 3,000 population? Or does it really seem that this drug will most likely be used in 1,000 and below?

Thank you for your question. I don't have any visibility on the data comparing below 1,000 and between the 1,000 and 3,000. So I can't really give you an answer. But I cannot be sure that these AEs are related to efficacy. The primary AEs we're talking about, particularly the complement platelet reduction and the renal function were class effects of the antisense. So this might be a random effect on patients. As far as the ALT increase, maybe we can speculate that, that's more likely to occur in the 1,000 and below population, mainly because HBsAg loss rates are related to the level of ALT increase.

If your ALT increases more than 3x baseline, you have an 85% chance of HBsAg loss. But if your ALT is below 3x baseline, your chance of HBsAg loss is actually only 35%. So most of the patients who achieved HBsAg loss were below 1,000 IU/mL. So I suspect the ALT rises will be seen in that population. As for the other AEs, they're probably going to be more random.

Next question comes from Christopher LoBianco.

This is Chris on for Stephen Scala. Can you provide any comments on time lines for gaining payer reimbursement in the U.S.? And what sort of prior authorization criteria do you expect for bepi in the U.S.

The time lines for the U.S., we are expecting approval probably by the end of this year and then the traditional negotiation with payers that will be ramping up during 2027. And regarding the prior authorization question, we are expecting, of course, antigen levels as per label as part of it and also NA treated restrictions. So those are the main 2 that we are expecting right now.

Next question comes from Colin White.

It's Colin White from UBS here. My question was just around how we should expect bepi to launch in each of the 3 major markets which you outlined. I mean, is there expected to be a large bolus of eligible patients that physicians would want to treat with bepi soon after launch? Or are there other factors that you think might lead to a more gradual launch in any of those markets?

Yes. Good question and a question that we are also thinking about. And as you can imagine, we don't have full clarity. We do expect a certain bolus as there are already a number of patients who are being treated for years and some of them waiting to be treated. We probably do not expect that bolus to be not the scale of hep C that we have seen just because there will -- we will continue to have probably a significant number of patients that will maybe choose to wait or be suggested to be treated by their physician as they get more experience with bepi.

So it's very difficult for me to give you very specific trajectory. But bottom line, we do expect some bolus. We will need to see what that looks like, again, not expecting that massive rush to demand treatment as soon as the approval happens.

Next question comes from Emmanuel Papadakis.

Maybe just -- well, a couple. I'll take a follow-up question on the one that was just asked and more from a reimbursement angle. To what extent do you expect there to be -- which is also the -- to an extent, the question that was asked earlier about prior authorizations, to what extent do you expect there to be broad unfettered reimbursement rapidly after approval, particularly in the developed markets, U.S. and Europe?

And then the other question I was going to ask was B United. If you could just remind us your expectation for functional cure rates, what's your ambition in that study? It's Phase II. So is that potentially pivotal? Or would you then need to initiate Phase III?

Yes, Emmanuel, I'm not sure if there is too much to add on what has been said. We do expect certain requirements, certain prior authorizations. Again, I'm not sure there is more than what we have said already. I don't know, I'm looking at Pedro. Anything more to add. Obviously, U.S., as we mentioned, U.S., China, Japan are the focus markets because of the prevalence and because of the willingness or readiness to treat. I will focus on those at the moment.

Yes. So for B United, I just want to -- a minor correction. B United is not a pivotal study. It is a Phase IIb study, and we're expecting the data from that about middle of next year, and we'll see from there. I don't think we're ready to give guidance on what the expectation is.

But I think the point you made, Mel, earlier, is the key one that it broadens the eligible patient population to those with surface antigens not studied in B-Well.

Next question comes from [ Shyam Kotadia. ]

Shyam Kotadia on for Rajan Sharma from Goldman Sachs. Sorry, just a clarification question for one that was asked earlier. So at week 48, where you had the patients that discontinued NA therapy and those that continued it, could you clarify what proportion actually discontinued? And if there was any differences in the functional cure rates at week 72 for those that discontinued NA therapy versus those that continued on it from week 48?

Overall, 24% of patients discontinued Nucleos(t)ide therapy and 19% had HBsAg loss, 3% patients -- sorry, 4% of patients had DNA undetectable without functional cure and add 1% of patients actually had DNA relapse. So the number of patients that didn't achieve a benefit is only 1% stop nucleoside analogues.

And again, to remind you, the definition of functional cure is that you must cessate your nucleoside analogue. Now if you go back -- we'll provide you with the slides, obviously, later. But if you go back to the pie chart slide, you will see that there are some patients that wind up being HBsAg below 0.05, and that does sometimes happen, but you have to completely cessate nucleoside analogue to meet the strict medical definition of functional cure.

Yes. It sounds like there is confusion about this, just to reiterate what Mel just said. Patients who did not stop nucleoside analogues at week 48 by default will not be defined as functional cure. So all those that are in the 19% defined as functional cure, these patients all stopped their nucleoside analogue backbone therapy. Those who continue might have -- end up having undetectable surface antigen, but they are not falling into the category of functional cure.

We have time for one last question. Last question comes from [ Zain. ]

I think I still have my hand up, but I'll take the question. It's on the discontinuation and dose -- so the dose discontinuations and dose interruptions in the trial, just in terms of how feasible you think that is to manage in the real-world setting. It sounds like given the expectation for weekly monitoring, that should be reasonably manageable to implement. But just your thoughts on that discontinuations and interruptions would be helpful.

Criteria for dose interruption and discontinuations. So that's the setting of the clinical trial. I think for guidance purposes, probably it will be better to err on the safety side. So -- but the actual patients who discontinued permanently were actually quite few for ALT abnormalities, only 4 patients discontinued for platelet abnormalities, only 8 patients and for complement activation without any clinical effects, 9 patients.

So these were relatively infrequent, I would say. I cannot give you the numbers for those interruptions. They're probably going to be higher and likely that the adverse events were not as profound. But I think you're right. There needs to be some element of monitoring for these patients for safety reasons. So the weekly monitoring phase definitely needs to be done for the first 12 weeks.

Thank you. With this, I'd like to hand over to Nina to close the next call.

Thank you very much. We are at the hour. I really appreciate the interest. I just want to transmit the excitement here at EASL is actually very high. The data, as Kaivan said and Mel, are called transformational at a number of occasions. And from this point on, we have the next 6 months where we expect regulatory approvals in our major markets, and we are looking forward to sharing those updates as we get them. Thank you. Thanks, everyone. Talk to you soon.

Ladies and gentlemen, a warm welcome to the GSK's Q1 '26 Results Call. I'm delighted to be joined today by Luke Miels, Nina Mojas, Deborah Waterhouse, Tony Wood and Julie Brown, and in our Q&A session will be joined by David Redfern. Today's call will last approximately 1 hour with a presentation taking around 30 minutes and the remaining time for your questions. [Operator Instructions] Before we start, please turn to Slide 3. This is the usual safe harbor statement. We will comment on our performance using constant exchange rates or CER, unless otherwise stated. I'll now hand over to Luke.

Thank you, and welcome, everyone. Q1 performance was strong. Sales were up 5% to more than GBP 7.6 billion. Growth was driven by Specialty Medicines, which were up 14%, with vaccines also contributing particularly through strong Shingrix sales. Core operating profit grew 10% and EPS was up 9%. Cash generation was strong at GBP 1.4 billion. And our Q1 dividend declared today is 17p. Looking forward, we expect another year of profitable growth reflected in the guidance confirmed today.

Next slide, please. In February, we set out our priorities to drive value. We've made a good start, but we've got more to do. In a minute, Nina will share progress on how we're delivering growth, including the launches of Nucala COPD, Exdensur and Blenrep. We're also assessing our pipeline on an ongoing basis, the aim being to progress high potential assets more aggressively. As we identify differentiated profiles that fit an unmet need or address a gap in the market, we will then and are using scientific courage to make decisions in an accelerated way.

This includes internal development as well as BD. Now we're already making progress here with our assets in COPD, with our ADCs in oncology and with efimosfermin in MASH. Now we'll talk more about these and other high-value opportunities at Q2 results, and this will include an update on our HIV pipeline instead of an HIV-only event in June. Continuing to underpin this are our efforts to simplify how we work with greater pace, accountability and focus. I'll now hand over to Nina.

Thank you, Luke. Please turn to the next slide. Commercial momentum continued in Q1, driven by Shingrix and strong growth for key products across our specialty portfolio, which grew 14%. General Medicines was down 6% in the quarter, driven by declining sales of the older established portfolio. Trelegy performance did not offset the broader portfolio decline as its growth in the U.S. was limited by increasing co-pay requirements due to Medicare redesign. These are especially pronounced in the first quarter and are expected to be less relevant in the rest of the year. As Luke mentioned, we are focused on the products that drive the most value, including new launches and growth contributors.

Next slide, please. Shingrix was a key driver in Q1, setting a record for quarterly sales, delivering more than GBP 1 billion, up 20%. Quarterly patterns continued with strong sales in Q1, driven by Europe, where sales were up 51%, following uptake in national immunization programs and private market demand. And the U.S., where sales grew 12%, driven by inventory movements, including the launch of the new prefilled syringe.

Moving forward, this year, we expect tougher comparators for Europe and Japan as most large immunization programs annualize. Further penetration opportunities remain with around 11% of the eligible population immunized in our top 10 markets outside the U.S. In oncology, Jemperli was again a key growth contributor, delivering GBP 232 million, up 40%, driven by significant overall survival benefit in endometrial cancer.

At the Society of Gynecological Oncology, we presented data from a 4-year follow-up of the RUBY study, which showed an overall survival benefit over time with 66% reduction in risk of death for patients with the dMMR, MSI-high endometrial cancer. We look forward to the continued development of this medicine, including in rectal cancer with pivotal results from AZUR-1 in the second half of the year.

Next slide, please. Nucala also delivered double-digit growth in Q1 following its expansion into COPD in the U.S. last year. U.S. growth was driven by a broad COPD label and the halo effect on other indications. Total brand new patient starts are now at their highest level, growing 65% year-on-year, and we are accelerating momentum towards market leadership in COPD with around 45% of market share. COPD launches outside of the U.S., including Europe and China, have similar strong initial signals. For example, in China, we are already capturing around 1 in 2 new patients, representing a strong early launch in one of the largest markets globally with around 100 million people living with COPD.

In the severe asthma space, our focus is now on Exdensur for which access in the U.S. is still limited ahead of obtaining the J-code. Severe asthma is an area where significant opportunity remains as only 30% of eligible patients are receiving a biologic. The ultra-long-acting dosing of Exdensur is a key value driver with around 97% of patients preferring 6 monthly dosing versus current options. This is also valued by prescribers as they understand that longer dosing intervals lead to greater adherence and therefore, better outcomes. Currently, 65% of patients discontinued their short-acting biologic in the first 12 months. The next critical milestone in the U.S. is obtaining the J-code, which is expected early July, after which we expect access to be unrestricted.

Next slide, please. Moving to Blenrep, our community-ready antibody drug conjugate for multiple myeloma. Simple administration and overall safety remains a differentiating factor as 70% of patients are in the community and accessibility to competitor options remains a challenge. In the U.S., we now have a majority of use in the community, an important indicator of success as academic centers tend to be the early adopters. Our data showing an extended benefit versus standard of care is resonating as is the simplicity of our REMS and coordination of eye care professionals. The number of U.S. HCPs prescribing is growing with many repeating. Outside of the U.S., we have second-line approval in 19 markets, most recently in China, and we are progressing with launches in all major markets, including the U.K., Germany and Japan. And with that, I will hand over to Deborah.

Thank you, Nina. I'm delighted to share another strong quarter of double-digit HIV sales growth of 10%, driven by our long-acting portfolio in Dovato. Demand and market share increased across all regions, most notably in the U.S., where sales grew at 15%, with treatment market share outpacing the competition. In Europe, we continue to capitalize on our long-standing market share leadership position. Competitive execution is powering our portfolio transition to INSTI-led long-acting regimens, which consistently represent more than 70% of our total HIV growth and more than 1/3 of total U.S. sales.

With treatment accounting for around 90% of the total HIV market, we're delighted that Cabenuva grew 31% in Q1, fueled by patient demand. We also saw accelerated switches from competitor products, reaching 79% in the U.S. this quarter. Apretude grew strongly at 44% in the quarter, withstanding impact from a competitor launch and reinforcing the importance of our more than 99% effective, highly tolerable single-shot long-acting injectable for HIV prevention. We're outpacing the field with our patient-centered pipeline built on a foundation of long-acting integrase inhibitors, the gold standard of HIV care.

For 3x yearly Cabenuva for treatment, our CUATRO Phase III registrational study start is on track, and we expect to launch in 2028. Building on the success of 6x yearly Cabenuva, the first and only complete long-acting injectable for HIV treatment, we believe this potential option will establish a new standard of care, highly desired by patients and doctors whilst doubling provider administration capacity. Our 3x yearly Apretude for PrEP is set to redefine HIV prevention once again with registrational study data anticipated in H2 2026 and an H1 2027 launch.

We strongly believe this asset delivered through one injection with dosing frequency linked to routine sexually transmitted infection testing cycles has the optimal PrEP profile, better aligned to patient and HCP preference. At CROI, we shared data underscoring the strength of our pipeline assets, which we are evaluating for twice yearly long-acting injectable treatment, and we remain on track to launch by the end of the decade. Data for VH184, our first third-generation INSTI with IP protection through to 2040 demonstrated potential for twice yearly dosing and an enhanced in vitro resistance profile versus BIC.

Our capsid inhibitor, VH499, also showed promising potential for twice yearly dosing. This differentiated asset is highly potent and has a low risk of DDIs. And data for our bNAb lotivibart showed high efficacy for 3x yearly dosing when combined with monthly cabotegravir. We look forward to sharing twice yearly data later in 2026. As we advance our pipeline at pace, continue to deliver strong portfolio performance and prepare for our 2 upcoming 3x yearly launches, we are well positioned to manage the dolutegravir loss of exclusivity and drive sustained long-term growth. And as Luke said earlier, we will share more about the HIV pipeline at Q2 results. I'll now hand over to Tony.

Thank you, Deborah. Next slide, please. In R&D, our top priority is to accelerate development to deliver new products to patients faster. And as you heard from Luke, we've been taking specific actions to advance our most exciting opportunities. In 2025, we started 7 Phase III trials with 10 more starting this year. We're making bold investment choices to drive value in the late-stage pipeline. For example, our pivotal second-line trial in small cell lung cancer, EMBOLD-301 for Ris-Rez, our B7-H3 ADC is recruiting well.

We anticipate the expansion of the Ris-Rez program with a number of Phase III trials planned, including in genitourinary cancers, which start later this year. Similarly, for Mo-Rez, our B7-H4 ADC, we've recruited more than 200 patients into BEHOLD -1 and presented Phase I data for ovarian and endometrial cancers at SGO earlier this month. We have now initiated 2 Phase III studies with 3 more scheduled to start recruiting before the end of the year. More on Mo-Rez in a moment. StrateGIST-3, the first Phase III trial for velzatinib in second-line GIST started recruiting at the end of last year, less than 12 months after acquiring the asset.

A second Phase III trial in a first-line patient population will start in the second half. Elsewhere in oncology at ASCO this year, we have 5 oral abstracts accepted for presentation, including data from the DREAMM-9 study, which will inform dosing strategy for newly diagnosed multiple myeloma patients. This schedule will be employed in DREAMM-10 and in PrECOG, an upcoming cooperative group study. In RI&I, we acquired efimosfermin in May 2025, where our priority was to advance this asset into Phase III. Our 2 pivotal studies started last year, ZENITH-1 and 2 in F2, F3 stage MASH and are recruiting well with the NEBULA program for advanced MASH on track to start later this year.

Moving to pivotal readouts. We reported positive headline results for bepi during the quarter, which I will cover shortly, and we have 4 further Phase III readouts to come in the second half for Jemperli in rectal cancer, camlipixant in refractory chronic cough, Exdensur in EGPA and our 3x yearly pre-exposure prophylaxis for HIV. Lastly, our business development activities continue to complement and enhance our portfolio. In Q1, we announced 2 acquisitions, ozureprubart in food allergies and HS235 in pulmonary hypertension. Both have clinically validated MOAs and the potential to be best-in-class. These assets build on GSK's existing expertise in respiratory and inflammation.

Next slide, please. As I briefly mentioned, we've announced positive Phase III data for our functional cure for chronic hepatitis B, bepirovirsen. The B-Well 1 & 2 data show a statistically significant and clinically meaningful increase in the rate of functional cure and the full data will be presented at EASL in May. This outcome is important for patients because chronic hepatitis B infection is associated with high rates of liver cancer and an increase in all-cause mortality. A recent U.S. epidemiology study in hepatitis B patients showed that loss of surface antigen was associated with an 89% reduced risk of hepatocellular carcinoma and a 62% reduced risk in all-cause mortality.

Regulatory reviews for bepi are progressing well. Bepi now has breakthrough designation in the U.S. and a PDUFA date of the 26th of October and has been accepted for priority review in China. Commercial preparations are underway in these 2 markets, which represent around 2/3 of the commercial opportunity globally. Next slide, please. Turning to pipeline progress in oncology and our global BEHOLD- 1 Phase I study of Mo-Rez in advanced endometrial cancer and platinum-resistant ovarian cancer. Mo-Rez is a B7-H4 targeting ADC, and B7-H4 is overexpressed in many gynecological tumors with low expression in normal tissues.

In this dose escalation study, Mo-Rez showed encouraging antitumor activity. At the highest doses, confirmed ORR was 62% in PROC and 67% in advanced EC with responses observed regardless of B7-H4 expression. Durability of response data were also encouraging. In the highest dose PROC cohort, only 1 patient from 21 progressed within 6 months. Mo-Rez was generally well tolerated with low discontinuation rates and incidence of ILD. Only about 3% of patients reported mild to moderate pneumonitis. Based on these exciting data and additional data from our partner, Hansoh, we plan to start 5 pivotal trials this year in EC and OC.

Next slide, please. Elsewhere in our oncology portfolio, our partner, Hansoh, presented new Ris-Rez data at a plenary session at AACR earlier this month. The data are from a Hansoh-sponsored Phase I study called ARTEMIS-101, which looked at Ris-Rez in combination with PD-L1 in 40 patients with second-line plus non-squamous non-small cell lung cancer. The data show a 47% ORR with a median PFS of 14 months. The combination was generally well tolerated with Grade 3 adverse events mostly reflecting hematological toxicity consistent with similar ADCs. Four cases of treatment-related ILD were reported in the study, and these were grade 1 or 2.

These exciting data were used to support the start of a Phase III non-small cell lung cancer trial in China, and we plan to initiate a Phase II study for Ris-Rez in combination with Jemperli in a global population. Next slide, please. As I mentioned, accessing innovation through BD continues to be key to acceleration and growth. In February, we announced an agreement to acquire 35Pharma. Their lead asset is HS235, a potential best-in-class clinically validated activin signaling inhibitor to treat Group 1 and Group 2 pulmonary hypertension. HS235 is currently in Phase I development.

PAH is a progressive and life-limiting disease with high symptom burden and suboptimal patient outcomes. 5-year survival rates are around 50%. This is an underserved area in cardiopulmonary medicine with few available disease-modifying treatment options and significant growth potential. HS235 has the potential to treat patients while reducing bleeding-related side effects and providing metabolic benefits versus existing therapies. Entering cardiopulmonary disease complements GSK's commercial footprint, providing new opportunities to achieve broader coverage across the multiple chronic diseases, which affect the lung, liver and kidney. We successfully closed the transaction on the 15th of April and look forward to moving this asset into Phase II development at pace. I'll now hand over to Julie.

Thank you, Tony, and good afternoon, everyone. Next slide, please. Starting with the income statement for the quarter. Sales grew 5% and gross margin improved 110 basis points due to the growth of Specialty and Shingrix benefiting product mix this quarter. SG&A declined 2%, helped by positive IP settlements. On an underlying basis, SG&A grew 2%, demonstrating P&L leverage and continued productivity improvements. R&D spend was driven by accelerated investment in the pipeline, including the efimosfermin and velzatinib pivotal trials. We will continue to invest in R&D as we initiate multiple late-stage trials across our specialty portfolio. Royalties benefited from Abrysvo and Comirnaty income streams. And operating profit grew 10% in the quarter, including the legal settlements, which were worth 3 percentage points. EPS grew 9%, impacted by a higher tax rate and increased finance expenses, partially offset by the benefits of the share buyback.

Next slide, please. Turning to the cash flow and capital allocation. Cash generation was strong, albeit partially masked by the impact of adverse currency. CGFO was slightly ahead of last year with increased operating profit and IP income from the CureVac settlement, broadly offset by the timing of trade payables. Free cash flow benefited from the $250 million special dividend received as part of the changes to the ViiV shareholding structure. Looking ahead, we remain on track to reach our target of more than GBP 10 billion of CGFO with cash flows weighted as normal towards half 2.

Next slide, please. Strong cash generation and strategic actions have supported our capital allocation priorities with net debt at 1.4x EBITDA. Investments in BD primarily comprised the GBP 1.4 billion upfront to acquire RAPT Therapeutics. Shareholder returns totaled over GBP 0.9 billion, and the share buyback is on track to be completed at the half year. In the second quarter, we expect to have an outflow of $950 million for the acquisition of 35Pharma. And we are optimizing the portfolio and generating cash income to reinvest in the business, including the ViiV special dividend, the divestment of the Rockville manufacturing site and the out-licensing of linerixibat. These transactions will positively impact net debt by $1.2 billion in the first half, including linerixibat completed in Q2, yielding $400 million.

Next slide, please. Looking to the full year, we are confirming the guidance shared in February. In terms of phasing, we remain on track for our full year product group guidance with a few things to note. First, vaccines growth in Q1 benefited from the U.S. Shingrix prefilled syringe stocking. And from Q2 onwards, we will begin to annualize the publicly funded programs in Japan and certain EU countries last year. Second, Gen Med growth is expected to be half 2 weighted. Notably, in the second quarter, Trelegy has a tough comparator due to prior year true-up benefits and international markets are expected to remain challenging.

We still expect operating profit growth to be predominantly half 2 weighted given the phasing of productivity benefits. And you'll recall, we will also be comping the RSV IP settlement received in Q2 last year. Next slide, please. Turning to our road map, which shows our commitment to deliver. We've made a strong start to the year in terms of execution, pipeline and disciplined capital allocation, including the acquisition of 2 new high-potential assets. And with that, I am happy to hand back to Luke.

Thanks, Julie. In summary, we've made a good start to 2026. We're completely focused on managing the business to drive top line growth and accelerate the pipeline, and we're committed to taking the critical steps needed to do this. We look forward to updating you more at our Q2 results in July. Thank you, and we'll now move to Q&A.

[Operator Instructions] First question comes from Kerry Holford.

Nina, please one for you on Exdensur. On the slide you showed, you talked of around 65% of patients discontinuing short-acting biologics in respiratory within the first 12 months. So that seems higher than I might have thought. So I'm just interested to see if you've got more detail on why those patients are discontinuing? Does it relate to efficacy, safety, perhaps compliance difficulties relating to the monthly dosing? And then also what happens to those patients who discontinue? Do you see them return?

Yes, sure. So Kerry, there are a number of reasons, but one of them and a significant one is compliance and the requirement for frequent dosing, which, as you know, varies from every 2 weeks to every 4 weeks for short acting. What happens to those patients? They will usually go back to inhaled medicines and some of them eventually will -- might come back again to a biologic. I'm not sure what that proportion would be, but we usually characterize patients who have not been on a biologic for 12 months as new to biologic. But in a nutshell, a number of reasons, compliance being a significant part of that.

Next question comes from in Zain Ebrahim.

Zain Ebrahim, JPMorgan. My question is on the strategy update that you're expected to provide with the Q2 results. Just what could we expect to learn from you there in terms of your pipeline? How much emphasis should we expect from you on the midterm outlook to 2031 versus the longer-term outlook beyond 2031? And you've made comments at Q1 about -- or Q4 even about the HIV business, and we've seen the 6 monthly data since then. So could we still expect you to provide an outlook on how HIV might look in 2031?

Sure, no worries, Zain. I mean the -- we've obviously been very busy. There's been a very aggressive prosecution of opportunities to accelerate the late-stage pipeline. I direct you to the bottom right-hand corner on Slide 13 in Tony's presentation. I think it's a good summary of it. And so yes, I think the timing made sense at that point to take more time to lay out the whole portfolio. Both in terms of things that we can do that have a midterm impact as well as longer-term impact. And HIV will be embedded within that because, again, we want people to look at the total business in aggregate and the progress that we're making there. So yes, I think that's a good summary at this point. Thanks, Zain.

Next question comes from Graham Parry.

Great. It's a question on bepirovirsen. The PDUFA is coming in October. We've got data coming at EASL. Perhaps you could just outline the opportunity you see for the molecule. Do you see it more as a high-priced U.S.-centric asset or lower-priced, higher-volume asset across China? And can you achieve differential pricing across the regions? And on label expectation, are you expecting a label for the broad population or just the low hepatitis B surface antigen group, I think it's less than 1,000 international units per mil population that you flagged in the headline press release has better functional cure rates?

Sure, no worries. Nina, do you want to -- or maybe, Tony, if you go into the -- maybe the data EASL reg pathway and then we can get to the [indiscernible].

Yes. So Graham, I'm not going to get into the details of the label. But just to remind you that the B-Well 1 & 2 studies were chosen from the population that had a surface antigen level of 3,000 or less. So I think it's important to understand that the complete B-Well population will cover that broader group. That's about 65% of the ITT population. The 1,000 group is about 45%. And as I've said in the past, the data we have suggests that there is a relationship between surface antigen level and outcome, but you shouldn't interpret that as being a linear one.

Yes. And I mean, the other thing I'd add before Nina, if you want to add anything else, if you look at the 1,000 cutoff surface antigen is about 45% of the population. U.S. patients, the bulk of them are vertically infected. It's around 1.2 million, of whom about just over 300,000 are on treatment today. Europe is a little more in terms of 1.4 million and yes, about 200,000 on treatment. China is much larger in terms of 57 million sort of infected, but only 16 million are diagnosed and they have much greater usage of pegylated interferon there.

So yes, I mean, the treated population is around 10 million. But what we're being thoughtful about is particularly the strategy in China. I think the strategy in the U.S. and Europe is very clear. What we're reflecting on very actively is the pathway to launch in China. Nina, anything you want to add on that?

Yes, maybe I can just add. So the way we think about it is the way we see the opportunity, about 70% of the opportunity are between U.S. and China as Luke mentioned, U.S. in hundreds of thousands in treated patients diagnosed are probably only about 1/3 of the total. And the way we see the opportunity now reflects really those patients who are currently treated. Those are patients who have high desire to be treated. And again, still in the U.S., U.S. market is highly focused on relatively limited areas. So there are about 5 states in the U.S. where hep B is prevalent and treated, and these are unsurprisingly states that have relatively high number of immigrants from Asian and African countries.

And those who are treated clearly have access to treatment. So this is unlike hep C -- this is patient population that have insurance that have means to be treated and then have desire to be treated. So that gives you a little bit sense about where we are going and how we are going to approach that. It's quite focused area geographically. In China, about 70% of patients or patient of potential market potentially is in about top 15% of the accounts. So again, very focused approach in a country where hepatitis B is considered to some extent to be a stigma with very high desire of treatment. That's why you have very high use of interferon, which is not a pleasant drug to be on for a very long time.

And then just one more -- Graham, one final point to finish off. Remember, we said before that 15% to 20% functional cure across the population would be considered clinically meaningful, and that's reflected in the expedited designations that we're getting, including the most recent one, obviously, from the FDA.

Next question comes from Rajan Sharma.

Just one on HIV. And obviously, we're expecting some competitor data for a once-weekly oral treatment option this year. Some of the physician feedback that we've had suggests that there'll be strong demand for that. So Deborah, just wanted to understand how you think about that from a ViiV perspective in terms of near-term impact? And then ultimately, do you think that, that is restrictive to an ultra-long-acting injectable?

