Swedish Orphan Biovitrum Aktie

Ladies and gentlemen, welcome to the SOBI Q2 Results 2026 Conference Call and live Webcast. I am Valentina, the Chorus Call operator. [Operator Instructions]. The conference must not be recorded for publication or broadcast.

At this time, it's my pleasure to hand over to Guido Oelkers, CEO. Please go ahead.

Yes. Thank you. Hello, everyone. This is Guido Oelkers, CEO of SOBI. So we are delighted to welcome you to the second quarter and half year of 2026 conference call for investors and analysts. Our presentation was posted on subi.com earlier today. Please turn to Slide #2. We would like to remind you of the usual provisions on statements about expectations and projections of future wins. Unless stated otherwise, we are making comments that mostly relate to the second quarter at constant currency exchange rates and SEK 1 million.

Please turn to the next slide. Today, we plan to cover the key aspects of our Q2 report. I'm joined by Henrik Stenqvist, our CFO, and Lydia Abad-France, Head of R&D and Chief Medical Officer. We plan to review this presentation first and have Q&A until around the 3:00 p.m. today. Central Eastern European time.

For those on the phone, please join the queue for questions by pressing star one. If joining on HD audio, please use a virtual keypad and press star. We propose that you ask only 1 or maximum 2 questions at a time. Please turn to Slide #4. I Key is about the key takeaways for Q2.

Let me start with the key messages. From what has been a very strong quarter for Sobi. In Q2, we delivered revenue growth of 29% and at constant exchange rates, alongside adjusted EBITDA margin of 35%, which clearly demonstrates both the strength of our portfolio and the quality of our execution. This performance was broad-based driven over our strategic portfolio supported across all regions, which again highlights the resilience and scalability of our business model.

We are pleased with the progress with our latest newest launches, such as Asper Valley in Europe, and at the same time, we delivered positive data from the REDUCE-IT trial for postatinered. We continue to make tangible progress across the entire pipeline. We are advancing Gamifant and interferon gamma-driven sepsis with Embrase 2 expected to initiate it in the second half of this year. Additionally, while we received a complete response letter for NAS related to manufacturing, -- the path to submission is clear, and we are taking the necessary steps to address the concerns of the agency. Importantly, based on the strong first half performance, we are increasing our full year outlook, which reflects both the momentum of what we are seeing today and our confidence in continued delivery.

So overall, the message for the quarter is very clear. We are delivering strong growth, making consistent progress in the pipeline and building further confidence in our trajectory. Please turn to the next slide. Let's take a closer look at the Q2 performance. Growth was very well diversified across regions and segments. We delivered total net sales of just under SEK 7.8 billion in the quarter, corresponding to growth of 29% at constant exchange rates. -- which is particularly important here is the quality of that growth. It is driven primarily across our strategic portfolio, which accounts around 2/3 of our group sales in Q2 and continues to grow significantly faster than the rest. -- in the rest of the year.

From our geographic perspective, the growth was very well diversified across all regions, North America delivered growth of 33%. International markets grew by 45% and Europe contributed 23%. And at the product level, we continue to see strong contributions from Dr. Led toward and Gummy fund, whilst new launches such as OsperVelley are building momentum and expanding their contribution. Taken together, this is a growth profile that is diversified, sustainable and increasingly driven by high-value innovative medicine. Please turn to the next slide.

Let me now turn to our pipeline and development progress. We continue to execute against a focused and disciplined development strategy, which with multiple programs advancing in parallel and delivering important milestones. During the quarter, we announced positive top line results of REDUCE-2 with Potginerad, which demonstrated meaningful reduction alongside its favorable efficacy and tolerability profile. At the same time, we are progressing gummy front in interferon gamma ties where we are aligning closely with regulatory authorities and preparing to initiate the EMBRACE 2 study in the second half of the year.

Across the broader portfolio, we continue to see steady progress in regulatory filings, life cycle management and new indication development which together underpin a strong and balanced pipeline. Overall, this pipeline replements a diversified set of launches throughout 2028, and supporting our ambition to reach approximately SEK 55 billion in revenues by 2030.

Let's look at a few products in more detail. to walk next slide, please. Altaba continues to perform extremely strongly and is establishing itself as a best-in-class product in hemophilia A prophylaxis. In Q2, Autowork delivered very strong growth with sales increasingly significantly on a year-to-year basis. supported by both new patient uptake and continued geographic expansion. We have now launched in 30 markets, including key European markets.

We are progressing a 3-wave launch strategy, allowing us to increasingly expand our share of the total market potential in the segment. During the quarter, our combined hemophilia A sales grew by 41% at constant exchange rate -- this performance reflects the strong clinical profile of Alto work and the disciplined launch execution.

Please turn to the next slide. The launch strategy in nephrology is progressing well across markets, and we are seeing encourage early momentum supported by an expanding evidence base. During the quarter, we continued to expand access, including approval in the U.K. and we are seeing increasing uptake in markets where reimbursement is already in place. National reimbursement is now in place in Spain or by coming towards the end of Q2. We are introduced -- we have introduced the infused on-body delivery system, with the first patient dosed and very positive initial feedback, which reinforces the differentiation of the product. Importantly, the new term outlook long-term outlook and real-world data continue to support the clinical profile in line with the strong pivotal Valeant data. We are well on track to reach our 2026 target of 400 to 500 patients in nephrology, which underpins our confidence in the long-term potential of this franchise.

Please turn to the next slide. So Doptelet continues to deliver consistent performance and is now firmly established as a leading global franchise. Growth is being diversified and is built on a differentiated product portfolio including strong efficacy, pure dietary restriction combined with an excellent execution. We are also continuing to expand it internationally with the recent launches across Asia, Latin America and other regions. Contributing to an increasing ex-U.S. contribution over time. Overall, this remains a highly attractive asset with continued strong growth performance and a growing significant potential in international regions.

Let's turn to the next slide. And speak about Gamifant and HLH and MAS. The U.S. launch in MAS continues to perform well with strong momentum driven by increasing the physician awareness and new patient demand. Growth is also being supported by the expansion in international markets following the FDA label.

In parallel, we have now completed -- we have not completed filing in both Europe and Japan, with a regulatory decision expected in Japan in H2, providing additional future growth opportunities for the product.

Let's move to the next slide. Regarding Gamifant in interferon-driven sepsis. This represents a significant opportunity, both medically and strategically, and we are making good progress in defining the development pathway. We had our first meeting with the emergency task force on the design of the IDS program. And based on the feedback we are pursuing a large registrational Phase IIb/III study in Europe through the EMBRACE 2 study, which we expect to initiate in the second half of this year. This study will be conducted in collaboration with the Hellenic Institute for the study in Sepsis based on the data, we will then decide on the regulatory pathway.

This provides a clear fast-to-market approach in the area of significant unmet medical need. While there's a lot of work still to be done, we believe that this presents a very meaningful opportunity to address in a high unmet medical need and further strengthens our pipeline.

Let's move to the next slide. Turning to our Gout franchise. We are building a leadership position across multiple segments in the gold market. For NAS, we received a complete response letter in June related to manufacturing, not the outcome we obviously would have wished for. However, it is important to note that this is not related to clinical efficacy, clinical safety or efficacy concerns. And we have a clear plan to resubmit within the next 6 to 12 months.

For ports to generate, the positive REDUCE-2 data represent a significant milestone, demonstrating strong efficacy and a favorable safety profile. We are pleased with the data that we have seen so far. We are on track for further data readouts and plan to progress towards filing in 2027.

Together, these assets provide the foundation for a meaningful and valuable franchise with significant long-term potential.

Slide #13, please. Let me now turn to guidance. Based on our strong performance in the first half of the year. We are increasing our full year outlook. We delivered outstanding first half growth of 26% at constant exchange rate alongside strong margin development. At the same time, we have made significant progress across our pipeline while continuing to execute on multiple key launches.

Taken together, this gives us increasing confidence in our ability to deliver both growth and profitability for the full year.

Now I'd like to hand over to Lydia.

Thank you, Guido, and hello, everyone. I will start with the pipeline milestones on the next slide, please. We continued our strong run during the second quarter. We received the top line data for odetinerab in its first on the 2 pivotal studies, and the results confirm our excitement. I will come back to this in a minute.

For NAST, the FDA issued a complete response letter, which lays out a clear and actionable path towards resubmission and I will share more details on that too. The results on the second line combination LOTIS 5 of Siloda and rituximab became available in June.

Based on the study outcome, we will use the lots results to convert the current third line conditional approval to full approval for Sinnomta monotherapy, especially in region international countries like Brazil, Australia and the Middle East region, where we see strong potential to help patients. New positive string of data from and CRI studies was presented at EAS, which I will detail later on. The certification of infused device for Aspabelli in the EU takes the way for home used by people 12 years and older.

The initial feedback from patients and physicians highlights the greater convenience compared to the previous solution. Kineret was approved in Japan for Still's disease, making another medicine now available for our growing presence in Japan. And we completed enrollment in the PACIFICA trial of ongoing chronic myelofibrosis, which we already discussed at the last earnings call. Next slide, please.

Turning to gout. Clinical results for Podetinura strengthened our decision to make this asset part of the Sobi portfolio and our ambition to build a gout franchise. We reported positive top line results from the pivotal Phase III REDUCE 2 study. Both the 75 and 50-milligram doses met the primary efficacy endpoint with 69% and 56.6% and of patients, respectively, achieving turmeric acid level below 6 milligrams per deciliter at 6 months compared with 8% of placebo.

Importantly, Potetinura was overall well tolerated with a safety profile consistent with previous studies. We expect to present detailed data at the Congress later this year, and we continue to expect the reduce 1 top line readout in the fourth quarter. On NAP, we received a complete response letter from FDA. The CRA is related to CMC and contract manufacturing facility topics, which are addressable.

The feedback provides a clear and actionable path forward, and we are actively engaging with the FDA and manufacturing partners as we work towards the submission.

Importantly, the FDA identified no concerns regarding clinical efficacy or safety profile of NAV that impacts approvability. So we remain confident in the long-term potential of NAV and committed to bring this treatment option to patients with noncontrolled gap.

Next slide, please. While in gold is under eager review for severe hypertriglyceridemia, above 880 milligrams per destigitor, new dates that were presented at the EAS conference. This full analysis of the pivotal and CORE II studies looked at patients with severe hypertriglyceridemia defined as TG levels of at least 80 -- this threshold is recognized by European guidelines as requiring urgent intervention to reduce the risk of acute pancreatitis.

And this is the population we are aiming for with the European submission. The analysis included 455 patients and focus on those at highest risk of acute pancreatitis. Things have demonstrated an 85% reduction in the relative risk of acute pancreatitis events placebo-adjusted reduction in TG levels with the 80-milligram dose after 6 months of treatment.

Importantly, 85% of treated patients achieved TG levels below 80 -- what we find particularly encouraging is that this data further strengthen the growing body of evidence linking teacher reduction with meaningful clinical outcomes. Acute pancreatitis is one of the most serious complications of severe hypertriglyceridemia. And these results reinforce the potential value of Triola begun biomarker reduction only. Overall, we believe this data support the efficacy and safety profile of [indiscernible] in severe hypertriglyceridemia above 880. The days transing our confidence in its potential to address a significant unmet medical need.

Next slide, please. Looking ahead, we continue to see a strong and diversified stream of pipeline milestones across this next year. Expanding nephrology, immunology, hematology and specialty curve. In the second half of 2026, we expect several important regulatory and clinical data events. This includes regulatory decisions in Japan for stable in C3G and primary ACM PDGM as well as Gamifant in HLH Mas.

In golf, we expect the reduced on top line data readout for Proteturia and in severe hyperclusteridemia above 880, we anticipate CHMP opinion for Kingold.

Moving into 2027. We expect continued momentum across the portfolio. Key anticipated milestones include the planned FDA submission for poppetinerat and the resubmission for NAST, regulatory progress for Gamifant in HLH mass in Europe an important Phase III readout for Bango in both myelofibrosis and Vestosyndrome.

Taken together, these milestones illustrate the breadth of our development portfolio and our continued focus on delivering innovation for patients living with rare and debilitating diseases.

And with that, I would like to hand over to Henrik. Next slide, please.

Thank you, Lydia. Hello, everyone, and please turn to Slide 20. I -- we will now take a look at some key financial metrics for the quarter. looking on the table to the right, we see our revenues of SEK 7.8 billion, corresponding to a growth of 29% in constant currencies. The adjusted gross margin of 77% in the quarter is in line with last year, and this is due to a mix of offsetting products and country mix effects.

Operating expenses, excluding nonrecurring items and amortization for the quarter increased by 24% at CER compared to Q2 2025. also excluding nonrecurring items and amortization increased by 15% at CER, driven by launch and prelaunch costs for Aspaveli in nephrology. Aspen Kingos. And these costs were partially offset by lower costs for Bogota R&D expenses increased by 47% at CER, excluding nonrecurring items, mainly due to the additional the those development programs. And as a reminder, we had only a part of a 1/4 of those costs in Q1.

And as a result, adjusted EBITDA for the quarter amounted to SEK 2.8 billion, equal to a margin of 35% compared to 34% for the same period last year. Operating cash flow for the quarter was SEK 1.9 billion compared to SEK 1.4 billion in Q2 last year. This increase reflects higher operating profit, but also partially offset by inventory buildup to support our launches.

And that gave the net debt at the end of the quarter just above SEK 16 billion. and a debt-to-EBITDA ratio of 1.3x compared to 1.5x in the previous quarter.

Please now turn to Slide 21 and the financial outlook for the full year 2026. As usual, this is based on revenue growth at constant exchange rates and adjusted EBITDA margin. So for the full year '26, we have raised the outlook for both revenue and adjusted EBITDA margin.

We anticipate revenue to grow at mid- to high teens percentage at and previously low double-digit percentage, and we expect momentum to continue with out-of-box Doptelet and Ganesan being the main growth drivers in full year 2026. However, on a percentage basis, we are up against high comps in H2, which will naturally bring down the revenue growth in H2 compared to the situation in H1, and this is how we come to growth of mid- to high teens for 2026.

Beyfortus, although not expected to be a major growth driver remains difficult for us to forecast, but we don't believe the fundamentals have changed with regards to recommendations and reimbursement. Related to adjusted EBITDA margin on that guidance, our margin in H1 was 37%. In the second half of the year, we will have the benefit of after seasonal royalties on our bottom line, as well as some NAS costs that we own now from 2 reals, where we will ensure a strong and well-prepared market entry to address the larger patient opportunity in HFG, which we expect to launch next year. And finally, and as usual, we will continue to be diligent with cost containment in the rest of our business.

So with this, I hand back to Guido. Thank you.

To conclude, then maybe we can go to the next slide. SOBI continues to execute across all dimensions. We are delivering robust financial performance, driving successful launches and advancing a differentiated pipeline. At the same time, we are making a disciplined strategic choices that position us well for long-term value creation.

With this positive readout of Pozdeutinurad and REDUCE-2 we have significantly derisked this asset and look forward to continue to progress it towards approval. So overall, we are entering the second half of the year with a strong momentum and increasing confidence about our growth trajectory.

With this, I would like to hand over to Q&A.

[Operator Instructions]. The first question comes from Christopher Uhde from SEB.

Probably for Guido and maybe Lydia. So Arrowhead has a few trials reading out in Q3 that include acute pancreatitis as endpoints. So what do you see as -- or perhaps hear from your stakeholders as the bar in terms of magnitude of pancreatitis reduction for them to hit that was threatening things as chances of being the clear preferred therapy in Europe.

And my second question is basically on why the NASP CRL came and what the impact is. So specifically for Lydia,I think the NAS BLA was originally delayed by about a year as the team worked to get CMC right. So what detail can you share to help us understand the extent to which what happened here was foreseeable or that it was out of your hands such as because of regulator bandwidth and related to the uptick in CRLs that we've seen.

So obviously, then obviously, this feeds into what you can say about your confidence in terms of being able to fully address all the outstanding issues within the time frame you've mentioned.

Yes. Thank you. Maybe we start with the competition with Arrowhead, and then I hand over to Lydia. I mean you look at the situation [ Everhad ] being behind us we are now already in the market with FCS. And obviously, you know that we are preparing the approval when the launch for for the broader indication as early as beginning of next year.

So from this perspective, we are the lead -- we have very strong data on SDG reduction, which is probably more comparable with the Arrowhead product, and we have new when you account for these data properly. And then you have the -- we have the data in AP reduction, which obviously upped the bars super high.

Now, these are not comparative trials. A lot of things can happen. But for them to beat or need is not going to be evident. In any case, we have a time advantage and we have not obviously insinuated that we take the entire market.

We just said that we are exploiting the lead position, and we will be up we don't underestimate the competitor, but we think that we have here an edge. And we are building these teams out. This is for us a key priority launch. And we are well on the way in terms of building these teams.

I mean, it's one of our foremost points. So yes, they will come, but the market is large enough. We think that we are in the lead. And it's -- and it's for them to try to meet our efficacy level and the bar is super high. And these are noncomparative trials, obviously. So Lydia, you want to comment maybe on the -- what you expect in these trials and maybe then talk about NASP.

Yes. So when it comes to Vedanta, basically, we always need to be very cautious as it says you cannot compare head-to-head trials because you can find differences in the patient population. We need to be also aware that, for example, we already have a had a start also with the auto injector that is something that for this type of current treatment is bringing a lot of value to patients.

So I think that we want to see the data first. It's not only about efficacy. We need to look at also the safety profile. So there are many nuances here, but we remain very confident that rings is going to be a very strong asset for this indication. So I think that let's wait and see the data first when it comes yes, probably soon, and then we can comment more based on the facts.

But we are remaining very confident on what Trina can deliver. And maybe I can touch briefly on the CRL. And yes, you are right. We had already previous discussions with FDA. And as you know, some of the manufacturing facilities outside the U.S. that that have been resolved.

So there are now CMC questions and data that we need to address. And I think the most accurate thing I can say is what we are doing now after receiving the CRL is that we will be meeting with FDA to affect the time lines and we plan to resubmit because what it's clear is that there is a very tough, a clear path and actionable that we can deliver. And yes, that's what we will be doing in the next months being this obviously a high priority for us.

The next question comes from Kirsty Ross-Stewart from BNP Pariba.

It's Kirsty Ross-Stewart from BNP Paribas. So maybe just a quick 1 on Altosoft growth, obviously very impressive in the quarter. So just as you progress through your kind of 3-way launch plan. Can you provide a bit of color on the opportunity associated with kind of each wave of the launch plan relative to your SEK 10 billion set guidance? And bigger picture, just how long can you sustain -- or do you think you see sustain double-digit growth post 2026?

And then on the sepsis Phase II/III program, based on some relatively rudimentary statistical assets, I think that the 1,800 patients target across 3 arms of the trial implies that you're powering this trial for kind of high single-digit delta versus placebo, which would imply a little bit of a step down from the 12% LC you saw in the Phase II trial. So firstly, maybe is that a fair assumption? And can you just explain how you're thinking about your expectations for the corn as you go into the registrational trial.

Yes. Thank you for your question. Maybe I'll start quickly with we think that we can sustain this for quite a while. I mean, if you extrapolate the sales numbers that we already achieved in the quarter the product is on a good way. We are clearly on track to make this SEK 10 billion mark. Yes, no question. And we will -- we don't know yet when we will achieve it, but there's a lot of growth opportunities still in Europe and there's obviously significant growth in some of the international markets, as you will see. So we are not worried about this. This is it is -- and also the -- when you think about Alto in combination with Elocta, the number will already be this year extremely substantially. So maybe I refer now to Lydia on the Sepsis trial.

Yes. So yes, you are absolutely right that the plan to have patients recruited. And we recently received the feedback from EMA and the emergency passport. And that's what we are now reviewing and implementing in the protocol. So it's a bit early to comment on details on the statistical power arms design, et cetera. And we will be very happy to come back to all of you once we have finalized the protocol based on all this feedback that has been positive because it's really allowing us to go through a registrational Phase IIb/III trial. So at this point in time, no more details that I can provide, but the good news is that we have this feedback very clear that we are now working to implement in our protocol.

And I think, Kirsty, it's fair to say that we -- and Lydia, we will not power the study for a single-digit difference I think that's -- yes, I think this is clear why would we do that.

The next question comes from Mitchell Kapoor from H.C. Wainwright.

This is Amit on for Mitchell. Congrats on the strong quarter. Just 2 questions, 1 on the NAS I was wondering if the post-CRLFD meeting has already been scheduled and if the 6- to 12-month resubmission estimate is based on direct FDA feedback or at Sobi's internal estimate -- and are there any milestones between now and resubmission we should be looking out for?

And the second question on the guidance I guess, what level of sales growth are you modeling in the second half to reach that midpoint of the revised range? And what do you expect to drive this growth? Where have you embedded the most conservatism.

Maybe Lydia, you start is as.

Yes, sure. So the meeting with FDA has not been scheduled yet. We have 90 days to align with FDA on that. So -- but this is something that we are planning, and it will be scheduled soon. So that's the first question related to that meeting.

And then the second part on the 6 to 12 months, this is still our estimate and we have 12 months to resubmit and we are looking into every way to accelerate and to make it the close to as possible, but it's a little bit early to be more precise on that. So it's something that is based on our assumptions and we have not yet had that discussion with FDA to really fix the next resubmission date. But in the meantime, we will be working and the CMC team already has started internally and with the external manufacturing facilities to address the issues.

To the team in the technical operation know exactly what needs to be addressed they're working on this, and they've prompted our advice with regard to the time line.

Normally, we are not so precise on guidance, but I understand Henrik has a good day. Maybe you can elaborate on your guidance.

Yes, I can. Of course, H2 will naturally come down in terms of growth rates because of the high comps that we have from H2 last year. But I think you were asking for a number, and it's obviously, an H2 growth of some low double digit -- low to mid-double-digit growth, but we won't give any exact number.

Got it. And I guess, just for the NASP CRL, just the last part of the first question was, are there any particular milestones we should be looking for between now and the resubmission kind of other than obviously the FDA meeting?

No, not really. We just need to meet with FDA and agree on the next plan for the recognition, but nothing in between that we will need to communicate.

The next question comes from Harry Gillis from Berenberg.

Could you please let us know what were the biggest drivers of the top line guidance range, so which drugs had the biggest difference in H1 versus your prior expectations?

And then number two, could you please discuss how you're thinking of the Gamifant sepsis opportunity in terms of the U.S. And I believe this is an ex U.S. or just European-only trial? How are you thinking about the opportunity there will also be go alone or perhaps look for a partner?

And then if I could ask a third question, as we try and model [ Triangle ] sales next year in Europe in the larger HTG indication, -- how should we think about that piece of launch somewhere between Altabox and Aspavelli or is this more of an Aspaveli type launch just considering it's obviously a new area, but the drug is already on the market. You're already speaking to physicians in the smaller indication.

With regard to the growth drivers as well as guidance, it's clearly Doptelet and I to work because it's an exceptional performance. And obviously, and and Doptelet was not obvious that we can still retain such a strong growth momentum also in markets like the U.S. and I mean, internationally anyway booming.

And so this clearly sticking out. But the performance is obviously driven by across board and very pleased also with the Kineret performance.

With regard to Gamifant and IDS, I mean, -- this is a decision that we have taken. It's only driven by speed because we felt that the emergency task for us was giving us understanding what we try to achieve. And we basically have to set up, and our goal is to make the drug available as fast as possible.

And obviously, we will update you then on the -- on our approach to the U.S., we will democratize access, obviously, to the product, but we thought if we get to a very kind of fast track approach in Europe, then that and we believe in the product that will pave the way for other geographies.

Lydia, do you want to comment?

Yes, sure. So you're absolutely right. The objective is based on the feedback from EMA and the emergency platform. We have a path for, let's say, the fast to market, but the ultimate goal remains to get an approval for games in this indication globally, but it will be a stepwise approach.

And this was -- it's just speed that prompted us. This is a part -- and then with regard to Cingal, mean we have not set this out. But you have seen the global ambition. It's 1 of our biggest -- it's going to be one of our biggest products. And I think you have to see this in this slide. I mean it's always tough because you will -- over time, you will have this uptake -- and this is probably an uptick commercially.

I mean, if it it may take more time than, let's say, the uptake than it work, but it's a very large area. So we are optimistic, but we have not yet provided a detailed guidance. So -- but we have given you an idea where we see this thing globally turning out, and it's going to be a very huge product to us.

Next question comes from Gonzalo Artiac from Danske Bank.

Gonzalo Artiach from Danske Bank. I have a couple of them. The first 1 is anasatelli. We see that sales went slightly down versus Q1. I was wondering if you could give us some color on the launch trajectory in kidney rare diseases and why we have not seen signs of growth in Q2. How should we see this drug in this launch period going forward in terms of looking forward estimates?

And the second question is following the previous one on Gamifant on sepsis. Just so I understand. Have you spoken with on this opportunity already or only with EMA? And is the decision of going only for Europe, also driven by study design or more stringent longer endpoints with much if required...

Maybe, Kydia, you start with the sepsis and then we follow to talk about EMA.

Thank you, for the one -- I will start with this idea, please. And yes, we -- the answer is yes, we've talked now only with and that is based on this state to market and really having a clear path towards a registrational trial in Europe. Having said that, that does not mean that we are not talking to experts in the U.S. because this is not -- we have a long-term plan for Camifon, as I mentioned before, and it's an ambition of having a global asset for Idea. So we've started some conversations with the U.S. experts but not yet with a delay.

And it's -- again, we have a very high attention level at the lipid in EMA. We didn't want to lose this momentum. It's a time decision. And with regard to us Aspaveli, let's say, the -- this is -- the variance is more driven by PNH than by I mean we have -- when we say that we are very confident with our patient numbers that basically tells you that we are -- we have a very good uptake in terms of number of patients in comparison to what we set out to the market.

And this -- and obviously, Spain came on board a little bit late. You see an effect in Germany. It always takes some time to bring these patients on. But the the launch is well on the way. And obviously, that patient numbers ultimately have to translate into sales. And we have stabilized this P&H business, but -- that means also that there should be an accumulation effect. So there's nothing wrong with the launch.

We are clearly confident to exceed or meet at least our guidance in terms of number of patients. So product is in the right trajectory. And you will see this in the later quarters.

The next question comes from Johan Junius from SB1 Markets.

Plenty of good questions before. But to go back to the NASP details just for the framework of the process. Could you -- once you will have the time table more established following the next meeting, will you communicate that? And also, will that communication provide more substance into the details that is at hand. Of course you using contract manufacturing in the process. And also, please remind us about the balance you submit, what's the time line to be expected after the submission.

Lydia?

So and I'm sorry because I could not hear the end. So you were asking when we submitted.

Yes, the last bit was once you do submit 12 months or a bit or nearer, what's the time line afterwards we can expect?

That was the last bit.

Okay. So -- we submitted in June last year, we were expecting -- so we had our PDUFA was June this year. Now we have this up to 12 months to rest of it, and then we will try to shorten. I don't think that we can provide very detailed information on exactly the time lines for each of the ports.

But once we submit, we have 6 months for the review of FDA of the rest of Mission this year.

Yes. And following the meeting that will take place, then you will have a better view on the time lines. And will you at that stage, communicate that and will also provide some more details regarding the as the issues.

I think that, that's a piece that we need to decide once we meet with FDA. So probably in the next quarter call, we can bring more details, but it will be high-level detail information.

Are there more questions?

No, that was the last question. The over to you for any closing remarks.

Yes. Thank you so much, and for your interest. I know it's a summer season. So more we appreciate that you're dialing in. As you can see, we we feel quite bullish about this business, 29% growth is giving us a lot of confidence for the coming months and for the rest of the year. And with strong earnings supporting this business and progress, obviously, in the portfolio and the pipeline. Even though not everything has worked out according to plan, but that's life. But the majority of things that's important projects clearly prevailed. I think this is what matters. Thank you so much, and wish you a great week. Look forward to reconnecting with you. Thank you.

Ladies and gentlemen, the conference is now over. Thank you for choosing Chorus Call, and thank you for participating in the conference. You may now disconnect your lines. Goodbye.

Ladies and gentlemen, welcome to the Sobi Q1 2026 Report Conference Call and Live Webcast. I am Valentina, the Chorus Call operator. [Operator Instructions] The conference is being recorded. [Operator Instructions] The conference must not be recorded for publication or broadcast.

At this time, it's my pleasure to hand over to Guido Oelkers, CEO. Please go ahead.

Thank you. Hello, everyone. This is Guido Oelkers, CEO of Sobi. We are delighted to welcome you to the first quarter 2026 conference call for investors and analysts. Our presentation was posted on sobi.com earlier today. Please turn to the next slide. We would like to remind you of the usual provisions on statements about expectations and projections of future events. Unless stated otherwise, we are making comments that mostly relate to the first quarter at constant exchange rates in million Swedish krona.

Please turn to the next slide. Today, we plan to cover the key aspects of our Q1 report. I'm joined by Henrik Stenqvist, our CFO; and Lydia Abad-Franch, Head of R&D and Chief Medical Officer. We plan to review the presentation first and then have a Q&A until around 1:30 p.m. Central Eastern European Time. [Operator Instructions] Please turn to the next slide.

We have delivered a very strong start in Q1 2026 operationally and financially with 24% revenue growth at constant exchange rate and an adjusted EBITA at 38%, reflecting strong commercial execution across the portfolio, disciplined cost management, continued strategic investment for long-term growth. These numbers speak for the resilience of our portfolio in turbulent times. I think important to note is the progress we have made with our 6 launches. And the strategic portfolio grew by 55%, contributing 63% of our total business. This dynamic growth was driven by key launches, including Altuvoct, Gamifant and now the European and international launch of Aspaveli in C3G and IC-MPGN.

In addition, we have been able to achieve our milestones for Tryngolza in sHTG and submitted and launched FCS as well as completed the transaction of Arthrosi, which is obviously an important milestone for us that enhances both the breadth of our pipeline, but also our long-term growth trajectory. Overall, Q1 demonstrates strong execution across the business, and I would like to reiterate the resilience of our business even in ambiguous times and we continue progressing our momentum for the years to come. Please turn to the next slide.

Let's take a look -- a closer look at the Q1 performance. Growth was well diversified across regions and segments. Each region contributed and our key products continue to scale effectively. Our strategic portfolio is now the central engine of Sobi's performance, representing our shift towards high-value, high innovation assets and as mentioned, representing 63% of our revenues in Q1. All regions delivered solid growth and continue to build momentum quarter after quarter.

Let me take you now through some of the key products. But before doing this, let's reiterate, let's turn to the next slide and review what our program is ahead and that we have shared with you during the recent Capital Market Day. Looking ahead of our priority programs and launch cadence, we continue progressing a broad set of opportunities, creating material opportunities for growth and diversifying our portfolio. We had a very good start with Aspaveli in Q1 and are in the process to roll out the indication C3G and IC-MPGN across our territory. With regard to NASP, we wait for FDA's decision before end of Q2 and discuss the first data readout for Pozdeutinurad at latest by the end of Q2. For Tryngolza, we have had a good start to the FCS launch in Europe and continue building relationships with key lipid centers. The launch of FCS is an important foundational step for the planned launch of sHTG.

In the quarter, we also filed Tryngolza in Europe in the indication sHTG. Overall, this pipeline represents a strong and diversified set of launches throughout 2028, supporting our ambition to reach approximately SEK 55 billion of revenues by 2030.

Please turn to Page 7 for the next slide. Altuvoct continues to be a true standout in our portfolio. In Q1, Altuvoct continued to show exuberant growth with 186% and is consistently gaining market share as the launch progresses. We have also launched across the major EU5 markets, although it's worth mentioning or noting that some of these launches are still at a very early stage of rollout. During the quarter, our combined hemophilia A business grew by 25% at CER. This performance reflects the strong clinical profile of Altuvoct and the disciplined launch execution. We have now launched in 27 countries with key markets such as U.K., Italy and France being at an early stage. We can expect to demonstrate exuberant growth in Wave 3 and Wave 2 countries for some time. Overall strong momentum and clear path for sustained growth.

Let me now move to Gamifant. In the first quarter, Gamifant delivered SEK 734 million in sales, up 47% at constant exchange rate. Growth is driven by the U.S. launch in MAS, where Gamifant is now the first approved treatment for both adults and children with MAS in Still's disease with an uptake continuing to build awareness will increase. From a regulatory perspective, we have completed filings in both the U.S. and -- sorry, in both in Europe and Japan in HLH/MAS, supporting further geographic expansion. We are now also progressing in interferon gamma-driven sepsis, where the Phase IIa EMBRACE study has shown proof of concept and we are now engaging with regulators on next steps and will provide -- we will provide an update latest by Q2 reporting. Overall, Gamifant is delivering strong commercial momentum today with multiple longer-term growth opportunities ahead.

Please turn to the next slide. Let me turn now to Aspaveli. In Q1, we are encouraged by the strong uptake of Aspaveli in C3G. The product delivered SEK 371 million in revenues, representing 21% growth versus last quarter. This performance reflects the new momentum from our European and international launch in C3G and IC-MPGN, whilst PNH remained stable, in line with our expectations. As a reminder, C3G and IC-MPGN are areas of high unmet medical need. Today's standard of care does not adequately hold long-term progression and disease progression, and this is something that both physicians and patients are acutely aware of.

Aspaveli directly addresses a key driver of the disease biology supported by what is believed to be best-in-class. During the quarter, we began our nephrology launch in Europe with Germany as an initial focus. I'm pleased to say that the launch is tracking ahead of our internal expectations. We see very positive feedback from the market, including some engagement from nephrologists and a clear preference share for Aspaveli among HCPs from recent research findings. These initial segments improve our belief in the long-term potential of Aspaveli in nephrology. For orientation, our 2026 target is to have 400 to 500 patients on Aspaveli therapy.

Please turn to the next slide. Doptelet continues to deliver very strong growth momentum. In the first quarter, sales reached SEK 1.4 billion, up 44% at constant exchange rates. This performance is driven by strong clinical -- strong clinical profile with high efficacy and fewer dietary restrictions, making it an important option in ITP. Doptelet has become a truly global franchise with growth across all 3 regions, but in particular, strong growth in the international region. While some demand -- while demand in the U.S. is consistently expanding, we continue to increase penetration in Europe and experienced exponential growth in international markets, particularly in Asia, meaning Japan, and strong growth across other subregions, reinforcing the long-term potential opportunity. Consequently, we expect a material increase of the international contribution in 2026. Overall, Doptelet in 2026 remains a key growth driver, supported by both established and newly launched markets.

Please turn to the next slide. Arthrosi Therapeutics is an important step in building our leadership in gout and broaden our immunology therapy area. We completed the acquisition during the quarter, added a high-quality late-stage portfolio targeting significant unmet medical need. The portfolio is anchored by 2 complementary programs. Firstly, NASP. We have PDUFA date on June 26 and expect feedback from the FDA during the forthcoming weeks. We are ready to launch in chronic refractory gout during Q3. Second, Pozdeutinurad, next-generation once-daily URAT1 inhibitor for progressive gout with a planned launch in 2028. Pozdeutinurad represents the primary economic opportunity for Sobi in our gout franchise. For Pozdeutinurad, the key Phase III readouts are coming this year, including REDUCE-2 data in Q2 and REDUCE-1 in the second half. We are eagerly looking forward to sharing the data when available with you. Overall, this acquisition strengthen our pipeline, expand our presence in gout and adds multiple value-creating milestones in the years to come.

Please turn to the next slide, and I'd now like to hand over to Lydia.

Thank you, Guido. Hi, everyone. As per usual, I will start with the pipeline milestone on the next slide, please. We started the year on a very strong foot. Aspaveli in the nephrology indications, C3G in primary IC-MPGN was approved in the European Union in January, 1 month ahead of the scheduled time line. We got positive top line data for interferon gamma -- for Gamifant in interferon gamma-driven sepsis that enable us to move forward with the clinical development program. And we also got some new data from the EMBRACE study, which I will talk about shortly. We submitted Tryngolza for severe hypertriglyceridemia to the European Medicines Agency. And we also fully enrolled all patients in the PACIFICA trial of Vonjo in chronic myelofibrosis. PACIFICA is our confirmatory Phase III trial, key to get full FDA approval, and our attention is now on preparing for database lock and subsequent submission next year.

Next slide, please. Turning to Gamifant in interferon gamma-driven sepsis. The initial data from the EMBRACE proof-of-concept study was presented last month in Brussels at ISICEM in the International Symposium on Intensive Care and Emergency Medicine. During our Capital Markets Day, we already shared the key study results of EMBRACE that show an improvement in organ dysfunction as measured with the SOFA score and patient survival with emapalumab at the end of treatment on day 28. 60% of patients in the high-dose emapalumab arm achieved the primary endpoint of decrease in SOFA score compared to 40% in the standard treatment plus placebo. This is shown in the left chart, which was presented at ISICEM. These results translate into 5 patients needed to treat to improve organ function of 1 patient, which is very encouraging in sepsis.

Last week, the long-term mortality follow-up was presented at the World Sepsis Congress. It confirmed a maintained survival benefit with emapalumab high dose, as you can see on the right chart. At the end of the study treatment day 28, we saw a 12% point benefit of the high-dose treatment and very similar results were seen in the follow-up period, showing maintained survival benefit at day 60 and 90. This further supports the proof of concept and our belief in advancing the clinical development of Gamifant for interferon gamma-driven sepsis.

Next slide, please. Looking ahead, we anticipate continued momentum with major regulatory milestones across U.S., Europe and Japan as well as key clinical data. In the first half of 2026, we plan for the NASP FDA decision in June, the first Pozdeutinurad readout from the REDUCE-2 pivotal trial in progressive gout and the LOTIS-5 data readout in relapsed/refractory diffuse large B-cell lymphoma. Later in the year, we expect the Japanese regulatory decisions for both Aspaveli in the nephrology indications and for Gamifant in HLH/MAS. We will see the second Pozdeutinurad readout in this case from the REDUCE-1 pivotal trial. And finally, the Tryngolza CHMP opinion in severe hypertriglyceridemia is also expected before end of the year.

