Good morning, everyone, and welcome to Oppenheimer's 34th Annual Healthcare Conference. I'm Jeff Jones, a senior analyst here on the biotech team, and I'm delighted to welcome Ahmed Mousa of Vicore Pharma to tell us the story, about their IPF programs and more. So, Ahmed, I'll turn it over to you. Yeah, perfect. Thank you, Jeff, and thanks, everyone, for joining. I'll go ahead and share some of the slides that I'll present. Perfect, and we'll start off just with the forward-looking statement disclaimer. And then, for those of you not familiar with Vicore, just a quick company snapshot. So the company's really built a really nice skill set around understanding and modulating the angiotensin II pathway, and in particular, activating the angiotensin II type 2 receptor, the AT2 receptor, which we believe can play a key role in a number of different diseases, starting with idiopathic pulmonary fibrosis. The company's headquarters are in Stockholm. I'm based in Cambridge, and we have a really nice clinical and CMC team in the Copenhagen area as well. We're publicly listed on the Stockholm Exchange, with about a $160 million market cap and about a $50 million cash position, and fortunate to be supported by some great specialists in Europe, HealthCap and HBM, as well as having brought in some new U.S. specialists as the company advances, including OrbiMed and Suvretta in a financing over the summer last year. Just a quick look at the company's pipeline. So, you know, the company's very focused on advancing a molecule called C21 for IPF, where we've shown some really exciting phase IIa data, interim phase IIa data. We'll be finishing that phase IIa study and reporting on it in the first half of this year. Also in the first half of this year, we'll be initiating a phase IIb study for the compound in IPF. We continue to think about the franchise that this molecule and that the mechanism of action can represent for diseases outside of idiopathic pulmonary fibrosis. And one of the diseases we like in particular is pulmonary arterial hypertension. So that's up there as well, although we continue to evaluate the exact approach. In addition to that, we've been developing a digital therapy, a little bit different, for anxiety associated with pulmonary fibrosis. And this is actually a digital app that you can have on your phone or your tablet, and it can help patients who have been diagnosed with pulmonary fibrosis deal with the psychological burdens of the disease. We read out positively on a pivotal study early in this year, and I'm excited to talk a little bit more about the path forward for that molecule as well. And then finally, we continue to look at different follow-on molecules for a number of different indications, which are currently in the preclinical and IND-enabling stage. So maybe focusing in really on IPF, which is where the bulk of our effort is. You know, first, why is IPF an area that we're motivated, you know, to go after? And I first, I think, first and foremost, there's such a high unmet need in this, in this space. There are currently two approved therapies for IPF, nintedanib, and pirfenidone. These therapies offer, unfortunately, limited efficacy benefits. So the prognosis after diagnosis is three to five years survival, so worse than a number of different cancers. And in addition to kind of a limited efficacy profile, the standard of care therapies also carry tolerability issues, including significant GI side effects, nausea, vomiting, diarrhea. Actually, because of those things, as you can see here, the majority of patients who are diagnosed with the disease decide not to initiate treatment. And even those who do initiate treatment have a fairly rapid discontinuation rate, average duration of treatment of 10, 10 months. Notwithstanding all of that, it's actually quite a significant commercial opportunity. So despite the limited uptake, it's, it's already a $4.3 billion market. And certainly, we believe if you can offer, you know, kind of more efficacious therapies, better tolerated therapies, you can certainly unlock, a much greater level of upside. Now, the challenge in IPF, though, has been, you know, there've been a number of failures recently and even over the past several years. And so it's a tough disease to go after. So the question becomes, why are we enthusiastic about the Vicore approach, and how do we think we're different from some of the other ways that, you know, IPF's been approached as a disease? And what we really like about our mechanism of action, activating this AT2 receptor, which is shown kind of in red on the right, is that it's an upstream endogenous tissue repair system, and we're supercharging it to drive against the disease. So to give you a little bit of a picture on this angiotensin II pathway, when you have the release of angiotensin II in the body, it actually activates two receptors, the AT1R and the AT2R. And essentially, these receptors have opposite effects. So the AT1R is a hypertensive, inflammatory, and fibrotic, you know, set of processes, while, while the AT2R resolves those processes. What's interesting is the AT1R is quite ubiquitously expressed in the body and tissues and constitutively expressed. So it's normally present in a basal healthy state. Whereas the AT2 receptor is actually quite selectively expressed both in tissues and in time. So it actually tends to be expressed only after maybe there's been AT1R expression and fibrosis, hypertension for some period of time to resolve it. But actually, what's interesting is one of the very few tissues where you find AT2 expression basally is the lung. And so that's quite interesting for us. And, you know, that's one of the things that we're harnessing with this mechanism of action. But essentially, you know, when you have angiotensin II release, the net effect then becomes the hypertension, the inflammation, the fibrosis. And that's why there's been the development of ACE inhibitors and angiotensin receptor blockers to control the increase in blood pressure associated with AT1R activation. But what we're doing here then with our drug candidate C21 is selectively activating this kind of response or resolution process with the AT2 receptor in order to go after the disease. And we like that it's so far upstream, you know, because IPF is such a profound pathological set of processes, and we think we need an upstream intervention in order to effectively deal with it. And the