Great. Good morning, everyone. I'm Alex Thompson, biotech analyst here at Stifel. Happy to introduce Ahmed Mousa, CEO of Vicore Pharma. Hand over to Ahmed to do a brief presentation, and then we'll ask some questions after that. Sound good?
!Sounds great. Thank you, Alex. Thanks for having me. And yes, as Alex mentioned, I'm Ahmed Mousa, CEO of Vicore Pharma. Show the typical disclaimers about forward-looking statements. Vicore Pharma is a company that's built a strong expertise in the biology of the angiotensin II pathway and also really a strong chemistry expertise in modulating the GPCR angiotensin II type II receptor, a tough receptor to target and to modulate and certainly to agonize, which is what we're doing for our lead program and IPF that I'll talk more about. The company's listed on the Stockholm Exchange, about $200 million market cap, presence in Copenhagen as well. I'm based out of Boston. We have about a $125 million cash position after completing a recent $85 million financing round.
Most of our cash position is going to be directed towards driving the advancement of Buloxibutid into a phase IIb program for IPF. That's what I'll focus on for today. We do have an early stage platform as well where we are going to go after diseases with high unmet need in the inflammation and fibrosis space. We can talk more about that over the coming months and years. Now, in terms of Buloxibutid, our lead program for idiopathic pulmonary fibrosis, we're very excited about it for really three key reasons. One is it's an upstream mechanism of action, upstream both of fibrosis and a number of the standard of care and emerging therapies as well.
It drives an effect preclinically, and our initial clinical evidence reflects this as well, that has a reparative or resolution of fibrosis effect, which we think is the right way to go after IPF. We reported earlier this year at the American Thoracic Society phase IIa data that reflects improvement of lung function durable across nine months. It's a mean improvement in lung function was seen in our data set, 216 milliliters. And a really safe and well-tolerated therapy in development to date. We don't have the side effects associated with the standard of care therapies and IPF, as well as some of the emerging therapies as well.
And really, the third piece of the puzzle is a robust phase IIb that's designed with a regulatory endpoint, 52-week change in lung function, as well as a relatively large size for a rare disease, 270 patients. IPF is a huge commercial market and a huge unmet need, which really motivates our work in this space. Only a quarter of patients in the U.S. initiate therapy. They discontinue within about 10 months, and notwithstanding that, the current standard of care treatment does over $4.5 billion a year, and so really, kind of significant unmet need, particularly because of the mortality associated with the disease, prognosis worse than most cancers, only 3-to-5-year survival.
So really unlocking something very valuable for patients as well as something very attractive commercially if you can find a therapy that would both be beneficial in terms of efficacy as well as something that's better tolerated than the current standard of care. The way that we were going after this disease is by agonizing the angiotensin II type II receptors. That's shown here in the orange at the right.
This is an endogenous tissue repair and fibrosis resolution system, so it's designed in your body to drive an antifibrotic, vasodilatory, and anti-inflammatory effect, and so the idea here is we agonize this receptor and supercharge this fibrosis resolution system. The system is actually one that exists in the lungs. The receptor is highly expressed on a precursor cell called the alveolar epithelial type II cells. These cells are shown here in healthy air sac or alveolus, and two key functions of the AEC2 cells that we highlight are differentiation into the gas exchange cells, so type I epithelial cells to maintain that capability, as well as the production of surfactant to maintain alveolar integrity and prevent alveolar collapse.
Here, when you then look at this cell type, these precursor AEC2 cells that carry our receptor in the context of IPF on the left-hand side, IPF is a disease of injury to the lung. That injury targets the epithelial layer of the alveolus, causing apoptosis and dysfunction of the epithelium, including these type II epithelial cells, as well as in the type I epithelium. What this then ultimately does is it drives a depletion of the gas exchange capability as well as the dysfunction of the AEC2 cells prevents their replenishment of type I gas exchange cells, but also prevents the production of surfactant protein driving prefibrotic alveolar collapse. These are things that then occur even before the fibrosis.
So in that sense, IPF is a disease that, of course, involves fibrosis, but also involves epithelial damage, reducing gas exchange capability and the ability ultimately to have kind of adequate lung function. Now, the injury to the epithelium is also the trigger for the initiation of fibrosis. So the type II epithelial cells are one of the main cell types that, when they are injured, release TGF beta-1 to drive the fibrotic process that drives epithelial to mesenchymal transition. So the epithelial cells now become fibroblasts.
And ultimately, those fibroblasts are activated by the TGF beta-1, migrate into the interstitium, become myofibroblasts, and deposit the collagen, building fibrosis in the space between the air sacs and the vasculature, the interstitial space, as they call it. In addition to that buildup of fibrosis, IPF is also known to be associated with dysregulation in enzymes called matrix metalloproteinases.
