Welcome to Cereno Scientific's Capital Markets Day. My name is Tove Bergenholt, and I'm the Head of Investor Relations and Communications here. It's a pleasure to welcome you all to an event filled with where we'll talk about the business, operations, and our strategic focus. Just a note that there will be forward-looking statements that will be mentioned in this context, and that should be based on the current expectations of what we know today, and this material should be considered with that in mind. With that, I'm pleased to welcome Mike Ward to facilitate our day. Mike is an experienced biotech journalist and commentator with a long history in media and as a moderator at industry events such as BIO-Europe and LSX. He's working today with Global Thought Leadership at Clarivate as well. Welcome, Mike.
Thank you very much, Tove. Yeah, so and also apart from being the global head of thought leadership at Clarivate, I also host a podcast called BioBiz Buzz. And in fact, in one of the early episodes of BioBiz Buzz , I actually interviewed Sten. So if you want to sort of listen to that, it's easy to download. I thought we've got a really, really busy agenda today. You've probably seen the handouts. So I'm going to try and keep things ticking along as quickly as possible. But I thought it'd be useful just to sort of set a sort of a context of where we are. So we've just finished 2025. At the beginning of the year, there was a lot of uncertainty in the industry. People were sort of concerned because there were changes at the FDA and what implications was that going to have.
There was also sort of disruptions in the sort of the capital markets. But actually, when we look at what happened in 2025, we saw 46 new medical entities approved by the FDA and 18 BLAs. So in fact, that was on a par with what we would usually see. So there wasn't the sort of the disruption in the approvals process that people were concerned about. But what was really important was, of those new approvals, 67% of them were focused on rare diseases. And that was a big jump up from what we had seen previously. Only in sort of 2021 did we see it go over 50%. And the thinking was, well, is this a new benchmark or is this just an outlier?
But actually, some of the noises that are coming out of the FDA is rare diseases is actually a place that they really want to double down on. Also, what's worth looking at is the top 10 best-selling drugs, all getting revenues of over $10 billion each. 8 of those are going to go off patent by 2032. So the total of those top 10 is $175 billion. $145 billion of that is going to have loss of exclusivity by 2032. And therefore, the pharmaceutical industry really has to sort of get its act together to replenish those potential lost revenues. And so therefore, there was an expectation there would be sort of M&A and lots of licensing deals. On the M&A front, we didn't see many big blockbuster M&As taking place. There were about 4 or 5.
But what we did see is we saw a lot of smaller deals as, again, they're backfilling and sort of adding on. So they're called bolt-on acquisitions. The other thing, though, that is more important is on licensing, we saw a record number of deals done where pharmaceutical companies would in-license assets from biotechs. The sort of total value of those deals was $292.5 billion. That was a record. So you can sort of see, in fact, there's a lot of activity. Interestingly, a lot of the focus, whether it's actually from sort of the venture capitalists and investors or whether it's from pharmaceutical companies, is that they are really, really keen on those companies who are doing something that is differentiated, that is going to be meaningful to patients, but actually has been somewhat de-risked. So it's late stage.
So if you're in that sort of late stage space, if you're able to differentiate and you're actually addressing an unmet medical need, you're actually in the sweet spot for whether it's potential partnerships with big pharma or with investments. So that's essentially where we are. When we actually look at sort of the markets, what we actually saw, again, after a couple of years of where we saw the markets for biotechs go down, we actually saw an uplift. So in the last, during 2025, the XBI, which is an index of the smallest biotechs in the U.S., was up 37%. So what that means is that investors who had moved away from the sector are coming back. Now, interestingly, they're still away from where we were four or five years ago. So there's still actually a lot of headroom to catch up.
So there's still sort of plenty of opport.nities there. So that's just sort of—I thought it'd give you sort of a sense of where we are. As I say, we've got a busy agenda today. It's designed to connect sort of our understanding of what's actually happening in the space, sort of the potential of the patient impact of what Cereno is doing, sort of the clinical progress, the market opportunity, and also upcoming value triggers. Those are the things that we hope you're going to learn from today's session. OK, so that's my little introduction. Now it gives me great pleasure to introduce Sten Sörensen, the CEO. And I'm going to have a little fireside chat with Sten. So come and join me, sir.
Welcome. Thank you, Mike.
OK, so one of the interesting things is when talking to investors and pharmaceutical business development directors, et cetera, and I ask them about how they do their due diligence. Obviously, there's always the sort of the scientific due diligence. But what is probably the most important is actually the sort of the personalities behind those companies, the people who are actually going to execute. So I thought that what we could do is over the next 10 minutes or so just actually get a sort of a better understanding of what does the leadership of Cereno look like? And by that, I mean, what makes you tick? So you're now the CEO. You've had involvement with other companies. What was it? How did you become the CEO in the first place?
Good question. I think the origin is my interest. I think it's the wanting to be part of something that's very valuable and that's disruptive, meaning if successful, you will create massive value to whoever you do it. That's done in other sectors. I think my interest in biology, the human body, and why you get sickness and what you can do about it has propelled me into this sector and to various roles within it. So that's the background. And I think if you have that curiosity and are fortunate enough to eventually work with the best thought leaders in the sector, as we spoke about earlier, if you have a good balance between your mouth and your ears and especially focus on your ears when you meet these people, you can learn a lot.
So I think that being able to work with thought leaders, but then again having a holistic mind to connect the dots. So if you want to be disruptive, you have to be a pioneer. If you want to be a pioneer, you have to be able to connect the dots and run with the opportunity, create gravity towards your vision, and be ahead of the curve. So everybody is here. You want to be ahead. That's a pioneering effort. And I think if you want to do that, you have to be a leader of the vision and then of the team.
OK, but specifically, how was it that Cereno became on your radar or you became on their radar?
Yeah, so I have had a couple of journeys before from my first global job in Chicago in the U.S. for Monsanto, Monsanto Pharma . I was recruited as fairly young, product manager, 29 years old from Sweden. I was given a phone and a product that sold about SEK 2 billion a year, very good margin, 70% margin. Nobody really took care of this product. This was launched many years before I got the job. I discovered that there was a lot of science out there in the world that nobody really looked at. I connected with a dear colleague on the medical side, Dr. Perez . We postulated, having reviewed all this science, that we could change the use of the drug that I was product manager for.
We would create very good value, quality of life to patients, and also have them live longer in heart failure specifically. That was the first journey. Having that global job, you can pick up the phone and call any thought leader in the world, the best people in the world. They'll pick up the phone. You then have to have the courage to get that done. That's a great position to be in. Eventually, this turned out to be a successful story. We increased survival with 30%. It was paid by, again, my marketing budget or our marketing budget. I rose in the hierarchy and became global marketing head. I was able to finance the study. You should know that if you want to be a pioneer, sometimes politics gets in the way.
So in this case, I had to finance it from the marketing position, not from R&D. But that was a successful one, published in New England Journal of Medicine. And I moved on then to Astra and had a similar journey with Astra's beta blocker, a very well-known metoprolol drug used for many years in other cardiovascular diseases. But it was forbidden to be used in heart failure. And met Dr. and Professor Gunnar Olsson at that time. And we had a similar idea to repurpose into heart failure this beta blocker. And we were successful with that, too. That also took some political maneuvering to get that financed. But we were brave. We could connect the dots. And then we got the company with us and the thought leaders in the world. And that had the same impact, about 30% improved survival and quality of life.
But it also was an enormous commercial success for AstraZeneca. It went from SEK 2 billion to plus SEK 20 billion sales per year after this trial was completed, not entirely based on heart failure, but the cardioprotective branding of that compound. So when I met Cereno, I was introduced by the managing director for Gothenburg University's ventures, Clementina. And she said, I need to strengthen the board in some companies. Would you like to meet them? And when I met the group and the founders behind Cereno, it was founded in 2012. And I was approached in 2014. I was immediately struck by the technology. So you can hear I'm technology and science driven. You have to believe in the science and the opportunity of it.
So when I understood that this company was based and formed on the basis of epigenetic modulation through HDAC inhibition, I knew they were onto something hot. And nobody else was there. So the company was formed ahead of the curve, so to speak. So that's a long story for you. But that's the background.
I love the idea that you use the marketing budget to pay for the clinical research because you actually had a vision and you believed in it. And yeah, that's an interesting, almost like a business case study on its own.
Yeah, it is. Yeah, it is. I mean, it ended up on Wall Street Journal's. The second section is about business. The story is there, actually. It's titled "The Physician Who Didn't Take No for an Answer." That was my colleague, Dr. Perez. He was still with the company. At that time, I had moved on and recruited into AstraZeneca globally.
Yeah, and I mean, you were talking, again, about bringing in other people. Now, clearly, one of the skills of a leader is actually creating the team that is also going to help you drive the vision. So when you were deciding you were going to take the helm at Cereno, firstly, what was the biggest surprise you had when you came into the company? And then what did you do to actually start building up the infrastructure that you would need to fulfill your mission?
Well, I mean, the technology and the brains that had focused and identified this opportunity, it was actually for thrombosis prevention, as many of you might know. They've done that fantastic identification of the early opportunity. So I was struck by that and by the technology I had found of a drug that's been used for 50-60 years for a completely different disease and not at all discovered for HDAC inhibition. That discovery came much later in that molecule's life. But what I was struck about, and this is not unusual, is that there is no business plan. There were no real patents protecting the idea. There were no money. So that's a long road if you don't have that. And the group was researchers, so patent and researchers and so on. So they needed more experience, capacity, and competence there.
I was one of them who joined then in 2014. But I quickly wanted to be the CEO because of my previous experiences and driving visionary concepts.
Also being able to control the politics.
Yeah, well, yeah, exactly. And even startups are not necessarily without politics. But in a smaller scale, I don't think we've had too much of that in Cereno, actually. But yeah, so I was struck by that. And I realized, and I worked like that through my life, is that you have to get the best people around your vision. You have to attract them. So you will see our scientific advisory board if you don't know it already. And you will see some new names here today. I've always worked with the best people in the world on these concepts. And we are doing that now with Cereno. So I think what you have to do if you want to be a pioneer, you have to be able to attract people to follow that vision and be part of that vision.
I have not been doing that attractiveness myself. We have recent examples from the team who pulled in these major names to work with us and connected through old connections. That's the same with me when I joined Cereno. The old work, the previous work that I did together with my colleagues in these heart failure trials, the people then that were pioneers together with me and others are now involved in this effort with Cereno because they think it's a fantastic opportunity.
Yeah, I mean, I guess you've got the advantage of having already proved the concept of repurposing your existing molecules.
Yes, and I mean, I'm not we and I'm not alone of doing repurposing successfully. But in heart failure, I don't think there's another person on the planet that have done it twice. And I think so the people there were successful through those trials and other work they did. And with this technology described to them, they wanted to join immediately. So I think that is trust and having been on the journey before and also being able to identify scientifically and medically the potential of what's being behind the vision.
Right, this has been great. I mean, it's just like I've learned even more. And we've spoken quite a few times. What I'd like now to do is invite you to actually more formally describe, therefore, what the company progress has been and what the momentum is as a kickoff to this afternoon's proceedings. So Sten. The platform is yours.
Thank you. The platform is yours. So I should also say welcome to all of you here, shareholders and others, analysts, and so on. It's a pleasure for us that you are coming here and listening to our story and our efforts to drive this vision. Without shareholders and investors and long-term investors, you can't do this journey. So thank you for being here. I will go through a few slides in our vision to help patients like this and also patients that we have here in the room today. And you will hear more about that later. So you might know that we are based in Gothenburg, in Mölndal, actually, at GoCo, which is a health care research center that's fairly new, established a few years back. We have lived there soon two years. We have one part of the floor.
I think you can see it there if it's the first under GoCo or the third. I don't remember now. The company was formed in 2012. We are pioneering the effort of epigenetic modulation into, as we nowadays say, cardiopulmonary diseases, so heart and lung diseases. We are pursuing this HDAC inhibition, which is a new way of utilizing HDAC inhibition into these diseases, never been done before. We have two clinical programs with HDAC inhibitors. We have another program that's in the preclinical. I mentioned before here in the talk with Mike that Cereno has been able to attract some of the best minds on the planet in relation to cardiovascular diseases and pulmonary diseases. These listed here are on our scientific advisory board. I won't go into the names in detail.
I can mention Deepak L. Bhatt is running Mount Sinai Health System, eight hospitals in New York. He has 270 cardiologists reporting to him on all cardiovascular business. He's also the editor of the Bible for cardiologists, the Braunwald book . We also have a collaboration with the University of Michigan, Michael Holinstat, an innovator and professor and thought leader in thrombosis. And Don deBethizy here, I should mention. He is vice chairman of argenx. It is a EUR 50 billion biotech company. And he has been a disruptor in other technologies. He's brought companies to the U.S. stock market very successfully, et cetera, et cetera. He started his scientific career at U.S. Tobacco Company . A super smart guy who is an advisor both to our science, R&D programs, and to our business. Now, why do we pursue HDAC inhibition?
Well, epigenetic modulation through this mode of action uncouples the regulation mechanism around our genetic code. You know the DNA is there as a map to produce a factory of proteins. So the proteins need that map to be produced. The DNA is regulated through various mechanisms. One of the mechanisms is HDACs. When we use our technology, we can uncouple blockades in that regulation that has happened for various reasons. It can be external. It can be genetic. It can be behavioral changes that have caused this disruption, so to speak, of the regulation of the protein production. Researchers around the world have documented that HDAC activity is dangerous if it's too much. It can be uncoupled by HDAC inhibition so the DNA can work correctly as a map again.
