Welcome to the Jefferies 2025 Global Healthcare Conference. It is my pleasure to introduce Ahmed Mousa, CEO of Vicore Pharma.
Thank you, Christina. My name is Ahmed Mousa. I'm CEO of Vicore Pharma and refer to our forward-looking statement disclaimers. It's great to be here. Thanks to the Jefferies team for hosting us. Vicore Pharma is a Swedish-listed company with a $300 million market cap, about $137 million cash position after completing a recent financing round. The team is based in the Nordics and in the United States. I'm based in Boston myself, and we're very fortunate to be backed by a really nice group of specialist shareholders, both in the United States and in Europe. Vicore Pharma's focus is on developing a program, and we're currently in later-stage clinical development in a large phase IIb for a disease called idiopathic pulmonary fibrosis. This is quite a tough disease that has a mortality, unfortunately, of only three to four years.
There are currently available standard of care therapies, but unfortunately, those standard of care therapies don't significantly change that mortality picture that I mentioned. So, you know, more difficult in terms of that than many cancers. In addition to that tough mortality profile and drugs that are available that don't significantly impact it, they also are very tough to tolerate. And so the standard of care therapy is actually only initiated by a small subpopulation of IPF patients in the United States, and there's a pretty rapid discontinuation time of only 10 months. It's a tough landscape with really a need for better tolerated and more efficacious drugs. But in addition to that, even despite all of those limitations, the IPF market to date has been over $4 billion last year, and it's estimated to continue to grow significantly to over $10 billion by 2030.
The landscape in IPF at the stage of Vicore Pharma's development program, Buloxibutid, and more advanced is actually fairly limited. There are three drugs in phase III development ahead of Buloxibutid. Nerandomilast was actually just approved as Jascayd some weeks ago, which has incremental efficacy. It has some tolerability issues, but it's still great to have a new option available to patients. Again, as I mentioned previously, you still have this high unmet need for better tolerated and more efficacious therapies. United Therapeutics has recently showed in the first of their two phase IIIs a higher level of efficacy, although still we're speaking to reduction of decline in lung function, and that therapy is associated with some greater tolerability issues. It causes a lot of cough, and there's a significant amount of nebulization, so you have to work with a big nebulizer four times a day.
Finally, in phase III development is Bristol Myers Squibb's LPA1 antagonist, which has previously shown more incremental efficacy as well. It'll be, of course, great to see next year how that does on the efficacy profile. You know, I think that ultimately also the world of IPF and the way that clinicians and regulators think about this space is one where combination therapy is desired. When you think about these therapies, certainly the way we think about these therapies are ones that can be combined with a potentially successful Buloxibutid as they show efficacy in their respective clinical development programs.
Now, why go after the mechanism of action that we are, and why do we believe that we have the ability to potentially be disease modifying in a space where many companies have ultimately tried to develop drugs in IPF and failed, and also those who have succeeded have shown incremental levels of efficacy? I think the starting point is really going after an intervention point that we believe can drive resolution of fibrosis and tissue repair. The way we do this is by activating a receptor called the angiotensin II type II receptor, which is antifibrotic, vasodilatory, and anti-inflammatory. While the AT2 receptor is an intervention point that does not have significant drug development history, this is a first-in-class molecule, the AT1 receptor does. The AT1 receptor is actually the opposing force of this AT2 receptor system.
It actually drives hypertension, inflammation, and fibrosis as a suitable response to infection, injury, and different types of insults. This mechanism, this AT1 mechanism, has been effectively and safely blocked by ARBs, angiotensin receptor blockers like losartan and the SARTAN class, as well as ACE inhibitors. We think similarly, activating this countervailing force can also be both safe and effective, as well as potent in both pulmonary fibrosis, but actually a number of other fibrotic and inflammatory conditions as well. Now, what's also nice is that there's a great deal of evidence that this receptor that we're activating is highly expressed in the lung. We also understand in what actually particular cellular compartments you find significant levels of that expression.
