Thanks, everyone, again for joining us for this year's, our second annual Healthcare Innovation Conference here in Boston. I'm Vamil Dewan, one of the BioPharma analysts here at Guggenheim, joined from the Guggenheim side by Daniel Crozet, one of the members of the team. Next up in this room, we have Vicore Pharma. Pleased to be joined by Ahmed Mousa, the CEO. Interesting story, I think, still getting appreciated by the broader market here. Pleased to have you here to walk through things. Maybe just to kick things off, because I think Vicore is a story that's a little bit less well understood. Maybe you can just give a little bit of the background of the company and how you've gotten to this point. Then we'll talk more about the data generation data and the plans forward. Yeah, absolutely. No, thank you, Vamil and Dan, for having us. We're really excited to be here at your conference. Yeah, so Vicore Pharma is a company that's advancing programs in the angiotensin II pathway. In particular, we've zeroed in for our lead projects on a receptor in that pathway called the angiotensin II type II receptor. It is an endogenous tissue repair and fibrosis resolution and antihypertensive system. We think it's a very interesting intervention point for a number of fibrotic and inflammatory-oriented diseases. Kind of the lead project here is in idiopathic pulmonary fibrosis. The inception of the company is really around the creation of molecules that could effectively activate this pathway. It is a little bit of a challenge because the molecules are GPCR, it has receptors that are structurally similar but do opposing effects. You really have to have an excellent kind of medicinal chemistry approach in order to selectively and potently activate this pathway. That's the kind of inception of the company, is kind of the creation of the molecules that could effectively do this. Okay, and so maybe you mentioned lead program here and the pathway. For For IPF specifically, can you talk why this pathway, it's attractive to target in IPF? Absolutely. I think one of the reasons why the company keyed in on pulmonary fibrosis and IPF specifically early on is because this is a receptor that tends to be relatively limited in its expression in a healthy person. If you do not have a lot going on, you will not find it in many tissues. It tends to be upregulated in expression as you have fibrotic or inflammatory conditions, basically your body's way of trying to then make this receptor available to resolve those conditions. Interestingly, there is significant basal expression. One of the few places where you find it is in the lung in a healthy person. There is evidence that it is further upregulated. Because of that strong level of even basal expression, we think that it is an interesting place to go after for idiopathic pulmonary fibrosis at the outset. Okay, and it does seem from our review of the literature and our conversations before that there's a broad range of effects potentially for your product. If you had to sort of narrow it down, again, in IPF specifically, what's the main driver, a couple of drivers that you think is making the impact that you're seeing so far? Absolutely. The way we think about idiopathic pulmonary fibrosis is that the inception of the disease is this micro injury to the epithelial layer of the alveolus. Basically, that layer of the air sac is the interface between the oxygen and then kind of the diffusion into that interstitial compartment so that oxygen can get into the pulmonary vasculature. It is that epithelial layer that starts to become damaged due to the micro injury associated with IPF. You have a basically loss of epithelial function. That epithelial dysfunction is what, in our view, and I think supported by a number of academic groups and a great deal of research, is what initiates that pro-fibrotic process. I would say the core of what buloxibutid is doing and the agonism of this angiotensin II type II receptor is protecting and regenerating the epithelial layer of the alveolus so that basically you can repair the injury associated with IPF and attenuate the pro-fibrotic signal that then results in the buildup of collagen in the interstitial compartment of the lung. I would think about it as an epithelial targeting project as kind of the main driver of its activity. Okay, great. You have released some data from a phase IIA trial. Maybe before we dig into the details, give an overview on what that trial designed and kind of what you showed, and then a couple of follow-up questions we'll probably have on that. Absolutely. The project was, of course, well advanced in the clinic. We've done phase I work where we show no DLTs, no MTDs, so overall a safe and well tolerated drug. We did see some hair loss or hair thinning and can talk a little bit more about that as well in phase I as well as in the phase II setting. In the phase IIA study that we did for buloxibutid and IPF, we went after a treatment-naive monotherapy population in order to get a clear signal of activity on this molecule. We studied the drug over a 36-week period. Now, you'll often see phase IIA studies in IPF run over 12 weeks. We think that's not quite the right way to look at this disease in the sense that if your mechanism has a significant anti-inflammatory effect, you can reduce swelling and allow for greater lung function as measured by forced vital capacity. If you really want to interrogate whether a molecule would have an effect on fibrotic build and collagen deposition and these types of dynamics, you need to look further out than 12 weeks. That is why at Vicore, we looked at the effect of the drug over a nine-month period. Essentially, we then studied the drug in this, it was an open label study, monotherapy, as I'd mentioned. What we saw is that we were able with this drug to stabilize lung function out to about four to six months. There was a period of improvement in lung function in the treatment population. When you go out to that 36-week time point, you actually have an improvement in lung function of over 200 ml, which is quite striking in the sense that typically in IPF, what you would expect is actually a decline in lung function. That decline in lung function would