This is what we're pursuing into cardiovascular and lung diseases that are rare as our first initial targets. And what has been documented in animal work and other work is that you can reverse the pathological remodeling that happens in these orphan diseases, both in myocytes or in connective tissue fibrosis. We also know that HDAC inhibition is anti-inflammatory. Many of these diseases have a strong anti-inflammatory component. We are also able to reduce pulmonary pressure. And in addition, we have documented that we can prevent thrombosis without increasing bleeding risk. There are micro thromboses happening in these diseases. So that's an added benefit even in these rare diseases to have that capacity. Now, there's a lot of attraction to Cereno for what we're doing because we're pioneers. And people want to be part of a pioneering effort if it's a significant potential. So that's one.
We're not doing this alone. Last year, there were 37-50 publications, abstracts, review articles, et cetera, around HDAC and HDAC inhibition and the potential that this has for cardiovascular, pulmonary, and even other diseases. One of them here I just listed was in November, I think, in Nature. Nature is one of the best peer-reviewed scientific journals that we have. Also in The Lancet, our scientific advisory board decided when we started to work with them that they wanted to produce a white paper, which means a paper to push the industry, clinicians, and the investors to invest in HDAC inhibition for new medicine. That was published in The Lancet in 2021, partly by our scientific advisory board. Now, so we have the thought leaders. The science is moving even without Cereno.
What's happening more is we've had 60 press releases around Cereno last year. We have 50 new quality scientific journalists and business journalists aligned and interested in our story. We've been invited to five panel discussions somewhere in the world to discuss what we do and what it means in cardiology or pulmonary diseases. We've been to more than one conference a month. There's been scientific conferences presenting Cereno data at various conferences out in these various diseases. In addition, of course, we are proud that we were shortlisted as Company of the Year in Europe among 10 biotech companies in Europe as a finalist to win that award in 2025. This was in July in London. We had to look good, had to look the part.
Also, I was happy to be shortlisted as the CEO of the Year in Europe in another life science award ceremony later in November. Then another thing that happened was that our chief scientific officer was awarded as the most important exit dealmaker for Gothenburg University Holdings that was once forming Cereno, helping to form Cereno. So Björn Dahlöf got that award. So three awards, one award win and two listings, I should say. All right, so a lot of buzz around Cereno, more than before. And that's also because we have started to prove that it's not just a vision. We're seeing impact. So what are we pursuing? So we have these three drugs in development, CS1. We are about to start phase IIb in the pulmonary arterial hypertension, the rare disease that will help this woman when we get there significantly.
We have a second generation, if you will, HDAC inhibitor in CS014. You might have seen a press release yesterday, Tove, that we have sharpened our focus, so to speak, how this drug should be developed best to get to the market with the highest probability, lowest cost, and shortest time. We have moved from IPF as an initial target to pulmonary hypertension, ILD, or interstitial lung disease. You'll hear more about that later. That drug is being prepared for phase II. We'll talk about the milestones. We aim to submit an IND and get it accepted this year. The third asset is an in-licensed asset from the University of Michigan. It's going to address rare thrombotic disorders as the initial target. Here's the press release, actually. I'll just mention why, I think.
This disease is a rare disease, high unmet need [in the] patient population, very poor prognosis. There is a need for disease-modifying therapies, which is our key aim with this approach. We believe that HDAC inhibition through this drug, CS014, has a significant potential to deliver value. Now, let's look at last year. We believe we have delivered on all the fundamental milestones for value inflections that we set out to do last year. Positive phase II data readout early in the year. We were approached to initiate an expanded access program. We pursued it, got it approved by FDA. It's been running all year and was just last patient, last visit completed, later data this year. We got fast-track designation from FDA, meaning that they believe we have something important.
They only give that to companies and drugs that have something important if we succeed for the patient. So we have a hotline to FDA for help or advice if we need it. We got green light for our phase IIb trial in PH for CS1 in December. And we also had a successful completion of phase I for our second generation, CS014. That was in July, I think. So we moved that ahead also. Now, how has that impacted the valuation of the company? You know, I know, we know that if you move your development path, you de-risk the development for investors and for potential buyers, partners. So what has happened to our valuation over this time from 2024 to here?
This is a valuation on fundamentals, you know calculating penetration on the market, market potential, what is the risk to fail or probability of success, how much money will it take, when will they get there, and what's the competition, and so on. So it's gone from SEK 2.3 billion to SEK 6.6 billion, 21 SEK per share today, today, not later, today. So that's what happened if you value the company on fundamentals. Let's look at what has happened with Cereno over the time since we started. Over there to the left, no valuation, no money. A little later, 10 shareholders, board, company formed. Nine months after I became CEO, we listed the company on AktieTorget, raised SEK 32 million, valuation SEK 84 million, 300 shareholders. Fast forward to 2023, market cap SEK 1.2 billion, uplisted on Nasdaq First North, 7,000 shareholders. Last year, SEK 2.1 billion, 12,000 shareholders.
We're included in Nasdaq First North 25 index. So you know that's, I should say, that's the retail market valuation. You can note this is only SEK 2.1 billion. The analysts today value us at SEK 6 billion, three times as much on fundamentals. So there's a gap between a market's valuation and analyst valuation. And sooner or later, the market valuation, well, usually catches up. So if you want to advance assets like we do, you de-risk them through documenting what you have. So the risk goes down. You move through phases. And we aim to do exactly that and do a deal at the right time. And through this de-risking, you have the value creation. So yeah, why are we in orphan disease? You can see it here. It's high unmet need.
Orphan Drug Designation protects the drugs in Europe and the U.S., premium pricing, faster development timelines, less capital intensive. We have an incentivized development plan through regulatory authorities. There's a very attractive deal value. We'll look at that later. There's a high revenue potential for those who get to market. These are the patients we want to help. Thank you, Mike. One minute when you step on the stage.
Thank you very much, Sten. It's important that we keep to time. I think for the purposes of the time we're keeping, because our next guest is coming online, we will leave the questions till the end. So if you've got any questions for Sten, save them up. So our next speaker, Sten mentioned both in our conversation and then in his presentation about key opinion leaders that they've got within their ecosystem. And it's a great pleasure that our next speaker is Professor Marc Humbert. Now, Professor Humbert, he's the Dean and Professor of Respiratory Medicine at the University Paris-Saclay Faculty of Medicine in Le Kremlin-Bicêtre, in France. And he's also the Director of Respiratory and Intensive Care Medicine at the Department of French Pulmonary Hypertension Reference Center. And he has other roles and jobs. He's clearly a very, very busy person.
He's a past president of the European Respiratory Society, Chief Editor of the European Respiratory Journal, and of huge relevance to today's meeting and this audience. Marc is going to be the PI for Cereno's CS1 phase IIB trial. Marc has also received many, well, several scientific distinctions that are just too many to mention, given the fact we've got such a short time. But one of the things I would like to say is that I work at Clarivate. We're able to track all the top researchers. And since 2018, he's appeared each year in the most highly cited researchers, particularly in the field of clinical medicine. So I would now like to introduce Professor Humbert. So let's go.
Thanks for asking me to join. I'm going to share my slides. You will let me know if you cannot see them. You should now see my slides. It's a great pleasure to be with you today. In the next 15 minutes, I'm going to give you an overview on pulmonary arterial hypertension in 2026. My name is Marc Humbert. I'm the Director of the French Reference Center for Pulmonary Hypertension. I work for the University Paris-Saclay for Assistance Publique-Hôpitaux de Paris and for Inserm. My focus is clearly pulmonary arterial hypertension. What is pulmonary arterial hypertension? It's a rare disease. It's a very, very serious disease. It's fatal if you don't give treatment. Currently, despite quite a lot of drug discovery, the unmet need is still very high, with a median survival around 7 years.
There is no cure for PH except if you perform lung transplantation, which is, per se, another problem for the patients. In the cartoon, you can see in a healthy lung the red lines, which are thick. At the bottom, you see the smaller red line indicating that the vessels are obstructed. They are remodeled. They do not let the flow go through the vessel. This will induce heart failure because the heart pumps through the pulmonary arteries. Our condition, PH, it's a pulmonary vascular condition inducing right heart failure. It's a cardiopulmonary disease. We have definitions. I'm not going to bother you too much on definitions. The diagnosis of PH is a very robust one. There is no room for uncertainty because the condition is so severe. We want to be very clear on the diagnosis.
When we measure the pressure, we measure it with a small catheter. This small catheter flows to the heart, to the pulmonary arteries. We can measure the pressure. Any value of mean pulmonary artery pressure above 20 mm of mercury defines pulmonary hypertension. Pulmonary hypertension is difficult to diagnose because the symptoms are not specific at all. The most common ones are shortness of breath, fatigue, and palpitations, and some chest pain. It's very, very difficult to diagnose PH at an early stage. When the disease has evolved to right heart failure, it's much more simple to diagnose. But it's too late because the patients have a very high risk of death. We have possibilities to estimate the pressure with echocardiography. Echocardiography is a beautiful tool, which allows us to measure pressure and to measure also cardiac signs.
Thanks to that, when the patients have a possibility of pulmonary hypertension, for example, in a patient who is short of breath, but this shortness of breath cannot be explained by simple diseases like asthma, chronic obstructive pulmonary disease, interstitial lung disease, left heart failure, et cetera, we go to echocardiography. Thanks to echocardiography, we can estimate the pressure. We don't measure the pressure. We estimate. There is a very complex algorithm. If we have a high probability of pulmonary hypertension, we do perform the right heart catheter in expert centers. Pulmonary hypertension, it's not only pulmonary artery hypertension. There are many causes of pulmonary hypertension. Clearly, we are specialists of rare and treatable forms of pulmonary hypertension, namely PAH, pulmonary artery hypertension. You see, there are other causes due to lung disease, heart disease, embolism, et cetera.
But here, we are in a rare condition with several medical therapies and transplantations. But we still have an unmet need. So to understand what pulmonary hypertension relates to, especially pulmonary arterial hypertension, you see on the left-hand side a normal small pulmonary artery. It is very thin. And if the blood flow increases by 5 x, it will inflate like a balloon. It's not resistant to flow. And the heart will pump through a non-resistant vessel. Here on the right-hand side, you see the major remodeling, which is a characteristic of pulmonary arterial hypertension. And you see the lumen here, the window here, is very, very small. And when the blood will go through this thick, remodeled, highly resistant vessel, it will lead to heart failure very, very fast. So we know more and more about pulmonary arterial hypertension. I've worked all my life on that condition.
When I started, there was no understanding and no management. Now we know more. We know that the disease is rare but not exceptional. In France, it's between 15 and 50 per million, and the same in most countries in the world. We know that the small cells, which are lining the vessels, are dysfunctional. The cells are called endothelial cells. Endothelial cell dysfunction is major in PH. We know that it leads to right heart failure. Several agents have been approved in the last 30 years with an orphan drug status. We don't have a cure. Many patients are refractory to therapy and require transplantation. The survival has improved from around 3 years to around 7 years. When you imagine that most of our patients are diagnosed between 40 and 60 years of age, this life expectancy is not satisfactory.
So we understand more and more endothelial cell dysfunction. We know that endothelial cells are important to modulate constriction and dilatation of the vessels. And you see here on the left-hand side a normal pulmonary artery. On the right-hand side, a remodeled, very thick pulmonary artery. And we can play with vasodilators. And we can block vasoconstriction. But it is not the key cause of pulmonary hypertension. It is just a symptomatic treatment. And you see, 20 years ago, in the New England Journal of Medicine, we made a summary of the treatment approaches. There were three pathways. These three pathways can be targeted with three drugs. But despite these three pathways derived from very, very good research, you see several Nobel Prize-winning colleagues. Despite all this major research and the beautiful clinical research published always in the New England Journal of Medicine, the life expectancy remains not good.
You see, here we lost it was 15 years ago. We lost around 12%-15% of our patients per year. We need to develop novel therapies. One approach was to combine the three pathway drugs together. We do more and more what we call upfront combination therapy with two or three drugs, especially in patients who present high risk of death. You see that we have parameters. I'm not going to bother you with the list. We know in the clinic how to define low risk of death at one year, intermediate risk of death, and high risk of death. You see that we are not very ambitious. Low risk is less than 5%. It remains quite high. There is room for improvement. We have simplified the risk strata instrument.
We know more and more how to define and how to predict outcomes in our patients. We know who are the patients in need of therapy. We have an algorithm, very complex. I'm not here to teach. I'm here just to show that when you have PAH, you should go to an expert center. You should receive therapies based on risk assessment. Risk assessment will define your initial treatment, your follow-up treatment, and the need for transplantation. It is a very professional approach. We are very comfortable with the treatments we have in hand. However, these treatments are not enough. The big problem with PH is remodeling. You see on the screen here the major remodeling with here the endothelial cells, here the smooth muscle cells, here the inflammatory and adventitial cells. This is a remodeled vessel.
My research with my group, which has been recognized very much recently, is to understand what are the mechanisms. We know more and more about the mechanisms. No doubt, I'm not going to explain that to you. But very simply, the pulmonary vessels are in a state of balance. It is a well-balanced, what we call homeostasis. Usually, you have two pathways which are well-balanced together. But in PH, you have BMPR2 mutations or BMPR2 dysfunction. This will lead to a decrease in the protective pathway and an excess in the proliferative pathway. This explains why the patients develop remodeled vessels. We have understood very well that issue. The most recent drug developed for PH is called sotatercept. It's a drug which rebalances these pathways. With this drug, you improve the walk distance. You improve the outcome.