It's in these stem cells called these alveolar epithelial type II cells that you see the AT2 receptor, both in a healthy individual as well as upregulated levels in interstitial lung disease like IPF. You also see expression in fibroblasts, myofibroblasts, and endothelial cells that's upregulated in IPF. While these might relatively seem small, they're actually, we believe, clinically relevant. I guess focusing in then on the primary kind of cell that has the expression of these receptors, we can talk a little bit about what exactly these type II epithelial cells, these stem cells, do in the lung. They sit in the alveolus, the air sacs, and there are millions of these at the distal end of the lung. The type II epithelial cells are responsible for differentiating into type I epithelial cells, which are the gas exchange cells.
When you're trying to breathe in, oxygen comes through into the air sacs and should diffuse out, and it diffuses through these cells that are replenished by the type II epithelial cells. The second key function of type II epithelial cells that we highlight is the production of surfactant protein, which is important to maintain alveolar integrity. Essentially, this allows the air sacs to keep their inflated shape against the surface tension of water, which would otherwise cause these alveoli to kind of collapse on themselves. This schematic shows a little bit what's happening in IPF on the left-hand side and what we believe our mechanism of action does about that. You see on the left-hand side, IPF, like other pulmonary fibrosis, is a disease of alveolar injury, injury to the air sacs.
You're breathing in different pollutants, different chemicals, and this micro-injury over years or decades is postulated to be a key driver of pulmonary fibrosis. That injury is then impacting the epithelial cells. The type I epithelial cells, those gas exchange cells, they start to die off, and then the type II epithelial cells also become dysfunctional and apoptotic, and it means that they're unable to then replenish gas exchange capability. What that means is that even before you have pulmonary fibrosis in IPF, you have epithelial injury that causes a loss of gas exchange capability. The second piece of the puzzle is the injury to these type II epithelial cells means that you start having a reduced level of surfactant production in this compartment, and that causes a known phenomenon in IPF, which is prefibrotic alveolar collapse due to that loss of surfactant production.
This is because the surface tension of water causes these alveoli to kind of collapse on themselves like a pancake. You know what happens then from there is the injured type II epithelial cells, now not only are they unable to kind of have their normal function, when they become injured, they're actually the main orchestrator of the fibrotic process by releasing TGF beta-1 and other profibrotic cytokines. That then causes what's known as epithelial to mesenchymal transition. The epithelial cells become fibroblasts, the fibroblasts become activated, they start migrating into this interstitial space around the alveolus, and then they start depositing collagen. That's how you have then the buildup of fibrosis. What that does, it acts as a physical barrier to oxygen diffusion from the air sac into the pulmonary vasculature.
The last piece of the puzzle that's an important part of this disease is the dysfunction in the vasculature. You actually have a thickening of the endothelial cell compartment in the blood vessels, and this leads to pulmonary hypertension. Actually, as these endothelial cells become dysfunctional, they start actually driving profibrotic factors as well. Then you start having more fibrosis because you have more TGF beta-1 and other profibrotic factors being released from these endothelial cells that have become kind of crushed by the buildup of collagen in the interstitium. A pretty tough disease. On the right-hand side then, what our mechanism does about this is by activating the type II receptor on these stem cells, these type II epithelial cells, we drive a refunctionalization and a proliferation of this cell type.
Essentially, that enables a replenishment of the gas exchange cells, the type I epithelial cells, so you can restore that gas exchange capability. When you refunctionalize these cells, they start producing surfactant again, so you can address the prefibrotic alveolar collapse. Not only that, when you're able to refunctionalize these cells, you attenuate that profibrotic injury signal, the TGF beta-1 signal. That means you're able to naturally stop the buildup of fibroblasts and their ability to deposit collagen in the interstitial space. Finally, on the vascular side, and again, this is a mechanism in the angiotensin II pathway, so it's known to be vasoactive, causes a local vasodilation as well as a reversal of the vascular remodeling. It enables basically easier oxygenation of the blood and stops that vascular compartment from becoming a profibrotic driver.
