Good morning, everyone, and welcome back to day dwo of Oppenheimer's 35th annual Healthcare conference. I am Jeff Jones, one of the senior analysts on the biotech team, and I'm delighted to welcome Vicore Pharma and their CEO, Ahmed Mousa, for a presentation on the company's lead program in IPF. Ahmed, I'll turn it over to you. Yeah, perfect. Thank you, Jeff, for the introduction, and thanks certainly for hosting us and allowing us to have the opportunity to tell you more about our mechanism of action for resolution of fibrosis and our lead program in IPF. Before I start off, I'll just refer to the typical forward-looking statement disclaimers. Just to give a quick introduction to Vicore, we're a team that's spread across Stockholm, Sweden, where we're headquartered, Copenhagen, and Denmark, as well as in the Boston and Cambridge area where I'm based. We're about a SEK 200 million market cap company. We're listed on the Stockholm Exchange publicly, and we have about SEK 125 million cash position as of the end of the third quarter. We're really fortunate to be backed by a broad base of specialist investors in both the United States and Europe. As you mentioned, Jeff, our lead program is in IPF, where we've initiated last year a large phase 2b study. The name of the therapy there is buloxibutid; it used to be called C21. Excited to tell you more about how that study is going. We have a partnership with Nippon Shinyaku on Japanese rights for that program. We're also advancing follow-on compounds in this pathway that we think can be efficacious in a range of fibrotic diseases and excited to talk about that more over time as well. A lesson focus for us today is a digital therapy for anxiety associated with pulmonary fibrosis in our portfolio as well. First, maybe to talk a little bit about the unmet need and the commercial opportunity in IPF. It is a deadly disease when patients are diagnosed with IPF; the survival, unfortunately, is only three to four years, and that's despite two currently available therapies, pirfenidone and nintedanib. Those therapies, in addition to having a limited efficacy in this disease, they also have a significant tolerability profile. They cause gastrointestinal side effects as well as other side effects that make it difficult for patients to stay on therapy as well. As a result of these features, actually, only about a quarter of patients in the United States initiate treatment with the currently available antifibrotics, and there's a high discontinuation rate, short time on therapy, average treatment duration of only 10 months. Notwithstanding that, the market is, as of last year, over $4.5 billion estimated to continue to grow. It is, in addition to being a high unmet need, a significant commercial opportunity. Really what's needed here is drugs that are both more effective, right, that take this disease from one that has such a poor prognosis and one that patients can live longer with, with a higher quality of life, and also therapies that are better tolerated that the patients are able to take with less difficulty. That is maybe where our approach then comes in. We're really excited to be advancing a mechanism of action that's quite unique relative to both what's currently available as well as what's in the clinical development pipeline. It's an upstream mechanism of action that has a really strong translational data set, and it is designed to agonize a receptor on a precursor cell in the alveolus to drive a mechanism that induces alveolar repair, reduces and resolves fibrosis in the interstitium, and addresses the vascular dysfunction associated with the disease as well. Consistent with this upstream mechanism of action, we have a really nice phase 2a data set that reflects an improvement in lung function by over 200 ml over a 36-week study. Showing that we have the ability with this phase 2a study to not only stabilize lung function, but also improve it and do it in a durable way over a more extended period of time. We also were very pleased to see in this phase 2a study, and consistent with other studies of this molecule that we've conducted, a nice tolerability profile, no treatment-related significant adverse events. We don't have the GI tolerability issues that are associated with both the standard of care as well as some of the emerging therapies. That final phase 2a data set we reported last year. Last year, as I mentioned, we initiated a phase 2b study. This is really to, as best as possible, confirm the clinical activity that we observed in the phase 2a. It is designed with the regulatory endpoint of a 52-week treatment period, relatively large size for a rare disease like IPF, 270 patients, 90 per arm, and will be allowing patients who are on background therapy and nintedanib or not on standard of care and running this study across a number of different countries. Maybe to talk a little bit more about the mechanism of action that we're approaching here. In this schematic of the angiotensin II pathway, the therapy that we're working on agonizes this AT2 receptor that's shown here in orange on the right. As part of the angiotensin II pathway, there are really the AT2 receptor and the AT1 receptor. In a simplistic way, you could see them as opposing forces. The AT1 receptor is one that drives a set of hypertensive, inflammatory, and fibrotic processes within the body. This is the body's natural rescue system. When you have a drop in blood pressure, other types of injuries, insults, or infections, the system kicks in quite quickly through angiotensin II peptide release in order to drive this type of activity. Inhibiting this pathway has actually been a serious drug development effort historically because aberrant signaling on this pathway can cause increased hypertension, increased blood pressure. The development of ACE inhibitors, which block conversion of angiotensin I to angiotensin II, or angiotensin receptor blockers like losartan and the rest of the sartan class, was designed to really block this side of the pathway. Highly underexplored then is actually this opposing force and maybe looking at