be to the order of over 100 ml over that nine-month period, depending on the population that you're looking at, maybe even according to some of the older literature, up to 180 ml over that 36-week period. It was really exciting to see this clear signal of clinical activity and evidence of a disease-modifying effect, which again, we think is consistent with this mechanism of action where I talked about repairing the injury to attenuate the fibrotic drive. A lot of the other mechanisms of action that go after IPF are trying to downregulate collagen depositing activity. That is not an invalid way to go after this disease, but we think that it is not too surprising then that what you are ultimately able to do is slow the progression of the disease because you are kind of downregulating the fibroblast activity, but you are not really addressing the injury that is upstream of that collagen deposition. Okay, that's great. I think as we've looked at that data and had some general conversation with investors on the data too, as we've gotten more familiar with the IPF space, I think a couple of questions come up about that data. That's the one that the study was, a lot of it was enrolled in patients in India. It was obviously an open label for a phase IIA trial. There's a fair number of discontinuations over the course of the trial. Maybe you can just talk to those three points in terms of enrollment, the patients, and is there anybody in India patients that patients with IPF in India could be, is it different in some way than patients in other geographies, the reproducibility of that data in another trial? Just sort of the open label and the nature of people staying in the trial. Absolutely. You basically touched on three key points that folks look at when they're looking at our phase IIA dataset, which is, yeah, how do we think about it being open label versus placebo-controlled? We did have higher than typical level of discontinuation. How do we think about that in this phase IIA trial? Then finally, we had enrollment out of India at about 70-75%. How do we think about that as well? I think that at the outset, setting the scene, when you're thinking about running a phase IIA trial in a treatment-naive monotherapy population, you have to go for certain geographies in order to have access to that patient population. This study was initiated in 2020. Essentially, the thought was to go after India, Russia, Ukraine, and then the United Kingdom in order to get that treatment-naive population. In India, Russia, Ukraine, there was a view that you could get for market access reasons, right? Folks wouldn't have, unfortunately, access to the available standard of care. So they'd be motivated to come onto clinical trials for a monotherapy study. In the United Kingdom, the NHS was more restrictive at the time in terms of access to the standard of care therapies until patients became more progressed so that there was a population that would be motivated to come onto a trial ahead of having access to standard of care. What happened then, unfortunately, is of course the war started in Russia and Ukraine. Those sites closed fairly early in the study progression. The NHS guidelines also were updated such that nintedanib and pirfenidone became more accessible. It kind of limited the ability to really make this an attractive trial for that population as well. That is what ultimately resulted in, that is why we ultimately had a higher enrollment level in India just to kind of give a little bit of that context. When you then look at kind of IPF in India versus other countries, there is certainly nothing unique to the disease progression and features relative to the global heterogeneity of this disease. It is a heterogeneous disease, but it is also evident that the Indian population sits within that global heterogeneity. Certainly when you think about the hallmark of diagnosing IPF, which is a high-resolution CT scan and particular features that are in that CT scan, those are observable and kind of able to be looked at centrally. Actually, what was done in the phase IIA studies, we had one expert clinician out of the United Kingdom, a radiologist who's done this for many phase II and phase III studies, centrally confirmed the diagnosis of IPF based on these high-resolution CT scans. We have a high degree of conviction that this is a representative population and that this is a population that truly had IPF. When you then think about the placebo arm piece, what we did there is actually we've done more recently a synthetic control arm to really say, okay, let's contextualize this open label study with a real-world population that is treatment-naive and not taking anything else. Actually, we did significant baseline matching work. We pulled in basically patients from a very large dataset that matched as closely as possible the features of the patients who were actually enrolled in our phase IIA trial. We found that that population that actually enrolled in our, sorry, that population from the real world that has the matching kind of lung function characteristics, age, gender, other features, had a decline on average in lung function of 115 ml over a 36-week period. What it tells you is that when you have this signal of improvement in a population that has these baseline features, that is something that's entirely unexpected. Now you know that intuitively because people in IPF don't have improvement in lung function, but this actually quantitatively allows you to understand what a placebo population would have done. Now in terms of the discontinuations, most of those discontinuations occurred in the first 12 weeks of our study. Essentially the reasons provided as the reasons for discontinuation of the study were for most of these patients, COVID-related. Folks were afraid of getting COVID. They didn't want to come back to the clinical sites. Folks were moving around at this kind of time of uncertainty. Certainly when you think about the course of clinical progression in this disease, it's longer term than having folks like really understand whether they're benefiting or not benefiting from a therapy over such a short period of time. It's the same reason why we wanted to do a 36-week study. We