Afternoon, everyone. Welcome back to Oppenheimer's 36th Annual Healthcare Conference. I'm Jeff Jones. I'm one of the biotech analysts on the team. I'm delighted to welcome Ahmed Mousa, CEO of Vicore Pharma. Ahmed, welcome. I hope you've had some good meetings today. Love for you to dive into the Vicore Pharma story, and then we'll jump in with some questions at the end. Thanks for having us, Jeff. I refer to our forward-looking statement disclaimers. Really happy to introduce Vicore Pharma. We are currently a Nasdaq Stockholm Exchange-listed company, so publicly listed on the European Exchange, with about a $380 million market cap, about a $140 million cash position, with a presence both in Europe and in the United States. I'm personally based in Boston, where we have a small but growing office here as well. Vicore Pharma is really focused on advancing its lead program, which is a molecule called buloxibutid, for late-stage development in a disease called idiopathic pulmonary fibrosis. We do have some earlier-stage preclinical compounds, but I'll focus on the clinical side for today. With that strong focus, I think the first question becomes: Why look at IPF? I think first and foremost is the unfortunate severity of the disease. This is a disease that has, unfortunately, a, you know, kind of survival of only three to four years after diagnosis. Quite a fatal disease, unfortunately, worse than many cancers in terms of that type of prognosis. It is an orphan disease, although a larger orphan disease, with about 150,000 patients in the United States. There are three currently approved therapies for IPF, but unfortunately, they don't significantly impact that mortality picture. There's a lot to be desired in terms of drugs that could be more efficacious. On top of that, these therapies also have significant tolerability issues, which makes them challenging to take. This is part of the reason that only about a quarter actually of patients in the United States that are diagnosed with IPF even ever initiate one of these standard of care treatments, and there's also a relatively high discontinuation rate. Average time on treatment for those patients who choose to initiate is only, unfortunately, about 10 months. Both better-tolerated therapies as well as more efficacious therapies that can help with this fatal disease are highly desirable. I would say, pairing with that kind of significant unmet need for this tough disease is also a significant commercial opportunity. Even though I just mentioned that there's only a minority of patients who initiate therapy and a high discontinuation rate, already in 2024, it was over a $4 billion market expected to continue to go steadily to over $10 billion in 2030. In addition to a significant commercial opportunity, a high unmet need, it's also a relatively limited late-stage development landscape. One of the three approved therapies that I mentioned is Boehringer Ingelheim's nintedanib, and there are two other therapies that are currently in phase III. Vicore's buloxibutid is really the fourth one up in development in our view. The therapies that we're looking at here don't really change that paradigm that I've articulated in terms of having therapies that are having an incremental effect on lung function, haven't yet shown a significant impact on mortality, and also having significant kind of tolerability or side effect issues. I would say there's both, you know, a really high need for better-tolerated therapies, as well as something that has the potential to really change the paradigm for efficacy, and we think we can do both of those things with Vicore's buloxibutid. It's an oral small molecule. It's shown really good tolerability to date. There is one mild to moderate hair loss signal, which we'll talk a little bit about in a clinical data set, but that's ultimately manageable in the context of this disease. Really, we've seen very exciting initial clinical data in a phase II-A setting. That's made us very excited to advance the drug in currently phase IIb development. That's the landscape that we're looking at. I think one of the key challenges in IPF is the landscape's actually fairly limited because a number of programs have failed recently and in the past years in phase II and phase III development. We think that's a product of mechanism selection, we've selected a mechanism that's very different from other approaches for this disease type, which we think is the right way to go after IPF. What we do with buloxibutid, our lead candidate, is agonize a receptor called the AT2 receptor, the angiotensin II type 2 receptor. It's shown here in orange. This is essentially a endogenous tissue repair and fibrosis resolution system, it drives anti-fibrotic, vasodilatory, and anti-inflammatory effects. We think supercharging this receptor against the disease is the right way to go after it. It's a pleiotropic set of processes that's driven, and we think that for a profound disease like IPF, that's the right way to go. The angiotensin II pathway target that we're going after actually can be placed a little bit in context of the AT1 receptor, which is shown at the left-hand