And with that, I would like to hand over to Henrik. Next slide, please.

Thank you, Lydia, and hello, everyone. Please turn to next slide, and we take a look at some key financial metrics for the quarter. So in Q1, our revenues of SEK 7.2 billion correspond to revenue growth of 24% at CER and hematology increased by 24% and our combined hemophilia A portfolio increased by 25% as Altuvoct continued its strong launch momentum and is now launched in all major EU markets. Doptelet increased by 44% at CER, driven by strong growth in all 3 regions. And Aspaveli in nephrology, as we saw, is now launched in its first market with positive feedback.

In Immunology, we saw strong double-digit growth in both Gamifant and Kineret, offset by lower RSV royalties. Specialty Care also increased by 24% at CER, driven by new patients in Tryngolza on FCS and patient growth in some other specialty care medicines. If we look at the table on the right, then the adjusted gross margin of 77% in the quarter is in line with last year. Gross margin was positively impacted by product mix and country mix effects, offset by lower Beyfortus royalties. Operating expenses, excluding nonrecurring items and amortization for the quarter increased by 15% at CER compared to Q1 '25, reflecting the increased activity level in the company.

SG&A also excluding nonrecurring items and amortization increased by 12% at CER, driven by launch and prelaunch costs for Altuvoct, Aspaveli in nephrology, NASP and Tryngolza. And R&D expenses increased by 22% at CER, excluding nonrecurring items, mainly due to the addition of Arthrosi development programs as well as increases related to Tryngolza and Vonjo. And as a result, the adjusted EBITA for the quarter amounted to SEK 2.8 billion, equal to a margin of 38% compared to 36% for the same period last year.

Operating cash flow for the quarter was SEK 1.1 billion. Higher operating profit was offset by higher working capital buildup due to 3 main items: Arthrosi transaction-related payments, inventory prepayments and lower Beyfortus royalty payments following lower sales last year. And as a result, the net debt at the end of the quarter was just below SEK 18 billion, net debt-to-EBITDA ratio of 1.5x.

Please turn to next slide and the financial outlook for the full year 2026. As usual, this outlook is based on revenue growth at constant exchange rates and adjusted EBITA margin. For the full year 2026, the outlook remains unchanged. We anticipate revenue to grow at low double-digit percentage at CER and an adjusted EBITA margin in the mid-30s percentage of revenue. The key drivers for the 2026 outlook that we discussed in connection with the Q4 report in February are still relevant. On the revenue guidance, we expect continued progress with our existing commercial portfolio with Altuvoct being a continued key growth driver.

Beyfortus, not to be too repetitive, remains difficult for us to forecast, but we don't believe that the fundamentals have changed with regards to recommendations and reimbursement. Regarding our EBITA margin guidance, I want to reiterate some key costs that we will have in 2026 that are new or accelerated compared to 2025. First, we have the prelaunch and launch costs for Aspaveli and NASP. While we had some of those costs in Q1, they will continue to accelerate as we get approval in additional countries for Aspaveli and as we get fully staffed for NASP closer to launch.

Second, filing and prelaunch costs related to Tryngolza in sHTG. In March, we submitted to EMA for the indication expansion for sHTG. So we will also continue to see the additional costs moving forward as we near launch. Third, the acquisition of Arthrosi adds the R&D cost of 2 ongoing Phase III studies and preparation for regulatory submission. Finally, we're also planning the continued development of Gamifant in IDS, and this is something we will come back to after our interactions with regulators. And all these costs will partly be offset with reallocation of resources and cost containment in the rest of the business, including the full year impact of the cost savings initiatives from 2025.

And with this, I now hand back to Guido. Thank you.

Thank you, Henrik. And let me close by summarizing the key messages from today and a brief recap from our recent CMD. First, Q1 2026 reflects a very strong execution across our entire portfolio and regions with robust financial performance, broad-based growth, as mentioned, across the portfolio, coupled with disciplined execution. The robustness of our commercial portfolio, especially in uncertain geopolitical times, is a testament of our diversified portfolio and the people who are working at Sobi.

As outlined in our Capital Market Day, we see 6 major launches as key drivers towards our 2030 ambition. And in the quarter, we continue to make strong progress in this direction with the new launch for Aspaveli in nephrology, the filing for Tryngolza in sHTG and the launch of FCS. We continue to see strong momentum in Altuvoct. Gamifant. We have strengthened our position in gout through the Arthrosi acquisition and continue to progress the pipeline with multiple value-creating opportunities. Overall, we remain confident in our strategy, in our execution and in our ability to deliver sustainable long-term value for both patients and our shareholders.

With that, I'd like to hand over for Q&A.

[Operator Instructions]

The first question comes from Shirley Chen from Barclays.

May I ask about Aspaveli C3G launch. Could you please share with us a bit more initial market and clinician feedbacks on the new indications? And also just wondering how do you find the competition dynamics so far in your launched countries?

Yes. Thank you. I mean we have just recently performed a survey across the various countries. We're on the market in Germany, obviously, always being the first and then also in the other 2 German-speaking countries. So we can see some feedback and in various international markets. And the feedback actually across the survey, but also from the conferences and ads that we have is that there is a very strong preference for Aspaveli versus other new launches or a new launch in this indication. And it's referring to the profile -- you may remember the triangle that we pointed out with the efficacy in proteinuria, the stabilization of eGFR already after 6 months and also the important data on staining. And this seems to resonate. And we get a very strong preference share actually in high priority centers and priority centers.

So we think that we still have some room to cover when it comes also to community-based nephrologists, but our approach was more top down. We're very happy with where we stand right now. And when you think about the overall magnitude, I mean, this is really early days. I mean we didn't launch in Germany until the late second half of January. And already, this -- what we have achieved is moving our performance. When we outlined this, we were probably more stable at PNH. And this early launch is already moving the product by 21%. And that gives you, let's say, a take that the product is quite -- that the launch is quite meaningful, granted its early days, but we don't want to get ahead of ourselves. But it's -- we are very pleased. And so performance, number of patients, feedback from physicians are very consistent and very excited to take the product forward.

The next question comes from Christopher Uhde from SEB.

Christopher Uhde from SEB. My first question, I guess they'll both be on the pipeline. So probably for Lydia, I guess. Pozdeutinurad, would you please tell us how you view the bar for success there? And also in terms of the timing of REDUCE-1, is it more likely to be sort of in Q3 or Q4? And then my second question is on the sepsis longer-term follow-up. Just hadn't planned to ask on it, but since you showed the data there, 120 days, I believe, was the actual endpoint. And obviously, you have that data in-house. I'm just curious how that looks compared to the 90-day cutoff that you show, obviously, it's benefited the patients longer than Kineret did in its trial, but curious to hear what the 120-day looks like.

So if you want, I can start with the IDS. And as you probably know, the end of treatment was day 28, and there is where we were measuring the efficacy. Then all the sepsis trials look at mortality until day 90. That's the standard in sepsis. And the only reason why we follow up until day 120 for safety to reassure the safety profile of emapalumab is because of the long half-life of emapalumab. If emapalumab had a shorter half-life, we would have just follow-up patients until day 90. So that's where you look at mortality. If you look at all the sepsis trials that are published, they follow either 30 days, 60 or 90. 90 is the standard. So that's why we are collecting the safety data to reassure that the use of Gamifant in IDS has not increased any safety concerns.

When it comes to, -- as you know, the primary endpoint is the reduction in serum uric acid. And what we've seen so far is the Phase II data, which is very reassuring. So I think that we are expecting very good results, but we need to be careful. And then that's what we will see top line data, as Guido has mentioned in his presentation. And later, we will see the tophi reduction -- the tophi resolution and the flare reduction. So we are expecting very strong data. When it comes to the timing, I can reassure you that we are very excited and working very closely with the team -- our gout franchise team together with the extra Arthrosi people, and we are trying to push the data as fast as possible. But I think we need to be careful. Our plan is to have it before the end of Q2. If we can bring it earlier, of course, we will let all of you know. But for the time being, we are planning for the end of Q2.

Okay. Can you just clarify though on the -- in terms of the bar, I mean, is there a particular level of sUA you need? Or is it just stat sig?

Yes. So what we expect is it's what we have from the previous trials. And again, this is a large pivotal trial, 2 sister clinical trials in these indications. So I think it's maybe premature to say, okay, this will be fine or not. So we expect a very important reduction in serum uric acid because of the mode of action and because of, obviously, the data that we've seen. So more to come probably in, yes, very short few months.

The next question comes from Kirsty Ross-Stewart from BNP Paribas.

Kirsty Ross-Stewart from BNP Paribas. So with respect to Aspaveli, the step-up in Q1 sales is impressive given the expectations for relatively moderate ramp in the nephrology indication. So is it fair to assume you're tracking ahead or at least the top end of your 400 to 500 nephrology patient target that you set for the year? And then on Altuvoct, you're highlighting kind of material headroom for future growth from the second wave of launches and comfortably on track to reach double-digit growth this year in the Hem A portfolio. So just wondering how long do you anticipate you can sustain that double-digit growth in the Hem A franchise?

Yes. Thank you. Maybe let's start with the easy bit. But I mean, let's -- we obviously don't want to reset expectations 3 months into the year for Aspaveli. But if anything, you get a sense, I mean, you do the math that we clearly have no reasons to believe that we don't reach this range. I mean this is -- I mean, if anything, our confidence to make Aspaveli an important product for Sobi in nephrology has significantly increased based on the data points we have collected in the first quarter. And -- but we will update you in Q2, but we are on a very, very important slope and we also outlined that we are ahead of our internal expectations.

With regard to Altuvoct, I mean, this will -- we have not reached -- I think we will -- can look forward to significant growth in the years to come as there's still some quite a bit of headroom. I mean we have seen early signs of really spectacular growth in international markets. And we have the growth opportunities in Europe, particularly in the second wave countries or in the later-stage opportunities like France. We still have significant room for growth in Spain and in the U.K. And let's say, in Italy. So this strong growth momentum that you see is clearly going to be with us.

And for me, gratifying is when you look at the quarterly business size of the hemophilia A business and the momentum of Altuvoct, we are clearly on track for our ambition that we set out that we believe that our hemophilia A franchise is going to be a blockbuster franchise. And so very strong momentum and very optimistic for this franchise. I hope I could give you some sense because typically, we don't reforecast during the first quarter on the product level.

The next question comes from Mattias Haggblom from Handelsbanken.

Mattias Haggblom from Handelsbanken. Two questions, please. Firstly, on Altuvoct. So Roche said on their earnings call last week that strength in Hemlibra for the quarter had been driven by switches back from Altuviiio or Altuvoct and mentioned the fact that Hemlibra doesn't cause inhibitors as one of the drivers. So could you comment on what switching dynamic you see in your region, plus also remind me what real-world evidence suggests for inhibitor incidence among Altuvoct patients?

And then secondly, again, on Aspaveli, during 2025, product was largely flat until Q4 when there was a sequential decline quarter-over-quarter. But in Q1, sales up sequentially significantly, well more than the year-over-year 20% growth that you referenced. So was all of the sequential increase linked to the C3G launch as you claim PNH was stable? And was C3G all demand driven? Or was there any stocking to call out?

Yes. Let's start with the easy bit. With Altuvoct, when you grow 86%, I mean, we may have the one or the other patient. But when you gain -- I mean, this is less than 1%. I mean, so -- I take the 99% any day. And so we don't have a problem with switching and whatsoever. And obviously, we don't see a problem of inhibitors. I mean, anyway, this is a known risk, obviously, that you have a factor. But what we see though is a lot of very positive feedback from patients who are on the product and actually have switched from Hemlibra and telling us, let's say, no, have a much broader set of opportunities to live their life at the fullest and don't have to worry about bleeding, particularly during exercise. So I think maybe, Lydia, you want to comment on the risk of inhibitors?

Sure. Yes. So obviously, Hemlibra does not get risk of inhibitors because it's not Factor VIII replacement therapy. And as Guido mentioned, the development of inhibitors is a known risk. It's in our SmPC. And what we've seen, it's really on the patients that we have in the market. And as you remember, probably in the clinical development program, which was extremely large was there were no patients who develop inhibitors in the real world, we've seen. But obviously, those were patients that you get a mix of product of patients with different medical history, meaning that we know that some of those patients that have developed an inhibitor with Altuvoct, they already had previous inhibitors with other factors.

There are others that develop an inhibitor while being on Altuvoct, but receiving different Factor VIII products because an emergency situation that did not have at hand the product. So there are multiple confounding factors that reassure us on the benefit risk profile of Altuvoct that remains unchanged when it comes to inhibitor development.

And then with regard to Aspaveli, indeed, what you can see as an evolution is that, yes, it's clearly an incremental benefit of the C3G launch and IC-MPGN. That's the reason why we are quite positive and excited, Mattias.

The next question comes from Harry Gillis from Berenberg.

I actually have one question on Doptelet, if I may. You called out the very strong growth in international markets and by the end of this year, that becoming a much more significant share of the product's overall sales. Could you maybe provide us some sort of information on the split regarding the U.S. and ex-U.S. just as we approach '27 and that U.S. LOE, so we can try and model that with a little bit more accuracy. And then just a second question, if I may, on the full year '26 guidance. So Q1, super strong start, 24% constant currency growth, Aspaveli ahead of internal expectations, Altuviiio going extremely well. I suppose what would you need to see? And by what point in the year to lift your expectation for low double-digit top line, just given the strength we've seen so far, plus with additional NASP launch as well potentially benefiting the end of the year?

Thank you, Harry. I mean, with regard to Doptelet, I mean, the -- at this stage, what we can say is the majority is still coming from our U.S. business. And what we will do is in order to -- as part of the guidance and next year, we'll probably break out the split more clearly. But what you can expect because the growth of Doptelet in international markets has not been dissimilar to our Altuvoct growth overall. And if anything, better that tells you that, that ratio is going to favor, obviously, the outside of U.S. markets. And so that's basically when you think about next year, that impact may not be as large as to be feared. Anyway, it comes in the second half, but we will do everything we can.

I mean, so the -- will probably provide a good view, let's say, when we talk about guidance for next year. But at this stage, I think it's -- we won't do this. And with regard to guidance improvement, I mean, we obviously take this quarter-by-quarter. And let's hope we have a good quarter next quarter. And then I think we may be in a good informed decision. I mean you know our patterns from the past. We are historically a bit of a slow start when it comes to guidance upgrades.

Got it. Can I just ask one follow-up. Could you just say the Doptelet LOE in second half of next year? And can you provide any more like specifics on the exact timing?

Henrik, what is our messaging there? Maybe you can...

Yes, it's mid next year in the second half. We haven't been specific on the month, but it's the summer next year.

Yes.

The next question comes from Georg Tigalonov-Bjerke from ABG.

This is Georg Tigalonov-Bjerke from ABG. Congrats on a strong quarter. I have 2 questions, please. So first, the Gamifant year-over-year growth was still very strong, however, somewhat short of expectations after 2 quarters with very strong sequential growth, too. So do we already start to see some signs of plateauing in secondary HLH in the U.S.? Or were there some other temporary slowing drivers this quarter?

And then secondly, regarding Aspaveli in C3G and IC-MPGN, when do you expect to secure reimbursement in the major markets outside Germany on a country-by-country basis?

Yes. I think with regard to Gamifant, I wouldn't see the growth as an indicator. I mean, 47% is probably not so bad, but the -- I mean, I don't feel too shy about it. But it's fair to say that this is not a quarter where we -- which is indicative. I think there is a very strong underlying demand. Gamifant has a bit of still like historical lumpiness due to the dependency on heavier patients. And well, this -- I think it will be a very important opportunity for us this year. I mean this one you can see. And obviously, there will be a base effect at one stage, but we can still -- we look forward to a very important year for Gamifant.

As far as Aspaveli is concerned, the -- sorry, your main angle regarding Aspaveli, can you just quickly remind me, just excuse me.

Yes, that was regarding reimbursement in the major markets.

Reimbursement. Sorry. So what we expect, I mean, you will not -- that basically during the next couple of months, we expect positive decisions and in Spain and the U.K. And of the major markets, I will not -- we are not yet announcing here the list of all markets. But that of the EU5 markets, they will be the next in line during this year.

[Operator Instructions]

We now have a follow-up question from Christopher Uhde from SEB.

On Tryngolza, it's obviously super early days, super rare population, but can you tell us a little bit about what you're seeing there in terms of the centers, the doctors and so on, the types of patients as it relates to the ability to predict what happens in the MCS launch?

Yes. I mean we have a very good uptake in the launches in the launch countries. I mean, granted, this is now Germany, Poland. Austria. And basically building up this franchise. I mean the benefits of the product versus the existing one Hemlibra are intuitive, and we have expanded in any of those markets share. I think the importance for us of the launch is more the connectivity to the lipid centers, which will be at the core of value creation also for sHTG next year. And I think that the connectivity works out very well and the feedback we got from the product is very positive, particularly on the tolerability. And -- but it's a small indication. So hence, sales were not yet too large. But the -- I think for us, the key is we have also quite a number of patients now on managed access and early access programs. That number will increase. So we use the time wisely now to prepare ourselves for the large indication next year.

Ladies and gentlemen, that was the last question. I would now like to turn the conference back over to Guido Oelkers for any closing remarks.

Yes. Thank you so much for your attention. I know that this is a very popular day, and there are some other smaller or larger companies waiting for you. And I hope it will be worth your while. Thanks for your attention and look forward to be in dialogue with you very soon. Thank you.

Ladies and gentlemen, the conference is now over. Thank you for choosing Chorus Call, and thank you for participating in the conference. You may now disconnect your lines. Goodbye.

Hello, everybody, and welcome to everyone who's here today in Stockholm and also to everyone who's joining us online for Sobi's Capital Market Day 2026. I hope you'll find this session in the next few hours valuable, and I hope you feel some of the real excitement that we feel about Sobi right now in terms of the progression of the company and also some of the really exciting medicines that we have in our development pipeline, which we want to bring to many patients around the world.

So to get us started, I just want to please take note of the standard forward-looking statements. I just want to take a minute to briefly go through what you'll expect for the Capital Markets Day in the next few hours. We will have an opening session by Guido, which will take us through the strategy and our new 2030 outlook. Then that will be followed by Lydia, who will go through some of the exciting developments we have in our clinical development pipeline right now.

And then continuing with that, we have 3 sessions doing more of a focused dive on certain therapeutic areas. So the first one will be on gout, which where we now have 2 products. And I'm very pleased to say we have the Chief Medical Officer from Arthrosi Therapeutics, Robert Keenan with us today. So also a very warm welcome to Sobi and also to all the people from Arthrosi, who are joining the Sobi Group. We then will have two distinguished professors, which will talk about severe hypertriglyceridemia and also sepsis. So these will be 2 also exciting sessions.

Another part we will hear briefly from our regional heads. So really what's happening on the ground who are the people who are leading our businesses in our 3 regions globally?

And then towards the end, we will have Henrik, which will close us out with the financial outlook and his view of the business as we go into the next few years. Then at the very end, Guido will close with some remarks, and then we will open it up to a Q&A session. So that's briefly how we will run the day. And with that, I'll hand over to Guido, who will start us off.

Thank you, Gerard, and welcome, everybody to this year's and to our second Capital Market Day. And it's really it's a joy to be here because this marks a little bit of a unique moment in time for Sobi and Gerard was talking about it, that we're very excited, obviously, what -- about this moment of time, given the bolus of new products that are coming our way and that we are going to launch within the next years.

So with this said, I really would like to start, and maybe more with a personal note. And this chart, I'm coming to in a few seconds. When I started in May 2017, I mean, it feels like a long time ago, Sobi was clearly a very different company then. We were having an opportunity in hemophilia.

We had a portfolio of distribution products in rare diseases, and we needed to get first claim or a turf in hemophilia because without making strides into this indication, there was no future really for this company.

And so we evolved from a very humble beginning with -- on a very different scale at the time. Having said this, when we set the Capital Market Day around 5 years ago, Sobi was already more diversified geographically at the time in the early days, 3/4 of our business came from Europe. And what a vast difference it is today, as you will see later, but also from a portfolio much more focused, obviously, very different scale.

Now at the time, 5 years ago, when we set our ambition '25 -- by '25 to quite a few people said, will they achieve this? Is this ambition really properly calibrated? Or is this too ambitious?

Quite a few skeptics and quite frankly, when you look at the Slides 21 and 2020, during COVID days, this ambition didn't feel so great, to be honest. And we had to think were we a little bit too forthcoming, and it was a bit humbling at times. And there was not a single quarterly meeting where we were not reminded of our ambition, particularly I was reminded of what this could mean.

And frankly, I mean, probably till 2024 somewhere, then the people start believing that we could be ahead. And it was -- for us, it was very gratifying to be honest, to be ahead of the '25 target in '24 and obviously, significantly ahead, as you can see from the slide, by '25.

And I'm telling you this not because we want to get a great gratitude or whatever. I'm telling you this because I wanted to give you a taste of the company, we are of the organization we are, and this is a company that is characterized by a lot of resilience by passion to win by this uncompromising willingness to succeed, because this is what ultimately makes a difference in today's world, where you will always have headwinds, but it's about what you make out of this.

Because I wanted to tell you this, particularly when you judge now forward-looking, what we want to achieve, that you get a sense, we are not doing these ambitions lightheartedly. We are thinking about is obviously quite a lot, but we are ambitious, and I think we should. So when you look at more at the stats of what we have achieved over the last 5 years, I mean, they speak for themselves. We have nearly doubled our business over the last 5 years. We have significant EBITDA growth, and you will see that we're not only having grown EBITDA, we have prepared our future, not only for tomorrow, but also for tomorrow after tomorrow.

You look at the enterprise, where we are very gratified, obviously, that the capital market is understanding us much better and giving us some credit for the performance today, hopefully, also for tomorrow. And we have been measured in building up this company and not going overboard in terms of number of people.

When you think about our strategy, where we are today. This strategy has been reasonably consistent over the last years when we set it out in 2017. It was always about strategic or therapeutic leadership granted at the time when we articulated it, it was much more of hemophilia than extended to hematology. We added then immunology and in specialty care over the time, in particular, now with the emergence of Tryngolza has become a bit of a different meaning.

But we always were thinking, how could we angle ourselves in certain areas an important position. It was about globalizing the footprint, initially taking a big reasonable share in United States, because as everybody knows in this audience, you cannot be a leader in rare disease if you don't have a proper position in the United States.

And it was always about putting the patient at the center of what we are doing, and this is now an important element also to our sustainability agenda, as I will point out later, and it is about unlocking value in our pipeline. And when I look at today at our pipeline, I'm very proud of what we have achieved, and Lydia will talk about this later, because this has been an area where we also had some skepticism, but it's very nice to see how it has evolved over the last 2 years.

Let's go through the first area, which is therapeutic area leadership. So these are, for us, therapeutic area leadership starts from the quality of the assets. And these are all assets either first-in-class or best-in-class that we have thoughtfully acquired or licensed in over the last years to build our portfolio in the area of hematology, immunology and as I said, in -- with Tryngolza latest in Specialty Care, and we will talk more specifically about these assets in the later presentation.

When you think about globalization, I think it's important to note that today, we are covering more than 90% of the global rare disease market direct. And we have built new organizations. So the focus from getting the right footprint in the U.S. has been broadened now to make sure that we are also participating in the global growth of the rare disease market and more recent establishments of new organization have been important markets like Japan, in Korea, in Australia and in Brazil.

So these are not small random markets. These are important markets that are relevant for our development and that will drive growth today, tomorrow and tomorrow after tomorrow. Let's talk about sustainability because this gives you also an example of the company of who we are.

I told you that patient commitment we were never short of. In fact, when I started, I wasn't quite sure whether we are part of an image brochure. I had to learn this is really right at the center of what Sobi is. And I'll give you an example because you can talk, talk is very cheap, but 2 years ago, Christmas Eve, we got a request in for a young patient in Southern Europe, suffering from primary HLH.

Now the product is not approved in Europe. So we had to overcome quite a few hurdles. 24th of December, not the time typically where everybody is waiting for a little bit of excitement at the office. 24 hours later, the product was delivered. We were compliant with all the necessary regulations that needed to be acquired -- that you needed to follow for a product that was not registered in Europe, but it was absolutely important to save this patient, and this patient was successfully transitioned to stem cell therapy.

And we didn't have to ask any of our employees, please do this. It was self-understood. And this is what patient commitment and patient centricity means for this company, and it generates obviously a gigantic energy. And that's the reason why we are able to do what we are able to do. The other thing is, obviously, that we have to be responsible in what we are doing. It's -- this business is all about trust, and it is about responsibility of being compliant with all these regulations.

So this meant the combination of patient centricity and responsibility allowed us to score last year in a survey by PatientView, 518 patient organizations globally were surveyed, and we scored #1 amongst 31 companies ahead of some of the big pharma companies, who believe that they have the right to play in rare disease.

And at the same time, we also are obviously cognizant of the environment. We are not having the largest carbon footprint, obviously, because we have no site, and it's a rare disease, it's small units. Having said this, we have set ourselves scientific-based targets. We have reduced the carbon footprint since '23 and at the same time, increased obviously significantly our business. So we just wanted to make sure that we also -- that you hear this from us. This is really the heart of what we are doing, and we are very pleased that we are now in the '25 sustainability book of S&P, and we were selected as 1 of 19 pharma companies in this book. So we were very pleased that people recognize that we have a broader agenda in terms of sustainability.

With this, now let's talk about innovation, and Lydia will cover this much more. Just wanted to give you a little bit of a taste how we have evolved over the last years. We have now 3 hubs globally covering Basel, Boston, obviously Stockholm or in any order, you wish to look at them. They allow us to be connected to key centers in R&D communities around the world, and it is not just the hubs, it's the number and the quality, obviously, of people. Just one example is the number of MD PhD. This doesn't mean that other academic grades are not important, but it just gives you a flavor that the company has evolved over the last years.

We also got awarded for the products that we sourced in, which are typically best or first-in-class 12 articles in the New England Journal of Medicine. This is just one of the parameters. So I'm sure you can apply many others. I just wanted to give you a flavor how this works. And we have got 10 major approvals with FDA and EMA -- and/or EMA over the last years. And this evolution of building capabilities, taking advantage of a global footprint, has prompted us to think, is there more that we could do at Sobi? And so we took -- we made an effort to think, can we push the boundaries of science a little bit further? And have we earned the right now to go a little bit earlier in the development cycle? And we concluded, yes, it's the right time. And we will talk about one of these initiatives, and Professor Giamarellos will talk about it, and I'm super happy that he has made an effort to come here today talking about interferon gamma-driven sepsis.

And I don't want to steal his thunder. It's -- we think that we are right here at an edge and very pleased that he is sharing with us today some of the Phase II results. The other one is chronic synovitis, which is still a high area -- an area of high unmet medical need, and Lydia, as a previous treater, is going to talk about it. Another one is VEXAS with our JAK2 inhibitor.

So as you can see, we are evolving as a Sobi. So we are not a commercialization engine. We want to play an important role in development. And I think our track record has qualified us to do so. Let's go to the meat of the presentation and why we believe that we can build a company to the scale that we want to share with you in a few moments.

And the reason is that we have 6 launches by '28. We have already launched Altuvoct in hemophilia A, Gamifant in HLH/MAS last year. We have undergoing the launch with C3G, IC-MPGN, very excited about this launch. We have now 2 markets, live in this very debilitating nephrology indication.

We are expecting middle of year the launch of NASP in uncontrolled gout. We are looking forward to launch Tryngolza in SHTG, and I'm very happy that Professor Parhofer has taken the time to talk about this important area and how he thinks about our data for Tryngolza. One should note though that we are already in the midst of the launch of Tryngolza and FCS.

So we have launched in Germany and also in Austria today, and we roll out the product during the year in the normal sequence in Europe. And we are looking forward to the launch if everything was the way we think in '28 pozdeutinurad comes with the acquisition of Arthrosi. And I'm very happy that Robert is here that he is not only coming here, but that he has accepted to join us, which is life is always an interview, and I'm happy that we interviewed well with him so that he accepted his -- the role with us because he is actually as a previous treater of gout. He is one -- he used to be a professor at Duke and one of the key leaders in rheumatology in U.S. I'm very happy that he has joined our team.

So this basically gives you a taste, and then obviously, IDS I talked about. And I'm very excited about this presentation because it's an evolving field, it's risk. But if it works, it's high reward, but it's also a huge difference for a high unmet medical area of needs.

So when you thought -- when you look at this number of launches that will come our way, we thought it's time for a Capital Market Day, and it's time to reset the ambition and to pivot for a new Sobi and over the next coming years. And this is basically what we have in mind.

So when you think about us, we are cognizant that we will lose exclusivity in the U.S. obviously, for Doptelet. So that's what we have to make up, but we believe that we can sustain our strategic growth portfolio as we have articulated it in the past and our foundation products, and then build these 6 major launches on top of what the company is today and basically transform. Sobi and double Sobi over the next 5 years. So that's our ambition as we laid it out.

We have a couple of priority development projects with IDS, as I told you, with VEXAS and with synovitis. They are, at this stage, if they happen to be relevant for us in this planning cycle, fantastic, we have not accounted for them given the discounting that we use typically, but also it's -- they are at an early stage. So they're not featuring. But frankly, as we will have -- carry the expenses, that's the reason why we moved them actually to the left side. We wanted to be at least clear, we paid for them, and we hope we get some benefit. And if we get the benefit before 2030, fantastic. If not, then we hope that we will be very relevant into the mid-30s and beyond.

And then we -- no surprise, we stay ambitious. We want to build the company beyond. So we will look for further BD initiatives, particular to strengthen our therapeutic areas, but also probably to think more of franchises similar to the -- through the acquisition where we're now building a franchise with NASP in chronic refractory gout. So this sets the scene, we want to double the company and why do we believe that we can be so audacious to now take the company forward. And I think that requires now a look into the respective assets.

So let's look at Altuvoct. With Altuvoct, we are still at a relatively early stage of evolution. Only 2 major markets are now having a launch history with more than 12 months, relatively recent launches in the U.K., in France and Italy, just a few months in average, and we are looking forward to 16 more new launches this year and next year. So we are in this early spring of a product life cycle, where life feels very light and very exciting, and we believe that we have a spectacular product. And Sofiane, the Head of Europe will later share some of his views, who knows this therapeutic area extremely well and what he wants to do with it.

And the other thing is that we want to raise the bar. So a very high unmet medical need area is synovitis as I pointed out, Lydia will talk about it and why we think that we cannot be satisfied with hemophilia A treatment as we know it today, why we need to take it one step forward.

Let's talk about Aspaveli in C3G and IC-MPGN. This is obviously a very serious disease and just look at the stats, 70% of children, 50% of adults end up after -- in average after 10 years with end-stage renal disease. So pretty high unmet medical need despite available therapy today, but clearly not addressing the core disease pathology as a C3 inhibitor, central to the complement system like Aspaveli is going to do.

So we look at the opportunity for Aspaveli the following: Around 13,000 patients diagnosed today in our territory; 8,000 in Europe, 5,000 in international. What we believe is going to happen is that over time, diagnosis rate is going to go up, and we're expecting actually a paper in this regard in the next 2 months. We believe also that treatment rate is going to go up.

And that basically paves a way for a product like Aspaveli now to take advantage of it, with obviously supremely strong data as Lydia is going to show you in 3 dimensions, and this gives us confidence that already this year, even though we have to vaccinate -- patients have to go through a vaccination schedule, in the launch countries, many patients will be in the community setting, so we need to activate patients. It will take some time. But already this year, we hope to, and we believe that we can have 400 to 500 patients by the end of the year on drug paid or unpaid, it doesn't matter for us because it's -- over time, it's going to wash itself out.

And this means when you think -- when you believe that your diagnosis rate is going to go up, we believe that we roughly can achieve 25% of diagnosed patients. And that's the reason why we believe we will have 4,000 to 5,000 patients. And why we believe that Aspaveli, in conjunction with our PNH franchise, can become a blockbuster product for Sobi.

Let's turn the page to Tryngolza, and we talked about this and Professor Parhofer will be much more eloquently talking about the disease. We just -- I just wanted to mention this disease is not about only reducing triglycerides, but also preventing pancreatitis. Now our product, Tryngolza, has demonstrated both unprecedented levels of triglyceride reduction for these patients with super high triglycerides, but at the same time, also a reduction of pancreatitis events and pancreatitis is not something lightheartedly we were talking about this before this event and 1/3 of patients ending up with persistent organ failure and 5% to 8%, these are the stats, let's say, ending up with premature death.

So that is clearly something that needs to be addressed and Tryngolza being in a very positive position. So the way we are thinking about this launch and why we believe we have a right to play in this area is we are in the midst, as I told you, with an FCS launch, genetically driven very high triglycerides. Our focal point is really very much the lipid centers in Europe. And we accounted for 700, 600 in EU5 as we previously quoted. We want to do a good job covering those, and then branching out, and who knows how quickly this disease will be more democratized and other specialties will think of playing a role in this treatment.

Very hard to predict, but this is the way we are going to encounter it. We will broaden. And clearly, we want to make sure that we have built up a referral system back to the lipid centers, where treatment is taking place today.

So there are 1 million patients in Europe, 300,000 of them would be classified as refractory. We obviously are fully aware that we need to still pass the hurdle and first need to get regulatory approval, and then need to get a respectable price. You have seen the assumption that Ionis have published for United States. We'll see what this means for Europe, but the initial discussions we had with people who are either close or previously worked for different reimbursement bodies in Europe is very positive. So we are very much looking forward to this launch, and that's the reason why we also believe that this is a very significant opportunity also for Sobi, not only for Ionis.

Let's think about chronic refractory gout or progressive gout as we would term it pozdeutinurad. So this is gout as such is the most common inflammatory arthritis with super high unmet medical need. And Rob has a few more exciting photos than the way layman like me, was able to collect. And its effect, in second line, around 200,000 patients in the United States. This is the second line. We think that with the oral once-daily next-generation URAT1 inhibitor, we could make a huge difference to those patients.

We got very satisfied in the diligence when we did -- when we worked on as over the -- AI over nearly a year with a preclinical and clinical package and Phase III is fully enrolled. We expect the -- in H1 already, the first Phase III study to read out. And we felt that this was an opportunity that we should not miss.

And it is an opportunity that we should not miss because this is the way we are thinking about this launch, and we are getting into gears now with the NASP launch, we are expecting PDUFA mid of this year. We have today here, Duane, who is leading our North American franchise, and he can share with you some of his thinking on how he thinks about this launch and also how he thinks about pozdeutinurad.

And basically, what it means is in the first phase, it's a top -- classical top downish approach, we will obviously learn about the disease area we will get familiar with the different stakeholders, with patients, and then launch an opportunity that is obviously of scale in this market, whilst we don't want to underestimate the role of NASP, obviously, as an anchor, particularly for these really refractory patients and very severe patients where it will play an important role.

The next opportunity is obviously sepsis. And I just wanted to give a prelude, and I don't want to steal obviously Professor Giamarellos' thunder, but as you know, I mean, this is probably more commonly known, around 11 million deaths are attributed according to WHO to globally to sepsis. We did a recent survey with specialists in an ICU setting, how they view this area. And they clearly, no surprise. They said it's a huge unmet medical need, but what was interesting for us is, as I said, 10% mortality improvement would be considered as extremely clinically significant.

And I think this is an important part also Professor Giamarellos' presentation tell us how he views this setting as he is, obviously, a specialist in the field. So the way we look at this as an opportunity for Gamifant. You know that Gamifant plays an important role in a hyperinflammation-driven disease like HLH previously, only primary HLH, now we are branching out to secondary HLH, and we will have a significant growth opportunity still on the -- in the HLH setting, no question.

But the other huge opportunity is obviously now coming our way is in this subset of interferon gamma-driven sepsis, which based on Professor Giamarellos research, is affecting around 20% of patients, and then your numbers start spiraling because this is still a significant cohort in the U.S. alone based on more moderated stats. This would be a patient cohort of 300,000 alone. And there -- this is a way you can take it.

So a very material opportunity for the company, but we obviously attached to a significant risk profile. Very briefly, when you think about our aspiration on the global side, only so much the globalization efforts, the setup of new companies will still pay dividends today, tomorrow, tomorrow after tomorrow. And this is a rough estimate, we would be not surprised if our international business will be more than 20% by 2030, but this is not a guidance, this is just an extrapolation of the current momentum.

What is our position on AI? As a mid-cap company, we just have to prioritize. We have to be selective where we can achieve the largest impact. And it's no surprise that I cannot say, "Oh, let's set up a team, a task force of 500 people. And now let's focus only on AI." That's not part of our remit. And I don't think that any of the investors or analysts will want us to do so. But what we have done is we have selected those areas where we can affect most, let's say, our value chain, and this is a focus on commercialization and this is a focus on R&D. And in R&D, it's all about productivity. And you have seen the fruits of this work last year already, thanks to Lydia's effort, and it is about speed and obviously a field force effectiveness. And I just want to mention, let's say, that we have set up a company called Florio in Munich that Lydia is going to talk about that is today the largest rare disease platform for patients in Europe period.

So why are we so audacious? And why are we still a rare disease company, you may wonder? And the reason why I want to say, clearly, we are is because we always relate back to our science-based medical foundation and our patient centricity. Then science and unmet medical need sometimes lead us into larger areas, like in the case of SIDS or sHTG, where we started in FCS or refractory to progressive gout.