Yes. Thanks, Rajan. So in terms of the once-weekly oral that's being launched for next year and later this year, I think, is islatravir plus lenacapavir. So I think what we have communicated is critical to successful regimens that are robust in HIVs having an integrase inhibitor at the core. Today, about 85% of people globally are an integrase inhibitor-based regimen. And certainly, where we've got 2 drug regimens such as Dovato, having an integrated at the core, I think, is pretty critical.

So I think it will be interesting to see the data. But I think for me, when you get to really outstanding weekly orals, it will be with an integrated at the core. And then, of course, there are -- let's see where we are with islatravir. Obviously, we've had -- we've seen challenges with islatravir at higher doses in terms of depletion of CD4 counts. And I think physicians have questions about longer term, will that manifest itself even at a lower dose if somebody is on this medicine for a long time. However, undoubtedly, there will be some uptake.

And all the research that we've done says that the weekly orals cannibalizes the daily orals. Actually, our research shows that it doesn't impact long-acting injectables because that is a very specific patient segment where you've got people who struggle to adhere who really feel very stigmatized by taking a tablet every day or are really worried about people discovering their status as well as obviously the benefit of directly observed therapy. So I think the long-acting injectable segment won't be impacted by the once weekly, but the daily orals are most likely to be.

Next question comes from Sachin Jain. You might be on mute. We're just trying to unmute Sachin. I think you dialed in via phone.

Sorry about that. Hope you can hear me now. Two quick questions, please. One on CALM, I'm sure you're expecting this, level of excitement headed into CALM-2 with CALM-1 in-house, I guess. And then secondly, on HIV, one of your key narratives, obviously, Luke, and R&D team is acceleration of key assets. Given the importance of long-acting injectables, just wondering if there's any scope to shorten or skip the Phase II work around Q6M combos and accelerate Phase III such that launches are ahead of, I guess, a 2030, '31 time line?

Sure, Sachin. I think you get a pass on 2 questions. I think you asked a question last time. So Deborah, super quick on acceleration options and then Tony on CALM, please.

So Sachin, we are looking to accelerate through execution and delivery of our Q6M or twice yearly in treatment and in PrEP. The FDA will not allow us or anybody else actually to skip the Phase II part of the development journey. We have to demonstrate the level of efficacy, safety as well as the kind of appropriate partner for our Q6M. So we'll go through the journey of development to demonstrate all of that, but we're in dialogue with the FDA, and there's nowhere we can skip the Phase II.

Thanks, Deborah. Tony?

Sachin, Look, as you'll appreciate, only a small number of people inside GSK have seen the CALM-1 data, and we'll update you all when the CALM-2 data is in-house. It's on track. We have last patient, last visit has already occurred. So we're very much on track for publication around the middle of the year, as I've indicated. And perhaps just a reminder for everyone, here again, 15% to 20% reduction relative to placebo in Phase III at 24 weeks would be seen as significant.

Next question comes from Matthew Weston.

It's actually a follow-on to Sachin's secret second question. Deborah, in your opening comments, you expect confidence in the long-acting 6-month treatment regime on the market by the end of the decade. But given that we haven't yet achieved 6 months IM dosing for VH184, I have to be honest and say we're struggling to get to that time line. Sach asked if you could accelerate it and you said no. So can you walk through the steps for development gives you the confidence in being there at the end of the decade?

So we've got Phase II program, which has already started for VH184 because I think what people sometimes think is when we present the data at CROI, that's where we are in the process. We've already started the Phase II-A, which is the oral step we need to go through with VH184. We're expecting the VH499 Phase II to start in the second half of the year. And then basically, we would be starting the Phase III, which we are in dialogue with regulators over as well as our Phase II program in 2028, and that allows us then to generate the data that will give us an end of decade launch.

So that's how everything is set out at the moment. Obviously, you talk to the regulators every step of the way as you design your clinical trials, you agree the endpoints and then you move on to the next stage. So as we stand here today, the dialogue that we have had with the regulators, the Phase II program that we are in the process of agreeing and our proposed Phase III would lead us to an end of 2030 approval.

Next question comes from Peter Verdult.

Pete here from BNP. Just one question, just a follow-up on bepi ahead of EASL. In fact, there's a massive disconnect between your ambition in terms of commercial ambitions for the product and I think consensus which is only a couple of hundred million baked in. I realize we cannot go into any B-Well details, but I would like to understand how GSK thinks about getting surface antigen testing part and parcel of standard practice. KOL feedback tells us this is rarely done presently.

And then in terms of the checks that we've done with the community, they seem to be pointing to a sort of functional cure rate near 25% for the infusion across the community to be really high. I know it could be static anywhere between 15% to 20%, but anything you're willing to say on testing? And what is clinically meaningful from the docs you speak to as we await the EASL data?

Sure. No worries, Peter. I think very fair questions. I mean, structurally, we've seen this in multiple disease areas. If there's no solution, there's no point looking for the problem. So many of these patients, if you look at the U.S., diagnosis rates, a prevalence of 1.2, I said before, only 500,000 are diagnosed in Europe is a similar ratio. Japan is probably the best of all of them.

But our expectation is and the feedback that we've got is that once you've got the accessible treatment option because the downstream consequences of this infection are deeply unpleasant, for the individual and the health care system, we expect that testing to increase. Nina, I don't know if you wanted to add any of the work that you guys have done to assess this or any other insights?

Yes. And Peter, I'm not surprised. This is a new, in a way, new approach in treatment of hepatitis B. So a lot of these things are obviously very known to us as barriers like antigen surface testing, like diagnosis. And we will -- we are going into that very -- with eyes wide open, aware of that. But what is very obvious is that there are reasons why people are -- want to be treated. It's a reduction of hepatocellular carcinoma, first thing.

The other one, just stigma of hepatitis B. And that comes with available options for treatment that are lifelong and patients or physicians are not very keen on lifelong treatment. That's a big, big motivator to change. Testing will -- is available. It's just not used because it doesn't help with anything. It doesn't guide current treatment. It's not required for initiation of treatment. As soon as there are options that are requiring testing, we believe that is going to increase.

And just the last one, I think we just need to remind ourselves, reduction of DNA at the moment is the standard, which is followed in practice. For patients who have reduced DNA and who have also reduced antigen level expression, their risk of hepatocellular carcinoma is dropping by over 70%, close to 80%, so it's a very significant driver of medical value and benefit. And that's what we see in the initial conversations with the regulators.

As you can see, we have SENKO designation in Japan. We have breakthrough designation in the U.S. It is very much recognized by the health care authorities. We are going into this into what is a new way of treating this disease. And I think you need to allow us also a certain level of, well, uncertainty how this is -- how quickly this is going to be realized. But definitely, the value of the drug is very clearly recognized.

And then just a reminder on functional cure rates because as Nina mentioned, the current broadly used approach is nucleoside and nucleotide therapy for which the combination of DNA and surface antigen reduction for functional cure is less than 2% for a lifelong therapy.

Yes. And if you look at pegylated interferon, Peter, as you know, I mean, it's 12 months of treatment and flu-like symptoms for between 2% to 4% resolution. In China, experts would state it's slightly higher, but a heavy burden on the patients. So as Nina said, we're being very thoughtful about this. And -- but there's a high commitment to this asset. And I think we've got something that will get experts attention at EASL. So let's see.

Next question comes from James Gordon.

James Gordon from Barclays. The question was about Exdensur. So the early launch progress, I know it's early and whether you are seeing any switching from existing more frequent IL-5. I know there's the nimble extensive switch trial that showed Exdensur was inferior to Nucala. So does that mean it's harder to get switches? Or are you still seeing some people do a switch? And just what do you think this launch will look like once you get the J-code? I can see how that can hold it back a bit.

But then once you got the J-code, would it still be quite slow and steady because you're only then really going for the incident, not like the people are already on biologics if you're not switching? And if I could squeeze in a follow-up because a few other people did. Just on camlipixant, I hear the comment on 15% to 20% benefit of Phase III being significant. But I think the Phase II was about twice as good as that. So why would it be so much lower? And isn't the 15% to 20% pretty similar to what Merck had with their P2X3 that ultimately, I know there's some differences, but ultimately, that wasn't approved by the FDA with about a 15% to 20% benefit.

Sure. So James, I'll answer the second question super quickly. So I think the key thing is duration of effect and also the placebo adjusted. That's the operative term. And the element with Merck's product really was the off-target effect, in fact, it's a much more promiscuously binding molecule in terms of addressing the receptors of P3X3, which are present in the taste buds. And so you get this taste dysgeusia, which unblinded the product and also limited their dose selection.

So you had higher disturbance toxicity and lower efficacy plus some regulatory issues around cough monitoring. So I think we're talking apples and pears there, but we've taken those lessons and integrated them into not only the assessment of the clinical program, and we're looking forward to getting those results. Tony, do you want to go through Nina then go through where we are commercially with the launch and then I'm happy to add anything else.

Yes. So let me just -- first of all, a little bit about NIMBLE and its design. It was a nonregistrational study, so not a filing requirement. And what's important to understand about the population in NIMBLE is they were very well controlled. So the general exacerbation rate was low. It was not designed to make comparisons across switch in the various arms. And in fact, if I allow that comparison to be made, the absolute -- sorry, the difference in exacerbation rates was 0.08 per year.

If that implies that a patient on therapy would need 12.5 years to realize a single additional exacerbation. And you put that into the context of the benefit for compliance that's associated with the longer-acting agent. As Nina answered earlier, I think you have the importance of depemokimab as a long-acting agent in that population. I won't go any further on that, but the study was not designed to draw the conclusion that you have, James.

Thanks, Nina?

Yes. Just to add. So at the moment, the number of patients that are initiating actually about 70% of them are coming from other biologics. In terms of the question, and obviously, we would want majority of the patients to be bio-naive. Just your question about are we looking at just the incidents. Remember, only about 30% of patients are on biologic. There is actually way more patients who are bio-naive than those who are bio-exposed. So there is a significant pool of patients who are available.

In terms of access and J-code, so this is a therapy area where J-code is very relevant. We -- it is going to unlock vast majority of the market at the moment, only about 20% of the commercial patients in the U.S. have access, and this is very normal in this therapy area. J-code is really a significant barrier initially and then it opens the opportunity as the J-code becomes available.

Yes. And James, I'd just add some other market research, which I think is quite encouraging. So if you look at who's prescribing at this point, about 57% of the patients prescribed by pulmonologists, about 23% by allergists, which is in line with what we expected. Unaided awareness is ahead of benchmarks and the intent to use is nicely at benchmark and the main driver is questions around access, which is what we expect, particularly when you're buying a 6-monthly treatment. So we've got that approach, but obviously, the [ ungating ] factor is the J-code.

And actually, if you look at the T2 faith and belief in terms of sustained suppression of the key T2 drivers, this is beyond other biologics at this point. So we're quietly assembling the pieces which will drive usage of this product. But very similar to Blenrep, I think we need to wait until we're into the second quarter before we can give you the full picture. Also, we've just started launch in Japan. I was there the other day, very good traction. And Germany was also there the other day, and they've got good traction and good start already. So I would say we just need to keep watching this space and stay focused.

Next question comes from Sarita Kapila.

Recently, there was a change to the Florida ADAP. So Biktarvy access was removed and Descovy was restricted. So how should we think about this change in the broader signals for HIV reimbursement in the U.S.? Is there any risk that we see similar changes elsewhere?

Thanks, Sarita. Deborah?

Yes. So thanks for the question, Sarita. So ADAP is the safety net program for people who are living with HIV who do not have insurance. And because states are strapped for cash. They are looking at ways to save money on ADAP. And what Florida did was 2 things. They reduced the threshold by which you were able to access ADAP and they restricted Biktarvy and Descovy. There was a court case brought immediately by the community around the threshold at which you can enter ADAP and they weren't. So it went back to being 400% of the poverty threshold versus 150. So that was reversed.

But there is the opportunity and that always has been actually to sort of tighten the formulary. And that is currently taking place in Florida, and we've seen people switching off Descovy and Biktarvy onto other medicines, obviously, Dovato and Cabenuva as well. So I think this is an area of focus as it has been for a while. I think the court case that was brought immediately by the community was very helpful because the threshold of when you can benefit from ADAP was not successfully reduced.

But I think we should expect other states to look at ADAP and to make sure that it's being run efficiently and effectively. But overall, I don't think you're going to see a reduction. I think what you might see is some changes to formulary. But as we know, it's very guideline-driven therapy area. The community are now pushing back at the restriction of Descovy and Biktarvy. So that may in its own right, end up being reversed. But at the moment, that is still in place.

Next question comes from Michael Leuchten.

If I could please just go back to the Q2 business update. Just trying to understand, is this meant to be a comprehensive review, both top line and bottom line trajectory? Or is it meant to be a portfolio update around the pipeline, including ViiV, please?

Thanks, Michael. The latter. I mean we've found in the past when we do meet the management events as stand-alone, they're useful to get granularity, but the portfolio is becoming broad enough and complex enough. We thought it would be helpful for you and shareholders for us to step you through why we're so enthusiastic and what we've been doing with our time over the last few months in terms of accelerating these assets. So that's the intent and to give, yes, just greater granularity, more depth on the data.

Next question comes from Simon Baker.

A slightly broader one, just going back to one of your opening comments, Luke. You talked about accelerating pipeline delivery. I wonder if you could just sort of dig down and give us a little bit more color on that. Is that about changing decision-making processes now? Or is it about changing development practice and trial design going forward? So just some color on what that phrase means in reality would be great.

Yes, sure, Simon. And I always make damn sure I attach any statement to something that we're actually doing in practice. So be short of that. What does that look like? So every 2 weeks, Tony, Nina and myself, Mondher and Deborah, if it's HIV with David. We look through all the clinical execution, look at what studies are on track, which are not. And then it may trigger a discussion around the protocol design, the execution on the ground. The meeting then may pivot to some life cycle opportunities that we've got, if Julie found some money under the bed that we can accelerate those programs and the economic justification and the clinical justification for doing that.

So very dynamically managing the portfolio. But again, we're not sort of writing e-mails to each other and 10 layers of management. It's us interacting directly with the team leaders who are managing those programs and looking them in the eyes and they get to look us in the eyes about what -- where the program is at, what's going right, what's not going right and how do we fix it? Or if there's an opportunity, how do we exploit that without having to sort of have onerously endless meetings to discuss that. So out of that, we're creating a more aggressive culture in terms of pursuing opportunities, but also one that people have to back up in what they're doing with the facts or at least a logical explanation scientifically, clinically why that may be a good decision to make.

And then we want to gauge the level of risk we're taking. So it's really everything that you're saying. The core focus is I strongly -- and you guys know this better than me, I strongly believe the way that we're going to create value is to accelerate what we have in the late-stage portfolio and get it to patients faster in a more broad fashion if there are opportunities for life cycle management. and then translate that into faster top line growth and commercial success. So -- and if we do that, we should be creating value for our shareholders. So that's how it works. We also have other ways, again, to redirect resources. And if we see something not working, we either fix it or take the resources away and give them to someone else. So it's a Darwinian process, and it's designed to transparently create value.

Next question comes from Steve Scala.

A question on Shingrix with 3 brief parts. First, can you quantify the magnitude of U.S. inventory stocking? Second, are things improving in China? And thirdly, it seems like you're all in on dementia starting a 34,000-patient trial after being cautious for a long time. Is that how to read it?

Great. Thanks, Steve. So I'll answer the inventory one pretty quickly. And then maybe, Nina, if you wanted to cover China. I mean if you look at the U.S., the IZ right now is around 45%. So that's up 3.5 points versus same time last year, which is in the range that we gave you of 2 to 4 patient points each year. If you look at the remaining effort, there's about 70 million people above 50 who remain unvaccinated. About 1/3 of them have intent to get vaccinated. That's material based on the market research.

But again, we're concentrating on the comorbid subpopulation that are more motivated and their doctors and pharmacists are more motivated to do that. All the market research on pharmacists and doctors is stable. In Q1, actually Shingrix was the #1 priority for pharmacists to vaccinate, which is same as last year before we get to the flu season. In terms of stocking, we did launch the PFS to fully liquid in '26. It's easier for pharmacists. We don't factor any demand increase because of that, but it's just easier for the pharmacists to employ it. The wholesalers were pretty steady. So Q1 26.6 million doses.

If you look at the end of last year, it was 0.5 million. If you look at same time last year, it was 0.4 million, so very much in the typical range. There is some increase in retail inventory. So -- and that's associated with the PFS. So it was 2.4. If you look at same time last year, it was 1.7 million doses and at the end of 2025, which is not necessarily a fair comparator of the flu season, 1.4 million. So stocking has a component there, but we're also seeing reasonable underlying demand following the strategy of focusing on comorbid. Nina, anything you wanted to add on U.S. or China, and then we'll go to Tony.

Yes. So just briefly on China, the number of doses administered to patients is increasing. So that demand is improving. You will not see that in the sales numbers because that's going out from the available stock at. Probably for this year, at least majority of this year, we would not see sales numbers changing on the GSK side as that stock is being reduced.

Thanks, Nina. So work in progress very much in China. Tony?

Yes. And Steve, on [ Fin ] dementia, I would say this is just the latest in the plan we described. It sits alongside both study that we have running in the U.K. and now a pragmatic study in Finland to give you some details, this is dementia diagnosis. And as you said, around 30,000 individuals. It's Shingrix versus placebo study and the data capture is largely passed through a registry basis. It's on a 3-year follow-up. But I would look at it very much as just the next example in what will become a collection of studies that explore outcomes with Shingrix in both dementia and indeed outcomes that I'm doing in partnership with Mondher and the med affairs team.

Yes, I would stress that MACE component, Steve. Great. Thanks for your question.

Yes. We have time for 2 more short questions, please. Emmanuel Papadakis.

I'm tempted to ask Julie about the money under the bed, but I'll take one on Jemperli. Maybe you could talk a little bit about the softer Q1 relative to expectations after a pretty strong run of results. Particularly interested in how endometrial and rectal outlook is shaping up. I mean you do have AZUR-1 and 2 pending, but they're in the MSI-H setting and you already have a tumor-agnostic MSI-H label. So I would imagine they're going to have pretty limited impact. Is it going to be JADE in head and neck that really catalyze the next step up? And what's the sort of quantum of commercial opportunity there?

Great. Thanks, Emmanuel. Nina, do you want to cover?

Yes. Look, I think we have talked about this before. We -- of the EUR 2 billion that we have communicated externally for Jemperli endometrial cancer is about EUR 1 billion and then colorectal and head and neck is the -- we see it as another EUR 1 billion. And at the moment, we are on track for that. AZUR-1 is going to read out later this year, very high belief and confidence that -- that's a positive study as we have seen already. So -- and then to obviously significantly higher opportunity in head and neck definitely.

Yes. And I'd add, Emmanuel, we've still got a lot to do operationally in the U.S. in terms of endometrial. If you look at the stats, about 60% of oncologists just used Keytruda despite the overall survival. So we've got plenty of area to target those individuals, and we do have their market research that if a physician can recite the survival benefit, they're a lot more likely, obviously, to use Jemperli. So again, we remain very committed to this product and look forward to updating you as we get those readouts.

Just to complete the picture as well, we have the chemo-free study in EC, which you'll have data this year as well as looking to expand the population there, too.

Last question, correct?

Exactly. Last question comes from Seamus.

So just quickly, I wanted to get a sense on Nucala and the uptake there. Where are you seeing the emergence of sort of broader utilization? And how do you feel that actually positions Exdensur over time in that opportunity?

Thanks, Seamus. So about -- if you look at the growth of Nucala in the U.S., about 50% of that volume is from COPD. Globally, it's about 1/3. And then you've got EGPA, HES and other indications for Nucala more broadly. But as we launch Exdensur, we take the resources of Nucala, excluding COPD. So we have a team in the U.S. who's still promoting COPD and doing quite well, as you can see, but all of the other indications are no longer promoted.

We're 100% committed to Exdensur, and that's the strategy. And I'll just come back to the relative volatility of these patient populations, which I think surprises everyone and creates a degree of churn that we're looking to exploit with Exdensur. So great. I'll stop there. Hopefully, I answered your question, Seamus. If I didn't, I'm happy to follow up offline. Thanks, everyone. Appreciate your interest in the company, and I hope the question-and-answer session was useful. Thank you.

Good morning, everyone, and thanks for joining on day 3 of our Biopharma Innovation Summit. Very pleased to start the day this morning with a fireside chat with Kaivan Khavandi, who's Head of Respiratory, Inflammation and Immunology, R&D at GSK, quite a lot of disease areas there.

So Kaivan, thank you for joining us. Maybe just to kick off, if you could just give us a brief intro on yourself and your background, which just for people who may be less familiar.

Sure. Yes. So I'm a physician scientist, trained in inflammatory mechanisms of cardiopulmonary risk, had a lab at King's College London, and practice at Guy's and St. Thomas'. I've worked in the industry across large pharma, Pfizer, GSK, across I&I, internal medicine, cardiovascular medicine and also a brief stint at BenevolentAI as CMO. And at GSK, I lead an organization that spans from target concepts through to approval for Specialty Medicines, as Rajan said, spanning respiratory, immunology and inflammation and also lead an organization across enterprise at GSK for translational sciences.

Perfect. So within those areas, there's obviously a lot of catalysts this year. And maybe we'll start with camlipixant. So we've got the Phase III readout coming later this year. Before we get into the details, can we just talk through the opportunity in chronic cough? I think it's something that's still debated amongst investors and in the market. So it would be helpful to get your perspectives there.

Yes, sure. So chronic cough is very prevalent. Refractory chronic cough has a prevalence of about 40 million globally and is debilitating. This is a cough that's defined as lasting more than 8 weeks, but actually in many of those individuals relates to a bouts of cough that are frankly incompatible with normal life, 100 coughs an hour. You can imagine what that looks like if, for example, if I had that symptom now, it would be -- it wouldn't be feasible, obviously, to participate in this panel, you're driving on a motorway. And the consequences we see from that as well as daily activities of living is things like incontinence, rib fractures. And interestingly, even in our own program, we can see the patients that are being recruited into the study have been on some mad things like opioids and neuropathic meds. So the patients are desperate. There's a significant demand for a safe and effective medicine.

But the other point I'd add is that if you go to any academic respiratory center, there will be a department that's focused on obstructive lung disease. There'll be a department that's focused on interstitial lung disease and there'll be a department that's focused on cough. So the respiratory community is already heavily invested in that space, but they haven't had an effective therapeutic. So whilst it might feel novel to investors and to some degree to large pharma, actually, the demand has been there for decades.

Okay. And then maybe just in terms of the target product profile, could you just run us through there? So with Merck's gefapixant, which is obviously the same mechanism, there was a 15% reduction in placebo-adjusted 24-hour cough frequency at 24 weeks. Is that a fair bar for camlipixant?

Yes. So if you think about a 15% relative risk reduction and you're talking about patients that have in our study have been enriched for those with over 20 coughs per hour. It relates to a very clinically important difference. Gefapixant to many -- to a large extent, actually derisk the efficacy of the pathway as you described. But obviously, in the U.S., at least, we're unable to translate that into a compelling benefit risk proposition. Obviously, their program was compromised because of the lack of selectivity for P2X3 and the taste disturbance is problematic. But the 15% threshold, we believe, and this has been substantiated by investigators and the external community is certainly clinically important.

Okay. And the other thing that's notable here is that if you look at the Phase II data, both for gefapixant and for gefapixant and camlipixant, you're at sort of 30-plus risk reductions. Why would that be lower in a Phase III trial?

I mean if you think about refractory chronic cough in the context of analogous diseases like pain or maybe IBS, migraine, there is almost universally a discounting of placebo-adjusted efficacy when you move into pivotal programs with longer treatment duration. So that is a placebo-adjusted target value. The change from baseline, we would probably expect to be similar to the data you described in Phase II. So it's really a function of the operating characteristics of a pivotal program.

Okay. And then I guess the other thing looking at the Phase II, so the camlipixant data, which was, I think, run by BELLUS right before the acquisition, that was a reduction at week 4 versus gefapixant, which used a 12-week endpoint. And again, it was kind of comparable reductions. Is that speed of onset important here?

Yes, I think so. And again, as a sort of base assumption, we might assume similar efficacy to gefapixant, but the benefit risk calculus is different because of the selectivity. But I think speed of onset is important, durability of response across, obviously, the primary efficacy time points designed into CALM-1 and CALM-2, which is up to 24 weeks is important.

Okay. And then just on that tolerability, so taste disturbance. Obviously, it's clear from the Phase II that camlipixant has a lower rate of taste disturbances there. But what do you think is acceptable from a clinical perspective? And then obviously, just bearing in mind that there were some issues with the gefapixant AdComm around whether that trial was actually sufficiently blinded.

Yes. So gefapixant experienced a very problematic level of taste disturbance. It was over 50%, I think, over 60%. And imagine running a study where you're meant to be blinded to the active arm. And 6 out of 10 of those patients are experiencing taste disturbance. So highly problematic for the conduct of a pivotal well-controlled study. That hasn't been a problem for us. We see the blinded data, it's low. And -- but in terms of what's acceptable then for patients, we're expecting based on the order of magnitude greater in fact, 100-fold greater selectivity, we were expecting an order of magnitude lower problematic taste disturbance and almost no taste disturbance that would result in discontinuation. And we're confident that's the profile we're going to see. So that would relate to 7% or less. I expect we'll see even lower level of taste disturbance with camlipixant.

Okay. And then just switching to the Phase III, which expected this year. So there's CALM-1, there's CALM-2. Can you just go back a little bit and remind us what the rationale is for 2 trials here? And then also why CALM-2 is now reading out later than CALM-1?

Yes. So BELLUS initiated the studies. And so given the environment they were in, they were staggered. So that's the only reason why CALM-1 and CALM-2 are not reading out at the same time. Since we took over the studies, we have increased the sample size for a couple of reasons. One was that there's an appreciation that as part of the gefapixant AdComm, the FDA would want to see data on patient-reported outcomes with an appropriate clinical instruments, which we've introduced into the study with the chronic cough diary. And so as well as powering for 24-hour cough frequency, it's a quantitative measure, we wanted to make sure we were able to evaluate measures related to the CCD. So that result in increase in sample size from, I think, 600 and something to over 700.

The second was really a positive interaction we had with the FDA, which was to agree that we would enrich the study 3:1, 3 being the proportion of patients with over 20 coughs per hour at baseline and the remainder being 8 to 20. And so again, to translate that ratio forward, we had to -- we then increase the sample size further. CALM-1 is completed. CALM-2 has actually -- I saw your comments, Rajan, beforehand. CALM-2 has completed enrollment. We just -- it's open on clinicaltrials.gov because of the long-term extension.

Okay. So you beat me to that question. And then just on that enrichment, is that both in CALM-1 and CALM-2.

Yes.

Okay. And then the other thing -- the other difference in the studies is obviously the timing of the endpoints. So CALM-1 is cough frequency at week 12. CALM-2 is cough frequency at 24 weeks. Could you just kind of talk to the rationale for those 2 different endpoints? Is that an FDA requirement?

That's what we had agreed -- that's what was agreed with FDA end of Phase II. There's obviously limited precedents for refractory chronic cough. But given the characteristics that I described, I think it was important to have confirmatory efficacy in a second pivotal study. I don't think there's a line in the sand in terms of what primary efficacy you would need to go up to for -- to demonstrate benefit risk. Obviously, in one study, we've got 12 weeks. We felt that 24 weeks was an appropriate time point to support durability of response. And then obviously, the second point is ensuring there's an adequate safety database for the file.

Okay. And then just on the 2 data, the trials again, is there the requirement from the FDA that you need 2 positive trials to file here?

Well, again, limited precedents. We'd agreed with them that we would conduct 2 pivotal studies. We'll evaluate the primary efficacy individually in each study. We will, of course, then pull data. As you know, the FDA's lens will be one of benefit risk, and they'll look at a range of efficacy measures and safety measures. So I suspect we would obviously pull across the 12-week endpoints across both studies and then look to what we can substantiate from 24 weeks with CALM-2.

Okay. Sounds good. And then just on the trial eligibility. So there's refractory chronic cough and there's also unexplained chronic cough. Are you confident that you have enough sort of a dispersion of both of those patient groups? And how should we think about potential differences in efficacy, if any?