side. The AT1 receptor does the opposite of the AT2. It's a hypertensive, inflammatory, and fibrotic set of processes that are driven, that's actually an intervention point that's blocked by ARBs and ACE inhibitors. ARBs and ACE inhibitors have both been very fruitful for the industry as drugs that are safe and well tolerated, also play a role in diseases including hypertension, but also beyond hypertension, a number of other fibrotic and inflammatory conditions. We think just as ACE inhibitors and ARBs blocking the AT1 side of this pathway can be very useful, we think activating the protective arm or the repair and resolution arm, the AT2 side, can also be fruitful across a range of indications, starting with the lung and starting with IPF. Maybe a little bit of then context to take this AT2 receptor that we're activating into the lung itself. What we see here is an alveolus or an air sac, and the receptor that we're activating sits largely on a precursor cell called an alveolar epithelial type 2 cell. This cell plays two important functions, one of which is to differentiate into type 1 epithelial cells, which are gas exchange cells. Actually the cells responsible for allowing oxygen to come out of your air sac and carbon dioxide to come back through, as well as production of surfactant protein, which breaks up the natural surface tension of water. This is a bit of a schematic that looks at what happens in IPF on the left-hand side in the lung, and what we believe our mechanism does about it on the right-hand side. Here you have in the center an alveolus or an air sac. The objective is to breathe in oxygen for it to cross the epithelial layer, the type 1 epithelial cells, to diffuse through the interstitium in the lung, into the pulmonary vasculature, where it can oxygenate blood. What happens then in IPF is the epithelial layer of the alveolus of the air sac becomes injured, right? This micro injury that could be the product of a combination of environmental and genetic factors, causes apoptosis, death, and dysfunction essentially, of the epithelial compartment. That apoptosis and dysfunction causes a loss of that type one epithelial compartment. These type 1 epithelial cells start dying off. They no longer can facilitate the gas exchange, you have an impaired gas exchange capability in this disease. Second of all, with the dysfunction of the type 2 epithelial cells, you don't have the production of surfactant protein, that actually causes these alveoli to collapse due to the loss of that surfactant protein. This means that you're unable to really have these alveoli participate in gas exchange. In addition to that, the injury to the type 2 epithelial cells is what then drives the fibrotic process, right? When these cells are injured, they're actually the main cell type that orchestrate the scarring, and they do this by releasing significant amounts of pro-fibrotic cytokines, including TGF-beta 1. That TGF-beta 1 then drives a number of processes that cause the buildup of fibroblasts, their migration into this interstitial space, and ultimately their deposition of collagen, the building blocks of fibrotic matrix. That literally then builds a physical barrier to oxygen diffusion between the air sac and the pulmonary vasculature. In addition to that, of course, the fibrotic buildup can then physically constrict the lung, and it can also put pressure on the pulmonary vasculature, basically squeezing on these vessels as well. Tough disease, it involves multiple different compartments. Essentially what we believe we do about this is fundamentally by agonizing the type 2 receptor that's expressed on these precursor cells, these type 2 epithelial cells, we believe we drive a reproliferation or refunctionalization of the cell type. Which means that you can cause a differentiation of this cell type into type 1 epithelial cells again, because they're replenished, so you replenish your gas exchange capability. You also can address that pre-fibrotic alveolar collapse because once these cells are producing surfactant protein again, that addresses the surface tension of water. You're also then able to attenuate or stop that signal of pro-fibrotic drive because you've refunctionalized that cell type. That's quite important to basically stop new fibrotic buildup. This mechanism of action is also known to cause resolution of fibrosis, and it does that by upregulating collagenase matrix metalloproteinases that essentially can digest existing fibrotic matrix. Finally, you know, this is a mechanism in the angiotensin II pathway. It's vasoactive, and it drives a local vasodilatory effect and a reversal of the vascular remodeling that's associated with the disease state as well. Quite a profound way to go after IPF, and we think a comprehensive way that has the kind of disease-modifying potential. We've shown some really nice preclinical data around what we've done. I won't go into that today, but rather, look a little bit at what we've seen clinically, which is also consistent with the mechanistic concept and what we've generated preclinically. What we did with this drug is test it in a single-arm open label study