All right. Good afternoon, everyone. Thank you for joining, those of you in the room, as well as those of you on the webcast. My name is Faisal Rashid. I'm one of the senior biotech analysts here at Jefferies. I'm very pleased to have with us today management team of Vicore Pharma. We have CEO Ahmed Mousa, CMO Bernt van den Blink. With that, thank you for being here. Ahmed, can I ask you to please introduce the company? Absolutely. Thanks for having us, Faisal. Vicore Pharma is a company that's focused on fibrotic diseases, and in particular, we've zeroed in on pulmonary fibrosis and IPF as a lead indication. The way we're going after pulmonary fibrosis is very different than others. Pulmonary fibrosis is a disease where you have injury to the epithelium, injury to the air sacs, the alveolar compartment, and that injury is what triggers then both fibrotic process as well as vascular dysfunction. A number of the companies that have developed therapies for IPF have gone after the fibrotic buildup. Actually, before the fibrotic buildup, there's this epithelial injury, and it's that epithelial injury that induces the fibrosis that is the key driver of fibrosis. We are going towards the source of the disease in our view, and we're addressing the epithelial injury by agonizing a receptor that's highly expressed on precursor cells on alveolar epithelial type 2 cells. Basically agonizing this target on this cell type allows you to refunctionalize this cell type, drive its reproliferation, so you bring it out of a senescence state and essentially allow it to attenuate the pro-fibrotic drive. The mechanism that we're going after also drives resolution of fibrosis. It's not just about renormalizing the injured cells so they're not driving TGF-beta 1 and other pro-fibrotic cytokines, but also actually upregulating collagenase matrix metalloproteinase production so that you can resolve existing fibrotic matrix. Finally, this is a mechanism of action that is vasoactive, and it drives a resolution of the vascular dysfunction that is associated with idiopathic pulmonary fibrosis, which I think is becoming increasingly recognized. We are really excited to develop this program, which has shown a great preclinical data set, has shown a really nice phase IIa signal in a small open-label nine-month study. We have shown improvement in lung function over a long-term, which is essentially unprecedented in IPF. What we are really excited about right now is an ongoing 52-week phase IIb study in IPF, which is enrolling about 400 patients, recently completed enrollment, and we are looking forward to reading out next year in the middle of the year. Got it. I remember the first time I met you, Ahmed, we talked about your phase IIa AIR study. If you remember, the question I asked you was, single-arm study in IPF, that's kind of different. Convince me on why and how we can believe this. I want to ask you that question again. Yeah. Walk us through that study and the key findings and what you take away from it? Absolutely. Right, in an IPF setting, typically these studies are run placebo-controlled. This study was a little bit different in that it was run open label setting. I think what was really excellent about this phase IIa study is it studied the drug over 36 weeks. Most IPF phase IIa studies are 12-week studies, and 12 weeks, in our view, is insufficient to fully understand the effect of a therapy for pulmonary fibrosis, because inflammation is also part of this disease and what you're measuring in IPF trials is forced vital capacity or essentially milliliters of lung capacity. If you reduce inflammation and you reduce swelling, you can provide for a positive impact on FVC in the short-term, but over the long term, there's still the potential for that fibrotic buildup to overtake it. What we see with our Phase IIa data set is not just a quick effect on forced vital capacity, but rather a slow initially stabilization followed by improvement in lung function. Of course, I know that folks become more comforted when they see a placebo arm in a trial, and it certainly is something that I agree with. At the same time, the effect size that we observed and the signal that we observed, one of improvement, is something that's quite distinct from what you'd expect an IPF patient to do over that nine-month period. No matter what kind of placebo arm you have, there's a true signal of clinical efficacy. We actually confirmed this recently by running a large synthetic control arm analysis where we essentially did placebo-matched patients who are placebo group matched on baseline characteristics to who we actually ultimately enrolled in our phase IIa trial. We confirmed that what you'd expect happens, right? That this synthetic control arm has a decline in lung function, a significant decline in lung function, and that's quite contrasted from what we observed in our phase IIa. Again, I think that this improvement in lung function ties back to this mechanism of action, which is very different from others that have been developed in the field. Got it. Going back to that mechanism of action, the nine-month duration I think is important because part of the mechanism of the drug, as you mentioned, could be just that it's vasoactive as well. Is it your view that nine months allows you to see beyond just the vasoactive part of the mechanism and into true disease modification as well? Is that a fair way to think about it? We think so, and there's evidence of that. For example, there's a matrix metalloproteinase, a collagenase called MMP-13, and there's been a number of studies