I wouldn't expect to see differences in efficacy. Again, what we've characterized as the population there's a high burden of cough. Everybody in the study has at least 8 coughs per hour at baseline. We've been clear in terms of exclusion criteria to make sure it's not confounded by patients with, for example, uncontrolled asthma or fluctuating underlying disease activity related to something like interstitial lung disease. So we've been clear around comorbidities we've been clear around the burden of cough that's coming into the study. Beyond that, I think we'd be expecting to see consistent efficacy across the population.

Okay. And you alluded to it earlier, but gefapixant, there was an AdComm ahead of the nonapproval as it turned out. Is it reasonable to expect that there will be an FDA AdComm for camlipixant?

I don't know, depend on obviously, when we got the data from CALM-1 and CALM-2. I think if there was the learnings that we took from gefapixant position us well. So we've been able to anticipate some of the things that whether it's the FDA reviews or an external expert panel would be asking, and I mentioned one of those earlier, which was as well as the intrinsic properties of camlipixant being favorable to gefapixant we were able to enrich the study based on cough frequency that was coming in, but really importantly, this chronic cough diary that we had an opportunity to align with the FDA and introduce into the study as a key secondary endpoint.

Okay. And then I guess the 2 other concerns with gefapixant at the AdComm were, firstly, there was a question as to whether the trial was truly blinded because of the AE profile, but it sounds like you're quite confident that, that's been solved for through the selectivity. Then there is also sort of these high placebo responses, which was an issue that was raised as well as the variability in baseline cough frequency. So can you just kind of run through why you're confident that you won't have those issues?

You will always have a placebo response in a setting like this. It's to be expected. And I think it just comes back to the point we made earlier that there might be a target value you'd expect as a change from baseline in your active group. To account for placebo behavior in a study like this, we've made sure 2 things. One is we had a placebo run-in. So you can imagine then in your day 1 onwards, you've already accounted for that acute placebo response, which gefapixant weren't able to. We're also then able to exclude patients that had an exaggerated placebo response as part of the run-in, but also how we think about clinically important target values and it comes back to the 15% being a placebo-adjusted threshold.

Okay. And then final one on camlipixant. Just I think there's a concern amongst investors as well, and I think it was actually raised again at the gefapixant AdComm from one of the speakers there that there's a risk that treating for chronic cough is masking or there's misdiagnosis of a more serious underlying condition. So again, thinking as a former physician, how do you think that GSK can solve for that?

Well, it will be quite exciting for us. So from a trial point of view, as I say, we were quite disciplined around making sure that we exclude patients with interstitial lung disease, chronic obstructive pulmonary disease and uncontrolled asthma, CF, chronic bronchitis. So our trial population is clean in that respect that we're not going to be confounded by fluctuating underlying disease activity in any setting like this, and there's multiple, of course, the sort of clinical perspective will be -- you need to treat the underlying disease that's always kind of easier said than done. It's the same thing if we come to talk about the 35 pharma opportunity in pulmonary hypertension, treating the underlying disease is being done passively as part of clinical management, and these patients are then presenting with highly burdensome cough on top of that standard of care.

So actually, no, I think from a clinical point of view, these patients are presenting, they might be under a pulmonologist, and they're still presenting with coughs of over 20 per hour. So I think clinical management obviously would then relate to both managing the underlying disease and providing them with an efficacious medicine for the cough.

Okay. Maybe we'll move on to bepi, which is another kind of key data point. This year, we're expecting the full data at EASL. Before we go to that, I think your guidance was to file for approval with the FDA in Q1. I think we've got a week left of Q1 technically. So could you confirm if you have filed now?

We're on track. We normally -- we disclose when we get acceptance to file. And so we're on track to disclose acceptance to file within Q1.

Okay. Perfect. So in terms of the top line data, you've announced the top line is a positive trial. I think you've previously talked to, and at least Tony has a 15% functional cure rate as being clinically meaningful in this setting. Why is it 15% that is clinically meaningful? And how should we think about kind of implementation in the clinic?

Yes. So 15% is related to a very high bar of functional cure, which is undetectable surface antigen, importantly, 6 months of all treatments, including nucleoside analogs. And what that relates to is a clear quantitative prediction of improved outcomes for hepatocellular carcinoma, up to 70% reduction in the likelihood of hard endpoints related to malignancy and in turn, mortality. So when we think about clinical importance, it's a combination of responder proportion and the target value set. In this instance, the target value has cure in the title. So it's an ambitious endpoint. So I think it's very easy to qualify why 15% is important.

To put that into context, nucleoside analogs get to less than 1%. You'll see when we present the data at EASL in the controlled trial setting exactly what nucleoside analogs are able to achieve against that endpoint, but it's negligible. So yes, this is a step change in terms of the efficacy that we can offer patients.

Okay. And then beyond that functional cure rate, when we do see the data, is there anything else that we should be focused on to kind of put the profile into context?

We've designed a study where we're able to demonstrate durability of response as well. So some of these patients are going into a long-term follow-up. So I think the combination of achieving functional cure at that target value and maintaining it is the other sort of consideration that I would focus on.

Okay. And then just in terms of B-Well and B2 (sic) [ B-Well 2 ], which were the 2 trials, to my eye, they looked pretty similar in terms of design eligibility. Is there any reason we should expect differences in efficacy between the 2? Is this a scenario? And then peak opportunity in terms of the commercial opportunity here. So I think you've guided to GBP 2 billion in peak sales potential. Could you just walk us through how we get there? Is this something that will take a few years of education? Or is it something that there is a warehouse population of patients that are waiting for the product?

It depends on the geography. So whilst I think there's an acknowledgment that the burden of chronic hepatitis B is enormous in low and middle-income countries, and there is obviously an opportunity there around awareness and expanding the treatable markets. Actually, the currently diagnosed population is skewed towards markets like the U.S. So I think you've got an attractive proposition where you've got markets like the U.S. that are ready to go. They've diagnosed the patient population, and they're looking for an innovative new therapeutic. And then you've got the low and middle-income countries where, as you say, I think there's an expansion of diagnosis that's going to come with an effective therapeutic.

And so actually, when you look at the sort of relative contributions that we're thinking about, it's not as atypical as, I guess, some of the speculation I've seen externally, where it's actually a fairly representative contribution from markets like the U.S. versus markets like China.

Okay. That makes sense. The other thing I wanted to talk about is some of the deal activity that you've been involved in relatively recently. We'll run through some of the deals in and some of the assets that you bought in, in a second. But I just wanted to get an understanding in terms of your contribution and kind of the R&D organization more broadly. So I think it's been a very clear strategy that Luke's communicated that you're looking for assets which are validated from a biological perspective or the mechanistic perspective, where there's white space where you can improve. So I'd just be interested in how the R&D organization sort of is involved in that process?

Well, I guess the first thing to say is that the business development organization reports into Tony Wood and the R&D organization. So Chris and I sit on the same leadership team. So we work very closely with one another R&D has strategies within each category for Vaccines, ID, Oncology and Specialty. Those strategies inform the search and evaluation, and then we have a very well-oiled machine actually in terms of then triaging against criteria that ranges from, as you say, translational confidence through to unmet need, through to market proposition, through to development tractability.

And I've worked in, as I mentioned, a few organizations, consulted many more organizations. I think it is truly a finely tuned system at this point. And then that's then triaged upwards to the R&D leaders, so myself for specialty. And then beyond that, we'll come to Nina, Tony and Luke. Luke obviously does have ideas of his own. And so he will also initiate interest in certain activities, again, aligned with the overarching R&D strategy and then it plugs into the same sort of triaging process. And of course, we've been working with Luke for several years before he took the helm as well.

Okay. And then just in terms of that strategy in terms of finding the differentiation or some white space on unvalidated mechanisms, how do you think about that relative to time to market? And you can make the argument that if there is another GLP with another 1 percentage point of weight loss, is there a reason to be launching that 5 years later? Similarly, with the checkpoint inhibitors, there are 5 or 6, and beyond the 3 or 4 big ones, there was not really much of a commercial impact. So how do you assess those opportunities? And are there areas where there is -- is there a matrix? Do you think about these are the key things that we need to hit, which will offset late to market?

Yes. That's a good question. I guess that paradigm of best-in-class and first-in-class is starting to be, I think, challenged a little bit because you can be first-in-class and then you can almost -- you can rest assured that if it's a credible mechanism, someone's going to be on your tail, particularly with China's involvement. And then best-in-class is, again, sometimes a bit of a fallacy because you're only best as a function of getting your indication correct, your population correct.

So when Luke talks about validated targets, that's not mutually exclusive from thinking about how to further differentiate by selecting the right population, thinking about responder phenotypes and ultimately resulting in a differentiated medicine profile. And I think when you think about all the deals we've done, none of them are pure fast followers. We bag the validated biology so that we would discharge that risk and then we're able to experiment but with assurance around populations that will ultimately result in a more compelling market proposition at launch.

Okay. So one of the recent deals that you have done is RAPT. And then maybe just against that criteria that you set out. So Xolair obviously derisked the IgE mechanism. Could you just outline what the residual unmet need is and how ozureprubart is solving for that?

RAPT is a particularly, I think, unique setting where you've got a mechanism that was validated for type 1 hypersensitivity reactions and T2 pathways, which obviously received a lot of attention in the last 10 years with many successful therapeutics like Nucala, like Dupixent, but was relatively overlooked by circumstance because of Xolair was almost ahead of the curve in terms of that journey. And obviously, as you know, it was a consortia effort that led to the indication and marketing authorization for food allergy.

So you've got a validated pathway that had been overlooked. And despite all of that, the success of Xolair in its first year demonstrates the desperate need for patients and prescribers in the food allergy space against the backdrop where the standard of care is effectively what I would describe as primitive, which is avoid the allergen, easier said than done with cross-contamination, et cetera, of food and then guidance that if you then have a life-threatening anaphylactic reaction, carrying EpiPen with you.

So the type of efficacy that we're seeing with IgE mAbs, I think, is game changing. The problem is the market data suggests that even with that encouraging uptake, most of that use is through a 2-weekly administration. That is problematic for patients, particularly when you think about pediatrics, adolescents, and ultimately a preventative therapeutic. And it's also problematic with Xolair because I don't know if you've seen the USPI, but there's a nomogram. And again, you asked me for my clinical opinion earlier, I would not want to be having a complex nomogram with an axis of baseline IgE levels and an axis of weight, which at either end of those bookends excludes patients up to 120 kilograms, but down to 50 kilograms and then IgE levels as low as 500. So it's frankly, a very attractive setting to be able to observe all of that and then come in with a 3 monthly therapeutic.

Okay. And then food allergy in itself is obviously quite broad. There's multiple allergens within that. Are there any that you're specifically focused on? Or is there anywhere that IgE is probably the most relevant pathway to be targeting?

IgE is responsible for, I think, approximately 95% of food allergies. And what's important is that it's allergen agnostic. So relative to things like oral immunotherapies, which are allergen-specific, IgE takes that complexity out of the routine management of food allergy and the trial has been designed in that way where they mandate patients with 2 or more food allergens.

Okay. And then I guess one concern that we hear from some physicians and other companies that are developing alternative food allergy products is that IgE antibodies are not disease-modifying, and there are some concerns about sort of long-term blocking of IgE, particularly in pediatrics. How do you think about those?

I'll start off with the second one. Xolair has been marketed for asthma, including in pediatric populations for, I think, 23 years. So I've seen no data that is caused for concern with chronic treatment in pediatric populations. To your former point, disease modifying is always an interesting term, right? It seems to mean different things to different people.

I think in this space, what's important is that you've got an efficacious therapeutic that relieves the burden and therefore, results in strong adherence that allows the patients to -- yes, live more normal lives without the concern of a life-threatening anaphylactic reaction. So I'm not really sure what disease modifying would constitute unless you've totally rewired your underlying immune system, that currently, I don't think is an attractable proposition.

Okay. I guess it's sort of some of the immunotherapies can increase sort of -- or reduce the risk of, like, for example, we've seen with some therapies that you can go from having 1/3 of a peanut to a full peanut. So it's just sort of reset or rewiring the immune system as you talked to.

Okay. I mean that's something that we can obviously consider as well in terms of reintroducing food -- studied food as part of LCI. As you know, the oral immunotherapies haven't been very effective and are starting to be withdrawn.

Okay. Just in the interest of time, maybe we can move to the FGF21 space. So you obviously did a deal there. I think it was last year. And that obviously clearly plays through the strategy that you outlined. But there were multiple FGF21 deals done last year. I think Luke said on the full year results call that he thinks that you've got the best deal and the best-in-class profile. Could you just discuss that product profile and why you think it is best-in-class?

Yes. Well, I think we can qualify this because we had -- pick of the litter, obviously, because we were the first to make the deal. Again, given our broader portfolio, ultra-long-acting COPD, we've got a lot of experience in settings where there's significant burden of comorbidities in specialized internal medicine indications and where there's polypharmacy. And we appreciate that you're not protected if you don't take the medicine because it has a high burden.

So therefore, the FGF21 proposition, I'll start off with the class because I think it's important to talk about the class. The class has demonstrated histopathological reversal of cirrhosis. That's something that was considered to be unachievable even 5 years ago. So I think the FGF21 class is demonstrating a true step change in terms of what you can expect from efficacy in F2, F3 MASH, but also cirrhotic MASH, potentially in alcohol-related liver disease as well.

Then we thought about the attributes of efimosfermin, which were around immunogenicity, antidrug antibodies. I think objectively, it appears to have more favorable properties to prevent ADAs. Second was around scalability. Obviously, this is a prevalent indication, and we're hoping that it's going to be widely used once launched, and we wanted to make sure that the ability to scale and the COG proposition was attractive, and we felt that efimosfermin had better characteristics than the others. The former points around ADAs and also potentially what we've seen in terms of time of onset might indicate support that efimosfermin may have a more rapid onset and a more durable response that might then also be better tolerated.

And finally, the sort of the clear proposition is that a weekly therapeutic versus a monthly is a material differentiator in an area like MASH. MASH is the liver manifestation of the metabolic syndrome. So these patients often have dysglycemia, if not diabetes, hypertension, heart failure, chronic kidney disease. They're going to be on multiple therapeutics. And so it's not trivial to have to inject yourself every 2 weeks for the rest of your life. So I think that's a material differentiator as well.

Okay. And then how do you think about the opportunity in the context of the GLP-1s? And then again, we had a -- we spoke to a KOL at this event last year. He's actually coming in later as well. And his view that the majority of patients will be on a GLP-1 and they had MASH. And those are, of course, weekly for now. So how do you reconcile the fact that there is an advantage for the less frequent administration if patients are maybe already used to being on a weekly injection?

Yes. So given my background, I started off with, you'll appreciate that I've been closely involved with incretin-based therapeutics for 15 years. And they are effective at targeting MASH resolution. They're less effective at fibrosis improvement in F2, F3 and they are ineffective in cirrhotic MASH, to the extent that the GLP-1s have shown an effect that was unfavorable versus placebo in cirrhotic MASH.

And so when we think about that, and we did think about this very carefully when we did the deal, even if you assume the most optimistic scenario, which is unrealistic because of the tolerability and persistence on GLP-1s, which is less than 50%, as you know, in a year for a chronic therapeutic, that's a problem. But even in the most extreme scenario where everyone is on a GLP-1, the efficacy of FGF21 is preserved, and we are permitting use of GLP-1 as background therapy in the trials. So very binary clear differentiation for cirrhotic MASH differentiated based on best-in-disease fibrosis improvement in F2, F3 MASH and efficacy is preserved on top of GLP-1 as -- and if you think about the sequence of treatment here, they have been prescribing GLP-1 in primary care. By the time they get to specialized care in a hepatologist, they're going to be looking at products like FGF21.

Okay. I realize we've only got 5 minutes left, but I wanted to very quickly ask about respiratory as well. So the pipeline is actually and the portfolio that you have is very broad in terms of modalities, different frequencies of administration. So just thinking about COPD alone, you have 2 IL-5s. You have an IL-33 and also a TSLP as well as the -- well, the TSLP has been investigated by other companies and then you have the PDE3/4. So could you just unpack all of that and think -- help us think about how those all coexist in COPD?

So it ties in with your earlier comments around Luke strategy for validated pathway. So superficially, you might -- as you kind of framed it, you might think, well, you've got an IL-5 and IL-33, you've got a TSLP, so has many others. The first thing is obviously the ultra-long-acting properties across that portfolio, and we're going to be looking forward to seeing the success of that with Exdensur in asthma in the coming months. For COPD, I think that ultra-long-acting characteristic is even more important for all the reasons I described for MASH and obviously, twice yearly in that instance.

But what I'd emphasize is that GSK probably has more data in respiratory medicine and translational data for respiratory medicine than any other company or a single academic organization in the world. And so what we have done is COPD is a heterogeneous disease. The bookends of COPD are wider than asthma and COPD. So in other words, there's more overlap between cohorts of patients with asthma and COPD than there is within COPD. We recognize that. We've got data spanning inhaled therapeutics, first wave of monoclonal advanced therapies, now PD3/4, IL-33, TSLP, novel undisclosed mechanisms like the Empirico oligonucleotide deal. And so we have a causal map of what's driving disease in this prevalent disease classification of COPD at the level of the underlying biology, and we've mapped all of those mechanisms accordingly to where they're going to be most relevant to the underlying biology. So those pathways are not stacked up on top of each other.

A really good example is IL-33. We've been, frankly, quietly happy to be in a little bit of a stealth state with what is a best-in-class IL-33, whilst the competition have taken forward that mechanism into precedented trial designs and populations that really don't speak to the underlying biology of IL-33. I'm going to be careful around disclosing too much around IL-33 and what we consider to be the target trait pairing, but it's a good example of where we're mapping that to slightly different treatable traits in COPD. Importantly, COPD affects 300 million to 400 million people globally. It's the third leading cause of death. So you're able to segment the disease classification, but each one of those mechanisms is still mapped to a scalable area of the market.

Okay. And then just in the last couple of minutes, also I wanted to touch on AI in drug discovery. It's something that we get more and more questions on from investors. And given that your former role was a CMO at AI drug development company, I just wanted to get your perspectives on the advancements that we've seen in the industry, and then how those are being utilized at GSK.

It's a perfect segue from what the conversation we just had actually. So AI, I think, has achieved maturity, certainly at GSK, I expect in many other companies around medicine design, so structure-based antibody design. We use AI heavily for oligonucleotide sequencing to be able to exploit that potential time frame to go from target committed to candidate ready within a time frame of under a year.

But the next frontier for AI, in my view, is uncontroversially biology. And biology as it relates to drug development is the complex proposition of the intersection between underlying disease biology and what your mechanism is able to do. You then have to obviously reason over that data and decide and triage between an infinite number of targets, but targets they're relatively commoditized. As you know, there's a huge clustering of many companies around a relatively narrow target space at the moment. And we've seen multiple instances where old targets have had a renaissance because someone has cracked the target trait pairing.

When you take that into clinical developments, you're then taking forward what is undoubtedly a multivariate proposition or frankly, a mega variant proposition, but you're using univariate decision criteria as to whether it's advance. So against that backdrop, AI allows us to reason over multimodal data. And at GSK, we've been very intentional in building field-leading human data sets with proteomics, genetics, transcriptomics, now spatial transcriptomics as well.

We're able to pair that underlying cell phenotype to tissue and structural changes based on explanted tissue but also complex cross-sectional imaging. We then link that to the types of endpoints that are important to how patients feel, function and survive. And we're then able to reason over those data sets in a way that is not possible manually, but even with sort of conventional biostatistical approaches. And we've now got the early proof points of what happens when you're able to reason across those latent edges of different modes of data that historically you would have never been able to, for example, considered a structural change of small airway remodeling with patients that have been treated with IL-5 and how that relates to parenchyma remodeling as relevant to idiopathic pulmonary fibrosis.

One of the outputs of that type of AI reasoning over multimodal data sets resulted in our conviction around IL-33 TSLP combination therapeutic approaches. So that was an instance where we're able to use genetic instrumentation using combinatorial variant approaches and a novel methodology, but then linking that to all of those modes of data from cell to tissue to structural architecture through to clinical consequence.

Perfect. Thank you very much for your time here, Kaivan. It was a great chat.

Thank you. Thanks.

Great. Thank you for coming, everybody. I'm James Gordon, Barclays European pharma and biotech analyst. And today, I've got the pleasure of hosting a fireside with GSK. So we're going to hear from GSK Chief Strategy Officer and Chairman of ViiV, David Redfern. Thanks for joining us today, David.

Thanks, James. Always great to be in Miami. Very nice to be here.

And we've got quite a lot to talk about because David's got a pretty broad remit. So I think we're going to try and talk a bit about the strategy for the overall GSK Group, but we're also going to talk about business development. And then as Chair of ViiV, we can also have a chat on HIV as well. So maybe just to start off, though, so you've got a new CEO, Luke Miels, although he's not entirely new because he's been there a while. Any early feedback about changes under Luke? What are we seeing on what changes might we have?

Yes. Well, we're 2.5 months in. I mean I think -- I mean, firstly, I think Luke will be much more expressive in the second half of the year. But that said, I wouldn't expect any kind of big strategic shifts in the direction of GSK. I think the therapy areas that we play in respiratory inflammation and immunology, oncology, increasingly a very fast-growing business in oncology in both solid and hematological tumors and pretty much everything in infectious disease. Obviously, we have a big vaccine business as well as HIV and increasingly in things like hepatitis B. So that is clear. I think capital allocation, very clear.

We're very clear on the dividend, investing in the business, business development. Luke has been a big driver of that with Tony Wood and I over the last few years. That continues. You've seen us be pretty active on that this year and the guidance that we've given that Emma set out, he has reaffirmed. So I think you should think of Luke is very much focused on doubling down on execution, driving growth, simplifying the business and particularly over the last few weeks, really getting into the R&D pipeline and particularly the sort of the Phase II assets, so we can talk more about those, things like B7-H3, B7-H4, TSLP program, FGF21 that we got from Boston Pharma and really digging in with the teams on how we make things like dose escalation, dose optimization decisions in a bolder, quicker way, how we can recruit patients, set up the protocols, run the studies faster. So there's a real focus on pipeline execution, particularly the mid- to late-stage assets that are really going to drive the growth in the 2030s.

And you mentioned M&A, and so you're also heavily involved in business development. So maybe first, what are the two deals you've done recently because we've had two quite recent deals. So why did you go for those assets? What's the appeal?

Yes. So we have been busy, and it's very much part of the strategy to continue to invest to build the pipeline, particularly through the 2030s. So the two M&A deals, we've done more than that. We've also done some licensing deals with people like Frontier. But we bought and have now closed RAPT, which brings a medicine for food allergy, very similar to Xolair, which is doing incredibly well here in the United States, but with a much longer half-life and then potentially up to 12-week dosing and a simplified dosing regimen. I mean food allergy, massive issue, 17 million people here in the U.S., enormous burden on the health care cost in terms of hospitalizations and so forth.

It obviously builds on our respiratory expertise. We have an allergy sales force. And we think -- the RAPT asset is an improved version of Xolair because of the longer half-life and a simpler dosing regimen. And also potentially, we can access the 25% of patients that either through weight or IgE level, Xolair can't. So we're excited about that. And that's pretty symptomatic of the type of deals that we're trying to do, which is some level of scientific derisking, so either precedented target or a precedented mechanism, but with the potential to be best-in-class through some differentiation and in therapy areas where we have a very clear capability and right to win or very close adjacencies to those. And the second deal we announced, I think, only last week, 35Pharma, a Montreal-based biotech company that has a drug for pulmonary hypertension.

So again, built on our respiratory expertise. We've had drugs previously VOLIBRIS and FLOLAN in that area. Again, precedented mechanism. This is an activin pathway inhibitor, but potentially spares something called BMP-9 and 10, which is involved in increased bleeding risk. So this is -- think of this as sotatercept like the Merck asset, but potentially with less bleeding. It's very early, I have to say. So there is a bit more clinical risk around this. It's only in Phase I, but potentially a very big medicine in that indication.

And I think of GSK is having quite a focus on infectious disease and oncology, which these 2 aren't in. Is it just chance that these aren't infectious disease in oncology? Or is it quite deliberate you want it to be broader?

Well, it's not chance. I mean we have -- I mean, infectious disease, definitely, we're very strong in, but we're extremely strong in respiratory, and we're building out adjacencies and things like inflammation with the Boston Pharma deal. We've got a lot of science around fibrosis developed with lung fibrosis. So it's natural to move that into the huge indications of liver fibrosis. So I don't -- this is not a chance. We're very thoughtful of where we go. We will do deals in oncology as well.

And in terms of the scale of deals you do, I said these are sort of moderate-sized deals rather massive deals. Is that also quite a deliberate thing that rather than want to do one big bet, you want to have quite a broad portfolio of assets?

Yes, I think so. I mean we've never ruled out doing a bigger deal if the returns and the stars aligned on it. But I think we've been pretty active doing a series of these sorts of deals. What we're really trying to do is drive meaningful growth through the 2030s. I mean that is what is behind all of this. I think the pipeline is building up extremely well to be able to do that.

And would you consider doing deals for assets that were launched this decade? Or you think that the outlook is strong for this decade such that it's only really post 2030s you want to be having a boost?

We wouldn't rule it out. I mean we clearly bought Sierra a few years ago now, which gave us Momelotinib, Ojjaara in myelofibrosis and particularly myelofibrosis patients with anemia, which is a significant proportion of them. That was a very late-stage asset. It's doing incredibly well. But there aren't that many unencumbered really late-stage assets, and they're extremely expensive. So I think we're in a pretty good space doing what we're doing.

Makes sense. If we could switch to talking about new product launches because there's a few things going on there. I actually one of them -- I hosted a panel yesterday, which was about respiratory, which got a lot of interest. And we were talking about longer-acting therapies in respiratory. So you've got Exdensur, a longer-acting IL-5 is 6 monthly. How should we think about that fitting versus the other drugs that are already out there that are biologics that are shorter acting?

Yes. I mean we're super excited about Exdensur, every 6-month dosing, I think that is very significant compared to the shorter-acting IL-5, which are 4 to 6 weeks. The thing about severe asthma is it's very underpenetrated with biologic agents, only about 27% of asthma patients take a biologic agent. So there's a real opportunity for increased bio penetration market development here. And I think all the feedback we're getting, and as I say, it's early days, but the qualitative feedback from physicians, [indiscernible] 6 monthly dosing will be extremely helpful in increasing that penetration. We will, of course, get some switches. I mean there will be patients that will naturally want to switch from every month to every 6 months, obviously, a lot more convenient. But we're really focused on driving Exdensur into that bio-naive population. Early days, but everything is on track.

And I think there was a study that came out that showed it wasn't quite noninferior for an Exdensur versus Nucala. But does that impact how you plan to do the launch?

We're pretty relaxed. I mean that was a nimble study. It wasn't statistically powered to show that. The switch indication is in the label. All of that was disclosed to the FDA. So I don't think -- we don't anticipate that will impact the launch, and it reinforced actually the safety data of the product. So we're pretty relaxed about that.

And is this a category where it can take some time to get insurance coverage, and that's a bit of a headache?

Well, there's nothing particularly unusual about it. I mean it always takes a quarter or two to go through the discussions with the insurance companies, but we expect this very much to be in the ordinary course. I think the payer proposition for it given the burden of severe asthma exacerbations often lead to hospitalizations and so forth. So we don't anticipate anything being particularly difficult or unusual. It always takes a quarter or two.

And the other thing I'd say about Exdensur is it's Part B. There's about 25% of severe asthma patients that are Medicare patients here in the United States. That's very different actually from COPD, where Medicare is the majority of the patients. So we are also in the process to get the J-code, which will take a few months. But everything on track, all in the ordinary course. And I think we're very excited about the potential. And of course, we're talking about severe asthma. We've started the studies now in COPD as well.

And maybe just on that, so we also talked about COPD yesterday. So you've got the only IL-5 approved for COPD. How is that launch going?

