Good afternoon, everyone, and welcome back to the afternoon sessions. Hello to everyone listening on the webcast. I'm Steve Seedhouse, biotech analyst at Cantor, r eally a privilege to have our next presenting company and join us for fireside chat. This is Vicore Pharma, and I'm joined by CEO Ahmed Mousa. I'm looking forward to the conversation, and to start, maybe I would just invite you to make some opening comments, introduce yourself and the company for those who are not familiar. Obviously, ex-U.S. listed companies. So we'd love you just to make some opening comments and sort of where you're strategically positioned, really, in the IPF landscape is where we'll focus the most. Yeah, absolutely. No, thank you for having us, Steve. It's great to be here. Yeah, my name is Ahmed Mousa. I'm the CEO of Vicore Pharma. And as Steve mentioned, we're a company that's really focused on advancing a drug into late-stage clinical development for idiopathic pulmonary fibrosis. It's a terrible disease with a three-year to four-year survival after diagnosis, unfortunately, so worse than many cancers. And at the same time, it has, unfortunately, a standard of care that leaves a lot to be desired, both in terms of efficacy and tolerability. On top of that, it's an attractive opportunity from a commercial perspective. The standard of care, even though it leaves much to be desired. It had over $4 billion in sales last year. And that certainly can expand, we believe, multifold if you're able to then have better-tolerated and more effective therapies. Now, the challenge in IPF as a landscape has been that there have been so many failures. So the commercial opportunities there, the unmet need is there, but there have been a number of companies that have failed in phase II and phase III. And really, the belief is at Vicore that that has a lot to do. There are a number of factors for it, but we think one of the key things that has to do is mechanism selection. A lot of approaches seeking to antagonize targets that ultimately downregulate collagen deposition. And that's not an invalid way to go after this disease, but we think it's a very partial and incomplete way to go after this disease. So just trying to stop new fibrotic build. And we have a mechanism that sits quite upstream of the process. We think it sits at the start of the process. And we think that's a much more interesting way to go after the disease. And it can lead to significantly better potency on the efficacy side. And also, we've seen to date that the therapy that we're advancing is much better tolerated. Yeah. Great. Thanks for that introduction. So you've mentioned briefly just the potential advantages of your mechanism relative to the competitive approaches that maybe target fibroblast activation or TGF beta production. But how does your mechanism, in fact, or how would you expect it to reduce fibrosis and inflammation maybe differently, as you mentioned, maybe more upstream and just speak more to the selective approach of the mechanism, both in terms of target and cell type, which is an interesting wrinkle? Absolutely, so at the core, what pulmonary fibrosis is, is injury that results in scarring or fibrotic build that then cuts off the ability to breathe, right, so you have millions of air sacs at the distal end of your lung. When there's injury that causes the drive in fibrosis, literally, you have scarring that builds up around those air sacs, and that prevents the oxygen from diffusing out of the air sac into the capillaries or the small blood vessels that sit in your lung, and what basically we think is an effective way to go after this disease is to take the cell type, which are these alveolar epithelial type II cells. These are stem cells. They become injured as part of this disease process. And when they become injured, they essentially do a few things. One is they stop regenerating into the gas exchange cells. So basically, when you stop these stem cells from functioning properly, you have a reduced gas exchange capability. So basically, that means even if you have no fibrosis, by having less gas exchange cells, you have less gas exchange capability, i.e., oxygen is unable to leave your air sac and go into the pulmonary vasculature. The second piece of the puzzle is these stem cells are responsible for making air sacs stay inflated in their shape. So they release surfactant proteins that break up the natural surface tension of water. And water has a very high surface tension. When you see a drop of water on the table, it doesn't spread everywhere. It kind of keeps its bubble shape. Well, that level of surface tension in the absence of these surfactant proteins basically causes the alveoli or the air sacs to collapse like a pancake. And I think the point we're trying to make then here is the injury to these stem cells, first and foremost, even before there's any fibrosis, causes a lot of damage that reduces lung function. But then what's even more terrible about this is the damage to these stem cells, these type II epithelial cells, causes the fibrosis. So basically, these type II epithelial cells are one of the main cell types that release massive amounts of TGF beta. And they're basically saying, we're injured, build a scar tissue around us. And that signal keeps going and going. And so that means you have that buildup in fibrosis in that interstitial space. And when we say interstitial space, we mean the space between the air sacs and the blood vessels, the pulmonary vasculature. And that literally creates a physical barrier that the oxygen then can't diffuse down. And then finally, vascular dysfunction is a known part of this disease. And so you tend to have remodeling of the endothelium, a