But at heart, our toolkit is a toolkit of a rare disease company. And yes, we can scale to give adequate coverage to the opportunity, but we're not losing our identity of who we are. And we have done this as an example of COVID-19 for Kineret treatment, where Professor Giamarellos did a pivotal work that allowed us to get U.S. and EMA approval.

These are some of the milestones, I think, in the interest of time that we can cover also in discussions with IR, we just wanted to make sure on that journey over the next 5 years, there are a couple of milestones and catalysts, you should be mindful of.

I just want to tell you that we want to bring Gamifant into Europe and into Japan, and we're expecting decisions over this year, respectively, next year. We will have, obviously, an FDA decision in June on NASP. We want to bring Aspaveli also into Japan, where we think it's a massive opportunity for the group. And we want to make sure that we have the filing right now in Q1 for Tryngolza and launching next year in SHTG. And obviously, we are excited to present to your excitement is probably a gross understatement when we present the data for pozdeutinurad later this year and obviously, IDS.

So in summary, we have delivered against the strategy. This company is a much larger, more diversified, and obviously, company than it has ever been with significant organizational capabilities. We want to take this company now forward. We want to double it in the next -- on the next trajectory, and we also believe that with the portfolio of the 6 products plus the products that we have now in the pipeline and the BD that we obviously still have to perform, so we don't expect any credits for this. We have a good pathway to grow this company today tomorrow, tomorrow after tomorrow. Thank you. And on this note, I'd now like to hand over to Lydia, who will share you the excitement of our innovation engine. Thank you.

Thank you, Guido. Thank you, everyone, for joining us here at this Capital Market Day, and it's my pleasure to be here today sharing some of the data and the new products that are coming our way. So maybe I should start by saying that since 2020, we have truly transformed R&D and the medical affairs organization in a delivery engine with our -- we are running global clinical trials. We are having a larger and broader coverage in terms of regulatory, and we have science that it's really moving the field.

So if we look at our clinical development capabilities, we are currently running more than 40 clinical trials globally. We maintain in-house the strategy and the oversize what we outsource to CROs for flexibility and scalability. If we look at the regulatory approvals over the last year, we see that we have a remarkable year with 36 approvals across major markets. And major markets, we always think the U.S., Europe, Japan, but we're reaching really countries, as Guido was mentioning, like Brazil, like Australia, and that is based on the fact that we have the team and the systems that enable for efficient submissions.

And all of this is flanked by a strong scientific leadership. And only in 2025, we had more than 40 peer-reviewed manuscripts published in the therapeutic areas that we operate in, increasing the awareness on these diseases, which most of them are rare, but also on our assets. So this really -- it's something that we feel very proud, but Guido has mentioned that before we really have a long-standing commitment to patients and to the patient community. And this was reflected in the peer review survey, and that was run in more than 500 rare disease patient organizations across 58 countries, and they rank -- Sobi was ranked as the most reputable company in the rare disease space.

So this is something that really reflects our long-standing commitment to patients, but also our systematic approach of working with them, as I will talk later on. This all within a relatively lean R&D organization that give us agility really to also take on new opportunities and partnerships.

So if we look at what has happened in the last 24 months, so how our pipeline has progressed, it has been really a remarkable period for Sobi. We have 5 major approvals. Altuvoct in hemophilia A, Aspaveli for the nephrology indications, Gamifant in secondary HLH macrophage activation syndrome, Doptelet in ITP, and then Tryngolza in the familiar chylomicronemia syndrome. But on the top of those 5 major approvals in this period, we have 2 ongoing submissions that are under review, applications under review, NASP for uncontrolled gout and Kineret for Still's disease in Japan.

So this is really something that it's enabled the near-to-midterm growth and really it's supporting the ambition of doubling Sobi by 2030. But here, this is what we see short term. But what do we have in the pipeline moving forward? And I'm very proud to share this slide with all of you. So on the bottom part of the graph, you see what I just mentioned on the previous slide, the near-term opportunities, those assets that have been already approved in some of the major markets or are ongoing and those that are registration. But now I want you to focus on the upper part of the table, where you see our next wave of catalysts that will be -- drive the growth of Sobi moving forward.

So currently, we have 3 indications in Phase II, meaning very early-stage development phase. We have interferon gamma-driven sepsis, and you will hear all about it by Professor Giamarellos. And then we have 2 additional indications for pacritinib, 1 in VEXAS syndrome, and I will come back to that, and then one in CMML. This is a research collaboration in the U.S. Then we have 5 assets in Phase III. Out of those 5 assets, 2 are running confirmatory trials. We have pacritinib in chronic myelofibrosis in patients with platelets below 50,000, our PACIFICA trial, which is the confirmatory, and it's running, and we expect really -- I will talk a little bit later about it.

Then we have loncastuximab tesirine for relapsed-refractory diffuse large B-cell lymphoma, also running LOTIS-5, which is a confirmatory trial. And then we have pozdeutinurad, running 2 Phase III clinical trials, and we are really looking forward to the data later during the year. We will be running a study to further expand avatrombopag in this case, in severe aplastic anemia. This is a study that we will be running in some countries in Asia Pacific. And then, of course, we have olezarsen in severe hypertriglyceridemia. Here, the data has been already published. And as Guido just said, we will be submitting this quarter in Europe. So that's why it's already almost in registration phase.

So with all of this, you see that we are not only addressing our major markets, but we are pursuing really an intense geographic expansion really to reach all patients with rare and debilitating diseases that could benefit from our assets.

So with this, I will start moving into a little bit going into some of the assets, a little bit in depth. So the first one, Altuvoct, and Altuvoct, it's a high sustained ultra-long Factor VIII replacement therapy, basically elevates the Factor VIII levels to the non-hemophilia range for the majority of the week with once-weekly prophylaxis with once-weekly dosing.

And this is really normalizing hemostasis is something that is unprecedented in hemophilia, and it has been driven a paradigm shift. The first thing obviously was to assess, okay, is it effective? Can it prevent bleeds because that's our main objective as physicians really to control and prevent the bleeds.

And this data has been presented 2 weeks ago at EHA, where the data from the extended, which is the long-term extension study from the pivotal trial, where we see that patients, the average mean ABR, it's 0 with almost all patients having no spontaneous bleeds. And this data from the adults, it's also replicated in the pediatric population, which we know it's much more active by definition.

If we look at the surgeries, the surgeries are the main challenge where you really show if a product can really control hemostasis. And again, here, Altuvoct has completely transformed the approach of major surgeries in patients with hemophilia because with only one additional dose, patients have been able to undergo major surgeries like replacement of joints.

And then it has been assessed like 98% being excellent or good response and 97%, not requiring any blood transfusions. So basically, what Altuvoct has done in this transformation of care in hemophilia, it's really achieving this normalization of hemostasis with near 0 bleeds for the patients, which is something that is remarkable with a robust surgical protection.

And then this data, it's really confirmed in the real world. So what Guido was mentioning is, can we be even bolder what can we achieve more with Altuvoct. And obviously, joint health is one of the main areas that these patients can still have as one of the main problems. So we are focusing on joint health, physical being an overall improvement of quality of life.

So I will talk a little bit about synovitis because it's still a major, and the most common complication of these patients. So hemophilia patients are treated to really replace the missing coagulation missing clotting factor. But what we know is that in those joints, there are micro bleeds that are not really even perceived by the patients and that are not well adequately controlled if you don't have proper hemostasis.

Those repeated bleedings, what they do is that they create an inflammation on the membrane, which is the synovial membrane that covers the joint internally. And we find that thickens and you can see here in this picture, the difference between a normal joint and a joint with a chronic synovitis. I've seen patients with this and really, it's obviously creating a lot of pain. This -- they cannot basically walk, and the treatment can go from really very intensified Factor VIII treatment with anti-inflammatory drugs intra-articular corticosteroids, synovectomy that can be with radioisotopes or that can be surgical or if you can lead even to joint replacement, really affecting massively the quality of life of the patients.

So what we are going to explore with Altuvoct is that if we can not only prevent because these patients that are having pristine joints, and they don't bleed, they will never get to these synovitis. But what we want to go is one step further and see can we not only prevent, but also improve synovitis in patients with severe hemophilia A. And we are doing that by generating data with a wealth of clinical trials. And here, you have the FREEDOM study, which is focusing on joint health and physical activity. Patients will have tracker devices. We are using the Florio platform, and it will -- we have already presented some data at EHA this 2 weeks ago.

We're running the SHINE study, where we will be assessing joints with already existing synovitis, treated with once-weekly Altuvoct and see how the synovitis improves. And these studies are obviously with technical imaging like ultrasounds and MRI to really assess how the chronic synovitis is evolving.

And then the LIBERTY study, it's basically the post-trial access, a little bit talking about our commitment to patients because we are running our clinical trials globally. And obviously, the launches that don't happen at the same time everywhere. So LIBERTY is the post-trial access that every patient from all our clinical trials will join until they're in their respective country, the product is approved.

And then obviously, you could say, okay, yes, but it is -- everything is a controlled environment. So we also want to understand what's the real-world evidence that is generated with Altuvoct and that's why we are running the ALTITUDE trial, which is really long-term real-world evidence collection of data of patients treated with Altuvoct for more than 4 years.

So as you see, we are expanding beyond just bleed control to really physical activity, joint health, synovitis and brother patient outcomes because that it's really translating these unprecedented levels of protection to very concrete endpoints and to very concrete unmet medical needs that now are not addressed with the current therapies.

So moving into Aspaveli in our nephrology indications. So these are a spectrum of complement-mediated chronic kidney diseases that are heterogeneous and can have different presentations. But where the main disease driver is really the glomeruli deposition of C3. This is really the key driver, which is creating kidney damage and renal inflammation.

The journey to diagnosis is not easy. Patients need to biopsies to get the confirmation, but we know that currently until now, treatments available were supportive care in mono suppressive that we're not addressing the root cause of the disease. So that was -- that's the reason why, as Guido has presented before, between 50% and 70% of the patients end up in kidney failure.

And most of them needing dialysis or kidney transplantation. If you receive a kidney transplantation, obviously, you would need immunosuppressive therapy for life, but the sad thing is that if you are not addressing the root cause of the disease, the disease will relapse in almost 90% of the cases.

So this is really dramatic for patients because the limitations of their lives are going to be very important. And there is -- that's why there is really a great unmet medical need for truly disease-modifying treatments. And that brings us to Aspaveli. And really, Aspaveli, it's addressing the disease at its source, the biological source of the disease. It's a C3 inhibitor, so really targeting the C3 activation and really restoring control across all complement pathways.

And it has demonstrated that it brings the 3 most relevant parameters that have been defined in the community in order to assess the effectiveness of a product. In terms of histological improvement, you see that more than 70% of the patients had no deposits of complement in the biopsies performed after treatment.

There was a 68% proteinuria reduction with more than 50% of the patients achieving a proteinuria level below 1 gram per gram. And finally, there was an eGFR stabilization with an improvement of really the renal function. All of this, it's important that you understand, this was a trial. So these results were consistent across all the populations, meaning C3G and primary IC-MPGN, adults and pediatrics, and native and transplanted kidneys.

All of that with a safety profile that was consistent with what we knew already from pegcetacoplan in other indications. So if you need to remember one thing and keep one image in your head, please remember this image of how the deposits were really clear. And talking to nephrologists, this is like, it's unheard of. They have never seen a treatment that could clear the deposits in this way. And really, they say it's like if the disease was disappearing.

So we have very strong data, and we are really taking major steps towards the global launch. The data was published last November in the New England Journal of Medicine. We just got the approval in January in Europe. As I said, this broad label, including C3G primary IC-MPGN, adults and adolescents, transplanted patients with no EGFR or proteinuria restrictions.

It's also approved in many -- in a series of other countries like Australia, Brazil, Saudi Arabia, Korea, Switzerland, and we have submitted in many more. So we are really doing parallel submissions in many -- too many regulatory agencies to bring the product to as many patients as possible.

And we will be launching together with this indication, the EnFuse on-body device to increase really the convenience for the patients. But we are not stopping here. And obviously, we know that this product is fantastic and the data is strong. Strongest data that has been published for these rare diseases. So we are looking into additional areas. And we will be exploring the study was conducted, and the indication is for patients above 12 years of age.

So we will be looking into patients below 12 years. And we're thinking about potential use in patients that have to undergo or transplant. In other patient populations that clinical trials, it's always a very restricted patient population. You don't want to have patients with other comorbidities. So we will be exploring, let's say, outside the population that was exploring in the pivotal trials, some economic and patient value, and then we will be looking in additional potential new indications.

So a lot of things ongoing for Aspaveli and moving on now to Gamifant. Guido has mentioned, we have already approval in primary HLH in the U.S., secondary HLH macrophage activation syndrome. It's approved in the U.S. We have submitted in Europe and Japan, and we expect to have regulatory decisions in the next 12 months. And IDS will be covered by Professor Giamarellos. So I will just want to take some time to focus on the broad HLH that Guido has already mentioned.

And this is one set of data that was presented also recently, last December at ASH by a U.S. group, where what they were doing, is they look across -- the survival across different HLH triggers, meaning infections, malignancies, autoimmunity. So they have 2 cohorts; one that was the historical cohort in the lower line on the slide. And in green, the emapalumab-treated patients. So what they saw is that there was a 37% improvement in survival when the patients with this broad HLH were treated with emapalumab. So this is the basis for our next trials. And obviously, we will be bringing additional information once we have to be shared with all of you.

So Vonjo, going to Vonjo, all of you know, our main focus is to get the full approval of Vonjo in chronic myelofibrosis. Our indication is in patients with platelets below 50,000, but we want to broaden the label. And we have already -- we have started discussions with regulators on what additional sets of data. We have some data from PERSIST 2. We have data that has been published at congresses from centers in the real world from the U.S. that have already used in patients with platelets above 50,000, but we are also running a study called the PACER study, which is real-world effectiveness of patients treated with pacritinib and platelets above 50,000.

So it's an observational chart review that we will have the readout in 2027. And obviously, this will be supportive data when we discuss with regulators. VEXAS, I think we've discussed previously that it's a new disease that was discovered in 2020. It's severe with multi-systemic hyperinflammation causing organ damage, thrombosis and high mortality that can -- that it's up to 40% after 5 years of diagnosis. So really, it's a very severe condition with no approved treatments. So we're running the PAXIS trial, which is really the first clinical trial ever conducted in this disease.

It's a Phase II dose-finding study. We can share that the interest in the community has been massive. We have been recruiting ahead of schedule. And now we are pausing the recruitment because of the interim analysis that we already had preplanned. So we expect great data readout in 2027. But Guido has already mentioned that it's not only about the assets, and the potential that they have, but also how we are enabling our teams to go beyond and to really increase our development.

So the increase the value chain, enabling the acceleration of our development cycle times. And if we look at the clinical development, we have different models and tools really to gain insights into our data and the disease pathways.

On the regulatory side, we have AI support for scientific offering, really improving the speed and the consistency of our documents. And we have submission and review platforms as well to compress our global approval time lines. And in medical affairs, we have real-world data platforms, and I will be talking about Florio in the next slide. All of this with an integrated PV and medical information system, and really, altogether, these connected capabilities enable us for a dynamic resource allocation, reducing the cycle time and really delivering our pipeline faster for patients.

Florio, it has really evolved into a leading rare disease patient platform. And currently, it's a state-of-the-art medical device with 7 applications that is used in more than 26 countries. It's important that it has been co-created with patients and health care providers. And it really empowers patients to be in control of their disease and to have meaningful discussions with their physicians about their treatment.

It also enables the health care providers to see to understand the patient, the treatment benefits and really to monitor and adjust the treatments as needed. And to the community, it's really allowing the collection of real-world data that then it's published and really helps us understanding this data in rare diseases where having access to data, it's critical to collect really meaningful information.

So everything that we do, it's anchored really on our ambition to unlock innovation, driven by science for our patients with rare and debilitating diseases. So we have a strong R&D organization with global reach. We have a robust delivery of pipeline, as you've seen, and we are expanding into new disease areas.

And that's we have a new wave of catalyst of innovation medicines that really will help the growth of Sobi moving forward.

So in summary, we are innovating faster. We are reaching more patients, and we deliver long-lasting value through science. So I just can say that I'm really truly thrilled about the infinite possibilities for Sobi moving forward. Thank you.

And with that, I would like to hand over to Rob.

Well, I just want to, first of all, thank Sobi, for the opportunity to speak with all of you about something I'm very, very passionate about, and that's gout patients, and actually treating both progressive and uncontrolled gout patients especially.

So just real quick, I'm not going to spend too much time on this slide, but I kind of want to point out that gout is not a disease of kings or the glut knee or anything like that. We all make uric acid. We all have uric acid flowing through our veins. And most of that uric acid that we make is endogenous. And it's basically formed from the breakdown or cell turnover nucleic acid to purines, and purines to uric acid.

Now of course, if you eat a bucket a shrimp, eat a stake, and then wash it down with 6 beers, your uric acid is going to go up. But unlike gout patients, your body can maintain that homeostasis by increasing the excretion through the kidney as well as through the gut.

Now in general, we only we only excrete about 10% of what we filtered through our kidneys. And what gout patients do is they actually hold on to more than we actually hold on to more. So over time, uric acid stays up, crystals deposit, and it obviously causes a lot of, not only acute flares, but a lot of disability that goes along with it, which we'll talk a little bit more about here in a minute. But you can see on the right hand of the slide that the kidney has multiple transporters to handle uric acid. But the one I want to focus on is that you're at one transporter on the apical surface of the proximal tubule.

Now gout patients, there you're at one holds on to too much uric acid. And that's a big issue with not just a handful of patients, but about 90% of the patients who have gout. So really 90% of the patients are almost 90% of the patients aren't overproducers or they're not glutens, and they're not drinking beer all the time, they actually can't eliminate or can't excrete uric acid at the level where they don't develop problems with it. But with that problem that gout patients have, we figured out how to basically solve it, and we'll talk about that here in another slide or 2.

So as serum uric acid levels stay high, above that limit of solubility, above 6.8 milligrams per deciliter, over time, as it stays, uric acid becomes soluble and basically deposits in the form of needle-shaped crystals, you have microscopic needle-shaped crystals into joints and soft tissue. You can see on the bottom left-hand part of the slide that patients, when they first have that gout flare, they've had crystal deposition going on for years. It could be 3 years, it could be 5 years, it could be 10 years, even before that first flare happens.

So all that's subclinical. So this is going on for a matter of time. So it's not just the flares that cause issues. It's actually the underlying crystal deposition that actually causes most of the joint damage and issues over a long period of time, in addition to the disability and morbidity that goes along with it.

So you might be more familiar with the gout flare the typical, what you think about gout, you get a big hot swollen red toe, and that's due to that crystal deposition and the igniting, so to speak, of the immune system from those microscopic crystals in the joint space and soft tissue. So that obviously activates, that foreign body activates macrophages. And subsequently, you get the release of IL-1 beta, activation of neutrophils, other cytokines, and that is where you typically think, oh, you can't lay a sheet over it. They can't walk. They can't do anything during that acute flare of that acute gout attack.

But again, it kind of goes beyond more so than those acute attacks. And you can see in this slide again that when you're inactively treated, the gout progresses. So it goes from the asymptomatic hyperuricemia and crystal deposition to subsequently early symptomatic gout, where you have intermittent flares, they could come along once or twice a month, they can come on every 6 months, once a year, but as their uric acid is not controlled, and it stays elevated, things get worse, like with a lot of other things that aren't treated adequately or ignored, things get worse.

So over time, if a patient is put on -- and there may or may not be -- unfortunately, may or may not be put on proper urate lowering therapy like a xanthine oxidase inhibitor early on, they might just deal with the flares. They might go to their primary care physician or their provider and say, "Oh, I had a flare." They'll give them steroids, they'll give them colchicine, they'll give them NSAIDs, and then send them on their way until it happens, again, then they treat it again same way.

They don't actually address the underlying issue that causes these acute flares. Now the other issue, an important issue I want to make sure everybody realizes is that, again, I want to emphasize, this is a systemic disease, systemic illness that causes systemic inflammation. So in between all those gout flares is a low-grade inflammation, that's just waiting for another ignite or, so to speak, that can cause that acute flare, whether it's a stressor, whether that's -- they did drink too many beers or didn't eat too much shrimp that causes that fluctuation in uric acid.

So what are we going to do about this patient population, especially those who have progressed beyond, didn't tolerate or quite frankly, the xanthine oxidase inhibitors didn't work, well, for starters, there's NASP. And this, I'm not going to spend too much time on this because I know you're familiar with this product and this drug as well.

But this is a medication that can kind of quickly eliminate that crystal deposition, which would eventually obviously remove all that etiology, all that chronic inflammation that chronic inflammation that until recently, it hasn't really been appreciated to contribute, not just tag along with, but actually contribute and be an independent risk factor for myocardial infarctions, cardiovascular disease, insulin-resistant metabolic syndrome.

So it's a very, very -- not just as important to the patient, not just to prevent flares, but also prevent and decrease risk for other comorbid diseases. And you can see in this pivotal trial, these pivotal trials with NASP that the serum urate levels were dropped from almost 9 milligrams per deciliter, 94%, 95%. And importantly, -- and this is important with treatment when you treat gout patients, the SUA was sustained throughout the course of 6 months. So what does that mean? So what that means is, clinically, you see incredible results. You see this patient here, and you can imagine baseline, the morbidity this patient had, you probably couldn't grasp a pin or grasp the coffee -- a cup of coffee or put on a shoe adequately or easily. He had to probably use a shoehorn. He had to probably use a lot of different tools to help himself get through his daily activities?

But you can see just after 6 doses, how quickly that crystal deposition that probably took 10, 15, 20 years to actually develop was reversed. And that's huge and that plays a huge impact on this patient's quality of life, to the point where you say, well, that's an infusion every -- for a few hours, every 4 weeks, I can tell you, I've used a lot of uricase over the last -- well, since it was approved 15 -- first time 15 years ago, and I would have patients coming driving 4 hours and sitting in a chair for 6 hours, every 2 weeks, just to get this kind of benefit because -- and when patients mistakenly, I think gout patients have a bad rap about not being compliant with medications, et cetera, but really is truly if they don't have something that works, why would they be compliant. If you're taking something that's not doing anything, you continue to have flares, you continue to have tophi, why would you continue to take it? So patients have a bad reputation.

Unfortunately, that they're not compliant, but if you give them something that works, they will be compliant, and they will can take -- they will take the drug, and we'll continue to take the drug as they see an improvement, and they see an improvement in their quality of life.

So I mentioned 90% of patients, the issue is an excretion issue, right? And when I talked to patients, the savvy patient, especially, I explained to them, I say, well, most likely, the issue is your kidneys are holding on to too much uric acid, and they're like, "Well, why don't you just give me something that fixes my kidneys." And I'm like, "Well, we don't really have anything good. We only have these things that prevent the production of uric acid, not actually increase or improve the excretion or bring your kidney back to that homeostatic state where it should be like everybody else is that doesn't have gout."

But I think, again, right now, we figured that out, we figured out how to overcome that obstacle, and actually with a highly selective or at URAT1 inhibitor, we can actually sustain again, that keyword, sustain low levels -- lower levels of uric acid. So we can not only prevent further crystal deposition, but we can flip that saturation where the uric acid is more saturated in the joints than it is in the blood.

So now the -- now it's reversed. Now we can put those sharp microscopic needle-shaped of inflammation back into the solute, excreted and basically, again, improve the patient's quality of life by reducing tophi, eliminating tophi and eliminating flares.

And we can do this because it's in like previous or predecessors of uricosuric or URAT1 inhibitors, we have a very favorable PK/PD profile with a relatively long half life. So you'll only need to dose it once a day here again, it helps compliance with the patient population. And because of this PK profile, PK/PD profile, it is a -- has a very good, excellent, actually renal and hepatic safety profile.

And again, importantly, with this patient population doesn't require dosing titration either. And we can talk about a little bit more about what we've seen in the clinical trials so far in our Phase II studies. We had a large Phase II study. And this study was placebo versus 50 milligrams in pozdeutinurad or 75 milligram in pozdeutinurad. And you can see in the 75 milligram in this ITT population, which was just defined as anybody who got at least 1 dose of drug that 82% of the patients out below 6 milligrams per deciliter, which is kind of -- which is where we want to be below that limit of solubility as a general target across the board, but what's more important, especially for that progressive disease population and uncontrolled population, is that you want them below 5%, below 4%, even below 3, at least for a period of time. The lower you get them, the faster those crystals come out of resolution like we just saw with the photographs on the NASP patient.

And the 75 milligram got patients down; below 6, 82% of the time; below 5, 73%; below 4, or 55% of the time; and 1/4 of the patients got down below 3 milligrams per deciliter. And again, importantly, if you look on the right side, the figure, again, importantly, this was sustained. So the 50 milligram gout patients down to about 5 milligrams per deciliter, while the 75 milligram gout patients down at 3.5 milligrams per deciliter.

Now this study was our 203 tophaceous study. So everybody is a smaller study, so but everybody had clinically visible tophi of their hands, wrist, ankles or feet, and it was an allopurinol-controlled trial. We enrolled 42 patients. And not only do we measure tophi in these patients, we also everybody got a dual-energy CT scan, which is -- which allows you to actually visibly see and quantify the crystal deposition.

And you can see in the 75-milligram dose again, a baseline that was almost 9 milligrams per deciliter baseline. We had a significant improvement, about 90% of the patients at 3 months got below 6, almost 70% got below 5 in the 75-milligram dose. And this was again sustained not only through months 3, 6, 12 and 18. But again, it shows that the durability and the sustainability of the medication and again, an important piece when treating this patient population.

And if you look on the right part, the right side of the slide, you can see that -- and this is the first time this has ever been done and ever been shown an oral medication, a once-daily oral medication actually completely resolved tophi by month 6. And you can see the 75 milligram 1/3 of the patients have at least one completely resolved tophus by month 6. And as time went on, as you'd expect, they had an even better response. So by month 12, and then month 18, they had a 40% and 50% response rate. And then in the allopurinol group, the monotherapy in this study, we actually added 75 starting at month 7. And you can see that when it was added to allopurinol, they had a synergistic effect.

And basically, you had better results where they went from only 8% allopurinol to 25% after 6 months, and then 44% after another 6 months. Now interestingly, this patient here was in our 203 study, our tophaceous study, and they had obviously tophi as depicted with green on the baseline. And this patient actually didn't -- one of the patients that had a complete response, but this patient had such a clinically impactful response that by month 6, this patient was not flaring at all when previously he was flaring once or twice a month up to this point for the last several years.

So just absolute in misery. It kept them from work, it kept them out of work. It just kept them into the doctor's office and by month 6, this patient has completely stopped flaring. And by month 12, his crystal deposition is in his feet and ankles was down from 14.79 centimeters cube to 1.1 centimeters cube and by month 18, he just had trace uric acid crystals left over that were just probably sucked in and embedded over being that he's had gout for almost 20 years at this time.

Also about this patient. This patient was actually literally begging the investigator to let him in the Phase III trial. And because he had already been on drug, obviously, excluded him. But again, thankful to Sobi that we've already in the process of figuring out a plan to get him the drug. So he won't -- because he doesn't even want to go back to try to you take anything else because, again, the previous drugs he was on, the xanthine oxidase inhibitor didn't work.

And finally, our Phase III trials are fully enrolled and completed ahead of schedule, as was mentioned, we -- the global study was enrolled about 3 months ahead of schedule. The U.S.-only study was enrolled about 4 months ahead of schedule. And that speaks to the kind of the word gets around with investigators. If a medication, if a drug is: a, easy to use; b, the patients aren't complaining about it or having issues or a lot of adverse events from the drug.

So it enrolled extremely quickly, it also speaks to the need of type of medication like this where you have patients who about 40% or so either fail or don't tolerate xanthine oxidase inhibitor, and then with this study, it was designed to maximize how many patients actually got active treatment.

So we had an arm of 75-milligram dose, arm of 50-milligram dose and a placebo dose, but it was randomized 2:2:1. So you had 80% chance of actually being on active drug. And the primary endpoint, of course, was SUA less than 6, but secondary endpoints included tophi reduction. So we actually enrich the patient population with tophaceous gout patients. So about 25% of the patients total have clinically visible tophi.

And another secondary endpoint was resolution of flares. And the information and the data we've got from our 203 study, or tophaceous small study was actually the reason why we actually got FDA fast-track designation in 2024, for therapy in patients with gout and the progressive patient population with tophi.

So we're right really and truly right on the cusp. And again, I get a little too excited about this stuff, but we're on the cusp of having a huge unmet medical need met. NASP and pozdeutinurad could become the first meaningful innovations for the treatment or the chronic treatment of gout in really 15 years. And this in itself is exciting to me.

As I see this patient population in a huge need, they're extremely, extremely appreciative when it comes to -- when it -- when their life has basically turned around and changed when they're coming out of the wheelchair at age 39 because they had such severe gout or they're able to pick up their granddaughter or they're able to actually -- and this was one of the patients in our Phase III trial, the patient couldn't write or hold a pen for over the last 5 years.

He, for the first time, wrote a letter to the investigator, thanking her for allowing him to come into the study. And this was just after 6 months of being on study-driven. It was blinded, it didn't take a genius to figure out he was on active drug. Thank you.

Thank you, Rob. Just quickly before coffee would like to take an opportunity to have a bit of a discussion with our regional heads. So I'd like to invite Norbert, Sofiane and Duane to come to the stage. So these are the guys who are really driving at home on the ground in the regions for us here at Sobi. So it's good to hear it directly from them.

And we thought, I'd just take a few minutes before coffee just to hear a little bit of what's happening in their respective regions. So we start with Duane, who's heading our North America. Duane, you're in the middle of launching Gamifant, you have 2 big launches that you just heard from NASP positive right coming. How are you feeling about that? How is the organization getting ready for all of these activities?

Well, so we've been preparing for quite some time -- a couple of years ago, we took an approach of additional capability building because in this organization, you were always solving for the unknown as well as for the growth assets that we have in place or that we're beginning to launch. So one of the things that was on one of the slides that I don't think it was up today. No, your first the one that you had on before with prior to that.

Yes. If you look at the U.S. growth from the CAGR 5-year CAGR what that doesn't contemplate is over $250 million of sales that evaporated. So we have the -- as you know, we have the royalty with Bay Fortis, but that doesn't get to hit my P&L.

So the product that we had, Synagis, which was 4 children -- babies at risk, was over $250 million we had to solve for in addition to the continuous growth we had for our foundation products and for our launch products as well as our growth products.

So Gamifant was very important for us. Kineret was foundational for us. Doptelet was very important. And last year, we had our peak sales for Gamifant and Doptelet. Now clearly, Synagis was an experience where we had loss of -- where we had competition coming in.

Now we have loss of exclusivity with Doptelet by second half of 2027. We need to be solving for that. So when you think about the idea of just launches and other assets, it's always on our mind, how do we build a team and an infrastructure that enables us to do this very well and be prepared when it happens because we're solving for the unknown at the unknown time.

And there -- and that's the example of the opportunity we have now with the gout franchise with NASP and Arthrosi, or AR882. It's hard for me to pronounce for sellable words, so I just say AR882. So I think the -- essentially, we've been preparing for this launch for some time. In the last 12 months, we've had a strategy in place. We've had the capabilities built. We have onboarded several of our team members, but we will be completed with that onboarding before the PDUFA date in June.

And right now, we're already shaping the market in many ways with disease state education, with publications and scientific dissemination, as you can see on the slide. Our go-to-market model has a lot of the leadership and a lot of the field salespeople that have come from franchises that know and understand gout.

And we're identifying early adopters and those are typically the physicians and the infusion centers that understand pegylated uricase and understand that in some cases, you have a lot of patients that have walked away from that opportunity. And the way we look at it is we're providing a greater opportunity for convenience with a safety profile that's strong and a competitive efficacy. So we're very bullish, and we're very excited about the opportunity.

Thanks, Duane. Maybe switching to Europe to Sofiane. I mean, we've -- it's been a spectacular launch winning with Altuvoct, but the question I often get is how much is left? How much runway is there? So how do you see it right now with the launch of Altuvoct?

Yes. Sure. I think overall, region Europe will strongly contribute to Sobi growth journey, and it has started already in '25, 20% growth, and this is mainly driven by Altuvoct. So we had a very strong patient uptake in many countries where we have launched. And what was really spectacular to see that our strategy focusing on competition has had that expand in the patient pool, and therefore, increasing the market share of hemophilia and Sobi and this is really important for us to mention, as you can see here, after 6 months of launch, more than half of patients are coming from competition, and this is really value creation for us.

So of course, in '26, we're not going to stop there because we still have a lot. As Guido mentioned earlier, there will be many countries to come in the launch sequence to not mention U.K., France and Italy, which just got reimbursement in January. So those are the countries that are going to continue to strongly grow the product in '26 and beyond.

So '26, we're expecting a very strong growth, a very strong patient uptake. And to add to what Lydia has explained around synovitis, we are also building the scientific platform to strengthen the positioning of Altuvoct through the synovitis data to support the normalized hemostasis, and that will provide long-term volume growth, of course. So strong patient uptake and in the future, growing through volumes and consumption. That's a trajectory that will lead to $10 billion, even more.

And in the midst of all this, you're also preparing for the Aspaveli launch, and then also for next year in SHGT. Do you feel you have the ticket to win in both of these areas coming?

Yes. Not only I got the ticket, but I think I've already jumped in a high-speed train, I think. And Guido, he doesn't want me to become -- I mean, bored with only Altuvoct. So again, these are various challenges to take. I'm so glad to share with you some talk about this. I mean Aspaveli and nephrology, in particular, we have made a significant progress over the past months. With the prelaunch activities, we've been able to really map out the market, understand the patient identification and localize them at the center level.

The same as we have identified key centers and key prescribers. So I think this was done. And prior to the EMA approval, which happened January this year, the medical team and particularly the MSL went out in the field have engaged through medical education programs as well as compassionate use and also data dissemination of VALIANT data. So I think we've been able to cover 60% to 80% of the target customers in nephrology, which is huge in just a few months.

And now with the EMA approval, now we have activated the commercial team through the camps that are going to go now to activate the market. And as Guido alluded to earlier, I mean, it takes time to get patients ready for switches and initiation as we need to go through a little bit of structured vaccination protocol that could take 3 to 4 months. So I think now the objective is really to set this up and make the centers and doctors and patients up to speed to start the initiation. And we hope to see the ramp-up coming strongly in Q3, Q4 as we will need more time to establish the activation and processes for patient initiation.

Okay. And so switching to Norbert, I mean your -- you oversee a huge amount, a very diverse area, not just health care systems, but also cultures. What's your view on sort of what's the critical success factors here and what regions are of specific interest?

Well, the most critical success factor is actually to prioritize and understand exactly this heterogeneity. If you look where Sobi started when I joined to internationalize, it was only a few countries and a few products. Today, we are looking at different societies and different economies with their own dynamics, with their own competitive situations, with their own medical needs, with their own access system, with their own regulatory system. Unlike Europe, where you can unlock before an approval several markets at once, you have to go market after market and market.

So the first thing before you even start is learning what does the market look like? To whom do I have to listen, who are the people that know how do I target and segment? You build a knowledge base, you build a strategy, you find the right people on the ground, you try to understand the cultural and economic context, and then the model evolves.

And this is when you basically adapt your corporate strategy of a product to the targeted market. And then the really important moment comes because you start to decide how to enter what is the model. And you have seen Guido showing the development of employees that does not exactly match in the growing curve, the development of business of launches. So we have been able in international to do this large number of organizational rollouts by finding ideal models with local partners.

So we did basically anything from a stand-alone greenfield to a fully out-licensed partnership in these markets. And we will always adapt and choose what is the winning combination to keep a small team to be focused on the medicalization, to be focused on the competitive situation and to be focused on the patient.

Back in this Capital Market Day when we were launching 25 by '25, we were also launching our ambition to make our drugs available to more patients around the globe. And as Guido mentioned and others mentioned before me, the patient is at the center. We have this opportunity to provide human beings with medicine, but otherwise would not be there and to look at pictures like the joints that we saw and many other things, I don't even want to think upon seeing them, can now be brought by us to serve larger parts and communities. And so it is about being flexible and being agile and never give up.

And we just announced recently with Penn Pharma deal. I mean, maybe you can give us some comments there in this Latin America and what's -- how that's helping us?

Yes. So if you look at the market sizes of the world, you have clearly very predominant U.S. followed by -- if you cluster it many European countries, if you don't cluster it for the larger ones. But you've also China in there, you have Japan in there. You have Brazil in there. Brazil is the most important Latin American market. And it is not only large in terms of monetary value, it is also very large in terms of scientific capability.

They have a very, very high developed network of specialized physicians in rare diseases, in other diseases. They are also a huge contributor to clinical trials. You can unlock huge patient potentials. You're looking here at the society, not only growing in economy, but being also comparably young.

You're looking at entirely different demographics if you compare it to Europe, the U.S. or Japan. So Brazil for us is basically the door of entrance into Latin America. We found within the partner who has very successfully identified the opportunity to bring rare disease products and solutions there together with different partners. We partnered with them. We had a very good and strong understanding on how to bring the business forward. So we jointly developed into a model where we now acquired a good part of it.

We own now 60% of the economics, and we're working from Brazil out to other Latin American markets. If you look into Argentine, if you look into Mexico, the size of the 2 combined gives another Brazil and then also at Colombia. So with getting Latin America finally also into our array of geographies and markets, we will be -- I'm not sure the only, but for sure, one of the best prepared companies on the planet to roll out any rare disease solution into all relevant geographies with our own presence and with our know-how and with that of our partners. So this pinned is so much more than just a deal to access the market. It is another step in our philosophy to occupy relevant segment.

