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 Markets Day 2026. I hope you 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, 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. That will be followed by Lydia, who will go through some of the exciting developments we have in our clinical development pipeline right now. Continuing with that, we have three sessions, doing more of a focused dive on certain therapeutic areas. The first one will be on gout, which is where we now have two products, and I'm very pleased to say we have the Chief Medical Officer from Arthrosi Therapeutics, Rob Keenan, with us today. 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 two 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 three 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 and as we go into the next few years. And 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, which will start us off.
Yeah. Thank you, Gerard, and welcome everybody to this year's and to our second Capital Market Day. It's really, it's a joy to be here because, you know, 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. With this said, you know, I really would like to start and maybe more with a personal note, you know, and this chart I'm coming to in a few seconds. You know, when I started in May 2017, I mean, it feels like a long time ago, Sobi was clearly a very different company then. You know, we were having an opportunity in hemophilia.
We had a portfolio of distribution products in rare diseases, and we needed to get first, you know, claim our turf in hemophilia, because without making strides into this indication, there was no future really for this company. And, you know, so we evolved from a very humble beginning with, you know, on a very different scale at the time. Having said this, you know, when we set the Capital Markets Day around five years ago, Sobi was already more diversified geographically. You know, at the time, in the early days, three-quarters of our business came from Europe, and, you know, 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 2025, by 2025, you know, quite a few people said, "will they achieve this? Is this ambition really properly calibrated, or is this too ambitious?" You know, quite a few skeptics. And, you know, and quite frankly, when you look at the slides, you know, 2021 and 2020 , during COVID days, you know, this did- ambition didn't feel so great, to be honest. And, you know, and we had to think, you know, were we a little bit too forthcoming? And it was a bit humbling at times, you know, and there was not a single quarterly meeting where we were not reminded of our ambition. Particularly, I was reminded what this could mean. And you know what?
Frankly, I mean, probably till 2024, somewhere then the people start believing that we could be ahead. It was... You know, for us, it was very gratifying, to be honest, to be ahead of the 2025 target in 2024, and obviously significantly ahead, as you can see from the slide, by 2025. I'm telling you this not because, you know, we want to get, you know, a great gratitude or whatever. I'm telling you this because, you know, 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, and 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 is about what you make out of this. Because I wanted to tell you this, we, particularly when you judge now, forward-looking, what we want to achieve, that you get a sense, you know, we are not doing these ambitions lightheartedly. We are thinking about this, obviously, quite, quite a lot, but we are ambitious, and I think we should. So when you look at the more, the stats of what we have achieved over the last five years, I mean, they speak for themselves. We have nearly doubled our business over the last five 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. 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, you know, at the time when we articulated it, this was much more of hemophilia than extended to hematology. We added then immunology and, you know, and specialty care over the time, particularly now with the emergence of TRYNGOLZA, has become a bit of a different meaning.
We always were thinking of how could we angle ourself in certain areas an important position. It was about globalizing the footprint, initially taking a big reasonable share in United States, because as everybody know in this audience, you cannot be a leader in rare disease if you don't have a proper position in United States. 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. It is about unlocking value in our pipeline. When I look at today at our pipeline, I'm very proud of what we have achieved.
You know, Lydia will talk about this later because, you know, 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 two years. Let's go through the first area, which is therapeutic area leadership. These are, for us, therapeutic area leadership starts from the quality of the assets. 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, you know, important markets like Japan, in Korea, in Australia, and in Brazil. So these are not, you know, 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. You know, I told you that patient commitment, we were never short of.
In fact, you know, when I started, I wasn't quite sure whether we are part of an image brochure. I had to learn, you know, this is really right at the center of what Sobi is. You know, I give you an example because, you know, you can talk. Talk is very cheap, but, you know, 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. Twenty-fourth of December, you know, not the time typically where everybody is waiting for a little bit of excitement at the office. Twenty four hours later, the product was delivered.
We were compliant with all the necessary regulations 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, you know, we didn't have to ask any of our employees to please do this. It was self-understood, and this is what patient commitment and patient centricity means for this company, and it, 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, you know, 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 Patient View, 518 patient organizations globally were surveyed, and we scored number one among 31 companies, ahead of some of the big pharma companies who believe that they have a right to play in rare disease. And at the same time, you know, we also are obviously cognizant of the environment. We are not having the largest carbon footprint, obviously, because we have no site and, you know, it's rare disease, it's small units. Having said this... You know, we have set ourselves scientific-based targets. We have reduced the carbon footprint since 2023, 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 at the heart of what we are doing, and we are very pleased, you know, that we are now in the 2025 sustainability book of S&P, and we were selected as one of 19 pharma companies in this book. So we were very pleased, you know, 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.
You know, it is not just the number, you know, 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, you know, graduate 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. 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.
This evolution, you know, of building capabilities, taking advantage of a global footprint, has prompted us to think, is there more that we could do as Sobi? And so we took and 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 early in the development cycle? And we concluded, yes, it's the right time, and, you know, we will talk about one of these initiatives, and Professor Giamarellos will talk about it. I'm super happy that he has made an effort to come here today, talking about interferon gamma-driven sepsis. And, you know, 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, a med- an area of high unmet medical need, and, and Julia, as a previous treater, is gonna talk about it. Another one is VEXAS with our JAK2 inhibitor. As you can see, we are evolving as a Sobi. 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, you know, the- 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. The reason is that we have 6 launches by 2028. We have already launched ALTUVIIIO in hemophilia A, Gamifant in HLH/ MAS last year. We have undergoing the launch with C3G, IC-MPGN.
Very excited about this launch, have now two markets live, you know, in this very debilitating nephrology indication. We are expecting mid-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 that we are already in the midst of the launch of TRYNGOLZA in 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.