that have shown that this is an important enzyme for digesting existing fibrotic matrix. It's part of that resolution of fibrosis or fibrolytic effect. What we see in our phase IIa trial is that we increase significantly across the 36 weeks MMP-13 expression in the periphery of the IPF patients who are enrolled in our study. That's nice evidence that we're driving exactly these mechanistic features that we believe can have a disease-modifying effect. Got it. Okay. Then with respect to the phase IIa, the patients that were enrolled in the study, how did that compare to comparable studies that have been run contemporaneously in the IPF landscape? Yeah. Why don't I let our Chief Medical Officer, Bernt, talk a little bit about that? Yeah, sure. This study, as you may know, was enrolled in regions where we were seeking patients who were not on standard of care, who were treatment-naive, to be able to get a very clear and clean signal. We enrolled the study in India, Ukraine, Russia, and the U.K. Unfortunately, during the study, Russia invaded Ukraine, and those sites were taken out. Three-quarters of the patients were enrolled in India. Obviously, we were looking at how representative are these patients, and we've done some initial analysis that we just presented at ATS. Basically what we can see is that both on baseline characteristics, but also when we look at HRCT patterns and HRCT sort of representations, these patients really match a global external data set quite well. We do see some minor differences. We see, for example, that the lung volume is a little bit smaller in India patients, but that is well expected and explained by also a slightly different, slightly smaller height in the patients from India. What we found remarkable is that the patients actually overall had very similar characteristics, fit very well in the global distribution. We did find the patient had a little bit more fibrosis. That surprised us a little bit, but I think in the end, we see this as a quite positive signal. In the past, we've heard sort of some concerns in the field that patient advanced fibrosis might be beyond repair, but actually these patients with somewhat more fibrosis actually are the patients where we're also seeing quite some impressive improvements in FVC. I think underlying the potential for real meaningful clinical benefit of buloxibutid in these patients. Got it. Ahmed, you mentioned some of the effect that the drug is having on the matrix metalloproteinase. I think you guys also did some interesting translational work on vascular remodeling and other kind of proof of mechanism type of studies. Could you walk through a little bit of that? Yeah. On the vascular side, first of all, this receptor that we're activating, the angiotensin II type 2 receptor, sits in the angiotensin pathway. It's not a surprise that it's vasoactive. Essentially what it does is it drives a local vasodilation. It's the opposing force to the AT1 system in the body. We see the really nice benefits of that local vasodilatory, along with kind of addressing the vascular dysfunction associated with the disease across a number of models. For example, we take a classical model of pulmonary hypertension, the Sugen/hypoxia model. This is a model where the pulmonary vasculature is injured, and that basically causes the vessel walls to thicken, and that causes then the lumen or the space of the vessel for blood to flow to decrease, and that's what causes then ultimately that hypertension. That also causes interstitial pulmonary fibrosis because when you injure the endothelial compartment of the vessels, they start spitting out TGF-beta 1 and other injury signals. What we see in the Sugen/hypoxia model is we're able to address the vessel thickness. We're able to bring that down to a more normal state. We're able to address the lumen size to kind of re-bring that. We're also able to address the follow-on pulmonary fibrosis that exists as a result of that vascular injury. I think where the really nice connection, and we actually have data in the same setup with treprostinil. What you see is the effects are similar in the Sugen/hypoxia model, and I think also it ties nicely to what United Therapeutics has shown in the TETON-1 and the TETON-2 results, that a drug that has a vascular effect can also have an effect on FVC in an IPF setting. That's because we believe that as fibrosis builds in this disease state, it drives the vascular dysfunction, and that vascular dysfunction drives actually more pulmonary fibrosis, sort of like a vicious cycle. The ability to intervene and to address that kind of remodeling of the pulmonary vasculature, we think ultimately will be hugely beneficial in IPF directly. Got it. Maybe a slightly off-topic question, just given investors are very laser-focused on your phase IIb and IPF, but given what you're describing here on the mechanism, we saw inhaled treprostinil start out in PAH, then go to PH-ILD, and then now have positive results in IPF. For you guys, it seems like you'd almost do the opposite. Have you thought about the potential of the drug in PAH and exploring that hypothesis? I think that's exactly right. I think that's something that's very actively on our list. I think that there are a number of reasons why from a mechanistic and a principles-based perspective, we think we can play very well in both Group 1 and Group 3 pulmonary hypertension. I think whether we ultimately go for those disease states depends on a number of different factors. Certainly what's really nice is the ASPIRE Phase IIb study in IPF is still an opportunity for