We highlight in particular MMPs that are associated with the breakdown of existing fibrotic matrix, collagenase MMPs. Those are taken down, allowing the fibrosis to build in the interstitium. Then finally, there's a vascular component to this disease. There's a high overlap of IPF patients and patients with pulmonary hypertension. The vascular dysfunction causes both constriction in the capillaries as well as endothelial cell dysfunction, making it hard for oxygen to really be received in the vasculature. Now, on the right-hand side, what our AT2 mechanism does about all of that is really, first and foremost, by agonizing the type II receptor on these precursor AEC2 cells, we refunctionalize these important cell types. We allow for the protection of the cell type.
It can replenish the type I gas exchange capability, and it can produce surfactant to address prefibrotic alveolar collapse due to the loss of those proteins' production. In addition to that, when you refunctionalize these type II epithelial cells, they no longer release that damage signal. So there's a significant decrease in TGF beta-1 expression and also a downregulation of the signaling through TGF beta-1 as well. Now, that drives down then the kind of buildup of new fibrosis. But also, we have data sets reflecting that we upregulate the production of collagenase MMPs to address fibrosis that already exists in the interstitium. In addition, we address the vasculature. This is a mechanism that's been shown preclinically and clinically to drive vasodilation and endothelial cell function.
So really, an upstream approach that comprehensively addresses the epithelium, the interstitium, as well as the endothelium and vasculature. Now, in order to demonstrate the clinical efficacy side of things, we did an open-label, approximately nine-month clinical study. Patients with IPF took buloxibutid 100 milligrams twice daily over that nine-month period. And we measured the lung function, which is the key endpoint over that period of time as well. From a baseline characteristics perspective, the phase IIa characteristics shown at the left. On the right-hand side, examples are the phase III leading to the approval of the standard of care therapy and nintedanib.
Quite similar and point out in particular a percent predicted FVC in our patient population of 75%, which is nicely in line with other IPF studies. In terms of side effect profile, the treatment emergent adverse events are shown in the right-hand column. Really nice profile reflecting good GI tolerability, which is distinct from the standard of care therapies that drive significant diarrhea, nausea, as well as other GI side effects. Low overall rate of exacerbations and cough, as well as no treatment-related serious adverse events, so quite a nice safety profile, and this phase IIa is consistent with a broader data set for this drug that we've generated in over 350 healthy subjects and patients.
Now, from an efficacy perspective, very nice to see that we were able to stabilize lung function over about 20 weeks, followed by drive a period of improvement in lung function after 36 weeks. As I'd mentioned, a mean improvement in lung function of over 200 ml, which is quite distinct from the expected untreated decline of 180 mL for about that time period. This is also a nice data set in that it's robust to outliers.
So both mean and median are above baseline with a median improvement in lung function over 60 milliliters and 65% of the patients in this data set having improvement in lung function. Also consistent when you kind of look at some of these smaller subpopulations, including different radiological status, gender, as well as different enrollment geography. I'll skip through these. Nice to see also some systemic biomarkers that are consistent with the mechanism of action, trend in decrease in TGF beta-1 in the periphery, as well as an increase in key collagenase matrix metalloproteinases that can digest the collagen MMP-13. So this is kind of a reflection that you're both reducing the fibrotic drive, but also addressing existing fibrosis as well.
What we've now initiated and conducted the capital raise to be able to complete is this phase IIb trial, which is a randomized placebo-controlled trial with patients on nintedanib standard of care and not on standard of care, looking at the regulatory endpoint change in FVC at 52 weeks. We'll be investigating both the same dose as the phase IIa, 100 milligrams oral small molecule twice daily, as well as 50 milligrams twice a day as well, along with a placebo group. Maybe, Alex, I'll stop there and happy to talk more about the study that we've now initiated or any other part of the story.
Yeah, definitely. Appreciate the overview. I think as folks dig into the IIa, I think one of the key questions in this space is just translatability from IIa to to phase III. And obviously, there's been a lot of historical failures. I do want to talk about some of the more, I guess, the recent positive data from BI and phase III. But I guess when you look at the IIa data set, what gives you confidence in the realness of what is a very large signal here? When you look at the secondary endpoints, the biomarkers, what is the how do you push back on the fact that this is an open-label trial?
Yeah, it's a great question. I think there are a few pieces to that puzzle. I think first and foremost, when you look at one of the reasons why we've seen lack of translatability from phase IIa to phase IIb, or phase III is the presence of extreme outliers in the data set. So when you take out one or two outperforming or underperforming patients, the nature of the data set changes. And I would say that the phase IIa data set is robust to outliers in that you have this majority of patients improving in lung function, 65%, 80% performing better than the expected untreated decline.
So this is not a data set where if we just took a couple out, we would have a different result. And I think that's distinct from a number of the IPF kind of phase IIa to later stage development failures.