activating the side of the pathway to resolve fibrosis, drive vasodilation, as well as mediate anti-inflammatory processes. That is what we are really looking to do here with a selective AT2 receptor agonist through the molecule that we are advancing. Maybe when we put this then in the context of the lung, this is a cross-section of schematic that would be a cross-section of the lung, and this would be the alveolus or the air sac. This is the pulmonary capillaries that need to be oxygenated in order to allow patients to be able to have a normal gas exchange process. You have kind of the interstitium or the space in between where in IPF there's typically a fibrotic buildup. IPF as a disease is one that involves injury to the alveolus and in particular injury to the epithelial layer of the alveolus that drives a runaway wound healing or scarring process in the interstitium. That process really hits this epithelial layer, and it hits these alveolar epithelial type II cells, which are a cell type that's a precursor cell responsible for replenishing the gas exchange capability of the alveolus. It allows patients to be able to, or sorry, individuals to be able to have effective gas exchange. It also produces what's called surfactant protein in the air sac as well. This is a protein that is critical for maintaining the integrity of the alveolus and ensuring that it can withstand the surface tension associated with water. When you have injury to these type 2 epithelial cells in IPF, the first two things that happen is you stop the ability to maintain the cells that do the gas exchange because these cell types are the downward lineage of the type 2 epithelial cells. You also have, unfortunately, a loss of surfactant production. Actually, what that does is it causes these alveoli to then collapse due to the surface tension of water. In IPF, there's a notion that even before you have a buildup of fibrosis, you actually have some loss of lung function due to this prefibrotic alveolar collapse due to the damage that the disease state is causing. In addition to that, you have a loss of some of that gas exchange capability. The inability for oxygenation, even from the kind of epithelial layer of the alveolus. The disease is so much more insidious than that because when you injure these type 2 epithelial cells, they're actually one of the key cell types that mediates the wound healing process. They actually are a cell type that are a key trigger that release TGF beta-1, which is widely recognized to be a profibrotic cytokine that orchestrates the buildup of fibrosis in the lung interstitium. When these injured cells then start releasing TGF beta-1, you have an activation of these fibroblasts. They migrate into the lung interstitium. They proliferate. They then transition into what are called myofibroblasts. And myofibroblasts are the cell type that deposit collagen or build fibrosis in the space between the pulmonary vasculature and the alveolar compartment, which frustrates the ability to have oxygenation of the blood supply. In addition to that, IPF is also a disease that's known to involve vascular dysfunction. You have vasoconstriction, you have a thickening of the blood vessel walls in a way that also frustrates the ability to oxygenate blood. It is a really tough disease, and it really involves more than just buildup of fibrosis in the interstitium, although that's a key part of the disease. The question is then, what happens when we agonize this AT2 receptor that's sitting on these precursor alveolar epithelial type II cells? First and foremost, our mechanism drives a functionalization signal to these type II epithelial cells. They're able to continue to survive, proliferate, and actually fulfill their normal function, which is releasing surfactant protein. You can then have maintenance of the integrity of the alveolus and avoid that alveolar collapse that we mentioned. It also then allows a replenishment of the gas exchange epithelial cells, the type I epithelial cells, which are a downward lineage. You maintain that or replenish that gas exchange capability. Next, when you refunctionalize this cell type, you attenuate the wound healing signal. You are essentially now downregulating the expression and signaling via the TGF beta-1 pathway and its downstream consequences, which means you have reduced fibroblast activation, migration, transition to myofibroblasts and collagen deposition. A third piece of the puzzle is that in IPF, there's known to be a downregulation of collagenase matrix metalloproteinases. These are specifically enzymes that would otherwise be available to digest or chop up collagen. There's evidence that this mechanism of action would drive an upregulation in order to not only stop new fibrosis from building, but also resolve fibrotic build that's existing currently. Finally, the mechanism of action has an effect on the vasculature. It's known to be a vasodilator. It's part of its natural role to be a response to that hypertension signal. It can drive local vasodilation and resolution associated with the remodeling of the vasculature and the endothelial layer in that compartment as well. We really think that this is a nice approach and an upstream and comprehensive way to go after the disease. It's a little bit different than some of the other approaches that we've seen in this space where really there's certainly not invalid ways to go after the disease where you identify receptors that might be or targets that might be associated with the build in fibrosis and you try to block those. We have some examples that are here. Certainly that antagonistic approach is quite valid. There are successful drugs that have gone there, but we think that this might be a way to go beyond in terms of driving a better efficacy signal. I think that it provides greater dosing flexibility. When you're trying to antagonize factors that might be associated with wound healing process, it might be the case that you need to really strongly antagonize in the sense that you have 24/7 target coverage. You're making sure that your dose is sufficient, pharmacokinetics