over approximately nine months in treatment-naive IPF patients. We, of course, looked at safety and tolerability, but as a key secondary endpoint, we looked at the impact on FVC, forced vital capacity or lung function. This is the regulatory endpoint in IPF, so very relevant to test it and to look at it from even an early stage. The baseline characteristics that we enrolled in our phase II-A open label study are shown on the left-hand side here. This is I would say, a typical IPF patient population, and we have actually comparison to the INPULSIS trials, which are the phase III that led to the approval of one of the current standard of care therapies. It's a disease of older individuals. It tends to be skewed more towards men. We did have a higher Asian population because we enrolled our study out of India, and I can talk a little bit about that later. A little bit lower BMI, I think, as a result of that. Percent predicted FVC, which is a measure of the lung status, is in line with what you see in the INPULSIS trials, in our phase II-A trial, and then we went after a treatment-naive population in monotherapy, similar setup to the INPULSIS trials as well. From a treatment-emergent adverse events perspective, we saw a relatively clean profile. This is shown in the right-hand side here. Good GI tolerability. We don't have the tolerability issues associated with nintedanib and some of the other standard of care, shown here for comparison, the INPULSIS studies, again, on the left-hand side and the AE profile there. We had a low rate of exacerbations and cough worsening, and thankfully, we did not observe any treatment-related serious adverse events in the study. Overall, a good tolerability profile. We did observe 19% mild to moderate hair loss or hair thinning. This was observed in a reversible fashion, i.e., the hair did come back as patients discontinued the study. We think that this is ultimately a manageable- a side effect, given that IPF is a fatal disease and one that is dominantly afflicting older men. At the same time, we are looking at lower dose in addition to this dose of buloxibutid in the phase II-B setting, and I can talk a little bit more about that as a potential way to mitigate this side effect. What we then saw from an efficacy perspective is really what got all of us very exciting here, and this is shown here in green. The impact of the drug on lung function over the 36-week period of time, you see kind of out to about 16 weeks, a stabilization in lung function, followed by a period of improvement out to 36 weeks, ultimately by over 200 ml in this open label study. There's a dotted line representing, you know, what you'd expect from the literature for an untreated patient population. Quite a nice effect, a disease-modifying effect, and very, very different from what both current standard of care and emerging therapies have shown, where they essentially are only able to slow the decline of lung function, so still below the zero line on a graphic like this. What we also then did to better understand our data set was generate a synthetic control arm, or a set of synthetic control arms using a real-world database of IPF patients. We actually leveraged a data set of over 10,000 IPF patients. We pulled in those patients, that met the inclusion criteria of our phase II-A trial, and then we actually generated over 30,000 randomly sampled control groups, of kind of 48 patients, so same number that it originally enrolled in the trial. We essentially found the placebo arms that most closely matched the baseline characteristics of those who enrolled in our trial, and those 408 kind of top matching placebo arms became the comparison cohort for the synthetic control arm analysis. What you see here is, on the right-hand side, essentially the FVC trajectory of these 408 very closely matched placebo arms. What you see here is an average decline of about 115 ml in lung function over 36 weeks across this cohort with a good diversity, and this is pretty consistent with IPF. It is a heterogeneous disease. There are different courses and trajectories. What was also then interesting is we used this data set to provide an imputation analysis of the phase II-A data set. The phase II-A study, the open label study, was run during COVID, and there were a number of discontinuations. We saw in the observed data set this over 200- millilitre improvement in lung function. Here we actually did an imputation analysis, and we assumed that each patient who discontinued the trial would have had a placebo-like decline. Even if you make that assumption, you still ultimately see an improvement in lung function of 20 ml, which is still an outstanding effect, both compared to the current standard of care and emerging therapies, as well as a significant effect with a very low p-value compared to what you observe in the placebo arm as well. A really nice way to contextualize the phase II-A data set that we generated previously. What this gave us conviction to do is to run what's currently ongoing. It's a phase IIb study, which is enrolling 360 patients, and including patients with taking buloxibutid at the same dose as the