thickening of the blood vessel walls, and a narrowing of the pulmonary vasculature. And what that ultimately means, again, is it gets harder and harder for the oxygen to get through. And essentially, what our mechanism does is, first and foremost, it's a refunctionalization and a proliferation signal to these type II epithelial cells. So basically, we reactivate them. We cause them to divide again. And that does a couple of things. First of all, now you have this reservoir of stem cells that can replenish the type I gas exchange cells. So it means you replenish the gas exchange capability, and you actually regenerate the epithelial layer after that injury. So we think that's beneficial before the fibrosis and in some sense independent of the fibrosis. In addition to that, you are refunctionalizing the cell type, so you have then more surfactant production or a reinvigoration of surfactant production, which means then you're able to address that alveolar collapse, which again is reducing the lung function. And then beyond that, when you refunctionalize this cell type, naturally, what then happens is it stops releasing the injury signal, so what that means, Steve, is then you have a reduction in that pathological TGF beta secretion. And that stops the fibroblasts from activating, migrating into the interstitium, turning into myofibroblasts, and ultimately then depositing collagen, and so that's perfect in the sense that it also addresses then that classical kind of fibrotic part of the disease process. And then finally, this mechanism, which sits in the angiotensin II pathway, so it is naturally designed to impact the vasculature, is a vasodilator and also has been shown to address the remodeling of the pulmonary vasculature associated with the disease state. So basically, what we're saying is we're able to address the injury to the epithelium. And that has an impact in stopping the fibrosis in the interstitium. We can resolve the fibrosis in the interstitium, and we can address the pulmonary vasculature to make it easy for blood to be oxygenated. Yeah. I mean, one of the things that has stood out to me just from the mechanism in your data, and we'll talk more about the phase IIa AIR study and the implications there, is that it is plausible, just given the multi-pronged sort of consequences of the mechanism, that you would see early effect and late effect, right, given the sort of healing nature, but also a bona fide improvement and healing as opposed to just a slowing of progression, and so fascinating mechanism. We'll talk more about the data. We'd love to just, before we do that, though, on the overall IPF landscape, I mean, you mentioned the deficiencies of some of the current approaches. There's been some recent development too, some phase III successes with BI and then more recently United Therapeutics. So can you maybe talk about just what you see in some of those top-line data and just what those advances for the field you think will mean and where Vicore really fits sort of amid this new and potentially improved, one could argue, therapeutic landscape in IPF? Yeah, absolutely, so first, earlier in May, BI reported first positive phase III in over a decade in IPF, which was great to see. They have a PDE4 inhibitor, nerandomilast, which basically showed the ability at 52 weeks to drive an improvement in lung function relative to placebo of about 68 ml, so it's still slowing the decline of lung function, not stabilizing or improving it, but it's nice to have, let's call it, another tool in the toolkit because the two standard of care therapies can be very difficult to tolerate. Patients only stay on these therapies on average for 10 months, and so to have another therapy, even if it's not super differentiated from an efficacy perspective, can be very helpful to patients. Now, I would say that I would classify kind of that mechanism more in the classical kind of antifibrotic space. It should be able to slow the decline of lung function by slowing the deposition of new collagen. What's then a little bit more interesting maybe is yesterday's announcement by United Therapeutics of a positive phase III with inhaled treprostinil, Tyvaso, where they showed a 95 ml difference from the placebo arm to the treatment arm, and it's a bigger numerical effect, which I think is interesting, and there's also, in addition to that, of course, with Tyvaso, they've shown data preclinically that they have an antifibrotic effect, but also it's well known to have a vasodilatory effect. This drug is already approved in pulmonary hypertension. And for me, I think that that combination of mechanisms, while it's tough to think that vasodilation alone can have a big impact for IPF patients, I think that there is something special about these types of combinatorial approaches or mechanisms that can drive multiple things at once. And so I think it's interesting to see and nice to see that you're able to do that. And I would say, mechanistically, we see the Vicore approach is going even a step then beyond it, having the vascular impact, the impact in the interstitium, but also then the epithelial repair and regeneration impact, which makes us also excited. Great. So let's revisit the phase IIa study just to recap some of the findings there. And it'll set the stage, obviously, for what you're planning in the phase IIb Aspire study. But maybe just talk about AIR, the phase IIa study, and the overall premise and approach and really the strength then of the conclusions that you drew from it. So it's an open-label study, single-arm, antifibrotic, naive, enrolled a large proportion of patients, I believe, from India. So maybe we could just tackle each of those features. I mean, sort of how did