You see here, it's time to death, transplantation, or hospitalization due to PH. You see, you have less events, but you still have events. But you improve quite well the situation. So currently, in 2026, we have four major pathways. And most of my patients in Paris are treated with four therapies. But despite that, there is an unmet need. And many of my patients do quite well. But they have no certainty about their long-term outcomes. And we really need to develop new solutions to improve outcomes in pulmonary arterial hypertension. So you remember the therapies targeting nitric oxide, endothelin-1, prostacyclin, and now TGF-beta. And these pathways are well taken care of. We have now an algorithm of treatment. And for you, what matters is risk, risk, risk, risk everywhere. We measure risk. And we have a treatment goal. It is low risk.
In my country currently, despite the fact that we have a network of expert centers sharing knowledge and guidelines, less than half of the patients are at treatment goal. So there is room for improvement, of course. This is the natural course of PH. With therapies, sometimes we slow decline. Sometimes we obtain a small disease improvement. Sometimes we obtain, as in cancer, partial remission, complete remission. We almost never reach cure. It almost never occurs. So there is a lot of room. We need disease-modifying drugs. In that setting, many, many people work. Many people work. You could be a little bit shocked to see that there are 15 drugs approved. But there is room for improvement.
PH, it's a drug, it's a disease with a lot of opportunities because we have strong labs, strong clinical centers, very good partnership with pharma and with patient organizations, and strong support from our national government and European and international bodies. So here you see many people work on novel therapies, et cetera. I would like to spend a couple of minutes on what we call epigenetic alterations. This is the focus of the Cereno compound. Clearly, epigenetic modulation will be certainly a novel pathway to consider in PH. So I'm not going to repeat what I just said. Pulmonary hypertension, it's a disease of the lung vessels resulting in right ventricle failure, disability, and death. You have several ways to try to modulate what is called epigenetics.
And with epigenetic modulation, you can certainly restore a better function of the vessels and the heart in pulmonary hypertension. So there are several ways to interfere with epigenetics. You have the non-coding RNAs. You have the DNA methylation. But you have histone modification, which is very important. And HDAC inhibitors are certainly very important to consider in PH in order to improve the lung condition, the right heart consequences. So right now, it's my final slide. And I thank you for your attention. The elements of cardiovascular and pulmonary diseases addressed by HDAC inhibitor are many. There are certainly possibilities to improve remodeling of the vessel, improve the fibrosis around the vessel in the heart, improve inflammation, lead to pulmonary pressure reduction, and have some anti-thrombotic action, which will result into degradation of the pulmonary vascular disease. So clearly, we have a lot of progress behind us.
There is a lot to come. I'm very pleased to speak with you. I will stay for a while to address questions, if any. Thank you very much for your attention.
Thank you very much, Professor Humbert. And in fact, Professor Humbert will be on sort of the panel discussion, which we will be starting in about 15 minutes. So thank you very much. Some very, very interesting slides. And actually thought beautifully illustrated. So it was actually I understood it. So if someone like I, a mere journalist, can understand it, you did a very good job, sir. So the next presentation actually is going to be coming from sort of somebody that sort of represents probably one of the most important groups in this whole story. And that is the patient. So to provide a patient perspective, I'm pleased and delighted to introduce Hall Skåra. Hall is a Founding Member and the Past President of the Norwegian Pulmonary Hypertension Patient Association. It began working as a consultant for PHA Europe in 2017.
One of his key responsibilities has actually been leading the White Spots Program, which is aiming to establish sort of new pulmonary hypertension patient associations in countries where they didn't exist. He's providing sort of your ongoing support for these associations. It's been pretty successful. There are only a few countries now that actually remain without a PH patient association. He's got plenty of other roles. I'm going to sort of leave the floor to you, sir. Thank you.
Thank you. Well, thank you very much. Thank you to Cereno for inviting me. Thank you for recognizing the importance of the patient voice. Because behind every data point and behind every investment decision, there is a person living with this disease. My name is Hall Skåra. I'm actually Norwegian. My journey started in 2003. I started becoming short of breath. There was no indication before this happening that I would have a disease like this. I just started noticing that I was short of breath. Then I was pretty active. I lived very healthy. I exercised a lot. This is from the years before I was losing my hair. You can see. This is quite a long time ago. I went to the doctor. I complained.
I said, I think something is wrong because I'm short of breath. So he took a lot of tests, blood tests, and all other kind of tests. Everything was normal. But I insisted because I knew my body. I knew something was wrong. So he sent me to the local hospital. There I did a bicycle test. To my surprise, I did as well as expected. But I've been thinking about this afterwards. I think this is because I was in good shape. When I did as expected, this was worse than, for me, normal because I was in better shape than normal. So I was just told to go back home. Everything was OK. Continue to exercise. Things would probably be OK. But I started to get gradually worse.
After two years more, I realized something is seriously wrong because then I started having problems going up steps and things like this. So I went back. This time, I met with a pulmonologist. He put a little oximeter on my finger to measure my oxygen, which was normal at rest. But then we went down to the basement of the hospital. We walked quickly up the steps. Then he looked at this oximeter. He said something is wrong because I had very low oxygen in my blood after that trip up. So then I was sent to the main hospital in Oslo. That was what I needed. Just after two days, they found the diagnosis that I had this disease, pulmonary arterial hypertension. The reason for this disease, they could not find. So it's called idiopathic.
I was told, probably as the years go by, you will see and the reason will show up eventually. Now it's been 21 years. Still, there is no reason. So the reason for this, I don't know. My first reaction was angry. I was angry at my body because I had treated my body very well. I did everything I should by living a very healthy lifestyle. And this is the response of the body to give me such a serious disease, life-threatening chronic disease that could not be cured. I had been reading on the internet. I knew that if this was the disease I got, it would be very serious for me. What I read on Dr. Google was that 2.8 years was what was expected after the diagnosis. So as I said, I was 46 at that point.
I thought I would not be able to be 50 years old. I had a family with two teenage sons. I remember we were in a hospital room after the right heart catheterization. This is how you diagnose this disease. They go in with instruments inside your heart and measure. We were sitting there, me and my wife and the oldest son. The doctor came back. He told the diagnosis. My wife immediately started crying. I don't know why. But the first thing that came into my mind was, "Will I be able to be a grandfather one day, to live long enough to be a grandfather?" The doctor said, "Why not?" But then I saw he looked at my oldest son to see how old he was. So I knew this is serious business.
A lot of people get depressed when they get this disease. We have done some surveys. About 40%-45% of the patients get depressed. Of course, you think about that you're going to die. You forget to live. This was kind of the case with me also a little bit in the beginning. First thing I did was I went to the bank. I transferred all my accounts to my wife so that it would be easier for her the day I was gone. Strange things. But for instance, if I was listening to music, then I would think, oh, this would fit well in the funeral. For instance, I listened to Bob Dylan and Forever Young. I thought, oh, this would be a nice song to play in my funeral.
If you know this song, there is a phrase that says, "I wish you a strong foundation when the winds of changes shift." I think I had a strong foundation because I decided at that point that I would accept this disease. I would do whatever I could to live as long as possible and live with good life quality. There were no associations in Norway. I started the Patient Association. We became part of the large Lung and Health Association in Norway. Then after some years, we became part of the Umbrella Association, PHA Europe. I started working more for them. Somebody else took over the Norwegian Association. Talking about work, by the way, after my diagnosis, I went down to a 50% position. After six, seven years, I stopped working completely. I worked in a large computer company.
I had a management role. For some reason, that did not feel interesting anymore. I had much more interest in working and trying to help other people with this disease. Through my work in PHA Europe, we had some unmet needs that we tried to address. The first unmet need is that it takes way too long to get diagnosed. The problem with this disease is that you get the symptoms are so diffuse that you're short of breath. Well, if you're out of shape or if you have asthma or whatever, you're short of breath. You need to go on the operating table to get a real good diagnosis. So our hope is that we can find a way to diagnose patients earlier, maybe through a blood sample.
But if not, we need to help create awareness for this disease because today, it takes 2-3 years after you go to the doctor the first time until you get your final diagnosis. And with me, as you saw, it took 2 years. So these are some of the things we do. So my son, he's an athlete. He played on the national team for Norway for basketball. And I convinced them to play one of their matches with blue lips, which can be one of the symptoms of PH. So they all painted their lips blue. The opposing team did the same when they heard about this. And this created news in Norway. It was in the papers and so on. And then we were invited to a TV show, me, my son, and my doctor.
We talked about the disease and created a lot of awareness for this. Another way I created awareness was through a TV program, which I think also you hear here in Sweden. It's called Hva feiler det deg? O r What's Your Diagnosis? And it's a kind of interesting concept. You have two teams. One team is a doctor team. Another team has no medical background. The team without medical background, they can use the internet. The doctors cannot. You give them hints about your symptoms and so on. One of the hints was boxes of Viagra, which is actually an entry-level medication for PH. This is what I use. I take Viagra in the morning, in the day, in the afternoon. I've taken about 22,000 Viagra pills since I got this disease.
People often ask me, do you have any side effects with this? Anyway, one of the doctors, he was a cardiologist. Right away when he saw this, he knew what kind of disease I had. We had a Patient Association meeting after this. One woman stood up and said she watched the program. She went to the doctors. She said, I think I have this. They diagnosed her with this disease. This is an interesting area because we, as a patient community and the pharma industry, we have the same goal. We want to put patients on drugs as early as possible to make them live as long as possible also. The second unmet need, I would say, is we really need a true disease-modifying drug because, as we heard today, the drugs are not true modifying drugs.
So whenever I hear about a new company, I hear about a new pathway. And I hear the words disease-modifying, I get very excited. And all the patients get very excited because then there is a potential that maybe you can have a drug that can reverse all the things that happen inside your lungs. And as Professor Humbert talked about, there are different types of PH. And you have this type of PH where you have a lung disease. And they have no drugs. So when I talked about this 2.8 years, it's even worse for them. And this is a large group of people. So if you have a company with a drug for these kind of people, you have a big, big market.
And then the third unmet need, and this I often see when I travel around to different associations in the world, many of them, they don't get access to medication. So we are very lucky in Norway, Sweden, and so on with the universal health care. But if you go to Eastern Europe, if you go to South America, et cetera, they don't get access to all the available medication. So my plea to a new company delivering drugs to the market, please help as many patients as you can. So the question is now, after 21 years and by the way, this is very unusual to live this long with this disease. So I have been very lucky. So the question is, have I become a grandfather? Because now, certainly, my boys are older. My oldest is 39 this year. And the other one is 35.
But they have not yet had any children. But I've told them, you know there's no worry because I plan to stick around for many years still. And especially when I hear about new drugs, I think I can stick around for many more years. So thank you.
Well, thank you, Hall. Again, yeah, really, really interesting to sort of hear your journey. And also, kudos to the fact that what you're doing for other people with your work, with the associations, et cetera. So congratulations to that. I'd like now to ask you to join us. We're going to have a panel discussion. We're going to have so if you can join us, Marc is going to be here. And I'd also like to introduce Dr. Rahul Agrawal, who is the CMO and the head of R&D at Cereno. So actually, Rahul, do you want to sit there as well?
Sure. I'll sit here.
Actually, I'm going to start with you, Rahul, because you heard both Professor Humbert and you heard from Hall. And I was just sort of thinking, you're a company that is trying to provide some solution to this. So what resonated with you from what was being said by both Professor Humbert and Hall?
I think what resonates and this is where we at Cereno are so passionate about is, on the one hand, even though there are some drugs on the market, they are sort of only, if I may call it that way, short-term solutions. So they're not really tackling the root cause or not disease-modifying. And science and here, we heard from Professor Humbert, who has been really pivotal in this worldwide, that there is progress, but still not sufficient. And when one hears from Hall regarding the patient perspective, there's a huge burden, not just for the patients, but also for the families. And I think this gives us at Cereno even a bigger purpose to really try to make a difference with a drug, which is accessible, but which is also easy to take.
So we think it's good that it's an oral drug, maybe once daily, that we can combine it with other drugs. So all these characteristics and properties, we feel, are so important to take into consideration.
Right, right. And Professor Humbert, you're clearly you've got a lot of experience in this area. You are able to sort of show us the scope of what is out there. And you're clearly sort of the vanguard of the research. But you're now coming on board as sort of the principal investigator for Cereno's CS1 phase IIb trial. I'm just wondering, what did you see in what Cereno was offering that actually excited you and got you to sort of say, yes, I want to be part of this?
Thank you for the question. Yeah, it's an important fact. I mean, we don't say yes to everybody. We select. And we are very careful in the selection. Clearly, Cereno's compound is not a me-too . It is targeting a novel pathway. Second, it positions itself in the landscape of established therapies. So it doesn't replace anything because we do not need replacement right now. We need to have something adding. And last, it has some characteristics that are unique to that drug class. And we would like to see in a phase IIb good quality study whether this approach adds something to the current landscape of PH therapies. So that's my very simple reply. And of course, I know also some of the people working at Cereno, they have a long history of partnership with my community.
As you have heard from the patient organization, we have a strong network, which works very well for many years.
But I mean, sort of looking at, say, for example, epigenetic modulation. Now, from what I understand, epigenetics is something that it's almost philosophical, sort of trying to get one's head around. So as you sort of look at this approach, how challenging is it going to be to almost like educate other people who aren't as focused as you are on this space to actually sort of take on board what has been developed here?