It's going extremely well. I mean we showed some data in Q4. There's been a big spike up in Nucala NBRx. I think there's also probably a halo effect from the COPD indication across asthma and nasal polyps. So yes, Nucala is doing very well. I think the metric that is really resonating is a 35% reduction in exacerbations leading to hospitalizations. And that's what you're really trying to do because it's a progressive disease. It's incredible the burden of COPD if you go into any emergency hospital, how many patients have COPD and taking out resource, 10% of patients that are admitted never come out of hospital and 50% die within 5 years. So there's a real unmet medical need to come up with new agents.

Actually, just on that point of new agents, and there's some other mechanisms as well. So we've got Dupixent of [ 413 ]that's approved for COPD. And then we're also soon going to get some data for an IL-33. I believe TSLPs also in development. I think you've got quite a few, including some longer-acting versions going after all those targets. So when could you broaden what you're doing in COPD? And how do we segment...

We have Nucala today. We're running trials in different levels of severity of COPD patients now just getting underway underway [ ADJUVANT ] and VIGILANT trials with Exdensur for 6 monthly. We also have potentially the 6-monthly TSLP. We will definitely take that into COPD and we still remain pretty excited around the science of IL-33. And obviously -- and we have an IL-33 that we are progressing, and there is obviously the potential to create combinations of those over time. We're doing a lot of work on patient stratification, a lot of AI actually has been very helpful in -- because COPD was always thought of as just sort of one disease caused by smoking, but actually, you can stratify it in many different ways. Eosinophil level is clearly one.

I mean, very simply, the IL-5s are most suitable of eosinophils over 300, maybe TSLPs above 150 and IL-33 across all levels. But I think we will get a lot more sophisticated as we move these clinical development programs forward in really identifying different categories of COPD patients that these can work for.

What if we shift to your other launch, which is Blenrep? Yes. So I don't know how accurate the IQVIA data is, but that looked like a pretty strong ramp initially in Q4. There may be a little bit softer at the beginning of the year. But is that data very reliable? And how is the launch actually going?

Again, it's very early days, but we're very pleased with everything we've seen so far. You can't totally rely on IQVIA, although it is showing very strong growth, but it's obviously Part B as well. So IQVIA is incomplete. I mean, two things are very important with Blenrep. Firstly, it's an incredibly efficacious medicine. We saw that from the DREAMM-7 results, progression-free survival, almost 3x the standard of care with daratumumab and a 50% reduction in the risk of death. So it's very meaningful. That efficacy is absolutely resonating with the hematology community. I think there is a real enthusiasm for a BCMA agent post the first line or post CD38. And the other thing about Blenrep, it's a very simple infusion, takes about 25 minutes to half an hour, can be given on an outpatient basis.

So it's incredibly well suited for the community. And here in the U.S., 70% of patients and hematologists are in the community. So we're excited about that. It's obviously third line initially in the U.S., second line in the rest of the world. We're just rolling out ex U.S. The U.K. was the first market. No hard data points at this point, but everything very much on track.

And is there a lot of work to do in terms of training both the doctors and also ophthalmologists. And so I think at one point, GSK talked about going slow to go fast. Do you need to go quite slow before you go fast or you quite...

I mean I think what we mean by that is we're very keen that the early patient experience for both the patient and the hematologist is positive. So we're encouraging the hemes to be very thoughtful around which patients they put on it initially and then work very closely with them.

On the REMS, it's much simpler than Blenrep 1.0. It does require an eye exam each dose in the United States. In the U.K., it's just for the 4 doses, but that can be done routinely by a high street optician. It's a very simple slit test. They're very experienced in dealing with cancer patients. We've trained several thousand opticians across the U.S. And the qualitative feedback we're getting from hematologists and the opticians is that process is all working pretty well. And the paperwork associated with it is actually massively simplified.

Great. Well, I definitely want to ask lots about HIV because of your ViiV Chairman role. Maybe I'll just ask one about the pipeline before switching to HIV. So one of the interesting readouts, I think, this year is camlipixant. So there's two elements. Just generally, how excited are you about these readouts for chronic cough? And then the other question, could there be differences between the two trials? Because I think I've heard a comment from GSK that the second trial might have people that cough even more, like the more acute patients and more severe patients. So how do you think about the two different trials and the overall excitement for the program?

Yes. I mean, look, refractory chronic cough is a serious condition. We know that there's about 1.8 million people in America being under the care of a pulmonologist. The pathway there is often quite different. 50% of them have probably seen 3 other different types of doctors, allergists, GPs and so forth on the route. And there's really nothing today that really treats it. They're taking a mixture of OTC cough medicine, sometimes pain medication opiates and so forth. So we're very clear on the unmet medical need. The studies, KALM-1 and KALM-2 will read out in a pooled analysis in the middle of the year. All of that is on track. You're right, KALM-2 has got slightly more patients in and more frequent coughers.

So there may be a slight difference. I think I'm right in -- although it's a pooled analysis, effectively, both trials have to statistically hit to ensure that the overall trial hits. So we'll see in the middle of the year. I mean I would remind you that the Phase II data showed a 34% reduction in cough frequency. The Phase III is a 12-week endpoint. We probably expect it to be a bit lower. The 15% to 20% mark will probably be about par because it's a bigger trial. We probably expect a bit more placebo effect, but we shall see. We're not too far away now. So we'll probably have a discussion post results.

That sounds good. In that case, I'd definitely like to switch to HIV. To start with -- so there was the CROI conference recently where you presented quite a few data points. And in particular, I was interested in the data you had for 4 monthly, but even more so what you might be able to do for 6 monthly. So maybe just briefly, what did you present there? And then what does that say about what your longer-term plans might now look like?

Yes. So actually, James, at the CROI, we didn't present much on 4 monthly, but for both PrEP and treatment, 4 monthly very much on track. So the PrEP will read out this year and hopefully launch next year. Treatment is about a year, later than that, and we will start the pivotal bridging study later this year. What we really presented at CROI and what we're very excited about is our 6 monthly treatment options. And we presented PK data on our third-generation Integrase 184 which we've already shown has a very broad resistance profile against all much broader set of mutations than cabotegravir or dolutegravir, which has been very well received by the community and by the KEs.

We showed PK data on that, that showed that we're very confident of going to a 6-month formulation. And similarly 499, our capsid inhibitor, which is very similar actually to lenacapavir, but with less drug-drug interactions. We showed PK data on that. which is very affirming to a 6-month formulation. So the next stage now is to test 6 monthly formulations of those in infected individuals. So I think -- and then the third piece of data that we showed from R&D was our neutralizing antibody N6LS. We showed 4-month data on that, but we've got data coming in 6 months. And again, that was very effective.

So we've got some options of how we build a 6-month pipeline here. But I think we've got growing confidence that we're going to potentially have a best-in-class 6 monthly treatment and there's more work -- clinical work to do. We will do meet the management event at some point in the middle of this year and go into a lot more detail around this.

And why would you pursue one of the 6 monthly options versus the other? So my understanding is that a broadly neutralizing antibody, it wouldn't work for absolutely all strains of HIV and you still need to get the 6-month data, but you've got some 4-month data that looks encouraging. But the capsid, you've already got 6 months data, and it could work for everyone. So why not already just go forward with the capsid...

Yes, that's a very good question. And it's a question that we are still thinking through it. There's no doubt the capsid is going to be broader. And I think 184 plus 499 has the potential to be a very significant medicine. With the antibody, there's actually been quite a lot of science over the last year or so around the impact of antibodies on the latent reservoir in HIV even in patients that are virally suppressed.

So there's work going on to look to see whether there are particular patient groups that, that might be important for. And I think -- and I know Andy Dickinson was here before Gilead, it's all about having options. It's a bit like we had Juluca and Dovato. There are a diverse group of patients and having different combinations that could be important for different groups.

I mean to that point, it's a big opportunity, and they both sound interesting. Could you just take them both forward?

We could.. So watch this space, and we'll update you later in the year.

And actually, just -- so we had Gilead on first, and there's been some talk about less frequent orals. So I don't believe you've announced a less frequent oral program, but you've got a third-generation integrase look very effective. Could that -- is it the sort of drug that could be made into a less frequent oral?

The [ PKN ] 184 is such that, that's probably not the optimal medicine to be in a more frequent oral, but we are certainly looking at possibilities in that. I think our main focus is very much 6 monthly, but we are open-minded on other things.

And what about the route of administration? Does that matter? Because some people have noticed your products at the moment are intramuscular, some competitors are going for subcu. But then if you're talking about something where you've only got to get it twice a year anyway, how important is whether it's IM, IV, subcu?

I think it's very important in PrEP. We haven't got on to PrEP, but -- there's no doubt [indiscernible], even though it's doing well, there are quite a lot of nodules issues from the subcu formulation. I think in treatment, our aim is very much to develop an IM formulation. We'll have to see. I think that's definitely possible for 499. We've got a bit more work to do with 184. But there is less pain, there's less nodules associated with IM in our view and all the research we've done.

But I would say, I mean, the thing that's underestimated a little bit, the chemistry around these long-acting formulation, integrase chemistry itself is very complicated. I think part of the secret sauce of ViiV has been it integrase chemistry, both inside ViiV, but also with our great partner with Shionogi. And I think we've got real competitive advantage there.

And if Gilead is able to bring along a once-a-week PrEP as a pill next year, do you think that would be a big challenge for Apretude as a 2-month or a 4-month injection?

I think in the PrEP market, I mean, I agree with Gilead. I mean the PrEP market is growing strongly and having a second entrant in long-acting is absolutely helping that. I think having different options is always good. At this point, Apretude is continuing to grow very strongly along the lines of the last couple of quarters. I think if you -- if there is a once weekly, I'm not sure that's necessarily coming next year. I mean it will cannibalize the daily orals for sure. But we're focused on long-acting.

Great. Well, I'm looking forward to this HIV event and hearing more. And with that, I can say we're out of time. So thanks a lot for joining...

Thanks, James. Thanks, everyone, for coming.

Ladies and gentlemen, a warm welcome to the GSK Full Year 2025 Results Call. I'm delighted to be joined today by Luke Miels, Nina Mojas, Deborah Waterhouse, Tony Wood and Julie Brown. And in our Q&A session, we will be joined by David Redfone. Today's call will last approximately 1 hour with the presentation taking around 30 minutes and the remaining time for your questions. Please ask only 1 to 2 questions so that everyone has a chance to participate. Before we start, please turn to Slide 3. This is the usual safe harbor statement. We will comment on our performance using constant exchange rates, or CER, unless otherwise stated. I will now hand over to Luke.

Thank you, and welcome, everyone. My introduction today will have 2 parts: Headline results for 2025 and our key focus areas in 2026 to drive value. Starting with 2025 results were strong. Sales were up 7% to more than GBP 32 billion. Growth was driven by Specialty Medicines, which were up 17% with vaccines also contributing. Core operating profit grew 11% and EPS was up 12%. Cash generation was strong at GBP 8.9 billion, supporting future investment and returns to shareholders, enabling the dividend upgrade of 2p to 66p declared today. R&D output remained very positive with 5 FDA approvals and 7 new pivotal trial starts, and we maintained our high standards for being a responsible business. Looking forward, we expect another year of profitable growth reflected in the guidance given today. Next slide, please. In 2026, we expect momentum to continue, and we'll get there by focusing on execution and operational delivery. There are 3 areas where we're focused. The first is driving top line growth by maximizing launch products like Blenrep and Exdensur and ensuring success in overall operational execution. Second, accelerating key assets in our late-stage portfolio like B7-H3, B7-H4 and Velzatinib in oncology and Effi in MASH and in our earlier portfolio like the ultra-long-acting TSLP for respiratory diseases and regimen selection for our 6-monthly treatment for HIV. And third, continue to execute business development where we see a clear pathway to value creation and our recent addition of the food allergy IgE antibody, Ozekibart is consistent with this. Underpinning this will be a drive to simplify how we work with greater pace, accountability and focus. And this starts by matching our best people and resources to the best opportunities to create value. Linked to this, changes have already been made to the executive team, bringing on commercial leaders with deep industry experience to increase our focus on products and execution. And this includes Nina Moz, our new Head of Global Product Strategy, who I worked with for a number of years at AstraZeneca and Roche, who will present the commercial update. And importantly, we'll have an increased focus on leveraging practical use of AI and technology. And I'll now hand over to Nina.

Thanks, Luke. Please turn to the next slide. Overall sales for the year were up 7%, with strong growth driven by specialty, up 17% and another year of growth in all regions.

Next slide, please. Respiratory Immunology and Inflammation full year sales were up 18%, driven by strong Benlysta and Nucala performance. In the year, Benlysta grew 22%, driven by higher demand and supported by all major guidelines. 82% of U.S. bio-naive patients are now starting on Benlysta due to its differentiated profile with organ damage prevention and more than 14 years of safety and experience. Nucala grew 15% and delivered $2 billion for the year. This is the 10th consecutive year of double-digit growth for Nucala. Moving to oncology. Sales were up 43% -- in the year, Jemperli sales were up 89%, reflecting our differentiated profile in endometrial cancer.

Ojjaara grew 60%, driven by growth in all markets following the new data at EHA, emphasizing the importance of early intervention. And based on these data, NCCN included Ojjaara as Category 1 for patients with anemia. We expect this to drive uptake in first line, although growth will be slower than what we have seen with second line.

ZEJULA sales decreased, reflecting FDA labeling restrictions, and we remain focused on the potential we have for BLENREP now approved in 15 markets globally. Deborah will cover HIV shortly. Given the continued strong performance and momentum across the specialty portfolio, we are expecting sales to grow low double digit for 2026. Next slide, please. The strong performance of Nucala in '25 was driven by our successful launch in COPD. This launch also had a halo effect on all of Nucala's indications, resulting in higher market share in asthma and nasal polyps, also fueling brand growth in '26. We are applying the lessons from the severe asthma market with Nucala to the launch of Exdensur, which is now approved in the U.S., U.K. and Japan.

We know that there is a significant opportunity in the bio-naive population as only 27% of U.S. eligible patients are on a biologic.

And market research shows that 97% of patients would prefer or like to switch to a biologic with 6 monthly dosing. And Exdensur has demonstrated a 72% reduction in exacerbations leading to hospitalizations in an indication where we know lack of therapy adherence leads to worse clinical outcomes.

The second key launch this year is for BLENREP, our off-the-shelf BCMA agent for multiple myeloma available in the community setting where 70% of patients are treated. We've made fast progress on our launch in the U.K. and are applying lessons learned in the U.S., particularly around Eye Care networks. We've now engaged around 18,000 eye care professionals in the U.S., enabling smooth collaboration between treating physicians and Eye Care professionals and have had positive feedback on the simplification of our REMS. We continue to expect this to be a slow ramp-up as we support prescribers and patients to ensure a positive first experience and robust adoption. I will now hand over to Deborah to cover HIV.

Thank you, Nina. We entered 2026 confident in our unique position to lead the next transformation in HIV care. Sales growth was 11% in the year, powered by accelerated patient demand for our long-acting injectables and our foundational oral 2-drug regimen, Dovato. Demand continued to increase across all regions, most notably in the U.S., which grew 14% in 2025, continuing to outpace competition in market share gain.

With the only commercially established long-acting HIV treatment regimen backed by over 4 years of real-world data, we're delivering long-acting innovation at scale and are delighted with our ongoing portfolio transition to long-acting regimens. In 2025, over 75% of our growth came from long-acting injectables, which now represent around 1/3 of U.S. sales.

With treatment accounting for 90% of the total $22 billion HIV market, we are pleased that Cabenuva grew 42% in 2025, fueled by patient demand and accelerated switches from competitor products, reaching more than 75% in the U.S. this quarter. In long-acting prevention, Aplitude grew 62% in 2025, withstanding any impact from a competitor launch. In 2026, we expect continued growth momentum. And so today, we are guiding mid- to high single-digit growth.

This quarter, we also announced Pfizer will exit ViiV and Sinogi's shareholding will increase, simplifying Vii shareholder structure. GSK will maintain the same position. We look forward to continuing our highly successful collaboration to advance our pipeline and portfolio of long-acting HIV medicines.

Moving on to our industry-led long-acting pipeline. Powered by unmatched patient insight, we are set to deliver transformative launches over the next decade, enabling us to navigate the dolutegravir loss of exclusivity and accelerate long-term growth. We believe twice yearly treatment presents our most significant commercial opportunity and through a combination of novel assets, presents the potential to change the HIV treatment paradigm once again. At CROI, we will share data that will help inform our regimen selection for twice yearly HIV treatment. Starting with VH184, a potential first-in-class third-generation entity with IP protection through to at least 2040. We'll present key data on its unique resistance profile versus the competitor and findings from an ongoing first time in-human trial exploring its significant potential for up to twice yearly dosing.

We strongly believe this asset has the power to redefine the long-acting landscape, and we remain extremely confident in its potential to become the backbone of our long-acting treatment regimens. To pair with that entity once selected, we are evaluating 2 partners, VH499 and our BNAbN6LS. Data at CROI for VH499 will show potential dosing durations. For N6LS, one of the broadest and most potent bNAbs in development, we'll share more data focused on Q4M dosing with Q6M dosing data expected this year. This year, we'll also begin QUATRO, our Phase III registrational study for 4 monthly HIV treatment. This critical step builds on our Q2M success, and we are on track to file in 2027 and launch in 2028. At launch, we still expect to have the only long-acting treatment options on the market for years to come. Our strategy is clear and our execution is strong. We are fully confident and well positioned to drive sustained long-term performance, and we'll continue to update you on our Q6M regimen selection.

We look forward to introducing you to our new Head of R&D, Charlotte Allison, who will succeed Kim Smith upon her retirement at the end of Q1. I'll now hand back to Nina.

Thanks, Deborah. Turning to vaccines. Sales were GBP 9.2 billion in the year, up 2%, driven by European and international region sales of Shingrix and Bexero. Shingrix sales were GBP 3.6 billion, up 8%, driven by Europe and international region, offset by the U.S. In Europe, sales were supported by our focus on comorbid patients. And in international region, Japan continued to grow following expanded public funding. And in China, we saw similar sales to 2024. In '26, we expect market performance outside of the U.S. and China to benefit Shingrix sales, offset by slowing U.S. immunization rates and our partner in China managing inventory.

In meningitis, sales were up 12% with strong continuous growth across Europe and international, driven primarily by Bexero, up 16% for the year. Bexero demand increased in Europe, partly due to MenB outbreaks. Ex U.S. represents 69% of Bexero's global full year sales, demonstrating continued growth from national immunization programs and geographic expansion. In the U.S., we retained MenB market leadership with 74% market share and have seen positive signs for MenB with initial stock building. Turning to Arexvy. Sales were up 2% for the year, also driven by ex-U.S. growth. We continue to monitor the evolving pediatric vaccine landscape in the U.S. At this time, insurance coverage remains as before, and we expect the recent HHS changes to be manageable given GSK's broad portfolio of vaccines. For '26, we expect sales growth to be in the range of low single-digit decline to stable. Next slide, please.

Turning to GenMed. Sales were slightly down for the year. Strong growth of TRELEGY was offset by other respiratory and established products. Globally, TRELEGY continues to be the top-selling brand for asthma and COPD. And in the U.S., the C class is growing with TRELEGY leading in share driven by gold guidelines and strong execution. In anti-infectives, we are taking a targeted approach to align access to BLUJEPA in uncomplicated UTIs with positive initial insights. And for complicated UTIs, we now have a PDUFA date of 18th of June for tebipenem in the U.S. Looking forward, we expect sales growth to be in the range of low single-digit decline to stable, reflecting pricing pressures and generic competition of our established portfolio. And in the U.S., across the broader portfolio, we navigated the impact of the Medicare redesign from the Inflation Reduction Act near the upper end of our $400 million to $500 million range. I will now hand over to Tony to talk to you about our progress in R&D.

Thank you, Nina. Next slide, please. Starting with the pipeline. There's greater focus and opportunity here than ever before. Our top priority is to accelerate development to deliver new products to patients faster. In 2025, we secured 5 FDA regulatory approvals and started 7 new pivotal trials, 3 for Exdensur in COPD, 2 for efimisfermin in NASH, for Velzatinib in second-line GIST and RRS, our B7-H3 ADC in extensive stage small cell lung cancer. I'm delighted with the progress we're making to deliver the pipeline, shorten development time lines and access world-leading innovation through BD.

Next slide, please. In respiratory, we've extended our leadership through a focus on exacerbation prevention with long-acting treatments and now have approval for Exdensur, the world's first and only 6-monthly biologic to treat patients with severe eosinophilic asthma. Also in respiratory, COPD is a growing area of significant unmet need. A patient hospitalized with an exacerbation has less than a 50% chance of survival over a 5-year period, alongside a cost to U.S. health care of around $7 billion per year. Our work to understand the role that inflammation plays in chronic airway disease has led to an emerging and differentiated pipeline of long-acting options for COPD patients.

Starting with Exdensur, the Phase III ENDURA trial to recruit patients at moderate risk of exacerbations, while vigilant is the first ever study of an antibody for patients at an early stage of disease who are at risk of rapid progression. Our Phase II trial investigating the ultra-long-acting TS monoclonal antibody GSK283 in asthma patients is on track to generate data by the end of this year and will further guide development of a 6-monthly option for patients with a low T2 phenotype. The portfolio also includes a PDE3/4 inhibitor with potential for DPI use in Phase I development in China, complementing our leadership position with TRELEGY.

Looking now to refractory chronic cough. I'm pleased to confirm that we achieved last patient first visit for the KALM-2 study in December. And we're now on track to report Phase III data from the total program around mid-2026, in line with our prior guidance. We believe Camlipixant will provide an effective treatment in RCC, where there are no approved therapies in the U.S. and approximately 10 million patients diagnosed globally who could benefit from this medicine.

Next slide, please. A focus on inflammatory pathways of disease and how this leads to fibrosis, particularly in the lung, liver and kidney, underpins our development programs in fibro-inflammatory mechanisms. We are pleased with the progress of Efimosfermin, our potential best-in-class once-monthly FGF21 analog, which started Phase III trials for MASH last year. As a reminder, in Phase II, Effi demonstrated sustained improvement in fibrosis and resolution of NASH in patients with F2, F3 stage disease. These data supported the start of our AZENIT-1 and 2 pivotal studies. We plan to start the Nebula Phase III studies, which will recruit a more advanced F4 patient population later this year.

Also in our hepatology pipeline is GSK-990, an siRNA therapeutic targeting HST17B13. Consistent with human genetics of this target, preliminary data from the Phase II STARLIGHT study in alcoholic liver disease demonstrates favorable trends in reduced liver enzymes despite ongoing alcohol consumption and this with no emerging safety concerns. These assets have the potential to reverse cirrhosis where 20% to 50% of patients with associated complications die within 1 year.

Next slide, please. Last month, we were pleased to announce positive results from the B-WELL 1 and B-WELL 2 studies, our Phase III trials of Bepirovirsen for the treatment of patients with chronic hepatitis B, a disease which affects more than 250 million people worldwide, causing over 1 million deaths each year. We believe that bepi has the potential to transform chronic hepatitis B treatment and become the first ever fixed course of therapy with functional cure at a significantly higher rate than today's standard of care. This is important because chronic hepatitis B accounts for around 56% of liver cancer cases and real-world evidence shows that functional cure reduces this risk by around 90%. We look forward to sharing these data with regulators during the first half of the year and at an upcoming scientific congress. Next slide, please. Our oncology pipeline is a critical part of the portfolio.

Starting with BLENREP. We anticipate mature OS data from DREAM-7 in early 2028 to support second-line registration in the U.S. In the first-line transplant ineligible setting, DREAM-10 is recruiting well, and we recently expanded the number of U.S sites to increase U.S. patient participation. DREAM-10 uses a lower dose when compared to second-line studies and evaluate dual endpoints of MRD and PFS. Interim MRD and safety data are expected in early 2028. Also in the first-line setting, we'll start a study looking at BLENREP cord regimen in a younger fitter population later this year.

Moving now to Ojjaara, we continue to generate data to support decision-making for myelofibrosis patients with anemia and a Phase II study in myelodysplastic syndrome is currently recruiting. We also continue to develop life cycle indications for Jemperli. Later this year, we anticipate results from a pivotal ASO-1 trial for Jemperli in DMMR locally advanced rectal cancer. ASO-1 was designed following the publication of transformative data, which showed 100% complete clinical response rate in a single center monotherapy study. We're excited about Jemperli's potential for patients with this disease. Velzatinib, our KIT inhibitor, which targets all clinically relevant enzyme mutations has started Phase III in second-line GIST with first line to start later this year. Velzatinib has the potential to replace current standard of care and is designed to offer a well-tolerated schedule with greater efficacy against resistant mutations.

Moving now to our other ADCs. Our B7-H3 targeting molecule, which I will now call Ris-Rez, recently received its fifth regulatory designation with orphan drug status in SCLC. With this transformative potential in mind, we've initiated a global program encompassing multiple solid tumor trials for RisRes called EMBOLD. The first of these studies, EMBOLD SCLC-301 has started ex U.S. recruitment in second and third line. U.S. recruitment will start later this year and include tarlatamab exposed patients. We have extensive plans for additional Ris-Rez Phase III starts in the next 12 to 18 months. In the first half of this year, we also plan to start recruitment for pivotal Phase III trials for MORES, our B7-H4 ADC in platinum-resistant ovarian cancer and in patients with recurrent endometrial cancer. We're targeting a conference this year to present interim data from our early phase BEHOLD-1 study for patients with ovarian and endometrial cancers, and we anticipate further pivotal study starts for this molecule during 2026.

Next slide, please. Business development is a core part of how we're accelerating our pipeline and accessing innovation. Two weeks ago, we announced an agreement to acquire Rapp Therapeutics, whose lead asset is Ozureprubart, a potential best-in-class long-acting anti-IgE monoclonal for food allergy, which is currently in Phase II. Food allergy is a chronic inflammatory condition with severe reactions leading to anaphylaxis, emergency care and persistent lifestyle disruption. In the U.S., severe food allergies impact over 17 million patients with an estimated $33 billion cost of economic burden, underscoring the need for more effective treatment options. We expect the deal to close this quarter and look forward to progressing this important asset into Phase III development.

Next slide, please. In conclusion, 2025 saw further strong momentum in the pipeline, which continues into 2026. We have critical data readouts to come for bepi, Camli, Jemperli, Q4M Prep and ensure for EGPA. We also have 10 pivotal starts planned for this year, including more than 5 from our ADCs, 2 for advanced MASH and Quattro, our Q4M treatment Phase III trial for HIV, all of which are supporting our growth in specialty medicines. I'm excited about our progress and our prospects. I'll now hand over to Julie.

Thank you, Tony, and good afternoon, everyone. Next slide, please. Starting with the income statement for the full year with growth rates stated at CER. As highlighted, sales grew 7%, whilst core operating profit grew 11% -- this leverage was primarily driven by a 3% increase in SG&A as investment in product launches was balanced with productivity improvements.

Additionally, royalty income benefited from the RSV IP settlement, the new mRNA royalty streams and Kesimpta performance. And R&D growth of 11% reflects our acceleration of investment across multiple key specialty assets. Core EPS grew 12%, supported by the share buyback and lower interest expense due to strong operating cash flows. And finally, turning to total results. Growth primarily reflects the impact of the Zantac charge taken in 2024. Next slide, please. The operating margin increased 110 basis points in 2025, bringing total accretion at CER to 470 bps over the last 4 years.

This increase was primarily driven by SG&A margin improvement of 90 bps, whilst gross margin continued to benefit from the portfolio transition towards specialty, growing 40 basis points. R&D expenditure increased as we reinvested the additional royalty income into our pipeline to support the initiation of the Phase III Efimosfermin trials and prepared pivotal trials for the ADCs in multiple indications. Incorporated within this margin improvement were core charges of GBP 300 million taken in Q4, split evenly across supply chain and SG&A to drive productivity benefits.

And currency was a headwind to margin, lowering the reported margin to 29.9% for the year. Next slide, please. Turning to the cash flow. Cash generated from operations was GBP 8.9 billion or more than GBP 10 billion, excluding Zantac payments, up GBP 1.6 billion year-on-year, driven by higher operating profit, favorable RAR movements and the CureVac settlement, partially offset by increased trade receivables. Free cash flow increased to GBP 4 billion or more than GBP 5 billion, excluding Zantac, driven by strong CFO.