us to look at different signals and clues on whether we believe we'll be able to have an impact on pulmonary hypertension. For example, we're taking baseline high-resolution CT scans from all of the patients, then we're taking scans at the end of the 12-month dosing period, and they're actually ways of imaging and quantifying vessel features. This can give us some clue on how we're impacting the vasculature in this relatively large patient population. We can also look at peripheral biomarkers like BNP to see how we're playing as well. We think there'll be great principle and great starting point, but also maybe some nice clues from our phase IIb study as well. Interesting. Yes, that truly is like the opposite of what United Therapeutics did where they found IPF within their ILD study. Exactly. Yeah. Interesting. Okay. Let's zoom in then on your Phase IIb ASPIRE study. You mentioned you recently completed enrollment of the study. Can you remind us the trial design for that? Yeah, sure. The ASPIRE Phase IIb study is a global, very robust, randomized, placebo-controlled study. It has enrolled ahead of schedule. We've enrolled a total of 378 patients across U.S., approximately 25%, Europe approximately 25%, Australia and Asia, South Korea and Taiwan, and South America. Two doses that we're investigating versus placebo randomized in a 1:1 ratio. It's a 52-week study. It's a really very considerably large study. Primary endpoint FVC, key secondary endpoint very similar to the TETON study, including exacerbations, death, and 10% FVC decline. Next to that, we're of course looking at all the relevant domains, quality of life including cough. As Ahmed mentioned, we're looking at HRCT parameters both to look at underlying fibrosis. Are we really modulating the fibrosis, but also exploring vascular events with vascular volume and remodeling. Got it. I believe you had upsized the study while you were midstream in the enrollment. Can you remind us the reason for upsizing the study, and what the powering assumptions were for the study both before the upsizing and after the upsizing? Yeah. First of all, thematically, I think we designed this study in the middle of 2024, and I think that as the landscape evolved and we continued to look at other therapies, we candidly realized how low the bar was, right? It was great to see a new therapy approved in nerandomilast, at the same time a relatively incremental effect on lung function, particularly a relatively incremental effect at 52 weeks relative to the 12-week data set that they had produced previously. In addition to that, a continued reminder of how important tolerability is. The inhaled treprostinil showed a nice effect, but a relatively high discontinuation rate and feedback from clinicians that tolerability and ease of use for this patient population was very important. That made us more enthusiastic about our therapy because it overall has a good tolerability profile, and we really want to make sure that we don't miss out on an opportunity to provide for patients a therapy that would be quite meaningful for them. Essentially the idea was to increase the sample size so that we can detect a broader range of effect sizes, ultimately an effect size of around 80% power to detect an effect size of about 95, 96 ml difference in lung function between the placebo and the treatment arm, which we think would be certainly a transformational type of effect when combined with this tolerability profile. Got it. Okay. The idea was that if you want to be able to show stat sig at a lower level that would still be competitive with what you were seeing coming out from some of these other studies? Exactly. What we also saw along the way between design and readout, in addition to seeing FIBRONEER having an approximately 70 mL impact on lung function, we saw unfortunately the Pliant program not working out, Horizon Amgen having an IPF therapy that unfortunately didn't work out. BMS, after we'd started to look at our design, put out their phase II data for their LPA1, which was relatively incremental. We're of course looking forward to their phase III results as well. I think it really underscored that there was really an opportunity here across a range of effect sizes that were broader than what our initial powering had indicated. Got it. That makes sense. Just to ask you a sort of tricky question here. Given the bar that's been set by FIBRONEER is admittedly pretty low, and especially with that tolerability profile, what is the goal in ASPIRE? Must it be stat sig or? Because the way I think about it is if you show an outcome where it's 90 mL difference, clean profile, misses the stats, I would look at that and say, "That looks like a drug that should go to phase III. That's a great question. I would say as a publicly traded company, we hope to be not put into that position. It is a phase II. There's still a phase III after. The idea is we power it so that people can understand what the effect is, we can understand what the effect is in a confident way. Recall that the TETON studies were approaching 600 patients enrolled. Our ASPIRE study's approaching 400 patients enrolled for a phase II. We do believe that this will be a solid basis for us to understand what the drug is doing. I think we'll be able to hopefully get alignment with the clinical and the investor community around that as well. Got it. When FDA says it will be a review issue, I feel like that's kind of the answer you're giving me. In terms of background therapy, Bernt, you had mentioned that in the phase IIa, you guys had tried to run that study