believe that the reasons for discontinuation were not associated with kind of some sort of signal of these people would have otherwise not progressed well with our drug. Certainly, when you look at the differential baseline characteristics, they look similar for those who stayed in the study versus those who discontinued. There is no signal that these patients who were coming in were somehow different or would not benefit from the treatment. The other thing that we then did with this synthetic placebo arm is we used that to conservatively impute our dataset. Basically, what we were trying to do in this imputation analysis is say, what if we are wrong? What if actually each patient that discontinued from our study as they discontinued would have had a placebo-like trajectory, a trajectory of progression, that 115 ml over 36-week trajectory? If you do that type of an imputation, you still end up with a statistically significant result in terms of the difference between that 115 ml synthetic control arm versus what the treatment arm would have looked like with kind of complete data. Again, assuming everyone basically who discontinued declined, you still have that signal of improvement. Of course, it is more modest at 20 ml improvement at 36 weeks. Again, that still represents something that is quite significant in view of the landscape and certainly would be considered a very impactful therapy for patients. Okay. Maybe just one, you touched earlier on the hair loss, hair thinning. Did that play a role in the discontinuation? Or maybe you just describe what that side effect is. That didn't play a significant role in the discontinuations in the sense that it was only one of the patients who discontinued throughout the study cited the kind of hair loss or hair thinning as a reason. Certainly it's something that was known from the phase I. So it's something that we make as part of the informed consent process and that we walk through with patients, remembering that this is a disease that's largely of older men. It's majority older men, mid-60s and above. When you also then look at kind of the patient population and unfortunately this is a really tough disease, it's one that has mortality after diagnosis of only three to four years, we don't think it's kind of the major driver of discontinuations in our phase IIA. We think that it's ultimately something that from a risk-reward basis would be ultimately accepted. One thing that we're doing in our phase IIB study that's now ongoing is we're testing the same doses of the phase IIA as well as a lower dose. Since the hair loss or hair thinning effect is dose-dependent, this could be an opportunity if that lower dose is efficacious to clear or mitigate that side effect. Okay. Great. Let me turn to Daniel, then dive a little deeper on this phase IIB. Yeah, great. Thanks, Vamil. The IIB initiated late last year, top-line data expected probably in 2027. Can you speak a little bit more to the trial design? You mentioned the two doses that are tested, but also the key inclusion and exclusion criteria. Anything else you think is important? Yeah, so we're running a gold standard study with this phase IIB in the sense that we have the regulatory endpoint. The change in lung function is measured by forced vital capacity at 52 weeks. Same endpoint for the ongoing and completed phase IIIs in this field. Also a broad inclusion criteria that's again, not identical, but similar to a number of these other phase III studies. Finally, the positioning of this drug now that we have our monotherapy signal is as a frontline therapy on top of standard of care. We're allowing patients who are on nintedanib standard of care or who are not on standard of care either because they don't want to take it because of the side effects or limited efficacy, or they've tried to take it and did not tolerate it or otherwise chose to kind of discontinue. That's kind of the type of population that we're enrolling. The study, as I mentioned, is kind of two doses, same doses in the phase IIA as well as a half dose. We're enrolling this study across 14 different countries and over 100 clinical sites. It's about a 300-patient study. Quite a large phase IIB as well. Okay, great. I think you've mentioned before there'll be a futility analysis built into this trial. Can you maybe speak to at what milestone this will be run and how it will be interpreted and communicated to the street, the potential timing, anything there? Absolutely. Like other IPF studies, because of the logistics associated with it, we wouldn't have an efficacy interim, but we can do a futility analysis. We'll conduct this futility analysis after the first third of patients who've been enrolled, which we've enrolled well over a third now, have completed that one-year treatment period. We'll certainly report the result, but the result is essentially futility or not. It's not more granular than that. Okay. And then assuming positive data here, can you maybe discuss the anticipated regulatory path? Do you believe approval will require one or two phase III trials? Yeah, absolutely. Because of the nature of the phase IIB that we're running, and I believe it is the largest phase IIB kind of that would be run in this space to date, we do believe that this will be part of the package for supporting substantial evidence of efficacy for buloxibutid and that we can have the ability to run a single phase III for approval. This ultimately, of course, is a discussion with the FDA at the end of phase II, end of phase II meeting, but that's certainly something that we're looking for, particularly given the effect size that we're targeting, which is better than the therapies that have been developed to date or those that have more recently read out in phase III, which again, we're still talking about slowing the decline of lung function rather than stabilizing or even potentially improving lung function over that time period. Okay, thank you. Maybe moving on to the landscape a little bit. This has obviously evolved quite a bit since the last time we've hosted you for Fireside Chat. You had the approval of Jascade a few weeks ago, some new data from competitors like United Therapeutics. Maybe you can kind of discuss