Zantac payments in 2025 were GBP 1.2 billion, and the settlement process is now materially complete with GBP 1.9 billion paid in total, drawing a line under this matter. Next slide, please. Turning to capital allocation. Underlying free cash generation was strong at over GBP 8 billion before investment decisions.

GBP 4.5 billion was deployed in CapEx and BD as we added 3 potentially best-in-class clinical stage specialty assets to the pipeline and completed multiple early-stage and platform deals. Shareholder distributions totaled GBP 4 billion through the dividend and the share buyback with 93 million shares repurchased at an average price of 1473 and the remaining GBP 0.6 billion will be completed in half 1.

Overall, our balance sheet remains strong with net debt to EBITDA relatively stable year-on-year at 1.3x, including the absorption of Zantac and the buyback. Next slide, please. Now turning to the guidance for 2026 with growth rates stated at CER. Starting with our headline guidance, we expect sales growth of 3% to 5%, core operating profit and core EPS to both grow at 7% to 9% and to pay a dividend of 70p, a 6% increase. Product area growth is once again led by specialty at a low double-digit percentage growth, including mid- to high single-digit growth for HIV.

Vaccines and GenMed are both expected to be a low single-digit decline to stable, and we expect sales growth to be evenly phased through the year. Turning to the P&L. Gross margin is expected to continue to benefit from supply chain efficiencies and the portfolio transition towards specialty. SG&A will grow at a low single-digit percentage, benefiting from the acceleration of productivity initiatives.

And R&D will continue to grow ahead of sales as we invest to advance the pipeline. Interest charges and the tax rate are expected to increase year-on-year. However, these will be offset by the benefits of the share buyback to EPS. Importantly, the phasing of operating profit growth will be heavily weighted towards the second half, reflecting the GBP 300 million of charges taken in Q4 '25 and impacted by the annualization of the RSV settlement in the second quarter.

Additionally, currency could be a headwind. If rates hold at the closing rates on the 28th of January, we would expect an impact of minus 3% on sales and minus 6% on operating profit. Next slide, please. Before I finish, I wanted to take a moment to share the continued performance of the business. In 2021, we provided outlooks on 4 financial KPIs for the 5-year period to 2026. We have delivered consistent revenue growth and improvements in operational efficiency. We are on track to deliver against all the 4 KPIs. Taking the midpoint of our 2026 guidance ranges would lead to delivery of 8% sales and 13% operating profit CAGR over this period.

Additionally, cash generation has been significantly enhanced, and we're on track to reach more than GBP 10 billion in 2026. This, together with shareholder returns and a strengthened balance sheet, lay strong foundations for the next phase of growth. Our usual IR road map is shown in the appendix, signaling the major value inflections in 2026 and '27. Thank you. And with that, I'm pleased to hand back to Luke.

Thanks, Julie. Looking forward, I see 2 clear things we need to do to create value for shareholders. The first one is top line. This means delivering on our ambition for 2031 and addressing the loss of Dolutegravir exclusivity. The second is the pipeline. We need to accelerate what we have and add to it via Smart BD, and we also need our labs to produce more competitive products. So to do these 2 things, we need to evolve as a company.

Products are the key in this business, and we need to be more product-centric. And to accelerate the pipeline, we need to have more scientific courage and be more agile to capitalize on opportunities when we see them. Each quarter, you'll hear more detail about how we're going to make this happen.

Next slide, please. To conclude, 2025 was a strong year for GSK. For 2026, we're guiding for another year of top line growth and operating leverage. And for the long term, we know what we need to do to create value for shareholders and patients. And the focus is now on evolving the company to do it. Thank you, and we'll now move to Q&A.

And the first question comes from James Gordon from Barclays.

James Gordon from Barclays. First one, respiratory. Can you elaborate on R&D and commercial strategy in COPD and asthma? Because you've now got Nucala, Exdensur and then IL-33 and TSP all in development, but some overlapping products. I don't want to double count. And so how do we think about segmenting this given you've got products going for the same disease and also quite a lot of these mechanisms also have multiple competitors also looking at them for the same diseases. The second question was HIV, and I heard the comments on long-acting strong uptake and exciting next-generation data at CORI. So when could we see the 6 monthly treatment and PrEP Phase III trial start now? And commercially, what is the implications of the 4 month and 6 monthly in terms of your TAM? Because I've seen before you talked about the majority of sales in HIV being long-acting in 2031, but then that might partly just because the orals are going to go away by then. So what's the TAM increase if these work? And maybe if I could just squeeze in a clarification, the $40 billion plus revenue target, which has been reiterated, just is that the original assets? Or is that also including some of the recent acquisitions you were talking about and the BD you're talking about, please?

Great. Thanks, James, and I appreciate the question. So Tony, should we go into COPD and then I might add a little bit of color at the end of that in terms of how we position the assets and what our thinking is. It's obviously always dynamic. And then, Deborah, do you want to cover HIV? I think we're in very healthy shape there, some more color there. And then Julie, did you want to cover the assumptions around the 40. Again, I'll just take this opportunity just in case we get any other questions to reiterate the commitment to the 40. And again, I think we have a clear pathway for that. So Tony, over to you.

Yes. Let me start. Thanks for the question, James. First of all, I'm really pleased with the progress we're making in respiratory. Obviously, just a mark last year, the Nucala approval in COPD in the middle of the year and then at the end of the year, Exdensur in severe eosinophilic asthma as the first ultra-long-acting entry in our pipeline. I think what's important to understand about COPD, James, obviously, huge opportunity there, 300 million individuals globally and significant cost to the U.S. health care system, as I outlined in the presentation. But it's a complex disease. It's a heterogeneous disease. And that's why we're placing ourselves across a range of different long-acting mechanisms.

The way you can think about it is there is a high EO population. This is where IL-5 and Exdensur and Nucala are positioned. And again, let me just emphasize there that we have a label which covers both the bronchitic and the emphysemic and mixed population is important when one considers the reality of the hospital admission for a COPD patient. You can then think about the intermediate T2 population, which is the 150 to 300. We were delighted to see the Nucala label there, but that's where we see, for example, our long-acting TSLP starting to play increasingly in the future. And then the low 2 population, and that's where we're positioning IL-33.

So what we have, of course, is already starting in that high T2 population, the EUA 1 and 2 studies, that's the GE population that we're looking at. And the Vigilance study, which, as I mentioned in the script, looks as a brand-new approach, looking at rapid progressors in that high eosinophil population.

We also have ongoing Phase I and Phase II studies for the long-acting TSLPs and IL-33 mechanisms in the context of the stratification that I described. And then just to finish off, we'll be expecting in both of those to be starting pivotal studies over the next 2 to 3 years once we have been informed by ongoing Phase I and Phase II work and competitor insights. And then lastly, just to finish off, important to emphasize, we also have the HRS9821 molecule, which is the first nominated candidate from our ongoing collaboration that's focused on dyspnea, which is associated to pain associated with breathing and fits nicely into our cell portfolio given that, that molecule has an opportunity to be a DPI administered agent. And then lastly, in the low group, we have the recent deal we did with Empirico012, and that's now called GSK821. That's a long-acting oligo, which is aimed at a broad spectrum, as I indicated. We haven't disclosed the mechanism yet, but we will in the future as we gather more data. And James, what I will say is we get a REIT...

Yes. And James, what I will say is we're going to resist the temptation as a company to construct a lovely PowerPoint slide that shows how we'll carefully capture this bit and have trade-offs amongst our products. I mean, there is a strategic intent here, but we also recognize there's a [indiscernible] Dimension here, in terms of the data that these targets generate, but also the competition gets a vote as well.

I mean, ultimately, the long-acting institution. The launch for Nucala COPD in the U.S. is going very well and it was just there on Monday, we have around well, depending on which data set, 43% to 46% of new patient starts already. The market research and the messaging is really resonating. But we have transferred all of our new Catareps to Exdensur and Nucala OPD is being promoted by the Trelegy legacy team. because, again, we need to place our bets on the future and the ultimate future with 5 and higher EOR is going to be long-acting Exdensur for COPD. So thanks, James. I appreciate that question.

Deborah, do you want to give an update?

Thanks, Lee. So the key thing that I want to reemphasize is that we're on track to select our Q6M treatment regimen in the middle of the year. And as I said, we're going to do a meet the management event midyear where I'll lay out a lot more detail about the pipeline. But let me just give you a top line view now. So let's start with treatment. The treatment market is $20 billion in value, 90% of the value of the total HIV market. as I said in my presentation, Q6M is clearly our biggest opportunity in treatment. We're very confident in the assets that we've got to choose from and the COI data that we'll present will show just how strong those assets are, particularly VH184, which is unique, third generation, really potent integrated inhibitor. And we believe that to have a really potent regimen, you need to have an integrated inhibitor at the core. So in terms of what kind of studies will start Q6M treatment, you'll see us move into Phase II this year.

That puts us on track for our commitment, which is the 28 to 30 launch for our Q6M in treatment. In terms of PrEP, it's a different pathway because with the medicine that we're developing for Q6M PrEP, it's a prodrug of cabotegravir, which we've talked about before. And that means that we'll be able to go from Phase I to Phase III relatively rapidly and the Phase I will be starting this year where we'll then progress the dose selection and then we'll do a bridging study from the data that we already have from Q2M.

So our Q6M pathway is clear, and we're very confident in our ability to deliver against our milestones but don't underestimate Q4. There is a huge desire for Q4M treatment and in prep. And we know that many clinicians are really looking forward to opening up their clinic capacity, which will double from what they've got today with Q2M for Q4M. And I think what you're going to see is a rapid cannibalization to Q2M to Q4. And then actually, you will see a rapid cannibalization from Q4 to Q6. And as I've said before, particularly in treatment, you see the market really open up as we progress through longer and longer durations between administration. So the addressable market for Q2M is about 15% of patients. When we get to 4%, we get to 30% of patients. And then you've got with Q6M in treatment, 50% of patients who would be very willing to take a long-acting injectable. That is a big chunk of the market, which is why we are so excited about the offering that Q6M in treatment and in PrEP, but particularly in treatment will offer.

Thanks, Deborah. Julie, quick answer on the other GBP 40 billion. I think everyone knows, but let's confirm it.

Yes, sure. Thanks, James, for the question. So in terms of what we've included of the recent deals, IDRx has included Efimosfermin, together with the earlier stage Hengrui license, PDE34. Rapp obviously has just been announced, so it's not included at all in the LRF. And clearly, we continue, as Luke mentioned, to support our BD to build and continue to build the pipeline.

Great. Thanks, Julie. Next question please.

Next question comes from Simon Baker from Redburn.

Two, if I may, please. Firstly, on Blenrep. In light of the early feedback that you've had, you talked about the response to the REMS program. Can you just update us on how we should be thinking about the launch trajectory for Blenrep?

And then secondly, a slightly bigger picture question for you, Luke. You did mention some of the facets of your strategy. I just wonder if you could give us a bit more detail on how and in what form we're going to learn more about that strategy over the course of the year. Is this something where there will be additional disclosure as we go through the quarterly calls? Or are you envisaging having Capital Markets Day or similar events to lay out the strategy in that sort of for...

Thanks, Simon. I'll come to Nina in a second. I mean I think, as I said earlier, and thanks for your questions. Look, what you'll get from us is a very clear communication. If it's on track, you'll hear about it. If it's not, we'll call it out. And I really want to use these forums to regular update on our progress and where we're going to. So I think these are a very effective forum to do it, and we'll see how that evolves over time.

Nina, I mean, again, as I said in my intro, I mean, Nina and I have worked together a long time. She has huge experience in oncology and is now responsible for the whole portfolio in partnership with Tony. And also, we've had a number of other members join the team that have been in their roles during this commercial transformation.

And there's a lot of history with those individuals at Aventus and Roche and AstraZeneca. So they are people that many of you will know, and they've got a very strong record. And the aim of bringing them into the team again is just to rebalance and increase the focus on the portfolio, the pipeline and product execution.

So with that intro, Nina, over to you on BLENREP in terms of launch uptake and initial feedback.

Yes. Thank you. Just checking, you can hear me. Yes. Great. Yes, Simon. So you remember, BLENREP was launched in the U.S. just at the end of November. So there are not many -- we can't really share a significant update based on the sales numbers. But what we do know, we launched in the U.K. middle of the year. And the dynamic is opening the accounts is systematic.

It's happening, but it is definitely slower because of the coordination of care with Eye Care professionals. By now, we have about 70% of patients covered in the accounts that are open in the U.K. And based on the uptake there, we are actually extremely satisfied. Two things. There is huge interest to try Blenrep. And then we know that we have done good homework in guiding physicians how to use the drug. Physicians are very much aware of the need of extended dosing intervals to reduce or to avoid eye-related side effects. Now translating that to the U.S., we expect similar dynamic.

So the timing of opening the accounts is going to take a bit of time, longer probably than what you would see with an asset that doesn't need that coordination of care. But what we did learn from the first launch, as an example, I think I mentioned we are actively educating 18,000 eye care professionals. As an illustration, comparing to the first launch of BLENREP we had only about 5,000 to 6,000 eye care professionals engaged in our program, helping teachers to treat the patients. REMS has been a big factor. I think you know that. It has been received very positively.

Currently, REMS is not an issue. Physicians are very much used to REMS programs and BLENREP is very similar. Eye care professionals scale, as we said, we are going to reach a significantly higher number. And then communicating to the physicians how to use the drug that extended dosing is very relevant to enable early positive experience. And I would say that's what we see so far.

To your question, what can we expect? -- what we said before, it is not going to be a quick ramp-up. It's going to be a slow ramp-up, but the positive initial experience is more relevant than starting a high number of patients very early and then having a negative experience.

Thanks, Nina. And I would just add one other interesting data point is if we look at usage right now for BLENREP, it's about 50-50 between academic and community, which our strategy is to focus on the community. And with the product that is being relaunched and not a lot of experience in the community, I think this is an encouraging trajectory because at this point, you'd expect volume to be dominated by the academic centers who tend to move on newer things earlier. But we can see, to Nina's point, the strategy of focusing on the community, building confidence, supporting them to dose the first 5 patients appears to be showing promise. And we will give you a lot more granularity at the Q1 update, including on Exdensur.

Next question comes from Michael Leuchten from Jefferies.

Two, please. On for Luke. It's been reported that there is a reduction in R&D staff, I think about 350 people in the U.S. and also in the U.K. Just wondering, is that part of a broader program, normal attrition? Just wonder if you could put that into context. And then back to Nina on Exdensur. -- there's a few ways one could launch a product like this, especially early on to go into treatment experienced patients where, I guess, it'd be easier to make an argument to get patients on drug more quickly or into a naive population to broaden up the market. Can you talk about a little bit of the launch curve for 2026? So how should we think about this as the year progresses?

Thanks, Michael. So I'll cover the first one. I mean we're going to manage the business -- and where we say success, we'll reinforce it. If we have programs that are less promising or Tony and Nina in managing the portfolio decide to cull something, then we're going to be very dynamic and shift resources behind to where we can get the best return, generate assets that are most compelling. And ultimately, in doing this, we will have happy shareholders at the end of the process. So this is very much this element of accelerating R&D and simplifying how we work. And you'll see more of that. What we can assure you is that we will run the business with great discipline. And where we can see an opportunity, we will rapidly move resources, people, headcount, capital to support that. Nina?

Yes. I can take that. Thank you, Michael. Just as a reminder, Michael, and I think this information basically guides the strategy. we have about mid-20s biopenetration in severe asthma. So about 25% of eligible patients now receive biologics any. And of those who start on biologics, 65% will discontinue in the first 12 months. And that tells you if we would go for switch, active switch, that business wouldn't last very long because patients are dropping anyway. And I think we need to look at it in that context. Our main objective, I think Luke mentioned that when we talk about our sales force is going for bio-naive patients. It's very legitimate to expect there will be some switching, and there will be switching very likely from Nucala, hopefully also from other agents in severe asthma as well. What is more relevant is can Exdensur gain share from patients who would have otherwise started on other agents.

And 6 monthly dosing, I think you have seen everything that we have seen from both physicians and patients is that there is a huge level of enthusiasm for long-acting 6 monthly dosing, and that will hopefully translate into preferential use of Exdensur over other agents to initiate patients, but then also to start patients who otherwise wouldn't start on biologic yet.

Great. Thanks, Nina. And I think the positioning is the first and only biologic that delivers ultra-long protection in 2 doses that's landing extremely well when we look at market research and perception. Thanks, Michael.

Next question comes from Sachin Jain from Bank of America.

Perfect. A couple of questions, please. Just firstly for Nina and congrats on the new role. Perhaps a bit more detail on Blenrep. How many physicians have you had through the REMS certification process? And any cadence of how you think that will go through the year as a rate limiting factor? Second one for Deborah on the HIV event midyear. Clearly, we're looking to Q6M start. But I wonder if you will be disclosing how you think about the financials of that business through the LOE. And I guess 2 questions. One, how do you think about the rate of decline of this business relative to where consensus sits? And I guess Q6M isn't in the midterm guide. So do you plan on including it at that point if you start the Phase III? And then a quick one for you, Luke, just on your Slide 5 and high-level objectives. You've mentioned 2 things. One, simplification, do you intend to have any official cost savings program? And then secondly, R&D acceleration, are there any specific programs that you can target for earlier readouts or filing?

Thanks, Sachin. So I'll answer your last question, then we'll go to Deborah and then finish with Nina. I mean we are always looking to save money because I think it's always an opportunity cost, right? So if we can move resources behind particular assets where we think there is a higher payoff and return and they have the clinical profile to justify it, then we will do that. And we will continue that in a dynamic and disciplined fashion.

Areas for acceleration, again, I think naturally, the scale of B7-H3 RR is quite interesting. I think 584,7H4 -- it is a very competitive and dynamic area. But I think we're starting to see some color around the tox profile that could give us an edge. FGF21, we looked at all 3 of those companies. We think we have bought the best.

Again, you'd expect me to say that, but I think we can back that up in time with the profile of the frequency of the dosing and some of the profile of the product that will emerge in time. So they're probably the key ones, TCliP as well, long-acting TLP. Again, the target is being actively derisked by AstraZeneca. And I think that we have a plan to move that asset forward and rapidly because it is a very attractive area. We think long-acting can really reframe to Nina's earlier point about how respiratory diseases are treated. Deborah, over to you on HIV.

Okay. Thank you, Sachin, for the question. So -- if we think about Q6M first, so we are intending to set out our HIV story in the middle of the year. And at that point, once we've done a regimen selection and we then commence with Phase II, we will put that into our long-range forecast, which is how we always operate when products get to that Phase II phase. So you'll see that happen midyear.

You then asked about the evolution of the kind of the portfolio over time. So let me just give you a top line view, and we will come back and talk more about this when we set out the HIV evolution in the middle of the year. So we've seen a relatively rapid decline of Triumeq as the guidelines have moved away from Triumeq. And what's happened is over the last 12 months, it's created dynamism in the market and Dovato has benefited significantly as has Cabenuva. So the amount that's sitting in Triumeq and Tpic, as you can see, is going down quite significantly in advance of the loss of exclusivity of dolutegravir, which is, to remind you, a glide path, not a cliff starting in April 28 in the U.S. and then July 2 in Europe with obviously Dovato and Juluca in the U.S. having intellectual property coverage now until end of '29 for Dovato and July 2030 for Juluca. So the glide path is coming down. We're already seeing a move away from the old dolutegravir regimens into our newer regimens, and that is going to continue. And then what's going to happen is we will continue to power forward with Cabenuva Q2M.

It's doing incredibly well, growing fast. Apretude has not been dented by the launch of yes2Go. So that will also continue to grow '26 and beyond. And then what we will see is Q4M, both treatment and PrEP coming in and powering longer acting forward again until we reach the point at which we launch Q6M. And then we've got 2 brand-new molecules with intellectual property coverage, composition of matter patents through into the 2040s. And so you see a dip in '29 and '30 for the franchise as we face into the largest erosion through the exclusivity loss. And then we come back out into growth in 2031 and beyond. And that growth in that decade is going to be a significant contributor to GSK's success in the 2030s because we are incredibly confident in the value to patients that the Q6M will bring. So if that hopefully gives you a sort of a view as to how it's going to evolve, we will share more detail in the middle of the year. But I just want everybody to understand that HIV will be a big contributor to GSK's success this decade and into the future.

Right. Thanks, Deborah. Nina, quick answer and then we'll try to squeeze one more question ...

Yes, definitely. Sachin, thank you, first of all, trying to avoid the situation where you will chase me next quarter for the same number, REMS hundreds -- hundreds. And obviously, that's just a start.

Yes. I mean we feel happy about where we're at. One more question and we have time for that.

Next question comes from Steve Scala, TD Colin.

Two questions. First on Camlipixant. If GSK needs 2 positive trials to file, which is what the company has said previously, then what's the purpose of the pooled analysis? And/or has FDA confirmed it will accept filing based on pooled data even if one trial is negative? And secondly, on Shingrix, what were sales to GEFA in Q4? And what is your level of confidence in '26 on this drug?

Sure. Tony, do you want to cover?

Yes. Steve, I'm not going to get into details of regulatory strategy. But as you define, what it's giving us is the option to take the approach, both as independent and ultimately pooled studies. However it's worth saying that we remain confident in the outcomes for both KALM-1 & KALM-2...

Yes. And Steve, there was a shipment in December. We can give you that number offline. I don't have the top of my head. What I will say is that the underlying demand is improving in China. So it's up 6x since the start of 2025. Now it's a low base. And we've grown the market share versus gunway. So now we have 93% market share in that population, which is an operational improvement. And what is driving this? We've shifted the strategy to the one that we launched in Australia and also drove in Germany, and now we're employing in the U.S., which is also helping us get some traction there. Julie has told me it's $100 million we did at the end of last year. So there's still some stock in the pipe. But again, we'll give you more color on Q1, but it's heading in the right direction along with Shingrix in aggregate. So I think we'll stop there because I know a lot of you need to join another call, and I want to respect that. Thank you again for investing the time to construct such thoughtful questions and joining the call and your interest in the company, and we look forward to updating you further next quarter. Thank you.

Good morning, everyone. Welcome to day 2 of the 2026 JPMorgan Healthcare Conference, where it's my pleasure to host the GSK fireside session with Tony Wood, the Head of R&D. I'm Zain Ebrahim, European pharma analyst, and we'll move straight into questions. Tony, if that's okay.

Yes, you bet. Let me just say good morning to everyone as well, and thanks for getting out of bed so early. I'm sure not all of you have the advantage of jet lag that I do, so I appreciate it.

So Tony, you've been Head of R&D at GSK for 3.5 years now. How would you reflect on your time as Head of R&D over the last 3.5 years? What are the achievements that you're most pleased with? What are you looking forward to in the future?

Yes. And look, wow, time passes quickly. When I started, I said my first priority would be pipeline execution, and I couldn't be happier with the momentum that we've developed in the pipeline. We got 13 positive Phase III readouts in 2024. That naturally led to 2025, which was a real banner year for us with 5 out of 5 of the approvals we were looking for.

And as we look forward, 15 scale launches with a potential of greater than 2 billion peak year sales, which really underpin the growth objectives for the company out to 2031. And sitting behind that a next wave pipeline that is, of around about 25 assets and is increasingly beginning to illustrate the underpinnings of our R&D strategy. I mean I can't help but just emphasize a few of the approvals that we got last year because it was such an important year for us.

You'll remember, of course, at the end of the year, we had approvals for depemokimab, now Exdensur as the first ultra-long-acting biologic for respiratory disease. And importantly, remember, a medicine that is effective in reducing the severe exacerbations associated with eosinophilic asthma to a degree of about 70%.

And that obviously has a significant impact on hospitalizations. With only 2 administrations a year, that's going to be a really important aspect of us moving the work that we've done with Nucala in clinical remission even further. With Nucala in mind, I was delighted with the COPD label that we got in the middle of last year, particularly with the breadth of the population indication in that heterogeneous disease, and the indication at greater than 150 cells per microliter.

Again, Nucala prevents 35% of exacerbations that lead to hospitalization. And for those of you who don't follow the COPD area, it's worthwhile emphasizing, that comes with an enormous burden in the U.S. health care system, the 1.8 million ED visits a year, estimated about 7 billion. And for the patients involved, if you're admitted to hospital with COPD exacerbation, your 5-year survival rate is only 50%.

So significant. And then BLENREP, of course, delighted with the fact that we got the secured label that we did there in the third-line setting. Important to emphasize that 30% of myeloma patients are in third-line plus setting and 70% of myeloma patients receive care in the community. And BLENREP is a convenient off-the-shelf option for those folks.

Approvals in BluJEpa and PennEVI, I won't go into detail until we can move on in the pipeline. And then with that, having been said, continued momentum into this year. I'm sure a lot of people are interested to hear more about the BEPI data. Obviously, we were delighted to be able to announce that we had met the outcomes for the B-Well study at the top level.

I'm not going to be drawn on what those data are. As you might imagine, we want to make sure they're presented in the right way, and you should expect us hear more from us at EASL on that topic. But if you allow me just a few more minutes before I pause and give you -- I promise I'm not going to spend 40 minutes answering your first question.

Just a few minutes to stress a few points about chronic hepatitis B and BEPI. I mean, for me, the important thing is the first real advance in 30 years. To put it into context, it's -- hepatitis B has enormous epidemiology, 250 million people living with the disease. It's underdiagnosed. It's poorly treated. Current standard of care achieves a functional cure, which is essentially the removal of surface antigen after you withdraw therapy, only at the level of 1% or 2%.

And remember that hepatitis B drives 56% of liver cancers. There are 1.1 million chronic hepatitis B-related deaths every year. And as I've said in the past, we now have a medicine in which we're aiming at a 15% to 20% functional cure in the selected population that we have for B-Well. I'm sure we might come back to that. So I won't belabor the point.

One final thing to stress, though, because I do want people to appreciate the consequences of being able to provide a functional cure for hepatitis B. We provided data at -- this is real-world evidence from Drysdale that was published last year, presented at APASL and the Global Hepatology Summit.

And what those data show is that if you can achieve functional loss of surface antigen, you get an almost 90% reduction in the risk of hepatocellular carcinoma and a 60% reduction in the risk of all-cause mortality. So enormous epidemiology, a disease with dreadful long-term consequences and now the first effective functional cure and progress in more than 30 years.

So really delighted with that. Finally, then just to give you some numbers on what's ahead of us. As I said, 15 reg files already accepted since the start of 2025, 15 scaled assets. We talked about at the end of last year that we started 4 new pivotal studies. I expect more this year, potentially up to 10. So I couldn't be in a happier position with regards to the momentum in the portfolio. And what you can expect from Luke and myself in that context is a continued focus on growth of the company and acceleration of R&D and the use of technology to achieve that. So a bit of a long one, but I wanted to get a few key points across to everybody before we got started.

Definitely. And I want to double-click on some of those key points in terms of the progress you mentioned on each of the drugs that you called out. But before we go there, just thinking about R&D productivity, given the pipeline progress that you've mentioned, how do you measure R&D productivity? And how has that improved or evolved in the time as your Head of R&D? Which areas do you think, in particular, are improving and where do you see scope for further improvement?

Yes. And look, let's first of all, kind of focus on what R&D productivity is all about. And if I can emphasize the position, Luke and I work very closely together. We have a super working relationship. He's going to be focused, as I mentioned, on pipeline growth and acceleration of R&D and the application of technology. I'll get on to a little bit more in terms of the application of technology in a moment, but I wanted to give you a sense of the momentum that we've got building in our late-stage development pipeline and the progress that we're making there.

Our end-to-end success rates, and by that, I mean, from preclinical to approval. They've more than doubled since 2018. That takes us back to the partnership that I had with [ Hal ] initially, our cycle times measured as last patient visit to the first file in a major market have more than halved from '21 to '24, they're upper quartile. And of course, because of all of that, we're upper quartile in volume of launches and R&D spend per launch as well.

Now this is an area where there's always a need to continue to improve, and there's much more to come. That is not just around ensuring the acceleration of those 15 opportunities that underpin the growth propositions of the company, as I mentioned, but you'll see an increasing focus to bring more of our business, the proportion of business in specialty, which has been growing and a comprehensive tech program that I expect to impact not only in the sorts of areas that we've been talking about, but in aspects of earlier R&D as well. And I might come on to that in a moment. So I'll pause there.