phase II-A, 100 mg twice daily, half dose, 50 mg twice daily. Again, this may be an opportunity to mitigate that hair loss effect that we observed, as we do believe, based on some dose modeling preclinically, that we think a 50-milligram dose could also be efficacious and also a placebo arm in this study. We're also now enrolling patients who are on background standard of care or not on standard of care, and we're allowing patients on both nintedanib and pirfenidone standard of care into the study. We'll look at, as a primary endpoint, the impact of the drug over 52 weeks on lung function as measured by forced vital capacity, which is the regulatory endpoint in this study. Maybe, Jeff, I'm happy to stop there and take any questions. Sure, we can actually... I've got a question just on the current study design, and maybe it's here. They're on stable nintedanib or standard of care. The patients can be on standard of care or not in the study. Is that correct? That's correct. Then in terms of the safety profile, the adverse event that you mentioned most commonly in nintedanib is the GI tolerability. If I recall from the safety table, your GI adverse events were very low, single digit. So how does that, the idea of combination therapy, flow with, as you think about buloxibutid versus, either, you know, the recent approved drug from BI or, you know, a potential approval from the Unither program? What do opportunities look like for differentiation based on combination with standard of care? I think both from a tolerability and from an efficacy perspective, there's a nice opportunity to combine. In our phase II-B, you know, we're allowing patients on background standard of care, either nintedanib or pirfenidone, which is the recently approved therapy or not on standard of care. Currently, our enrollment is showing about 60% of patients enrolling are on a background therapy. Of course, it's largely nintedanib, and 40% are not on a background standard of care. When you think about it from an efficacy perspective, because this mechanism is so different, it's likely to play a complementary role in our view, rather than kind of overlap. We think it should play nicely from that perspective, that-... you know, includes thinking about both nintedanib and nerandomilast, as well as TYVASO, United Therapeutics, drug that had a successful phase III last year. In addition to that, as you mentioned, and is shown here, because we don't have the GI tolerability issues associated with nintedanib, and nerandomilast unfortunately has some GI tolerability issues as well, we should also be able to work well in combination without exacerbating those types of tolerability challenges. And you talked at length about the mechanism of action, and, you know, it's doing a number of things in terms of, you know, anti-inflammatory, anti-fibrotic, you know, repair of the lung tissue, and cells. As we look at some of these other therapies, are there likely to be products where you see a synergistic effect with standard of care, or more or less likely? Vasodilatory activity is one that comes up here and with TYVASO. Are there ways you're thinking about what might or might not be a better partner for standard of care? I think we'll still have to see on what might work best. It's hard, it's hard to know if we'll find synergy. What I will generally say is, this is kind of back a little bit to the mechanism, right? When you think about some of the standard of care therapies, they tend to play in the zone of trying to downregulate collagen deposition activity ultimately, which is kind of in this interstitial zone. That is a little bit different than what buloxibutid is doing by kind of trying to attenuate the pro-fibrosis signal at the outset. They should have some complementary effect. As you mentioned, TYVASO has a effect where it's shown the ability to impact vascular remodeling in a positive way, as a vasodilatory effect, as well as an impact on vascular remodeling. Our drug is also showing the same type of effect. It'll be interesting to see also, you know, what the level of complementarity is. What I would generally say is, as we look at a lot of these FVC kind of decline trajectories, there's a lot of room in the landscape for improvement. If we're able to replicate, you know, kind of the signal that we generated in the phase II-A signal or even the ability to stabilize lung function, we should have the opportunity, hopefully, to work well with a lot of these other drugs then as well. Yeah. I mean, from a combination perspective, as you noted when you were showing the synthetic control arm data, you know, you were seeing a modest improvement in lung function. Most of these programs aren't showing an improvement in lung function, they're showing a slowing of the decline. There's a lot of upside as you think about the opportunity to combine these products, combine mechanism of action, and really broadly, you know, look at complementary mechanisms here. Yeah. No, completely agree. When you were showing the old phase II-A data, you know, you very briefly commented on the number of dropouts. Just could you know, because the number is pretty