We are looking forward to the launch, if everything goes the way we think, you know, 28, pozdeutinurad, you know, comes with the acquisition of Arthrosi, and I'm very happy that Robert is here, that he is not only coming here, but that, you know, he has accepted to join us, which is... You know, life is always an interview, and I'm happy, you know, that we interviewed well with him so that he accepted his- the role with us because, you know, he is a- actually, he is a previous treater of gout. He's one- he used to be a professor at Duke and one of the key leaders in rheumatology in the U.S. I'm very happy that he has joined our team. This basically gives you a taste, and then obviously, ideas I talked about.
You know, I'm very excited about this presentation because, you know, it's an evolving field, it's risk, but if it works, it's high reward, but it's also a huge difference for for a high unmet medical area of needs. Yeah. So when you look at this, you know, 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 six major launches on top of what the company is today, and basically transform Sobi and double Sobi over the next five years. So that's our, that's our ambition as we lay it out. We have a couple of priority development projects with IDS, as I told you, with VEXAS and with synovitis. They are at the stage, if they happen to be, you know, relevant for us in this planning cycle, fantastic. We have not accounted for them, given the discounting that we use, typically, but also, you know, it's—they are in 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 want it to be at least clear. You know, we've 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 they will be very relevant into the mid-2030s and beyond. And then we, you know, no surprise, you know, 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. You know, 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? I think that requires now a look into the respective assets. Let's look at ALTUVIIIO. With ALTUVIIIO, we are still at a relatively early stage of evolution. Only two major markets are now having a launch history with more than 12 months. You know, 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, you know, and we believe that we have a spectacular product.
Sofiane, the head of Europe, will later share some of his views, you know, who knows this therapeutic area extremely well and what he wants to do with it. 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, you know, a very serious disease, and just look at the stats, 70% of children, 50% of adults, end up, on average, after 10 years with end-stage renal disease.
Also, 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, 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 are expecting actually a paper in this regard in the next 2 months. We believe also that treatment rate is going to go up, and, you know, and that basically paves way for, for a product like, Aspaveli now to take advantage of it with obviously supremely strong data, as Lydia is going to show you in three dimensions.
You know, and this gives us confidence that already this year, even though, you know, we have to vaccinate, patients have to go through a vaccination schedule, you know, 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 400-500 patients by the end of the year on drug, paid or unpaid. Doesn't matter for us because, you know, it's a, you know, over time, it's gonna wash itself out.
This means, you know, 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, you know, we will have 4,000-5,000 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, you know. Professor Parhofer will be much more eloquently talking about the disease. I just wanted to mention, you know, 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, you know, patients with super high triglycerides, but at the same time, also reduction of pancreatitis events.
You know, pancreatitis is not something lightheartedly. We were talking about this before this event, and, you know, one-third of patients ending up with persistent organ failure, and 5%-8%, you know, these are the stats, let's say, ending up as premature death. So clearly something that needs to be addressed and, you know, 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, you know, we are in the midst, as I told you, with an FCS launch, genetically driven, a very high triglycerides. Our focal point is really very much the lipid centers in Europe, and we accounted for 700-600 in EU 5, as we previously quoted.
We want to do a good job, you know, covering those and then branching out. And, you know, who knows how quickly this disease will be more democratized and other specialties will think, you know, of playing a role in this, in this treatment? Very hard to predict, but this is the way we are going to encounter it. You know, 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. At 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, you know, 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 for pozdeutinurad inhibitor. So this is, you know, gout as such, is the most common inflammatory arthritis with super high unmet medical need. And, you know, the, the, you know, Rob has a few more exciting photos than the way, you know, a layman like me was able to collect.
You know, its effects in second line are on 200,000 patients in the United States. This is a 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, you know, when we worked on over nearly a year with a preclinical and clinical package. You know, phase III is fully enrolled. We expect the H1 already, the first study, phase III study to read out. And we felt that this was an opportunity that we should not miss.
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 NASP, 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, and also how he thinks about podostatin inhibit. Basically, what it means is in the first phase, it's a top-classical, top-down 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 off scale in this market.
While 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, you know, I just wanted to give a prelude, and I don't want to steal, obviously, Professor Giamarellos-Bourboulis's thunder. But, you know, as you know, I mean, this is probably more commonly known. Around 11 million deaths are attributed, according to WHO, to, globally, to sepsis. You know, we did a recent survey, with specialists in an ICU setting, how they view this area, and they clearly, you know, no surprise, they said it's a huge unmet medical need. But what was interesting for us is that they said, you know, "10% mortality improvement would be considered as extremely-...
Clinically significant, and I think this is an important part also of Professor Giamarellos' presentation to tell us how he views this, 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 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, you know, based on Professor Giamarellos' research, is affecting around 20% of patients. And, you know, 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, you know, and there you and this is a way you can take it. So a very material opportunity for the company, but, you know, we obviously attach to a significant risk profile. Very briefly, you know, 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, you know, and this is a rough estimate, you know, 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? You know, as a mid-cap company, we just have to prioritize.
You know, 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 know, 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.
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. Why are we so audacious, and why are we still a rare disease company, you may wonder? 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. Science and unmet medical lead sometimes lead us into larger areas, like in the case of IDS or sHTG, where we started in FCS or refractory to progressive gout. 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. Yeah?
We have done this at the example of COVID-19 for kidney treatment, where Professor Giamarellos-Bourboulis did the 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, you know, also in discussions, you know, with IR. We just wanted to make sure, you know, on that journey over the next five years, we have a couple of milestones and catalysts you should be, you should be mindful of. I just want to tell you now 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 Gamifant—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, you know, that we have, you know, the filing right now in Q1 for TRYNGOLZA and launching next year in sHTG. And obviously, we are excited to present to you. Excitement is probably a gross understatement when we present the data for pozdeutinurad AR882 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 on the next trajectory.
We also believe that we see portfolio of the six products, plus the products that we have now in the pipeline, and, you know, 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'll 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 Markets Day. 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 into a delivery engine. See, 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 oversight, while we outsource to CROs for flexibility and scalability.