at all times, and also that you're able to have full receptor occupancy, which can be a challenge as well. One of the other challenges associated with selecting antagonism of targets that might be associated with wound healing processes is some of those targets can also be associated with normal processes, including maintenance of extracellular matrix and tissues. When you think about the expression of the receptors that are going after, in some of these cases, the emerging therapies and even existing therapies have a broad expression profile in the body. This might be one of the issues that relates to then having some of that on target, off-tissue signaling that leads to tolerability issues. One of the reasons why we're so excited about driving an endogenous tissue repair system is also that this system in particular is usually upregulated only in the disease contexts. The expression profile in a normal person, which is kind of shown here on the left for the AT2 receptor gene from the protein atlas, is quite limited largely to the lung. I think this also can allow for an advantage as well in terms of driving therapeutic efficacy in a tolerable way. In addition to kind of the principles by which we think that this will be a well-tolerated therapy, we're also pleased to have a safety database for this drug. Actually, over 350 individuals who've been dosed for various periods of time, up to about nine months in the 36-week phase 2a AIR trial. We've not identified to date significant safety risks associated with the therapy. That's been quite heartening. Maybe from here, I'll go into our phase 2a dataset in IPF. I will talk a little bit about the AIR study, which was an open-label 36-week study where IPF patients who are treatment naive were enrolled and spirometry was taken quite frequently, as you can see here with FVC measurements to measure the change in lung function from baseline out to 36 weeks. In terms of the baseline characteristics that we enrolled, you'll see on the left-hand side the baseline characteristics for our phase 2a AIR study. We have put on the right-hand column the baseline characteristics of the phase 3 studies that led to the approval of one of the two standards of care in nintedanib and of the INPULSIS trials. In terms of age, gender, and in particular, baseline percentage predicted FVC, we were quite nicely in line with the phase 3 studies. Our study did enroll more out of India, so you will see that we have a larger Asian population in our study. Like the INPULSIS studies, we utilized treatment-naive patients in the trial. Next, in terms of the adverse event profile, as we mentioned, on the right-hand column, you can see this. The 36-week AIR study had good GI tolerability, so we did not see a signal there, which is contrasted with nintedanib and you can see kind of in the left-hand column, 60% diarrhea as well as other types of gastrointestinal side effects. We were pleased to see a low rate of exacerbations and cough worsening. No drug-related serious adverse events were observed in the study as well, which was quite nice. In addition to the tolerability profile over the 36 weeks, we were very pleased to see then also an outstanding efficacy signal where we had ultimately at 36 weeks an over 200 ml improvement in FVC from baseline, which is quite a contrast to what you would expect untreated patient population with IPF to do with 180 ml decline. This reflects a signal that potentially a disease-modifying therapy. It was nice to see that this effect was robust outliers. 65% of the patients had improvement in lung function at 36 weeks, which is contrasted with what you might expect on standard of care, 25% in, for example, cases of intent trials, as well as really what you'd expect, a natural population who's not undergoing treatment, expecting only a single-digit percentage of patients out that far to have stable or some modestly higher lung function level. Recently, just a few weeks ago, we were pleased to get a fast-track designation to further expedite the development of our program. Really what we have ongoing now is a phase 2b study. We call it Aspire. As I mentioned, it's a randomized double-blind placebo-controlled study. We are including patients who are on intent standard of care, not on standard of care. We are investigating both the same dose as the phase 2a, 100 mg twice daily, as well as a lower dose, 50 milligrams twice daily. We will be assessing the primary endpoint as change in FVC from baseline at 52 weeks, which is a regulatory endpoint for IPF. We are pleased to be running this study across approximately 100 sites across 14 different countries to really have broad distribution patient population. While we observed an outstanding effect in the AIR trial in terms of an improvement in lung function, we are also conservatively powering the phase 2b ASPIRE study relative to that to detect 80% power to detect 125 ml difference between treatment arm and placebo. That would represent a stabilization of lung function under the assumption of a very mild placebo arm because certainly in a disease state like this, it would be very attractive for patients and a significant commercial opportunity to have a therapy that could stabilize lung function as well. Maybe I'll stop there and happy to take any questions, Jeff. Sure. Thank you for that, Ahmed. Just a quick, in terms of the ASPIRE trial that is running now, have you provided any updates just in terms of where you are in enrollment? I don't recall quite when you opened the study, so have recently has that opened? Yeah. We opened the study in Q3. It's a little bit early to start guiding on enrollment progress. We're, of course, opening across the 14 countries, and those are largely open. Then opening the sites, we have a number of sites that are open as well, but it's still a little bit too early to project out time-wise. Okay. In terms of study design, the AIR study, as you noted, these patients were all treatment naive. Are these patients in the ASPIRE trial also treatment naive, or will you include standard of care or access to standard of