your overall view on the landscape, how it's evolved, what the biggest unmet need still is, and how you view buloxibutid fitting into there. Yeah. Maybe to set the scene before some of the recent data, right? Two approved drugs, pirfenidone and nintedanib, incrementally slow the decline of lung function, have poor tolerability. I mentioned this kind of this disease with only unfortunately three to four years of survival post-diagnosis on average. Many people do not even initiate the standard of care therapy. In the U.S., actually a minority, about a quarter of patients only will even initiate pirfenidone or nintedanib therapy because of the limited efficacy and tough tolerability profile, cause a lot of GI side effects, nausea, diarrhea. These are things that people decide they do not want to live with in order to maximize, of course, quality of life in the remaining years, particularly since the survival benefit may be limited on these therapies. Jascade, which has recently been approved near endemolast, showed an impact on lung function, a differential on lung function of 69 ml between the placebo arm and the treatment arm. This is certainly a statistically significant effect, but I would say that most clinicians would see it as a modest effect in terms of you still have a decline of lung function that you're slowing, maybe in the zone of nintedanib in terms of overall efficacy, although there's been no kind of direct comparison study. I think what makes some clinicians excited or a number of clinicians excited about this therapy is it is gentler, it looks like based on the phase III data than nintedanib. It actually might have a nice uptake in the United States. It has been approved a few weeks ago. We'll have to see how that ultimately plays out. That's Jascade. It looks like it might be popular because it's a little bit better, easier to tolerate, but it still shouldn't impact or unfortunately shouldn't impact the efficacy side of things significantly. United Therapeutics then, which has the second of the three drugs that are ahead of buloxibutid in development, showed a stronger effect on lung function, a 96 ml difference in lung function at 52 weeks, but a tougher tolerability profile. It's a drug that's already approved for pulmonary hypertension. It's Tyvaso. It's known to a number of clinicians and it can be challenging for patients to take four times a day nebulized, causes flush, coughing, headache, and other side effects. Nonetheless, it still is kind of meaningful clinical effect. The second phase III that they're running will read out in the first half of next year. I think people are eagerly anticipating this. The third drug in development is the BMS LPA1, and that hasn't yet read out and is expected to read out next year. I would say how we think about positioning relative to these is there's a strong clinician and regulator interest to combine therapies, right? At Vicore, we think about buloxibutid as being something we'd like to position at an early stage on top of the available standard of care. Certainly that's why we're running our phase IIB with nintedanib. Actually, as we then think about moving forward phase III in commercial setting, if Jascade does launch well and is available and is being used by clinicians, we would like to see what the combination of Jascade and buloxibutid would look like. Certainly we would think about it in the same way as Tyvaso as well. I think that's how clinicians want to go after this type of disease as well. Certainly a lot of open room in terms of unmet clinical need and also a lot of room in terms of combinations that can drive greater efficacy. Okay. We have a couple of minutes left, Chair. Maybe just to round out the discussion for everyone, in terms of your current cash position, maybe you can give a sense of where things stand currently. Yeah. So about $90 million cash position as of the end of last quarter on September 30, which allows us to generate the readout on the study that the study design that I just articulated, plus have OpEx for about a year thereafter. Okay. How are you thinking about your catalyst? You mentioned maybe utility analysis, top-line data. What are the key things? That That is just what we focus on. Absolutely. Like other companies are developing drugs in IPF, these studies are lengthier because one-year dosing period, but also it's a rare disease. It does take a little bit of time to find and enroll the patients. We've guided that we're looking to complete enrollment in the first half of 2026. We'll certainly look forward to reporting that we've completed enrollment of the study. We'll have the 52-week period for dosing thereafter before top-line results. You could think about top-line results a year after that kind of first half of 2026 completion enrollment, plus about a couple of months in order to clean and organize the data. We'll also have then the futility analysis that we discussed where a third of patients have completed the treatment as well. Okay. Last question, beyond IPF and everything we talked about, seems like a broad opportunity here. Are there indications you're thinking that this could potentially play a role in the future? Absolutely. When again, we step back and look at this mechanism of action, it's the body's opposing force. This AT2 receptor that we're activating is the body's opposing force to the AT1 receptor, which is a pro-hypertensive, pro-inflammatory, and pro-fibrotic set of processes. ARBs or angiotensin receptor blockers like losartan and the SARTAN class are AT1R antagonists. Those have played a significant role in a number of diseases. Similarly, we believe that AT2 agonists then can also hopefully be safe and well tolerated in a number of diseases and provide for significant therapeutic efficacy. There are a number of conditions outside of the lung where we think this target can be very interesting. We have active efforts in the early stage pipeline on that. We look forward to talking about that more over time as well. Okay. I think in the interest of time, we're going to have to leave it there. Thanks so much for joining us again. We'll keep an eye on how things go over the next year. Perfect. Thank you, Vamil. Thank you, Dan. Thanks.