Yeah, we have been very educational in our field. And you have seen the way from the very simple pipe constricting and dilating to the very complex TGF-beta superfamily modulation. Now, as you say, we are in a more not philosophical, but complex thinking. I mean, epigenetics, what makes somebody different from another one because of small molecules interfering with DNA, RNA, and very basic modulators of cell function. So we will manage because I think in recent years, we have been able to communicate well on the advances in PH. Here, we really try once again to restore something which is currently dysfunctional in PH. So the thinking is very similar to the previous thinking, although we target more complex mechanisms. So I'm not concerned with communication. I wish it works. And if it works, we'll make the story as simple as possible.
We will try to understand if we can further refine that approach because certainly, it's a very important step forward. If that approach works, it will open a new field.
Yeah. And actually, so having seen your presentation, you're clearly a very accomplished science communicator. So if anybody's going to be able to do that, I'm sure that you are going to be that person. Hall, so from sort of the patient perspective, sort of what you heard from Professor Humbert and also what you already understand about what Cereno is doing, as well as what other companies are doing, what gives you confidence that, for example, in your wish that you will see you will become a grandfather? What have you seen that actually makes you believe that that is potentially a reality?
Well, I continue to see development in the medical field. I continue to see medication that's not, as Professor Humbert said, just the replacement for medication, but new pathways. The more pathways we get, I think the higher chances will be that you find something that will really be disease-modifying.
Right. But it's interesting. I mean, you're representing sort of your patient groups. And we know that a lot of pharma companies, biotech companies are embracing patient centricity and want to hear the voice of the patient. But from that sort of patient perspective or the patient advocacy perspective, what would you actually like either sort of the pharma companies or even sort of your expert researchers like Professor Humbert to actually do to help you understand that they're listening?
Well, I think they are already doing many of the things that they should do. For instance, the fact that I'm here today shows that you are listening to the patient, which is very good. And I worked a lot with Professor Humbert and the medical community. And they are including us also. So I think we see more and more that the patients are involved in the medical field, not necessarily to provide any medical new knowledge, but to provide the patient side of things. So for instance, we work on empowering ourselves to gain more knowledge, to understand, for instance, how trial works and so on, so that we can be part of, for instance, a scientific committee, help to develop a protocol, help to tell what are the endpoints that you'd look at, help maybe with documentation to make it understandable for the patient, and so on.
I think together, pharma and the health care community, plus the patients, it's a very powerful collaboration.
Rahul, do you have any thoughts from where you're sitting on that patient engagement and how it shaped your thinking?
So very much so. What Hall is saying, we're also putting that into practice. For example, Hall will be helping us with the steering committee, also shaping the protocol that we are planning now for the phase IIb trial because the patient perspective is so important. I'll give you an example. We were talking about that questionnaires, PH-SYMPACT Questionnaire, which is FDA approved, very important, but very tedious to fill out. Hall was sharing his experience, how hard and how tedious it is to do such a course. So we have, of course, included many of the perspectives. We will be continuing to do so. What is important for patients, for caretakers, of course, also not neglecting the science. All in all, though, the final goal is naturally, we're a biotech. We're in the private industry.
We want to get the drug to the market because if it's not on the market, it will not benefit any patients. So of course, we need to have the commercial clear path forward on how to be well differentiated, how to be then hopefully also, of course, commercially successful, to be able to give it and provide this therapy, which is hopefully beneficial, to the patients. So we're taking all of these considerations into account. We're hoping to include all the major stakeholders, like the world-renowned experts, like Professor Humbert and Hall Skåra, who is very active and also a very eloquent speaker, as you could hear. We're grateful for that opportunity.
Yeah. And we will explore a little bit later on in some of the other discussions what that sort of clear view looks like. But I'm going to ask you a question. And I'm going to ask Professor Humbert also how the voice of the patient sort of influences his thinking. So you can sort of think about that while I ask the follow-up to you, Rahul, which is when creating something that is new, this is potentially new for regulators. And Hall sort of mentioned about endpoints, et cetera. What involvement have you had to have or are you having in discussions with regulators to sort of create that clear view to an understanding of what would be a meaningful endpoint, both scientifically, but also for patients?
I think the most important thing is to really include all the major stakeholders into the discussion. It is, of course, the scientific community. It is absolutely the patients. It is the regulators. But we also have to listen to the market. What does the market need? Where is the unmet need? How are we different? How are we attractive to be sort of considered? So I think it is very, very important to be doing that. I've had the pleasure of working on the R&D side, where I was also involved, for example, in the development of riociguat, a drug many, many years back that shows how old I am now. But we developed that and brought that to the market. But I've also worked on the commercialization of many drugs, several launches.
It is important to really consider the main block builders for the entire value chain, starting from the patient need, the science, the needs that there are, the commercial aspects, all of that. Then one has to, of course, be in dialogue with all these different stakeholders. Absolutely. There are many others, by the way, regulators, payers, and which we do not want to bore you with a long, long list. But that's what we like to do in the background and what we are also doing here.
Yeah. So Professor Humbert, so yeah, I'm sort of intrigued to understand the sort of influence that the patient voice is actually having on your thinking, sort of your developing ideas to treat these at the moment not well-treated diseases. We haven't got your sound.
Yeah, sorry. Yeah, I muted myself. So thank you very much. Yeah, the patient voice is central. Central. And this is the reason why we work. This is the reason why we want to make a difference. You know, when I started, it's a while ago now, I started. And I was almost the same age than the average patients in my department. And most of my patients were either transplanted or dead one year later. So for me, it was really a big stress, to be frank. I felt very sorry for the patients, of course, for their families. And I decided with my group to try to make something to improve that. So of course, we started with transplantation, very invasive treatments, et cetera, et cetera. And we had success. We had quite a lot of success.
And then we tried to improve, simplify, and find new ways to improve them. And we always try to remember what the patients want. The patient wants to feel better. They want to function better, be less short of breath. And they want to survive better. I mean, they cannot accept the death rate of the condition. But it is important to remember that they want to feel better. So that's part of the priorities we have. And on top of that, now we are an established community with a lot of good achievements. And now when we develop our guidelines, when we develop our working group, we always put patients in the group. So for example, the European Guidelines on Pulmonary Hypertension, I'm the lead author of these guidelines published in 2022. We included two patients in the committee. And these two patients are authors of the guidelines.
When we published the guidelines, we thought, well, we had two patients, but it's not enough. We want to make a guideline in simple words because in fact, people like Hal are very able to understand our jargon. But the usual patients, they are a little bit lost when they see what we write. So we did a guideline in plain language. And then we said, well, plain language in English, my French patients don't understand English as well as you think. And so we decided to do it in 12 different European languages. So the more we move on, the more we keep the patient in the central position, in the driver's seat. And on top of that, we want them to be included. So we try to be inclusive, even those who are not game players today. They should be able to enter the game.
So a company like Cereno, which tries to develop a new solution for the patients, they have understood that. They have engaged Hall with them and others. Myself, I'm very pleased to work with the Patient Association because it always helps us think about what is our objective. Of course, my objective is to understand everything. But I know I will fail. But if I understand what the patients want and if I try to make something meaningful for them, it's very useful. And usually, it's very important also for the payers, for the regulators. And when we write an article, we always think, what will be the understanding of the people who will, at the end of the day, pay for the treatment we develop or approve it at the European or American or elsewhere level? So the patient is central. We work for them. They are partners.
I'm very sure in the next 10 years, we will make a very big difference in the field.
Yeah. It seems to me that part of that is disease modification. I mean, that seems to be almost like the Holy Grail. That would be, if that is achievable, that is the one that's going to get sort of real-world outcomes for patients. I mean, how excited are you about that disease modification potential that you've seen Cereno already show you?
Yeah, yeah. No, I'm a scientist. So of course, I want to understand what the words mean. So of course, disease modification, it's a very beautiful wording. And I think everybody can put something positive on top of these words. So I worked with a very large group. It was very interesting. We published that a year ago. And we worked with a very large group of patients, regulators, payers, scientists, clinical doctors on the concept of disease modification in PH. And we realized that it is a very, very good objective. But to make this wording into a scientific condition, we need to define what it means. And that's the reason why I showed very briefly a very simple cartoon with different courses of the disease, from natural history to small improvement to cure. And clearly, disease modification, it's not minor improvement. It could be cure, of course.
But we thought that in scientific words, the word remission could be a good synonym of disease modification. And we can call it disease modification. But we can also call it room for improvement in such a way that you can be considered as in remission. So it means that you will live for a very long time with very little consequences of these otherwise deadly diseases because sometimes we forget. When you see Hal on stage, you forget Hal was near death when he was diagnosed. And now he's blooming because of his body quality and the quality of management. But clearly, this disease is very, very severe. So disease modification means something. And me, in medical terms, I aim for remission today.
Great. So well, thank you very much for the insights. I think what we've been able to do there is what we were looking to identify, sort of meaningful change that patients need, want, desire, and is going to give them healthy, meaningful lives. So I'd like the audience to thank the sort of participation and the contributions for our external guests, Hall and Marc. Thank you very much. And also, thanks to Rahul. Thanks to Rahul.
Thank you.
We're now going to have a coffee break for 10 minutes. Then we're going to be starting back promptly because we've got a lot to get through. I hope you've enjoyed the first half. Thank you. Thank you. Excellent. Okay, so welcome back to the sort of the final session of today's Capital Markets Day. It sort of gives me great pleasure to introduce back to the stage Dr. Rahul Agrawal, who you've already met on the sort of the previous panel discussion. As you can sort of see, he's going to talk about sort of advancing CS1 into Phase 2b in PAH. He's basically going to give us an overview of CS1, the sort of the rationale, the mechanism, differentiation, and also, I guess, the sort of where you are now. The floor is yours, sir.
Thank you so much, Mike, and welcome back from the coffee break. I hope you can see from the presentations, from Cereno, of course, but also from Professor Humbert and Hall, why we personally are so excited to really progress CS1 to the next stage.
I'd like to share that excitement with you because we believe we're at an inflection point now. I'd like to share some details, some backgrounds, and then show you where we are heading, what the next steps are, and why this excitement and maybe this innovativeness to make a difference in the lives of patients we think is sort of the best pathway forward. So, CS1, and this is the aim that we want to show also: we want to slow, halt, and reverse PH disease progression. You heard from Marc Humbert that these are sort of the new focus, this is the new focus of disease development, of the drug development there is the last few years. It was symptomatic vasodilation even further? Away. Away, sorry. That way. Thank you. Thank you. Wow, that was great technical help, thanks.
What we want to do is definitely be on that path where we change the trajectory of the disease. We want to do that in a fashion that is also amenable for patients. That means it should be a drug which is oral, preferably once daily, and naturally combinable with other drugs. You know, maybe that many of the drugs that are on the market do have some side effects, have to be taken with caution, and we think here we have a very promising solution.
Reverse remodeling. I think you have seen a few pictures now in the last few minutes as well. This is on the right hand, or from your side on the left-hand side, a healthy vessel on the right-hand side, how it progresses, and I think it illustrates how hard it becomes for patients to really then also, in the end, breathe, and how I was describing that in a very eloquent fashion. We definitely want to halt that progression, to slow that progression, but definitely make a difference which has a lasting effect for patients. As you know, and as we have shared over the last few months, besides the preclinical data that we have, we have also seen some very promising signals in the phase IIa trial that we have shown and shared with you over the last few months.
What we saw there was, number one, and this was, of course, the primary endpoint, we achieved a very good safety and tolerability profile, which is, again, naturally very important that patients can take the drug and tolerate it. Besides that, and this also got us very exciting, we saw some signals which we also shared with you. One, and you know that this is a very important one: how is the right heart functioning? And you may have a recollection that I had often mentioned this global longitudinal strain, a very important and objectifiable prognostic factor for a treatment in PAH. And we saw very many promising sort of signals regarding GLS improvements, sustainability, and also tricuspid regurgitation improvements, keeping in mind that this trial that we did in the phase IIa was only for three months, and even in this short period we saw these improvements.
Besides that, we also saw signals in improved quality of life. You may recall we had done the PH-SYMPACT. You may recall we had also looked at functional class and Minnesota Living with Heart Failure questionnaires. And in all of those, we saw a very nice trend towards either sustaining it or improving it even further, again keeping in mind this was over a relatively short period of three months only, and still we saw that. In addition to that, we also, and you may recall that, we had also used the prognostically most promising and important risk score, that is, the REVEAL Risk Score.
There we saw an improvement in a large proportion of patients by one point, and we had also translated what it means, and it is also published in the literature, that if patients over three months improve by one point in the REVEAL Risk Score, that translates into an approximately 23% improvement in mortality within 12 months. So that means that if we can improve the REVEAL Risk Score within three months by one point, that translates in an improvement in survival. Again, very, very promising signals. We had shared all of those with you before.
These things, together with the fact that we also got very good feedback from the sites, as you may recall, there were 10 sites in the U.S. that we had used for our phase IIa trial, we also got feedback from a few of them who wanted us to initiate an expanded access program, which we have performed, which is still ongoing. The last patient's last visit was just recently. We're going to do database lock and also share the data as soon as that comes out with you. All of these things point towards the fact that there are promising signals, patients are excited about it, and they're treating physicians as well. All of this has led us, of course, to see how we can develop it further and take it to the next stage. This is what I would like to share with you briefly.