you end up with this type of study and anything important to note of those features and the resulting data conclusions that arise? Yeah. Well, it's ultimately the case that what you want to do when you're positioning IPF therapies is test them when you're in the later stage in combination with the available standard of care. I do think it's interesting at an early stage to take a look at how the therapy performs by itself. And so for that, to have a monotherapy study, I think, is ultimately interesting. It helps you generate a clear clinical signal that your drug is active. So that was certainly one feature which I see as a positive. There was a treatment naive population, which, to be honest with you, I think that when you look at those who've failed prior standard of care versus those who haven't, particularly because oftentimes patients are taken off of the standard of care not due to progression, but rather due to tolerability issues, oftentimes you see in these data sets not significant differences. So I would say that IPF, of course, is overall a very heterogeneous disease. But certainly, once you've identified IPF patients, if you're able to generate a signal in a treatment naive population, I think that's a great first step before then testing it in combination with the standard of care. I think one of the really nice things about this IPF study is it studied the drug over 36 weeks. And I think that's very important in the context of this disease because when you have drugs that have some anti-inflammatory effects, which this drug does, we don't think it's the dominant effect, but it does have an anti-inflammatory effect. I think it's important to understand whether your effect is short-lived or whether it continues over time. And certainly, we've seen challenges in IPF studies where you see a short signal after 12 weeks that does not bear fruit as you continue to study the drug over longer periods later in development. So it's really nice to see that drug was studied over a 36-week period. As you'd mentioned, the study was run in an open-label format. I think that ultimately, if you have a good diagnostic oversight in the study and you're ensuring that you're truly bringing in IPF patients, what we can say is certainly we know that this disease is heterogeneous, but we also know that this is a disease of inexorable decline in lung function, right, and when you look at very big data sets, you only have single-digit percentage of patients after about a year who would have a stable lung function or something modestly above the baseline. This is not a disease where you'll have some subgroup who's improving in lung function without some sort of therapy or intervention, so I think what becomes important then is becoming confident that you have IPF patients, and certainly, that's what was done in this study. There was central reading using HRCT with one of the renowned pulmonary radiologists in the United Kingdom. So, looking at every single patient and allowing them into the study. One of the other features you mentioned, of course, is that, and this is part of the desire to get treatment naive patients to really look at how this drug behaves in a kind of clean way is we wound up enrolling a significant portion of patients out of India. I would say, again, when you look at the large data sets that look at India, IPF is heterogeneous. And I think that the data reflects that the Indian kind of heterogeneity sits within that broader universe of IPF. And so there's nothing particularly unique about kind of Indian IPF patients that would make them non-representative of the global population. And certainly, when you look at phase III trials in IPF, a number of the companies run the phase IIIs with a number of Indian sites. What's also nice is, and we can talk about the effect that we ultimately saw, which is a really nice improvement in lung function over 36 weeks. We saw that effect both in the patients who were enrolled from India, but we also enrolled a decent number of patients in the United Kingdom, and they also saw improvement in lung function at that time point. Yeah. I mean, let's talk about that. So because lung function really stabilized and improved ultimately consistently and with a magnitude that I just think is very rare, a greater than 200 ml increase from baseline over 36 weeks, that's a 7.5% increase. I mean, the question is just how surprising was that? And are there any sort of precedent data sets with such a large increase? Obviously, this must give you some conviction that you have a real drug here and a really promising mechanism. Yeah. I think that it certainly gives us a lot of excitement. Also, the improvement in lung function builds over a nine-month period, which is consistent with this type of mechanism of action. So it was really nice to see the improvement, the extent of improvement, the built-in improvement, or the dynamics of that improvement, which kind of follows slowing the build of new fibrosis, digesting the existing fibrosis, regenerating the epithelial layer, and then addressing that vascular remodeling component. So that was really nice to see. It was also really nice to see that there was a correlation between those with the probable UIP, which is typically associated with being a little bit earlier stage in the disease, less honeycombing, and those subgroup of patients having kind of the strongest side of the effect so that there's a natural kind of biological plausibility and consistency in the data set when you look at who is improving the most. But what's really nice to see is that you're able to even modestly improve the lung function in those later stage patients with a typical UIP pattern. So even those