Yes. Just maybe building on that with -- you mentioned technology. So AI and machine learning, we talk about a lot. How are you using that in your R&D process today?

And look, I mean, obviously, in general terms, there's an opportunity for AI and machine learning to improve efficiency of our business across a range of what we do, think about that as a reduction of time and cost. But really, from my lens, the bigger opportunity we see is in terms of transforming what we do in R&D.

And I'm going to pick from that a few different segments. We've focused extensively on solving the key problem, which is attrition at Phase II. For us, that goes further. It goes into not only the choice of targets with improved survival characteristics, but also the connection of those targets to very clearly defined patient populations. So think about the union of target and patient. In addition to that, I'm going to talk a little bit more about target and patient, give you some examples.

But before I move on to that, I don't want to give you the impression that that's our sole focus. Obviously, we've put a great deal of effort into AI/ML for what we call the predictive design of molecules that whether it's small molecules or protein therapeutics or oligonucleotides. And also, we're getting increasingly interested in new technologies, for example, through our partnership with flagship.

I may come on to that later as well. But -- and then obviously, I already mentioned effectiveness of running clinical studies themselves. But let's just go take a quick look back at that target to patient piece because there are a few things that I want to emphasize in the portfolio. You can look at our programs in COPD. I'm very excited about the breadth of the COPD portfolio we have.

Those of you who followed us meet the management on that particular topic will remember that we highlighted the fact that we have detailed COPD models across different dimensions of the disease. One highlight that comes from that is our opportunity, for example, to spot the potential in IL-33 and TSLP as combinations. You'll realize we're moving into steatotic liver disease, which we see as an enormous opportunity as well.

And their U.K. Biobank data together with detailed disease phenotyping, we hired Sarah Teichmann a few years ago and what her work is doing is allowing us to layer on top of the causality that comes from genetics, detailed understanding of the character of the disease caused by individual pathways.

And that was what sat behind our decision to license Efimosfermin, which sits alongside our program with GSK-990 gives us a really nice complementary approach to both the inflammation and fibrosis that's characteristic of steatotic lung disease. One more, and then I promise I'll pause as well. And you might have -- if you followed recent announcements, the Helix data relationship that we announced yesterday, that again, is similar principle, adding much more detailed phenotyping to [indiscernible] type data. And the Noetik deal that we also announced, that's the case in oncology, where we've built a comprehensive approach under [ Tony Ng's ] leadership with digital biologic twins and organoid capabilities.

It's going to allow us to really tease apart in the exciting areas, B7-H3 and B7-H4, who are likely to be the responding patients in that context. So hopefully, that gives you a sense of lots going on, underpinning all of that for us. It's not just about AI/ML, it's about collaborations and partnerships, which allow us to access or together generate data that then inform this multimodal approach that links causality from genetics through phenotype, ultimately to clinical readouts that can be initially descriptive of the progression of the disease and image, for example.

And then the last step in all of that eventually will be as we continue to explore these areas, the connection of that through to outcomes that patients care about. And you'll see that play out very much in our SLD portfolio.

And you mentioned a few licensing deals there and business development. So Boston Pharmaceuticals being one this time last year, it was IDRx. And earlier this week, you announced the collaboration with Summit on ivonescimab. So just how should we think about the pace of business development going forward, the appetite for more BD? What are your key focus areas? What are you looking to supplement?

Yes. Look, we're very pleased with the BD we've done. Obviously, Luke and I have been close partners together with David and his team in all of that. And so what you should expect to see is pretty much more of the same. And if I can sort of bucket that in 2 ways. The deals you mentioned, the IDRx deal and the Boston Pharma deal, very much in our sweet spot, deals for which we are looking for assets where there's an opportunity for them to drive near term -- by near term, I mean 31 sales, deals for which we expect to be able to accelerate for both IDRx and indeed, Boston Pharma.

I mentioned we have pivotal studies that we started within the fall last year. They both fit in that category. We've gone literally from deal signing to pivotal study starts within 6 months in both of those indications. And I won't go into any more detail about what we see as being exciting in the assets in and of themselves, but they're very well aligned to both our research strategies and our commercial strategies.

In general, there's a theme sitting behind them in terms of the pursuit of long-acting agents. And in addition to that, I mentioned data and tech-based collaborations. I won't repeat what I've already said, but it is worthwhile emphasizing at early stages. What a lot of the work that we're doing in understanding patient and target is illustrating for us is really the need to begin to change, if you like, or reprogram the cellular proposition associated with the diseases that we're interested in. And that's why you see a focus in ADCs, which are doing that through depletion of particular cell types, oligonucleotides, which reprogram.

I'd point you to the Empirico deal that we signed at the end of last year with EMP-012, which will be a long-acting siRNA in Phase I for broad opportunities in COPD and then the LTZ deal, again at the end of last year, and that's looking to take the sort of principles that have applied to T cell engagement and apply those principles to macrophages.

So what you should expect to see is more of the same. In terms of Luke's focus on the growth of the company, I'd just take you back to strategically aligned with our areas of commercial interest for me, technically aligned in R&D and a general focus on long-acting agents.

And just maybe pivoting slightly and building on your team of long-acting agents, the most recent one that we've seen in terms of approval is depemokimab or Exdensur. So early commentary on how that launch is progressing, which patients do you see as the most likely to benefit from a 6-monthly option, 6-monthly health care administered option versus self-administered monthly or every 2-month options?

Yes. Look, obviously, only just got approval, so it's very early days. The feedback we have from both patients and health care professionals for Exdensur is they really do value the long-acting component of it. I think we've got early feedback that suggests that upwards of 80% of pulmonologists see it as potentially becoming standard of care in the treatment of severe eosinophilic asthma.

And I think it's a feature of bio penetration in lung disease that's worthwhile emphasizing in the context of Exdensur. And that is that -- if you look for those who are -- by penetration is low. It's typically less than 30%. In addition to that, compliance is also low. A year in, typically only 35% of patients are complying with their medications.

So there's a real recognition that 6-month treatment is the tipping point at which we expect compliance to pick up. And that coupled with the point that I emphasized earlier that you have about a 50% reduction in risk of exacerbation, the 70% reduction in severe exacerbations. It's worthwhile emphasizing in the SWIFT-1 and SWIFT-2 studies for those who were on depemokimab, high 60 percentage of individuals experienced no exacerbations at all.

And that kind of brings us back to the point that I made about clinical remission and what we're doing with Nucala. That is essentially moving patients to a position where exacerbations are no longer a threat that is part of the reality of living with the disease. In addition, you can begin to tailor off on steroids, for example. So delighted with the early insights we're getting for depe and I'd say early days at the moment.

And Exdensur, you also have the NIMBLE study reading out. So could you contextualize for us what that study is trying to achieve? What are you looking to see there? And how important that is to support the launch in asthma?

Yes. I'll expand it to a number of different studies, so I can give you the context of what's going on around depemokimab. Clearly, the important registrational studies with SWIFT-1 and SWIFT-2. Then what we had was another set of studies that we read out, which are read out, which I been tiering as the next most important. They were the AGILE studies, and that was about an extension to look for the duration of effect that we've seen with Nucala out to 2 years.

And it was also about switching individuals who were on the control arm on to depe and being able to show that you had durability of effect and continued efficacy in the context of the headline data that we got from SWIFT-1 and SWIFT-2. NIMBLE was really an informational study.

We have the data in-house and we're analyzing it, but it's not a significant component of our registration package. It was asking a question in terms of switching, but it's worthwhile emphasizing that, again, the feedback that we've had from health care professionals that is emerging is that many of them -- around 50% would consider going straight into naive patients with depemokimab.

Right now, we initially looked at as sort of largely a switch market, but that seems to be diminishing. So really, for me, it's all about SWIFT-1 and SWIFT-2. The other studies have a lesser importance in terms of the registration.

And the other studies that you started as well in Phase III in COPD for Exdensur. So you talked about the success of MATINEE and the rollout there has been strong in terms of NBRx share. So just what were the learnings from MATINEE that you've applied to the design of the extensive trials? And when can we see data there?

Yes. And if you remember, when we were running the MATINEE study, a lot of people were asking me if I had so much confidence in IL-5, why wasn't I already starting the Phase III pivotal studies with depemokimab. And that was because I wanted to be able to learn from the broader experience of the MATINEE studies in the patient population to consider characteristics that would allow me to design the subsequent pivotal studies for COPD with a still increased probability of success and how best to describe it? Clinical effectiveness in the protocol design.

So this is an area where as a result of what we learned from MATINEE, we've deployed, again, an AI/ML solution to help us look at -- and there are 2 distinct sets of studies that we started for depe. There is the ENDURA-1 and 2, that's the paired Phase III study in the moderate to severe COPD patients where GOLD guidelines currently indicate IL-5.

I wanted to learn what I could from the MATINEE experience to make sure that I had the best possible effectiveness of those studies. But importantly for us as well, we also wanted to see if we looked at more detailed characteristics of the patients and their progression, could we identify a less severe population, mild to moderate, where progression propositions into the more severe disease would be a risk for those patients. And could we use depemokimab as an opportunity to help the trajectory for those individuals.

That's what's behind vigilant. And so waiting for MATINEE was about securing that overall proposition. I might, if you're okay, use this as an opportunity to talk about the broader COPD portfolio because I'm particularly excited by the assets that we've built there. A common theme across all of our COPD portfolio, again, is in the ultra-long-acting area. And let me just stress a point that I made earlier. ultra-long-acting brings confidence in protection.

And if you have a disease in which a hospitalization really does reduce the quality of your life, your prognosis, COPD patients never return to the place they started after an exacerbation. So really important for us. in the ultra-long-acting portfolio. COPD, having said that, is a heterogeneous disease. We were delighted with Nucala to get a label, which covered both bronchitic and emphysemic individuals.

And so as we're looking to expand our long-acting respiratory portfolio, we have T-slip. That was a deal that we did a couple of years ago now -- well, actually, I think it was the beginning of last year, initially for low T2 asthma, but we're also looking to position that. As I mentioned earlier into COPD, that sits alongside IL-33.

And this is another area where through collaborations with Cambridge University and with the Boston University Center for Regenerative Medicine, where together with the data that we've gleaned from our own clinical studies, we're developing a detailed understanding of the underlying phenotypes stratification, if you like, of COPD patients. All of that is playing into the path by which we will initially establish doses and confirm those responsive patient populations across 33 and T-slip and then move into pivotal studies.

You should expect to hear more from us in terms of those pivotal studies in the next 2 to 3 years. But I really am delighted with the position that we have with our long-acting agents. As I mentioned, we're not leaving it there. The deal with Empirico looks at a broader approach. We haven't disclosed the target yet.

So I'm going to keep that close to my heart, if you don't mind. And then I can't -- just to complete the picture, the Hengrui deal, which we signed at the end of -- at the beginning of last year, delighted about the -- it's a real lead of that deal. It gives us access to 11 mechanisms. We've split them pretty much 50-50 between oncology and R.

And the first example there is the PDE3/4 molecule there. That likely will be deployed against dyspnea, which is pain with breathing. If you look at how the Verona asset is being deployed from GOLD guidelines. So you can see I've got a pretty comprehensive portfolio looking to deal with COPD. And again -- as well as the health care burdens that I mentioned, a disease that impacts 300 million individuals.

And how is your PDE3/4 differentiated from the Verona or Merck asset?

Yes. Let me just take a couple of minutes to sort of describe it. PDE3/4 has been of interest in inhaled therapies since I was in shorts. I kind of been following that mechanism. I've had a few goes at it myself and my days as a medicinal chemist. And I'd say it's not entirely clear yet between the 3 and 4 mechanisms, whether or not the effect is more about bronchodilation.

And in fact, if you look at the Verona data, most of their data is really an improvement in lung function rather than a reduction in exacerbations. So what I wanted was not to be too clever, I wanted to exploit the fact that somebody had already shown me what the right profile was, except that, of course, their molecule is nebulized, which gives significant patient compliance issues. You have to sit down and spend time inhaling the medicine. We think that the 3, 4 that we have with Hengrui potentially could be part of a DPI and then it fits beautifully, of course, with our Trelegy franchise. So that's how you'll see us begin to differentiate that asset.

And my last question in the respiratory space is on camlipixant, where we'll have data later this year. So could you talk through latest expectations on timing of that data, the unmet need that you see in refractory chronic cough and what we should be looking to see in terms of placebo do benefit when we see that data later this year?

Yes, sure. So an eagerly anticipated readout from everyone, I think. Let me just start a little bit with the epe of refractory chronic cough to begin with. It's, again, a disease that fits and do I get from a friend help later. It's a disease that very much fits in the poorly treated and therefore, underdiagnosed category. Right now, we see about 28 million patients globally, 10 million with a cough that lasts more than a year.

I'll come on and describe the characteristics of that cough in a minute. And those 10 million, we see 3 million in the U.S., 3 million in Europe. There are about 1.8 million individuals who are already currently managed by pulmonologists. And these folks have had a journey of typically seeing 3 health care specialists before they arrive at a pulmonologist. Imagine a life in which you're coughing between [ 500 ] and 950 times a day.

Imagine that cough being clustered in such a way that it leads to broken ribs, incontinence, vomiting, depression on top of the stigma associated with sitting on an airplane or in a restaurant next to somebody who's literally coughing all of the time. And so there is huge medical need here. Unsurprisingly, only 3% of patients are satisfied with current treatment options. So that's what really caught our attention about camlipixant.

And again, an area that I've been following for the majority of my career in the early days as a medicinal chemist, these [indiscernible] receptors. And P2X3 is overexpressed in the no-dose ganglia of your lungs. And as that overexpression raises, it's that sensitization, which causes the coughing. Now it's an area in which the ability to get a molecule that targeted that without incidentally hitting P2X2 was really a big problem.

Because if you hit P2X2, you cause a very unpleasant taste disturbance, and that's the problem that Merck has been handling. We found camlipixant with a molecule that had vastly improved preclinical and clinical selectivity. Merck's incidence of taste disturbance is somewhere in the region of 60%, well less than 6%. And so that, coupled with what we saw in the SOV data, which was a 35% reduction in the coughing frequency across both doses actually with only, as I say, 6% taste disturbance really set this up as a case where we felt not only could we find an important medicine for these people. But we had one whereby the characteristics of the molecule itself would overcome one of the major obstacles that Merck faced with gefapixant, which was functional unblinding of the study because of taste.

Now having said that, this is another example where actually being second is pretty beneficial for us because we've been able to learn from the other aspects -- sorry, excuse me, the other aspects of the CRL that Merck got. We've worked closely with the agency in terms of the data processing and the patient-reported outcomes, for example. And we've designed the study as well to take account of some of the degree of placebo effect. There are 2 studies running, KALM-1 and KALM-2.

For those of you who are tracking them, let me just give you the headline on where they are. KALM-1, last patient, last visit at the end of last year, as we said, we're currently transferring data. You'll appreciate when you're using a digital device to count cough, data transfer is something that we need to pay careful attention to. And the second study, KALM-2, which we extended because I was given the opportunity through regulatory interactions to increase the number of high coughers into that population.

That now has the last patient first visit. We expect it will complete around about the middle of the year, and we'll report as we do typically for these Phase III studies, on both Phase III studies together with the intention ultimately is to pool the data. So as far as I'm concerned, everything is proceeding as we would expect with respect to KALM-1 and KALM-2. We have the best molecule. We have a really great clinical trial design, and we remain confident in the outcome on the basis of what we've seen from the SOT Phase II study. By the way, we see 15% to 20% improvement in daily coughing frequency as being clinically significant for those of you who are trying to get ahead of when we report the results.

That's very helpful. And maybe now shifting gears to oncology and maybe starting with BLENREP, where you had approval in the U.S. late last year in third line plus to begin with. You've had approval ex U.S. and second-line plus. How is that initial launch going? And maybe broadly, how are you thinking about the development plan going forward based on your latest discussions with the FDA?

Yes. So let's just start with the launch, first of all, obviously, early days. And you'll remember, we got the label first in the U.K. So a couple of things to stress about that U.K. experience. So far, we've got 50% share in the Tier 1 HCPs in the U.K., around about 10% to 15% in the second-line patients. So that's all starting in the way that we'd hoped.

You'll remember, Luke said we're going to go slow to go big, and this is really all about ensuring that we help the treating physicians get the right network of care that's required to be able to administer BLENREP.

What we hear about the REMS is great feedback in terms of the simplification that we were able to establish there. We've trained several hundred HCPs. By the end of the second quarter, we expect that to be at 7,500. Let me just talk about a few things in terms of third line and the path into second and first line to sort of preempt a few more questions that you have. Worthwhile emphasizing third line plus in the U.S. is 30% of myeloma patients. The market is currently around about $20 billion.

It's projected to grow to $40 billion by the end of the decade. Our expectations for BLENREP greater than $3 billion. So I think even with third line at 30%, we're in great shape. Obviously, we want to get to second line. You can think about the major components of second line being the continued following of the DREAMM-7 study.

The FDA approved third-line BLENREP on the basis of the third-line patients who are in DREAMM. They progress more rapidly. So as you'd imagine, the data were more mature in that setting. And just to reiterate it for everyone because it's not often we get the opportunity to have data with this sort of impact on patients. There's a halving of the risk of death and a nearly tripling of progression-free survival.

That's from 12 months out to 30-odd months. So a really significant impact for these patients for whom actually, there are very few options. Myeloma needs new mechanisms. And BLENREP is really the first off-the-shelf opportunity in that setting. So particularly for community use, where, as I mentioned earlier, about 70% of patients are treated. So you should expect to see us continue to follow the maturation of the DREAMM-7 data. We're running a single-arm study that we're calling DREAMM-15 that we're looking at different combinations. And we're continuing to progress with the DREAMM-10 study, which is in the first line. What's important there is we have reduced loading dose and then increased dose intervals in the first-line setting. That will be an MRD to PFS endpoint.

Typically, you look at MRD 9 to 12 months in. And obviously, we'll be continuing to evaluate with the real-world experience of managing the ocular side effects. All of that together to cut a long story short, potentially gives us the opportunity for refiling in second line and first line at the end of 2028.

That's very clear. And we've seen -- you mentioned lack of options. We have seen some data now from MajesTEC-3, the DARZALEX/TECVAYLI combination, which looks quite compelling data. So what's your perspective on the efficacy there and how the treatment landscape might evolve with the launch of DARZALEX and TECVAYLI and how that could impact BLENREP?

Yes. So look, first of all, as I said, it's great news for myeloma patients. They need new options, and this is another BCMA-based opportunity for them with great efficacy in the triplet that you mentioned. I think though, if I go back to the point that I made that 70% of myeloma patients are treated in the community.

And let me sort of just describe the treatment experience with BLENREP. In the first year, you'll get between 5 and 8 infusions. These are 30-minute infusion delivered in an outpatient setting. In the second year, typically looking at 4 infusions, we know that you can stop therapy when grade 2 or 3 ocular events start to appear, and you can do that without impacting efficacy.

The MajesTEC data in the TCE setting still have the reality of treatment with TCEs. These are incredibly powerful medicines. So you get hypogammaglobulinemia, which means that you're going to need -- you need IgG infusions. Grade 3 infection rate is still high in that group. If you follow the data closely, you'll see that actually the Kaplan-Meier cross over in the first phases. So clearly an important opportunity, but we see the convenience of BLENREP and the non-life-threatening side effect profile as being something that will give us advantage in the community setting.

Actually, it's worth -- it reminds me to say one more thing about the DREAMM-10 first-line study that I forgot to mention. We'll also, of course, be looking to add a quad arm to that to look at those individuals treated in more hospital settings, particularly for those who can tolerate the quad regimen. But I very much see this as great news for patients, but we're operating in a different segment and the simplicity of BLENREP relative to managing the side effects with the TCEs, I think, is something that looks like it will continue to persist.

And thinking about HIV, I think you said you will have an update in the middle of the year about your 6 monthly options. So can you remind us what you're thinking there, what we should expect to see from you at that event in the middle of the year?

Yes. I mean let me just on behalf of David, give you a sort of a broad overview of what's going to happen this year. I think, David, if you don't mind, I'll quote what you said yesterday that this is going to be a year in which you'll hear much more from us on HIV.

One of the key pivotal readouts that we're expecting this year that will come with a file is the Q4M PrEP data. We're also going to start a Q4M treatment. And I think what's really important to emphasize here, remember, treatment is by far the majority of the long-acting opportunity. And we are the only ones with an existing licensed Q2M treatment option. What's really important about treatment is the backbone of an integrase inhibitor. Integrase, for those of you who know a little bit about me, my history is in HIV and integrase was a transformational identification of mechanism of action, one that has fantastic durability, but one that's been relatively difficult to find chemical matter for.

So we're delighted that we'll be in a position where the Q4M treatment will start this year. We're very excited with VH184, which is the third-generation integrase inhibitor that has not only the characteristics, which we think will support it as a component of Q6M.

And that's the point actually which you see a bigger conversion of the market from oral into long-acting. So very comfortable that it has the appropriate characteristics to support that as well as an improved resistance profile. And if you'd ask me, what did I expect to see an improved resistance profile on top of dolutegravir, it would have been, wow, that's a stretch.

So we're in great shape because of our partnership with [indiscernible] on that, I'd probably better stop there given that we're out of time.

Thanks, Tony. Yes, we are at the top of the session, but thanks a lot for this at the time. It's been a great discussion. Thanks, everyone, for being here, and enjoy the rest of the conference.

Great. Thank you, Zain.

Thanks, everyone.

So we're ready now to start the next session. It's my pleasure to be able to introduce GSK. And from GSK, we have Deborah Waterhouse, who's the CEO of ViiV, and also Kimberly Smith, who's the SVP and Head of R&D of ViiV, the HIV business. So I think probably the best thing to do here is actually if I hand over to Deborah to see if she's got any sort of opening remarks, just kind of what's the state of the nation on HIV ViiV at the moment. And then we can move into some Q&A.

Great. Thanks, Graham. So it's been a fantastic year for ViiV. We have had really strong growth, above expectation. In Q3, for example, we grew 12%. Year-to-date, we're growing 10%, and our outlook for the year has been increased to around 10%.

The growth is really driven by our long-acting injectable franchise. This is really important to us, because it's a set of medicines informed by patient insights. People want to make HIV a smaller part of their life and the long-acting injectables are really delivering against that. And the reflection is therefore in the growth that we're seeing, more than 40% growth for Cabenuva and 75% growth for our long-acting injectable in PrEP Apretude. So really happy with the momentum of the long-acting injectable franchise, whilst also obviously, our orals, particularly Dovato, continue to do well.

And then the other thing that's been happening is pipeline progress. Sure we're going to talk quite a lot about that today, Graham, but really happy with the way we are seeing the future of the franchise unfold, which is absolutely focused on long-acting injectables every 2 months for PrEP and treatment today, moving to every 4 months and ultimately every 6 months. And we know that as we increase the duration between administration, the population, the addressable market as it were for the medicines expand. And so that's why we're so confident that we can navigate the loss of exclusivity of dolutegravir and see ViiV come out the other end of the patent glide path rather than the cliff, as we call it, really healthy. And that into the 2030s, we will be back to significant profitable growth, which is obviously very critical to the future of GSK. So looking forward to our conversation today.

Great. Well, I might just kick actually off on sort of current business. So maybe just help break down what's driving the growth and the shift away from triple to dual to long-acting, really where is the key growth drivers now? I think it was -- Q3 was predominantly long-acting, but help us understand what that mix of business looks like at the moment?

Yes, sure. So if I look to quarter 3, which is pretty representative of the year actually, so we grew 12%, 10% was volume growth and 2% was positive pricing. The pricing has been either negative and positive, a little bit up and down through the year. But fundamentally, our growth this year is based on volume growth. And that's mainly driven by the long-acting injectables. So 75% of our growth was from the long-acting injectables.

Dovato continues to grow kind of mid-20s. You've got Cabenuva growing mid-40s and Apretude 70%. So as you can see, a majority of the momentum in the business is driven by long-acting injectables. And we're super happy with the progress that we're making there.

And you upgraded the guidance for ViiV at the Q3. So what was the predominant driver of that?

Cabenuva. Honestly, Cabenuva this year has taken us by surprise. I mean we're very enthusiastic, as you would imagine us to say, about that product. And I just spent 2 days in Miami with big providers talking about the momentum of their patient base. And they say Cabenuva is the one medicine that everybody comes in and asks for, because they can see what a difference it can make to their lives. It's absolutely liberating once you're on that medicine. And the demand is significant. And actually, the thing that stops it from growing even faster, which we can talk about later, is the capacity that the clinics have for long-acting injectables, and we're seeing that expand, but they can't keep up with demand at the moment. So that's why I'm so hopeful for the future of that medicine.

Okay. And so if you break down the franchise at the moment, what proportion of the overall franchise is Cabenuva right now, or long-acting right now? And where do you see that in 5 years, or particularly by the time you get to dolutegravir LOE?

So at the moment, we are expecting this year the long-acting injectables in the U.S. to be about 30% of our overall business and 70% is oral. It's just a little bit less than that ViiV overall. But obviously, the market we focus on is the U.S., because that's where a majority of the margin and the sales are made. So you've got a 30%-70% split.

By the time we get to 2028, for ViiV overall, the long-acting injectables will be about 40% of our business, and that's the year, obviously, that we lose exclusivity of Tivicay and Triumeq in the U.S. only. And so as the decade continues, you'll see our long-acting injectables become a larger and larger percent of our business. And we're hoping that by the time we get to about 2030, which is when you'll have seen the majority of the dolutegravir loss of exclusivity take place and significant growth in the long-acting injectables, we're about 80% to 90% long-acting injectables at that point.

And right now, we have most of the patients coming from that are going into Cabenuva for the first time. So is that newly diagnosed? Is it more switches from oral? And of that, how much is GSK versus older regimens?

Yes. So obviously, the label is the switch-only. So everything is coming from switch. 75% of Cabenuva's source of business is from our competitors. 25% is from our own portfolio, and that's a mixture of Tivicay, Triumeq-containing regimens, and Dovato. But actually, a majority of the business is coming from our competitors, all the ones that you would have expected.

And then -- so the label switch, but do you see anybody going on an initiation of an oral therapy and then switching? Is that a strategy that is emerging in demand or...

That's a good point. So we don't see people going on as they've been newly diagnosed. But what we are seeing is the minute people are virally suppressed, they are then moving over. And sometimes you see people starting on Juluca, which is cabotegravir/rilpivirine once daily oral, and moving into the Cabenuva. And then there's also a study that we've done, which Kim can talk about, which shows that you can rapidly suppress on Dovato and then move on to Cabenuva, and people significantly had a preference for Cabenuva in that study.

Yes. That was the CLARITY. Yes, we shall come on to that.

We'll come on to that.

Okay, cool. And then if you look at your market research, what proportion of the existing HIV population do you think you can target with 2 monthly Cabenuva. I know you've sort of kind of done the work around this, and then we'll come on to Q4M, but like just talk through the strategy of what proportion of the market becomes accessible as you start to lengthen the treatment paradigm.

I think the right word that you have used there is accessible or addressable. This doesn't mean that the numbers I'm about to give you are what I think the share is going to be, because obviously, you have to go through the payer journey, specialty pharmacy, et cetera, et cetera. But when you have an every 2-month long-acting injectable, the addressable market is about 15%. So 15% of patients would be willing to take an every 2-month injectable.

It doubles when you get to every 4 months, so you're at 30%. By the time you get up to Q6M, you're at 50%, because at that point, you've got a group of people who just don't want to have an injectable. They don't like needles. They don't want to come into the physician's office and have to have the medicine administered, but you've got half the market at that point who would be open to a long-acting injectable.

And that's really why we developed the products in the first place, because we felt that strong community need for something that makes HIV a smaller part of their life, liberates them from stigma, liberates them from taking tablets every day, liberates them from forgetting to take their tablets, and adherence for some people is a real issue. So that's where we see the market evolving.

And how granular is your data and what's the barrier to taking injectable? Is it just the needle? Is it intramuscular? Is it frequency? Is it I've got to go to the physician's office? If you've got sort of more color on that?