If we look at the regulatory approvals over the last year, we see that we had a remarkable year with 36 approvals across major markets. Major markets, we always think the U.S., Europe, Japan, but we are 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. All of this is flanked by strong scientific leadership. Only in 2025, we had more than 40 peer review 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. 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 Sobi was ranked as the most reputable company in the rare disease space. So this is something that really reflects our longest standing commitment to patient, 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 had five major approvals, ALTUVIIIO in hemophilia A, Aspaveli for the nephrology indications, Gamifant in secondary HLH macrophage activation syndrome, DOPTELET in ITP, and then TRYNGOLZA in the familial chylomicronemia syndrome. But on top of those five major approvals, in this period, we have two 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.
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 on registration. I want you to focus on the upper part of the table, where you see our next wave of catalysts that will be, you know, drive the growth of Sobi moving forward. Currently, we have three 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. We have two additional indications for, you know, pacritinib, one in VEXAS syndrome, and I will come back to that, and one in CMML. This is a research collaboration in the U.S. We have five assets in phase III.
Out of those five assets, two are running confirmatory trials. We have, eh, 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. We have loncastuximab tesirine for relapsed refractory diffuse large B-cell lymphoma, also running LOTIS-5 , which is a confirmatory trial. We have pozdeutinurad running two 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.... 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, it's ALTUVIIIO, and ALTUVIIIO, it's a high sustain, ultra-long factor replacement therapy. Basically elevates the factor 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 it's unprecedented in hemophilia, and it has been driving 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 two 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 zero, 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.
Again, here, ALTUVIIIO 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 ALTUVIIIO has done in this transformation of care in hemophilia, it's really achieving this normalization of hemostasis with near zero bleeds for the patients, which it's something that it's 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 ALTUVIIIO? And obviously, joint health, it's 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, and 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 microbleeds 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 treatment with anti-inflammatory drugs, intra-articular corticosteroids, synovectomy that can be with radioisotopes or that can be surgical, or it can lead even to joint replacement, really affecting massively the quality of life of the patients. So what we are going to explore with ALTUVIIIO 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 this 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.
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 two weeks ago. We're running the SHINE study, where we will be assessing joints with already existing synovitis, treated with once-weekly ALTUVIIIO and see how the synovitis improves. These studies are all obviously with technical imaging, like ultrasounds and MRI, to really assess how the chronic synovitis is evolving. Then the LIBERTY study, it's basically the post-trial axis, 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, yeah, but it's everything is a controlled environment." So we also want to understand what's the real-world evidence that is generated with ALTUVIIIO, and that's why we are running the ALTUVIIIO trial, which is really long-term, real-world evidence collection of data of patients treated with ALTUVIIIO for more than four years. So, as you see, we are expanding beyond just bleed control to really physical activity, joint health, synovitis, and broader 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.
You know, these are a spectrum from complement-mediated chronic kidney diseases that are heterogeneous and can have different presentations, but where the main disease driver is really the glomeruli, the position 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 immunosuppressives that were not addressing the root cause of the disease. That's the reason why, 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, at 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 three 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 one 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.
Talking to nephrologists, this is like... It's, 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 a 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, to many regulatory agencies to bring the product to as many patients as possible.
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, it's 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. You know, 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, you know, 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 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-Bourboulis. So I will just want to take some time to focus on the broad HLH that Guido has already mentioned.
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, it's they look across the survival across different HLH triggers, meaning infections, malignancies, autoimmunity. So they had two cohorts, one that was the historical cohort in red, 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 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 multisystemic hyperinflammation, causing organ damage, thrombosis, and high mortality 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 pre-planned. So we expect data readout in 2027.
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 increase the value chains, enabling the acceleration of our development cycle times. 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 authoring, really improving the speed and the consistency of our documents. We have submission and review platforms as well to compress our global approval timelines. 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 living rare disease patient platform, and currently, it's a state-of-the-art medical device with seven applications that is used in more than 26 countries. It's important that it has been co-created with patients and healthcare 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 healthcare providers to see, to understand the patient, the treatment benefits, and really to monitor and adjust the treatments as needed.
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.
I just can say that I'm really truly thrilled about the infinite possibilities for Sobi moving forward. Thank you. With that, I would like to hand over to Rob.
Well, I just wanna, 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 gonna spend too much time on this slide, but I kinda wanna point out that, you know, gout is not a disease of kings or the gluttony 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 of shrimp, eat a steak, and then wash it down with six beers, your uric acid is gonna 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 excrete about 10% of what we filter through our kidneys. And what gout patients do is they actually hold on to more than we actually hold on to. 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 wanna focus on is that URAT1 transporter on the apical surface of the proximal tubule. Now, gout patients, their URAT1 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, or almost 90% of the patients, aren't overproducers, or they're not gluttons, and they're not drinking beer all the time. They actually can't eliminate or can't excrete uric acid at the level where, you know, they don't develop problems with it.
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 two. As serum uric acid levels stay high, above that limit of solubility, above 6.8 mg per deciliter, over time, as it stays, uric acid becomes soluble and basically deposits in the form of needle-shaped crystals, yeah, 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. Could be 3 years, could be 5 years, could be 10 years even before that first flare happens. All that's subclinical.
So this is going on for a matter of time, and 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, the disability and, and morbidity that goes along with it. So you might be more familiar with a gout flare, the typical, what you think of about gout. You get, you know, a big, hot, swollen, red toe, and that's due to that crystal deposition and the, 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, that acute gout attack. But again, it kinda goes beyond more so than those acute attacks. And you can see in this slide again, that when you're inadequately 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 on once or twice a month, they can come on every six 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's put on, and they may or may not be put, unfortunately, 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, you know, 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, and important issue I want to make sure everybody realizes, is that-...