patients, you're able to preserve the lung function they have and maybe modestly increase it as well as what we saw in the phase IIa data set. As I'd mentioned, it's also nice to see that you're able to see this improvement in lung function across the different subgroups from the geographies. But in addition to that, overall, most of the patients having improvement in lung function, 65%. One of the other problems we've seen in IPF studies is some of these data sets have been driven by like one or two outliers that have one or two liters of improvement or decline in lung function. But we have improvement in lung function at both mean and median and 65% improving in lung function. So really nice to see that consistency in the data set as well. Indeed, yeah. So I mean, the median patient improved, I mean, 63 ml, which is obviously super impressive. The mean, though, was even higher, as I mentioned, greater than 200 ml. So you did have some sort of really profound responders. I'm wondering if there's anything you can learn that is unique about those patients, anything you can learn from demographics or fitting the mechanism of action to a particular patient, or is it just too small numbers? I think it's small numbers to draw any absolute conclusions. I mean, one hypothesis is that if you think about earlier stage patients that might have a disease state which is more dominated by reduced gas exchange capability due to less epithelial and then also some prefibrotic alveolar collapse, we think that there's a potentially more tractable in a more expedient manner, right? So that rather than having to face the biological hurdle of reducing new fibrotic build and digesting existing collagen in order to provide for a greater FVC impact, that that might be something you can do a little bit quicker. And that's certainly what we saw when I mentioned kind of a little bit earlier stage or the ones who had that kind of higher improvement in lung function, like less fibrosis level at baseline when you look at the scans, the high-resolution CT scans. You were ultimately able to develop a synthetic control arm that really increases the confidence in that result. Can you just maybe touch on how that was the methodology there and just the conviction and the utility of that? Yeah, absolutely. So, right, as you mentioned, the population that we looked at, treatment naive and certain inclusion criteria, it'd be interesting to say, "Okay, how does such a group perform if we were then first inclusion criteria match?" So we went and worked with a company called Qureight that has a database of 10,000 IPF patients, a significant portion of that actually out of the U.K., where we also enrolled some of the clinical trial. And basically, in those 10,000 patients, we went down to the subgroup of those that met the inclusion criteria of our trial, so everything that would have allowed them to participate. And then we actually took that subgroup and we generated 20,000 placebo cohorts, placebo arms, kind of agglomerations of those groupings of patients. We actually took the 408 that kind of matched our baseline characteristics in our study of the patients who came in the closest. When you look at those kind of 400-ish placebo arms, you wind up seeing a cohort that has an average decline in lung function of 114 ml. It's a nice contextualization. It tells you that this is a group of patients who naturally at baseline would not improve in lung function. They would decline. It's a nice way to also then view the data set that we generated as well. Yes. Pretty profound. Moving on to the phase IIb study then, this is the Aspire study. I think one of the features here is you're adding a lower 50 mg b.i.d. dose in this study. Maybe just talk about the rationale. Yeah, absolutely. I'm happy to do that. So what we saw in our phase IIa at 100 milligrams, and we'd also seen this at the phase I, was some hair loss or hair thinning. So 19% of patients in the phase IIa reported mild to moderate hair thinning or hair loss. This was reversible. So all patients after they came off of therapy had recovery of hair. And also, even during the study, most of them were reported to have recovery as well, so kind of a period of shedding. The 50 mg dose is a look at whether we can hopefully eliminate or significantly mitigate that effect. And based on our dose modeling exercises, which include, of course, looking at a lot of our preclinical data, we do believe that the 50 mg dose still is therapeutically effective. It'll be interesting to explore that in the phase IIb that's ongoing. Also in dosing, is once daily QD dosing here just not appropriate given the chemical structure and the PK? I would say that the challenge with IPF is because you're basically signal of activity is 52-week FVC, and because these studies are so big, long, and expensive, it's tough to do a lot of dose modeling. What we know is this drug is quite safe and well tolerated in the context of this disease. So it's possible that a once daily would be effective, but we think that we're trying to maximize the therapeutic potential. We believe that this is a Cmax-driven effect, and we're interested in the idea of capturing that twice daily. Certainly, when you look at the other standard of care, which is nintedanib is twice daily, pirfenidone is three times daily, we don't think that's outside of the realm of what a patient would consider feasible or pliable to do. Certainly, one of the potential challenges associated with Tyvaso, they've shown a nice effect, but it's a nebulized therapy that has to be taken four times a day, and you have to kind of sit for these sessions. So that's a little bit of a challenge. And we feel like still twice daily oral