other reason why we like this pathway is that it, by having the agonist mechanism of action, you have an exaggerated PD effect, which means that you can hit the target and it'll have the downstream impact, and you don't need 100% target occupancy, and you don't need 24/7 receptor coverage. That's maybe in contrast to other approaches that might involve downstream antagonism of, for example, one of the factors that are involved in the fibrotic cascade. Those are a few reasons why we like this particular mechanism of action. But as I'd mentioned, it's not just that we think we have the right mechanism, but we also think we have the right kind of tissues as well. The target AT2 receptor is actually highly expressed in healthy lung tissue, as I'd mentioned, and this is some autoradiography work on the left where we've essentially, you know, confirmed just that. Now, on the right, you also see that, you know, through the work of Vicore and academic groups, we've actually identified not only that this AT2 receptor is expressed highly in the lung, but it's actually expressed on a precursor cell called the alveolar epithelial type II cell. And so the question becomes, you know, what does this alveolar epithelial type II cell, you know, that has the target that we're activating do, for the functioning of a healthy alveolus? And there are two features that we'd highlight. One is these AEC II cells. They differentiate in the alveolar epithelial type I cells. And those are the cell type that are responsible for gas exchange in the lung. So oxygen comes through and carbon dioxide out. And the second thing that we'd highlight is these AEC II cells produce surfactant proteins that break up the natural surface tension of water. That's actually quite important because in order for the alveolus to maintain its integrity, there has to be a breakup of that surface tension. Otherwise, there's an alveolar collapse. But if we then push forward and ask the question, well, what happens to the alveolus and what happens to these AEC II cells that have the target that we're activating in a disease state like IPF? In that state, there's micro injury to the lung, to the alveolus, and to the AEC II cells. First and foremost, you just have the death and dysfunction of these important precursor cells. They're no longer producing surfactant, and they're no longer differentiating into those gas exchange AEC I cells, right? That's a terrible part of the disease. But actually, the second thing that starts to happen is the injury drives the release of this master regulator of fibrosis, this profibrotic cytokine, TGF-β1. That's released both from the alveolar epithelial type II cells as well as macrophages in the alveolus. This TGF-β1 cytokine drives a number of processes. You know, two I'd highlight here are the epithelial to mesenchymal transition. What that means is these precursor AECII cells, instead of differentiating into gas exchange cells, are now being pushed to differentiate into fibroblasts, then ultimately myofibroblasts. That's, you know, quite important for the disease progression because the myofibroblasts are then the cell type that actually drive the collagen deposition and the fibrotic process. And then the second piece of the puzzle is that this TGF-β1 also interrupts the normal balance of matrix metalloproteinases, which are a set of enzymes, among whom some will break down the collagen in the extracellular matrix. So then, you know, when a disease state like this, we ask the question, well, what happens when you activate then this AT2 receptor on the alveolar epithelial type II cells, and how can this, you know, resolve the disease process? And first and foremost, activating the AT2 receptor promotes the viability of these precursor AECII cells. So it allows them to continue producing surfactant, to keep the alveolar integrity, and it allows them to continue differentiating into the gas exchange AECI cells. The second thing that I'd highlight is this cell type inhibits TGF, or sorry, the activation of the AT2 receptor inhibits TGF-β1. It actually inhibits both the expression of TGF-β1 as well as its receptor and inhibits the signaling through the two main pathways, this Smad and the ERK1/2 pathways. And we think that's an important part of the efficacy, you know, kind of, that this drug candidate and this mechanism of action shows. And then finally, we have some really nice molecular biology work showing that we're able to inhibit that epithelial to mesenchymal transition that's driven by TGF-β1, by activating the AT2 receptor using C21 and to also inhibit the collagen depositing activity of the myofibroblasts. So, you know, we have kind of data behind each of these, and I won't go into all of that today, but just to highlight maybe one translational experiment where we show the evidence behind our mechanism of action. This is a human precision cut lung slices model from IPF patients. So this is actually human, IPF lung tissue that we've taken, and we're able to add clinically relevant doses of our drug candidate C21 and show that in a, you know, kind of dose-dependent way, we're able to, or concentration-dependent way, we're able to reduce the levels of TGF-β1 as well as the levels of collagen protein in these lung tissues. And so we think this is a nice experiment, showing that we're able to drive our mechanism of action in this ex vivo, in this ex vivo model. But in addition to that, we can actually look at TGF-β1 even in some of our phase IIA work. So, in our phase IIA study, when we reported interim data, among other things, we took blood samples from our IPF patients at baseline as well as after six months of treatment. At baseline, you'll see that there are a number of patients who had elevated levels of TGF-β1 in the blood. And we were actually able to show that after six months of treatment, we could bring those TGF-β1 levels down, which we think is a nice evidence that we're driving the desired mechanism of action. And I guess you can take it then from, you know, kind of the preclinical, translational, and mechanistic evidence to then look at what we were able to show in our interim phase IIA. This was a phase IIA study, open label, with 52 patients enrolled. They were treatment naive, and we used our drug in monotherapy and looked at both safety and tolerability in monotherapy as well as a 9-month treatment duration, looking at lung function as measured by forced vital