You know that we have orphan drug designation since some time, not only with the FDA but also with EMA. That is, of course, a very good sign where the authorities also see promise in what we're doing. Beginning of this year, we had a very good interaction in preparation for the phase IIb trial with the FDA, a so-called Type C meeting, where we shared our view, our thoughts on how we would like to design the trial, and we got good feedback. It was a very good interaction, and we got good feedback. We, of course, complied with some of their thoughts as well. In that due course, we also got a fast-track designation. What does that mean?
That means, and Cereno was briefly alluding to that today as well, that here the authorities see a certain promise for the improvement in patients' lives with the approach that we have. So a fast-track designation means that we have sort of a direct line, or if you'd like a shorter line, to the authorities. We can interact with them much more closely for the steps we're taking, how we're taking them, and what we're doing. So again, something very, very positive for us: a fast-track designation. And towards the end of the year, so in December, we also got the clearance from the FDA for our phase IIb trial design, the endpoints, and what we're looking at also, of course, as secondary endpoints. And I'd like to share that with you in a few moments, how that is going to look like.
So all in all, very promising steps that we have taken, especially in the last 12 months, to really solidify, on the basis of the phase IIa trial, on the basis of what we're hearing, seeing, to take the next steps. One thing which I would like to share with you, and Marc Humbert briefly also shared, that is a recent publication that was written together with sort of leading experts, not only from the FDA and EMA, but also opinion leaders - and by the way, Marc Humbert was one of the authors, and a few other names you'll be seeing - who said that clearly there has to be a paradigm shift towards disease modification. Keep in mind what Cereno was saying at the beginning: our drug is on that track. We want to sort of go onto that track of disease modification of this very serious entity.
Mainly symptoms management to slow, halt, and reverse PH disease progression, and this is the picture that Marc Humbert had also shown. I'd like to briefly take you through this. What you see in the dark gray arrow is how the natural disease progresses: very serious and, of course, an outcome we don't want to see. Level one is slowing decline. That is what the drugs, the vasodilating drugs, so far have been able to do: to slow the decline. But now the paradigm shift is to either reach Level 2, 3, 4, or, in the best of sense, a cure. Have drugs so far been able to do that? There is, of course, the most recent one which was on the market, which has shown to be moving towards Level 2, but they do not have the designation for disease modification because they could not really show that.
They have shown morbidity, mortality decrease, but really no signs of disease improvement in that sense. So the main goal now is, for new drugs - and we definitely are aiming for that - that we have not only a disease improvement but maybe also partial or complete remission, because preclinical data is very promising. Clinical, we have to go that route and show that, hopefully. So this is where we are, and just wanted to share with you that this Lancet publication, which came out beginning of last year, shows and underlines the paradigm shift. What we want to do is definitely take these things into consideration in our phase IIb trial.
And with that, we have a highly innovative trial, and I want to share with you this excitement that I already have and the team has, why we're excited, and I hope that at the end of listening to this, you'll be at least as excited as we are regarding the trial design. So, the Clinical Steering Committee is led by Professor Humbert . Mike had briefly introduced him, past President for the ERS, Chief Editor of the European Respiratory Journal as well—that is, the Blue Journal, where most of the major publications happen. He has over 1,100 publications. He is one of the most cited researchers, and still very much humble and modest, as you could see. And he has been the PI for several studies. He is the world-renowned leader. He is the author of the guidelines, not only of the European guidelines but also the global ones.
I still have a few more slides to show, though, Mike. OK. And yeah, and Sandeep Sahay is a rising star. He is also an author of the American guidelines and was also an author on the Lancet paper that I just showed you on the last slide. So both of them are authors. Besides these two very renowned researchers, we also have others who are well-known, among others, so from Latin America, in Brazil, it's Professor Meyer , who is also on the guidelines of, again, the World Guidelines for pH, but also, of course, the Latin American ones. You'll be recognizing one Swedish name: Göran Rådegran. He is the head of the Pulmonary Arterial Society in Sweden. He is also an author and co-author, I should say, of the European guidelines and a very active member.
As a fifth person, you'll have a recognized name here: Dr. Bhatt, who is one of the leading cardiologists in the world, one of the most recognized ones, most cited ones. So we are having a very distinguished steering committee who will help us guide in this trial. With that, we want to make sure that we really have the highest quality that we bring: credibility, quality, and with that also, hopefully, great execution with a world-leading CRO. So, the phase IIb trial is going to be approximately 125 patients in approximately 10 countries, so globally. We want to start with the first patient before the summer, so in Q2, and that's going to go extend up to top line in 2028. How does the study design look like? Again, as I was saying, it's going to be highly innovative and something very new. Why?
I'll give you that. So far, all the primary endpoints were for 6 months, based on the vasodilation, but we think, because it's disease modifying, and we are, of course, also taking into consideration the latest publications' ideas, we are going to extend it to 9 months and going to look at the primary endpoint after 9 months. That means we're going to look at the pulmonary vascular resistance, which is determined through the right heart catheter, so an invasive, of course, methodology, but that is what is required by EMA and FDA. So we're going to do the PVR as a primary endpoint after 9 months. We are, of course, going to look at, in the secondary endpoints, 6-minute walk test, functional class, quality of life, because naturally the well-being of the patient is first and foremost for us as well.
So we're going to capture all of those things. In addition to that, we are, first of all, looking after nine months (so this is where we are going to have the primary endpoint) we are then going to look at that primary endpoint once all the patients have completed the two right heart catheters and we have the completion of all those patients. After that, we're going to follow up the patients further. On the one hand, we're going to include, again, something very innovative (no one has done that before) that we are going to also include a period of so-called medication withdrawal, which the FDA wants to show that we have disease modification. We are going to be the first ones to do that in a Phase 2B trial.
So, two things which are first: 9 months, and we're going to look at the patient or drug withdrawal as well and look at that. Then we're going to follow up the patients for 4 more further weeks. Every patient has a chance, which was on the placebo group, to be also on the verum group, and the verum will also, of course, then change and have a double-blind, randomized, placebo-controlled trial on a global level in leading sites. This is where we are. We are going to, of course, make sure that as soon as we have information, we would, of course, share that. We have a Data Safety Monitoring Board, that means, which will continuously look at patients. First and foremost, it's, of course, always safety, but naturally they're going to look at the whole picture of what is happening.
So important is: this is sort of the highest form and quality, which gives us also the biggest credibility for data. So, for the phase IIb, we would like to be as good, as fast, and as efficient as possible as could be. And using, of course, some very innovative tools and means here as well. How much more time do I have, Mike?
You can keep - this is im portant, so.
Thank you. Thank you so much. Then I'll take my time. All right. No. So this is the design, and the advantages - of course, we're going to look at the 9-month primary endpoint, and then we'll analyze it. So we do not have to wait till the end of everything that has happened. We will be looking at the primary endpoint. We will be looking at how the things are aligning, how the patients are doing.
Please keep in mind: the most important thing in a phase IIb trial is always the congruency of the data. That means: are all the major signals and parameters that we're measuring pointing in the right direction? That is what everyone looks at. That is what the authorities look at. That is what patients, of course, look at. That's what payers look at. That is what also defines the commercial success of a drug. So we're going to look at all of that. So, the study will evaluate safety and tolerability, optimal dose, and, as we said, patient population. They will be on top of standard of care, all of them. So, at least 3 months for sotatercept, 6 months. You may ask why 6 months for sotatercept? Very easy: because it has been shown that sotatercept has a plateau of effect after 6 months.
There's no increased improvement after 6 months. So, we're including patients who are on stable therapy or, in the latest one, 6 months. So we're including all patients and not excluding anything. We're doing, as I had said, a right heart catheter, which is sort of the gold standard for diagnosing, 6-minute walk test, a lot of the quality of life, functional assessments, biomarkers, everything that needs to be. We are including that. And it's so good that we have a world-class steering committee who are also helping us. And, by the way, besides the steering committee, I forgot to mention that and I apologize, Hall is also going to be an advisor to the steering committee, helping us, giving us the patient insights and what we also need to consider. So we are delighted to also have his support here. Maybe very important: I had mentioned the Data Safety Monitoring Board.
And maybe one thing which is very important as well to keep in mind: interim analyses is usually something which one, of course, does in a phase III trial. Because we are looking at a phase IIb trial right now. It's a rare, orphaned indication. So we want to ensure that there's data integrity, there's confidence in the data. We do not want to invalidate anything if we do it too early. But, of course, if the data is exceptional, if we have something which we could apply for conditional approval, we will go for that. If we have something regarding breakthrough therapy, we will look at that. We will go for that. So the options are there. Possibility is always there. We do not want to promise it because it, of course, all depends on the data. And regulatory milestones: definitely, we have already gone to the FDA.
We will now be going to the EMA. We'll be going to the Latin American authorities as well. We will be making sure that we have a very successful and well-coordinated activation of sites. We are working, as Sten had already mentioned, with a world-leading CRO in this field and one of the largest CROs in the world anyway. So they have the breadth, they have the infrastructure, and we are having a very good collaboration with them so far. This is the map. You may recognize it and, sort of, yeah. So it is the U.S., including Alaska, we're not getting into political discussions here, we have Europe and Latin America. First patient enrolled: the goal is before the summer in Q2 of this year. All right. This, as I had shown before, this is the aim. This is the overriding thought that we have.
This is what we're aiming for. It is based on something which we have—we see as very promising signals from the phase IIa. We have very good foundations scientifically from the preclinical data that we have had so far. So we think we're on a very good path to, hopefully, maximize the probability of technical success for this drug in the phase IIb trial. Thank you so much for your attention here. OK.
Thanks very much, Rahul. Thank you. So, I mean, clearly that phase II trial design is like super important. So I thought, OK, I'm going to give you some leeway. But actually, the next panel—so we've got two panels coming up now. And in the first, first of the sort of the panel discussions, we will explore a bit further the sort of the rationale, etc., that we're going to do.
So, on the panel there's yourself. So, Rahul, if you want—if you'd like to sit down. Sten, if you'd like to join me. And, of course, also I'd like to, for the first time, bring to the stage, Björn Dahlöf, who is the Chief Science Officer, or Chief Scientific Officer a t Cereno Scientific. So welcome, Björn. Yes, that's fine. So, as I say, we're going to have two panel discussions. The first one is sort of, you know, looking at the sort of clinical journey, right? The clinical development path for CS1 from Phase 2A to market. And, you know, as we just sort of, you know, heard, you know, Rahul sort of basically described, you know, what's a very, very elegant clinical trial design. And I'm really intrigued to understand almost the ideation process associated with that.
Now, Sten, I'm going to point the question at you, but then you can decide either whether you want to answer it or you can show your leadership and delegate it to one of your colleagues. Yeah, put some pressure
on me. Yeah. No, I think, you know, I coined or used the word "ahead of the curve" before. And I think we really have been ahead of the curve even with the 2A trial design. And we are well connected with the people who wrote the authors of the FDA-launched respiratory article with FDA and Mark Baers and others. So we knew already before it was written what would be expected of disease-modifying therapies, and that is the new goal. So we did that ahead of time. The article came out. And we have worked on this for a long time.
So we are fortunate to have that type of thought leaders involved in us early. Some of them have been since 2019. And as you saw now here, thought leaders are gravitating towards Cereno because we are a frontline when it comes to disease modification. I sometimes say that, thought leaders are a bit like surfers, you know? They want to be on the latest, biggest wave, because that propels their science and that keeps their thought leadership. And they have a passion to be thought leaders. They want to drive change. So they will jump on an opportunity if they think it's real. And you heard Marc Humbert say, you know, we are very, very selective who we work with. So I think we are fortunate to have that external gravitation into our idea.
We're also fortunate to have a management team and people involved in the company that has the capacity, the network, and the drive to get this done, both intellectually in conversations, and then designation, and then implementation. I think we are now very soon in the real implementation phase. We have a couple of discussions left, with thought leaders and with the regulatory authorities before we have all the regulatory authorities approving this. Then we can run with the trial. But that doesn't hinder us to get the first patient in Q2, I think. So that's my take on your question. Yes.
So, I mean, it's interesting what you're saying there about, you know, having, you know, within your team also people who sort of, you know, to be able to execute such a sort of clinical trial program. Because, you know, I've been covering the industry for a long, long time. And, you know, in the 1990s, I would meet biotech CEOs and I'd ask them, you know, what their ambition was. And they wanted to be a fully integrated pharmaceutical company. And they were going to take their asset, which was still preclinical, and they were going to take it all the way to the market. And the question I would always ask is: who have you got, right, in your management team who has ever actually done this? Mm-hmm.
So earlier on, when I was talking about sort of, you know, sort of you're creating a team, when you first took over, was this what you were thinking when you were sort of you're building that team?
Well, I was hoping for it. You know, when you start, you never know exactly, you know, how far and how good the data will be and so on. So again, you know, the vision, you know, if the fundamentals follow or are generated when you have your journey towards the vision, which is actually to help these patients and, you know, Hall and so on, if you create this, the intellectual science is sometimes already there, like in our case, you know, all of the review articles, etc., and the proof of concept studies in the models of PH, they were all already there, done by our substance by other researchers.
So, but you're hoping that you get to a stage like this. We got very, very early gravitation into us. And as you said early on, pharma companies invest in management. The first thing they want to check is management. It's very similar in the sense with thought leaders.
The reason we have the current Scientific Advisory Board is to personal connections and previous trust and delivery. That's also the case now with the new one, which Mark Baers and the others joining. It's related to previous work and connections through Rahul's career and so on. Yeah. So I think that's really part of this, the ability. To answer if I expected this: yeah, I did. You know, I've done it twice before, and the technology is so strong, so I did. But you know, I'm very happy that we're here. Right. So and you've got two of two of that team. Yeah. I should say that this guy, this doctor, the cardiologist and head of R&D, has around 250,000 patient-plus in his clinical work around the globe.