administration should be relatively easy. Yep. And this study is, I mean, this is a gold standard study. This is randomized, double-blind, global, 52-week, 90 patients per arm, so pretty sizable. I mean, it looks ostensibly like registrational-like in terms of its design and quality. C ould you have just gone into sort of parallel phase III studies? Could this, in fact, be pivotal? Just talk about maybe the registration strategy and why this trial was designed as robust as it was. Are you planning a subsequent phase III program? Yeah, absolutely. So I think a few things. One is we certainly think this study will and can hopefully, if successful, contribute to a registrational package. So we think it is part of that base of evidence. I think the other belief that we have is that we should be able to, with a successful phase IIb, engage with FDA to run a single phase III as part of our registrational program. And United Therapeutics, as an example, is running kind of two ongoing phase IIIs. So it's not a given that you get to run one. BI only ran one. But I think you have to have that discussion with FDA, and we think it'll contribute towards that. And certainly then, in terms of what the path forward looks like thereafter, if we can even capture something more attractive than that, I think that'll depend on effect size, unmet need, and of course, the dialogue with FDA and how they see the landscape. Got it. And maybe talk about the powering assumptions in this study because you had this large improvement in the prior study. The synthetic arm suggests an even larger, maybe placebo-adjusted effect would be anticipated. But certainly, you wouldn't have powered this study for a 300 ml effect size or something like that. So what were you assuming, and sort of how conservative did you lean in designing the study? Yeah, absolutely. So the study is designed to detect a 125 milliliter difference in lung function between the placebo arm and the treatment arm. And I think that's a reflection that we're powering conservatively relative to the signal that we saw in phase IIa. So we do not have to observe an improvement in lung function in order to have both a successful phase IIb as well as an incredibly positive result in terms of a drug that would be life-changing for patients and would be commercially quite attractive. And so that powering, it's like 80% power to detect 125 ml in difference in lung function between the placebo and the treatment arm. Okay. Just in the last couple of minutes, in terms of the overall corporate strategy, the stock is currently listed on Nasdaq Stockholm. Curious if you have any plans for future U.S. listing. Is that in the cards in the coming years? And then just current sort of cash runway and ability to execute on the phase IIb IPF study? Yeah, absolutely. So maybe on your second question, we're fully funded for our phase IIb readout as well as runway thereafter. We reported at the end of last quarter about $100 million cash on hand and a relatively small and efficient team that's executing on this trial and really quite focused on it as well. And then in terms of U.S. listing, absolutely. So I'm U.S.-based, and we think that coming onto the U.S. market at the right time makes a lot of sense. And we certainly think that looking at doing so potentially before the phase IIb readout could make a lot of sense as well, given that there's maybe the opportunity to capture greater upside both in the lead-up to a readout as well as at the time of a readout as well. Great. And then you have an existing partnership in Japan, and I'm just curious about strategically how you think about partnering in other regions, including maybe in the U.S. or Europe, or is this ultimately line of sight into commercializing the product at Vicore and building an organization that could do that? Yeah, absolutely. So I would say we're really happy to have done the partnership with Nippon Shinyaku. They're leaders in the pulmonary space. They actually discovered and developed one of the blockbuster pulmonary hypertension drugs, Uptravi, and then out licensed to ex-Japan, but then they developed and commercialized it in Japan themselves. So they know the KOLs, the academics, and they know drug development in the pulmonary space. So they're the perfect partner for an IPF therapy in Japan. I think beyond that, we'd like to see the phase IIb readout. So I think that we're really focused on executing on the study and demonstrating the efficacy before we kind of complicate the universe further. But what I do think is nice about IPF is, in addition to there being a lot of pharma interest in this space, it is a disease area where it is tractable for a small company to build the capability to run a phase III. It's been done before, and it's possible for folks to commercialize in this therapy space because the number of physicians in these specialty areas is a little bit more limited. So you can build a relatively small commercial sales force to capitalize on the significant commercial opportunity. Okay, well, certainly the phase IIb represents a really important inflection for Vicore, and we're at a moment in IPF where there's been some exciting developments, and so it feels like a tipping point really in that space also that you'll be able to participate in in the coming years, and we're looking forward to following that. Obviously, IPF is an area where we're really focused on as an analyst group at Cantor, so exciting to follow along the story, and appreciate you being at our conferences here, and really thanks for the conversation. It was terrific. Yeah, thank you, Steve. Great having you. Great being here. Thanks to everyone on the webcast and in the room as well for being here.