Again, I'm gonna emphasize, this is a systemic disease, a systemic illness that causes systemic inflammation. So in between all those gout flares is a low-grade inflammation that's just waiting for another igniter, so to speak, that can cause that acute flare, whether that's a stressor, whether that's they did drink too many beers or did eat too much shrimp, that causes that fluctuation in uric acid. So what are we gonna 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 gonna 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 kinda quickly eliminate those crystal deposition, which would eventually, obviously, remove all that etiology and all that nidus of chronic inflammation, a chronic inflammation that, until recently, 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 resistance, metabolic syndrome. So it's a very, very... Not just, it's 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 mg 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 six months.
So what, so what does that mean? So what that means is, clinically, you see incredible results. You see this patient here, can you... And you can imagine baseline, the morbidity this patient had, he probably couldn't grasp a pen or grasp 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 six doses, how quickly that crystal deposition that probably took 10, 15, 20 years to actually develop was reversed. And that's huge, and that's, that plays a huge impact on this patient's quality of life, to the point where you say, well, that's an infusion every, you know, for a few hours, every 4 weeks.
Well, I can tell you, I've used a lot of uricase over the last, well, since it was approved first time 15 years ago, and I would have patients coming, driving 4 hours and sit 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, it's 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 take the drug and will 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 talk to patients, the savvy patient, especially, I explain 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, you know, prevent the production of uric acid, not actually, you know, 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 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, that saturation where the, the uric acid is more saturated in the joints than it is in the blood. So now it's reversed.
Now we can put those sharp, microscopic, needle-shaped, you know, nidus of inflammation back into solution, excrete it, and basically, and again, improve the patient's quality of life by reducing tophi, eliminating tophi, and eliminating flares. And we can do this because it's... And like previous or predecessors of uricosurics or URAT1 inhibitors, we have a very favorable PK/PD profile with a relatively long half-life, so all we need is 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 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.
Well, in our phase II studies, we had a large phase II study, and this, this study was, placebo versus 50 mg of pozdeutinurad or 75 mg of pozdeutinurad. And you can see in the 75-mg , in this ITT population, which was just defined as anybody who got at least one, one, dose of drug, that 82% of the patients got below 6 mg per deciliter, which is kind of which is where we wanna be below that limit of solubility as a, as a general target across the board. But what's more important, especially for that progressive disease population and, 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 dissolution, like we just saw with the photographs from the NASP patient. The 75 mg got patients down below 6, 82% of the time, below 5, 73%, below 4, 55% of the time, and a quarter of the patients got down below 3 mg per deciliter. Again, importantly, if you look on the right side, the figure—again, importantly, this was sustained. The 50 mg got patients down to about 5 mg per deciliter, while the 75 mg got patients down at to 3.5 mg per deciliter. Now, this study was our 203 tophaceous study, so everybody... A smaller study, so e- but everybody had clinically visible tophi of their hands, wrists, ankles, or feet, and it was an allopurinol-controlled trial.
We enrolled 42 patients, and not only did 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. You can see in the 75 mg dose, again, a baseline that was, almost 9mg per deciliter baseline. We had, we had a significant improvement. About 90% of the patients at 3 months got below 6. Almost 70% got below 5 in the 75 mg 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.
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 mg, a third 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 then 50% response rate.
Then in the allopurinol group, the monotherapy in this study, we actually added 75, starting at month seven, and you can see that when it was added to allopurinol, they had a synergistic effect, and basically, you had even better results where the... went from only 8% allopurinol to 25% after six months, and then 44% after another six months. Now, interestingly, this patient here was in our 203 study, our tophaceous study, and they had obviously tophi, you as depicted it with green on the baseline.
This patient actually wasn'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 until this point for the last several years. So just absolute in misery. It, it kept him from, it kept him from work, it just, it kept him in the doctor's office, and by month 6, this patient had completely stopped flaring. And by month 12, his crystal deposition is, in his feet and ankles, was down from 14.79 cm³ to 1.1 cm³.
By month 18, he just had trace uric acid crystals left over that were just probably socked in and embedded over, you know, 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, he wouldn't. It excluded him. But you know, again, thankful to Sobi that we've already in the process of figuring out a plan to get him the drug so he, he won't 'cause he doesn't even wanna go back to try to take anything else, 'cause again, the previous drugs he was on, the xanthine oxidase inhibitors, didn't, didn't work. And finally, our phase III trials are fully enrolled and, and completed ahead of schedule. As was mentioned, we're.
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, you know, the kind of the word gets around with investigators if a medication, if a drug is 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 and also speaks to the need of this type of medication like this, where you have patients who, about 40% or so, either fail or don't tolerate a 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 mg dose, an arm of 50- mg dose, and a placebo dose, but it was randomized 2 to 2 to 1. So, you know, you had an 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 and 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, the information and the data we got from our two or three study, our tophaceous small study, was actually the reason why we actually got FDA Fast Track designation in 2024 for, 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 huge need. They're extremely appreciative, extremely appreciative when it comes to, when their life is basically turned around and changed, when they're coming out of a wheelchair, you know, 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 5, 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 drug. Even though it was blinded, it didn't take, it didn't take a genius to figure out he was on active drug. Thank you.
Thank you, Rob. Just quickly before coffee, we'd 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, you know, driving it home on the ground in the regions for us here at Sobi. So it's good to hear directly from them. And we thought to just take a few minutes just before coffee, just to hear a little bit 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 two big launches, which we just heard from NASP and pozdeutinurad 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.
Just maybe..
No, your first, the one that you had on before, with the... Prior to that. Yeah. 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, we have the royalty with, with Beyfortus, but that, that doesn't get to hit my P&L. So the product that we had, SYNAGIS, which was for 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, our growth products. So Gamifant was very important for us. Kineret was foundational for us. DOPTELET was very important.
Last year, we had our peak sales for Gamifant and DOPTELET. Clearly, Synagis was an experience where we had loss of, 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. 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. 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 four-syllable words, so I just say AR882. So I think, essentially, we, we've been preparing for this launch for some time. In the last 12 months, we've, 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.