Now, we have a great deal of preclinical evidence behind what I've just kind of talked about. A few kind of snippets from this are even just simple experiments where we take these type II epithelial cells, these stem cells, and expose them to bleomycin, which simulates the injury of IPF. You start to see that apoptosis, which can be inhibited by Buloxibutid in a concentration-dependent way. When you move it to more complex models, you see a consistent result. Here on the right-hand side, we have some data from human IPF precision-cut lung slices, and this is then IPF tissue from the lungs of patients who've had a lung transplant, and you're able to see that by adding our drug, you can increase surfactant production.
This is essentially evidence that not only are you addressing the prefibrotic alveolar collapse, but because those type II epithelial cells are the only cells that release these surfactant proteins, it also means you're refunctionalizing and driving proliferation of the cell type as postulated. We also, in these human IPF precision-cut lung slices, show a reduction of TGF beta, which is what you'd expect when you refunctionalize these cells, as well as a reduction of collagen deposition, which of course is the ultimate aim, to reduce that profibrotic drive. In addition to that, we've also looked at the impact of this mechanism directly on the primary human lung fibroblasts. This is then an experiment we did with Nordic Bioscience where you take those lung fibroblasts, you stimulate them to start producing fibrosis, and then you can measure the actual level of these fibrotic building blocks, ProC3.
Here you see Buloxibutid is able to significantly reduce the production of ProC3. Actually, we have for comparison Nerandomilast, which are two of the approved IPF therapies, and you see here a much more potent effect at the clinically relevant concentrations of the drug. In addition to actually stopping new fibrosis, this is evidence from our phase IIa data in IPF patients that we're driving resolution of fibrosis, which is what this mechanism's intended to do. Here you have an elevation of MMP-13 over a 36-week period in IPF patients who are taking our drug.
MMP-13 is a collagenase, so it's an enzyme that breaks up collagen, and we're able to show basically clinically that we're able to elevate this level of, elevate, sorry, this collagenase matrix metalloproteinase in a way that we believe then is consistent with the disease modifying signal that we've seen in the phase IIa that I'll talk more about. Finally, on the vascular side, you know we've seen Treprostinil show a really nice effect in the first of their two phase III studies in IPF, and we believe part of that is because reversal of vascular remodeling will reduce the profibrotic drive coming from that compartment. Here we show that Buloxibutid very nicely also impacts pulmonary hypertension and vascular remodeling quite potently in one of the classical models of pulmonary hypertension, the Sugen/Hypoxia model.
Maybe from here, I'll talk a little bit about the clinical data we've generated to date. Of course, we ran phase I development work with this drug, no dose-limiting toxicity, no maximum tolerated dose, and we moved from there into a phase IIa study over 36 weeks. This was an open-label study where we looked in IPF patients that were treatment naive and monotherapy, so just taking our drug, and we wanted to see, of course, the safety and tolerability as well as the change in lung function as measured by FVC from baseline. This is the regulatory endpoint for drugs in IPF as well. What we saw in terms of enrolled baseline characteristics shown in the left-hand side, we call this study AIR, is that we've enrolled a similar population as you would expect.
The right-hand side shows the INPULSIS study baseline characteristics, which were the phase IIIs that led to the approval of nintedanib, and I'd point out in particular % predicted FVC at baseline. Basically, lung status at baseline coming in quite similar to what you'd expect in some of these large phase III trials. In addition to kind of having this nice baseline population that's consistent with what we'd expect, we also saw a really good safety and tolerability profile in the phase IIa development, and that's shown treatment emergent adverse events on the right-hand side. We do not have that GI signal that's associated with the standard of care therapies. We had a low rate of exacerbations and cough worsening, and we actually had no drug-related serious adverse events, which was nice as well.