care? Yeah, we will include access to standard of care. Patients who are taking standard of care will be permitted to join the study. We anticipate that that subpopulation or that population will be 70%-80%. The bulk of the study will be patients who are on standard of care. We will also anticipate having 20%-30% of patients who are not currently taking standard of care, though that's not necessarily treatment naive, right? It could be patients who decided to discontinue either nintedanib or pirfenidone. Okay. All of that makes sense. In terms of, I mean, you spent a fair amount of time on the mechanism of action here, which is really intriguing. Do you have, again, the challenge with IPF studies is obviously the timeframe, not only to recruit them, but then that 52-week endpoint. Is there work you can do in the interim in models or precision cut lung slices from IPF patients or otherwise that could help provide further confidence in the mechanistic rationale here in the biological impact in addition to what you've generated in the phase 2a study? Yeah, absolutely. Actually, while I don't show them here for time, we have generated a significant translational dataset that supports some of the points that I was making here about what our mechanism does. For example, you mentioned precision cut lung slices. These are, for everyone, thin slices of human IPF lung tissue from IPF patients who are going to get a lung transplant. You can actually add your drug and see what it does to different things. I talked about our ability to, for example, increase surfactant production. We've observed that in precision cut lung slice models where we apply clinically relevant concentrations, i.e., the same range of concentration we'd expect a patient to be able to get into their lung after taking the doses of our drug. We see that elevation in surfactant production on the kind of human IPF lung slices. As another example, I mentioned that by functionalizing these type II epithelial cells, we stop them from giving that kind of wound healing signal and that TGF beta-1. Again, we see that significant reduction in TGF beta-1 production in the precision cut lung slices. As a third one, we talked a little bit about the collagenase MMPs. Again, here we have studies where we're able to elevate those enzymes that are able to digest the collagen and address the existing fibrosis. I'll also say we've seen some of those same signals clinically. When I talked about the AIR trial and the effect that we have on FVC, we have this improvement in lung function, but also at the same time, we took blood samples from these patients and we saw a trend over the 36 weeks in decrease in systemic TGF beta-1. It is known from prior studies that on average, patients with IPF do have elevated blood levels of TGF beta-1. When there's this increase in the lung, it's probably spilling over into the periphery. It's nice to see this trend where we can bring it down. Also, a really significant impact on one of the key collagenase matrix metalloproteinases, MMP-13, where we elevate levels of that collagenase, evidence that you're able to have an effect on resolving the fibrosis in the blood of these IPF patients over the 36-week treatment period. I would say, in addition to having a nice translational dataset, we also have some nice correlations to what we're seeing in the phase 2a study in the clinic. Of course, we're looking forward to doing even more work. We're thinking about how we compare or put side by side maybe our therapies with some of the emerging therapies, maybe even look at some different combinations over time as well. Okay. Great. Could you highlight for us where you guys sit financially from a cash position and view to runway? We look at the study that you're running now, I would guess data maybe in 2026. Where do you sit from a financial runway perspective? Yeah, absolutely. We did an $85 million financing round late last year. Fortunate to have the support of our current shareholder base, including HealthCap, one of the great specialists out of Sweden, HBM Healthcare Investments, as well as Invus, Redmile Group, and then bring in new investors, including Sanofi's corporate arm, making an investment in us as well as Capital Group. That places us as of the end of the third quarter at about $125 million cash position. That is sufficient for us to be able to achieve the phase 2b readout and have additional cash runway thereafter. We're financed for this phase 2b study. All right. Great. You mentioned you have some follow-on compounds being advanced as well. Are those things you anticipate taking into the clinic in the meantime? What other indications might you think about, or are you thinking about IPF as well there? Yeah, absolutely. What's nice is this upstream fibrotic resolution system that we talked a little bit about. It's not unique to the lung. It's actually quite a highly conserved system across mammalian species. It's also one that plays a role in a number of other organs. I would certainly say we are looking at a number of indications. We're capitalized to take the next program into phase 1 development. That's something that we would anticipate doing over time. We're quite intrigued by the potential to meet some very serious unmet needs in other organs as well. In particular, we're looking at, in the cardiometabolic space, chronic kidney disease and diabetic kidney disease as something that we might pursue in the future. That's certainly something to stay tuned on. In the lung, in addition to kind of the focus on interstitial lung diseases, we also, as I mentioned, have a robust effect in our translational models and as part of this mechanism of action on the vasculature. We also think about the broader range of pulmonary hypertension as potential places where this mechanism of action can play a significant role. Got it. Okay. Great. Ahmed, I think we are up on time. Really appreciate the time this morning and the update. I hope you have lots of great meetings today. With that, we will call it a day. Wonderful. Thanks for having me, Jeff. All right. Great to have you, Ahmed.