Mm-hmm.
Switching to Europe to Sofiane. I mean, you know, we've, it's been a spectacular launch, I mean, with ALTUVIIIO, 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 ALTUVIIIO?
Yeah, sure. I think overall, region Europe will strongly contribute to Sobi growth journey, and it has started already in 2025, 20% growth, and this is mainly driven by ALTUVIIIO. 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 expanding 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 six months of launch, more than half of patients are coming from competition, and this is really value creation for us. So of course, in 2026, 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, not to 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 2026 and beyond. So 2026, 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 ALTUVIIIO 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 SEK 10 billion, even more.
In the midst of all this, you're also preparing, you know, for the Aspaveli launch and then also for next year in sHTG. Do you feel you have the ticket to win in both of these areas coming?
Yeah.
How do you feel about that?
Not only, not only I got the ticket, but I think, I've already jumped in a high-speed train, I think. And, I know Guido, he doesn't want me to become, I mean, bored with only ALTUVIIIO. So again, these are very nice challenges to take. I'm so glad to share with you some thoughts about this. I mean, Aspaveli and nephrology in particular, we have made a significant progress over the past month. With the pre-launch 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.
They 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%-80% of the target customers in nephrology, which is huge in a 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 patient ready for switches and initiation, as we need to go through a little bit of structured vaccination protocol that could take 3-4 months. So I think now the objective is really to set this up and you know make the centers and doctors and patients up to speed to start the initiation.
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, you're... Now, you oversee a huge amount, a very diverse area, not just healthcare 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, when I joined to internationalize, it was only a few countries and a few products. Today, we are looking at different societies, at 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 and approve the several markets at once, here 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 a 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've did basically anything from a standalone 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. Yeah. Back in this Capital Markets 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 about seeing them, yeah, can now be brought by us to serve larger parts and communities. So it is about keep being flexible, and being agile and never give up.
We just announced recently with Pint Pharma deal. I mean, maybe you can give us some comments there and in this Latin America and what's how that's helping us.
Yeah. 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, by 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 ability. 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 a 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 with Pint, a 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, and 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 Argentina, you look into Mexico, the size of the two 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 own know-how and with that of our partners. So this Pint is so much more than just a deal to access a market. It is another step in our philosophy to occupy a relevant segment.
Great, thank you. Thank you, gentlemen. I hope you get a little bit of a glimpse. It's a short session, but just a little bit of idea of what's really happening on the ground in 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 2:45 P.M. 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.
For the second part of our CMD, it was a very short feature on Swedish standards, I understand, but we'll-- 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's a professor of metabolism and endocrinology, which will take us through severe hypertriglyceridemia. Professor 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, it's also something new for me because you, we are used to speak to our peers, and we are 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 would 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. 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%-30% of the population that have elevated triglyceride levels, most of them moderately elevated triglyceride levels, meaning between 150 mg and maybe 500 mg per deciliter. And then there's few people who have severely elevated triglyceride levels, meaning above 500 mg or even above 880 mg 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 or higher than triglycerides of 600 mg 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 mg and 500 mg per deciliter, but then it increases very significantly. In patients with more than 880 mg per deciliter, the risk is really significantly elevated. Let's have a closer look at severe hypertriglyceridemia. What you can see here, that in most patients with severe hypertriglyceridemia, you have a mixture between a genetic predisposition and secondary factors. In 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 variant, sometimes you can see the mutations, sometimes not. But they very often have additional factors such as diabetes, some alcohol abuse, some—not even abuse, just alcohol use, then probably also medications or concomitant diseases. Now, let me look a little bit more into the detail into, into this, why we get this severe hypertriglyceridemia. You have to know that triglyceride are transported in lipoproteins, and these lipoproteins are secreted from the gut and from the liver. But the way the triglycerides are catabolized is for both lipo- sorts of lipoproteins, very similar, and there's a key enzyme, which is lipoprotein lipase, which really is essential for the, catabolism of triglycerides.
In patients with familial chylomicronemia syndrome, the lipoprotein lipase does not work correctly because one of the components is defective, and usually not only one variant, but two variants. At the same time, we know that apoC-III, an apolipoprotein 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 activity, 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. There are 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 is a 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 mg and 7,000 mg per deciliter.
He had recurrent episodes of acute pancreatitis, at least seven 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." 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.
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 bi-weekly, and then 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. As I have discussed with several people before, we just started him last week now on olezarsen. Therefore, we are very happy that there's new drug development, and 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. The BALANCE program evaluated this drug in patients with FCS.
As you can see, that was a phase III randomized double-blind, placebo-controlled trial, which involved 66 patients with genetically defined FCS, and they had an average baseline triglyceride level of 2,600, and olezarsen 80 mg was tested versus 50 mg, versus placebo every four weeks for basically one year. It was published in the New England Journal in 2024. 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 two treatment groups, it goes down. You can see that there's a dose-dependent effect on triglyceride levels, with obviously the 80 mg being more, more potent.
The clinically more relevant result is actually shown on the right-hand side because you see here that this—the acute pancreatitis free survival for one year. 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 mg or 80 mg per deciliter. That's a very strong hint that this evidence that this reduction triglycerides translates 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 rarer patients with FCS.
This is also reflected in our guidelines, where it says that above a triglyceride level of 800 mg per deciliter, the risk for acute pancreatitis increases, and that doesn't only increase in FCS patients, but increases in all patients who have elevated, severely elevated triglyceride levels. 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. 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 hypertriglyceridemia, not FCS, again, 50 mg olezarsen versus 80 mg 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 triglyceride levels for the two sub-studies, I would like to say core and core two, you see that the triglyceride levels are much more stable than in the FCS study, which is probably reflects the higher number of patients.