Great. Thank you, gentlemen. I hope you have got a little bit of a glimpse such a short session with just a little bit of idea of what's really happening on the ground with our business. So right now, we'll have a coffee break. So we're a little bit behind time, but let's try and be back here at 14:45 grab a coffee. And of course, please talk to Duane, Norbert and Sofiane during the coffee break as well if you want to find out more about the region.

[Break]

For the second part of our CMD, it was a very short feet on Swedish standards, I understand, but we have an exciting lineup for you, which hopefully will be worth it. I'm very happy to open this session where we will have two special guests we have with us today. First of all, we'll start with Professor Parhofer from the University of Munich, who is a professor of metabolism and endocrinology, which will take us through severe hypertriglyceridemia. Mr. Parhofer?

Well, thank you very much for the kind introduction. It's a great pleasure to be here, and I would like to thank Sobi for having me here. It's actually is also something new for me because we are used to speak to our peers, and we sometimes speak to our patients. But it's rare that we speak to other, let's say, professionals or academics and that's why it's also something new for me here.

Now what I'd like to discuss with you is defining the unmet needs and current treatment landscape for managing severe hypertriglyceridemia. These are my potential conflicts of interest. But let me now start with some epidemiological data and what you see here is the distribution of triglyceride levels in the population. And you can see on the bottom of the figure, that the majority of us have normal triglyceride values.

And then there's about 20% to 30% of the population that have elevated triglyceride levels. Most of them moderately elevated triglyceride levels, meaning between 150 and maybe 500-milligram per deciliter. And then there's few people, or fewer people who have severely elevated triglyceride levels meaning above 500 or even above 880 milligrams per deciliter.

Now on the left-hand side, you see why that is relevant because we know from many epidemiological data that patients who have elevated triglyceride levels have an elevated risk for cardiovascular disease and that starts after a slightly elevated triglyceride levels. However, this is not linear, meaning that after higher than triglycerides of 600 milligrams or so, the risk flattens and does not increase anymore. On the other hand, the risk for acute pancreatitis is really strictly linear to the triglyceride level. And it's not that high in the patients, who have triglyceride levels between, let's say, 150 and 500 milligram per deciliter, but then it increases very significantly.

And in patients with more than 880 milligrams per deciliter, the risk is really significantly elevated. Let's have a closer look at severe hypertriglyceridemia. And what you can see here that in most patients with severe hypertriglyceridemia, you have a mixture between a genetic predisposition and secondary factors. And one group of patients shown here on the very left side, the genetic predisposition is extremely strong, thus you do not need any additional secondary factors. And that's what we call familial chylomicronemia syndrome where you usually can also define the genetic background of the severe hypertriglyceridemia.

The majority of patients, however, is more in the middle part where you have a genetic predisposition, sometimes you can define the variants, sometimes you can see the mutations, sometimes not, but they very often have additional factors such as diabetes, some alcohol abuse -- not even abuse just alcohol use, then probably also meditations or concomitant diseases.

Now let me look a little bit more into the detail into this, why we get this severe hypertriglyceridemia. You have to know that triglycerides are transported lipoproteins and these lipoproteins are secreted from the gut and from the liver. But the way that triglycerides are catabolized is for both sorts of lipoprotein is very similar. And there's a key enzyme, which is lipoprotein lipase, which really is essential for the catabolism of triglycerides. And in patients with familial chylomicronemia syndrome, the lipoprotein lipase does not work directly because one of the components is defect and usually not only one variant, but two variants.

At the same time, we know that apoC-III a lipoprotein from the lipid metabolism again plays a crucial role because it can inhibit the lipoprotein lipase dependent and independent catabolism of triglycerides. Thus, if you inhibit apoC-III, you basically reactivate LPL but you also activate other pathways to decrease triglycerides. And that's why inhibiting apoC-III is such an essential component for treating severe hypertriglyceridemia.

Let me go back briefly to the familial chylomicronemia syndrome. And what you can see here that there is a number of symptoms that characterizes these patients, the neuropsychiatric symptoms, there's skin symptoms. There's a very milky blood, I will show you a picture later, you actually have seen one before from Guido. But the most serious complication is this abdominal pain and especially in the form of an acute pancreatitis. And what you see here on the right-hand side is that hypertriglyceridemia-induced pancreatitis has a very high morbidity and mortality. And medical emergency requiring hospitalization and very often intensive care stays. And therefore, it's, of course, a goal to omit such episodes.

Now let me show you an example of one of the patients that we initially treated with volanesorsen and then now treated with olezarsen. And that's a 24-year-old male patient who had triglyceride levels between 2,000 and 7,000 milligrams per deciliter. He had to return episodes of acute pancreatis, at least 7 severe episodes, but probably several additional ones in between for which he did not go to the hospital because he said, "well, they just put me on fasting and I can do that at home too and then it improves again." And you can also see on the left-hand side how milky the blood really is in these patients with severe hypertriglyceridemia. If you have no elevated triglycerides, then this is totally yellowish clear. There are some skin manifestations, which you can see in the middle and on the right-hand side.

Now on the left-hand side of the slide, I show you the triglyceride levels of this patient starting in, I think, 2020. And you can see he had several episodes of acute pancreatitis and then when we started volanesorsen Waylivra at that time, you see that the triglyceride level is much, much lower, although there's also some episodes where the triglyceride levels are again elevated. This is either due to dietary mistakes or maybe also because the patient had to interrupt the medication because his thrombocytes were too low.

And the thrombocytes you see on the bottom part of the right-hand side and you see that over time, and this is a logarithmic scale, you can see that over time, the thrombocytes go slightly down and that is really a problem, let's say, with volanesorsen where you have to measure all the time thrombocytes weekly or biweekly and decide whether the medication can be given or not.

On the other hand, since he was started on volanesorsen he did not have any more episodes of acute pancreatitis. And as I have discussed with several people before, we just started the last week now on olezarsen. And therefore, we are very happy that this new drug development at olezarsen was first tested in familial chylomicronemia syndrome. It's again an apoC-III antisense oligonucleotide, but it's bound to another molecule, which allows the apoC-III antisense molecule to go directly to the liver and therefore, you need much less dosing. And the Balance program evaluated this drug in patients with FCS, and you can see that was a Phase III randomized, double-blind, placebo-controlled trial, which involves 60 seats patients with genetically defined FCS, and they had an average baseline triglyceride level of 2,600 and olezarsen 80 milligrams was tested versus 50 milligrams versus placebo every 4 weeks for basically 1 year. And it was published in the New England Journal in 2024.

And what you can see here on the left-hand side are the triglyceride levels. And you can see that in the placebo group shown on top, it goes up, while in the 2 treatment groups, it goes down. And you can see that there's a dose-dependent effect on triglyceride levels with obviously the 80 milligrams being more potent. The clinically more relevant result is actually shown on the right-hand side because you'll see here that the acute pancreatitis free survival for 1 year. And you can see that compared to the placebo group, where you can see again episodes of acute pancreatitis there was much less episodes of pancreatitis in those treated with olezarsen 50 or 80 milligram per deciliter. That's a very strong hint that this evidence that this reduction triglycerides translate into clinical benefit.

However, as mentioned before, many of our patients with severe hypertriglyceridemia do not have FCS. They have other forms. They have this genetic predisposition and then additional factors. And therefore, the question is would they also benefit from such treatment because that's where the clinical need is probably as a global perspective, much more relevant than for the rare patients with FCS. And this is also reflected in our guidelines where it says that above a triglyceride level of 880 milligrams per deciliter, the risk for acute pancreatitis increases. And that doesn't only increase in FCS patients, but it increases in all patients who have elevated -- severely elevated triglyceride levels.

And at the bottom part, you can see that our treatment strategies are not very good, yes, lifestyle, yes, avoid secondary phases, maybe try one of the established lipid-lowering drugs, but overall, these approaches do not work very well. And therefore, we were very happy when this drug olezarsen was also tested in patients with severe hypertriglyceridemia who did not have FCS. Thus FCS was an exclusion criteria in that study. And that paper was just published very recently again in the New England Journal of Medicine. It was a Phase III randomized double-blind placebo-controlled trial. Patients with severe hyperglyceridemia, not FCS, again, 50 milligrams olezarsen versus 80 milligrams versus placebo every 4 weeks for again 12 months. This time, a much bigger population, more than 1,000 patients were included, but you also see that the baseline triglyceride level was considerably lower and 19% of those had prior acute episodes of acute pancreatitis.

Now when we look at the triglycerides -- these were actually 2 studies, which were very similar and simultaneously published. But when you look at the triglyceride levels for the 2 sub-studies, I would like to say CORE and CORE2, you see that the triglyceride levels are much more stable than in the FCS study, which probably reflects the higher number of patients. And you see that also in the placebo group, there's a slight decrease probably because some of the secondary factors were also treated, but you also see that in the group where they received olezarsen 50 or 80 milligram per deciliter, the decrease was much, much more impressive. And there was -- as you can see significant decrease in triglyceride levels in both of the sub-studies.

And again, the clinically relevant question was does this translate into a decrease risk for acute pancreatitis. And this time, it's shown the other way around, where you see the new onset of acute pancreatitis. And you can see that in the combined olezarsen groups shown on the bottom with the green line, it's considerably reduced compared to the placebo group, where you also see there's a linear increase with time. And so olezarsen reduced the rate of acute pancreatitis by 85% and 86% of the 29 acute pancreatitis events occurred among patients with baseline triglyceride levels above 880 milligrams and prior pancreatitis. And as a clinician, we always -- we also always look at the other side, what is the number needed to treat.

So how many patients do you have to treat in order to avoid one episode. And what you can see here that for the pooled olezarsen patient group we have to treat 20 patients for 1 year to avoid one episode of pancreatitis. And if you select those patients who have really elevated triglycerides more than 880 and prior pancreatitis, this number goes down to 4. And I'm not sure whether you're familiar with this number needed to treat parameter, but that's extremely good numbers needed to treat, right? I mean in cardiovascular disease, we speak of 50, 80, 100 patients over 5 years sometimes to avoid one cardiovascular event. So that is a very, very impressive result.

Let me summarize hypertriglyceridemia overall it's common. Severe hypertriglyceridemia is uncommon. Acute pancreatitis is the most serious complication of severe hypertriglyceridemia. And patients with severe hypertriglyceridemia, FCS familial chylomicronemia syndrome, but also with less clear-cut genetic findings benefit from approaches addressing apoC-III and olezarsen reduces triglycerides and episodes of acute pancreatitis and the limiting side effect of thrombocytopenia, which was really limiting the use of volanesorsen/Waylivra is not observed with olezarsen. And with these pictures from Munich, I would like to thank you for your attention. Thank you very much.

Thank you, Professor Parhofer. As we continue, I'd like to invite Professor Giamarellos on the stage, Professor Giamarellos is Chair of the European Sepsis Alliance, and he's also the leader of the Hellenic Institute for sepsis. So please professor.

Thank you very much. I would like to thank very much Sobi for inviting me here and to give you some thoughts about precision management for sepsis. And with this, I would like to first of all to acquaint you with the keywords. Before jumping on to what sepsis is because all of you know that sepsis is a lethal condition for which nobody wishes to speak about. But the reality is it's very common. And I will soon come to this. The real key point here is what is precision. Do all of you have the same hair? No. Do all of you have the same color of eyes? No. Do all of you have the same height? No. So why should all of you since you are named that you have a disease, you need to get the same treatment. But it favors some conditions, I understand.

But can you imagine that some of you may benefit from the treatment and some others of you may get severe harm from treatment? And then it takes out, oh, the benefit is 3%. But the 3% of the treatment is average. There could be some patients who may get 40% benefit and others 100% harm. And then the question is how many of them are represented in total so that we get the average. So in other terms, we want to keep those who will get benefit and omit the others who may get even harm.

This is my conflict of interest disclosure for this presentation and allow me to speak to you about my daily fight the last 30 years, I'm a physician, where I have seen lots of deaths. Not knowing how is it possible for young children to die without any comorbidities. And how is it possible for aged people with a lot of comorbidities to survive in a rather easy way. Here, there is no winners only losses so far. But just because there were some losses somewhere in 2016, there was the idea we need to find a way to measure what sepsis is. And this is a score, which is called the SOFA score. And then in 1 year in 2017, and all around the globe, the real number of patients suffering from sepsis were measured. The more blue, the more sepsis you get, the total is almost 50 million new cases a year of which 11 million die.

In other terms, in 1 year, you have 3x the deaths that you had throughout the entire pandemic. How many they suffer in America, up to 2 million. How many in Europe, up to 4 million. And the question is what this is about. If you imagine sepsis, sepsis means that there is an infection, not necessarily bacterial infection. It could easily be viral. COVID-19 was a type of viral sepsis. So please don't narrow your mind into if there is need of antibiotics. No, no, no, no, no, it's not the case. Fungi, they kill people with hematologic conditions because of sepsis. Parasites, they kill a lot of people in Africa because of sepsis. So when infection comes, patients arrive at hospital. Some of them, they will deteriorate.

Imagine if it would be possible to find a biomarker to trace at that stage, the patients, they look like us. You cannot discriminate who will jump into sepsis and who will not. Imagine to have a biomarker to treat them early. So that's one option. This is what we call presepsis. So what's the difference between prespsis and sepsis? When you have real sepsis, you're in need of the ICU, you are deteriorated. Your lungs do not work, your blood pressure is low, your liver does not work. You have high chances to die. And all patients, they look the same, but not all patients have the same white blood cell count. Not all patients have the same ferritin. Not patients have the CRP. And you know what is unfair with these patients. They cannot speak to us.

All of us, if we can walk and go to the physician, we can defend ourselves. We can even say, I don't want that medication. These patients, they try to speak to us in an indirect way. They say to us. Here are the biomarkers in my bloodstream. Do something for that. And the mechanical ventilation, I'm sedated. I can't defend myself, but I tell you the signature of my blood.

So presepsis. If a biomarker is increased, which is called presepsin. The biomarker is called presepsin. And the biomarker tells that the patient will sooner or later get deteriorated by a biomarker, by cytokine, which is called interleukin-1. And we gave to these patients Anakinra. And this is the path to death, the first 90 days. All patients, 100% of them are alive at day 0. As the curves climb down, the patients they die and you see that by day 90 with that strategy, we managed to save lives in a statistically significant way. One question here. Does any of you ever considered that the patient with pneumonia who arrives at emergencies and who relatively appears mild. If his presepsin is increased and IL-1 has started to work, he has a chance of 40% not to be alive after day 90. I know shocking, but it's the reality.

Let's see what's happening in the ICU. Ferritin, 6% of the patients, they have real increased ferritin. They suffer from what is called cytokine storm by the way. Don't believe what was said during the pandemia that patients they were dying from cytokine storm. That's an easy explanation because it's difficult to jump into the mechanism. The real cytokine storm is only 5% of the patients and how you trace them by ferritin. And we just published in JAMA that in these patients, if you treat them with Anakinra, only this 5%, they get better. But today, I'm here to present you how a combination of proteins can frame a completely different endotype, which is driven by interferon gamma. And if you have a drug which blocks interferon gamma, either soluble or interferon gamma, ready bound of the cell, ready to stimulate the cell, you may save lives.

So what can lead you to stimulation of interferon gamma, any infection, lung, either community-acquired pneumonia or it's a common pneumonia or COVID-19 or influenza or urinary tract or intraabdominal or bacteremia. So just by the type of infection you cannot tell. Look what happens to these patients. Neutrophils or lymphocytes, they produce interferon gamma. Interferon gamma stimulates tissue macrophages. Where are tissue macrophages? The lung is full of tissue macrophages. The liver is full of tissue macrophages. And then all of a sudden, the stimulation drives overproduction of CXCL9. CXCL9 is a natural product.

Do you know where CXCL9 is, in lung cancer to protect us and to kill cancer cells. So can you imagine in the absence of cancer, if you spoil a substance, which is destined to kill cancer cells, what the substance can do in normal tissue. It leads to lung dysfunction, liver dysfunction, gut dysfunction and eventually, it kills. So the idea, if I block interferon gamma, I may save the patient. But the question is, again, how many of these patients indeed they suffer from sepsis driven by interferon gamma. This is a collaboration between my country, by Germany and Italy, and we ended up that this is the case for 20% of the patients.

But someone could argue here, yes, but all of you are friends, you find samples which were frozen in your fridges, you made the measurements. Now we want that you give us hard evidence of the incidence of the issue. And indeed, during the EMBRACE trial, we made repeated that prospectively. And we ended up that exactly the percentage was the same. In other terms, from those 50 million I spoke about at the very beginning, around 20%, they have sepsis driven by interferon gamma. So here are the patients. Interferon gamma is increased, CXCL9 is increased, but also they should not suffer from immunoparalysis. In other terms, HLA-DR should go up. And these patients, they are randomized. They all of them receive standard of care treatment according to the guidelines, and they're randomized to receive either placebo or a high dose or a low dose of emapalumab.

The trade name you know it already is Gamifant, and we follow up the patients. And how do we measure efficacy? So I've spoken to you already that we managed to find a score about sepsis dysfunction. The score is called SOFA score. And on a daily basis, you give points from 0 to 4 for 6 major organ functions. You add them all and the major a patient may get is 24. The more you have, the more the risk to death. If you are above 9, everybody accepts that the risk that you die is 50% at least. So the question is how much we had an average improvement of SOFA score at the end of treatment. So 40% the placebo, 43% the low dose, 60% the high dose giving already probability for statistical significance.

And previously, and I would like to thank you very much because we introduced to all of us the numbers needed to treat here, the question is how many I give treatment in order to improve the function of one of our patients, 5. Do you know what is important in sepsis? To be less than 70. Here, we are just at 5. But nowadays in the omics era, everything is presented into what is called the heatmaps. And here are the heat maps in other terms, the truth about the study, not percentages anymore, all patients together. From left to right, the placebo group. In the middle, the low-dose group. In the right, the high-dose group. What you see inside these heat maps, you see cells, something like a table. You have rows, every row is a single patient. You have columns. The columns are the days of follow-up. Day 0 means the treatment starts.

In order to understand what we speak about, please look at the index at the right. If you are red, you are already at a sofa 9. That means that in day 0, all our patients were equally severe. The more you turn dark, the more you worsen. If you are fully black, you die and all of a sudden, you see that the area of representation of black in the high-dose group is much less, less than 50% of what happens in the placebo group and the high-dose group. The improvement is spectacular. And if you compare statistically the heat maps, the benefit is huge relative benefit of 41%.

Let's see now the survivals. The survival curves, day 0, all people, 100% are alive. As we move down, people die. The mortality is 52% in the placebo group, 53% in the low-dose group, 40% in the high-dose group, translating to an absolute 12% decrease of mortality. Someone would say, so what? The answer is that in the guidelines for sepsis in the last 22 years, since the start of the Surviving Sepsis Campaign, whatever provides a survival benefit of 3% is part of the guidelines. Did any of us ever realize that drugs like tocilizumab used during the pandemic, dexamethasone used during the pandemic. Hydrocortisone used during the pandemic. They joined the guidelines, providing just 3% mortality decrease. And here, we are at 12%.

But since the moment I became a medical student, I was not believing in coincidence and in numbers. I wanted to have a clear-cut link between the mechanism and the clinical benefit. If I could not see that link, I would say maybe. Now let's see the link in other terms. What was the effector molecule, CXCL9. In our statistics, they pointed out that in order for someone to survive, CXCL9 should decrease at least 40%. What the graph is showing is the time to reach this at least 40% decrease of CXCL9 in the black line, which is the placebo, the blue line, which is the low dose, the red is the high dose at day 0, they start together, but look what happens at the very end. 24% efficacy decrease of CXCL9 in the placebo, 50% in the low dose and a maximized 85%, which is statistically significant by Cox regression analysis in the high dose.

So allow me now a bit to wrap up. Regarding the primary endpoint, which we set it out to be a decrease of SOFA score, which translates to an improvement of organ function, 20% decrease. The secondary endpoints. 12% decrease of mortality, 61% decrease of more potency of the high-dose group to reach the levels of CXCL9 that are needed to provide survival benefit. And all that without any concern coming from our DSMB. Thank you very much for your attention, and I'm looking forward to the questions.

Yes. Professor Giamarellos, I mean we will have probably a lot of questions in the Q&A session. I'm worried a little bit that there will be no questions for anybody else left after this presentation. I think it was really a crescendo and bringing up, obviously, this very new data. So maybe in the interest of time, if we could face this in a way, I don't want to disappoint you, but I'm sure 80% of our questions will be directed towards you because who are we after this presentation. But maybe we could continue with Henrik, our CFO, just bringing home the value creation journey, and then we will be back on stage together with Professor Parhofer and Rob and 3 members of the executive team. Thank you so much here. This was unbelievable. Thank you.

Hi, everyone. So now to something completely different. I want to discuss the financial aspects of our ambition and our value creation. Let's start with the track record. So this is an illustration of our share price performance in the period beginning of 2020 to the end of 2025. Of course, if we would have added the last 1.5 months, it would have looked even better.

But with 126% share price growth, we outperformed or we have outperformed relevant European health care and Swedish indices. So we created a lot of shareholder value through our growth, our diversification and our strong execution. This period was characterized by significant scaling of our business, of course, adding multiple best or first-in-class assets. We significantly expanded our global footprint that we -- as we heard from Norbert.

And from a product perspective, also broadening the portfolio as we entered into new indications. And we delivered all this despite sometimes very challenging macro environment with COVID, high inflation, geopolitical uncertainty and pricing pressures. So we really built a materially stronger financial platform. With the investments made in the period 2021 to 2023, we generated sales growth and also margin expansion. We saw sales growth across our regions. And in 2025, we had strong double-digit growth in all our 3 regions.

We also added, obviously, from a product perspective, a lot of sales, both in hematology and immunology. And we scaled SOBI to SEK 28 billion, corresponding to a 12% CAGR in this period at constant currencies. And we delivered this with improving margins reaching an adjusted EBITDA margin of 40% in 2025. Our model comes with a lot of cash generation, and I'm going to come back to that. With this performance, we are confident that we have the financial platform and financial capabilities to take on and drive the next phase of growth for the company. And as we take on that next phase of growth, it is about investing and it's about capability, building in order to take advantage of these opportunities that we have outlined today.

Our approach is disciplined. We will, of course, invest now, but we will do it in a way that sustains strong profitability. We will do that through reallocation of resources from more mature areas into new growth areas and also with cost discipline. And what this time line tells us is that we are planning for phased and sequenced launches, which will allow us to smoothen investment peaks and also benefit from scale as we grow our top line.

If I look a bit further and discuss our financial ambitions, we will grow revenues to SEK 55 billion. That is the ambition with an adjusted EBITDA margin in the upper 30s and all by 2030.

Some qualification of this ambition is that we have not, as we heard, included any revenue from Gamifant in IDS in the ambition because of its early stage. And furthermore, the ambition is based on current portfolio. So we have not included any business development or M&A additions. Then in terms of FX rates, we have used the 2025 average rates, which are the latest reported numbers, which means that obviously that there are no FX effects compared to 2025 in the numbers that we quote today.

The SEK 55 billion number represents a strong double-digit growth or double-digit CAGR. And we have estimated a risk corridor of plus/minus 10% on this number, just to recognize that there will be uncertainties also in the future. If we provide some more context to the ambition also across the P&L lines. To the left here is the track record, and we think that historical patterns are indicative also for what can be expected for the future. But with regards to our ambition for 2030, of course, in itself, the growth to SEK 55 billion will be crucial for the protection of margins because scale creates the opportunity of operating leverage.

When it comes to the R&D line, we estimate that to remain in the 11% to 14% of sales, depending, of course, on the portfolio evolution, not at least when it comes to the outer years. Considering that we are focusing on late stage, we think this is an appropriate target to have. For SG&A in the period, we expect that to increase in relative terms in the earlier years as we take on the launches. But at the same time, we expect SG&A to decrease in the outer years as we gain scale and as we reallocate resources from mature areas to growth areas. So the operating leverage will allow us to expand margins and to reach an adjusted EBITA margin in the high 30s by the end of this period.

Further on the margin ambition, Here, we have listed a couple of key levers that are very important for us in order to live up to the margin. And I repeat, it starts with the strong revenue growth that will be driven now by the key launches in the next few years that will be important for margins. But we also need to protect our gross margins through efficiencies and COGS improvement projects, such as the direct management of manufacturing within our outsourced model and then also tech transfers and process improvement projects that we have throughout the supply chain.

We will be disciplined, but we will benefit from the phased launches. It doesn't happen with the same intensity everywhere at the same time. We will also continue to reallocate resources into growth areas from more mature areas, and we expect to benefit also from economies of scope as we do, for example, in our hemophilia franchise. And we expect that also in our gout franchise as we build capabilities for a franchise, not only for individual products.

And last but not least, an ongoing cost discipline, just as we demonstrated in 2025 when we contained operating expenses and also carried out restructuring in our company. Key advantage with our business model is the strong operating cash flows and the strong cash conversion. Over this period, historically, we have materially increased operating cash flow up to SEK 8.6 billion in 2025. And over the period, we've had a very strong cash conversion, particularly in the last 2 years, where the cash conversion was around 80% of EBITA. This, of course, creates financial flexibility, and it allows us to very quickly delever every acquisition after every acquisition and business development activity that we've had. And this, of course, creates headroom for further business development aligned with our strategy.

I'm going to say a few words about capital allocation. And of course, primary objective is investing into organic growth into our development programs and launches, but also to continue to focus on cash generation because this will allow us to continue with disciplined and selective M&A and business development, focusing in late stages with strong discipline. And we, of course, plan to continue to build shareholder value through profitable growth and strong cash generation with a priority also for the long term.

To sum up this short section, I think it's clear that we have a proven performance track record and we have a strong financial platform with balance sheet strength. It's very crucial for us for our growth journey, obviously, to deliver now on the opportunities that we've outlined today. But when we do so, we need to invest, but we will do that with a continuous focus on profitability. Our ambition is to reach SEK 55 billion of revenues, delivered with an adjusted EBITA margin in the high 30s by 2030. And we think our strong cash generation and our disciplined capital allocation will create long-term value. So thank you for your attention.

Yes, I just wrap it up quickly and then give way for question and answers because we -- I think we were quite intoxicated by quite a number of the presentations, Professor Parhofer first and then Professor Giamarellos and also Rob. So maybe just go straight into the concluding remarks. I don't want to repeat what just -- what Henrik has mentioned. You've seen the stats. Our ambition is clear. We want to double the company, and we want to basically emulate the cycle that you have seen in the past and come on the high end towards the end. And we think that we have the credibility and we have also the executional ability to do so.

6 products is what really drives the company moving forward. And obviously, amongst those 5 opportunities to reach blockbuster potential, which is considering the size of Sobi of what it is today, quite remarkable. And we will obviously continue expanding globally and leverage the position that we have created over the last years, and we talked about this extensively and building further capabilities as we go along.

We are quite proud of what we have achieved. It's clear that we want also to be part of the AI community in a greater sense. But I think we have to be also measured and be selective and recognize that we are mid-cap and we don't get paid for the headline, we get paid for the endpoint. And I think this is one of the concluding remarks. I would like now to invite the speakers, Professor Giamarellos, Professor Parhofer and Rob on the left and then Henrik and Lydia here on the right. And then I think we can open the floor for Q&A because I'm sure there are plenty of Q&A -- questions at this point of time.

So maybe we start -- I mean, maybe we start with Viktor and then we make our way, yes, if this is okay. Viktor, please.

Viktor Sundberg, Nordea. [indiscernible] And how you view NASP versus KRYSTEXXA in that setting? In terms of efficacy, it seems like they are kind of similar. And in combination with methotrexate, maybe there are some tolerability issues. So I just want to get your view on that. And maybe on the same topic also for pozdeutinurad, could it be expanded or tested in patients with CKD and gout? And what potential do you see there?

All right. So the first question, I'll tackle first. So the -- so I think there's definitely patient populations for both if the best way to put it. So one of our colleagues always says some people like dogs, some people like cats. There's always going to be an opportunity for a patient population that has severe disability. You want to see reduction in the crystal deposition very quickly. You want to see results very quickly. Pozdeutinurad does a great job of reducing tophi and burden, but not quite as fast as a uricase, not quite as fast as NASP.

So if you have a patient that has significant disability, [indiscernible] wheelchair, flexion contractors or just sheer has trouble day-to-day activities due to having gout for 15 years, 20 years, 10 years and just having that significant debulking is needed in a quick manner. And for whatever reason, there might not be -- there might be some kind of compliance issue with oral therapies or they couldn't tolerate oral therapies for one reason or another, they need something that's infused. So again, some people like dogs, some people like cats, just like rheumatoid arthritis, some people prefer an infusion versus an injection. It's the same kind of mentality.

So you have this patient population that's going to be really the target. And I've used a lot of uricase, probably more uricase than most people in the world for that matter for gout. And there's definitely a patient population that's there that needs it. And with pozdeutinurad, I think it's a spectrum. You have patients you're going to be able to capture earlier prior to the point they need something like NASP. And those patients, you're going to be able to treat. And then again, you're going to have patients too, they're going to have to come off NASP because -- and they're going to be all maintained on something. And we know that those patients typically have already failed everything else. Febuxostat, allopurinol, Probenecid, benzbromarone, you know they've already failed, but then they could go to pozdeutinurad.

So I mean, they're definitely going to work not against each other, but with each other in that sense. And then as far as CKD, in our current Phase III trial, we have patients with GFRs as low as 30 mls per minute. So in CKD Stage IIIa, IIIb up to that point encompass about 90% of the gout patient population. So it's just there's going to be some patient populations that are below 30 that aren't going to be a good candidate for pozdeutinurad just given the mechanism of action. And -- but that's a very small percentage of the patient population. But I have no doubt in the data that we've seen to date in patients between 30 mls per minute and 45 mls per minute, it works. It works well. And of course, again, given the mechanism of action, you expect it to work better if you have a GFR greater than 45, but it still works and it's still going to be a great alternative to those patients who have failed allopurinol or febuxostat.

Yes. Christopher, maybe?

Christopher Uhde from SEB. My first is for you, Guido, I guess. On the M&A outlook going forward, what moved the needle historically versus in future? Because historically, Sobi enjoyed a niche that was too small for majors to really play in deeply. But with the growth outlook, does the size need to increase then for future deals? Or are there enough interesting assets still there that you could just increase the deal count instead? And in both cases, what can and will you do to ensure the organization keeps pace to support those assets properly so you don't have to leave value on the table. So that's the first one.

And then the second one is for Professor Giamarellos on Gamifant. I just wondered about the patient baseline characteristics and also noticed that originally, you plan to, as I understand, to randomize 1:1:1 but there were 20 patients on the high dose and 30 in the low. So what sort of happened there? Did you see any dose-limiting toxicities? Were there covariants that you used in the regression to account for baseline imbalances when assessing SOFA?

Maybe we start with Professor Giamarellos.

Thank you for the question. So always something which is a peculiar characteristic in sepsis trials is that you have sites which enroll 1 patient and other sites, which they enroll 3 patients or 4 patients or 5 patients. So when you add them up, you may end up with something like that. So for the sake of time, I could not present the full table with the demographic characteristics. But in terms of severity, the APACHE II in all patients were 20 and the median SOFA score in all 3 groups were 10. So no real difference between them.

And the easy part of the question is, obviously, if you want to know what somebody's strategy is, you need to see what he's doing. If you look at our last deal, pozdeutinurad, we acquired an asset that normally big pharma would have acquired provided that there were Phase III data available. So we went early, got comfortable and intoxicated by Rob's presentation at the time when he was on the other side. And we basically felt this was an opportunity not to miss.

So we got access to a product that was larger and therapeutically aligned and allowed us to have -- to build a franchise. So we will probably be more driven by the idea of building franchise. And if you want to know how we would like to keep the energy up, tomorrow morning, we are all together again, and then we talk about how we can beat forecast on this note, please.

Gonzalo Artiach from Danske Bank. I have one for Professor Parhofer and one for Sobi. And it's on the lipid profile on the patients that -- on the CORE and CORE 2 studies. I think it's very interesting that those patients see a reduction in remnant cholesterol, right? I mean, which I guess it includes IDL, VLDL and maybe LP(a), I don't know. Then you have like ApoB stays flat, but then we have an interesting increase in LDL. And my question is on this. I mean, how worried are you on this increase in LDL?

I guess that for patients that is above 880, this is not a major worry, probably cardiovascular risk is a secondary worry. But for those patients between 500 and 880, yes, what do you think of this increase? Because, I mean, LDL -- it's very like described as a -- it correlates with cardiovascular outcomes, but the other part, LDL, non-LDL particles are more like from epidemiological studies and real-world evidence.

Thank you for the question. I mean you have to see if you decrease triglyceride-rich lipoproteins, the way that they are metabolized is basically shifting to IDL and then LDL particles. So it's no surprise at all that you have a slight or minor increase in LDL particles. And of course, the first intention is this good or not. But again, you have to see that this is a minor increase from usually a very low level, and these are not patients with familial hypercholesterolemia.

So yes, you see that increase, but you usually do not see an increase in ApoB because the ApoB, which is more relevant with respect to cardiovascular disease, that is part of the triglyceride-rich lipoproteins and the LDL. So if you decrease triglyceride-rich lipoproteins, you have a decrease in ApoB there, but then you have a slight increase in the LDL fraction, which then basically results in an increase in LDL cholesterol, but no change in ApoB.

Summarizing, I do not think this is overall a relevant problem with respect to an increase in cardiovascular disease. And you also have to see if at the same time, you significantly decrease your risk for acute pancreatitis, you are probably very open to accept a minimal increase in risk in cardiovascular disease. Of course, we need long-term data, but I would not be too concerned with this.

Okay. Great. And one for Sobi, I guess, for Lydia. For those patients that are -- I mean, in the peak sales estimate that you have for Tryngolza, do you include any kind of potential use in those patients below 880? And from an M&A perspective, is it something that you're considering, for example, potential combination treatments with other modalities for lipid lowering?

So -- and maybe you can talk about more the sales. But obviously, what we are submitting and what we are really looking at, it's those above 880. That's clear because the benefit, it's outstanding, and there are no other products that have shown this reduction and not only in the triglycerides, but on the acute pancreatitis. So that's going to be our focus. If there has been -- there will be other uses, it's something that we are not considering in our forecast.

For the combination, obviously, and maybe I would defer to Professor Parhofer, but obviously, diet will continue. The regular treatments are going to be there. So that's how we are -- that were the inclusion criteria in our trial. So patients should have been already on stable treatment with the current available treatments like fibrates, et cetera. So that's what we are going to have on the label that patients should have been already treated and then we will -- but despite that having this lack of efficacy. So that's how we will be approaching and unless there are changes in the treatment guidelines, but I guess that maybe you want to add.

I did it, and this is a very interesting question because that's also a medical need that we have patients with moderately elevated triglyceride levels, and we do not really know whether they will benefit with respect to their cardiovascular risk if we, for example, already decreased LDL very significantly. But that's actually an open question. There, probably what you mentioned before, becomes more relevant that when you shift from moderately elevated triglycerides towards LDL and you shift basically one risk of cardiovascular disease to another one, then I'm not so sure whether you will see really benefit. That's why I think it would be very interesting to see an outcome trial, but then we speak about a huge patient number.

So our approach is more puristic. Please, Erik.

Erik Hultgard from DNB Carnegie. Two questions on sepsis, if I may. First, I was curious about what you think about how far you could get in terms of efficacy if you push doses higher of Gamifant. Did you measure, for example, interferon gamma depletion in the different dose cohorts?

And then secondly, it looks like mortality rates, the curves continue to separate over time. So is it an assumption that is valid that we would see a greater delta at the 120-day readout compared to 30 days?

Well, you understand very well that as a treating physician, I would like to maximize the efficacy of the drug. And of course, all the considerations that you have mentioned about the change of dosing and how we need to modulate that is something which is a topic of discussion with the regulators. But as a scientist, I cannot make any assumptions. But I hope that in the very end -- and of course, I work heavily on that, but in the very end results will speak on their own.

Well, I think Mattias was next, yes.

Mattias Häggblom, Handelsbanken. So firstly, for Professor Giamarellos. The heatmap slide suggests at least to me that placebo had a worse SOFA score at the beginning of the trial compared to the high-dose group. But apparently, given your response to an earlier question here, that was not the case. So if I ask you to speculate, what may then explain why mortality in placebo was higher than historical studies in this patient population have suggested?

And then secondly, for Professor Parhofer, brutal effect size by olezarsen in this patient population. The sponsor in the U.S. apparently is planning for a pricing of $15,000 to $20,000 per patient a year. Is that a price point that could resonate with the German reimbursement system? How should I think about that?

Should I go first?

Yes, please.

So your question brings me back to the way I started my presentation. In order to understand what this is about, you need to understand the term precision. Precision means that patients are different. Their organ dysfunction is coming from an immune dysregulation, which we call endotype. And here, we group patients into endotypes. Not all patients have the same risk for death. There are endotypes with risk of death of almost 70%. The macrophage activation-like syndrome, both in the hands of researchers from America, in our hands, in researchers from the Netherlands, has a death rate of 70%. Sepsis-induced immunoparalysis, which is the most common, has a death rate of 30%.

When it comes to IDS, the death rate is 50%. So it has nothing to do with if the standard of care is correct. It has nothing to do about the mentality of treating physicians. It is the first step all of us we need to do to understand what precision means. So we cannot compare what is the outcome of a patient population, which is framed to be guided for its destiny by an endotype to what is happening in the global patients with sepsis.

Professor Parhofer.

Well, I mean, as a clinician, as a scientist, I would say, yes, these people -- a lot of people would benefit from such a therapy. But then again, you have to look at what will the label be, right, which will probably reflect the studies. But then, of course, there will be regulatory aspects. And I think the regulatory bodies in Germany at least are very much keeping in mind what would be the price. So it's very difficult to predict. But I mean, these are -- the label and the regulatory aspects will probably determine to what segment of the population this treatment would be available.