The drug is known to cause hair loss or hair thinning, and it was mild to moderate and appeared in 19% of the population, and it was reversible in all of the individuals who experienced it. We ultimately feel this is a side effect profile that can be tolerated in the broader context of IPF and its mortality. We will also be in the phase IIb, and I'll talk more about this, testing the same dose as we're observing here in the phase IIa, 100 mg twice daily, as well as a lower dose to see if we can clear this effect with also an efficacious result on FVC.
In terms of what we saw on FVC, and this is the exciting part of the story, you know we saw essentially a stabilization of lung function out to about 20 weeks, followed by a period of improvement in lung function out to about 36 weeks. Ultimately, what this represents is an over 200 milliliter improvement from baseline in lung function, which is really nice compared to what you'd expect for an untreated population, and that's shown in the dotted line. It certainly is quite potent even relative to what you'd expect with the standard of care therapies, which is still kind of below the zero line, only a reduction in the slowing of decline of lung function.
Now, because we ran an open-label study, we also wanted to put this into context, and so we did a synthetic control arm analysis where we accessed a database of over 10,000 IPF patients. We narrowed that database to the patients who met the enrollment criteria for our phase IIa study, and then we essentially generated 20,000 randomly sampled control arms from the patients who met our enrollment criteria, and then we matched them on the lung function characteristics. Basically, you know, we identified ultimately 408 randomly sampled placebo arms that were as close, were essentially closely matched or as close as possible matched to the baseline characteristics of our enrolled IPF population. We were able to then look at how that kind of grouping of 408 placebo arms performed in terms of lung function.
What we see here is that we have an average decline across these placebo arms of 115 milliliters in lung function over 36 weeks, which is in line with what you'd expect based on the literature. The distribution of this is kind of shown on the right-hand side as well. You do see this kind of nicely lines up where you have a wide range of FVC outcomes, but concentrated around that 115 milliliter decline in lung function. We also used this synthetic control arm to impute the phase IIa data. You saw we showed observed values on the phase IIa data, an improvement in lung function of over 200 milliliters. The study was run during COVID, and we had a greater than typical level of dropouts.
Essentially, what we did here is we said, what if we assume that all of those patients who discontinued the study had a decline in lung function that matched the kind of placebo arm or the synthetic control arm analysis? Here, even following that type of a very conservative imputation, you still have a signal of improvement, though more modest in lung function, as well as a statistically significant result. What this reflects for us is that there's basically a signal of disease modifying effect that we observe, both of course on observed values, but even with a very conservative synthetic control arm analysis. What we're doing now to kind of validate the result we observed in phase IIa is a large phase IIb study.
It's a 360-patient study where we're running Buloxibutid in 100 milligram, same dose as the phase IIa, half dose, 50 milligram, to see if we can clear the hair loss effect, as well as a placebo group. We're allowing patients on nintedanib standard of care, Nerandomilast standard of care, not on standard of care. There's a 52-week treatment duration, so it's the same as kind of a phase III setup, as well as the same primary endpoint as a phase III study, change from baseline in FVC at 52 weeks. The study's being run across a number of geographies with significant enrollment out of the U.S. and Europe as well.
The study has recently been increased in size from 270 to 360 patients, and the main rationale for this was to add basically powering to detect a difference in lung function from the placebo arm to the treatment arm of basically 96 milliliters or greater. This is based in part on a matured IPF landscape where the three phase III therapies that I'd mentioned previously have kind of shown the different types of effects that they can demonstrate. Basically, the idea here is to capture the broadest possible range of FVC that would still represent the most efficacious drug in the landscape to date.
This is our status on enrollment of the ongoing phase IIb, so we have about half of the study enrolled as of a few weeks ago, a nice distribution of patients across the U.S., EU, and Asia Pacific as well, which is important in IPF studies to ensure kind of a heterogeneous population to be studied. Yeah, so we're very excited to continue advancement of the therapy for IPF in our phase IIb study and happy to take any questions.