The second piece of the puzzle is the length of the investigation of lung function. So in a number of these phase IIa failures, they investigated the effect over a 12-week period. And in many cases, because inflammation and fibrosis are so closely related, a target could drive an anti-inflammatory effect that ultimately doesn't provide durable benefit to patients because the fibrotic build continues. And so you can reduce swelling in the short term, but are you going to reduce fibrotic buildup in the long term? And again, I think there are two components to this. One, the nature of our mechanism is such that it's a durable effect, and we've seen that preclinically, but also now we've been able to show it in the phase IIa data set.
I would say the longer you go, the less likely it is that you're seeing things as a result of chance. If you think about these natural histories of IPF patients, only 4%-9% could be expected to have a stable or improved lung function from initiation, very different from a 65% data set. Those things provide a lot of confidence, along with, as you said, Alex, a biomarker data set. You have to take biomarkers with a grain of salt. You're measuring things systemically that are happening in the lung, and there can be variability. But at the same time, really nice reflection of and consistency with what we're seeing preclinically as well.
Brian, do you have a question?
Just to follow on that, when you think about patient selection, I mean, how important is it to be thinking about stage of IPF, cause of disease, to that granularity to kind of drive the difference that you continue to show? How are you thinking about that?
It's a great question. I mean, I think that IPF currently is looked at kind of in aggregate. There's emerging work on looking at different subsets. So for example, one of the key ways in which IPF patients might be segmented today is on radiologic status. Do you have the typical UIP or the probable UIP? Now, in the current larger data sets, both of those patient subgroups actually, on a large basis, have the same expected untreated decline trajectory, so the same slope of decline in lung function. And the standard of care therapies have the same impact on them.
Now, what's interesting is in our data set, we have a greater kind of improvement in the patients with a probable UIP who are kind of, you could consider them earlier stage patients as they don't have evidence of honeycombing. So that'll be an interesting thing to continue to investigate. At the same time, I think the data set that we've produced gives us confidence that we can address the entire population and that even those patients with the more entrenched fibrosis and evidence of honeycombing, we were able to drive a stabilization or even improvement in lung function overall. But I would say that in terms of late-stage clinical development, the field is still too early, I think, to do segmented R&D or clinical development work.
And just one follow-up to your point about you saw some benefit kind of in the later stage of the honeycombing. Is that still a function of just kind of slowing down, or is there any sort of recovery from the fibrosis?
Yeah. So IPF is a heterogeneous disease, but actually the state of the lung is also heterogeneous. You could have some tissues, especially in the upper lobes, that are almost fully healthy. And then in the lower lobes, it could be that it's totally gone. It's just fibrotic material, and that's the honeycombing. And so I think it's all a gradation. And I would say that the drug's effect then grades as well. The earlier stage the disease is, I think the easier it is for a mechanism like this to play a role. So if you think about prefibrotic alveolar collapse, there isn't even fibrosis, but there's a loss of lung function because of that loss of surfactant protein.
Well, if you can replenish the surfactant supply, you should be able to address that pretty easily or relatively easily. Whereas if, for example, you're trying to resolve existing fibrosis, I think that can happen, but I think it takes time. So I think that's also part of the reason why the effect in our drug builds over nine months. That's at least our hypothesis. And I think that there are some tissues you're never going to be able to do anything with. If there's already honeycombing and there are no cells to even have a receptor that you would agonize, then there's nothing you can do. There's nothing you can do there.
Thank you.
And I was curious, maybe one more question on the IIa and then think about the . No, is functional un blinding, and we've talked about this before, a question or something that you're thinking about from the IIa to the , especially with the hair loss and how that impacts the perception of an impact on FVC, which is to some degree an effort-based measure?
Sure. It's a good question. I think that when you look at what we saw in terms of hair loss or hair thinning, 19% of the phase IIa population experienced it. It was mild to moderate, and it was reversible both on treatment and with discontinuation. So what that means is actually most patients had a little bit of a period. Most of the 19% that had some hair shedding had kind of a period of hair shedding, and then it came back while they were on therapy, and then everyone had recovery after. So I would say the signal is not one that concerns us in terms of a functional unblinding.
I mean, if you think about what the standard of care and nintedanib did, over 50% of the patients have significant and quick onset like diarrhea and vomiting.
I would say that relative to other therapies in this landscape, we don't believe that would be a challenge for us. And then I guess your other question is then on treatment effect. I think it's tough to say that patients are going to perform better on spirometry over such a long period of time, whether that be nine months or one year, because you're ultimately talking about, yes, it is an effort-based measure, but you also can never overperform on spirometry. It's possible that you don't exert enough effort, but you're never going to exert more than you possibly could in terms of lung function. So it would have to be a very strange scenario in which someone, what, initially underperforms and then overperforms. So I think it's tough to think that that would occur.