in a clean way with no background. Right. Can you explain how you're treating background therapy in the phase IIb? Yeah, absolutely. We are allowing patients to be not on background therapy. That can be both treatment-naive as well as patients who did not tolerate pirfenidone and nintedanib in the past. We're allowing patients to enroll in a stable dose of background therapy, which is either nintedanib or nerandomilast. We did allow nerandomilast when that got approved in the U.S. In all fairness, it's only going to be a handful of patients. In this study, we have not allowed pirfenidone as we have a potential drug interaction with pirfenidone that we're still assessing whether we can and will allow that in phase III. Also taking into account sort of the relevance of pirfenidone by the time we go to market. Great. Do you have an expectation for the proportion of your study population based on the geographies and what you're seeing in the enrollment proportion that would have background therapy, and whether or not that will have an impact on the study? That's a good question. We set out to enroll at least 25% not on background therapy to be able to clearly assess if our drug is effective as monotherapy and also position it as a first-line treatment or a first monotherapy treatment. What we are seeing in our baseline characteristics and demographics is about 40% of patients are not on background therapy and 60% is on background therapy. What we have learned over the last year is that these patient populations behave a little bit differently than we had for a long time expected. We had expected that if you are on nintedanib, for example, you would have less decline in FVC. What we're very consistently seeing across all late-phase studies is patients on background therapy actually in the placebo arm show considerable decline. That means also that we know and expect, I think quite comfortably, that there will be sufficient window in placebo decline in both strata, in both not on background therapy, on therapy, sufficient window for us to assess the treatment benefit of buloxibutid. Great. Two things to talk about. While we're in this waiting period between the study enrollment completion and the results from the study, given it's a one-year period, some companies have had the chance to present their baseline characteristics data. Is t hat something that you guys are planning to do? Yeah, we are. We have submitted an abstract on baseline characteristics. We hope to present that in one of the fall larger respiratory meetings. We're fully expecting to be able to share that after the summer. Yeah. Got it. Okay. You guys had also disclosed that you do have an interim futility analysis built into the study. Can you explain to us how that works? Yeah, sure. We have planned on doing a futility analysis when approximately 30% of patients, or about 100 patients, have completed the study. This analysis will be done over the summer. It will be a blinded assessment for us. Our independent data monitoring committee will perform the analysis of this, and they will do that in the broader context of their duty to do a risk-benefit assessment. They will review all the available safety data, as they have done in the previous three DMC meetings, which all have gone in a very positive way, recommending to proceed without any modifications. The futility analysis is primarily there to make sure that we are not continuing the study if there is no benefit, or worse, if there will be a detrimental effect on patients. We do not expect that based on our prior DMC meetings and review of the blinded study data. On the other hand, it's also not an insignificant step. We do know that number of IPF trials have had to stop because of safety issues. We do see it as an important de-risking step in the progress of our study. Got it. When do you expect public disclosure of the results of the futility analysis? Early Q4. Got it. Okay, great. The IPF landscape has certainly evolved a bit in the last few years. Can you just comment on, in terms of the other programs that are in phase II and phase III, how you guys are seeing the competitive landscape and your position within that competitive landscape? Yeah. Again, I think that one of the key priorities in the clinical community is better-tolerated therapies, and I think there we're excellently positioned. We don't have the GI side effect associated with some of the standard of care therapies as well as some of the emerging therapies, or a cough profile, headache, flushing, other types of issues that have been observed with some of these emerging therapies. I think that's a really nice foundation both to get the clinical community excited about deploying buloxibutid in the future, if successful on the efficacy side, as well as making it a great initial combination partner for other therapies as well. I will note that we have an observation in the phase IIa of about 19% hair loss or hair thinning that's mild to moderate. It's reversible, and it's something where the clinical feedback has been that this is overall quite manageable in view of the profile of the other therapies as well as the patient population and the severity of the disease. We're quite excited with that kind of building block as a basis for then also looking at what we can do on the efficacy side, where again, I would say the therapies that we're looking at are ones that slow the decline of lung function and carry a lot of tolerability liabilities. There's one more phase III that we'll read out prior to buloxibutid. That's the ALOFT Phase III trial of the