He was recruited by the C-suite team, and it's specifically Pascal Soriot, who's CEO of AstraZeneca, to run his major trial around the world as his first job. He did many other things for AstraZeneca there. He's been at a biotech that was acquired by Novo Nordisk for EUR 1 billion two years ago soon. Then he joined Cereno for the same reason that Marc Humbert is at Cereno today. It's the same reason, but this is a business and science passion reason.
Yeah? Right, right. So I've got a question because CMO, CSO. So, yeah, who is responsible or how do you share the responsibilities for transitioning that through to the clinic? Sten wants to answer that question.
Yeah, I want to. Well, I don't want to answer that question. But because I just talked about Rahul now, Björn and I—Björn was the first person to define, together with our thought leaders, myself, this whole, disease-modifying concept for Cereno and our HDAC portfolio, which was just one drug originally. Björn has, as you saw, he's awarded, right? He won the most, multiple, entrepreneur, investment person for GU Ventures, last year. But Björn was instrumental also in the foundation of Vicore. Vicore is today running their 2B trial for IPF throughout the world. And Björn designed their basic research for them. So he was involved for a long time with that company. And so he had all—he has all the background around fibrosis, etc., etc. He's also one of the most published people in the country.
Just a few words about this mix between Björn's capacity, Rahul's operative performance, business acumen is a very good match in the executive team of Cereno.
All right. Yeah. No, I kind of take care of, I mean, in the position I'm now, the scientific integrity of what we are doing, so to say. I have also been involved in many studies. And I probably have on my belt around the same number of patients: 200,000. And, I mean, so, I mean, but I'm not so much an operational guy, more a kind of scientific guy to take care of the science side. But I think it's not that Rahul is one person doing some things and I'm another person doing other things. We really work as a team.
We have, I mean, I worked in isolation in many different capacities, but here it's really a team effort in what we are doing. So I was CMO for several years for the company. But I think you now take responsibility for that part, and I take kind of the science. So I think that works extremely well. Another comment to this, if you want to hear a little more about the team. So you've, we showcased the board or showed the board for you. So for instance, Professor Gunnar Olsson has been an instrumental executive at AstraZeneca. He's a professor in cardiology from Karolinska. I met him the first time in 1984. He educated me as a sales rep then. And later we joined forces to do the survival trial with the beta blocker in 1995. But Gunnar Olsson is on the board.
But he's also operating together with Björn and the team, the R&D team, and sometimes me to design and discuss and turn all these trial discussions upside down from his perspective. The same if you took, if you look at, for instance, business operations. So I mentioned Don deBethizy here, who's vice chairman of argenx, a $50 billion European biotech company. He's vice chairman of that. He's an advisor to both the board, to me personally, and to operations. And he's done a ton of things, both from a science, he's a scientist, but he's a big business guy. So he's spending time on Cereno. So we are a team of 10 operational-wise. And we have an active board involved in operation. And then we have the external thought leaders around the world, world-class CRO, and now a steering committee for the trial to get it done well and lead it.
So we're more—if I show you the operation of Cereno, you know, we're working probably 100 people every day is working with Cereno's various tasks and leadership. And we are 10 in the management team. So it's a big operation. Well, I remember when argenx only had 10 in the management team. Yeah. So you know the journey and how it's grown up. And it's now, as you say, it's a $50 billion. So over sort of this, over this century, they have grown from, you know, sort of a small little, you know, outfit in Ghent.
Yeah. Yeah. To where they are today. So, you know, you can dream.
Yeah. Exactly. And so it starts with biotech. And we'll return to that a little later. Yeah. Why biotech are so important. Yeah. So we'll get to that.
So you mentioned—or Rahul also mentioned, you know, conditional approvals and, you know, accelerated approvals, etc. And, you know, we've actually sort of seen this become, you know, almost a sort of a secret sauce for a lot of biotechs to be able to advance. I'm just sort of, you know, looking at what you've got there. What are the—you know, how is the opportunity of a conditional approval or, an accelerated approval, you know, how might that sort of shape what you're going to do in your operations? So, Rahul, do you want to start with that?
Sure. Basically, what we have done is we have now designed the trial in the most robust fashion, but left sort of possibilities to look at the data without disturbing the credibility of the data and the quality of the data.
This is a very fine line. One should keep that in mind. We're talking about a rare disease, phase IIb. But we still, of course, we'll be getting impatient. Hey, what is it all about? What are the results? We want to see them as fast as possible. We have built in a few sort of leverages where we hope that, for example, after the nine months, the Right Heart Catheterization, when all the patients have it, we will be looking at that. That's a primary endpoint. Secondary endpoints are different. We will be making sure that we have, at the right predefined points, an insight into those. Then, of course, we will share that because we'll analyze that at the fastest possible in the most compliant fashion, I should say.
If the data is good and we all are hoping for that, of course, it doesn't happen every day. But still, if the data is compelling and great, then, of course, we will take all the routes that are possible to go to the authorities, the fast track. And that was something very important. We have a direct line with the FDA. We will be applying for something similar with EMA as well so that if we have some things, we can always approach them and hopefully find - not shortcuts is maybe the wrong word - but still a direct line so that we can get that. Authorities are a first step, very important, to get the approval. Of course, there are many other steps. But we will do our utmost to be as fast as possible with the results.
Björn, I mean, conditional approval is something that the authorities would like to give to something that I think should come to the patient as fast as possible. Yeah. And what do they look at then? They look at safety, and they look at efficacy. I think we have an—I mean, given what Rahul says about the study showing great efficacy or robust results for the primary endpoint, we have an additional advantage that could help us in that regard, in conditional approval. That is that we have the safety profile of of this drug. We have 50 years of experience in the clinic. We have very good results in the population as such. That gives us an advantage that most new chemical entities don't have. So I think that could also increase the likelihood of being given a conditional approval.
And if you don't know what conditional approval is, that is that you get an approval to start to launch it to patients, given that you maybe add a study that comes later. So the condition is that you do another study, but you can already, at an earlier stage, go into patients so they can have the benefit of the drug. Sten?
Yes. Thank you, both of us. And, you know, of course, new chemical entities that have not been in man before for a certain disease, and any disease, have a higher rate of failure when they're exposed to a larger patient population. This is FDA's major concern. Mm-hmm.
You know, so so if you have a phase IIb trial that is effective and it doesn't show serious safety or tolerance concerns, they still want to see the phase III in a larger population because it's a new chemical entity. In a majority, almost like all cases, that's what FDA wants. Their major concern is safety for the patient. They don't want to let the drug out that can harm. So if you, as Björn said, you have a drug that's already been for 60 years in man in much higher dosages, the safety concerns are much, much lower when you use it, even if it's for a new indication.
If you don't see a lot of safety or tolerance issues in a phase IIb trial with placebo control, etc., over long term, which we are planning, the likelihood of FDA wanting to be involved in that discussion is higher than with any NCE. And if there is a dramatic effect on the efficacy, they might allow for conditional approval. So that would give we would reach patients such as Hall or his other colleagues as patients much faster than than you have to wait for a phase III trial. Another point that I wanted to make is that a lot of investors like a company to do intermittent reviews or analyze data and so on. And Rahul mentioned it before. And you know that the trials are 60 weeks. But you also know that the first treatment prepared was 9 months, 36 weeks.
That's where the analysis is going to be. In a way, it's not an interim analysis. That's not what it's called. It's an analysis done after nine months. So we don't have to wait 60 weeks for doing the analysis. We can do the analysis. And we will do the analysis then. And we will communicate around that analysis. And then, as we do that analysis, the study is continuing into the latter part of the study where you switch the patient to placebo or active drug. And you complete the trial. And then you study that part.
Yeah? Just to be clear about this. And I think it's important if you invest, how long time will it take till we get to the key milestones here? So please remember that. Yeah? Yeah.
And of course, after 36 weeks, there's a time for you to actually return to it. Yeah. We need to analyze the data and so on. And, you know, so again, many people think, as such as with our extended access program, that, you know, last patient in, you have the data next week. That's not the case. Yeah. You know, we need to database lock. And before that, you clean up if there are any mistakes or so on in whatever admin. So that takes time. You clean up. You lock the database. Then you analyze it. Yeah. And that process can only start when the last patient has done the 9-month visit. So it's not nine months to the analysis. It's quite long.
But you, Rahul, mentioned that you have secured the services of a world-class CRO. Oh, yes. Definitely. They're the people who it's together with people like the PIs, etc. It's their job to recruit patients. So presumably, you must have sort of confidence that you're going to be able to recruit patients. We have the best, best, so to say, opportunity to do this in a timely fashion and, and, quality-wise and everything.
So definitely. And, you know, yeah. So and, you know, there are benchmarks for recruitment pace in various countries, even in various centers. So when you start, and I know Rahul mentioned it earlier in one of his slides, you do a big feasibility study in more centers than we will have in the trial. I think more than 100 centers are being evaluated. So you evaluate them ahead of time. It's a big project. Many things are evaluated around those centers. And then you decide who are qualified.
So they have to be qualified to be involved in this trial. Yeah? So one of the key qualification parameters is that they have previous performance and also that they have a patient population that they can attract x% of into this trial. Yeah? So that is something you do ahead of time. So when you actually start a trial, you know that you have the best centers you can attract to this trial. And, of course, you want to do this with the top-level CRO you can. And we are doing that. So they have been contracted since in the spring. And we've worked with that CRO since May. They've been part of designing the protocol too with us, etc., etc. And they are a prime CRO in the PH field globally.
So the, you know, looking at the map, you had like North America, you had Europe, and Latin America. Is the focus, though, going to be are you sort of designed towards the FDA? And is that the first place you're going to try and file for approval as opposed to, I mean, visa or EMA? So I mean, we have to, of course, look at it strategically. The biggest market is the U.S. So of course, we are looking for that. We're aiming for that. And keep in mind that the site activation time is the shortest in the U.S. They have a centralized so-called IRB. In Europe, it's much more sort of, scattered, even though we have the EU. But still, unfortunately, one has to still do it in every country, every site often. So no, primary goal is to go first to the U.S.
And then naturally, we will also look at it strategically. Right, right.
And I mean, and the other question is, it's around, again, you've already got a partnership with the CRO. Now, often, biotech companies will try and secure a big pharma partner to assist with that clinical development. So, you know, I'm just wondering, at what point are you looking to woo such a partner? Sten?
Yes. Thank you. I will come to that later in my presentation. But, you know, here, in some circles, it's said that the sooner you can attract a partner within biotech, the better. That's normally for R&D kind of research platform situations, not drug platform situations.
But for a biotech like us, in a rare disease, you'd like to do the partnership when you have an approved phase IIb trial in a pioneering field with high unmet need. That's when you start to want to have interest. And you want to secure it somewhere between there and the end of the phase IIb and the trial data coming out. You'd love to have a phase III program together with a pharma. And then the pharma takes over the commercialization, etc. There are a few companies that go to the market. That's not our model. So, you know, we have numerous discussions with various partners from a global, regional, or local level around the world currently. And that started like a year ago, approximately. And the reason is that you saw how many deals that are made in pharma.
Their business development groups are super, super busy. They have $140 billion annual sales to cover in a few years. They need to bring in drugs to their pipeline. Yeah? So they're working and meeting many more than Cereno. But they're meeting with us. So, but they're constantly in a deal mode. They're constantly working to close deals now in many different with many different other targets for them. So we are one of them, right? And they're still allowing access or want or contacting us to have those discussions. At a certain point, the attractiveness between an asset and pharma ignites a deal discussion that might or might not come to fruition depending on various things, such as pricing, you know, how the deal structure is made, the deal value, and what are the, you know, rings and bells around the the contract.
but we are actively in that situation. And I think we are, as you said, I think, early on, we're at the sweet spot. And we can talk about that. I have a few slides related to that at the end.
Yeah. Yeah. And I mean, this is also a nice segue. So we've now finished clinical development path CS1 panel discussion. And we can now move over to the sort of the value proposition and the global PH market. So, Sten, it again, it's back to you. And just sort of, you know, sort of in those sort of discussions that you are having with your potential partners, you know, you clearly have to kind of like pitch the value proposition. So can you share with us what that is at the moment?
Yeah. I'll get to it. Yeah. But if you want to talk like this about it, I have a few slides on what we're providing. I think we've shared it. I think, you know, Rahul has done a good job of sharing what it is. I think Marc Humbert shared it. You know, there is an unmet need, a really high unmet need there. Fill that need. Yeah. So, you know, are you able to do it? Well, currently, the signals that we see and all the basic science around HDAC inhibition and epigenetic modulation that's published, all over the place at the moment, are, you know, enforcing that we will be able to do that. So but then, you know, you have to deliver the data. And somewhere between strong signals and confirmatory data, you know, a deal is made. So yeah.
It's not hard to discuss these things. Deals are many times not made for those reasons. They're made at a certain time. That doesn't always have to do with the value you have and the value you can deliver. It can just be the essence of time and priorities at various companies at the moment. Cereno is focused on just delivering an increasing value proposition for partners. We will attract a deal sooner or a little later than tomorrow. I can say, you know, just to be frank, I think we'll do a deal this year. You know, so it will be a local deal, regional deal, or global deal. That's my opinion. I will if we are in January next year. Hasn't done a deal, fine. You know, we'll be very close to a deal then.