All of the above. So every 2 months is too often for many people. They live a busy life, like everybody who's undoubtedly in the room and online today. So they just don't want to go in 6 times a year. You've got people that hate needles. So there's a proportion of people that feel strongly about that. And then there are other people who don't want to have to have the physician administering their medicine. They want the autonomy of doing that themselves at home. So there are a number of barriers.

The main barrier is actually capacity, though, not in terms of wanting the medicine, but the main barrier to getting the medicine is actually capacity at the health care professional clinics. And that's why we're so excited about Q4M, because obviously, that's going to double the capacity.

Yes. One additional build on that barrier is that Cabenuva or cabotegravir/rilpivirine is an NNRTI. A lot of people have been exposed to an NNRTI previously and may have resistance. So they aren't candidates for Cabenuva.

Got it. Okay. So in terms of the Q4M, that's an interesting point you made there. So part of the 15% to 30% isn't I'd rather take it less frequently, it's just that capacity being freed up at the clinic, because you're just halving the amount of patients going all the time.

Right. They double their capacity when we double the interval, and that will make a big difference. So when we talk to providers about Q4M, they want it yesterday, because they're getting asked about Cabenuva all the time, but they don't always have enough ability to give it to all the patients who are asking for it.

Got it. Okay. And then in terms of Q4M and how often patients would normally see their physician, I think I had it in my head that it was maybe every 6 months, but I think you made a comment more recently that every 4 months is also actually a fairly normal schedule.

Yes, 4 to 6 months is about right. I mean, so individuals that have been stable for a very long time, you'll see them twice a year. Even occasionally, you'll see them once a year. They're really, really reliable. So anywhere from every 4 months to every 6 months or every year.

And certainly, talking to providers over the last week, you forget people come in and have to have their viral loads taken a certain amount of times a year. But actually, there's a real focus on STI testing. So obviously, there are outbreaks, so sexually transmitted infections, and those are at a higher level than ever before. Particularly these days, you see a lot of gonorrhea, a lot of syphilis, a lot of hepatitis. And so that testing is also driving people in more frequently as well, both in the PrEP market, but also in the treatment market as well.

Got it. Okay. And then commercially, just on Apretude at the moment. Obviously, there's a competitor in the market now with lenacapavir or Yeztugo. So have you seen any impact on Apretude from that launch so far? And what's the sort of feedback you're getting from the prescribing community on the launch and how it compares to Apretude?

So we haven't seen any impact on Apretude. It grew 75% in Q3. The NBRx and the TRx remain on the same trajectory. As we think about the PrEP market, I mean, it's a market that's very underdeveloped. 1.2 million people could benefit from PrEP and currently only 400,000 people are on PrEP. My view of this market is it's going to continue to grow. You're going to see more and more people coming into this market, because actually they will be driven in by the option of a long-acting injectable. Long-acting injectables are superior to orals. And so you're going to see the volume of the market grow.

You've got 2 companies pushing their advertising, doing all the things that we do commercially. And you've also got a market that's in part branded, in part generic in terms of the orals. So there's also a value upgrade for people who go from, let's say, you're on a Truvada generic today, to Apretude or our competitor. That actually means the value per patient goes up. So I think that market is going to grow. I think we can be very successful in that market. And I think having a competitor actually is something that we think is going to benefit the market as it grows and evolves. And both of us will find our place. You've got obviously less frequent administration with our competitor, but you've got challenges with drug-drug interactions and nodules. You've got more frequent administration with Apretude, but you don't have the drug-drug interactions or the nodules. So it's going to come down to patient choice, I think.

Got it. Yes. And overall market growth, how penetrated do you think the market is at the moment between generic oral Apretude and then obviously, lenacapavir coming in as well? And where do you think that can get to over time?

So today, it's 5% long-acting injectables, which is almost all of it is Apretude currently, but obviously, Yeztugo is entering. Then you've got the rest of the market split between Descovy, which is about another 42%, and then the rest of it is generics. Over time, we believe that by the time we get to the end of the decade, about 80% of the market value is going to be in long-acting injectables. And then the remainder will be the orals.

And what about penetration? And if you look at the addressable pool, how...

So we think that you can get to 1 million patients, 1 million people who would benefit from PrEP. I mean today, the CDC is saying 1.2 million people would benefit from PrEP. There is actually other evidence out there from kind of some members of the CDC and also some significant Es, who are saying the addressable population for PrEP could actually be as high as 2.2 million.

So I think our view is, by the end of the decade, you'll be somewhere between 800,000 and 1 million people on PrEP, because the PrEP that we're bringing to market from a long-acting injectable perspective is really, really effective, because you don't have to remember to take tablets. You know you're covered. Whatever you decide to do on the weekend or the week nights, you just don't need to worry about HIV acquisition as something that's a cloud over your head. So I think it's going to be a really significant breakthrough involving the epidemic.

So 1 million patients. How much is it at the moment, though?

So we're currently at 400,000-odd at the moment. So we're halfway there.

Got it. But that's 400,000 across everything, including all generics?

Everything, yes.

And then talking to lenacapavir, I think you published some data, healthy volunteers data comparing contrast maybe clinical...

Yes, the CLARITY study was really designed to help providers to understand the injection experience with the 2 products. And so it basically took healthy volunteers, and they gave a dose of Apretude, which is a single IM injection, and they gave a dose of Yeztugo, which is 2 subcutaneous injections. And it basically just described what their experience was. And what we found was there was a high preference actually for the Apretude because of the discomfort that was associated with Yeztugo.

And so part of why we thought it was important to do this is that while Yeztugo is a subcutaneous delivered product, it's not what people would think of as a typical subcutaneous dose, because it's a relatively high-volume subcutaneous, those 1.5 milliliters x2 doses. And the product itself is quite viscous and a bit sort of oily. And so it requires a relatively difficult pressure in order to inject it. And that causes more pain than you typically would think of with a subcutaneous injection.

And that's really what we saw in the CLARITY study, which ended up leading to basically about 90% of the individuals, the healthy volunteers preferring the IM to the subcu. And actually 6 out of 7 of the HCPs preferred delivering the IM to the subcutaneous, which is particularly unusual, because you think about subcutaneous dosing being easy in general. But the reason for that is that because of that higher pressure, it causes pain. And providers never like to do anything that causes pain if we can avoid it.

And that study, was that just the single administration?

Single administration.

It doesn't account for the fact that you're doing less frequently...

Absolutely. It doesn't address the whole experience of being on Apretude or on being on Yeztugo. It really gives providers and potential individuals who might want to go on PrEP an idea about what that injection experience is like.

Okay. I might shift gears on to just reimbursement and pricing at the moment as well. So I think if you go back to Part D redesign, you flagged I think it was GBP 150 million, GBP 200 million headwind in 2025 from redesign. So just perhaps talk through how that panned out, if that panned out as expected through the course of the year?

Yes. So I think GSK gave a number of exposure between GBP 400 million and GBP 500 million exposure from the Part D redesign, and they have said that they're at the bottom end of that range, and we would say that we are at the bottom end of our range. So we're actually in line with what we've said as a kind of a broader GSK.

Got it. And have you seen any sort of channel mix changes through the year? I know you saw some flip flopping between Q1 and Q3. Just perhaps run through the dynamics of that, what drives that channel mix change, because it looks like it's sort of the gross to net flying around, but maybe just help people to understand that.

Yes. I mean, during the year, we've seen kind of more shifts at one point into the higher discounted channels, ADAP and Medicaid. And then we've seen, in the kind of the last quarter, a move much more back into commercially insured. It's not unusual to see those shifts over time actually. And we think it broadly nets out to a relatively stable picture for us. So we haven't seen anything that's driving a change in the market. But at the moment, we are a little more skewed towards the commercially insured patients than we normally are.

So actually, what would be the split if you break it down at the moment between the channels, so Medicare, Medicaid, ADAP, commercial?

So if you look at the whole market, so not necessarily just our business, but let's look at the whole of the HIV market, about 20% in Medicaid, 20% in Medicare, depending on the time period, 10% to 12% in ADAP, and then you've got 5% to 7% in things like the VA and Indian Health Services and all of that. And then the remainder is in the commercially insured. So that's broadly how our mix runs as a sort of an HIV therapy area.

Okay. So it's quite high Medicaid, ADAP exposure still. And then what we're seeing obviously in the kind of broader landscape at the moment is lots of MFN deals around Medicaid pricing. So does the fact that HIV is protected relatively high price and quite high exposure make that a little bit more difficult for an MFN-type negotiation for GSK and ViiV with the White House?

I mean, GSK is currently in the negotiation with White House. I'm not going to comment on kind of the particulars of that. I mean, what I'll say is that you've got obviously a very clear policy with the IRA, so you can forecast exactly what's going to happen to your business over what period. But the situation at the moment with MFN is each company is going to have their own individual deal, and GSK is in the middle of that dialogue. What we want is to make sure that access is maximized and the American patients get the best possible price. So we're going to continue with that dialogue, and we'll come back on that.

Just dynamically speaking, is it a fair assumption that the gross to net is smaller -- difference is smaller in HIV than it would be across perhaps other classes in the market.

The gross to net writ large is typical of specialty business. Yes, it's broadly in line with the specialty business.

Yes. I might just -- unless there's any other commercial questions, I might shift gears to pipeline and give Deborah where I can bring in a little bit more as well. So we touched a little bit on Q4M. One of the things you announced at Q3, though is you delayed the start of the Q4-monthly dosing for Cabenuva. Just run us through the impact of that on timing of readout. And then just what is it that's going on with the supply from J&J that led to that delay?

Yes. So we announced about a 6-month delay in start of the study, and it's just about the availability of clinical trial supply. And obviously, long-acting formulations are difficult to make, and that's why we're the only ones with a long-acting regimen on the market. And so a 6-month delay, that will mean that we will start the study in the middle of '26, and we plan to file in '27, and that means a mid-'28 launch to the Q4M regimen.

Got it. And the clinical trial supply issue, is that because J&J has to make it specifically, and it was about ramp-up of facilities, technology, et cetera?

Exactly.

So there's no other regulatory or any other type of concerns.

No, not at all.

And then in terms of the Q4M, what's the IP protection that you're expecting for that? Is that going to be just still based on the basic molecules? I think cabotegravir is 2031 on that basis? Or would you be aiming to get some additional IP protection from that formulation?

I mean, we're not going to comment on what we are currently applying for. We haven't got anything in the Orange book yet. So it's always wise never to show your hand. But I guess what I would say is, we would not be expecting generic entry until later than the 2031 date for the Q4M.

The thing to remember, however, is that we're expecting -- I mean, as you saw, Q1M was cannibalized very quickly into Q2M. Q2M will be cannibalized very quickly into Q4M, because basically, it's Cabenuva Q4M, every 4 months, rather than every 2. So our business will be sitting almost totally in the Q4M at the point of the loss of exclusivity. And we believe that we've got the opportunity then to see that business move through 2031.

In addition to that, we'll talk about it later, but we've got the Q6M, which is going to be a really, really strong value proposition given that we've got VH-184 third-generation integrase inhibitor at the core of that Q6M regimen most likely. So that's why we're feeling pretty good about that 2031 date not being a big issue for us.

And would it be your expectation that once people are on Q4M that they would still switch to Q6M? Or are you thinking that actually you're just going to have 2 separate sort of parallel franchises?

I think there'll be a mix. So individuals that are doing well on the Q4M regimen, many of them will likely stay on it. But what the Q6M regimen does is takes the individuals who wouldn't start on a long-acting regimen until they can only come in twice a year. That's going to expand the number of individuals who will be on a long-acting regimen. And so that's a really critical part.

The other part is that because these products are different, it is a larger proportion of individuals who are eligible. So there's no NNRTI that will be a part of that regimen that limits that. And so in addition, if we choose VH-184, which is where we're leaning at this point, that's a product that covers viruses that even have integrated resistance. And so it just really opens up a whole new population of individuals who are eligible for 6 months that wouldn't have been eligible for Cabenuva, for example.

I was going to come at that actually. So I remember a while back, a few years ago, you actually mentioned the fact that by the time of the launch of Q6M, you might have some cabotegravir resistance around the market. I think you even put a number on it, which I can't remember off the top of my head. But do you have a view that there would be particularly resistance to other integrase inhibitors, but particularly cabotegravir, is there going to be a high level of resistance there that VH-184 would cover? And is that a big part of where you see the shift?

Well, so resistance to cabotegravir is actually pretty rare. We don't get very much of -- we don't get very many failures and we don't get very much resistance. But there are a lot of individuals who have received first-generation integrase inhibitors, and those individuals are not who have failed those. They aren't candidates for Cabenuva. But they would be candidates potentially for 184 because of the fact that it covers viruses that have multiple resistance mutations. And so that's why it expands it significantly.

Do you have a sense of what proportion of the HIV population that would be today and where it may be by 2030?

What proportion will be resistant to integrase inhibitors? Yes, I don't know that sort of off the top of my head, but I can tell you, in general, what we see is very low likelihood of resistance when you fail dolutegravir or bictegravir, low likelihood of failure when you fail cabotegravir. But the people who failed, for example, raltegravir in the past have integrase mutations. And so you're talking really, I would say, in the teens, maybe individuals as a whole that have some level of integrase resistance.

We said 13% many years ago when we discussed...

That's very consistent.

That was, I couldn't remember the number. Okay. And then when you move to Q6M, I think you said 50% would be.

Addressable market.

Addressable market, and then you said that's not where you think penetration would be. So...

Well, this is really important, and it does depend on which regimen we choose. So I'll describe the kind of the breadth of the opportunity and then Kim can describe what she's thinking about from a pipeline perspective. So we think VH-184 is an extraordinary medicine. It's probably the one that we are most excited about in our whole portfolio. And the question is what do we put with it.

And we believe that we would have a program for Q6M treatment, which would be naive. And at the moment, as you know, the long-acting injectables are not naive. So we would be studying it in a naive population. We will be studying it in a switch population. We will be studying it in a viremic population, and we will be studying it in populations where you have traditionally seen resistance to integrases. And obviously, we'll be able to use the drug in people who are currently unable to take Cabenuva, because they're resistant to an NNRTI.

And it is extraordinary the number of people that we meet in community who are begging for something that allows them to access a long-acting injectable, because they've had in the past an NNRTI and they're unfortunately now unable to take the long-acting injectables. So the opportunity will be like dolutegravir, where we studied it in every population with a very significant clinical trial program, so that, that medicine had the opportunity to be accessed by the broadest possible patient pool.

Yes, a much wider group of individuals. So even nowadays, we have individuals who use Cabenuva off-label for individuals that are viremic, because they just won't adhere to orals. And so we don't have that indication because of all the things that we've talked about. So having a product that actually will cover all of those individuals, I think, is going to make a really big difference.

184 really brought more like dolutegravir in the future. So that's super exciting. Now what will we partner it with? So we've narrowed that down to really 2 choices. One is a capsid inhibitor. So VH-499 is a capsid inhibitor. It's relatively similar to lenacapavir with regard to its potency and its potential to be long-acting. But what we have as a benefit over lenacapavir is that it doesn't have that CYP3A4 inhibition. And so it won't have those drug-drug interactions that we see with lenacapavir.

We're also really looking to make sure that we can avoid sort of the challenge with the subcutaneous administration and the nodules. And so we're exploring both subcutaneous administration and IM, and we'll choose which way to administer based upon the tolerability and the PK.

The other option that we have to pair with it is a broadly neutralizing antibody or VH-109, also known as N6LS. And this is the CD4 binding site broadly neutralizing antibody. It's already in Phase IIb. We presented the Phase IIb data from the EMBRACE study at CROI last year. We showed 96% efficacy. We dosed in that study either IV or subcutaneously with Halozyme's PH20. We ultimately found that we saw more injection site reactions when we dosed it subcutaneous. So we're taking it forward IV.

In that EMBRACE study, we dosed it every 4 months in combination with cabotegravir. We are doing EMBRACE Part 2, which is looking at N6LS every 6 months, and we're very, very confident that it can be dosed every 6 months. That study is fully enrolled. And so next year, we'll see some data from that. And then at CROI of 2026, we will show the 12-month data from the EMBRACE study, and we're very excited about that.

So what you'll see at CROI -- and you're just coming to the point where we will make the decision around our 6-month regimen in the middle of next year, what you'll see at CROI is PK data on VH-184 basically showing that it has that long-acting potential that we've described. We'll also show some more resistance data that compares the ability to cover resistant viruses, comparing that to bictegravir. And so that will be present. We'll show that 12-month data from EMBRACE. So you'll see more on N6LS. And then we will also show PK data on VH-499, again, showing you the potential for it as a 6-month agent. And so it's all those pieces of data together that will combine to help us make that selection of the regimen in the middle of the year.

And then after the selection of the regimen, we will get into the Phase IIb studies, which will pinpoint exactly what's the dose for the 6-month regimen. So we're seeing a lot of progress. We're really excited. And our expectation is that we can get that 6-month regimen on the market by the end of the decade. And so we are on track to do that.

So just rewinding to some of that. So what you could end up with potentially is a regimen where you have an IV with an intramuscular, for example, or a subcu with an intramuscular. And so fair to assume that these would be given as a regimen, not as a single treatment. So there isn't going to be a single administration.

As a regimen. We're developing that as a regimen yes.

Yes. Okay. And then just going back over to the capsid inhibitors. So for capsid, just remind me what data you've got already on duration PK that gives you confidence you can get 6 months? Or is that the data at CROI?

That's the data that's coming at CROI. So what we shared last year at CROI was the proof-of-concept data that shows you the potency. And so we had roughly a 2-log drop, which is comparable to other capsid inhibitors.

And what was the dosing on that there?

You know what, I'd have to go back and look at that. I think we were mostly showing you the oral dosing, but this was really just to show you what the potential of the drug was. And so I don't remember exactly the range of doses. I think we went up as high as maybe 200 milligrams, but I'd have to get back to you on the details of that.

Okay. And then VH-184, we've already seen data showing 6 monthly viral suppression in some of the -- or PK, I should say, in some of the earlier data. But is it the viral suppression data what we should be looking at?

Actually, what you saw at CROI was, again, POC data that showed you the potency. We haven't shown you the detailed PK data. What we've shown you in PK data is CAB-ULA and the potential for that to be 4 months and potentially even 6 months, but we haven't shown that PK on VH-184 in detail yet.

So that's CROI as well?

Absolutely. It's going to be a big CROI for us.

Yes. And then N6LS, just remind us again what data we have there so far on potency efficacy. So you mentioned the 96%, but also on duration on that asset as well.

Right. So the study that we shared at CROI was the EMBRACE study. And in that study, we dosed N6LS every 4 months in combination with CAB once every month. And so that data showed 96% efficacy. And so well tolerated in general, but as I said, we made the decision to move forward with the IV. And so what you know about N6 is that it can be a part of a potent regimen. But what we also have learned in our PK studies is we can dose N6LS every 6 months. And so that's what EMBRACE Part 2 is. And so that doses every 6 months with CAB every 2 months. And so that's a study we recently enrolled. We'll see data on that in the middle of next year.

What you'll see at CROI is the 12-month data from the EMBRACE study. So first, we showed you through 6 months, 96% of individuals suppressed. At CROI, we'll show you out to 12 months to see were there any new failures after 6 months? And we'll still share that information, very exciting data. And so what we've shown you now about N6LS is that it has potency. So you've seen the POC that is basically, again, about a 2-log drop. You've seen the PK to tell you that we can use it as a 6-month agent. And now you've actually seen it in combination with an integrase inhibitor that shows that's a regimen that works.

Got it. Okay. So yes, lots to see at CROI. And then I think you talked about potentially holding a sort of investor meeting to discuss, and actually, would you hold that just to talk about the data? Or would you hold that once you've made a decision on what the regimen would be to go to Phase IIb and Phase III?

We'll hold it once we've made the decision. So what we always hear from you, Graham, and others, is that don't bring us together until you've got some really material data to share and some new news. So at the end of Q2-ish, we will be bringing regimen selection, new data. And then there's a couple of other things that we have.

There's a lot of surprises.

Yes, in our discovery group, which we're bringing forth as well. So I think it will be sort of an opportunity to reset again for the next period, both our financial and our pipeline expectations.

Got it. Okay. Competition. So there's another company out there that does some HIV drugs. So I guess the first thing to flag or to focus on is given that your focus is moving to Q6M is that Gilead last year did actually unveil they've got some 6-monthly integrase inhibitors. It looks like they've selected one now as well. So just your thoughts on how far ahead of Gilead you could be in terms of getting Q6M into the market just from what you see from them at the moment.

Well, we think we're pretty far ahead because, again, where they are from what I've seen is that they have a Phase Ib study that I think they said they'll share some data on. So we'll get a sense of whether some of the PK and maybe a little bit of the potency on that. We've already shown you that for our integrators. And so we've got pretty much that lined up. I think we're very confident that we can get out in 2030. I think the estimation for Gilead is maybe 2031 to '33. And so I think we're really quite confident we can be not only first to 6 months.

So obviously, we have the only long-acting treatment regimen now. We believe we will launch our second and maybe even our third long-acting injectable regimen before they're able to launch their first. And so we have led in this area, we continue to lead. We know that there will be other products that will come out, potentially weekly orals, but we think they compete a bit more with daily orals than with the long-acting injectables.

Yes, we always got the lenacapavir weekly oral, but they're also -- I think they said they were looking at monthly oral as well. So where do you think that competes in the paradigm? Is that still going to be competing with daily oral? Or is that something which could start to compete with long-acting injectables?

Yes, it's a good question. I think we really should distinguish whether or not we're talking about treatment or PrEP. And so there's a couple of -- Merck is also talking about a sort of a monthly oral for PrEP. Getting to a monthly oral for treatment is a pretty high bar. And so if that's accomplished, I still think by the time we get there, we'll also have 6-month long-acting injectable. And so I think the people who would choose a monthly oral are people who don't want an injection. And so coming back to that sort of 50-50 breakdown, I think that they would fit more in that oral group that doesn't -- the only reason they're choosing an oral over a 6-month injectable is basically they don't want a needle.

Got it. And then thinking commercially, so fast forward to 2031, '32, let's say, you got six-monthly long-acting injectable in the market, but you've got potentially some generic Cabenuva two-monthly. You've got potentially all of the Dovato generics in the market and so on. Do you think payers will be prepared still to pay for six-monthly long-acting? Or will that get pushed away as this is a convenience thing, and we don't want to pay for it?

So by the time we get to that 2031 period, we believe that all of the Q2M will have been cannibalized into Q4. It's going to be 1 to 2 as we saw 2 to 4. So actually, there isn't going to be a great deal of Q2M out there for a generic to enter and make any money from that particular presentation.

So then the question is, will payers pay for Q6M. The reason that we have spent such a lot of time and capital developing VH-184 is because it is unique. I think if you were just coming with the 6 months of Cabenuva, then that could be a challenge. But actually, from my perspective, you have got a unique value proposition there with VH-184, and then we will partner that with whatever is appropriate.

But if you've got a third-generation integrase that could be used in a long-acting injectable that is for naive switch, viremic, and obviously those that are currently resistant to the components of Cabenuva, then that is a pretty strong value proposition. And from everything that we understand, that will be something that will help end the HIV epidemic by keeping people virally suppressed. And on that basis, you don't then pass HIV on to those people that you're kind of having sex with. And therefore, it is part of the government's opportunity to end the HIV epidemic in America particularly, and get it under control. So I think we're going to find that payers are willing to pay for something that's so differentiated. It's all about innovation.

Yes, exactly.

Super clear. Clock is ticking. So we're out of time, but that's really interesting. Thanks very much for the time today, and thanks, everybody, for listening in. Thank you.

Thanks.

Good morning, everybody. My name is Michael Leuchten, covering analyst on Glaxo here at Jefferies. It's my pleasure to have Tony Wood with us this morning for the fireside chat, Chief Science Officer. Thank you for joining, Tony.

It's a pleasure.

What I wanted to start with is one of the questions we keep getting on Glaxo is sort of where are we headed with the R&D strategy? And I think the question is both organic and inorganic.

Yes. So let me just begin answering that to give you a sense of the journey we've been on for the last 3 years. And then I will embroider the organic versus inorganic components of it. So what remains still our central focus is the science of the immune system and the application of technologies. That should be a surprise to no one. You will all have been, I hope, on the journey of creating a very research unit focused R&D organization over the last 3 years.

Within that, of course, we then have, in addition, the internal versus external component. BD under Chris Sheldon reports directly to me. That was a deliberate design, recognizing that what we wanted to do is to bring together both external and internal opportunity at an appropriate point in portfolio decision-making. For the last 3 years, of course, that point has been the transition into marketed assets, which is why you've seen a lot of focus from Luke and myself on what he's called bolt-on deals, the likes of IDRx, the recent acquisition of the GIST opportunity, for example.

And what we focused therefore at the sort of highest level of capital allocation, the peri Phase III launch world was ensuring that the comparisons that we're making between internal and external assets against the broader research unit strategy, which I can give you in a little bit more detail after I stop -- promise I'm not going to answer this question for 20 minutes, is then a proper comparison of internal versus external opportunities.

So better capital allocation. And also for me as Head of R&D, a very clear lens on what was coming out of the internal organization and therefore, what I wanted to transform as we seek to deploy technology more deeply within the internal R&D footprint. So that's kind of the highest level of bit, Michael. Happy to stop there. I can embroider each of the research units from a sort of therapeutic focus in a little bit more detail if that would be useful.

Yes, that would be fantastic. So maybe if we pick on oncology in that context. So can you just run us through -- because you've got some very interesting assets. You mentioned the KIT inhibitor, I guess, B7-H3, but they were added from outside the organization. So if you apply that lens to oncology, what's coming out of the internal organization? What are the KPIs that you set? And what happens if they don't deliver to those KPIs?

Yes. So I might answer that in a slightly different sense because there's a particular approach that I've taken in oncology that I can then compare with the other research units as well. So very pleased about the focus we've got now in oncology. Obviously, momelotinib, a great example of the BD that I mentioned earlier, doing extremely well. You said yourself that we have both the IDRx and the GIST molecule building out our focus there.

And of course, a huge opportunity sitting in front of us for the B7-H3 especially, but also B7-H4 ADCs. Now in oncology, in general, what I wanted to do is pivot the organization's focus into assets where efficacy was apparent in monotherapy in Phase I. We've learned as an industry, I think, across IO that the challenges that you face when you pick assets that require combination and then large-scale studies to see effect just really make that approach particularly impractical.

Building all of that, of course, on where I stand with Jemperli, particularly in GU and GI cancers, so that we've got a bit of a foundation to build on. Oncology, you'll all appreciate as well is probably the paramount area in our industry where one can harvest near-term assets from the outside world.

And so what I wanted to do in building the internal organization in oncology was not to compete with what is inevitably a much more scaled external world, but rather to put in place the technology foundations that allow me to make better decisions about which assets I acquire from outside. We've built a significant data capability, be it through collaborations with the likes of Tempus and now building an internal capability, for example, in organoids. That was bringing Tony Ng in from UCL Kings as a leading academic in the field and the acquisition of CELLphenomics at the end of last year to build that capability.

So I very much think about oncology as it is using technology to enable better taste in terms of external acquisitions and partnerships and then using technology and partnerships to place those assets. Just 2 quick things on the ADCs. The Hengrui collaboration, of course, gives us a very contemporary ADC portfolio with technology that is already proven. Those of you who follow the field will understand that de novo invention of ADCs, not as straightforward as any of us would like.

And the pace and scale that we get from the -- sorry, the Hansoh partnership on the ADCs, coupled with our own focus internally, as I've just described, gives us an opportunity to compete at scale and with technology in the areas that I choose to go after. So that was the logic behind oncology.

Okay. That's very clear. And I guess maybe leaving it to you sort of the same lens apply to the other areas that you're active. And we can talk about respiratory, we can talk about HIV, we can talk about infectious disease, we can do MASH where you added an asset. I guess one good question might be, which area it needs most attention through that lens? Like where do you think there needs to be more to kind of get into the same logical sequence as you have just outlined?