Yes. We have performed, obviously, as you would, pricing studies, which we will not divulge today and where we feel that we have a product, at least that will allow us to have the necessary margins to try. But the guarantees, and we will have -- we will obviously look forward to the dialogue after registration with the relevant reimbursement authorities. But we have prepared health economic cases as you would do so. Sorry, next one, please.

Kirsty Ross-Stewart from BNP Paribas. One also for Professor Giamarellos. On the frequency and kind of process of doing IDS biomarker testing within hospitals on sepsis patients. Just any color on how frequently that's done now given the novelty of the endotype? And if there's any differences we should think about or know about kind of globally? And how long that process takes, how widely used it is, that would be super helpful.

And then, Henrik, maybe one for you on margins. Just wondering if you can put a little bit of color on the shape between kind of now and 2030. Obviously, there's scope for accretion, and that's great to see. But how should we think about the cadence of that? Is it steady accretion from here to the end of the decade? Or are there some years and some launches where you would encourage us to think about slightly higher investment? And maybe in the context of those launches, where do you feel like the biggest build-out is needed and where are the synergies?

Maybe Professor Giamarellos first.

So thank you for the question. In the way we are working so far, from the moment a sample arrives in the lab until you get the results and the classification into endotypes, it takes roughly 3.5 hours. The idea throughout all the development of the project is to make this shorter and of course, to make it available in many more hospital settings. This is something on which we are heavily working on.

Henrik?

Yes. So in terms of SG&A, in particular, so the answer is that in the earlier years, it will increase, earlier years, not only the first. And in the outer years, it will decrease. And when it comes to the impact and the size of the different opportunities, so in the short term, gout is the most impactful. But that is, of course, also in the slightly longer term, the area where we expect to see synergies.

Next question?

Harry Gillis from Berenberg. I have a couple for Sobi. Just if you could flesh out in any way you can a little bit more on your sort of peak sales or the assumptions underpinning your peak sales for Tryngolza and pozdeutinurad. I'm just thinking Ionis obviously recently doubled their peak from [ $1 billion to $2 billion ]. How you're thinking about your greater than [ $1 billion ]? It seems like there could be room for upside there. And maybe is this use really just in those 300,000 refractory patients?

And then on the gout side, I mean, KRYSTEXXA is doing over [ $1.3 billion ] in the U.S. alone in third line plus. Surely second line, I mean, you could be doing a lot more than [ $1 billion ] globally.

We like, obviously, to be ambitious, obviously, as you know. But at this point of time, we thought we guide at this level because it's sufficiently indicative. But with regard to Tryngolza, I think given the dialogue that we are going to have with payers and then also the -- and the total reimbursement situation in Europe, if we get the right feedback, I think this will feel already very good. There's a material opportunity, obviously, outside of Europe, no question and large patient populations, and this will make us think further. But I think at this point of time, we don't want to guide more. There's obviously just the mathematics would dictate you look at the epi data that there is a significant opportunity beyond. But this is -- I think, it's premature at this stage.

And with KRYSTEXXA, the way we looked at this, not very long ago, when you think of NASP, obviously, people thought is this really a product that can reach a certain level. Rob was talking about CKD patients. You look at the methotrexate exclusion criteria, there's already a very nice part of patient population alone if you would capture this one out of the 15,000, this is more than we need to achieve our proposition for NASP provided, obviously, provided that these patients want to have this fast -- experience this fast decrease of sUA for others, pozdeutinurad is obviously going to be a fantastic opportunity, and we clearly see a much larger opportunity for pozdeutinurad than for NASP, it's clear just by the simple math.

And also here, we have performed, obviously, patient surveys. We have performed -- we have done some research with regard to reimbursement as well. And we think that we have a clear picture, but that's not for today either. We want to make sure that we have stellar data. As you have seen, this could be the first oral treatment that will demonstrate tophi reduction. I mean, think about that for a second, what this could mean. And therefore, we take it one step at a time. I'm looking forward to the data presented in May. First Phase III readout, then we look at the next. And then I'm sure we can answer your question with more authority.

Other questions? Next, no, there's somebody in behind. Yes, please, sorry. I'm sorry.

Ben Jackson, Jefferies. Two for me, Henrik, probably most likely towards you. About the risk corridors on the top line, can you talk about what scenarios are driving the bottom end of that, the top end of that? And is it fairly binary? And also how you think about risk adjustment in general when you're setting that aim for 2030?

And then similarly, along a similar line there, you've been asked about pricing a lot. It's probably where the highest sensitivity is because you've given good details about patient populations and what you're targeting. But how do you think about when going from a rare disease population to a very broad population with that price changing? Is there any kind of thought process you can provide us in terms of color that allows you to underpin the assumptions you've given us today in terms of peak sales?

So with regards to the risk corridor, of course, we have worked with different scenarios with high potential or lower potential, and we have found that corridor getting to some kind of a midpoint for our SEK 55 billion adjustment. The SEK 55 billion adjustment as such is also risk-adjusted, of course.

And pricing is obvious. If you move from an FCS indication with an established price level like where Waylivra is today to an indication now broader indication, sHTG, that has to have consequences on the price. And that's what we modeled, obviously, based on the feedback that we got, it has to be a very different price level. And that will mean very likely that our FCS market is going to shrink, but we are obviously looking forward to a much larger opportunity in sHTG. We are clearly aware of this.

George [indiscernible] from ABG. So I have two questions. I think perhaps for Henrik. So on revenue guiding, you said no additional business development. But regarding R&D, is there any additional business development in those 11% to 14% until 2030?

No, that is also based on current portfolio. But of course, we don't know what current portfolio is in the outer years. So it's been topped up. So you can say that there is significant room for new projects there on the R&D line.

And then secondly, I'm curious if you can provide any flavor on how you arrived at the peak sales estimate of SEK 10 billion for Gamifant in interferon-gamma driven sepsis. Is there any risk adjustment there? Or anything else that explains why the figure isn't higher? I mean, isn't the sky really the limit here?

Yes. No. Some people believe it's the largest product in the world. And let's say -- but more seriously, I think it's a huge opportunity, clearly beyond SEK 1 billion. There's a risk adjustment taking place. And let's say -- but at this stage, let's get the phase of the pivotal trial under the belt. We get the pivotal trial, then we will all feel much more excited and we will be happy. The product, if it works, I mean, I think Professor Giamarellos has pointed it out, the difference you saw already in this granted small cohort, but consistently is spectacular. So it can make a huge difference on a much larger scale, but this is not the time.

Let's -- this is risk-adjusted, but it's not in our forecast. But we will -- if it happened to be in our planning cycle, we will also be quite comfortable to take advantage of it because we obviously will pay for the trial in the meantime. But it's a very material -- I mean you just do the math. I mean it's just spiraling.

Shirley Chen from Barclays. My question is about the further development of Gamifant in IDS. So in future -- for future trials, what level of interferon gamma pathway activation or what level of CXCL9 do you perhaps going to consider to be biologically meaningful target for Gamifant? Would you consider using that as a mandatory inclusion criteria to be able to capture the right patient population so that they can get benefits from the drug?

And also really get inspired from the heatmap data. So if we think sepsis as a heterogeneous disease and break IDS into different disease stages, where do you believe the window closes beyond which Gamifant is likely too late to be effective?

Well, thank you very much for both these questions, which are really insightful. The idea of IDS is to be a pro-inflammatory endotype. Pro-inflammatory endotypes are the endotypes of sepsis, which they have most of lethality, going beyond 40%, reaching even 50%. So HLA-DR is one of the elements in other terms, have HLA-DR more than -- at least so far, this is what our indications, 8,000 receptors per cell, so that there is no risk that you bring the patient into risk for secondary infection. That's one part.

The other part is that our data so far from the Phase IIa trial, they demonstrate that CXCL9 more than 2,200 kilograms per ml is the concentration which we need to go for. What is very interesting is your second question about the time window. And for those who probably are asking themselves, what does that mean? That means that from the moment you find these biomarkers, how early you need to give treatment. And actually, the way we have done that in the Phase IIa trial was not -- we trust on biology and not on the clock.

In other terms, if we find the biomarkers increase, we judge from the biomarker. That means that the endotype prevails, the endotype will destroy the patient. In other terms, it's pro-inflammatory. It's always active. Of course, it would be ideal to start treatment at 0 time. But for a pivotal trial to be of value, it should be pragmatic. And pragmatic means that if in some years from now, a physician who's not an expert, has reached to the drug, he should be able to give the drug to save his patients and not to watch the clock how much time has passed since the patient arrived at the hospital.

So the real validity of the Phase IIa data is that they are pragmatic. It is the first time in the history of sepsis, where there was no time frame from the moment of onset of sepsis until start of treatment. And this makes them clinically meaningful.

We have time, I think, for one more question. I can't decide now who is...

Christopher Uhde. A question on then Gamifant next steps. Essentially, how could a Phase IIb look? Are you thinking about the same dose levels, different dose levels, adaptive designs? And yes, how quickly can you move? And do you have the bandwidth to do that now? Or do you need to add to it?

Professor Giamarellos?

Well. Of course, there is a suggestion, which has been addressed to the regulatory. But of course, we understand that several times, the suggestion is nothing more coming from experts. What is needed is the wisdom of the regulatory, EMA and the FDA. And of course, we will obey into their suggestions in order to bring something which, as I said, is realistic, is pragmatic and can save lives.

Yes. So I'm really awfully sorry that the format of today does not cater for and doesn't allow for all questions. We have, obviously, our IR team, as you know, headed by Gerard. So if you have further questions, please refer to them, and we will make time available from a management perspective. So I'd like to thank you for your attention.

I'd like to thank the speakers for being available and making a trip and sharing with us their deep insights. I hope you found it useful. We are clearly excited, as you can see, about our future. With Henrik, we have already agreed to create space in our P&L that we already had to order one size of our suit smaller so that we feel we will comply with this understanding of lean management. And -- but on a more serious note, when you -- as we are in these days in the times of the Olympic spirit, I have had a meeting many years back with the goalie of the U.S. hockey team. And for some of you, you may remember, 1980 was the time where the Amateurs of United States won against the Russian at that time, a seemingly unbeatable team. And the goalie told me, he was a motivational speaker during one of our events, and he said to me, Guido, just make one thing you have to make sure, make sure that your memories will never be larger than your dreams. And I think this is what characterizes today.

Sobi, we have a lot of dreams, but we have a lot of substance as I hope we could convince you to take this company to the next step. Thank you so much for your attention. Wish you a fantastic day. Thank you.

Ladies and gentlemen, welcome to the Sobi Q4 2025 Report Conference Call and Live Webcast. I am Valentina, the Chorus Call operator. [Operator Instructions]

The conference is being recorded. [Operator Instructions]

The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to Guido Oelkers, CEO. Please go ahead.

Yes. Thank you, Valentina. Hello, everyone. This is Guido Oelkers, CEO of Sobi. We are delighted to welcome you to the fourth quarter and full year 2025 conference call for investors and analysts.

We posted this presentation to sobi.com earlier today. We would like to remind you of usual provisions on statements about expectations and projections of future events. Unless otherwise stated, we will make comments mostly relate to the second quarter at constant currency or fourth quarter, apologies, and in million Swedish krona.

Today, we plan to cover the key aspects of our Q4 report. I'm joined by Henrik Stenqvist, our CFO; and Lydia Abad-Franch, Head of R&D and Chief Medical Officer.

We plan to review the presentation first and then have a question-and-answer session until around 2:00 p.m. [Operator Instructions]

So with this, let's go straight to the key takeaways for the fourth quarter. It has been a quarter for Sobi along various dimensions, financially, strategically and scientifically. And I'm pleased to say that we demonstrated significant progress along all these 3 areas in 2025.

In the fourth quarter, we delivered 16% revenue growth at constant currency, driven by exceptional 37% growth of our strategic portfolio. This reflects the consistent execution we have shown all year and the fundamental demand for innovative medicine we bring to patients. For the full year, we delivered 15% growth at constant currency with a significant contribution from every region, and we maintained a 40% adjusted EBITDA margin driven by demonstrated operational excellence and also targeted cost alignment.

We also strengthened our immunology, respectively, gout franchise with the acquisition of Arthrosi, adding a late-stage gout asset that aligns perfectly with our long-term strategy and positions Sobi for leadership in a large underserved patient population.

We received EU approval of Aspaveli in nephrology with a broad label that we believe will reshape the treatment in both C3G and IC-MPGN. A strong quarter, a strong year and a business entering 2026 with strong momentum.

We are excited to have launched Tryngolza in FCS in Germany, while the main indication will be sHTG or as we called it previously, MCS above 880 milligram per deciliter expected, by the way, in Q1 2027, the launch, we are happy to make the drug available and inform the medical community about this breakthrough molecule.

In addition, we achieved positive proof-of-concept data for Gamifant in interferon gamma-driven sepsis, which is an area with a high unmet medical need.

Let's turn to Slide #5. Let's have a closer look at the Q4 performance. Growth across the -- it was broad but also balanced. Each region contributed as earlier outlined, and our key products continued to scale effectively.

Our strategic portfolio is now the central engine of Sobi's performance, representing a shift towards high-value, high-innovation assets, now representing 65% of our total revenues in Q4.

Please turn to Slide #6. For the full year 2025, Sobi delivered 15% growth at constant currency. This is a meaningful broad-based growth across all therapeutic areas, hematology, immunology and specialty care. Each of these pillars contributed significant value and each has multiple drivers still at early stages of the life cycle.

Our strategic portfolio has become 59% of our total business and is increasing as the Q4 numbers indicate. Our strategy to deliberately shift towards best-in-class next-generation therapies is paying off. This performance provides a solid foundation as we now move into 2026 with a richer pipeline, more launches and more geographic expansion.

Please turn to Slide #7. Turning to Altuvoct as true standout in our portfolio. In Q4, Altuvoct exceeded SEK 1 billion in sales and full year hemophilia A revenues surpassed SEK 6.8 billion. This trajectory reinforces Altuvoct as a best-in-class therapy and one that is increasingly becoming standard of care in many markets.

Our regional launch strategy foresees a rollout in 3 waves. Wave 1 includes the early launch countries, the DACH region and Spain; wave 2 with France launching in Q4 and Italy launching in January, is just beginning to unlock its full potential.

These are major hemophilia markets, and we are only at really early stages of penetration. And Wave 3, the remaining European countries and international markets represents an additional runway of growth over the next several years.

Please turn to Slide #8. Doptelet is another strong performer for Sobi quarter-on-quarter. It continues to deliver in Q4, and it grew 47% at constant currency. Doptelet has become a truly global brand with performance across Europe, North America and international. One should highlight Japan that launched in Q4 and demonstrated impressive uptake. As more international markets come online, we expected Doptelet's growth to remain strong, whilst we may see some moderation in the U.S. growth due to the Promacta generics in 2026.

Please turn to Slide #9. Aspaveli reached an important milestone in January with the EU approval for C3G and IC-MPGN. Our launch strategy in Germany is underway. A recent survey has shown that the awareness on pegcetacoplan's best-in-class efficacy has rapidly grown amongst nephrologists in Europe.

The recent publication of the VALIANT data in the New England Journal of Medicine was very helpful in this regard. However, it will take a while until this indication will change the economics of Sobi as we are building a new market with specific requirements prior to use and will obviously follow the usual launch sequence in Europe.

Notwithstanding, Aspaveli will become a key growth driver for Sobi during the coming years, and we are very pleased with the progress year-to-date. Please turn to Slide #10. Now turning to Beyfortus, where we see a decline in Q4 revenues compared to a very strong Q4 2024. Seasonality and inventory fluctuations have influenced the sales evolution on this category, but none of these dynamics has changed our view on the long-term adoption curve or on the fundamental demand outlook.

While there has been some changes to the overall vaccine policy, it is important to remember that the guidelines for RSV has remained as before. Beyfortus is still recommended for all newborns unless the mother has received a maternal RSV vaccine. Support from the pediatric associations and U.S. health care providers remain strong as does the continual real-world evidence readout from Beyfortus. Real-world evidence across 85,000 infants show an 83% reduction in RSV-related hospitalization.

We wanted to take a pulse on how prescribers are feeling about the next RSV season, and our survey included more than 100 U.S. physicians. 80% expect RSV immunization volumes in 26 out of 27 to match or exceed the current season and 90% expect Beyfortus to remain the product of choice, indicating a strong preference for the treatment, a perspective that appeared to be supported by recent reports.

Please turn to Slide #11. Gamifant has accelerated growth in Q4 again. We saw 70% growth in Q4, driven by the U.S. launch in MAS. Gamifant is the first approved therapy for macrophage activation syndrome and education efforts are resonating strongly with hematologists, oncologists and rheumatologists. We now completed filings in Europe and Japan for HLH/MAS, which will significantly broaden the patient reach and accelerated international growth.

We're excited about Gamifant's expansion over the next 2 quarters and look forward to the progress in 2026. You will hear more from Lydia on exciting developments in sepsis for the potential utility of Gamifant in -- as an interferon gamma scavenger.

Please turn to Slide #12. Looking ahead, Sobi is entering an unprecedented launch cycle. Between now and 2028, we expect 6 high-value medicines to reach the market by 2028. The acquisition of pozdeutinurad strengthen our long-term position in gout, while Tryngolza also positions us for leadership in severe hypertriglyceridemia. Our latest launch, Aspaveli in nephrology, targets an underserved patient population with substantial scientific and commercial potential.

These 6 launches will radically transform Sobi's trajectory well into the 2030s. To realize this potential, the potential of these assets, we need to commit significant resources for development, medical and commercial efforts in 2026. These commitments have been partially funded by our annualized impact of our cost alignment program in 2025 and business growth.

However, it will also moderate our expected EBITDA margin in 2026. Please turn to Slide 13. As we look forward to 2026, our strategic priorities are pretty clear and are the following. We will continue the strong rollout of Altuvoct, expand Gamifant in HLH/MAS in the U.S., execute the European launch of Aspaveli in C3G. We are preparing for the NASP launch in the United States. We will advance Gamifant into the next phase of IDS.

We will continue to progress our development programs for Vonjo and Altuvoct. And importantly, we plan to integrate Arthrosi therapeutics and conclude its Phase III program. These priorities position Sobi for rapid, sustainable growth, not just in 2026, but also propel Sobi into the next decade. However, the size of the opportunities correlate with the necessary commitment.

Coming from a very strong financial base and profitability in 2025, trade-off decisions between today, tomorrow and tomorrow after tomorrow needed to be made. Henrik will explain the economics of these choices in 2026 in more detail during this call at a later stage. However, it is a happy problem to have, and we are excited to progress such an impressive number of projects of transformational nature.

Hence, I'd like to now hand over to Lydia, who will share her perspective from an R&D's perspective of our portfolio. Lydia?

Thank you, Guido, and hello, everyone. So let's start with the pipeline milestone on the next slide, please. We are carrying a very strong momentum, and here is what happened in the fourth quarter. Aspaveli in C3G and primary IC-MPGN received CHMP positive opinion in the European Union and was submitted to PMDA in Japan with a pivotal VALIANT study published in the New England, and I will come back to this asset in more detail. Gamifant moved forward in HLH mass with filings in both Japan and Europe.

We also got positive top line data for Gamifant in interferon gamma-driven sepsis that enable us to move forward with the program. And the Tryngolza pivotal data from the CORE 1 and CORE 2 studies in severe hypertriglyceridemia was also published in the New England. We started building our R&D hub in Japan in 2022 and the submissions of Aspaveli and Gamifant in parallel to the European submission show that this approach is paying off and will enable us to earlier launches.

Finally, the 2 New England papers published last quarter also demonstrate that Sobi, together with our partners, are at the forefront of science, driving strong clinically meaningful data. Let's now have a deeper look at Aspaveli in nephrology, Gamifant in IDS and Tryngolza in severe hypertriglyceridemia.

Next slide, please. The global launch of Aspaveli in nephrology is now taking place. In 2025 and January this year, it was approved for both C3G and primary IC-MPGN in the European Union, Australia, Brazil, Saudi Arabia, South Korea and Switzerland. We are also having ongoing submissions in Japan, U.K., Canada and other global markets.

There is a very strong interest in the medical and patient community. From recent insights among physicians who treat these diseases, the vast majority believes that complement inhibition will lead to earlier diagnosis and screening strategies and will reduce the need to initiate immunosuppressive therapy.

We have also positive reports of the first infused uses in Brazil and South Korea. The rollout of this on-body device to simplify the infusion will take place in parallel with the launch of the nephrology indications. The Phase III VALIANT data published in the New England, together with the recently updated 1-year follow-up is very encouraging.

We plan to publish further long-term data from our Phase III extension trial, and we are setting up a Phase IV clinical program to create further evidence on the use of pegcetacoplan in real clinical practice.

Next slide, please. Turning to Gamifant in interferon gamma-driven sepsis. This could address a significant unmet medical need and an important burden to health care systems. Sepsis is life-threatening medical emergency, which arises when the body's response to infection causes injury to its own tissues and organs. This can lead to shock, multi-organ failure, disability and death, especially if it is not recognized early and treated promptly.

Sepsis is a leading cause of death worldwide, responsible for about 1 in 5 deaths. Almost 50 million people suffer from this condition and 11 million die from it. It also leads to high health care costs with an estimated $60 billion of hospital costs in the U.S. alone.

The Hellenic Institute for the Study of Sepsis or HIS, identify an endotype of sepsis, which is characterized by elevated CXCL9 and interferon gamma and an increased risk for 28-day mortality. We investigated this subset of sepsis patients in a research collaboration with HISS in a study called EMBRACE. The EMBRACE exploratory Phase IIa study has now shown an improvement in organ dysfunction and patient survival with emapalumab treatment.

This top line data supports the proof of concept and allow us to advance the development of Gamifant for this indication. We have started initial interactions with regulators and we'll discuss the next steps for clinical development with them. The data will be presented at the ISICEM Conference in Brussels next March, and you'll hear about this exactly new indication at our Capital Market Day on February 18.

Next slide, please. Another example of our scientific advancements is Tryngolza in severe hypertriglyceridemia. In November, the New England published the CORE 1 and CORE 2 studies, the pivotal data of olezarsen in this indication, and it was simultaneously presented at the American Heart Association Conference. Severe hypertriglyceridemia is characterized by triglycerides levels above 500 milligrams per deciliter.

It's a very severe condition. Patients face an increased risk of acute pancreatitis, which is a medical emergency that frequently requires hospitalization. It is associated with higher morbid mortality compared to acute pancreatitis of other causes. CORE 1 and CORE 2 evaluated olezarsen added to standard of care. The placebo-adjusted triglyceride lowering achieved in this trial was approximately double what is currently achievable for patients with severe hypertriglyceridemia.

It resulted in a reduction of triglycerides up to 72% with a durable response at 12 months. The primary purpose for severe hypertriglyceride lowering in severe hypertriglyceridemia is basically to reduce the risk of acute pancreatitis, which can be life-threatening. Current therapies have more modest triglyceride lowering effects in these patients and have not been proven to reduce the incidence of pancreatitis.

The CORE 1 and CORE 2 data demonstrated that olezarsen reduced the rate of acute pancreatitis by 85% in patients with severe hypertriglyceridemia, meaning that olezarsen is the first and only treatment that reduces acute pancreatitis risk in this group of patients.

This makes a strong case, which will be the basis for our European submission later this quarter in patients with severe hypertriglyceridemia with triglyceride levels above 880.

Next slide, please. Looking ahead, we anticipate continued momentum with the major regulatory submissions in the U.S., Europe and Japan as well as key clinical data. In the first half of 2026, we plan for the NASP FDA decision in June, the EU submission of Tryngolza in severe hypertriglyceridemia above 880 and the LOTIS-5 data readout in relapsed/refractory diffuse large B-cell lymphoma.

Later in the year, we will see initial study data from the Altuvoct FREEDOM study, including important joint health data, the Japanese regulatory decisions for Aspaveli in the nephrology indications and Gamifant in HLH mass. And we do expect EU CHMP opinion on Gamifant late in the year or early in 2027.

With that, I would like to hand over to Henrik. Next slide, please.

Thank you, Lydia, and hello, everyone. So please turn to Slide 21. And we will now take a look at some key financial metrics for the quarter. So in Q4, our revenues of SEK 7.8 billion correspond to a revenue growth of 16% at constant currencies. Hematology increased by 25% at CER, driven by the strong launch of Altuvoct and continued progress in Doptelet across all 3 regions.

In immunology, we saw strong double-digit growth in both Gamifant and Kineret offset by lower RSV royalties. And in Specialty Care, we initiated the launch of Tryngolza in the FCS indication. If we look at the table on the right and the adjusted gross margin, which was 81% in the quarter compared to 78% last year. We saw an improvement in gross margin from positive product and country mix effects, but this was somewhat offset by Beyfortus royalties and FX impacts.

Operating expenses, excluding nonrecurring items and amortization for the quarter increased by 3% at CER compared to Q4 '24. SG&A, also excluding nonrecurring items and amortization increased by 6% at CER, driven by launch and prelaunch costs for Altuvoct, Aspaveli in nephrology, NASP and Tryngolza. And this was partially offset by lower costs across Vonjo, Doptelet synergies and Elocta and the cost savings initiative we outlined in Q2. R&D expenses declined by 2% at CER, excluding nonrecurring items, mainly due to NASP programs that are now complete as well as the cost savings initiative from Q2.

And this was partially offset by development programs in Vonjo and Gamifant. And as a result, the adjusted EBITA for the quarter amounted to SEK 3.2 billion, equal to a margin of 41% compared to 34% for the same period last year.

Operating cash flow for the quarter was close to SEK 3 billion compared to SEK 1.8 billion last year, driven by improved operations. Our net debt at the end of the quarter was about SEK 10 billion and a net debt-to-EBITDA ratio of 0.9x. This does not reflect the expected acquisition of Arthrosi, which is planned to add about SEK 9 billion of debt or less than 1x EBITDA.

Next slide, please. If we now turn to full year performance, we delivered strong profitable growth in 2025, and we exceeded our updated guidance from Q3 on revenue and margin. For the full year '25, we achieved just above SEK 28 billion in revenue, equal to growth of 15% at CER. And this growth was driven by double-digit growth in each of our 3 regions, outlining the advantages we have in our portfolio and geographic diversification.

From a product perspective, Altuvoct, Doptelet and Gamifant were the main drivers, more than offsetting lower revenue from RSV and Vonjo. In 2025, we saw 0.8 percentage points increase in gross margin driven by products and country mix. And the adjusted EBITA margin for the full year was 40%, an increase of 4 percentage points versus last year as we saw strong operating leverage with revenue growth of 15% and OpEx growth of 4% at constant currencies.

Within R&D, spend decreased by 3%, mainly due to lower NASP development costs as well as the impact of our cost control measures. And in SG&A, OpEx increased by 8%, driven by launch of Altuvoct, but also prelaunch of Aspaveli in nephrology and NASP as well as higher activity for Gamifant. And these activities were partly offset by the cost measures we put in place in Q2 as well as generally a rigorous cost control.

Please turn to next slide, and we come to the financial outlook for the full year '26. And as usual, this outlook is based on revenue growth at constant exchange rates and adjusted EBITDA margin. For the full year 2026, we anticipate revenue to grow at low double-digit percentage at CER and an adjusted EBITDA margin in the mid-30s percentage of revenue.

On the revenue guidance, we certainly expect continued progress with our existing commercial portfolio, where Altuvoct is now approved and reimbursed in all major European markets, and we expect the product to continue to be a major growth driver in 2026 as markets still have plenty of room to grow. And we expect additional revenue benefit in the launches of Aspaveli in nephrology and NASP although mainly in the second half of the year due to the NASP PDUFA date expected in late June as well as the phased launch of Aspaveli across European markets as we get reimbursement country by country.

Beyfortus, as before, remains difficult for us to forecast since we are not running that business. But we don't believe that fundamentals have changed with regards to competition, recommendations and reimbursement. In regards to our EBITA margin guidance, I want to highlight some key investments that we will have in 2026 that are new or accelerated compared to 2025.

First, we have the prelaunch and launch costs for Aspaveli and NASP, both visible in 2025, but set to accelerate in 2026. Second, with the strong data from the pivotal Phase III trials in Tryngolza in SHTG and the opening of a large market opportunity, we will have costs in 2026 related to filing and prelaunch activities of that indication.

Third, we expect to finalize the acquisition of Arthrosi. And if so, we will be completing 2 ongoing Phase III studies and prepare for regulatory submission, adding those costs to our R&D line. And finally, we've included a continued development of Gamifant in IDS. We are still in discussions with health authorities, but we have assumed considering the positive signals from the Phase IIa study that we will take it to the next phase of development and further details are to be confirmed.

All these investment areas will be partly offset with reallocation of resources and cost containment in the rest of the business, including the full year impact of the cost-saving initiatives from 2025. And to conclude, it is, of course, critical that we adequately invest in these new areas in 2026 to position Sobi for the future.

And with this, I hand over to Guido. Thank you.

Thank you, Henrik. Please turn to Slide #25. To summarize, we not only demonstrated strong results in Q4 and for the full year in 2025, but we also achieved significant pipeline milestones that bolster our medium- and long-term outlook. We are broadening our portfolio in nephrology, immunology and specialty care, and we continue to bring transformative therapies to patients. Whilst we have shown you a more conservative perspective of our financial outlook in 2026, we do not want to miss the opportunity to familiarize you with the potentials that we will realize during the forthcoming years.

This will require more time than we typically have during an earnings call. Hence, we would like to share our thinking of this exciting innovative portfolio and our midterm outlook during the Capital Market Day with you here in Stockholm and in a live webcast 2 weeks from now. We will be joined by our clinical experts in areas such as gout, sHTG and Sepsis. We are very much looking forward to the dialogue as we transition Sobi into the next phase of economic transformation.

With this, we can now open the line, and we are happy to answer your questions. Thank you.

[Operator Instructions] The first question comes from Christopher Uhde from SEB.

Christopher Uhde From SEB. So I guess, first for Lydia, on Gamifant, you've talked about potentially resubmitting this product for years, I guess, to the EC. And so how sanguine are you on approval now? And I guess, if positive, what's -- if you're feeling positive about it, what's different about it this time around. And then I don't know if you're able to say on embrace in IDS, but did you see a dose response or reach a maximally tolerated dose. So that's the first question.

The second one is just on the Altuvoct. Is there any stocking in hemophilia A in general across both products? And how does demand in France look like? Is it like Elocta and Hemlibra, do you have any indications yet?

Christopher, this is Lydia. So your first question was on Gamifant in Europe, the submission on the HLH mass indication, if I'm correct. And then the second was on IDS. So for Gamifant in secondary HLH mass, Obviously, the data is based on the clinical trials, both Study 14 and Study 06. And you know that we got approval in the U.S.

So we went through the review and all the approval process with FDA. So we feel confident that this is going to be something that is going to be well received by regulators also in Europe. And we just submitted in December. So it's something that we are now in the starting phase of the discussions. When it comes to IDS, we will be presenting the data, as I mentioned, at the ISICEM conference in Brussels, which is the intensive care conference is the 45th Congress. So there, we will be presenting the data.

You know this is a proof-of-concept study that it was not powered for statistical significance. But what we see is that there is a clear signal on benefit both in organ dysfunction improvement and also in terms of mortality. But I cannot provide more details at this point in time because we will be presenting the data at the Clinical Congress, and we will be sharing also some details at the Capital Market Day. To Guido, I think the next one on...

Yes. And with regard to Altuvoct, there has not been any material stocking in the extraordinary course. And the good news is even though France is heavily penetrated, obviously, by nonfactor therapy, the launch uptake was very encouraging. So we have a very positive momentum also in France that reflects the launch curves actually of previous countries.

So it's not just an inverted commerce, tremendous German success, but it's carried and the first signals of the French launch is very, very encouraging. And maybe just be rounding it off, we wouldn't file in Europe if you would not think that there's a promise. So maybe we could move then to the next question. Thank you.

The next question comes from Gonzalo Artiach from Danske Bank.

Gonzalo Artiach from Danske Bank. First one is on Altuvoct. Very strong quarter. I guess that it's reflecting that the drug is already out there in the main EU markets. But have you felt any plateau in any of the main initial markets? And can we say that your initial peak sales expectations were too low and now you're looking to a higher peak sales goal? And my second question is more of a broad one. It would be great if you guys could shed some light on the type of organization you have to build around Tryngolza. How many people do you have to add to the team for this launch during this year?

Yes. Thank you for your questions. I mean we have seen now in Germany market shares of above 60% in prophylaxis, well above. And obviously, numerically, it just becomes more difficult because there seems to be a natural ceiling and to grow at the same exponential rate, but we're seeing continuous explosive growth, obviously, in the earlier launch countries.

So we are not seeing a plateau on a total level whatsoever. But obviously -- and we don't see a plateau yet in the earlier launch countries. We just see that the growth is not as rapid because, yes, numerically, it just becomes more difficult.

And then with regard to Tryngolza, right now, we obviously -- this is -- we provide -- we set up an organization in the light of the SCS launch and preparing the communication. So this is a -- I mean for the company we are, is a significant team, but it's by no way still comparable to what Ionis has indicated at this point of time for the U.S. But it is enough to cover well the 600 lipid centers in Europe, which is the primary focus of us today. And we will ramp up the organization.

I mean we have a very good sense, let's say, as we then get closer to the launch of the sHTG indication above 880 milligram per deciliter. So we are not setting out, but we will be competitively positioned. And the other thing is Tryngolza is not a product that Sobi will not be able to do. This we can see already because the main decision-making is today in these lipid centers.

So we will have to build a more peripheral referral system in Phase I. And at one stage, I think you have to assume that the treatment is more democratized and then you're talking obviously broader teams and how we solve this -- in that phase, we have to figure out. We know how to do it. I mean we have sized it already very clearly. So it's -- but it's not a skyrocketing calculation, but it is something we want to look at the right time. Next question maybe.

The next question comes from Erik Hultgard from DNB Carnegie.

I have 2, if I may. First on Aspaveli. I was wondering how much -- obviously, there is a huge opportunity in commercial within rare kidney. But I was just wondering how much we should expect Aspaveli to contribute in 2026, given some of the bottlenecks that you highlighted, including market access and other requirements for dosing such as vaccination.

Then my second question relates to Gamifant and if you could comment a bit on the sales split in the U.S. between primary and secondary HLH and what penetration level you have achieved so far in mass?

Thank you. Yes. No, I mean, the -- when you think about the rare kidney, I mean, we said that it will probably not this product is not going to change the economics of Sobi at scale in '26. And I think it's just by the launch sequence -- by the virtue of the launch sequence, it's by the fact that you need to go through a vaccination schedule that will take some time, and we will need to activate patients for this new therapy to actually be referred mostly in those areas from the community nephrologists to the key centers. That will take -- this activation will take a bit of time.

But nonetheless, we would expect to seek to create in Europe a very significant number of patients that is ahead of what we have achieved year-to-date in PNH, yes. So that gives you a feel so that we believe that this is an important indication. Now many of these patients will not start on January 1.

So that's the reason why the economic effect will be more moderated. But by no means are we holding back or believe that this is a small opportunity for Sobi. So -- but it becomes material then in the following year '27.

And with regard to Gamifant, essentially, it's -- today, it's probably more like 50-50 primary, secondary because we had also some patients in the past. But -- and that basically tells you that we -- of the potential in secondary, we probably have less than 50%. And this is in MAS. And that would not include obviously, utility of Gamifant in other areas. So our -- we are by far not there exploiting the full potential of Gamifant, Erik.

The next question comes from Mattias Haggblom from Handelsbanken.

I have 2 questions, please. So firstly, on RSV, I'm curious to better understand what's embedded in the guidance beyond the survey you referenced. So royalty rate is going up in the year, I guess we should assume 27%. Weakened royalties are dollar-denominated, I would presume. But then with regards to penetration in the next RSV season and the new vaccine schedule, your partner, Sanofi, last week said, and I quote, "what extent the vaccine will create confusion for parents and physicians, it's too early to say."

So is it fair to say that you are more optimistic than Sanofi? Or is your guidance helped by your partner? And then secondly, for Henrik, consensus appears to model roughly SEK 2 billion OpEx increase in 2026. Is there any way you can help us understand to what that -- to what extent that captures your current plans?

Yes. Maybe I'll start with the easy bit. I mean, we -- to be honest, for us, Beyfortus, we have a couple of pluses. We see an increase of our royalties rate. We also see that 2025 was artificially negatively influenced by various factors, late onset of season. I mean you just saw the recent surge of RSV again in January and by CDC data.

So clearly, it's an unusual season. But also clearly, as clarified by various parties, there was an inventory effect probably not insignificant. So by definition, you would see a positive out of this. And this has to be then balanced with a potential effect of competition and with a potential effect of muted immunization rate because of the ongoing debate in the United States.

Now what we try to clarify is that at least the physicians who are in charge, they feel undeterred at large to prescribe the product and provide access to it. We also wanted to clarify that at least the -- there is no restrictions of reimbursement.

And there's also an unbroken preference share for Beyfortus. Now how does this play out? I mean, that Sanofi will provide guidance from what I understand in Q2, I would not like to say, I mean, we don't have exaggerated growth expectations for Beyfortus whatsoever because we look at this more as a catalyst to fund our growth drivers that we have pointed out.

That's for us part of our plan. But we will see that there is some -- that the factors favoring a positive evolution of Beyfortus are not insignificant and we don't see it. We have not been able to point too many headwinds. So it's probably more moderate positive optimistic, but we don't have any exaggerated expectations on the other hand either. But we are really also dependent. We are triangulating different data points. We are dependent, obviously, on Sanofi who is promoting this product. And I'm sure they will enlighten us, but we are more cautiously optimistic. Henrik, you want to?