You see that also in the placebo group, there's a slight decrease, probably because some of the secondary factors were also treated. You also see that in the verum group, where they received olezarsen 50 mg or 80 mg per deciliter, the decrease was much, much more impressive, and there was, as you can see, a significant decrease in triglyceride levels in both of the sub-studies. Again, the clinically relevant question was, does this translate into a decreased risk for acute pancreatitis? This time, it's shown the other way around.
So 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 mg and prior pancreatitis. And as a clinician, we always, always, we also always look at the other side, what is the number needed to treat? So how many patients do we have to treat in order to avoid one episode?
What you can see here, that for the pooled olezarsen patient group, you have to treat 20 patients for 1 year to avoid 1 episode of pancreatitis. If you select those patients who have severely elevated triglycerides, more than 880 mg, and prior pancreatitis, this number goes down to 4. I'm not sure whether you're familiar with this number needed to treat parameter, but that's an 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 1 cardiovascular event. That is a very, very impressive result. Let me summarize. Hypertriglyceridemia overall is 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. 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. 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-Bourboulis to the stage. Professor Giamarellos-Bourboulis is chair of the European Sepsis Alliance, and he's also the leader of the Hellenic Institute for Sepsis. So please, Professor. Yep.
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. 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 into 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 a 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 a treatment is an average. There could be some patients who they 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. 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 one 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 one year, in one year, you have three times 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 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 pre- sepsis. So what's the difference between pre- sepsis and sepsis? When you have real sepsis, you are 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 all patients have this, this 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. I'm under mechanical ventilation, I'm sedated, I can't defend myself, but I tell you the signature of my blood." So pre-sepsis. 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 a cytokine, which is called interleukin-1 , and we gave to these patients anakinra. This is the path to death, the first 90 days. All patients, 100% of them, are alive at day zero.
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 a patient with pneumonia who arrives at the emergencies and who's relatively appears mild, if this procalcitonin 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 pandemic, 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 at JAMA that in these patients, if you treat them with anakinra, only this 5%, they get better. Today I'm here to present you how a combination of proteins can frame a completely different endotype, which is driven by interferon gamma. If you have a drug which blocks interferon gamma, either soluble or interferon gamma, ready, bound to the cell, ready to stimulate the cell, you may save lives. What can lead you to stimulation of interferon gamma? Any infection, lung, either community-acquired pneumonia, or nosocomial pneumonia, or COVID-19, or influenza, or urinary tract, or intraabdominal, or bacteremia. Just by the type of infection, you cannot tell. Look what happens to these patients. Neutrophils or lymphocytes, they will 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 that 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 when it happened 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 a 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 you 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 you know, nowadays, in the omics era, everything is presented into what is called the heat maps. 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 zero 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 zero, 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, a relative benefit of 41%. Let's see now the survivals. The survival curves, day zero, 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 realized 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, which is the high dose. At day zero, they start together, but look what happens in the very end. 24% efficacy and 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 up 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.
Yeah. Yeah, Professor Giamarellos, I mean, we will have probably a lot of questions in the Q&A session. I'm worried a little bit, you know, that there will be no questions for anybody else left after this presentation. I think it was really a crescendo, and, you know, and bringing up, obviously, this very new data. So maybe, you know, in the interest of time, if you could face this in a way, I don't want to disappoint you, but, you know, I'm sure 80% of all questions will be directed towards you because who are we, you know, 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, you know, together with Professor Parhofer, and Rob, and, you know, the three members of the executive team. Thank you so much. Yeah, this was unbelievable. Thank you.
Hi, everyone. So now to something completely different. I wanna 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 month and a half, it would have looked even better. But with 126% share price growth, we outperform or we have outperformed relevant European healthcare 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 a 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. We delivered all this despite sometimes very challenging macro environment with COVID, high inflation, geopolitical uncertainty, and pricing pressures. 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 three regions. We also added, obviously, from a product perspective, a lot of sales, both in hematology and immunology. 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 gonna come back to that. With this performance, we are confident that we have the financial platform and the financial capabilities to take on and drive the next phase of growth for the company. 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've outlined today. Our approach is disciplined. We will, of course, invest now, but we will do it in a way that sustains a 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 timeline 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 we 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.
In terms of FX rates, we have used the 2025 average rates, which are the latest reported numbers, which means then obviously that there are no FX effects compared to 2025 in the numbers that we quote today. The SEK 55 billion number represent a strong double-digit growth or double-digit CAGR, and we have estimated risk corridor of ±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, the, the, the...
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%-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 scales and as we reallocate resources from mature areas to growth areas.
So the operating leverage will allow us to expand margins and to reach a margin, an adjusted EBITDA 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, 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.
Over the period, we've had a very strong cash conversion, particularly in the last two years, when the cash conversion was around 80% of EBITDA. 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. This, of course, creates headroom for further business development aligned with our strategy. I'm going to say a few words about capital allocation. 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.
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 EBITDA 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.
Yeah, I just wrap it up quickly and then give way for question and answers, you know, because I think we were quite intoxicated by quite a number of the presentations, Professor Parhofer first, and then Professor Giamarellos-Bourboulis, and also Rob. So maybe just go straight into your concluding remarks. You know, 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, on the high end, towards the end. And we think that we have the credibility, and we have so also the executional ability to do so.
Six products is what really drives the company moving forward, and obviously, among those, you know, five opportunities to reach blockbuster potential, which is, you know, considering the size of Sobi of what it is today, quite remarkable. And we will obviously continue expanding globally and leverage the positions that we have created over the last years, you know, 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, you know, that we want to 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.
I think this is one of the, you know, concluding remarks. I would like now to invite, you know, the speakers, Professor Giamarellos-Bourboulis, 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 in this... at this point of time. So maybe we start, I mean, maybe we start with Viktor, and then we make our way. Yeah, if this is okay. Viktor, please.
Yeah, sure.
Yeah, please.
Sure. So Viktor Sundberg, Nordea. Thanks for taking my question. Just for Rob, maybe on gout. Hear your view on maybe the landscape on gout and, oh, thanks. How you view, you know, 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? Thanks.