Yes. So let me talk about the logical sequence for each of them quickly. There's nothing that I do that doesn't need more. So everything you'd expect me to say that as a Head of R&D, there's always things that I want to change. Hopefully, oncology is clear now. Let's do resp next. So we're fantastically positioned there with regards to lung disease. Couldn't be happier with the label we got for Nucala in the middle of the year for COPD and IL-5.

You'll appreciate an enormous opportunity, 300 million individuals with lung disease and COPD, a disease that if you are unfortunate enough to be hospitalized with has a prognosis that is worse than many cancers on a 5-year setting. So what we have there is the moving technology. We talked about ADCs for oncology for lung disease, think about it as a shift into long-acting monoclonals. We've led the world in the -- what we might call symptomatic relief of lung disease through bronchodilators.

Next up was establishing exacerbations as a key issue of improving and ultimately obtaining clinical remission in lung disease. Bepi now really well positioned with 2 significant Phase III objectives started in the long-acting IL-5 class for COPD and IL-33 and TSLP just behind that for both asthma and COPD. And you'll see us making decisions about moving those into pivotal studies around about '27, '28 when I've learned a little bit more about each of the assets.

That, coupled with where we are with camlipixant and the opportunity for the PDE3/4 inhibitor we have in the Hengrui collaboration, which sort of peppers the gaps, if you like, in the GOLD guidelines, positions us really well. As a consequence of that and our anchor point in T2 inflammation, you start to think about what comes next, which is fibrosis across the 3 tissues that I care most about for fibrosis. Remember, fibrosis is a component of almost half of all deaths.

And the tissues that I care most about there are liver, kidney and lung. Liver is the place where the -- really the opportunity to resolve fibrosis and the worst form of it cirrhosis in the context of liver is now starting to look mechanistically reasonable on the back of the FGF21 class, hence, the move into efi. So respiratory is really about finishing the job on exacerbations and using it as a bridge into fibro inflammation across the tissues that I described. HIV is all about long-acting treatment. Q4M will be up in '28, Q6M between '28 and '30. PrEP will follow alongside that.

And then lastly, quickly in infectious diseases, the bridge between fibroinflammation and infection is bepi, which we'll see a lot more data for in hepatitis B towards the end of the year. And for vaccines, very much focused on life cycle innovation, boosting associated with both Shingrix and Arexvy, while we build the technical platforms to a level of quality and surety that I'm now confident we have for mRNA and MAPS before I pull the trigger on large-scale Phase III studies in either of those areas given the cost of that proposition. So that's a quick walk across all of the individual areas.

No, that's very clear. I guess before we maybe drill into some of them in more detail, there is sort of this perception out there that Glaxo doesn't have a strong pipeline, which I think is unfair. And as you outlined, there is actually a lot of thinking and logic behind what it is you're doing. How do you comp your pipeline? And how do you look at whether it's competitive? Is it number of assets? Is it revenue potential? Are you agnostic to it? Like how do you...

Certainly not agnostic to. I mean one of the -- look, at the very highest level, capital allocation, I use the same approach that many of you who manage portfolios do yourselves. I'm looking for the intersection of medical need commercial opportunity. One of the big things I did in partnership with Luke when I took over was culled the portfolio of everything that didn't have the potential to at least be a major blockbuster.

And that, of course, at the level that one wants to make those changes is associated with medical need and epidemiology of disease as well as the confidence in the science and the operational characteristics of the studies that need to be developed in order to deliver. So that's very much sitting behind everything that I've just described in terms of the relative areas of focus within the portfolio.

Understood. And then maybe sort of as we think about catalysts for '26, so you outlined depe approval, and then obviously, that becomes more of a commercial question. We had BLENREP approved. So we're looking forward to that launch curve. So from your perspective, what would you suggest we focus on? Is it sort of jump early? Is it B7-H3 now going into Phase III? Like what do you think the next proof point is?

Yes, quite a few. And I just want to underscore the point about the quality of the portfolio because as you can imagine, I feel that quite a lot and as well as our operational characteristics. So it's 13 successful Phase III studies last year. That's a record for GSK, 5 filing launches this year, of which we're 4 down and one to go. So I would say our ability to execute, I feel is now well proven. They're all in areas which carry significant opportunity. And to your point, Michael, they are part of the commercial execution looking out towards 2031.

Behind that are another 15 scaled opportunities that also contribute to that '31 position. And there are numerous assets. So what I'm going to do is just take them roughly in chronological order rather than choose my favorites as it were.

First up, of course, in respiratory is -- well, actually, first up, as I mentioned earlier, is bepirovirsen in chronic hepatitis B. We'll have the data from the B-Well study early next year. Chronic hepatitis B, a huge opportunity in terms of epidemiology. Again, several hundred million individuals in a massively undiagnosed -- underdiagnosed and undertreated area, and we stand a very real chance for a molecule with the first real functional cure.

If we have more time, you'd be asking me what that looks like. So I'll tell you, sort of 15% will be deemed clinically significant. I hope based on the data that we have from B-Well and the stratification in that population that we should see something north of that.

Then in the middle of next year, we have camlipixant. CALM-1 is last subject, last visit. This year, CALM-2 reads out in the middle of next year. I've deliberately adjusted those studies so that I get higher coughing frequency individuals into CALM-2, which is increasing the probability of success of outcome. And we've taken care of a lot of the, let's call them, technical issues that Merck faced with gefapixant as we look through that.

So I mentioned earlier that the emerging COPD portfolio and depe in long-acting format. We've now got ENDURA-1 and ENDURA-2 and VIGILANT, waited until Nucala results because I wanted to design the characteristics of those studies in such a way that we learned from. The MATINEE study for the moderate-to-severe COPD patients. VIGILANT is an entirely new study, looking at progression characteristics in a previously untreated population, in the mild-to-moderate. And again, it's all about moving long-acting into ultimately clinical remission, if you like.

So COPD portfolio, the big one, of course, sitting behind all of that is the ADCs. I promise I'll stop after this, and you can ask another question. B7-H3 being the biggest opportunity there. We're very much, in molecule characteristics, building and understanding clinically of what an excellent molecule the B7-H3 molecule is. We have a number of expedited development assignments associated with that, which underscore the quality of the data.

You'll see more from Hansoh and from us next year, particularly in extensive stage small cell where we've now started pivotal studies, but as well as that signal finding that will clarify the position with regards to our focus for B7-H3, and that is largely in colorectal, where I already have a foundation of activity in the dMMR setting, thanks to Jemperli and building ultimately into prostate. I've been quietly building a portfolio for prostate through partnerships, and that will also be a significant focus.

Lung, it's impossible not to be in the area and not be part of non-small cell lung, but I'm expecting what we'll do there is be a close temporal second to Merck. There's still significant opportunity in that setting. So much more on B7-H3. I won't go on to H4. It's a similar sort of story.

Okay. Fantastic. So maybe in the 10 or so minutes we've got, let's try to do maybe HIV and MASH and see how we go. Just on HIV, so there will be a Capital Markets Day next year. Obviously, one of the concerns out there is that your competitor might be winning in the field, be that in PrEP or in treatment.

So you mention it every 4 months, but there's a decision point next year where Glaxo will decide what asset to take forward every 6 monthly in combination with 184. Can you just talk about the data points that we're still waiting for, what's going to trigger the decision that then allows you to go ahead?

look, I mean, before I get into Q6M because I do want to just underscore the reality of the situation in treatment. So for those of you who don't follow the field, 90% of the HIV market is in treatment. We're all worried about what happens to the market when dolutegravir comes off patent. Dolutegravir is a fantastic backbone to all oral therapies, something like 70% of people living with HIV have a dolutegravir-based regimen.

The answer to that generic dolutegravir, which is going to be very hard to compete with in an oral setting is to move into the long-acting injectable world. What we've shown is that, that not only brings a number of things that HIV, people living with HIV tell us they want, but it also brings huge opportunities and benefits in compliance in the difficult-to-treat population, and that is particularly in the U.S. where the majority of market that we're talking about exists.

We are the only ones with long-acting HIV treatment regimens. We already have the Q2 monthly regimen on the market. We've been in the lead in that area for nearly a decade now. And although Gilead are making great progress with lenacapavir in PrEP and certainly, one has to acknowledge that they do not have an integrase-based treatment regimen yet. And without integrase, treatment, I think, looks much, much harder. It's a unique mechanism in terms of its robustness and its efficacy.

As I said earlier, we expect to be on the market with the Q4M PrEp in '28. We have now a very well-established formulation. We had a minor delay with Janssen, and that was more about the drug product and the complexity of making a drug product that supports long-acting. Once you've got that right, there's a significant technical moat that provides opportunity there as well.

And secondarily, about the regulatory framework, which requires 3 consecutive doses in order to establish the long-acting steady-state proposition. That, of course, is going to be the same for everyone. So we're very well placed for the move to Q4M. As I said, keep in mind that's '28 matching with LOE for dolutegravir.

Next year, we will be making decisions on regimen selection amongst 3 integrase opportunities, chief amongst those, if you allow me to be a bit nerdy on the science, given my background at the moment from my standpoint is VH184, where we have the already established background in pharmacokinetics and an emerging resistance profile, which surprisingly is even better than dolutegravir. So very confident about that.

We're also making great progress, as it happens, with the other opportunity heading into the 6-month schedule, which would be an N6LS-containing regimen. This is a unique broadly acting monoclonal. It's the only example of the case where you can have a single monoclonal to get coverage. And we've published this year a number of very encouraging clinical data studies looking at both efficacy and tolerability against the background of a CAB combination. So trying to squeeze as much in as I can, Michael, in such short period of time.

Perfect. And then maybe lastly, I think MASH, the Efi deal is maybe a good one to circle back to decision-making on what to bring into the organization. You mentioned sort of the overlap with fibrosis, but obviously, there were multiple assets out there. You were a first mover and then others followed quite quickly. Can you just talk about why Efi? Why not the others? Like what decision factors?

Simply put, we're very much in the fibrotic world. My focus is more in the severe end, although we're running an F2/F3 study for Efi. We just started that pivotal study this year. That's about the most convenient regulatory path to a label, bearing in mind what I said earlier in terms of what's important to me to the clinical portfolio. But really, our focus is in the F3/F4 arena. And in that particular arena, you have significantly ill individuals. So the attendant mechanistic benefits that come with the FGF21 class in terms of lipid reduction, oxidative stress and insulin improvement are all important clinical features for people who are at that later stage of the disease.

What's also important for them is reduced dosing frequency. Efi is unique amongst all of the FGF21s. It has the longest half-life, and it is the one that is, therefore, most suitable for a Q4 monthly presentation. Then there are a couple of, let's call them, prosaic considerations. First of all, all of these molecules have some form of fusion, which is about extending their half-life. What I wanted was a molecule whose manufacturing process was rooted in standard mammalian systems. That's what Efi has. So it's more scalable.

And in addition, whenever you have a fusion of that type, you always worry about the production of autoantibodies across the class. Just to be clear, they are present, but not -- and not neutralizing yet. The TNF world tells you that you sometimes have to wait before neutralizing antibodies appear, but Efi has, again, by far the best profile with regards to neutralizing antibodies.

So put all of that together, and we felt we'd found the best molecule. We found it at a point in time at which I could tailor the pivotal study as well, always a good thing in terms of my BD objectives. I want to be able to inherit something that I have the opportunity to have exactly the Phase III study design that I'm looking for, and we found Efi at exactly the right point in time. And I think the economic or financial components of the deal so far, I would think we would argue that we did a pretty good deal on that front, too. Thanks to Chris Sheldon. So that's my Efi story.

Excellent. Okay. And then maybe lastly, in the last minute, if you were to do more BDs in areas of interest, would that be accommodated within your R&D budget? So if you picked up another, I don't know, 5 assets comes in, can that be tolerated within your R&D line? Or is there a budget conflict?

Look, I mean, you always want, as a head of R&D, to have a budget in which you feel you're spending every penny on things that are valuable, timely and technically advanced contributions to your portfolio. You asked me earlier about how is the internal R&D organization going. That is the component of our progress that I hope to be able to show you more of in the coming years. Inevitably, if you start early, it's going to take a little bit longer before it becomes apparent at the level that the folks in this room are interested in. That means that anything that I bring into my portfolio, be it an internal asset or an external asset, has to compete with what is already an optimized position in terms of allocation of capital.

And I continue, of course, to focus strongly on making R&D more effective so they can do more with what I've got. There's a big component of tech playing into all of that. But I'm always in a position when I bring something new in, whether it's from the outside world or the inside world, that I'm asking it not only to pay for itself, but to pay for the opportunities that it displaces in the portfolio.

Fantastic. I think it's all we have time for, Tony Wood, thank you so much.

Thanks, Michael.

Ladies and gentlemen, a very warm welcome to the GSK Q3 2025 Results Call.

I'm delighted to be joined today by Emma Walmsley, Luke Miels, Deborah Waterhouse, and Julie Brown, with Tony Wood, David Redfern, joining for Q&A.

Today's call will last approximately 1 hour with a presentation taking around 30 minutes and the remaining time for your questions. Please ask only one to two questions so that everyone has a chance to participate.

Before we start, please turn to Slide 3. This is the usual safe harbor statement. We will comment on our performance using Constant Exchange Rates, or CER, unless otherwise stated.

I will now hand over to Emma on Slide 4.

Thank you, and welcome to everybody joining us today. Please turn to the next slide. Our third quarter results once again demonstrate GSK's continued strong performance with positive momentum driving an upgrade in our guidance for the year. They also further demonstrate the quality and strength of GSK's portfolio with sales driven by sustained growth across specialty medicines in RI&I, oncology and HIV. Total sales were up 8% for the quarter, with leverage delivering core operating profit up 11% and core earnings per share up 14% to 55p.

Alongside this, we're continuing to make excellent progress in R&D, strengthening our late-stage portfolio and already securing four FDA approvals this year, including BLENREP last week and with the fifth, depemokimab before year-end.

Cash generation also continues to be very positive at GBP 6.3 billion for the year so far. This supports investment in our growth priorities and returns to shareholders, including a dividend of 16p for the quarter.

And finally, I'm very proud of the progress we continue to make with our trust priorities, in particular, this quarter with the positive Phase III data reported for our low-carbon version of Ventolin. This successful transition will reduce GSK's carbon footprint by up to 45%, and it's a meaningful development for the 35 million patients who rely on Ventolin worldwide, and we expect to launch in 2026.

Next slide, please. Our #1 priority remains investing for growth, and I'm pleased with the progress we are making, both in the late-stage portfolio and in the work ongoing to build the next wave of innovation at GSK. With the addition of efimosfermin, the long-acting FGF21 for steatotic liver disease, we now have 15 scale opportunities with peak year sales potential of greater than GBP 2 billion, all with the potential to launch before 2031.

By the end of the year, we expect new pivotal trials to have started for several of these 15 opportunities, depemokimab for COPD patients, efimosfermin in MASH, GSK'981 for second-line GIST and our GSK'227 ADC in extensive stage small cell lung cancer. It's worth noting that those last 3 assets have all come from focused, successful business development and BD remains a key driver of our pipeline expansion.

And we continue to add high-value innovation at earlier stages of development. For example, I'm excited by GSK'261, a new monoclonal antibody for polycystic kidney disease, which received orphan drug designation by the FDA. Lastly, and very importantly, we continue to optimize our supply chain to scale up capacity for our new medicines and vaccines.

Last month, we confirmed our intention to invest $30 billion in R&D and advanced manufacturing in the U.S. over the next 5 years, including the imminent construction of a new biologics flex factory in Pennsylvania. Next slide, please. Since 2021 and then GSK's successful launch as a new focused biopharma company, we've delivered 18 consecutive quarters of profitable sales growth, upgraded annual guidance each year, improved our medium-term outlooks and upgraded long-term outlooks twice from an initial GBP 33 billion by 2031 to now more than GBP 40 billion, all underpinned by a much stronger balance sheet.

We've all been resolutely focused on this step change in sharper operational performance alongside accelerating investment in R&D and significantly improving the quality and scale of GSK's innovation. So today, GSK is a very different company in performance, pipeline and prospects. And this team is determined to sustain and improve upon this track record. As we look ahead, we are again upgrading our guidance for the year with meaningful improvement for 2025 sales and profits.

And this momentum positions us well as we go into 2026 and to deliver on the long-term commitments for growth we've set out for shareholders. So let me now hand over to the team to take you through more of the detail on our performance, starting with Luke. Next slide, please.

Thanks, Emma. Please turn to the next slide. In Q3, we delivered growth across all our product areas and in the regions with GBP 8.5 billion of sales, up 8% versus last year. Growth in the quarter was driven by Specialty Medicines, up 16%. And and another quarter of strong Shingrix, Arexvy and meningitis demand in Europe. And in the U.S., we navigated the impact of the Medicare redesign from the IRA and the impact is now expected to be closer to the lower end of our GBP 400 million to GBP 500 million range.

Next slide, please. Specialty Medicine continues to be the most important driver of our diversified business with double-digit growth once again in all therapy areas. Starting with RI&I, sales were up 15%, driven by strong demand. Benlysta, our treatment for lupus grew 17% with global guidelines supporting earlier use of biologics and recommending Benlysta as a preferred treatment option.

84% of bio-naive patients are now starting on Benlysta, and we continue to differentiate with strong organ damage prevention data and a well-characterized safety profile. Nucala, our anti-IL-5 biologic, grew 14% in the quarter, driven by COPD uptake and continued growth across all in-line indications. Moving to our growing oncology portfolio, which is up 39%. Jemperli sales were up for the 10th quarter in a row as our teams continue to differentiate Jemperli from the competition, as the only immuno-oncology medicine to demonstrate overall survival in endometrial cancer. Jemperli's global market share in endometrial cancer is now higher than the leading competitor in DMMR.

And Ojjaara sales were up 51% in the quarter, driven by increasing first- and second-line patient demand in the U.S. and volume growth in Europe following EHA, where new data emphasized the importance of early intervention. And BLENREP is now in the early days of launch with approval in 8 markets and more on that in a minute.

And with the strong momentum we're seeing across RI&I and oncology and the continued performance of ViiV, we are now increasing our full year specialty guidance from low teens to mid-teens percentage growth. Next slide, please. In Q3, we had a very strong start for Nucala and COPD with the latest NBRx data showing we are now getting close to 1 out of every 2 prescriptions.

Our differentiated label is enabling us to reach a wide spectrum of COPD patients, including those with emphysemia and EOS counts down to 150. We've now reached 95% of our top ACP targets and have a broad formulary coverage. In this population, hospitalizations remain a critical unmet need with 1 in 2 patients dying within 5 years of their first admission, and there is plenty of room to grow in this market with less than 5% biologic penetration in the U.S.

The success we have had with this launch gives us further confidence in the potential we have for depemokimab, our long-acting IL-5, which we expect to launch early next year. There are 4 compelling reasons underpinning why we believe depe will be a very material medicine. First, there's plenty of room to grow in the market, starting with bio-naive patients as only 27% of them currently receive a biologic.

Second, patients discontinuing therapy is an issue with up to 65% of new patients on current biologics discontinuing therapy within the first 12 months. And unsurprisingly, less adherent patients have worse clinical outcomes, including around a 30% increased rate of inpatient and emergency department visits. The 72% reduction that depe has demonstrated in hospitalization with just 2 doses a year is material. And finally, we know ACPs want this medicine with 86% of pulmonologists surveyed believing it could become a standard of care.

Next slide, please. Our oncology portfolio is progressing well. Starting with BLENREP, we now have approval in 8 markets, 7 in Europe and international regions in the second-line plus population and now the U.S., where just last week, we received approval in the third-line plus setting. This U.S. approval is a significant step forward for the U.S. patients and the indication granted reflects that BLENREP has demonstrated superior efficacy versus the standard of care daratumumab triplet and now gives us certainty and the ability to launch.

Data from DREAMM-7 in this population is very compelling with a 51% reduction in the risk of death and a tripling of median progression-free survival versus the dara-based triplet. We see a significant opportunity here as of the 71,000 patients in the U.S. receiving treatment today, over 1/3 are treated in the third-line plus setting.

And BLENREP is the only anti-BCMA option, which is practically able to be used in the community where 70% of patients are treated and could benefit from a much needed novel MOA. We also have a new and significantly simplified REMS program, including, importantly, the use of optometrists versus the original REMS, which required ophthalmologists only. This will make it much easier for patients and HCPs to manage eye care. And while we anticipate a slower ramp-up in the U.S. with the initial third-line plus label, as we said previously, we will take the time to ensure a positive patient and provider experience to achieve the long-term potential of this highly effective drug.

Our clinical development and evidence generation plan continues. And again, working closely with the FDA, this will now be expanded in the U.S. and will support the use of BLENREP in earlier and all stages of multiple myeloma globally. In summary, we expect BLENREP to meaningfully advance treatment options for patients with multiple myeloma, and we continue to expect BLENREP to be a material growth driver for GSK in the next 3 to 4 years.

Moving to future indications for Jemperli. We're looking forward to the opportunity we have to change the lives of patients with rectal cancer. And following the transformative data showing a 100% complete response rate in Phase II, we initiated the AZUR-1 pivotal trial and expect to see results in the second half of 2026. And additional trials are ongoing to understand the benefit Jemperli can bring patients with colon and head and neck cancer.

Finally, we continue to progress our key oncology pipeline assets, starting with our B7-H3 antibody drug conjugate or GSK'227. We're now recruiting for our Phase III trial in second-line extensive stage small cell lung following a clear signal we saw in the early-stage clinical data from Hansoh, our partner. And our KIT inhibitor for GIST, GSK'981 acquired earlier this year, will start Phase III in second line by the end of the year and first line in 2026.

And GSK'584, our B7-H4 antibody drug conjugate is expected to advance to Phase III in endometrial and ovarian cancer next year. And overall, this oncology portfolio offers significant future growth opportunity for GSK and is a clear priority for investment and resources alongside RI&I.

And with that, I'll now hand over to Deborah to cover our great momentum in HIV.

Thank you, Luke. Our HIV portfolio continues to deliver double-digit growth, up 12% in the quarter, primarily driven by 10 points of strong patient demand growth for our long-acting injectables and Dovato. Demand continues to increase across all regions and major markets, particularly the U.S., which grew 17% and where we saw total share gain outpacing the competition.

We are delighted with the continued transition we are seeing to long-acting injectables. More than 75% of our growth now comes from long-acting injectables. And in the U.S., they already represent around 1/3 of our sales. Cabenuva, the first and only long-acting injectable HIV treatment regimen grew 48%, driven by strong patient demand. Our competitive performance is reinforced by the acceleration of Cabenuva switches from competitors in the U.S., which this quarter reached 75%.

As we anticipated, in long-acting prevention, we saw continued positive momentum of Apretude in the U.S. with competitive growth also of 75%. This quarter, we shared results from CLARITY, a Phase I study comparing acceptability and tolerability of single-dose CAB LA for PrEP marketed as Apretude and lenacapavir. We know patient experience is an important factor for injectables.

Results showed 69% of participants found CAB LA to be totally or very acceptable with 90% of participants and 86% of HCPs preferring CAB LA over lenacapavir in terms of injection experience after a single dose. These data add to the growing body of clinical and real-world efficacy, safety and tolerability data we have for Apretude and will help inform expectations and decision-making when initiating long-acting injectables for HIV prevention.

We expect continued growth momentum in Q4. And so today, we are upgrading our 2025 guidance from mid- to high single digit to grow around 10%. Next slide, please. Our industry-leading pipeline with best-in-class integrase inhibitors at the core continues to progress and have multiple long-acting options with strong profiles that deliver what we know patients want and need.

This pipeline will further drive the transition we are making in our portfolio to ultra-long-acting regimens and will help us navigate the dolutegravir loss of exclusivity towards the end of the decade. Building on our established 2 monthly injectable regimens, we believe 4 monthly dosing in PrEP and treatment will be important options, delivering longer dosing intervals and ensuring continuity of care.

We have a confirmed date from Janssen on rilpivirine Phase III clinical trial supply that leads to a delay to the start of Quattro, our Q4M treatment registrational study to H1 2026. Despite this, we remain on track to file in 2027, and we look forward to launching this next wave of innovation in 2028. building on continued strength and performance of our Q2M Cabenuva, the world's first and only LAI for HIV treatment.

At the launch of Q4M treatment, we still expect to have the only long-acting injectable treatment regimens on the market for years to come. Looking ahead to our twice yearly injectables, we're on track to confirm the dosing regimen for Q6M treatment in 2026 and expect to file and launch both Q6M for treatment and PrEP between 2028 and 2030. For Q6M treatment, we remain excited about the potential of VH184, our third-generation INSTI, which has the best resistance profile seen to date and IP protection through to at least 2040.

To partner with our selected INSTI, we are evaluating 2 assets, VH499, a capsid inhibitor and N6LS, one of the broadest and most potent bNAbs in development. Regarding N6LS, this quarter, we again showed more positive results from Part 2 of our Phase IIb study in BRACE and are pleased to confirm the next phase of this study is now fully recruited.

As a reminder, Q6M for treatment in PrEP is not yet in GSK's outlook for 2031. Our long-acting injectable portfolio is backed by 3 years of real-world evidence and implementation science. As we look to the future, we expect our industry-leading long-acting pipeline powered by unparalleled patient insight to deliver 5 launches through 2030. We remain confident in our ability to drive sustained long-term performance and look forward to sharing more at meet the management investor event in Q2 2026.

With that, I'll hand back to Luke.

Thanks, Deborah. Turning to Vaccines. Sales were up GBP 2.7 billion in the quarter, up 2%, driven by continued strong demand for Shingrix, Arexvy and Bexsero, particularly in Europe, which was up 35%. Shingrix sales grew 13% overall, largely due to the strong performance in Europe, up 48%, where we're driving across multiple markets and with significant new uptake in France, and a strong performance in Germany, the Netherlands and Poland.

In international, sales in Japan continue to grow following the expanded public funding. Ex U.S. sales now account for around 70% of global Shingrix sales. And in the U.S., penetration is now 43% of the eligible older adult population with immunization rates slowing as expected as we access harder-to-reach patients.

In meningitis, our portfolio was up 5%, driven by double-digit growth for Bexsero in Europe, where the updated recommendation and reimbursement in Germany continues to pull through and in France following a meningitis B outbreak and the implementation of mandatory newborn vaccination requirements, along with new reimbursed cohorts.

Also in the quarter, even though the ACIP recommendation came slightly after the back-to-school season window, we booked the first sales of our pentavalent vaccine, Penmenvy in the U.S. with initial CDC purchases. We expect this vaccine to simplify immunization schedules and contribute to increased coverage and protection against a serious life-threatening illness.

Turning to Arexvy. Growth was driven by Europe with good commercial progress in Germany, Spain and Belgium. International also grew driven by tender volumes in Canada. And in the U.S., we maintained our market-leading share in the older adults population. However, the U.S. declined due to lower preseason channel inventory build and slower market uptake in the 60-plus population.

In Q3, our flu vaccines were down in part due to competitive pressure in the market where we compete for healthy younger cohort populations who are harder to activate in older adults for flu vaccines. And Established Vaccines were down primarily due to the prior year impact of our divested brands. So in summary, with the Vaccines business, we now expect to land towards the top of our vaccines guidance range of declining low single digit to stable.

And as we look forward, although we continue to remain cautious in the near term on vaccines in the U.S., we are confident in the prospects pipeline and benefit this business offers over the long term. Next slide, please. Turning to General Medicines. Sales were up 4%, driven by the strong growth of Trelegy in all regions, up 25% in the quarter.

And the SITT class remains very strong, up around 23%, driven by GOLD guidelines, new data and competitive share of voice. Within the SITT class, Trelegy continues to gain more share than any other brand and is the top-selling brand for both COPD and asthma globally. We also have completed IRA negotiations on Trelegy in line with expectations and our outlook.

The remaining portion of the portfolio was stable, reflecting continued generic competition and expected adjustments in rebates and returns. We continue to expect sales to be broadly stable in 2025 and are looking forward to future opportunities in this portfolio, including launching low-carbon Ventolin and further establishing our anti-infective portfolio through building access in the U.S. for Blujepa in uncomplicated urinary tract infections and also filing tebipenem in complicated UTIs by the end of the year. All 3 of these represent practical innovation for important areas of medical need.

I'll now hand over to Julie.