Yes, sure. Well, it's difficult to comment on individual lines in the consensus forecast, particularly since I understand that consensus isn't totally updated. But I guess if you have the top line number or you have the top line growth and then you have a gross margin, which remain in the high 70s, sure, mathematically, you know more or less what numbers to have at OpEx to get to the mid-30s guidance. And of course, we are -- as I said, we are adding very important investments in 2026, where Arthrosi then is expected to be the largest among these new items. I can't really give you -- be more precise there on a particular number for OpEx.

The next question comes from Harry Gillis from Berenberg.

Can I just follow-up on the 2026 guidance, particularly on the margin. Can you quantify what impact the Arthrosi acquisition there either in percentage terms or in absolute OpEx spend in '26, just to try and figure out what the margin would have been ex Arthrosi? And then a quick one on Gamifant. I know you talk about communicating next steps in due course. Is the debate here whether you go straight to a pivotal trial or require Phase IIb before pivotal?

Henrik?

We don't want to give a specific number on specific items here in the guidance because, as you know, we guide on revenue growth and margin. But I think you know more or less the starting point here. And as I said, Arthrosi is the largest among the new investments compared to 2025.

And on Gamifant, we are encouraged, as Lydia pointed out, to think about the next step, which -- and validate this further with EMA, which could well be a pivotal trial.

Yes. So basically, based on the unmet medical need and the strength of the data, that's the discussion that we are going to have, and we are looking into all options. And obviously, one could be going directly to pivotal. But it will be too early to say anything before we complete the conversations that we have already started with the regulators.

Next question comes from Kirsty Ross-Stewart from BNP Paribas.

Kirsty Ross-Stewart from BNP Paribas. Just a quick on your comments around Beyfortus. You said that kind of you don't have exaggerated growth expectations. So can we take this to mean that you're kind of expecting a small amount of growth or more reasonable to assume that the Beyfortus royalty revenues remain flat in 2026?

And then also on the margins, would you be able to give us some color on how we should think about the evolution of this in the kind of midterm. Should be thinking about '26 as a transition extraordinary year given the big step-up in investment and then return towards the 40% margin longer term. I just think conscious would like some color given the launches that are being approached.

And then lastly, on Vonjo, saw a slightly stronger quarter in Q4 and GSK have made some comments that they're noticing some competition stepping up for their product. So could you just talk to the changes you've made in the commercial organization behind that product and whether we could expect that to return to growth in 2026?

Yes. Thank you. I mean what I meant is, I mean, we don't typically provide guidance on individual products. I think there's -- I cannot provide more color. I mean it's clearly not a growth driver for Sobi, but it's also not maybe we don't expect a declining product either.

And basically, with regard now to the midterm outlook, I mean, that's the reason why we actually wanted to have a Capital Market Day to provide you a perspective how we see the evolution of Sobi towards 2030, at least and how we see the long term. So basically, the segregation of our forecast into tomorrow, tomorrow after tomorrow and reflecting on today.

And with regard to Vonjo, I mean, we made some changes. We have a new leader of this business unit, and he has clearly the right degree of tenacity and mental readiness to try to take this product on. I think it's important that we accelerate now PACIFICA, which is then a stepping stone in conjunction with the other data that we have generated to get on equal terms in terms of label, as we outlined earlier and then obviously, guideline recommendation.

But we believe that Vonjo is a growth product for us this year. And that we are -- that we benefit from the volume growth that we had also last year, but, a, the volume growth will be amplified and b, we will not have this significant negative effect of gross to net adoption, which then led to price reductions at scale. So we believe that Vonjo should be better performing for us this year. But the turnaround and the inflection we don't expect this year, we expect that once we have reached equal status in terms of label and guideline recommendations, then you will see whether Sobi can be competitive in this area. Next question?

The next question comes from Viktor Sundberg from Nordea.

So just curious here also on your guidance in terms of the growth numbers you provided. So on Beyfortus, it sounds like you estimate a stable market heading into 2026. So in light of that, what kind of pulls have you expected that hold you back a bit of not having even higher growth goal if you assume flat or slightly increasing Beyfortus sales? And maybe related to that, too, when you talk about margins, it looks like hematology margins have steadily moved up to 40%, but you highlight some higher OpEx here. So I just wonder if these OpEx costs are expected to come early in the year or more to the second half of the year. That would be interesting to hear. And then I have a quick follow-up on Gamifant as well.

Yes. I mean I'll start and then maybe Henrik can talk about OpEx as well. But we are entering, I think, for Sobi at least, at least the last 8.5 years, I think we never had the foresight to launch 6 products. And some of these launches ongoing and 6 by 2028. And of these launches, products that have -- I mean, an unprecedented potential for the company that we are today.

I mean, in terms of size, these products -- I mean, product of this size, potential blockbusters are not just happened by a fluke. They have to be created, and we have to show commitment in terms of resources and effort, and we are ready for this. And this is what basically now happens to us in 2026 that we provide these resources to build Sobi for the future. And these were conscious trade-off decisions. And that's the reason why our forecast or our guidance is lower than the 2025 actual, and that basically is incorporated. And so maybe, Henrik, you want to comment more on the OpEx side and provide more color?

I think you referenced also hematology profitability development, and that is -- it's clearly up compared to a year ago, but that's a very natural consequence of the uptake in revenue from Altuvoct and also obviously products like Doptelet. And so when it comes to the split of OpEx over the year, I mean, it's clear that some of these items that I mentioned start to build up later in the year because if you take Arthrosi, for example, we haven't yet closed that transaction. So obviously, it cannot be a full quarter in Q1. Similarly with IDS, for example hasn't -- we're still in discussions with the regulators. So obviously, this will ramp during the year.

Okay. And just a quick one on Gamifant also. Just trying to understand maybe your view of the commercial opportunity for this product with expectations on this product being a hot topic among investors in Sobi. I guess if you're in the camp that's more negative, you would point to that it's an acute, not chronic condition, pricing could perhaps be a bit challenging, even though we, of course, don't have the data yet. But I'm just curious how you see the commercial opportunity in sepsis from your perspective.

Yes. I think the commercial opportunity is incredible. I mean it's not -- we don't want to tell you now that it's completely off the charts, but it is clearly, when you just look at the stats, 2 million patients in Europe, take away 20% of those with interferon gamma-driven sepsis, simple math. That's a lot of patients. And yes, and then you apply the dosing regime that was used in this proof-of-concept trial. And the irony is -- you may not even have to adjust on a price per unit because you need less units too much versus where we are today. So this is the way we have priced Gamifant. So it is -- but it's still a very, very significant opportunity for us.

But we need to hold our horses. Now we need to get into the next trial. And we are excited to share with you the, let's say, the next set of data at the Capital Market Day. And obviously, looking very much forward to March EasyChem, like Lydia pointed out. So -- but the opportunity is massive. I mean, clearly, beyond if it would come and if the pivotal data would support what we have -- what the early signals we have seen, clearly multibillion dollar opportunity. We can't avoid it. But it's early days, yes. So we need to now do the next step and be a little bit patient, but it is a spectacular opportunity for the size of company we are.

We now have a follow-up question from Mattias Haggblom from Handelsbanken.

Two quick follow-ups, if I may. So firstly, on sepsis. So with the CMD in mid-February, is it really realistic to assume you received feedback from both EMA and FDA prior to the CMD to help you guide the path forward? Or would insight from EMA be enough? And then secondly, with the conference with full disclosure from the proof-of-concept trial in mid-March, help us frame expectations what clinical data you can actually share at the CMD in February?

Yes. Thank you, Mattias. We will -- we are in constant dialogue, and we will see whether we can synchronize this and Lydia can talk about EMA and her expectations for EMA and FDA feedback in a moment. What can you expect at the conference?

There needs to be a little bit of mystery in life and let's say, to create a bit of suspense. But no, realistically, we will provide a few data that will help you to share the excitement we have in the company. That's -- this one, I think we can safely say because the -- I mean, it's a small study, but it's -- we are very satisfied with the outcome that otherwise, we would not have indicated what we have indicated. Lydia, what do you think in terms of feedback from EMA and FDA?

So maybe 2 comments on the regulatory side, we are moving full steam ahead. So we have already started the discussions, and we will have consultation with both agencies. So we are trying to move as fast as possible based on how, as I mentioned before, how large the unmet medical need is and the signal from the study. And maybe just wanted to maybe remind everyone on the call that obviously, what you've seen and what we've seen is like top line data of the 28 days, which was the primary endpoint at 28 days on the SOFA score and mortality, but the study has a follow-up up to 120 days.

So we also want to see the full data set because that will be doing additional data on mortality, not on the primary and secondary endpoints. But just to remind everyone that we will need to wait also until second end March to have the full data set. So we will share what we can at the Capital Market Day. And obviously, there will be more discussions on the data at the conference in Brussels.

Thank you, and thanks for your interest. I think we have now reached the end of this video conference. I hope you share our excitement around the company. We at least are looking really at unprecedented opportunities, as you can see for the group, for the company we are and very much look forward to continuing the dialogue. I mean, please contact our IR, and we can provide separate insights. Other than this, we would be excited to welcome you in Stockholm on the 18th of February. Thank you so much, and wish everybody a fantastic week.

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Good morning, everyone, and thank you for joining us today to the SOBI presentation. My name is [ Apolline Gilbert, ] and I will be moderating today's presentation. With that, I'm happy to leave the floor to Guido Oelkers, CEO of SOBI, that will then be joined by Gerard Tobin, Head of IR. Guido, over to you.

Yes. Thank you so much, and welcome to this year's presentation. It's really a joy to be here. And just to set the scene, I would like to share some slides with you on where we are and then to prove a little bit of the discussion. Forward-looking statement as per usual. So maybe some key takeaways as we start kicking off 2026. I mean, we can't talk about the Q4. We will have announced our Q4 guidance on the 5th of Feb.

But as you can see, we had a spectacular Q3 with a very strong underlying growth and very gratifying that our strategic portfolio was growing at 39%, making it now over 60% of our total business. With regard to acquisition, we -- as you probably have read, we acquired Arthrosi, and we'll talk a little bit more about this [ price ] and this will allow us to strengthen our gout franchise. We think it was a fantastic opportunity that we should have not missed out on.

With regard to pipeline, we will talk a little bit more about it later. We had some nice readouts foremost more recently, the readout in IDS interferon gamma-driven sepsis that we, I'm sure will spark maybe the one or the other question. And so we carry quite a lot of momentum now into 2026. So where you will see that we are quite bullish about our future. So this is now, let's say, just a little flash back Q3. As you can see, the growth is carried by quite a number of products and now the strategic growth portfolio, as I alluded to earlier, 64% of the total business.

So these are all products that have not been around 7 years ago. And with regard to the regional contribution, you can see it's quite evenly spread. We had a fantastic Q3 in North America, in Europe, but in all the regions and obviously, in international are performing extremely well. So straight to the Arthrosi, what did we see in this product? We are very happy that we were able to sign this agreement. We have not yet closed. So just be mindful of this.

We think it's a really highly selective next-generation URAT1 inhibitor and has best-in-class potential. We think it's a product that fits beautifully to our program called NASP and will be in second line. There's a very strong scientific rationale. I mean, we alluded to when we did the announcement that we have spent nearly a year on this acquisition on and off before we then were able to conclude the deal.

And we think it's addressing an underserved and growing population, and it will become in the years to come, very accretive, and it's a long patent life, so it will propel growth for us into the 30s. So when you think about the treatment paradigm, as you can see here quite illustrative, it sits beautifully in second line. And the product is a redesign of an earlier URAT1 inhibitor. And therefore, we believe it avoids some of the issues that were associated with those products. And we think that -- and we got convinced ourselves that it is a safe product with a potentially high efficacy, and it beautifully helps us to provide an entire franchise.

Just to remind you, we believe that we have PDUFA in June for NASP, so we can offer an entire franchise and go fully behind this. So when you think about us now moving into the next couple of years, it's quite gratifying for us that we have a swell of launches.

The launch for Altuvoct ongoing. We still had in the last -- in the second half of last year, quite a few new countries coming on stream, such as the U.K., France and in December, Italy. So this product will remain a growth driver for the company. We have the secondary HLH indication for Gamifant launch, we believe it's going to be very important for us as we move forward. We are launching now, as we speak, in C3G IC-MPGN, February in Germany and already launched in some of the Middle Eastern countries.

We have mid of year NASP in the U.S. in chronic refractory gout third line going after the KRYSTEXXA opportunity. And then in -- we are currently already -- we have launched Tryngolza, I should say, in an indication that we know very well for FCS because we are the preceding product with Waylivra, so very high triglyceride patients. And we're expecting the launch of MCS, meaning product -- meaning for patients above 880 milligram per deciliter of triglycerides, we are thinking of launching in Q1 next year.

And then we obviously have poducalide in Q1 2028. So I guess you can see it's a nice fully loaded launch schedule that gives us reasons to believe that we have a nice growth evolution of the company into the 30s and very happy that we have been able to accumulate such a late-stage pipeline. So -- but this is one part. So these are 6 launches that you can look forward to. And then there's another part, and this is the priority development projects that we are also focusing on. And here, I just want to focus on one area because we just had recently a Phase IIa readout of Gamifant in interferon gamma-driven sepsis.

And maybe go straight into the next -- to the next slide. So we believe that this could become a game changer for the company. Obviously, it's early days. But when you just look at the stats, it's a very significant patient population between 1.5 million to 2 million in Europe or the U.S. 20% of those patients have what we believe the endotype IDS. And this has been confirmed by a study -- by a pre-study with 5,500 patients, and you have mortality of around 40% to 50%.

So very significant high unmet medical need. And we believe that the product here by having an interferon gamma scavenger, we could potentially make a significant difference. Now we have had a readout recently with the EMBRACE study, Phase IIa study. This is -- these were 75 patients, 3 arms.

So what we found is that we had -- that we saw a strong signal with regard to the change of daily organ failure assessment -- daily sequential organ failure assessment SOFA score. And we had a second -- as a secondary endpoint, we saw also a very strong signal on mortality. Now this is -- this study was not powered, obviously, to show significance, I mean, 75 patients, but the signals were so strong that we felt compelled to make an announcement. And as we speak, we are consulting with the agencies given the high unmet medical need. And once we have done this, we will obviously come back to the community and we'll make the announcements on the next steps.

Now for us, we will make an announcement in February 5. We will talk a little bit about the guidance also for next -- for this year. And on the February 19, we will talk about at the Capital Market Day or 18, sorry, we will talk about how we see the evolution, how we see the economics of this playing out, but it's obvious that this is a very significant opportunity for the company, in particular, in conjunction to the 6 launches that I just displayed.

So basically, as we go now into the next phase, what are the milestones and the momentum that we want to carry into this year. I focus more on the '26 side. We have the ongoing launch. We have -- we're expecting a regular for C3G IC-MPGN. We got an EU approval. We are expecting a Japan regulatory decision, and we are very happy to work here with our partner, Asahi on this. Gamifant in HLH and MAS is ongoing. We expect also here a regulatory decision in Japan, and we will submit in Europe for secondary HLH and trying to make the product available as well. We will -- we have obviously completed IDS, the Phase IIa study.

We will have the follow-up data for the 120 days, and we'll then announce suit. We expect the publication on the 28-day data and possibly also the 120-day data at EziCam in March. And with regard to NASP, 27th of June is PDUFA date, and then we hope to launch the product swiftly thereafter. ZYNLONTA, it's not a product that we typically talk a lot about, but we believe is actually also an opportunity that we will not ignore. So we will get the -- for second line, the LOTIS 5 rate data readout as we -- ADC expects them in the first half this year.

And obviously, we hope to close the transaction with Arthrosi in Q1 as well. So a lot to do and a lot to look forward to. And this gives us the reasons why we are going into this year with a lot of optimism. So pretty strong momentum. We did, I think, a very thoughtful acquisition. We preempted here before the Phase III data, but we felt if we wanted to acquire this product and if this was meant to be ours, we had to do this ahead of the Phase III data, but we felt that we could take this risk because we reasoned it and we did quite a bit of work as previously outlined on the science to establish safety and also have a good understanding of efficacy.

So quite a few news coming through. And as I mentioned earlier, we feel that we have now enough to talk about to justify a Capital Market Day on the 18th of February and to provide further orientation as we speak. I think this sets the scene and maybe we can go into a Q&A session. Thank you.

Thank you very much, Guido. Will the audience have any questions to start with? Otherwise, I can kick start with one. Regarding Altuvoct, now that you have launched in 20 countries, do you have maybe an idea of how much of the current growth is going to come from patients that are switching from Elocta versus entirely new patients?

Yes. I mean we alluded to this in Q3. We -- the majority now of patients come from competition. And at the beginning, it was more like 50-50 now we get probably more like 70-30 from other therapies. And I mean, it's just an evolution. At the beginning, the switch from Elocta is so much easier. But we are also getting now quite a few patients from nonfactor therapy and very pleased with the evolution. I mean we are very -- we talked about that we have over 60% market share now in the early launch countries. And we think that we -- in prophylaxis, and we think that the best is still to come.

Okay. Great. And regarding the Arthrosi acquisition, you mentioned that it was more in terms of a time line that you felt was a good moment. Do you have any other strategic advantages that you saw to proceed to the acquisition ahead of the Phase III?

Yes. No, it's one of those things. We typically, mid-cap would not take a company of this size out ahead of Phase III data. But now -- but we felt -- in today's world, this is a pretty competitive environment. But we saw the opportunity, we felt if we wanted to have a chance to score this acquisition, we had to do this ahead of Phase III data because once the phase -- if the Phase III data turn out the way we believe that they could turn out, it would have been not our deal anymore and it would have been a multiple of what we have paid at the time. So it was for us, do we -- are we committed to this indication? We have spent quite a few years now on chronic refractory gout with NASP. So we feel that we have some internal knowledge about the disease. We looked at the data as they are available and spent quite a bit of time with the company. We think it's a spectacular asset and can only congratulate the organization that Arthrosi to what they have built up.

Okay. And regarding Tryngolza, you're in the middle of a launch prep ahead of the launch in 2027. Can you maybe touch point a bit on that?

Yes. I mean it's -- for us, it's a spectacular opportunity. We are -- we know FCS. This is around depending on which source you take, 1,000 to 3,000 patients in Europe, which is a very specialized disease area. We are now in the midst of the launch already. But I think it's a market tiers dream because you prelaunch in a way the bigger indication and the centers, the lipid centers are also the main audience at the center of the next indication. So for us, it's a beautiful way to introduce the product to prepare the larger indication. This indication will take us a little bit out of our comfort zone. It's just to orientate everybody in Europe alone, that's 1 million patients.

That's not -- you need to have a bit of a liberal stretch whether this is rare. And so it's not really rare. And -- but it's rare at core. And when we looked at how we can move this indication, we think that we could be -- we can have -- we have a right to play here, and we can provide -- build up a team that we can support and we can fund and we can go after. And the data in -- with 85% pancreatitis reduction is just spectacular and over 70% triglyceride reduction in this patients at risk.

And so we feel it's an opportunity. We don't want to miss. We have a spectacular partnership with Ionis, and we will give this our best shot we even created an internal organization of, we call it an incubator because it is a different way to think about and we are currently preparing the organization at scale to prepare this launch.

Okay. Amazing. Well, maybe one last question from me and if nothing from the audience, maybe we can give everyone a bit more time.

Yes, sure.

Could you maybe touch one quickly on the Beyfortus [indiscernible] development?

Yes. I mean this is -- there's obviously a lot of debate -- public debate on RSV prevention. And you could get the impression that the world has changed a little bit. But as I think eloquently was articulated yesterday by Sanofi, I mean, one thing has not changed -- what has changed is actually that you avoid today 50,000 hospitalization in the U.S. alone. That's not so bad. And particularly when you look at the baby incubated, particularly preterm babies, it's not really a spectacular image that you will have in mind. What has also not changed is actually when you look at the new guidelines that actually they are still endorsing Beyfortus for pre-term babies and other babies.

So it has not changed. And reimbursement has not changed. And we performed a study, obviously, in Q3 that we presented and where we saw an unchanged commitment of physicians to the disease, and we didn't see any limitation of access for patients to the products and reimbursement hasn't changed. So the way we look at it is while there has been a lot of discussion and debate, the actual facts, the fundamentals really have not changed. And so for us, we are quite happy to have this earnings stream because we use it as a catalyst to build this what we believe is a relatively ambitious program of transforming the company and investing into our future.

So we are very happy to have it, and we are confident that in our books, this doesn't need to be an exuberant growth portfolio. We have as an insulation of risk, we have an increasing royalty rate until 2028 that was helping us to offset potential negative effects, whether that's competitive nature. But again, there's a very strong preference share for Beyfortus over other antibodies.

And then we think that the minimum base case is that this is a stable earnings stream for us in the years to come with a possibility to grow. But it doesn't need to grow because we -- as you have seen, we have lots of other opportunities that will propel the company into the future. So we are actually quite -- whatever you call it, at least we are not feeling beaten up or we are positive about the announcement that we recently made.

And that you will -- sorry.

Yes, I just wanted to add, I mean, also when you look at it from a medical and local and state level, actually, what I've seen is the AAP is fully behind the full recommendations, all the 17 -- I read last night, 17 of the states are saying that they will keep the recommendations as is overall for vaccines. So you do see, I mean, full support for RSV to the point that it was a category label change. But other than that, the actual fundamental indication itself has not changed.

Okay. Amazing. And as you mentioned, you have your CMD coming up. Yes. I'm sure there will be a lot of surprises from you then as well.

Yes. No, I mean, we felt compelled given the number of new products and new modalities that we spend a little bit more time than usually available in different settings to talk about these products, and we'll provide some KOL perspective as well on how we want to think about it into the future and what is our ambition also for 2030.

Okay. Amazing. Are there any additional questions? No?

Well, Guido, Gerard, thank you so much for your time. It was great having you and all the best.

Yes. Thank you so much.

Thank you.

Hello, everyone. This is Guido Oelkers, CEO of Sobi. We are delighted to welcome you to this conference call following the announcement of the acquisition of Arthrosi today, pending, of course, to regulatory clearance. We have posted this presentation to sobi.com for your reference.

Please turn to Slide #2. We would like to remind you of the usual provisions on statements about expectations and projections of future events.

Please turn to Slide #3. I'm joined by Henrik Stenqvist, our CFO; and Lydia Abad-Franch, Head of R&D and Chief Medical Officer.

Please turn to Slide #4. We will present to you the acquisition details. I'll discuss the deal rationale, key opportunities. Julia will share the relevant scientific data, and Henrik will highlight the financial aspects. When you look at this slide, we're obviously excited to announce the addition of Pozdeutinurad AR882 to Sobi's gout pipeline through the acquisition of Arthrosi Therapeutics.

Let me start by outlining the strategic rationale behind this deal. But beforehand, a quick perspective on the product. Pozdeutinurad is a highly selective once-daily oral next-generation URAT1 inhibitor that has the potential to become a novel best-in-class therapy for patients with progressive gout.

The compound has shown clinically meaningful efficacy and strong safety profile in several large, well-designed Phase II trials. Importantly, 2 sizable Phase III studies are already fully enrolled and scheduled to read out next year. It should be noted that the product has been specifically designed to go overcome historical safety issues associated with the URAT1 class and demonstrated impressive efficacy levels in multiple Phase II.

Back to why we did the deal. Firstly, this acquisition represents a major commercial opportunity. In progressive gout alone, we see more than 200,000 patients in the U.S. an underserved population where innovative treatment options are urgently needed. Secondly, 882 also fits seamlessly into our broader gout strategy. It complements NASP, our registrational asset aimed at more severe uncontrolled disease, offering a second and third-line therapy, forms the foundation of a competitive franchise for us.

Thirdly, this acquisition brings a late-stage derisked asset into the pipeline, along with an experienced team that strengthens our overall capabilities in gout. Fourthly, and most importantly, the deal is expected to be accretive to net sales and earnings in the midterm, supporting sustained growth beyond the mid-2030s, which you will see reflected on the next slide.

Please turn to Slide #6. This addition to our pipeline and upcoming launches will drive long-term growth for Sobi. We have a strong wave of high-value launches through 2028 and that will underpin growth mid- to long term. 6 launches nicely synchronized over the coming years provides the fuel for sustained momentum. Our ongoing launches of Altuvoct and Gamifant will be complemented by Tryngolza in FCS this month.

Please note that we got a positive CHMP opinion for Aspaveli in C3G and IC-MPGN in Europe, and we are preparing the launch of NASP in Europe. We expect it to launch Tryngolza in MCS in 2027 and now starting in 2028, Pozdeutinurad for progressive gout will be another major growth driver, further solidifying our momentum. Beyond these launches, our Phase II pipeline may give further boost to this momentum. In short, this is not just about near-term launches, it is about building a portfolio that drives growth well into the next decade.

Please turn to Slide #7. Before we drive into details of the acquisition, let's take a step back, look at the broader context of gout. Gout is a growing global health challenge. Chronic gout is particularly problematic, especially when it progresses. It leads to tophi formation, chronic joint pain and joint damage, which significantly impacts patients' quality of life and mobility.

It also is associated with flares. These are intensely painful episodes and can severely limit mobility and daily function. For many patients, this means limitations, and burden for daily life, material cost on healthcare systems. The growing prevalence and the severe impact on patients underscore why there is such a large unmet medical need and why Sobi is committed to addressing it. These patients have limited options today, which creates a clear opportunity for differentiated solutions.

Please turn to Slide #8. Let's now look at how Sobi is building an innovative portfolio to address the unmet medical need in gout. There is a significant patient population that does not respond adequately to Xanthine oxidase inhibitors and is not eligible for uricase therapy. These patients have limited options today, which creates a clear opportunity for differentiated solutions. As shown here, treatment of chronic gout mostly follows 3 stages: first-line therapy usually treated with Xanthine oxidase inhibitors for early gout, second-line therapy for Uricosurics for progressive gout and third-line therapy for uricases of uncontrolled gout.

Pozdeutinurad is positioned as a first and best-in-class next-generation oral URAT1 inhibitor for progressive gout. It represents the first meaningful innovation in chronic gout in over 15 years, whilst NASP addresses uncontrolled gout. Together, these assets enable Sobi to serve patients across the spectrum of gout severity, creating a differentiated and innovative portfolio that meets a major unmet medical need.

Please turn to Slide #9, and I hand over now to Lydia.

Thank you, Guido. So moving to next slide, please. Let's now look at the scientific rationale behind Pozdeutinurad, also known as AR882 and why we are so excited to add this to our portfolio. Pozdeutinurad is a rationally engineered next-generation URAT1 inhibitor, leveraging a well-validated and highly efficacious mechanism in gout treatment. It has demonstrated an improved and steady pharmacodynamic and pharmacokinetic profile compared to predecessors, which has translated into durable efficacy and a more favorable safety profile, as I will explain in the next slide.

In several sizable well-designed Phase II clinical trials, it demonstrated strong efficacy outcomes, including serum uric acid lowering, tophi resolution and clinically meaningful reduction in gout flares. That's a key outcome for patients. The 2 large and fully enrolled Phase III studies are underway with first results expected in 2026 with subsequent submissions to regulatory authorities.

Please, next slide. Let's now take a closer look at the molecule at the center of this acquisition. Pozdeutinurad is a novel and selective small molecule URAT1 inhibitor, a uricosuric that increases the renal elimination of uric acid, designed to improve both safety and efficacy in treating chronic gout. By selectively inhibiting the URAT1 transporter, it helps the kidney to filter and excrete uric acid, effectively lowering serum urate levels and hence preventing urate crystal deposition. Notably, Pozdeutinurad was specifically designed to avoid the formation of the toxic metabolite associated with bromarone hepatotoxicity and clinical data to date support the view that this molecule has a safe liver profile.

Its modifications, particularly the exchange of hydrogen for deuterium in the benzofuran part of the molecule minimizes the formation of the hepatotoxic metabolite and the exchange of hydrogen for a hydroxy group in the ethyl moiety attached to the benzofuran should prevent interactions with cytochrome CYP3A4. In terms of renal safety, Pozdeutinurad does not carry the same risk for renal stones as traditional uricosurics by having a clearly differentiated chemical scaffold versus the traditional uricosurics that are also O1 and O3 substrates, leading to bolus excretion and absorption that causes major fluctuations in the renal handling of uric acid.

Instead, Pozdeutinurad has a favorable PK/PD profile due to its high URAT1 selectivity. Hence, the fraction excreted into the renal tumors is evenly distributed over the 24 hours period following dosing, supporting a sustained serum uric acid reduction without boluses of highly concentrated uric acid.

In summary, Pozdeutinurad's scaffold and modifications allow for precise engagement with key gating residues in the URAT1 binding pocket, maximizing potency while minimizing the risk of off-target effects and reactive metabolite formation. The design reduces the likelihood of nephrotoxicity and hepatotoxicity, which are dose-dependent and more common with agents that lack such selectivity or generate reactive intermediates. And this is why we are excited about this specifically designed molecule.

All of this is reflected in the available data from the long-term Phase II studies that have shown a well-tolerated safety profile with adverse events mostly mild to moderate and importantly, no significant or kidney function abnormalities. The drug is currently in Phase III and the program received FDA Fast Track designation in 2024. This profile positions Pozdeutinurad as a potential best-in-class oral therapy for chronic and progressive gout, addressing a major gap in the treatment landscape.

Please, next slide. Looking at some of the Phase II clinical data presented at international congresses, it hints to the excitement we feel about this product and its profile. In Study 202, a Phase II trial in 140 patients followed for 12 weeks, 71% to 82% of patients achieved serum urate levels below the therapeutic target of 6 milligram per deciliter with 50 and 75-milligram doses. Additionally, we observed a rapid reduction in serum uric acid within the first week of administration, which is sustained throughout treatment.

Please, next slide. In Study 203, another Phase II with 42 patients followed it for up to 18 months, we confirmed sustained efficacy, again, with a strong serum uric acid response rates for Pozdeutinurad alone and in combination with allopurinol. Importantly, Pozdeutinurad also demonstrated significant tophi resolution, both as monotherapy and when combined with allopurinol with up to 50% tophi resolution at 18 months and 44% at 12 months for combination therapy.

These results show that Pozdeutinurad delivers clinically meaningful efficacy in a diverse set of chronic gout patients, including those who are refractory to prior therapies and those with severe tophaceous disease. This positions Pozdeutinurad as potential best-in-class oral therapy, and we are eagerly awaiting for the full Phase III data to confirm this profile.

Please, next slide. This slide shows one of the most compelling aspects of Pozdeutinurad's clinical profile, which is its ability to achieve sustained resolution of tophi. In this Phase II study, patients receiving 75 milligram once daily showed dramatic reduction in crystal volume over time when assessed with dual energy computer tomography. Overall, that's a 98% reduction in crystal volume over 18 months, as shown in the imaging on the slide, and you can see the progress over different time points. This is clinically meaningful because these crystals drive progression of gout and the formation of tophi that can lead to joint destruction with bone erosion. Eliminating tophi not only improves symptoms but also addresses the underlying disease progress.

Please next slide. To close the clinical development overview, here is where we stand with Phase III. Both pivotal trials are now fully enrolled ahead of the schedule, which is a major milestone. REDUCE 1 completed enrollment in August and REDUCE 2 in March 2025. Patients are randomized to receive either 75 milligrams or 50 milligrams of Pozdeutinurad or placebo once daily for 12 months. And the primary endpoint is treatment response defined as achieving serum uric acid level below 6 milligram per deciliter at month 6. We expect top line data in 2026, which will be the key inflection point for the program, and we look forward to seeing the full data.

With that, I will hand over to Henrik. Thank you.

Thank you, Lydia. And please turn to Slide 17. And let me summarize the key transaction terms for this acquisition. So we've agreed to pay $950 million upfront to acquire the company, which is about SEK 9.1 billion. In addition, there are up to $550 million in potential clinical, regulatory and sales milestones, of which most relate to sales milestones. The upfront payment will be funded mainly through available credit facilities and partly through a new credit facility. As a result of the transaction, leverage is expected to increase to around 2x at the time of closing, but that level will be rapidly reduced over the course of 2026 through our underlying cash flows. The acquisition is expected to be highly accretive to our mid- to long-term growth and margin trajectory, but also in the short term, our ambition is to maintain a very competitive margin. As usual, we will guide for 2026 in February when we report full year 2025.

Finally, we expect the transaction to close in H1 2026, subject to customary closing conditions. In short, this is a well-structured deal that strengthens our portfolio, accelerates long-term growth and focuses on long-term shareholder value.

Over to Guido. Looks like you're on mute, Guido.

Sorry. Sorry. So please turn to Slide #19, please. And let's see -- one second. So this acquisition reinforces Sobi's strategy of sourcing first-in-class and best-in-class molecules to strengthen our portfolio and deliver differentiated value. Across our portfolio, you can see examples of this approach from Altuvoct, Gamifant and more recently, Tryngolza to mention a few. And now with Arthrosi, we had Pozdeutinurad potentially a first and best-in-class next-generation URAT1 inhibitor for progressive gout. This acquisition follows our strategy, building a portfolio of highly differentiated therapies that addresses significant unmet medical need and drive sustainable growth.

Please turn to Slide #20. To summarize this acquisition, it brings a highly strategic asset into Sobi's portfolio. 882 is a potentially best-in-class, highly potent and selective next-generation URAT1 inhibitor designed to reduce serum uric acid level, flares and tophi in patients with progressive gout. It addresses an underserved patient population that is currently sub-optimally treated with first-line therapies. The asset is in late-stage development with 2 global Phase III assets fully enrolled -- 2 global Phase III studies fully enrolled and expected to read out in '26.

This transaction expands Sobi's gout pipeline and a complementary capability in chronic and progressive gout whilst building on our existing expertise in this space. Finally, the acquisition is expected to be highly accretive to Sobi's mid- to long-term growth and margin trajectory, reinforcing our commitment to delivering sustainable shareholder value. In short, this deal catalyzes the formation of a portfolio that drives growth well into the next decade.

And now it's time to take questions.

[Operator Instructions] The first question comes from the line of Christopher Uhde from SEB.

I hope you can hear me. If not, please say so. So my first question is on CMC. What can you tell us about the status? I mean, obviously, a lot of start-ups cut corners on that, and then that's up to the acquirer to resolve. Could you tell us what remains to be done there?

And then in terms of the ex U.S. opportunity, so what -- you don't have head-to-head data against febuxostat, but obviously, the numbers look clearly better. But what do you need in terms of data to secure reimbursement in Europe? And what can you say about then the kind of pricing you think you might -- or what indications could you give us around pricing for the drug in the U.S. and Europe?

Thank you, Christopher. With regard to CMC first, this is -- has been progressing very well. The 2 manufacturers on the API and also on the DP and finished goods, they are actually FDA certified, working with many MNCs. So we didn't find there the typical flaws that you are alluding to, we feel actually quite encouraged now to progress this product, and it's a small molecule. I mean we had obviously a fair share of learning in this department overall. But this seems to be pretty much under control.

With regard to Europe, I mean, we will -- our case completely stands on the U.S. It's fair to say that based on U.S. approval, we will be able to launch in quite a few other international markets. And I think it will be a good time for you to provide a bit of a framework on how we are thinking on Europe is probably the Capital Market Day. I mean we know that there is obviously a high unmet medical need in Europe as well. But the question is to what degree can we get away with our direct comparative data. That's something that we will have a good look at. But we're expecting actually to have strong efficacy data that compare well with existing therapy during the course of next year.

The next question comes from Gonzalo Artiach from Danske Bank.

Could you give us some color on the potential operational synergies between NASP and [ POS ]? Will you guys use the same sales force and commercial infrastructure, I guess, yes. But how much do you have to add on top of the NASP investment there?

And my second question is on this second-line space. I mean, do you think that [ POS ] should be used before or it's going in practical terms to be used before febuxostat? And yes, based on just pricing opportunities here. And how do you see the Crystalys asset that has data in late 2027 also as URAT1 asset?

Yes. Thank you. I mean so this -- I mean, as we outlined, we position the product as a second line to, for instance, allopurinol and basically, we see an opportunity for the drug to actually to be honest, to replace febuxostat or at one stage, you will also probably have physicians who combine the product. But that has to be seen. The 2 pivotal trials are as a monotherapy. So that will be our ingoing hypothesis.

And then with regard to the commercial synergies, there is obviously -- there are obviously commercial synergies, even though the approach for physicians are slightly different. But we see clearly synergies also on the medical side. You will probably -- as we maybe during previous calls, we alluded to the fact that obviously, there is a very competitive field force out in the -- already in the [indiscernible] uricase sector. And in order -- but this deal obviously will allow us to build the field force that will be very competitive in gout.

So we will obviously add, but we will not -- we will not have to duplicate. We will augment our existing organization. And this will be -- and we will have -- be very competitive, obviously, when you think about the launch at the time. And with regard to with regard to Crystalys or other followers, will have to be seen. They are obviously a few years behind. And let's say, the -- how they will come out of their clinical trials. I mean we were -- we felt when we did the diligence that 882 is a very differentiated asset, and we shouldn't -- we should focus more of establishing the class than being worried about followers in this market.

The next question comes from the line of Mattias Häggblom from Handelsbanken.

Mattias Häggblom from Handelsbanken. Two questions, please. So with the 2 Phase II trials fully enrolled, was there any data that you, during due diligence, was able to evaluate from the ongoing trials, including adverse event rates on a pooled blinded basis?

And secondly, data from this asset started to emerge November '23 at the ACR meeting and then have seen updates on July '24 and '25, as Lydia alluded to. So can you share with us how long the Sobi team has been studying the asset? And if there was one particular data set or update that accelerated your interest?