All right. So the first, the first question I'll, I'll tackle first here. So I think there's, there's definitely patient populations for both, if the best way to put it. So, one of our colleagues always says, you know, "Some people like dogs, some people like cats." There's always gonna be an opportunity for a patient population that has severe disability. You wanna, you wanna see reduction in the crystal deposition very quickly. You want to see results very quickly. You know, 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, you know, that's in a wheelchair, flexion contractures, you know, or just severe or 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 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, you know, some people like dogs, some people like cats. Just like with rheumatoid arthritis, some people prefer, you know, an infusion versus an injection. It's the same kind of mentality.
So you have this patient population that's gonna 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. There's definitely a patient population that's there that needs it. I think, you know, it's a spectrum. You have patients you're gonna be able to capture earlier, prior to the point they need something like NASP, and those patients you're gonna be able to treat. Then again, you're gonna have patients, too, they're gonna have to come off NASP because—and they're gonna be maintained on something. We know that those patients typically have already failed everything else. You know, febuxostat, allopurinol, probenecid, benzbromarone. You know they've already failed, but then they could go, you know, to pozdeutinurad.
I mean, they're definitely gonna work not against each other, but with each other in that sense. As far as CKD, in our current phase III trial, we have patients with GFRs as low as 30 mL per minute. In CKD stage 3A, 3B, up to that point, encompass about 90% of the gout patient population. You know, it's just-- there's gonna be, there's gonna be some patient population that are below 30, that aren't gonna be a good candidate for pozdeutinurad, just given the mechanism of action. That's a very small percentage of the patient population. I have no doubt, in the data that we've seen to date in patients between 30 mL per minute and 45 mL per minute, it works. It works well.
You know, 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 gonna be a great alternative to those patients who have failed allopurinol, febuxostat.
Yeah. Christopher, maybe?
Thank you very much for taking my questions. 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-Bourboulis on Gamifant.
I just wondered about the patient baseline characteristics and also noticed that, you know, originally you planned 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 covariates that you used in the regression to account for baseline imbalances when assessing SOFA? Thank you.
Maybe we start with Professor Giamarellos.
Oh, thank you for the question. So, always something which is a peculiar characteristic in in sepsis trials is that you have sites which enroll one patient and other sites which they enroll three patients or four patients or five 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 three groups were 10, so no real difference between them.
Yeah. And, you know, the easy part of the question is, obviously, you know, if you want to know what somebody's strategy is, you need to see what he's doing. You look at our last deal, pozdeutinurad. We acquired an asset that normally, you know, 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 a f- you know, to build a franchise. So we will probably be more driven by the idea of being franchise.
If you want to know how we want to like to keep the energy up, tomorrow morning, we are all together again, and then we talk about how we can beat forecast. Yeah. On this note, please.
Hi, Gonzalo Artiach from Danske Bank. Thank you for taking my questions. 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 two 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 a, 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 mg, this is not a major worry, probably. Cardiovascular risk is a secondary worry.
But for those patients between 500 mg and 880 mg, what do you think of this increase? Because, I mean, LDL usually... 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 that question. I mean, you have to see if you decrease triglyceride-rich lipoproteins, the way that they're metabolized is basically shifting to IDL and then LDL particles, though 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. You also have to see if, at the same time, you decrease, 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 mg? And from an M&A perspective, is it something that you're considering, for example, potential combination treatments with other modalities for lipid lowering?
And maybe you can talk about more the sales?
Mm-hmm.
But obviously, what we are submitting and what we are really looking at, it's those above 880 mg. That's clear because the benefit, it's outstanding, and there are no other products that have shown this reduction, 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 think that, 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, and there, probably what you mentioned before becomes more relevant, that when you shift from moderately elevated triglycerides towards LDL, you and you shift basically one risk for 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.
Yeah. So our approach is more puristic, eh?
Yeah.
Please, Eric.
Yes, hi. Eric Hultagard 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 you know, 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, you know, I think Mattias was next, yeah, so.
Thanks so much. Matthias Haggblom from Handelsbanken. Firstly, for Professor Giamarellos, sorry. So the heat map 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, a brutal effect size by olezarsen in this patient population. You know, the sponsor in the U.S., apparently, is planning for a pricing of $15,000-$20,000 per patient a year. Is that a price point that could resonate with the German reimbursement system, or how should I think about that?
Should I go first?
Yeah, 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 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.
Yeah. We have performed, you know, obviously, as you would, you know, pricing studies, which we will not divulge today, and, you know, where we feel, you know, that we, we have a product. Yeah, at least, you know, that will allow us to have the necessary margins to try. But, you know, there are no guarantees, and we will have, we will obviously look forward to the dialogue after registration with the relevant reimbursement authorities. But, you know, we have prepared health economic cases as you would do so. Yeah. Sorry. Next one, please.
Hi, Kirsty Ross-Stewart from BNP Paribas. One also for Professor Giamarellos-Bourboulis. On the frequency and kind of process of doing IDS biomarker testing within hospitals and sepsis patients, just any color on how frequently that's done now, given the, the, you know, 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, that's great to see, but how should we think about the cadence of, 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, you know, 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-Bourboulis first. Yeah.
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 of 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?
Yeah.
Thank you.
In terms of SG&A in particular, 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. When it comes to the impact and the size of the different opportunities, 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.
Very good. Next question. Yeah.
Hi, Harry Gillis from Berenberg. Thank you for taking the questions. 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, you know, Ionis obviously recently doubled their peak from $1 billion to $2 billion. How you're thinking about your greater than $1 billion seems like there could be room for upside there, and maybe is this use really just in those 300,000 sort of 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 SEK 1 billion globally. Thanks.