large, you're going from 48 to 28 patients at that end, 36 weeks, and those patients out at 36 weeks are doing very well. Can you comment a little bit about what might have been driving some of those patient dropouts? Yeah. I think there are a few things to look at then here. First is the timing and the context for the study. The study was initiated in 2020. A lot of these dropouts were COVID driven as kind of the reason and rationale, and I can show a slide here that kind of has actually the individual reasons. Yeah. withdrawal by subject. As you can kind of see that the bulk of them. Most of the discontinuation, 70%, were in the first 12 weeks, and the bulk of those are oriented towards withdrawal by subject, so a decision by the patient. A lot of folks who cited kind of family or logistical reasons that might have been associated with the pandemic, as well as COVID-19 itself. We did have two patients who met the withdrawal criteria, i.e., they had the decline in lung function or cough that made them unable to perform the spirometry. I think that and that matches well with the study design too. The study design was asking patients to come back to clinical sites very often in the first 12 weeks, every other week, and that was, in hindsight, you know, a bit of a burden on patients. That's you know, that picture is then consistent. I think the first piece is you kind of feel like you understand, you know, kind of logically why this might have happened in the context of the pandemic. I think the second thing then is looking at the baseline characteristics of the patients who withdrew from the study versus those who stayed in. There, you don't see any kind of significant difference, maybe setting aside those two patients who did withdraw due to meeting the criteria to having the drop in FVC and the cough that made them unable to perform spirometry. You also then actually look at the FVC trajectory of the patients who withdrew, they weren't pulling the data set down. The trajectory of the patients as they withdrew was actually in line with the patients who remained on the study. You basically have kind of it all kind of moves together, and then you have these patients discontinuing rather than kind of some sort of data set that was pulling things down. It's a nice way from several angles to get a little bit of comfort that we understand why this happened, these patients don't look different, and they weren't really pulling down the data set. The final piece of the puzzle, as I mentioned, was kind of the synthetic control arm analysis that got us to an imputed number of 20- milliliter improvement in lung function, and that 20 ml is, of course, different than the 200 ml. The exercise that's behind that is basically to say: What if we're wrong? What if actually these patients, as they discontinued, would've performed thereafter like a placebo patient? Basically, the imputation analysis that gets us to that + 20 ml is very conservative in the sense that it assumes that every patient, as they discontinued, then had a placebo decline. Even if you assume that, you still get to a statistically significant result relative to the synthetic control arm. It gives a lot of conviction that we have a true clinical signal here, notwithstanding it being a bit of a smaller study, run in the context of the pandemic. Okay. Really helpful. Appreciate that. Just to highlight for you guys, I know cash was on one of the first slides, but cash and runway, and where that gets you in terms of timing of top-line data from the ongoing phase II-B. Yeah. At last report, we had approximately $140 million cash balance, U.S. dollar cash balance, which is sufficient capital for us to complete this study. We'll complete enrolment of this study in the first half of this year, planning to report top-line data in this ongoing phase II-B study in the middle of 2027. The capital's also sufficient for us to have OpEx for a year thereafter. Just to clarify, cash is OpEx post-data for a year? Exactly. into mid 2028. Okay. mid 2028. Obviously, that doesn't include a new study or anything like that? No. Yeah. Okay. Sufficient cash to read out data, which, obviously, if it's positive, will put you guys in a very good position. Any comments, just very briefly, on what you're doing beyond buloxibutid, in IPF or other work there? Yeah, absolutely. As I mentioned at the outset, you know, our view is this mechanism can be broadly applicable, like it is a highly conserved mechanism of action. It comes into play across a broad range of fibrotic and inflammatory conditions across different organs. Certainly in the lung, we think about the pulmonary hypertension space, but then outside of the lung, we also think about a number of fibrotic and inflammatory conditions, including in the renal space as well. Okay. All right. I think I am up on questions. Ahmed, great presentation and update on the program. You know, it's a long road, and you guys have stuck with it and continued to sort of refine the story and the data picture. Really looking forward to the updates as they become available. Thanks, Jeff. Appreciate it. All right. operator, you can take us clear.