Yes. I mean it's -- we have followed this asset for quite a long time. And the team that has worked on this, Mattias, on this asset is a very, very comprehensive interdisciplinary team that we brought to bear because obviously, we are launching this. We have made this acquisition prior to the announcement of the Phase III data. Lydia, we have also [ Nils ] here, who has led the scientific evaluation. But maybe Lydia first, you want to comment on what data pool we looked at and how we got comfortable that we can make this deal?

Yes. So thank you, Guido. And yes, Mattias, obviously, we have, as Guido mentioned, a cross-functional team looking at all the nonclinical and clinical data available so far. And that's what gave us the reassurance that not only the safety -- sorry, the efficacy profile, it's really above other assets in that space with very strong serum uric acid reduction. But on the top of that, the top high resolution and the control of the flares, which, as I mentioned, it's one of the most critical aspects for patients because that's what really impairs their quality of life. So that's the data that obviously has been presented, as you mentioned, during -- over the last years at the main international congresses. And that's what we've been looking into detail -- this available data so far.

And in terms of safety, the same, we've looked at the Phase II data in detail, and there has not been any safety signal that has really triggered any concerns when it comes to hepatic or renal safety. So that's why we've been really confident that with the data so far available from Phase II, we feel very secure on how this asset will be looking into -- moving into Phase III because otherwise, we would have seen potentially some signals, especially we are confident and that's why I think our [indiscernible] also decided in the Phase III trial, they included patients with previous history of nephrolithiasis if it has occurred 6 months before the inclusion of the trial. So that speaks of the reassurance that [indiscernible] has based on the safety profile of the product. So maybe [ Nils ], you were part of leading the -- [ Nils ] is the Head of Medical Affairs and Clinical Development. Maybe you want to comment as well a little bit more.

Yes, of course, Lydia. So I would say, first of all we are very confident with the Phase II data that we have reviewed and Lydia did present this data both on efficacy and the safety. I would say for the Phase III trial, there's maybe a couple of things just to highlight. First of all, as you could see, both of the trials enrolled ahead of time, very fast. I think this is a good sign. It sort of points to the unmet medical need, but also the robust design of the trials and the interest for the product. In terms of safety, these 2 Phase III trials, they are monitored by safety data monitoring committee. And so far, there has not been -- these have been very reassuring. There's been no safety issues raised. And therefore, we believe that the Phase II safety profile is maintained in the Phase III trials.

Yes. I think, Mattias, this gives you maybe a bit of a flavor. So we got comfortable based on the diligence, and this was -- we have been working on this asset for more than a year.

Okay, next question.

The next question comes from Kirsty Ross-Stewart from BNP.

Just a bit on the profile of the deal. So how soon following launch of the asset do you expect this deal could be accretive? I'm just wondering if you can add a little more detail on what you mean by kind of maintaining a highly competitive margin into 2026. Are you able to decrease the investment in NASP that you were going to be making in the first half of next year through some synergies that you acquired through Arthrosi?

And then just longer term, this seems kind of a little bit of move away from a kind of true rare disease indication. So just wondering from a strategic perspective in the company, is this kind of a sign of a direction you're looking to move into? Or are there kind of other assets -- sorry, other aspects that you're kind of trying to maximize by going through this deal?

Could you actually -- maybe acoustically, I didn't catch your first part of the question. I mean, can you just repeat this one? Sorry for this.

Yes, of course. Sorry, my line is bad. So just asking kind of how soon following launch do you expect the deal to be accretive and some more details on what you mean by a highly competitive margin into 2026 and whether there are kind of synergies and a wind down in the investment in NASP that you're able to make as a result of this deal?

Yes. Thank you. I mean, first of all, we are very much now looking forward to the launch of NASP next year. And there is no reason for us to decrease the investment on NASP in view of this new asset. And if anything, our conviction about the product still stands, and we want to give justice to this first start for the first portion. And by the way, this first launch NASP I think you would still qualify according to our definitions as a rare audience because it's really this group of maximum 15,000 patients that we are aiming at. And this base forms basically the nucleus. It gives us a spectacular connection to the community, to the physicians. And then it's extended, let's say, into the second line.

So whilst you can argue that the audience for this second-line gout is probably not as rare anymore, we started with a rare focus and then expand from there and it is in a high unmet medical need. So we are less worried now about definitions more than making -- more worried about making a difference to patients. And yes, it will allow us to put up an organization then in the second phase that is very competitive and -- but builds upon the core that has been laid -- will be laid next year. And so we -- and basically, we think that the product, as we said, is going to be very accretive as of the 2030 into the mid-30s and beyond and will be a significant growth driver for the company. And as such, then will really be a propeller for growth and earnings. And as of when we will have there a breakeven, we will probably give you more of a view at the Capital Market Day, but this would be now a bit premature. But clearly, the margin profile, the gross margin profile of the product is very advantageous and will allow us to move up the chain. And so I hope this answers the question.

The next question comes from the line of Lucy Coddington from Jefferies.

Just a couple left. I just noticed in the Phase III, you're evaluating 2 doses. It seemed like from the Phase II, the 75 milligram was the key dose. So is that just to have flexibility? Or was that a requirement to evaluate a lower dose? And then secondly, just in terms of the safety, in terms of the renal profile, would this allow you to expand use into patients with chronic kidney disease who perhaps are currently not allowed to be treated with URAT inhibitors?

Thank you. Lydia, please?

Yes. So the true dosing, it's basically normally in Phase III trials, you want to evaluate 2 doses. Obviously, the profile of the patients, it's like a spectrum. Not all patients are in the same level of severity. So we want to assess these 2 doses and our sources made that decision, obviously, in order to cover the full spectrum, but also to confirm which one of the 2 is basically the most efficacious. So we believe that this is the correct study design for a Phase III trial.

And in terms of -- the second question was for patients with chronic kidney disease that, as you rightfully say, were excluded from the study. I think that's a question that you -- that we will be able to answer once we see the Phase III data and we get the reassurance on the renal safety profile of the asset, and that might require additional subset of potential new studies that we will be deciding later on.

The next question comes from Viktor Sundberg from Nordea.

So maybe this has been covered, but just anything you can share on maybe the impact on financials short term when you consolidate the numbers from Arthrosi into Sobi's P&L? Secondly, I also guess some investors might remember the CTI acquisition and make a negative read across into this acquisition even if that is unfair. So any comment from Sobi that this time it's different?

And any learnings from your previous acquisitions that you have implemented here that would also be interesting to hear? And just finally, I guess you waited for the longer-term follow-up presented this summer on this drug. So what was the catalyst for deciding to go ahead? And anything in particular that triggered you to make the deal now?

Yes. Thank you, Viktor. I mean with regard to financial outlook. I mean, we will provide obviously a financial outlook at the right time when we present our Q4 results. But we think that this is a very manageable impact for us. And in this context, I'd like to remind everybody, obviously, that we have taken some precautionary measures already this year to create some space in the P&L. I know that we have a lot on the plate that we are now -- but it's -- all of this is really nicely sequenced. So we hope that we can demonstrate a very respectable results.

But yes, it's needless to say that the company at this stage is not providing a positive earning effect on day 1. But this is about obviously creating shareholder value and improving the value of our pipeline materially and then obviously driving and increasing our growth profile into the next decade. So it is a spectacular opportunity.

Now with regard to CTI, I mean, I like -- before I then comment on this, I'd like to say the following. The only guarantee that you have in life of failure is do nothing. That's a guarantee. And with this one, we have worked on this deal more than a year. We have probably had an internal team working on this, [indiscernible] of magnitude, 70 people. And we're using a probabilistic approach here. And yes, I mean, it's not like we have shut it off with CTI. There were some fair share of learnings, but we have conviction that this is going to work. And we have obviously, and it's helpful that this is an area that we have been working on for quite a few years now with NASP. So that means lots of KOL contacts. That means lots of discussions with patients, other stakeholders, yes.

So we -- at least you can say that we are going there in an informed way. And we are convinced that we can create some value, by the way, in a similar way that we are doing with so many other products. So we are not so a little bit more when you look at our current growth trajectory. And with regard to the longer term, we think that obviously, it's a fantastic catalyst for us to drive growth into the late 30s and probably beyond if the product has a long patent life. I hope I got all the nuances of your question, Viktor.

So maybe I -- because there was an aspect in -- if there was a catalyst for us to really...

Catalyst, yes.

So I think that, obviously, our main drivers have been the robust efficacy and safety data with the long-term sustained reductions in serum uric acid together with the knowledge of really the strong Arthrosi team that is built on gout experts and the strong momentum that we've seen in the Phase III trials, as we mentioned before, with this recruitment in very large clinical trials being achieved ahead of schedule. So I think if you put all those 3 things together, that's what reassure us on really willing to be part of this.

Thank you, Lydia. I sorry, I didn't -- I forgot about that. And with regard to the catalyst, I think, Viktor, you need to also realize we reason by the data that we are able to see success, if we would have waited for the final Phase III data the chances are this deal would have not been ours because there was quite a bit of interest for the company. So we -- in a way, but we did this not in a naive fashion.

[Operator Instructions]

Any other question? If not, then I would like to thank you...

There are no more questions.

For your interest, yes. Thank you. I'd like to thank everybody for your interest at such an early day -- time of the day and also doing quite a bit of fair work over the weekend. But you can hopefully share a little bit the excitement that we have gained over the last weeks and months and look forward to staying tuned. Thanks a lot and wish everybody a great week. Thank you.

Ladies and gentlemen, welcome to the Sobi Q3 Report 2025 Conference Call and Live Webcast. My name is Sandra, and I will be the operator for your call today. [Operator Instructions]

The conference is being recorded. The presentation will be followed by a Q&A session. [Operator Instructions]

The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to Guido Oelkers. CEO. Please go ahead, sir.

Yes. Thank you, and hello, everyone. I'm really delighted and we are overall delighted to welcome you to the third quarter 2025 conference for investors and analysts. As usual, we posted the presentation beforehand. As far as the next slide is concerned, the disclaimer, we would like to remind you of the usual provisions on statement about expectations and projections of future events. And unless stated otherwise, we will be making comments that most relate to the third quarter at constant currency rates in Swedish krona.

Today, we plan to cover the following key aspects of our Q3 report. I'm joined by Henrik Stenqvist, our CFO; and Lydia Abad-Franch, Head of R&D and Chief Medical Officer. We plan to review the presentation first and then open up for Q&A at around -- until around 2:00 p.m. [Operator Instructions] We propose you ask one or two questions max at a time. So with this said, let's go straight to the presentation. As we want to cover quite a few topics today on the quarter, I would like to provide you with an overview before driving into the specific -- diving into the specifics. So first, -- we delivered an outstanding Q3 performance with 21% growth at constant currency.

This was driven by a remarkable 39% growth of our strategic growth portfolio and a clear validation of our innovation-led strategy and commercial execution. Adjusted EBITDA was 47% on sales shows strong, obviously, business momentum, but also cost discipline. We took an impairment on Vonjo, reflecting the deferred uptake. We will explain later on how we drive growth moving forward. Material progress in our pipeline, let's say, foremost, the scheduled PDUFA date of NASP in June '26 and the approval of olezarsen in FCS as well as the readout of 2 Phase III studies in several -- in severe levels of triglycerides evidence the progress.

The momentum in so many different areas of our business have prompted us to increase guidance in terms of top and bottom line. Please turn to Slide #5. Let's have a closer look at our Q3 performance. We delivered net sales of over SEK 7.7 billion in the third quarter, representing a 21% increase at constant currency rate compared to last year. This growth is driven by continued success of our strategic growth products, as earlier mentioned, which accounts now for 64% of total sales. Whilst nearly all products performed well, the fantastic performance of Doptelet Gamifant and Altuvoct should be noted. Regions have performed well. Growth rates of 37% in the U.S., 21% in Europe and 43% in international demonstrate that the engine of our company is very productive. Let us go through the specifics by product. Turning to Doptelet, our largest product and key contributor to our growth story.

In Q3, Doptelet delivered 46% growth at constant currency, continuing its strong trajectory, as can be seen in the chart on the left, reflecting consistent demand and market expansion. This growth is underpinned by Doptelet's differentiated profile in ITP, excellent efficacy and fewer dietary restrictions make it a compelling option for both physicians and patients. Doptelet has performed well in the U.S., but the growth has been carried by all regions, including international markets. Japan launched 1 month ago and already showing very promising signals. Please turn to Slide #7.

In Q3, Beyfortus delivered just over SEK 1.16 billion in the early part of the season. RSV immunization rate for the '24-'25 season stood at 57%, indicating significant headroom for further growth. In view of the debate regarding the use of prevention medicine, we commissioned an independent survey with over 100 physicians. The summary of the findings are as follows: Beyfortus has been recognized as a competitive product with a high preference share of over 90% amongst HCPs. HCPs did not see restrictions or limitations in terms of access for patients and physicians.

And thirdly, from the survey, we also saw that physicians expect no decline in RSV cases for the season, although the season does seem to be starting later according to the latest CDC data. In summary, Beyfortus appears to be well positioned as the season begins, supported by strong clinical fundamentals and high prescriber confidence. Our take is that there is a typical uncertainty around the start of the RSV season and stocking levels. This was something we also saw with Synagis. Sanofi as a product owner, may provide additional color to the status during their report. Let's turn to Page #8.

Altuvoct delivered SEK 769 million in sales, resulting in haemophilia A sales of SEK 1.6 billion in the quarter, representing 31% year-on-year growth. On an annualized basis, we may exceed SEK 6 billion of haemophilia A sales this year. The market dynamics, as we talked about throughout the year, are continuing with continuous switches from Elocta and other competitors, including nonfactor products, which reinforce Altuvoct's competitive edge. Our launch strategy is progressing in 3 waves. We wanted to give some orientation that our current growth is primarily coming from early launch countries and obviously, more to expect during this year and the years to come. We expect to launch in Italy and France during this year. And when you look to the left of the slide, you can see, let's say, an increase in Q1 on Elocta.

This was primarily driven by tenders at the time, and this will normalize throughout the year. So in summary, a very encouraging story with Altuvoct and the overall haemophilia A franchise. Let's turn to Slide #9, Gamifant, which continues to deliver exceptional growth and strategic progress. In Q3, Gamifant generated SEK 733 million in sales, sales, up 98% year-over-year. A key milestone this quarter was the U.S. launch of Gamifant for macrophage activation syndrome in Still's disease. This marks the first ever approved treatment in both adult and pediatric patients with MAS and it gives us confidence to grow in HLH overall.

Looking ahead, we are advancing our Gamifant IDS program targeting immune dysregulation in Sepsis. The EMBRACE Phase IIa trial is actively recruiting with a primary endpoint expected by the end of 2025. We will provide a market update in our Q4 earnings. While still early, this doesn't -- this product has obviously very material space and potential in this indication. In the U.S. alone, there are approximately around 2 million sepsis patients hospitalized annually, while nearly 1 million require ICU care. IDS represents around 20% of these patients, and these patients have a mortality of 40%, highlighting the significant unmet medical need and the potential impact that Gamifant could make in this space. Looking forward to update you latest by Q4 -- by the Q4 reporting.

Please turn to Slide #10, Vonjo. Vonjo has demonstrated solid demand growth of 9% for the quarter versus previous year. but was down 11% due to gross to net adjustments primarily related to 340B and Medicare redesign. The disadvantage with regard to a narrow label versus competition despite the overall strong body of evidence has not allowed us to achieve our own ambitions yet. As a result, we have recorded an impairment charge of SEK 6.6 billion. Consequently, we focus on broadening our label in MF and internationalizing the product. PACIFICA has been accelerated and will become the key cornerstone in this regard. Lydia will give you an overview later in this regard. In addition, the development of the VEXAS indication is making significant progress.

The chart should illustrate and outline that we still expect Vonjo to become an important growth driver for Sobi, but later. Please turn to Slide #11. We have seen the positive margin evolution in our press release, and Henrik will cover it in the financials in more detail. This was driven by relatively -- relative OpEx reduction of around -- from 38% to 33% on [indiscernible] sales, driving margin improvement to 47%.

I just want to make a point that the efficiency program reported in Q2 helped us with the earnings this quarter. But more importantly, will give us headroom to support an important portfolio of launches and development projects in the years to come.

Hence, this initiative was an important strategic move for the company's evolution. Please turn to Slide #12. We have shared quite a few insights on our portfolio at previous events. Just to emphasize, 5 key and planned launches and 4 priority clinical projects evidence a strong ambition and commitment for the group. Before closing my section, I want to shed light on the opportunity with regard to Tryngolza or olezarsen. Please turn to Slide #13. Just to give a quick perspective on the disease area. We have got an approval for Tryngolza in Europe in FCS, an area that we are very familiar with via the preceding product called Waylivra. In September, the data from the CORE 1 and CORE 2 study, both Phase III studies were announced, which included over 1,000 patients with sHTG, including MCS patients and showed a 72% placebo-adjusted reduction in fasting triglycerides. Equally important, we observed an 85% reduction in acute pancreatitis events compared to placebo.

These data suggest a major breakthrough for patients with MCS and severe hypertriglyceridemia, while occurrence of acute pancreatitis is a major medical issue. The full data will be presented at the podium on November 8 at the American Heart Association Conference. These results position Tryngolza as a potential game changer in MCS treatment. Please turn to Slide #14. Let's now look at the commercial opportunity for Tryngolza, which we believe is highly significant in the treatment of MCS, meaning with more than 880 milligram per deciliter triglycerides. We have performed 2 deep dives on the disease over the last couple of weeks. In Europe, the cutoff point for the treatment of these patients will be at higher triglycerides level, as mentioned before, for multiple chylomicronemia syndrome or MCS, with a cutoff of 880 milligram per deciliter. In this indication, the number of patients in Europe 5, the leading 5 countries are around 700 patients, 700,000 patients.

The product will become very important for those poorly controlled with a high risk of acute pancreatitis. So meaning for a subgroup of those patients around about 1/3. Considering all these factors, the product will have a peak sales potential of over SEK 5 billion in EU5 alone. Please keep in mind that our territory extends to all Europe, and most of the international markets, so a total patient population of 4 million, which obviously need to be then adjusted for the ability to purchase or the ability to get reimbursement.

We will submit an EMA in 2026 for the MCS indication. But in totality, you can get, I think, a sense that this is a major opportunity for SOBI. I want to close my presentation by emphasizing that we had a very strong business performance in Q3, as you can see on the left, 21% growth, 47% adjusted EBITDA. We had significant pipeline progress. Given our momentum, we increased also our guidance for sales and EBITDA.

On this note, I would like to hand over to Henrik, who will lead you through the financials. Thank you.

Thank you, Guido, and hello, everyone. Please turn to Slide 17, and we will now take a look at some key financial metrics for the quarter. In Q3, our revenues of SEK 7.8 billion correspond to a revenue growth of 21% at constant currencies and 30% excluding seasonal Beyfortus royalties. We saw double-digit growth across all 3 segments and in each region. From a product perspective, growth was driven by Altuvoct, Gamifant and Kineret. If we look at the table on the right and the adjusted gross margin of 80% in the quarter compared to 81% last year. We saw an improvement in margin from positive mix effect and the new Aspaveli royalty agreement, but this was offset by lower Beyfortus royalties.

Operating expenses for the quarter were flat to last year at CER. SG&A, excluding nonrecurring items and amortization increased by 3% at CER, driven by launch and prelaunch costs for Altuvoct, Aspaveli in Nephrology and NASP. And this was partially offset by lower costs across Vonjo, Doptelet, Synagis and Zynlonta, including the cost savings initiative we outlined earlier this year. R&D expenses declined by 6% at CER, excluding nonrecurring items, mainly due to NASP programs that are now complete as well as the cost savings initiative announced in Q2. This was partially offset by development programs in Vonjo and Gamifant. And as a result, the adjusted EBITA for the quarter amounted to SEK 3.7 billion, equal to a margin of 47% compared to SEK 43 million for the same period last year.

The Q3 net earnings number is a reported loss of SEK 2.9 billion, and this is due to the impairment charge for Vonjo of SEK 6.6 billion. We remain confident that Vonjo will be a long-term growth driver, but also acknowledge that all expectations from our original case have not materialized. And the future growth opportunity comes from potential broader label and international expansion. We also continue the development of Vonjo in potential new indications in CMML and VEXAS. And excluding the impairment and other one-off items, the adjusted EPS grew by 40% in Q3. Operating cash flow for the quarter was SEK 1.8 billion compared to SEK 1.2 billion last year, driven by improved operations. And that gave a net debt at the end of the quarter of SEK 12.2 billion, maintaining the net debt-to-EBITDA ratio from Q2 of 1.1x.

Please now turn to Slide 18, and we will discuss the financial outlook for the full year 2025. And as usual, this outlook is based on revenue growth at constant exchange rates and adjusted EBITDA margin. For the full year '25, we have upgraded the revenue guidance from high single-digit percentage to low double-digit percentage growth at CER. We've also upgraded our adjusted EBITA margin guidance from in the mid-30s percentage of revenue to mid- to high 30s percentage of revenue. Through the first 3 quarters, we saw strong momentum across our portfolio with 15% growth at CER. We expect continued growth into Q4 across our commercial portfolio, primarily in Altuvoct, Doptelet and Gamifant. And this guidance also reflects adjusted expectations for Vonjo, reflecting the year-to-date performance.

Our year-to-date adjusted EBITDA margin of 40% gives us confidence that we will be able to deliver a full year margin in the mid- to high 30s. We will benefit in Q4 from expected continued revenue growth. But in addition, we see lower operating expenses than previously planned, mainly due to the realignment of SG&A and medical activities for NASP following the June 2026 PDUFA date as well as an accelerated impact from the restructuring activities that we announced in Q2 and this, together with a disciplined cost control. Despite this OpEx development, OpEx are expected to increase in Q4 quarter-over-quarter.

In SG&A costs will ramp up in Q4 for our 2 key launches, NASP in uncontrolled gout in the U.S. and in Europe for Aspaveli in nephrology. In R&D, we will continue to invest in our priority development projects at a slightly higher pace than in Q3. In addition, we'll be preparing for regulatory submission of Tryngolza, olezarsen in MCS.

And with this, I now hand over to Lydia. Thank you.

Thank you, Henrik, and hello, everyone. We start with the pipeline milestones on the next slide, please. In the third quarter of this year, we have continued the progress across our portfolio, and I would like to highlight several key achievements. NASP for uncontrolled gout has reached an important regulatory milestone with the FDA's acceptance of our biologics license application.

For Doptelet, we received FDA approval for an extension of the indication and launched a new sprinkle formulation designed specifically for pediatric patients with immune thrombocytopenia. Additionally, Doptelet's indication for ITP was approved by PMDA in Japan, further expanding its reach in international markets. And continuing in Japan, we have submitted our application to a PMDA for Kineret, seeking authorization to treat Still's disease.

We are also pleased about the EMA approval of Tryngolza for Familial Chylomicronemia Syndrome. We will soon transfer the marketing authorization from our partner, Ionis, to Sobi.

Finally, as Guido already discussed, Ionis reported positive top line data for Tryngolza in severe hypertriglyceridemia, which paves the way for expanding its indication. In addition to these milestones, we also see progress in other areas. Our studies for Vonjo in MF and VEXAS are accelerating. We will present new data from several assets at ACR this week and our reputation with patient groups has received good marks.

So in this slide, we will talk about Vonjo and the clinical program that is gaining speed. For the PACIFICA study, our expansion efforts have accelerated recruitment even further with the new countries and sites being successfully onboarded. Enrollment rate in the third quarter was 50% faster than in previous quarters. We remain on track to complete enrollment in 2026 and aim to get there earlier.

With respect to the PAXIS proof-of-concept study, recruitment is already ahead of schedule, thanks to strong interest from the VEXAS community. The full interim analysis group of 30 patients have been recruited in the first 4 months and we anticipate the interim analysis for futility and safety in the first half of 2026. The research collaboration on CMML is also progressing with a planned first patient in this year. This means we will soon have new evidence on myelofibrosis, VEXAS and CMML. And this will help us to further improve Vonjo's positioning in clinical practice and engage with regulatory authorities.

Next slide, please. Vonjo in VEXAS, together with Gamifant HLH/MAS will also be a topic at the ACR Congress this week, where we will have several oral and poster presentations. For our NASP program, we will have 2 oral presentations at ACR, demonstrating the robust efficacy of NASP on key parameters and clinical manifestations, such as serum uric acid levels, gout flares and patient-reported outcomes.

Today, I would like to highlight the long-term data for NASP, which will be one of our poster presentations. This is data from the 48-week extension to DISSOLVE I, our pivotal trial to assess long-term efficacy and safety of NASP in uncontrolled gout. As discussed at our investor call in September, NASP demonstrated a rapid and sustained serum uric acid reduction through 24 weeks of treatment. Similarly, there was a reduction in gout flares, and about 1/3 of patients have complete resolution of their tophi. Participants of the DISSOLVE I trial continue onto the blinded extension portion of the study for another 24 weeks of treatment.

On the left side, you see the long-term durability of NASP, consistently maintaining low serum uric acid levels. During the 48-week study period, serum uric acid levels consistently stayed at or below 2.4 milligram per deciliter for NASP, whereas the placebo group maintained levels comparable to their baseline value. In addition, there was also a reduction in gout flares. All patients in the NASP high-dose arm were flare free at the end of the study, while 23% of patients on placebo experienced flares. NASP was generally well tolerated with low discontinuation rates during the extension phase and no new safety signals were observed. Overall, these results confirm the durability of efficacy of NASP in uncontrolled gout. Alongside the oral presentation, poster sessions will also be featured, focusing on NASP and uncontrolled gout, including a new measure of caregiver burden. This focus on patients and caregivers brings me to the next slide, please.

If you can move to the next slide, please. Thank you. I'm proud to share that the rare disease patient groups have rated Sobi the most reputable rare disease company out of 31. This was the first time we appear in the patient view survey. This survey shares the perspective of 518 rare disease patient groups from 58 countries. Together, they represent the voice of 2.4 million patients. The group's rated Sobi highly on having a patient-centered approach and collaboration on quality and safety, as well as access information and integrity. This is very encouraging. It reflects our longest standing commitment to patients and our systemic approach on working with them.

Our Unite 4 Rare program bundles our activities in this area. It was co-created with patient organization representatives and has 4 pillars. We aim to deeply connect with patient communities worldwide, including those that are typically underserved. We also nurture our partnership with patient organizations in a sustainable and ethical way that helps them thrive. We collaborate with and involve patients in the development of our medicines, for example, in the design of our Sobi-sponsored clinical trials. And we're innovating the way we work, creating an environment that enables engagement with patients. We are honored by this, feedback and inspire to become even better. Next slide, please.

Looking ahead, we anticipate progress with the major regulatory submissions in the U.S., Europe and Japan. We plan to end this year with the Aspaveli CHMP opinion for C3G and IC-MPGN, the Japanese submission of Aspaveli in these nephrology indications, the submission of Gamifant in HLH/MAS also in Japan, and the IDS top line data. As Guido said, we aim to give you an update with the Q4 figures. Next year, we will be already launch NASP in the U.S., Aspaveli in C3G and IC-MPGN, both in Europe and Japan, as well as Gamifant in Japan. And finally, we plan to submit Gamifant HLH/MAS and Tryngolza in Multifactorial Chylomicronemia Syndrome to EMA.

And with that, I would like to hand back to Guido. Thank you.

Yes. Thank you, Lydia. So just summarizing maybe on the next slide. As you know, you have seen -- we believe that we had a pretty spectacular performance in Q3 with 21% growth, reaching an EBITDA margin of 47%and over sales. And this, as explained, this is driven by operating leverage, but also discipline in terms of cost and position us well for the future to support what is important to us.

We had to rebase, obviously, Vonjo, but I hope we clarified that we believe that Vonjo remains a growth product. Obviously, we have to make -- wait for the readout of PACIFICA and then for a broader label and internationalization to come to a material inflection point. But overall, we believe that this is an important product for us, and then we'll see what will come out of the new indications we're progressing right now very well.

We have made significant progress with regard to our pipeline, as Lydia pointed out eloquently. And here foremost, we would like to draw your attention to olezarsen and to NASP. So a business that truly, we have strong momentum, we have pipeline development. And as a consequence, we also were able to increase our guidance. And we look forward to your questions as you may have so.

Thank you so much. And maybe we'll go now to the Q&A session.

[Operator Instructions] Our first question comes from Ben Jackson from Jefferies.

Just 2 quick ones, if I may. Firstly, could you just talk about your assumption of Beyfortus that is in the current guidance and the upgraded guidance that you gave for the year? Obviously, you're talking about physicians saying that they're still expecting to see the same number of RSV cases. Does that mean you're expecting this largely to be a phasing thing with regards to this quarter? And then secondly, could you also just talk about the relative contribution of the realignment, the accelerated impact of the restructuring and also the cost control that you implemented with regards to the EBITDA margin, how it came out this year?

Just trying to get a sense of in 4Q, is that a reasonable exit rate to go into next year when thinking about costs and costs ramping up? Is that a fair assumption? And then if I could just squeeze a third one in, sorry, just to clarify, you said that you're going to update either on the market or update the market on the Gamifant study at 4Q. Could you just clarify whether you're going to update the market on the results or whether you're going to update what your thoughts are around how big the market could be at 4Q?

Yes. Maybe I'll start with the easy one and then Henrik will talk about, let's say, the financial part and then Lydia, maybe on what you can expect from us in Q4. On Beyfortus, I mean, we obviously don't control the product. And what we try to allude to the fact is from what we can see based on this interview, nothing wrong with the product. Product is a high preference share is, let's say, there's no limitation of access, all the worries that for some time, people had for patients as well as for physicians. Physicians feel that there's going to be more patients even though there has been a slow start of the season.

And then it's a question of how much inventory is in the trade. And then there -- which we cannot tell you. And then there's a question how quickly the season is going to pick up. What we hear from the physicians is that they are confident that the season will pick up. That does not necessarily mean that the calendar year is showing what the equally good results like last year. So that is a question really for Sanofi. But what we can say is we felt that's the reason why we have also performed this survey because we are not in charge of the business, obviously, but we wanted to get a feel, is there something we should take note of that should change our view on the product.

Now that doesn't help, obviously, with judging a calendar year. But what we found at least is that there's nothing wrong with the product. And then the question is, will that compensatory effect happen in Q4 or next year? And this is really something you have to ask Sanofi. But at least what we can say is that the product is in a good shape.

And maybe now to Henrik with regard to the financial question.

Yes. So if I understood you well, you wanted to understanding on the relative importance of the realignment of NASP spend to the standard review time by the FDA and our restructuring activities. Is that right?

Yes, that's right.

Yes. Then the answer is that the realignment of NASP spend was the larger of the 2.

Yes. So basically, what we will have to share by Q4, it's the top line data that we will be seeing. So the study is finalizing the recruitment. We will have the top line data by the end of this year. So that's what we will be able to share what is the data that we've seen and that will serve us to inform the next steps in terms of the development of Gamifant in the IDS program.

And sorry, just to be clear, that's at 4Q results or within 4Q, you expect that top line?

That would be at Q4 when we communicate the results.

The next question comes from Kirsty Ross-Stewart from BNP Paribas.

Maybe a first one just on kind of capital allocation. In light of the launches that you've got coming next year and now kind of pursuing the olezarsen indication in MCS, can you just provide an update on your kind of appetite to do further M&A? I know that, that was on the cards. I'm just wondering if your perspective on this is the same or has changed in light of the evidence you're making -- in the investments you're making next year or whether you still kind of got the capacity to continue to build out the portfolio further? And then the second one on Vonjo.

Can you just confirm whether the PACIFICA trial itself, you believe will give you the potential to gain the broader label authorization? I noticed that the chart in Slide 10 indicates that you're kind of expecting still an inflection in Vonjo next year. I just want to understand and how to reconcile that with the trial inclusion criteria, which I think has the same platelet count as the current label. And then just a very, very quick one on Beyfortus. Can you just remind us on how the tiered royalty is set? Is the lower sales that we may have seen this quarter, could that result in a lower royalty rate for the year or the step-up from last year's 25% royalty set regardless of the revenue?

Yes. Let's start with the -- let's maybe with Vonjo. And let's say, there, basically, what we see is that the inflection PACIFICA in conjunction with the other evidence may be enough to give us a label expansion, not on itself. It's a confirmatory trial, but if you are -- but as we are right now, we got a conditional approval, even with the additional evidence that we have generated, we cannot -- we are a little bit stuck to get a label extension. Lydia do you want to comment on this?

Yes. So as you said, PACIFICA, it's a confirmatory trial with the platelet count that we already have in the label. But what we have already started some discussions with the FDA in terms of what could be the totality of the data that we could present, including [indiscernible] existing data that we have already gathered from previous studies on patients with platelets above 50,000, plus real-world evidence and additional sources of data. So we are working on that, and that's what we would like to use as a basis for an expanded label. But obviously, the first step for everything is to complete the recruitment of PACIFICA to get the confirmatory data, and then we can add the additional sources of data.

So with regard to BD, I mean, I think we see this more like this. We have obviously not a lot to do with olezarsen, with the C3G IC-MPGN launch, which we will start the early next -- first quarter next year. We then have NASP in BLA expected in June next year. And then olezarsen submitted in Q1 and then probably becoming a launch then early '27. So it's -- and we have the ongoing launches for Altuvoct and Gamifant. So quite a bundle.

And so what we are looking for is architecturing, obviously, the company for long-term growth. And we can see that we will -- with these initiatives, we will soon have, again, bandwidth definitely in the R&D organization for additional projects in terms of pipeline. And we like to architecture growth that stretches then into the -- beyond the mid-30s, and this is what we are currently looking at when we look at opportunities. And obviously, we have a broader ambition, which is to become a leader in rare disease, and there's still some room.

But we -- it's not size for the sake of size. We need to be sure that we can manage this. And yes, as you have seen sometimes in most cases, we have got it right. Now in one case, we had to be -- we have a deferred uptake and we need to take this. But mostly, I think it was 21% growth is not so bad. And let's say, so we probably get more right than we get wrong. And then with regard to the Beyfortus royalties, first 2 years was 25%, and we guided the market that there are 2 elements to this. One is time and the other one is the size. And there's a mechanism that potentially goes up to 35%. But in the blended, it's probably the lower 30s. And so the royalty is going to increase for Beyfortus.

All right. Let's move on to the next question.

The next question comes from Viktor Sundberg from Nordea.

So first one on the Gamifant. It's quite a pickup in sales here in Q3, and you referred to some impact from your extended approval into Macrophage Activation in Still's disease. So I was just wondering, was this a major driver here? Or was it other factors? And just in general, also how the initial uptake is for this indication? And then I also have a second one on Gamifant, I can start here.

Yes. I mean, basically, the uptake, as you have seen, the previous quarters were all very strong. So the -- it's not just the launch. I mean it is the value system, the way the organization is currently set up with very strong medical access -- and obviously, commercial team is paying dividends. And then the new indication helped. But the company was -- the team was on a fantastic trajectory before.

And just now this 19% quarter-on-quarter growth clearly has benefited from the launch and the broadening of the indication. But basically, we are on track, as we always said, that we said with the new indication, we think that we have -- we can double the opportunity. We stand by this and all indications point into the right direction.

Okay. Great. And also another one here on Gamifant. As you mentioned, we have the EMBRACE trial coming up. And I guess sepsis is still quite a heterogeneous patient population if you account for your biomarker selection with comorbidities, et cetera. So I just wanted to understand your thinking if results show trends, but not statistically significant benefits on the SOFA score. Would you still jump into a Phase III? And do you see this trial as more of a chance of getting important data points for moving the program further? And maybe on the other hand, if the results are very, very robust, what's your thinking here of using accelerated approval in that case? Just trying to understand what outcomes that are on the table for this readout.

Yes. I mean, we debated it and then Lydia will comment on this in a minute. And maybe we'll see the bar for other treatment is not incredibly high in terms of mortality reduction because it's a devastating disease. And many companies have -- for many products, it has been a bit of a graveyard. Now we are more confident. Otherwise, we would have not endeavored this if there wasn't this pre trial, where we screened with Professor [ Giamarellos ] 5,500 patients understood the [ endotype ]. And as a consequence, it narrowed down the funnel quite considerably and believe that there is a mechanistic evidence of Interferon-gamma involved.

From my perspective, we'll really have to see what is the mix of SOFA score improvement and whether we see any signals of on mortality and then make sure that we do a sound decision. But Professor Giamarellos is the President of the [indiscernible] Association in Europe. He's is a very well-known KOL who has a lot of experience, and we will discuss this with him and obviously other KOLs, what the appropriate step is. I'm not sure that we have already the metrics in place. So Lydia, you want to comment?

Sure. Thanks. So yes, basically, sepsis is a very complex disease, as you mentioned in your question. And with this biomarker, we are really following this in vitro study and really targeting those patients where there is an increase in CXCL9. The study, as you mentioned, it's based on the primary endpoint is the SOFA score. And it's -- we will see some data on mortality. But obviously, as we know, these are very complex patient population. And I think we -- knowing how complex the disease is and the treatment landscape, what we need to do is really not to jump ahead.

So we will really look at the data step by step. In the meantime, there is an independent data safety monitoring board that has reviewed the data and has agreed that the study can continue with enrollment to finalize as we expected very soon. So I think it's -- it will be premature to say we have clear the path of if this is the target SOFA score improvement, this is how we are going to proceed. So we will be really discussing a, with KOLs, as Guido mentioned, but also with regulators. And based on that, we will make the decision on the next steps. So I'm sorry to be a little bit vague, but due to the complexity of this disease, I think it would be premature to really adventure some more specific endpoints here.

The next question comes from Henrietta Boeg from Deutsche Bank.