So, the real essence here is, do you want to take the risk now and, you know, run with it? Or do you want to wait until it's confirmatory? The risk is, depending on the price tag, is pretty low, in this market. If you look at the current valuation and future valuation, analyst valuation and forward, Merck bought Acceleron for $11 billion four years ago. So SEK 80 billion. Or, well, it was SEK 110 billion at that time. They valued sotatercept after phase IIb at SEK 80 million or $7 million at that time. Sotatercept is exceeding their expectations at the moment. And you heard Marc Humbert that additional therapies are needed, disease modifiers. Uh-huh. And, you know, so if we can deliver we have delivered so far as, as you know, I think, more than expected last year.
And we have now the setup for delivery on all aspects, I think. So the next thing is, when will the deal happen? Will it happen on this setup? Or will it happen when the data is done?
Yeah. That's my, you know, I think it will happen before. But I mean, it's interesting that you're sort of saying that about, you know, Acceleron or whatever. I mean, and how much it was worth. If you look at something like Metsera, right, in September, when Novo Nordisk first sort of decided that it threw its hat in the ring to acquire Metsera, it was $5 billion valuation. After a sort of an auction almost, you know, within sort of space of, you know, a few weeks, it was $10 billion. OK? So you can see how much value can be created immediately.
But interestingly, the technology and the key assets that made Metsera so attractive came from an Imperial College spinout called Zihipp, which was acquired by Metsera for about $110 million. And that was 18 months before that. So you can sort of see how, you know, sometimes the sort of the expectation of, you know, people trying to make a valuation that it can quite quickly amplify, which, again, must be quite exciting when you're thinking about something that is potentially disease modifying, which we've heard is really, really important. And I'd like to sort of like, you know, sort of talk about that when we sort of, you know, think about that sort of disease modification. You know, what does that yeah. How key is that? How key is it?
Well, you know, I think I really liked Marc Humbert's word that I haven't really captured before, the remission. Yeah. So I think, you know, we look at cancer. PH is not that very different from cancer, actually, in the vessel. You know, it's progressive, pathologic. There is no cure. But it has these components of a growth that's uncontrolled that wasn't a growth before, both in myocytes and the fibrosis connective tissue. So, you know, what the patient absolutely and you've heard Hall has been able to manage his disease diagnosis, you know, fantastically without a disease modifier, that rarely happens at all. So what everybody would be looking for, as you heard Marc Humbert say, is a cure. And if not a complete cure, make this slow down, make this stop, you know? So that's remission in a way that you slow it down, and then it stops.
And then, you know, how far can you go backwards? In animal, we have, you know, it's been reversed with VPA or, you know, CS1's component. So that might be possible. But I think, you know, this is the growth actually before sotatercept really was included, I mean, in the latest analysis of the penetration with a new concept in the PH market. So, you know, we will hit the market somewhere maybe there at 2031. It's not an official number. But that's the market is expected to be at $13 billion annually sales, so SEK 130 billion per year. And we believe that we will take a sizable portion of that market. Right. And that would correspond to, for a Cereno, you know, around $3 billion U.S. dollars sales per year.
You know, so that is a breakthrough therapy. And that's, from my opinion, potentially conservative because we are developing a drug that looks to be the safest and best tolerated drug on the PH market that's going to be oral so and combinable with the other products. So it's added therapy on top of what's there already. Ideally, such if it's successful now confirming disease modification, you'd like to get it at diagnosis. Yeah. Yeah. If it's safe and well tolerated, as this drug seems to be, you'd like to get it early. You want to slow down, halt the progression. And you can have to get the pressure down immediately. You can get the vasodilator. You might also want to have the sotatercept there, you know? And then you add this drug as early as you can.
So and so on, the whole $13 billion market, when we would enter, approximately, the growth is a big opportunity for this drug. But normally, the current practice is that you start at the most severe patient group. That's where you document your efficacy and your phase IIb and 3 trials. And that's how it's been done with Winrevair, sotatercept. That's how we are doing it now. So class 2 and 3, functional heart. And then successful there, you move backwards in your trials. And this is normally done when you have the first one approved or started in parallel with the phase III.
So how much of that growth is down to actually better and earlier diagnosis? Because how in, you know, in his presentation, he mentioned, you know, one of the big challenges is actually it's not very easy to diagnose the condition, particularly if you don't have any of the sort of the other sort of your normally expected sort of.
Yeah. I would, you know, just comment on two things. So one thing is the current practice and, you know, how many patients actually stay on therapy? You know, and maybe Hall has the explanation. I think it's around 50% that stay on the PH therapy that they're given, you know, all of the therapies that they're given because they don't tolerate them. And they quit for other reasons. So they don't feel well, you know? So that's not tolerating them.
So if you are able to add therapies to these patients that are tolerated and are easy to take, you might, with a drug like ours, actually expand the patients on drug, on drug. The other comment which you really asked for is, you know, how much is the diagnosis in this expansion? I don't think, Hall, that it's been calculated in here yet, the ability to better diagnose. So normally, as we've seen with most things, if it's IT or our ability to produce energy or our ability to develop science and new drugs, we are faster than we believe when we are standing here. And you look backwards, oh, that went fast. That went really fast, like with AI now. And I think the ambition in PH for diagnosis might go faster than we think.
So again, I think it's a conservative estimate, the market growth here and our penetration.
Just to add one comment. I mean, it's not the diagnosis that is difficult. It is the suspicion of the diagnosis. Shortness of breath. Yes. Because, I mean, it's quite simple, right? Heart catheterization, and you have your diagnosis. So it's about suspicion and maybe some screening. Who knows? I mean, so I think that's just a comment to that we don't need new diagnostic. But if one could have a blood sample that tells you, of course, that would simplify things quite a lot. But we're not there yet.
And the awareness, I think, has now risen thanks to the various disease, I mean, treatment approaches. 20 years ago, awareness was not that great. So this is something which I think speaks to the early diagnosis and improvement, hopefully, as well. Mm-hmm.
But so Marc, I mean, he showed us that slide with like all the treatments there are, right? Often, some of them are just looking at the sort of symptoms. And there isn't that disease modification. But is disease modification, which clearly is important, is that the only sort of attributes that you think CS1 is going to have that's going to, you know, enable you to capture market share? Or are there other attribu tes?
I mean, like Cereno said, I mean, it's the simplicity of the therapy, I mean, oral, once daily. It's oral. Oral once. And the safety profile. I mean, these will also help in that regard. Yeah.
So, you know, once a day, safe, well tolerated, quality of life is very important for this patient population. And FDA has highlighted that as the most important over everything else beyond safety. Yeah. So well-being, well-functioning patients is the number one. And then is the prognostic factor and so on. So a well-lived life is better than a poorly lived life for a bit longer. Yeah. So if you're able to offer a therapy that's, again, been in man for a long, long time at very low dosages now, which will probably have the best safety and tolerance profile on the market, will be easy to take and will also add the added impact on function and the development path and the slowing down, the remission part of this ambition, it will be an attractive proposition. Right.
I'm going to sort of like go a bit left field here. So this looks to me, you know, epigenetic modulation, HDAC inhibition. It's kind of like first in class of what you're trying to do. So I look at this. And again, you sort of see it with companies who, you know, develop a little breakthrough. But immediately, they're sort of saying, oh, and actually, we can use it for this and use it for this. And I'm thinking, you know, for example, if you think of Humira, right, the adalimumab, it started off in one little indication and then became, with all the add-ons, the biggest product going for like 20 years or what have you. So when you sort of look at sort of CS1, is this the start of a bigger franchise? Yeah.
I think, you know, we have discussed this for a long time. I think, actually, the first discussion around this was when we formed the Scientific Advisory Board because, you know, cardiology has for a long time sought to be able to address the root cause of the development. The knowledge around cardiology and pulmonary diseases and the role of inflammation, pathological processes that drive these diseases forward, such as connective tissue growth or fibrosis, myocyte growth, hypertrophy, et cetera, and other growth, you know, driving factors, such as, in this case, HDAC activation, you know, that has the interest in that has grown a lot over the last 30 years.
So, you know, when I and some of the people involved here introduced a new mode of action in a different way in heart failure, we added a therapy to the others that were there. And then we added beta blockers. So now there were 4. And then there were additional added. I think there are 7 in heart failure now, left heart failure. PAH is behind left heart failure in development because it's an orphan disease. It hasn't had the same attention and the same capital investments. So we are on a journey for these patients to help them get better therapy. And as Marc alluded to, there are many approaches now. Of course, a bit of the Holy Grail or the real objective is the remission. And of course, you want to do this in a safe and well-tolerated way.
But I think, you know, there's not one single solution for patients with a complex disease. We will be part of that movement with this concept. I'm pretty sure about that.
So yeah. So, I mean, and that's interesting because, of course, you know, again, what we're now sort of seeing you mentioned it's a complex disease. In other complex diseases, we're seeing, you know, companies actually create combinations. So they've got, well, this is really good for doing this. But we can combine it with another product to actually, you know, it's almost like a double whammy. So again, when thinking about sort of like, you know, partnerships or, you know, what, how you would sort of like, you know, build the business, have you sort of thought of where this might be used in combination with something else? Yeah.
I think, you know, I wanted to mention before. So when we formed the Scientific Advisory Board and Björn got stronger, stronger more involved in the company operationally as a CMO at that time, but with a science hat, which, you know, is on both CSO and CMO, Björn worked together with Dr. Bhatt and our new Scientific Advisory Board. And their push was very strong. You have a potential for disease modification here. Look, there are 600 articles on HDAC and PAH. You know, look at it. And we have a long list of indications in the company. We started early on on thrombosis. But when the Scientific Advisory Board came in and said, well, you can address the root cause, so we moved to rare diseases, PAH and the lung side.
You know, that's why we have cardiology. Is PAH a cardiology disease, a cardiovascular disease in the pulmonary artery and right heart failure eventually? It's not a lung disease as a primary problem. But but our drug has also an impact, proof of concept studies in lung fibrosis. So that's why our second drug is addressing that, but also that and orphan disease. It fits our business model. It fits the patient's very high unmet need from a commercial point of view and value proposition. But our list is longer. So I think and that's also one of the strategic reasons that we developed the next generation drug, a new chemical entity, is more attractive to bring to multiple indications. And you might know already that pharma's interest in filling the gap, the prime interest is not single projects.
It's molecules that have a clinical, strong clinical validation that can be expanded. Their biology can be applied to multiple indications. That's a sweet spot to fill the pipeline gap that Mike was talking about. That's exactly where we are. We have repeatable biology through our mode of action into several diseases that has these complications of inflammation, fibrosis, growth, myocyte, muscle growth, cardiac hypertrophy emanating into lung fibrosis or to heart failure, hypertrophy, refractory heart failure, et cetera. Thrombosis indications, rare or more general. And if you're going to go to many different indications, you want to optimize the molecule for that purpose, both from a commercial aspect, such as patentability, attractiveness. So most pharma like new chemical entity patents for broader indications. Yeah. So you want to do that. But you also want to optimize the molecule, which is what we have done with the second program, CS014.
Right. OK. OK. Well, this has been, again, sort of a really, really fascinating conversation. And what you were saying there, I think, nicely segues, right, into, you know, I guess, your closing presentation, where I guess you wrap it all up and sort of tell us what the strategic focus and the objectives are.
I'll try to do that for all of us. And let me know if I leave something out. But thanks a lot, Mike, for this so far. Thanks. Yeah. We come to the last portion. I hope you like the discussions we are having. So, you know, we are now very, very focused on execution. We are in the final stages of, you know, defining protocols, getting them approved, et cetera, in the various stages. But we are very much focused on execution.
So the CS1 phase IIb trial, we need to get also EMA South America approval. We have FDA, U.S. already, and the first patient in and latter part of this first segment of the year. For a second HDAC inhibitor, CS014, we are moving now to define our IND, so the package of information you need to put into the regulatory authorities to get their approval to take this chemical into a phase II program. We are already in the clinic. We provided that data on phase I. That's the first, you know, healthy volunteer study you do to just look at exposure, safety, and tolerance. Then you move to the next step, which is a phase II program. And we will do that drug in the lung disease, pulmonary hypertension, interstitial lung disease.
We are moving to get acceptance by the FDA by the end of this year. We talked about this, right? Make a deal with pharma. It's a primary objective for us this year beyond the R&D operations. We want our programs to be attractive enough that pharma cannot resist to take it. With the quality of the thought leaders around the program, the value proposition that we are driving, and with spokespeople around the program, such as Marc Humbert , who was instrumental in sotatercept development for Acceleron, which is now Winrevair and latest drug in the field, the first new concept in many, many years, he is now with Cereno working on our concept. He wants new drugs. He will be part of discussions if we want to seek third-party thoughts about what we're doing and the potential value of that for patients and the probability of success.
He will be part of those discussions that we will have with pharma during the year. We already have conversations around our programs with pharma. And of course, we love to expand our investor base for the company in Sweden and Nordics and globally. Now, let's look at the market. We were into that, right? So CS1, you know, it's playing in a will be playing in a market, introduced to a market that will be around $13 billion between $10 billion and $13 billion. I think it will be higher when we get there, quite a bit higher, actually. We will be introducing our drug there. There are analysts on the company currently that are estimating our peak sales of our drug to around $3 billion per year. Our own estimate is somewhere between $2 billion and $4 billion. And, you know, let's see where we eventually end up.