LPA1 antagonist that the BMS will do. It'll be very interesting to see what that overall profile looks like. I would say that based on the phase II data, the general expectation is, if positive, these are therapies that will still be more in the slowing decline of lung function and incremental efficacy zone. I think that there's a ton of opportunity to have a really nice impact in view of that landscape. Got it. How do you see the interplay between oral and inhaled therapies in IPF? Yeah. I think that as an oral therapy, we're quite well-positioned, right? I think that polypharmacy for oral therapies is quite straightforward. We're an easy-to-take twice-a-day therapy. I think that when you think about inhaled therapies, that certainly can be added on. I think that a question of how convenient is that particular therapy, like is it a dry powder versus a nebulized, how many times, how many sessions, will be, I think, relevant to the uptake of different potential inhaled therapies. I also think that as more inhaled therapies come through the development pipeline, there will probably be some question around whether polypharmacy in an inhaled setting will be possible. I think depending on the right administration set up, stacking on, for example, multiple nebulized therapies might be a little bit challenging. I think we're well-positioned in view of that potential dynamic as well. Got it. Should investors think about this similar to how they think about the PH space, where polypharmacy is likely over time to become the norm, and that a patient could be on, let's say, one oral and one inhaled without too much difficulty? Yes. I think that both pulmonologists, regulators, and the broad community see the desire to evolve the landscape for better efficacy via similar dynamic as in the pulmonary arterial hypertension space where there's doublet and triplet therapy and then different ultimately lines of therapy as well. Got it. Great. Ahmed, you're a lawyer, I have to ask, can you tell us about the IP status of the molecule? Yeah, absolutely. We're fortunate to have issued intellectual property that takes the IP life of the program out to 2042, and that's before considering patent term extension or supplementary patent certificate, further extension as well. We continue to work on further IP positioning around the formulation, drug substance, drug product, as well as method of use of the product in IPF and of course other potential future disease states as well. Got it. Can you tell us the current financing status of the company as well as the current listing status of the company? Yeah, absolutely. Currently listed on the Stockholm Exchange, the Nasdaq Stockholm. We're $110 million US dollar cash position as the end of last quarter. We've recently publicly filed a registration statement with the SEC to effectuate a dual listing in the United States. We're looking forward to completing the review process with the SEC and of course, review process with the US Nasdaq Exchange as well in order to soon trade in the United States as well as a dual listed company. Got it. Thank you for joining us at the Jefferies conference. I presume you've had a packed day of meetings. As you've gone about this, what is the one investor question where you are just sick of answering and you feel like, "Oh, man, I just wish investors would stop asking about X, Y, Z"? What is the one investor question, or what's the one question that you don't get that you wish people asked you more about? Both great questions. I think the one thing where we've done a lot of work, but I'm still happy to continue educating investors on is the features of the phase IIa that make us really believe in it, right? I understand there's the absence of a placebo arm, and even I would acknowledge, right, that does have value when you put that into a clinical development program. At the same time, I think when you take a broad view of what evidence is here to show us that this therapy is a really exciting one for IPF, you look at the translational package, you look at the mechanistic principle. I think it is easy to build enthusiasm, and certainly that was the basis on which I joined the company two and a half years ago. I think that in terms of what questions aren't we getting, I think what some investors appreciate, but maybe is not yet fully appreciated, is how big the commercial opportunity in IPF is. I think that this is a disease where only a small minority of patients are currently being treated. Data from last year reflects that about 25% of patients with IPF in the U.S. ever initiate therapy, and they discontinue at median of 10 months. I think when you think about the market size and the market opportunity, it really is quite large, and I think that that's something that is, again, as I mentioned, underappreciated by at least some investors. I think that as we have more IPF therapies coming forward, including some of the ones we mentioned in phase III, I think there will be a greater appreciation of that over time as well. Great. In terms of the phase IIb data, can you just remind us when did you finish enrolling and what does that mean in terms of last patient, last visit? Yeah. We've completed enrollment in April, a couple months ago. We're really pleased to enroll ahead of schedule, and we're guiding towards top-line readout in mid-2027, so mid next year. Got it. Okay. Why don't we do this a year from now? It'll hopefully be a very interesting time for the company. Absolutely. All right. Great. Well, thank you, Ahmed. Thank you, Bernt, for joining us today. Thanks for having us.