Just one on what extent can we extrapolate the 2025 margin performance exceeding expectations? And if you could talk about the margin outlook over the coming years, given the need to invest behind the gout and the C3G launches, that would be helpful. And then I guess just a follow-up on the sepsis data in Q4. So we'd have to wait until a follow-up, maybe 2026 for the Phase III details.

Yes. So let's start with margin expectation. I mean what we have done is that we said mid- to high 30s. And there is nothing more to say. I mean the -- right now, I mean, we come obviously year-to-date performance, you have seen the margins are ahead. We have -- on the other hand, we have 2 launches that we are now preparing one in NASP in a new therapy area and one in nephrology in Europe. And this will require some investments. And we haven't decided yet what to do, what to put in now. We know that we will definitely support the nephrology launch already this quarter now because it's basically under us. And -- but we -- I'm not saying -- Henrik, you want to comment on the margin?

No, I mean that's right. And we also have, obviously, the preparations for olezarsen in MCS. But also going into 2026, we expect continued strong momentum on the top line.

Yes. I mean that's the reason it came a bit short. Obviously, the savings have made a significant difference. But for that quarter, the expense line had a higher impact, but that doesn't mean that the savings were not -- that we have ring-fenced are not significant enough. They will help us, but business is increasing. We expect a good strong momentum that will give us some room to grow. And then we have some ring-fenced savings. We will give you a margin guidance in conjunction with Q4. And with regard to the data, now that's Q4 earnings report, then we will come latest with the Gamifant data. And if you have -- if we can report something earlier, let's say, we will report early.Yes. I mean that's the reason it came a bit short. Obviously, the savings have made a significant difference. But for that quarter, the expense line had a higher impact. But that doesn't mean that the savings were not -- that we have [ ring-fenced ] are not significant enough. They will help us. But business is increasing. We expect a good strong momentum that will give us some room to grow. And then we have some ring-fenced savings. We will give you a margin guidance in conjunction with Q4.

I mean -- but I think -- Lydia, do you want to comment?

Yes. I think, again, it's back to the data. Obviously, if there is outstanding data, maybe regulators want to ask even to move faster. But without data, I think we need to be cautious and just wait so that then we will be happy to report as soon as we can.

[Operator Instructions] The next question comes from [ George ] [indiscernible] from ABG.

This is George. I have 2. So firstly, have you [indiscernible] Sanofi any price pressure for Beyfortus? And secondly, regarding the submission of Gamifant in HLH in the EU, to what degree, if any, are you awaiting a final decision here until you have more visibility on the path forward for interferon gamma-driven sepsis as a strong readout potentially could make sense then to await the submission in HLH in order to maximize the exclusivity period in interferon gamma-driven sepsis?

Thank you I mean, with the price pressure, Sanofi can and will not discuss these things with us. We have not heard via our informal channels of this, but that doesn't mean -- I would not exclude that there is -- you really have to ask them, let's say, but we are not aware of it. And then with regard to HLH in Europe, I mean, we have supported now over 100 patients with primary and secondary HLH in Europe. We feel that it's -- that we owe it to the patients and let's say, that we get the product registered based on the data that we have generated that led to the approval in Europe. And you will hear from us Lydia to comment of this effort.

Yes, sure. So basically, the approval of Gamifant in the U.S. is based on the Study 06 and Study 14, where many of the patients, I would say, most of the patients on Study 14 were coming from Europe. So there is a strong interest in Europe of having access to this treatment because, obviously, these patients are having a condition that is life-threatening. This is our commitment to patients, and we have now data that has led to an approval by the FDA, and that's why we want to bring it to patients in Europe.

We do have a managed access program, compassionate use program in Europe, and we have provided access to treatment because of our intention to bring it to the different markets in Europe. So I think it's really our responsibility as a company to bring the product as soon as we can. And obviously, we are in conversations with EMA and with strong support from the community. And that's our commitment to the HLH community, and that's what we want to do as a first step.

And with regard to IDS, let's look at the results and then there will be -- if the product works well, for sure, we will be in very close dialogue with regulators given the high unmet medical need in this area, then we'll update you obviously.

There are no further questions. Back over to you for any closing remarks.

Yes. Thank you so much for your interest. I mean this -- we have quite a lot of items today and very much appreciate that you stay tuned. We are excited about this company, as you can see, not only from today's perspective, but also from tomorrow and tomorrow after tomorrow's perspective, looking at our pipeline, and we are here to build this business. And we feel that we have momentum. It's pointing into the right direction. We obviously have a bolus of new assets, but I think this is a happy problem to have. And let's say, then we will figure out how to manage financial expectations that a lot of people have for us. On this note, I wish you a great week, and thanks for being so flexible and joining our earnings call. Thank you so much. Wish you a great day.

Ladies and gentlemen, the conference is now over. Thank you for choosing Chorus Call, and thank you for participating in the conference. You may now disconnect your lines. Goodbye.

Hello, everyone. This is Guido Oelkers, CEO of Sobi. We are delighted to welcome you to this call to discuss the NASP program after we have just received the acceptance of the filing package with FDA for uncontrolled gout.

Please turn to Slide 2. We would like to remind you of the usual provisions on statements about expectations and projections of future events. With this said, please turn to Slide 3. I'm very pleased to have Dr. Herbert Baraf joining us today. He is Clinical Professor of Medicine at George Washington University, Associated clinical Professor at the University of Maryland and a Senior Clinical Adviser at the National Institute of Arthritis and Muscular and Skin Diseases at the National Institute of Health in Bethesda, Maryland.

Dr. Baraf was a founding member of Arthritis and -- of the Arthritis and Dramatism associates one of the largest private rheumatology practices in United States, he has served as a principal investigator on over 400 clinical trials, including several significant therapeutic gout trials.

We are also joined by Dr. Rehan Azeem, who is a medical development lead for the NASP program, here at Sobi as well as Matthew Winfield, our NASP core asset team leader at Sobi. Dr. Azeem has served in various medical research capacity on NASP, formerly SEL-212 for over 7 years, while present with Sobi and historically with Selecta Biosciences.

Please turn to Slide 4. And here, let me start with a high level of overview of the opportunity and unmet medical need and uncontrolled drought. This executive summary lays out the key pillars of our story. There's still a high unmet medical need in uncontrolled gout, a condition that while affecting a smaller subset of patients carries a disproportionately high impact in terms of pain, complication and mortality.

Uricase therapy is a proven and effective option for these patients, offering rapid and meaningful relief. However, despite its efficacy, uricase therapy remained significantly underutilized with limited market penetration. Yes, even in its current state, the market already exceeds USD 1 billion, underscoring the potential of the market.

NASP, our innovative investigational therapy is, hence, a significant opportunity for Sobi. It's monthly 2-component, the uricase regime -- regimen designed to deliver robust efficacy with the need of our oral systemic immunosuppression. This sets the stage for a deeper dive into the science, the high unmet medical need and the commercial opportunity.

With this said, I hand over to Dr. Baraf.

Thank you very much, Guido. So I'll be discussing the burden of uncontrolled gout and its pathogenesis. Next slide, please. So gout is a disease that has sort of exploded with increased survivability around the world in terms of life expectancy. It is a chronic inflammatory disease caused by a buildup of monosodium urate crystals, the precipitating salt of uric acid in the blood. This precipitates in the soft tissues and in the joints, particularly in cooler and under circulated places. Thus, the foot is the site of 50% of first attacks of gout and over time, these attacks become more frequent.

The global prevalence of gout is doubling every 30 years because we're living longer, people with kidney failure and heart failure or on diuretics, which raise serum uric acid levels. And so the prevalence around the world is increasing fairly rapidly. It is a -- it's worse with age with -- as life expectancy expands, it becomes worse. The global prevalence of gout is 3.2x higher in males than in females. But women who will hit the menopause begin to have the same incidence of gout as men do just that men begin sooner and with the loss of estrogen at menopause, uric acids rise.

Next slide, please. So why do these salts precipitate? They precipitate because the blood can only hold so much in solution of uric acid. Uric acid is a breakdown product of DNA, particularly the nucleic acids in DNA. And these are -- these break down to uric acid, and it's not particularly soluble. So over a blood level of 6.8 milligrams per deciliter the body uric -- the serum uric acid can't hold on to what's floating around and begins to precipitate. If you look at this graph, the light blue wedge really represents the accumulation of uric acid over time.

To the far left, you have a period of asymptomatic hyperuricemia where the precipitous really go unannounced, but they develop over time. And then all of a sudden, the first attack occurs, and that's represented by the orange spike on the left. And over time, if the serum uric acid is not controlled. These spikes occur more frequently, they last longer, more joints or effective. And as you get all the way to the far-right side, you begin to have chronic and persistent gout pain, inflammation in joints and accumulation of lumps of monosodium urate that we call tophi.

If we go to the next slide, please. What's happening physically in patients is on the far-left side, you have these crystals that deposit. These are crystals seen under compensated polarized like microscopy recovered from a joint. And these crystals are there long before the first attack ever occurs. That central picture is a gout flare. Again, 50% of first flares occur in the big toe, but they can involve any tissue. And in fact, they can -- the flares can involve the fingers, the shoulders, the knees, the ankles. And then over time, these collections of monosodium urate become so great that they erupt under the skin, they become visible.

So here's the hand of a physician who developed severe gout, uncontrolled gout because he was on no medications to keep the serum uric acid low. So as long as the uric acid is above 6.8 serum level, it will be precipitating into the tissues.

Let's move to the next slide, please. With age come comorbidities and hyperuricemia is associated with a number of comorbidities. There's a higher incidence of cardiovascular disease. Hyperuricemia is seen in the metabolic syndrome, whether it's cause or effect isn't clear. This syndrome includes obesity, diabetes, renal insufficiency, heart disease, hypercholesterolemia and all of the comorbidities that those conditions are associated with, including renal failure.

And chronic kidney disease is seen twice as -- gout is seen twice as often in patients with chronic renal disease and uric acid has adverse effects on the kidney. And the kidney, if not functioning, will cause the serum uric acid levels to rise because the kidneys can't excrete it.

Let us go to the next slide. So this accumulation of crystals causes chronic joint pain. Unsightly lumps in the patient with uncontrolled gout, social isolation, significant functional impairment and pain. And here are some quotes on the right. I think the one on the bottom right gout makes me feel helpless. I once had both hands swollen at the same time, couldn't even pick up a toothbrush or a pencil, count change button buttons, I had to defend -- I had to depend on my wife for everything.

And to the next slide, please. So how do we treat hyperuricemia, for the most part, 95% of patients do just fine if properly managed with uric acid lowering drugs with oral uric acid lowering drugs.

And the goal is to uric -- to lower the uric acid to less than 6.8 to less than 6. And in fact, the lower you get it, the more rapidly you can mobilize the deposits which are the root cause of gout. So with first-line therapy, we use xanthine oxidase inhibitors, particularly allopurinol or febuxostat. And if that fails even at maximal doses, we might add drugs that improve excretion of uric acid. Probenecid is the only drug in the U.S. that's currently approved, there have been others. And in Europe, benzbromarone is also used.

And when these fail, both UR and the American College of Rheumatology have produced guidelines that say that's where a uricase would fit in, where pegloticase or KRYSTEXXA would be used. And at the moment, that is the only uricase that's available on the market for patients with uncontrolled gout.

Let's move to the next slide, please. So here's the -- here's what uric acid does through the lifetime of the patient with gout, and we'll say the lifetime of the patient who's properly treated with ultimately with the uricase and then goes back on regular treatment. So uric acids remain high. Eventually, there are clinical manifestations, flares, persistent joint pain, tophi. Some patients don't respond all that well to oral uric acid lowering therapies and -- or physicians don't administer them properly in sufficient doses to lower the uric acid and the patient continues to have problems, and they have uncontrolled gout, which brings us to that buff color area where uricase is employed.

Now whereas oral uric acid lowering therapies will bring the uric acid down to 5 or maybe 4 and something rarely 3. Uricase drops it to almost unmeasurable levels. Uricase, we know one of the ways of mobilizing uric acid is to create a gradient between the solid deposits and a serum that has capacity to dissolve uric acid. And the greater that gradient is the more quickly you may mobilize crystals. But uricase is probably have a direct effect on urate -- on monosodium urate, where it's deposited, dissolving it into allantoin a more soluble substance that's easily excreted.

But in your case is given for a period of time until all these significant clinical manifestations of uncontrolled gout come under control. And then patients typically will come off of the uricase, and we'll go back to all uric acid lowering therapies, which at that point may be much easier may much -- may work easier to control serum uric acid and keep accumulations from recurring.

Let us go to the next slide. And by the way, those improvements are rather dramatic, whereas tophi may disappear over 5 years with standard oral therapies, we have seen improvement at 8 to 12 weeks in the clinical trial setting as well as in the clinic. So if uricase treatment is so efficacious, why is it underutilized because less than 5% of eligible patients, it's estimated somewhere between 100,000 and 200,000 patients in the U.S. would be classified as having uncontrolled gout. What limits it to just 5% because that's extensively the market that pegloticase currently has.

Well, there are safety concerns. The word anaphylaxis appears in the pegloticase package inserted 46 times. There were infusion nurses when it was first -- the drug was first approved and marketed who refused to infuse patients for fear that they would be -- the patients would be having severe unmanageable allergic reactions. The concern was a bit overblown. And over time, we learned that the way you could prevent these attacks is by learning whether or not the uricase was working and the uric acids were being dropped well below 1 or 2. And if the uricase -- if the serum uric acids had remained above 6 that meant there were antibodies, and the drug wouldn't be working.

There's some reluctance among physicians when we learned that using immunosuppressants might suppress the development of antidrug antibodies, which then suppressed the activity of uricase. There are some physicians who have been slow to learn that they can give standard immunosuppressants to make the uricase more tolerable, but also more effective. Twice monthly dosing is difficult, particularly for patients who have to travel for care, which is the current prescribing recommendation for pegloticase.

There's a shortage of rheumatologists, and a shortage of rheumatologists who are familiar with and able to infuse uricases for patients with gout, and that's been an inhibiting factor, insurance companies with pre-authorization requirements sometimes create an impediment. And some of these patients are just so damn sick from their other comorbidities, their heart disease, their renal disease, their pulmonary disease that they're just not candidates for a more vigorous therapy.

So these are the -- these are some of the factors that have kept the numbers down. And some of them are clearly fixable and some of them are structural and not fixable. But certainly, patients derive extraordinary life changing transformative benefits from a course of uricase therapy if they've got uncontrolled gout and are suffering all of the consequences of that.

And with that, I thank you for your attention, and I move things on to Rehan.

Thank you, Dr. Baraf. In the next few minutes, I will provide a high-level overview of nanoencapsulated sirolimus plus pegadricase, which I will refer to as NASP moving forward, its mechanism of action and key clinical Phase III results.

Next slide, please. NASP is an innovative investigational uricase therapy administered every 4 weeks through sequential infusions of nanoencapsulated sirolimus which I will refer to as NASP moving forward and pegadricase, a pegylated uricase enzyme derived from Candida utilis.

Since humans lack the production of uricase, this leads to uricases being immunogenic, triggering antibody production, reducing the effectiveness and increasing safety risk. Therefore, it is vital to mitigate the antibody production. First, NASP is infused to provide targeted antigen-specific Treg immunomodulation by inhibiting anti-drug antibodies specifically towards pegadricase without the need for additional oral broad immunosuppression.

Following the completion of NASP infusion, pegadricase is infused immediately in a sequential manner, given the immunogenic nature of uricases in humans, PEGylation has been added to further mitigate immune response and extend the uricase activity.

Now I will direct your attention to a short animation of mechanism of actions of NASP. Next slide, please.

[Presentation]

Thank you. The Phase III studies of NASP comprised of 2 studies, namely DISSOLVE I and DISSOLVE II. The objective of these robust parallel, double-blinded placebo-controlled studies was to compare the efficacy and safety of NASP administered every 4 weeks in patients with uncontrolled gout. DISSOLVE I was the U.S. trial, while DISSOLVE II was a global trial. For today's presentation, I will focus on discussing the pool data from these 2 studies.

There were 3 arms in each study. The 2 active treatment arms received sequential infusions of either a high dose NASP at 0.15 milligram per kilogram or low-dose NASP as 0.1-milligram. Within 30 minutes of completion of NASP infusion, patients in both treatment arms received a similar dose of 0.2 milligram per kilogram of pegadricase. Patients in the placebo arm received sequential infusions of normal saline.

The primary endpoint in the DISSOLVE program was defined as maintaining sUA target for at least 80% of weeks 21 to 24. During my presentation, I will also cover key clinical endpoints, including mean sUA reduction, gout flare incidence and production of tophaceous burden.

Next slide, please. When looking at the primary endpoint in the overall study population, a statistically significant higher proportion of patients in the NASP treatment arms maintained sUA control compared to those in placebo. With 51% and 43% of patients in the high and low dose of NASP, respectively, achieving the primary endpoint versus only 8% in placebo.

Next slide, please. This graph demonstrates the trajectory of rapid and sustained production of sUA levels for those patients who were on treatment during each dosing period. The Y-axis denotes mean sUA level in milligram per deciliter, while the X-axis shows time in terms of study visits done to assess sUA levels. The dashed black straight line in the middle of the graph denotes sUA clinical goal level for guidelines of 6-milligram per deciliter.

In comparison to the placebo group in black, patients on high- and low-dose NASP had a rapid and sustained reduction in sUA within 1 hour of the first infusion corresponding to a 94% and 95% reduction in sUA from baseline, highlighting the potency of pegadricase. When looking at subsequent treatment periods, those who maintain an active NASP treatment were able to maintain the low sUA levels, while this was not the case in patients in the placebo group, demonstrating the durability of NASP.

Next slide, please. An increase in the incidence of gout base is commonly reported by patients starting on urate lowering therapies due to the mobilization of urate crystals. For those patients who were on treatment during each dosing period, the percentage of patients who reported at least 1 gout flare during the first 12 weeks was similar between the active and placebo arms. This finding suggests that NASP does not worsen disease burden.

As the study progressed, there was a reduction in patients reporting gout flares in the high dose or low dose NASP arms as compared to placebo. This ultimately led to 95% and 94% of patients on high-dose and low-dose NASP being flare-free by the end of the study. Given that uncontrolled gout patients suffer from more frequent painful gout flares, the possibility of a treatment that does not increase these events while reducing disease burden may be positively viewed.

Next slide, please. To address the impact of NASP on progression of disease burden, we photographically examine changes in tophaceous burden as compared to baseline. Specifically looking at clinically meaningful complete resolution of tophi which was defined as 100% reduction in the area or complete disappearance of tophus without enlargement or any existing tophus or no new tophi.

In patients who received 6 doses of treatment, 49% in high-dose NASP, 70% in low-dose NASP and 5% in placebo achieved a complete resolution. This equates to roughly a 10x to 14x complete resolution of tophi with NASP versus placebo. On the right side of this slide are photographs of hand and foot of an uncontrolled gout patients on high-dose NASP received all 6 doses. As depicted at baseline, they have large visible tophi, which are completely resolved after receiving all 6 doses.

All the clinically relevant results presented here highlight that when patients are deemed responders to NASP. It is effective in reducing disease burden, including sUA, flares and tophi.

Next slide, please. Patients with uncontrolled gout have a twofold higher risk of developing CKD than those with controlled gout. When assessing response rates in the DISSOLVE subgroup of patients with Stage III CKD significantly higher proportion of patients in the 2 active NASP treatment arms maintain sUA control compared to those in placebo, equating to 52% and 61% of patients in the high and low dose of NASP, respectively, achieving the primary endpoint defined as maintaining sUA target for at least 80% of weeks 21 to 24.

Then looking at the right side, overall Stage III CKD patients on that treatment experienced slight improvement in kidney function compared to a slight decline seen in placebo patients. Next slide, please.

On this slide, I will be giving the adverse events of special interest. Notably, no difference was seen in gout flare incidents between NASP treatment and placebo groups. In addition, infections, hypertriglyceridemia and stomatitis are known adverse events attributed to the sirolimus component of NASP. There was a slight imbalance in infections between high and lower dose NASP. However, given that the study was run during the COVID pandemic, you can see that there is no difference in the COVID-19 infections amongst the treatment arms and placebo. Also, the rate of hypertriglyceridemia was similar amongst the 3 study arms.

As anticipated, the high dose had a higher rate of stomatitis compared to low dose. However, all events were mild to moderate in severity. Majority did not require any treatment and none of these events resulted in treatment discontinuation. Low incidence of infusion reactions, 3.4% versus 4.5% were observed in the high and low dose groups. This reflects a total of 7 infusion reactions across both treatment groups. These infusion reactions resolve affectation of study drug and supportive therapy. None of these infusion reactions required integration or hospitalization. This validates rationale for choosing the specific doses of NASP.

Finally, no major renal, cardiovascular or hepatic safety signals or risks were identified with NASP therapy. Generally, NASP was a well-tolerated therapy. Overall, the innovative mechanism of action of NASP combined with the substantial improvements in key clinical outcomes and safety profile offers a promising potential treatment alternative for people living with uncontrolled gout.

With that, I will hand it over to Guido. Thank you.

Thank you so much, Rehan, and please turn to Slide 25. This slide outlines our strategic growth for mass as we move from regulatory submission to launch readiness. It's a critical journey and that we step is designed to ensure that we maximize the impact and deliver value to patients and stakeholders. We have now completed the submission and received acceptance notification last week with a targeted PDUFA date of June 2026. This gives us a clear timeline to prepare for a successful launch and to ensure that we are fully prepared we have identified 4 key areas of focus.

First, we will -- we are working to highlight the significant unmet medical need in the space and the current underutilization of uricase based therapy. This sets the stage for last relevant. Second, we are strengthening the belief in mass efficacy and its unique clinical profile. Our data supports the differentiated value position, and we want to ensure that the message resonates clearly. We will continue to publish data and can even expect more data from pivotal programs at the upcoming AACR Congress in October.

Third, we are actively addressing financial and logistical barriers to treatment. And finally, we are focused on optimizing the experience to customers, caregivers and physicians. Altogether, this will pave the way for a successful launch and long-term adoption of NASP.

Please turn to Slide #26. This slide illustrates the compelling market opportunity for uricase therapy in the treatment of uncontrolled gout. Despite the large prevalence of gout, uricase remained significantly underutilized presenting both a clinical and commercial opportunity. In 2023, approximately 7.1 million people in the U.S. were diagnosed with gout of those roughly 100,000 with diagnosis, uncontrolled gout and actively managed by specialists, which is critical for identifying candidates for advanced therapies.

And finally, we arrive at the core addressable population of around 15,000 patients who are most likely to benefit from uricase treatment. The 15,000 patients represent the core opportunity for uricase-based interventions, less than half are on treatment with uricase today. Just remember that this subset of patients creates a market exceeding USD 1 billion annually with a room for a significant growth.

Please turn to Slide 27. Even though the filing is now complete, and our goal is to ensure that NASP reaches its full potential clinically, commercially and globally, we are a robust life cycle management strategy in place, and we have significant opportunities for market expansion. In terms of life cycle management, we are focused on enhancing NASP product profile. This includes ongoing data generation that could improve outcomes. We are addressing the unique needs of several special population with uncontrolled gout.

Additionally, we are focused on optimizing the experience for both patients and providers. That means improving support services and ensuring that NASP is easy to access and administer. In parallel, we are evaluating market expansion opportunities we see significant opportunities in countries such as Japan, Brazil, Middle East and Canada, and we are also exploring opportunities for Europe and other key markets moving forward.

Please turn to Slide 28. You will remember this slide from our quarterly calls. NASP is an important growth driver for Sobi, and we are launching actually 2 major -- we have 2 major launches in '26. Aspaveli and NASP, showing you the unrepresented opportunity or the unprecedented opportunity for Sobi in the year to come. And we are very excited to launch both products. First, Aspaveli in January in Europe. And then NASP during the mid of 2026.

Please turn to Slide 29. To close, we have reached an important milestone on the journey of NASP to deliver meaningful outcomes for patients while minimizing treatment burden in uncontrolled gout. NASP has demonstrated rapid and profound reduction in serum uric acid level, a critical therapeutic goal for uncontrolled gout. Beyond serum uric acid level, NASP has shown significant clinical benefits, patient experience, less clear, reduction in tophi side and overall improvement in quality of life. These outcomes speak to real-world impact of NASP that NASP can have.

This is delivered with a low treatment burden as NASP administered in a sequential monthly infusion and does not require a broad systemic immunosuppression. This simplifies the treatment regimen and reduces the burden of -- for both patients and providers. We are targeting a U.S. launch, as mentioned, mid of 2026 preparations and preparations are on the way, supported by a robust life cycle management plan to maximize this opportunity.

Not represents a major advancement in the treatment of uncontrolled gout combining efficacy, safety and convenience. We are excited about this potential to transform care and uncontrolled gout and improve lives.

So with this, you can sense we are truly excited about this forthcoming launch, we would like to give back -- hand back to the operator, and we will open the floor for questions.

[Operator Instructions] Our first question comes from Gonzalo Artiach from Danske Bank.

Gonzalo Artiach from Danske Bank. I have 2 for Dr. Baraf. The first one, it's on the comparison between KRYSTEXXA and NASP. And we know that from a response rate endpoint perspective, the COMPARE study did not show a statistical difference between the 2 drugs, but NASP patients showed lowering levels of serum urate maybe faster than KRYSTEXXA. So how would you compare these 2 options?

And the second question also for Dr. Baraf. It seems that on paper, KRYSTEXXA combined with methotrexate, which is already approved that combination has improved -- has an improved efficacy profile versus monotherapy. But you said that there is some reluctance on the use of this combo in the clinic. So in your practice, what proportion of patients eligible for uricase treatment would you put in the combination therapy and in monotherapy. And what will be your to go patient group treatment-naive patients for NASP or patients that do not respond properly to this methotrexate combination.

Let me see if I can retain all the elements of those 2 questions. In the COMPARE study, to me, what's struck me -- first of all, the comparison was between NASP, and pegloticase without methotrexate. And the primary endpoint was patients who achieved superior results in both the 3- and the 6-month periods. And it just -- NASP just missed superiority for the combination result, but at the 3-month result was superior.

If you look at the time of uric acid suppression in NASP, most of -- there was a superior outcome through probably the fourth month and then the loss of efficacy of NASP came up to the same level as the loss of efficacy with pegloticase, at least that's how I interpreted it. And it's the difference in the 2 curves probably would indicate that even if the patient didn't sustain a superior outcome at 6 months, I think it was numerically superior, the -- that period of time of difference likely led to a significant difference in the amount of urate burden at the end of the treatment period.

So my impression is that NASP performed superiorly in that setting. The practical question, who's going to get NASP as a first option and who's going to get pegloticase. I think pegloticase will still take the lion's share for a few reasons. One is that it's been in the marketplace and people are comfortable with it and certainly in the first few years. But the advantages for a 4-week versus a 2-week are those of convenience. There's a maldistribution of rheumatologists in the United States. And in addition to that, there's an inadequate supply of rheumatologists. And these would be the people who would be administering the drug.

So patients who have to travel the distance will find an every 4-week option better than an every 2-week option. It's conceivable that pegloticase will get in every 4-week indication. And then how does it differ? I think the main difference would be -- well, the initial difference would be, is the patient a good candidate for methotrexate? Does the patient drink? Is the patient reliable enough to take their co-therapy, their methotrexate on a regular basis, and not skip out on doses. NASP gives the doctor 100% control of the treatment end to end where you're relying, I don't think rheumatologists are at all worried about methotrexate except for the compliance issue and for the occasional patient, not so occasional in the gout population with an alcohol problem or with liver function abnormality.

So I think that's how it will sort out. And overall, I suspect that having 2 drugs in the market. Oh, and the last one is that both drugs are immunogenic. Once immunogenicity is established neither for either drug, the drug is no longer valuable. And although we don't have any data or any knowledge about cross-reactivity, we don't see cross reactivity with other biologics that have similar mechanisms of actions. For example, TNF inhibitors, there's no cross-reactivity of immunogenicity with the monoclonal antibodies used to inhibit TNF.

So that's -- so I think there's clearly a niche for a new entry and a new niche for an alternative, a niche for patients going from NASP to pegloticase or pegloticase to NASP that will probably be tested in the marketplace, not necessarily in the clinical trial world. But as a practical consideration, these patients are fairly desperate, and desperate patients require desperate measures. I hope that helps.

The next question comes from Mattias Häggblom from Handelsbanken.

I have 2 questions for Sobi, I guess. And the first one is the platform ImmTOR has never been manufacturing larger commercial volumes. So can you talk about your confidence in the CMC package? And if you can remind me how and where you intend to manufacture NASP and the status of any FDA audits? And then secondly, in 2020 at the CMD in December, you described the peak sales potential of the project at the time called SEL-212, a SEK 3 billion to SEK 5 billion in dollar terms at the time, $350 million to $600 million roughly. Is that still how you feel about the opportunity 5 years later? Or how would you describe it?

Yes. Let me start with the easy one, Mattias, I think we see the opportunity probably in the higher end of that range. So if anything, we are more confident about it. And we feel that we have the manufacturing process under control. We spent extensive time. I mean, for me, personally, the development of SEL-212 and now NASP has been -- it was not an easy journey, but it was a very rewarding one because the team has done a spectacular job and spend a lot of time on clinics but clinical development but also on CMC development and work with our partners, and this is at the end now to bring all of this together is very gratifying.

I mean, maybe I ask Matthew was the champion of NASP in our company, maybe how he sees the ImmTOR situation and how confident is he that we can bring this dollar to the market.

Yes. Thank you, Guido. Thanks for the question. As Guido quite rightly mentioned, we have various partners globally the combined will help us pull not only the supply chain but obviously available of products ready in particular for the first half of next year when the anticipated U.S. launch could take place.

As our technical operations team have been very close to our partnerships. We've got a very good relationship with all 5. We've been looking at site inspections. We've also been staying very, very close to what those audits are reading out from a [ mock ] perspective. We feel very confident around the current situation that we're in.

Clearly, now that we've initiated the BLA and we've had positive feedback from the FDA, those audits will now start to take place. We feel ready for those. Our partners feel ready for those. And although, obviously, it's going to be a big ask, we remain very confident that the supply chain will stay robust and that we will be prepared ready for that first half launch in the U.S.

The next question comes from Michael Leuchten from Jefferies.

Two questions, please. One for Dr. Baraf. Just going back to phasing of products. Just interested in the data that you showed on eGFR in the active arms versus control are quite compelling. And I suspect whether that's a spot estimate or just looking at the eGFR slope, that's quite a strong argument to use the product earlier than existing alternatives. So just going back to your comment that pegloticase will remain as the first-line option. Why wouldn't the data in and around the existing comorbidities push for early use already?

And then I guess related to that, what's the clinical burden of proof now for these comorbidities. Does it require CV outcome trials, or do you think there's enough data to make that case for the comorbidities?

And then a question for Guido. Just in terms of market access expenses, how do we think about the phasing of those as we head towards the June 2026 PDUFA?

Maybe you start.

I'll tackle the first question. I think the central part of that question is why do I think pegloticase will take the lion's share, certainly in the short term because of familiarity and comfort on the part of physicians who've already used it. That would be -- and perhaps the response rate, if you look at the 2 of them. But it's mostly familiarity. They're in the marketplace and we'd be adding to it. And the numbers are small. They may very well be significant. I don't -- I'm a person who performs clinical trials; I don't write them or strategize which wants to support.

So I can't tell you if the company would be doing a deeper dive there. I do know that the data was looked at with pegloticase because I was involved with that. And for that matter, with febuxostat. And despite robust lowering of serum uric acid, there was no clear renal benefit demonstrated in either of those development programs. So I think mostly out of habit, the second entry into the market. It usually takes a bit of time to get established, particularly with almost call it a boutique-type therapy like this, where there's a limited market and a limited number of specialists who engage in it.

Yes. Thank you. And maybe I just cover. We are building, obviously, a formidable team right now. We have already a core in place. we are waiting, obviously, for the confirmation on the BLA side. Now we plan for an appropriate launch, we will have the respective team size you're looking at a team that is not dissimilar to what we have built up for synergies at the time. And we think that for the kind of focus we will lay upon this product and the segmentation, we see a significant opportunity as Dr. Rehan was outlining in segments such as CKD patients, for instance, and others that and this gives a pretty large opportunity for us.

And then there is this blue ocean of patients that could benefit from the product for many of the uricases but not getting it. And so in a way, increased noise level should help the class as well as us. So that's really how we are thinking about it, but it's a significant undertaking hands. And I just want to reiterate this because it was a bit misunderstood. We have tightened the belt this year in areas that are not as core to us as in the past to make sure that we can marry in a way, earning expectations as well as give proper justice to the investment into the product.

Let me just add one other thing. There have been studies with pegloticase in patients with renal failure and studies with pegloticase in patients with renal transplants. Those are patients who wouldn't be able to take methotrexate. Methotrexate contraindicated in patients with severe renal disease. So that might be a group of patients that Sobi might focus on. I haven't had any discussions with Sobi. So I'm just sort of freewheeling here. But that would be an area where there'd be an advantage for NASP.

[Operator Instructions] The next question comes from Kirsty Ross-Stewart from BNP Paribas.

One for Dr. Baraf, just on kind of duration of treatment. I wonder if you could kind of just elaborate a little bit on the typical duration of treatment for uricase before going on to oral maintenance therapies and kind of the rate of patients who actually end up needing to go back on uricase. Is that something that happens maybe a bit of color around that?

And expectations maybe from Sobi side on NASP, I know that you said the kind of 6 doses in the trail, but is there a potential that the label allows kind of more doses than that? Is it kind of treat to a certain level of serum uric acid reduction.

And then maybe just a question on the opportunity kind of outside of the U.S. We said that you're kind of evaluating the opportunity in Europe. Can you maybe talk to some of the considerations that you're making there and kind of one of the challenges and differences versus the U.S.

So I'll address the duration and the retreatment questions. Duration-wise, when I was doing the Phase II trials for pegloticase about 15 years ago now, we reported 2 patients in a 12-week trial that had complete resolution of tophi. It was something that the company was looking at a high level of infusion reactions, about 20% -- about 40%, and they were looking at an 80% gout flare rate. And they were asking themselves what the hell we're doing with this stuff. And then I sent them these 2 photographs from my Palm's iris 71, 1.2-megapixel camera before and after photos and showed tophus resolution at 12 weeks.

So my initial impression was that you really don't need this type of treatment for more maybe 6 months duration of treatment you need before you bring them back down to a controllable level with uric acid lowering therapies. Then I saw more severe patients who had more sustained tophaceous deposits, but it's rare that a patient with the most extraordinary deposits will need more than a year of treatment. So that's the duration question where you bring them -- where you eliminate the clinical manifestations of the disease.

At that point, remember, uric acid comes from 2 sources: diet, about 10% and breakdown of DNA about 90%. And uric acid is eliminated about 70% or 80% through the kidneys and maybe 10%, 20% through the gout. So when a patient has tophi, where does the uric acid come from? It comes from the diet. It comes from the breakdown of DNA -- body DNA, blood cells, lining cells, skin cells, but it also comes in the uncontrolled gout patient from the tophi themselves. So you've got 3 forces adding uric acid into the serum. And after you've treated patients and [ debulk ] them, you have 2 sources. So they should be easier to control.

Oral therapy in gout management by primary care is terrible. We didn't talk about the untreated patient who comes to the uncontrolled gout position or the undertreated patient. In truth, if xanthine oxidase inhibitors were given correctly, which they probably never will be the size of the uncontrolled gout population would be much smaller. But now the patients under the focus of a specialist and once they achieve the clinical outcomes that the specialist is looking for, it's not that difficult to control the serum uric acid with oral drugs.

So the next question, retreatment, once antibodies form against the drug, which may occur after the therapy has stopped, you don't get treatment responses back. So we haven't examined this question, Savient then Horizon now Amgen has value -- Crealta has evaluated this question. Actually originally Savient and retreatment just is -- doesn't work. Patients have antibodies. They tend to react to the drug, and you can't eliminate those antibodies once they're formed. So retreatment is not an option. And that's why a patient needs retreatment a switch to having an alternative may be not known to be but may be a viable alternative.

Thank you, Dr. Baraf. With regard to the questions related to the study, maybe Rehan, do you want to comment?

Definitely. Thank you, Guido. As far as the DISSOLVE I and DISSOLVE II studies were concerned, as I mentioned, they were near mirror studies at each other. But the difference between DISSOLVE I and II were the study durations. DISSOLVE II was a 6-month study, evaluating the primary endpoint. While DISSOLVE I was the same. However, it also had a 6-month extension. So in addition to the initial 6 months of treatment, patients have followed up for additional 6 months for safety and efficacy. So a total of 12 months duration. And both data for the 6 months pool data for DISSOLVE I and DISSOLVE II in addition to the long-term extension have been submitted to the FDA for their evaluation. Thank you.

Thank you, Rehan. And with regard to Europe, I mean, first of all, our business case is built on a successful commercialization in the United States, and that basically prompted our guidance. The markets that we have indicated singled out other markets where we clearly see a path forward already.

With regard to Europe, we still have to do complete more work with payers to basically understand whether we can get an adequate price particularly in today's world where potentially compared to -- price comparisons with other OECD countries may be performed, but it is not essential for the economic case of this product.

Next question?

Ladies and gentlemen, that was the last question. I would now like to turn the conference back over to Guido Oelkers for any closing remarks.

Yes. First of all, I'd like to thank Dr. Baraf for his comments and for his presentation. Obviously, it's an honor to have such a distinguished expert in the field as part of our presentation. And I'd like to thank everybody for their keen interest. But as you can see, there are quite a bit of opportunities for us, and we try, obviously, to make a significant impact whether we stay in a junior position or not, time will tell, but I can reassure you that the team is very excited and very motivated to make a difference in chronic refractory gout.

On this note, I wish you a great day and look forward to staying tuned. Thank you.