CS014 is now targeted for PH-ILD. That market is $3 billion today and is expected to grow to $6 billion. Also a major market for an orphan disease. There is no analyst coverage, really, on this from a value point of view and penetration. We expect that penetration to be around $2 billion-$3 billion. Here you have part of the list. It's been with Cereno for a long time. We did this in 2019. You have PH there. You have PH-ILD down there. So, you know, we are just addressing two orphan diseases initially with this concept. We think that CS014 and the HDAC, it's a platform technology. Small molecule can be biology can be applied to many diseases with these characteristics that this drug and mode of action has.
So we haven't and we are not providing, you know, penetration, value, and possibilities on this yet. But we will be working on that. And we will showcase that both to our partners, potential partners, and to others, investors, et cetera, the expansion possibilities of our concept. So we have an HDAC portfolio, one in phase IIb and one that is approaching phase II. And we expect approval this year. And we have CS1 and PH. We have CS014 and PH-ILD. And we have also thrombotic disorders, where we have both CS014 recently published a manuscript on CS014's data in thrombosis prevention without increasing bleeding risk, which is the number one thing that any new drug needs to have in the thrombotic market. Three out of 100 die that are put on the current therapies. 25 out of 100 get some kind of bleeding.
So if you have a drug that can prevent thrombosis that has not serious side effects, you'd like to use something that doesn't cause bleeding and add it to the current therapy or just use it alone. So both CS585 and CS014 have documented that kind of data. CS585 is in-licensed from the University of Michigan. So let's, you know, so there's a you talked about this before, the high unmet. So we talk about high unmet need in the pharma industry for new pipeline products. Patients have high unmet need for new drugs. The pharma industry has high unmet need to fill their patent cliff gap of revenue-driving drugs. So let's talk a little about what kind of company is Cereno. It's a biotech. Who develops new drugs to patients today? Who is doing that? The innovation part, the pioneering efforts. It's not pharma.
Biotechs such as Cereno does 80% of the new pioneering efforts, innovative drugs. Around 14% of that is, you know, listed as coming from laboratories. But most of that goes into biotech. So biotech actually innovates 70% of the new drugs that eventually reach the market. Pharma, on the other hand, launches 80% of all drugs. What happens between those two things? A deal is made. That's where pharma that's how they're going to fill their gap. So they need they're launching 80% of all new drugs. But they're only developing innovatively 20%. So they're looking to China. They're looking a lot now. They're looking they're scanning the world for companies such as Cereno. And they want to make deals. So I mentioned this before. So we were recently at the biggest health care conference, the most important one every year is at it's called JP Morgan. It's a bank.
But the conference is called J.P. Morgan Healthcare Conference, invitation by J.P. Morgan. There are other biotech conferences around it. Every year, second week of January, you know, what they're looking for is first-in-class, significant patient value potential. They're looking for a small molecule primarily. That's complicated. They're looking for clinical late-stage compounds that are in that phase. They're looking for repeatable biology, multiple indications. Cereno's fit with this, first-in-class, significant patient value, disease modification, small molecule, CS1 and CS014 are both small molecules, clinical late-stage, both will soon be in phase II. One is in phase IIb. Repeatable biology, multiple indications possible to expand to, yes. Now, if you are in this space, PH, there's a big ticket deal potential here. The last one that was done with Merck was, I mentioned, $11 billion. They bought the whole company.
But the majority of the company's value was in sotatercept. So there is an analyst estimate on Cereno's deal value here. So you heard the $2.83 billion penetration. That's sales. This is deal value. Expected deal value on a successful 2B trial is around $2 billion. That's 20 billion SEK. That would be nice for investors and owners. The people sitting here are some of the majority owners in the company. So look here. Cereno delivered on all fundamental R&D milestones for value inflections last year. I showed this before. We went we tripled our analyst market valuation currently. What happened on the retail market? And this goes back all the way to June 16, when we actually launched the company on the stock market. What has happened over the years? We uplisted in June, June-July 2023 to Nasdaq First North.
We went up to SEK 3 billion in value. We have grown the shareholder base over various milestones that we have developed the company. Since May of last year, despite delivering a number of fundamentals, the market cap of the company and the share price has gone down. So I don't think Cereno is the only company experiencing that. But it's sometimes frustrating when you deliver fundamentals for a company, executive leadership, and also for shareholders, that the valuation and share price of the company goes down. But that's the reality we are facing. What happened? We grow the share price growth with 30% last year, the market cap growth with 30% last year, and total number of shareholders with 30% last year, if I abbreviate a little. That happened last year. We delivered the fundamentals.
So there is this gap between analyst valuation on fundamentals and a small retail market that is capital restrained, such as Sweden, for the company. We are valued at 1/3 today. This has happened during this time, 2023 to 2025, SEK 1 billion to SEK 2 billion. There was 100% growth. But the fundamentals was a 300% growth. We want to pursue our vision. That's looking ahead. We will continue to drive our vision and execute as well as we can. We think we're well set up to execute. We will continue to deliver on fundamentals. We will and want to grow our shareholder base, the share price, and the market cap, as we have done historically until now. We will make a deal with pharma. We don't know exactly when. I think it will be this year. That's it. Stay on the journey.
Well, thank you very much. So do we have any questions from the audience? Joe.
Hi. Thanks very much. Great CMD. Joe Hedden, Rx Securities. Just firstly, on the expanded access program, I'm just trying to get a handle on what data we might be seeing out of it. Are we looking at some of the measures that were in the core data, such as PVR, functional capacity, et cetera? What can we expect to be reported?
Yeah. I'll just do one sentence. I'll let Rahul answer the question. Why don't you answer directly, Rahul? You're the man. Thanks for asking that question. Very important.
EAP, first and foremost, it was for safety and tolerability. I know it sounds boring. It is very important for a chronic treatment that it is safe and tolerable. For EAP, first and foremost, we were looking at safety, tolerability. We are looking at other things, but not PVR or so because that would be an invasive measurement. We do not do that. We are looking at some echoparameters. We are doing that. Please keep in mind, these are 10 patients. The evaluation of the results will not be sort of like hardcore science. First and foremost, it's safety and tolerability.
Yeah. And maybe I also can add, Joe. So, you know, what you can do when you have this little material, remember, these patients have been on a journey, Hall. So you get included in you want to be in a trial. Or you're asked by a physician, do you want to be in a trial? There's a new drug. Are you fit for the trial and the exclusion criteria? And you go through that. And you sign a patient consent. And then you're on. And in this case, it wasn't placebo, no risk of getting placebo. You got the drug on top of your standard therapy after 90 days stable therapy. And then you were allowed to be there 3 months. These patients were included at different times to complete the 25 patients that we had in that trial in the U.S.
Those patients completed the trial at different times. At some point, when the study was completed, some investigators and their patients asked, "We want to get the expanded access program approved by the FDA. Please apply to the FDA. We want to keep the drug." So we did that. Then they were enrolled in the trial. But before you can get it enrolled in the trial, every site needs to approve again. So went through, I think it was nine months to get this. This is how the administration works. So the patients were without drug, most of the patients, more than a year before they got the drug back again. Now they've been on it for a year. Now they're off it again.
So now, when we are going to look at this, we're going to look at the very start and through their journey. We don't have all the parameters. We have just these few patients. So the patients can't really be compared with each other. They can't be grouped. So what you have to do is basically look at every patient, more like a patient case study, yeah, just to be clear.
OK. Thanks. Then if I could just ask on phase IIb design, what kind of placebo-adjusted improvement in PVR, the primary endpoint, are you going to consider as kind of the benchmark for success here? I mean, presumably, you have a number that you'd like to reach in either of those dose groups.
So PVR, as you're rightly saying, is the primary endpoint. We are statistically powering that trial for, first and foremost, statistical difference between sort of placebo, that is standard of care, all comers. Then we'll compare that with our group on top with CS1. So yes, what we are aiming right now, we were not fixing on one number because it will be changing. There are several other trials coming out. We'll be looking at those. Then, of course, we'll be aiming that. First and foremost, we want to reach the statistical significance. What is the perception? What is more important? I mean, usually, one says around 25%-30% PVR reduction. That is something very, very good. But the margin is getting smaller because, of course, the standard of care is expanding. Now, there are up to four drugs being given.
Then Winrevair may come on top of that. We have to look at that. The authorities are also taking that into consideration.
OK. So it's gone off. Oh, it's back on. So will you disclose what you've statistically, what have you powered for in terms of?
Sure. We'll do that when, sort of, keep in mind, right now, we have talked to the FDA. We'll be talking to EMA, the South American authorities. They may have different views. So once everything is collected together, we have finalized our sort of final design of the trial, then, of course, we'll share that. Absolutely.
Sure. And then perhaps just as the treatment algorithm is kind of changing in a way, sotatercept is becoming more and more ingrained, so it feels important to have a certain amount of exposure, presumably, of patients in the study. So is there any kind of, I don't know, criteria for making sure there's a good proportion of patients in that study? I mean, presumably, you're going to have more U.S. patients sotatercept exposed, for instance.
Yes. Right now, as you know, even though sotatercept is sort of more or less approved, but it is not available in most of the market so far. We'll be starting soon. And they have to be on sotatercept for at least six months stable therapy. So we are yes, we will include sotatercept patients. But they have to fulfill the inclusion criteria. Most probably, it will be in the U.S. and maybe one or two other singular markets. So number of patients, we don't know exactly. But we will take on all comers. And we will be looking at those patients and then the effect we have on top of that, absolutely.
OK. Thanks. Maybe just one more, like a broader philosophical one on treatment and how it's moving. I mean, you commented earlier, very much, you go kind of last line and try and move back in terms of adding treatments, adding treatments. We're at 4 now. CS1 would hopefully bring us 5. I mean, realistically, how far can that go? Is there some room for consolidation or perhaps simplifying the treatment algorithm at a certain point? Do you see those kind of murmurings happening? Or are we very much still in a, let's just add one more and see how we go?
I think that one comment to that is I alluded back to left heart failure. And there's seven, eight compounds now being utilized. And some have been dropped, like inotropic agents, because they actually were harmful, killed patients at that time. So I think that it hasn't stopped pharma or biotechnology companies developing new drugs because the unmet need is so strong that you will take the drug. And you will make room for the drug to help the patients. Both authorities, payers, and the patient organization will push for drugs that can help them. And, Hall, I think you agree with that. So I think no company should be discouraged for and you heard Marc Humbert maybe say that we are upfront, combined approach. So before, it was sequential. And the algorithm was like that. And initially, it was like three different vasodilators together.
Our first patient, one of the first, the remarkable patient case, you might remember, some of you, was on triple therapy. And she was in phase II, quite severe symptoms affected. And she'd been diagnosed three years earlier. She came in. She had approximately four years to live, maybe five. We moved her backwards with the drug to phase I and did some other remarkable things to her status. So I think that what physicians want to do, if they can and this is ultimately, I guess, eventually a payer acceptance. But what you want to do as a physician is help the patient. And what will happen is you probably reduce the vasodilators quite significantly. And you'll go with maybe one. And then you add on sotatercept or our drug. And you start that early, as early as you can. So I think that will happen by itself.
It hasn't stopped in heart failure. It won't stop here, I think. The total commercial or the total payer burden—remember now, in the administration in the U.S., they're cutting out the middleman. So they will ask patients to make the choice, not the insurance companies, not the doctor eventually. It's a patient organization. And the current administration is empowering the patient to make the choice of therapy, to pay for it out of what's allowed put that way as a benefit package rather than to the insurance companies. So I think that will help in the orphan drug space for patients to get what they need.
So do we have any other questions from the audience here? OK. So we've got oh, sorry. Oh.
Joakim Larsson, can you explain how the Stifel collaboration came about, as well as their role in Cereno moving forward?
Yeah. You know, Stifel is a big, successful bank in mostly large cap, M&A, capitalization, and things like that. So they are head office in New York. And they wanted to expand down and specifically into the health care space, biotechnology, and so on. So they acquired Bryan Garnier, who in Europe had a strong position in that segment. So they bought that bank. And that's how that started. Both Stifel and Bryan Garnier had been following Cereno for a couple of years. This is how the banks work. They look at the space. They look who's moving. Where can we be helpful? Is it big enough for us to spend our time on it? Do we have investors that want to go in or buyers, M&A buyers? And if you're a big bank and you don't have the mid, low cap segment, you don't move on that segment.
You can't afford it as a bank. It takes too much time. But if you buy yourself into that segment, you also buy the connections and the analysts and all of that. So that's what Stifel did. And with that came their. I've been with. I met Bryan Garnier several times. They contacted me. And many other banks have done. But immediately after that, Stifel has their objective very clear. They want to be a player in the Nordic area, in Europe. So they already are in Europe. But they wanted to be in this segment. So they contacted us immediately after that acquisition. And so they were part of their recent financing. And yeah, that's it. And we have an ongoing relationship with them. We were at their office in San Francisco when we were at J.P. Morgan and so on. So that's the relationship we have.
We have a relationship with other banks. So they are not the only one.
Great. Well, OK. I think that that's probably it. So I mean, we started today. Remember, I sort of said the agenda of the day. What we were planning to do is we were essentially going to connect the disease understanding, get a view on the potential patient impact, what clinical progress has been made, what the market opportunity is, and also what the upcoming value triggers is. And I think that you'll probably recognize I think we achieved all those objectives, especially from the contributions from both from your team, Sten, but also from Hall and from Marc. So I thank you for your attention. I hope you find it all very useful.
Thank you so much, everyone that attended. Thank you.
Thank you.