You know, we, we like obviously to be ambitious, obviously, as we, as you know. But, you know, at this point of time, you know, we thought, you know, we guide at this level because it's sufficiently indicative. You know, but, you know, for with regard to TRYNGOLZA, so I think, you know, given, you know, the dialogue that we are going to have with payers, and then also the, you know, the, and the reimbursement—the total reimbursement situation in Europe, if we get the right feedback, I think this will feel already very good. You know, there's a material opportunity, obviously, outside of Europe, no, no, no question. And, you know, large patient populations, and, you know, this will make us think further. But I think, you know, at this point of time, we don't want to guide more.
There's obviously, you know, just the math, mathematics would dictate, you know, you look at the epi data, that there's a significant opportunity beyond, but, you know, this is, I think is premature at this stage. And with KRYSTEXXA, you know, the, the way we looked at this, you know, not very long ago, when you think of NASP, obviously, people thought, "Well, is this really a product that can reach a certain level?" You know, Rob was talking about CKD patients. You know, you, you look at the methotrexate exclusion criteria, you know, 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, our proposition for NASP, provided, obviously, provided that these patients want to have this fast-- experience this fast decrease of, of SUA.
For others, pozdeutinurad is obviously going to be a fantastic opportunity, and, you know, we, we clearly see a much larger opportunity for pozdeutinurad than for, for NASH. 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, you know, we, we think that we have a clear picture, but, you know, that's not for, for today either. We want to make sure that we have, you know, stellar data. As you have seen, you know, this could be the first oral treatment that will demonstrate tophi reduction. Yeah. I mean, think about that for a second, what this could mean. And therefore, you know, we take it one step at a time.
I'm looking forward to the data, you know, presented in May, first phase III read out, then we look at the next. And, you know, then I'm sure we can answer your question with more authority. Other questions? Sorry.
No problem.
Sorry. It was next? Yeah.
There is...
Yep. No, there's somebody in behind. Yeah, please. Sorry. I'm sorry.
Thank you for the question. 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? Then 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, 'cause 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? Thank you.
So with regards to the risk corridor, of course, we have worked with different scenarios, you know, with high potential or lower potential, and we have found that corridor, you know, 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.
Yeah. You know, with pricing is obvious. You know, if you move from an FCS indication with an established price level, like where Waylivra is today, to an indication now, broader indication in sHTG, that has to have consequences on the price, and that's what we modeled. Obviously, based on the feedback that we got, you know, it has to be very different price level, and that would mean very likely that our FCS market is gonna shrink, but we are obviously looking forward to a much larger opportunity in sHTG. You're clearly aware of this.
Hi, George Tigalonov- Berke from ABG. So I have two questions, I think perhaps for Henrik. So on revenue guidance, you said that no additional business development, but regarding R&D, is there any additional business development in those 11%-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.
Mm-hmm. 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...
Yeah.
Anything else that explains why the figure isn't higher? I mean, isn't the sky really the limit here?
Yeah, no, you know, some people believe it's the largest product in the world, yeah? And, let's say, but, you know, more seriously, I think it is, it's a huge opportunity, clearly beyond SEK 1 billion, as a risk adjustment taking place, you know, we. And, let's say, but, you know, at this stage, let's get the phase, you know, the PIVOTAL trial under the belt. We get the PIVOTAL trial, then, you know, we will all feel much, much more excited, and, you know, we will be happy. You know, the product, if it works, you know, I mean, I think Professor Giamarellos has pointed it out, you know. The difference you saw already in this granted small cohort, but consistently, is spectacular. Yeah?
So it can make a huge difference on a large, much larger scale, but this is not the time. You know, let's. You know, this is risk-adjusted, but it's not in our forecast. Yeah? But we will. If it, if it happened to be in our, 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. Yeah, but it is, it's a very material. I mean, you just do the math. I mean, you know, it's, it's just spiraling, yeah. Thank you.
Thank you. Shirley Chen from Barclays. My question is about the further development of Gamifant ideas. So in future for future trials, what level of interferon gamma pathway activation or what level of CXCL9 do you perhaps gonna 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 getting inspired from the heat map data, so if we think sepsis as a heterogeneous disease and break ideas into different disease stages, where do you believe the window closes beyond which Gamifant is likely too late to be effective? Thank you.
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 infections. That's one part. The other part is that our data so far from the phase IIa trial, they demonstrate that CXCL9 more than 2.2 thousand picograms 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. Actually, the way we have done that in the phase IIa trial was not to—we trust on biology and not on the clock. In other terms, if we find the biomarkers increased, 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 zero time, but for a pivotal trial to be of value, it should be pragmatic.
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.
Yeah. We have time, I think, for one more question now. I can't decide now who is the... Well?
Thanks very much, Christopher Uhde . A question on the Gamifant, next steps. Essentially, how could a phase IIb look? Are you thinking about the same dose levels, different dose levels, adaptive designs? And, and, and, yeah, how quickly can you move, and, you know, do you have the bandwidth to do that now, or do you need to add to it? Thank you.
Professor Giamarellos?
Well, of course, there is a suggestion which has been addressed to the regulatory, but of course, you understand that, several times the suggestion is nothing more coming from experts. What is needed is the wisdom of the regulatory, the 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.
Yeah. So I'm really awfully sorry that, you know, the format of today does not cater for and doesn't allow for all questions. You know, we have, obviously, our IR team, as you know, headed by Gerard. So if you have further questions, please refer to them, you know, and, you know, 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, you know, for being available and, you know, making a trip, you know, Italy, and, you know, and sharing with us their deep insights. I hope you found it useful. You know, we are clearly excited, as you can see, about our future.
You know, with Henrik, we have already agreed, you know, 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, yeah, comply with his understanding of lean management. But on a more serious note, you know, when you've— You know, as we are into, in these days, you know, in the times of the Olympic spirit, you know, 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 a time where the amateurs of United States won against the Russian, at that time, a seemingly unbeatable team.
The goalie told me one, you know. And, you know, he was a motivational speaker doing 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. So 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.