So then on the , 270 patients, how are you thinking about the effect size for powering? And are you clearly assuming some regression after the IIa?
Yeah, look, I think that if you think about, I think you think about this a couple of ways. You're going from a smaller trial to a bigger trial. So absolutely regression to the mean is a factor. I think the second piece of the puzzle is that you think about what the unmet need is and what would be not just an impactful therapy, but a blockbuster therapy and one that would be huge for patients. And from our perspective, that would certainly be a safe therapy that stabilizes lung function. So we've powered the study on that basis where we want to see a stabilization of lung function.
And then when we think about what the placebo group will do in our study, we made the assumption, at least from a conservative powering perspective, that it's the mildest placebo arm seen in IPF trials. We basically assumed if we had that type of a placebo arm that we would still see a positive effect.
Yep. So the decision to not have standard of care in the IIa and then have a nintedanib in the , can you talk about that? And I also was curious about mechanistically if there's a thought or any impact on the cells that you're targeting by standard of care that might impact the mechanism.
Yeah. So I think that in terms of the phase IIa, I think the objective there really was to understand in an IPF patient population both the safety and tolerability of the therapy as well as the efficacy signal in monotherapy. So there would be no confusion. Of course, at the time that we initiated the phase IIa, we had no idea what we would see in terms of effect. And so I think it's good to see that you see this clear efficacy on lung function and the really nice safety and tolerability profile that was observed in phase I as well. But now that we're positioning the drug for the ultimate label, going frontline on top of standard of care is, I think, the right way to go in this disease space.
And so that's the reason for now kind of coming on top. Now, in terms of nintedanib and its TKI mechanism of action, I think that our view is these are quite distinct mechanisms of action, and I think there's certainly the potential for some additive effect, but there's no kind of hypothesis that we've generated on why we think there'd be any kind of issue. The question is, could nintedanib frustrate the activity of your molecule? Certainly, we've done the DDI work to confirm from that perspective it wouldn't occur. But from an efficacy perspective also, we don't see any reason why you should believe that would be the case.
Before we started, we were talking about recent developments in IPF. We have the first positive phase III, at least top line now in a long time. I guess what's your perspective on Boehringer's success going from IIa to and what that means about to design a real trial, a real mechanism, and getting that across the finish line?
Yeah, look, I think it's great for both IPF patients. I think they desperately need more options. And certainly, the IPF landscape is one that needs a number of new therapies and not just one. So I think it's excellent from that perspective. I think it's also excellent from translatability perspective, actually both from phase IIa to kind of phase III or phase IIb , but also even from the preclinical data sets to the clinical, because we've been a decade without really a positive phase III in this landscape, and there's been a lot of new preclinical developments. And so now we actually have a little bit of a data point where, for example, there's been a lot of work on generating these ex vivo precision cut lung slices models over the past decade.
Now actually someone can, for example, look at what the PDE4 molecule does in that type of an assay or some of these other fibrosis models and compare these different therapies. We're happy that we actually have a little bit of a new benchmark in the system that we can look at as well.
Any specific data points from the Boehringer development program that you can point to for your molecule now?
So I mean, in terms of their clinical data set, they've always said that the phase III is positive, so they haven't revealed any further information. So we're excited to see the detail. But when you think about it preclinically, certainly we've begun looking at the Nerandomilast, the PDE4 molecule versus ours in the battery of preclinical studies that we've done. And we've, of course, looked at a number of the papers that the BI has put out in this space as well. And we're going to talk more about that over time. And we think we compare quite favorably across a number of these translational models.
I think Brian's question alluded to it in some ways, but thinking about patient segmentation biomarkers moving forward, how are you thinking about implementing that in your and maybe de-risking phase III even further?
Yeah. I think, for the phase IIb , we're really going after the broad population, but we will look at, for example, continue to see do we have a differential effect on probable versus typical UIP. We will look at a number of biomarkers, and that will help us guide whether we want to do anything different, for example, in the phase III, but I would say certainly for the phase IIb , our objective is to go broad and really have a design that's quite similar to a number of others in the industry so it can be appropriately digested by the regulator as well.
Then maybe final question. You talk about your current pharma partnerships and your cash runway and the assumptions and what's baked into those.
Yeah, absolutely. So current pharma partnerships, we have a partnership with Nippon Shinyaku, who have Japanese rights to the program. So that's our present pharma partnership. We did have Sanofi invest in our recent financing round, but that's a no strings attached investment. So that's not a.
No first negotiation?
No.
Okay.
And then in terms of cash runway, we have about $125 million cash position currently, as I mentioned, and that takes us through the readout plus additional one year of runway. So we're capitalized to finish this study.
Great.