capacity. So I think first and foremost, you know, one question that's always asked is, you're driving such an upstream mechanism of action, can you do it safely? And the answer, fortunately, has been so far, you know, yes. So on the right-hand column here, you'll see the treatment emergent adverse events in our interim on a phase IIa. And really nice safety tolerability profile. We don't have the GI side effects that are associated with nintedanib standard of care shown here for reference on the left. But also, we didn't have any drug-related serious adverse events. And so this was quite exciting for us because, you know, again, that would be one of the key questions around driving such an upstream mechanism of action. And having a drug with this profile then differentiates it from the standard of care, but also allows for the opportunity to combine with other therapies in the future in our view as well. So that's, that's kind of on the safety profile. But then on the efficacy profile, what's really nice is that we were able to show over the nine-month period, you know, first a stabilization in the lung function over 12-16 weeks, you know, followed by a period of improvement in the lung function out to that 36-week endpoint on our interim analysis. For that, it's quite exciting and quite different from anything that, you know, kind of the standard of care has done or kind of, you know, a number of the emerging standard of care therapies, as well. You know, a few maybe points to note here is just it's interesting to see, you know, the breakdown between the probable UIP and the typical UIP patients at our nine-month endpoint. The probable UIP patients are those who, based on the high-resolution CT scan, are earlier stage. Typical UIP patients have a honeycombing in the lungs or evidence of the entrenched fibrosis. So it's, it's, it's not too surprising to see that in the milder patients, we're able to have that outsize effect on improving lung function. But also really nice to see that even those with the entrenched fibrosis, the honeycombing, are able to have an improvement, out to nine months of lung function. In addition to kind of the clinical data, we actually did a little bit of AI-based image analysis on the high-resolution CT scans. And you know, there were a number of things we were able to do with that. But these are kind of two examples. And one is we were able to confirm that we have the right types of fibrosis patterns reflective of IPF in our patient population where it's fibrosis that's dominant in the lower lobes versus the upper lobes. And another interesting thing is, you know, we were able to analyze based on the high-resolution CT scans, the kind of lung volume. And we saw a strong correlation between lung volume at baseline and then the FVC at baseline, which is consistent with other data sets that have been analyzed. So it's a nice reflection that there's a good correlation between FVC and the measured, measured lung volume. And this is something that's certainly going to be interesting for us as we push forward to continue to do more on the image, image analysis work. Maybe, you know, kind of wrapping up the phase IIA, what I'll actually move to next is just to talk a little bit about our recent regional partnership with C21 in Japan. So we were actually very pleased to sign and announce that partnership just on Friday. And it's a, it's a partnership that gives Nippon Shinyaku exclusive rights to develop and commercialize C21 for IPF in Japan. We received a $10 million upfront, up to $275 million in milestones, and then tiered royalties that extend into the low 20s. We were certainly very excited to partner with Nippon Shinyaku. They have a lot of local expertise in the development of drugs for rare respiratory diseases. They're actually the company responsible for the discovery and development of Uptravi for pulmonary arterial hypertension and have a number of other PAH drugs in their basket as well. And so we're really excited to kind of continue to work with them, both, you know, to ensure that we accelerate the development of C21 for IPF in Japan. But in addition, what's nice is we get also, you know, Nippon Shinyaku support, both financial and operational, in terms of a portion of the later stage, you know, kind of global development as well. So that's something we're quite excited by. And then maybe as kind of the last slide to share here is just what we're then planning on doing moving forward. And that's really a robust phase IIB study that we'll also plan to initiate in the first half of this year. That's randomized, double-blind placebo controlled with multiple doses. We'll include now patients who are on the nintedanib standard of care or not on standard of care. We'll have a 52-week treatment duration, so the same treatment duration that you would see in a phase III study for IPF. And we'll include 270 patients, which is essentially a number of patients sufficient to power the study to detect stabilization of lung function by our drug out to 52 weeks. We'll have assessments both in person and remotely at different time points. The primary endpoint will be that change in forced vital capacity from baseline at 52 weeks. We'll be exploring both that 100 mg twice daily dose that we investigated in the phase IIA, as well as a lower dose level, a 50 mg twice daily dose, which we believe will be effective based on translational data sets. But that's, of course, something that'll be interesting to explore as well. But maybe I'll stop there and happy to take any questions from the audience and from Jeff as well. Great. Thank you, Ahmed. I guess I know you've got, you've mentioned that there's going to be a little bit of additional data coming from the phase IIA trial later this year. Can you comment on sort of what sort of data we should be expecting there? Yeah, absolutely. And I'll put up this slide just so a reminder on kind of what we've shown so far. So what we've shown so far is 19 patients out to nine months of treatment. And what we'll then do is we'll actually show approximately 28 patients out to nine months of treatment with the final data set. Okay. So an additional nine patients, that'll be nice to see. And then again, this is no placebo arm there, so won't see a change or using, you know, sort of historical data there. In terms of the AE profile, you've noted it's quite clean, but you've got this one hair loss signal that's in there. Can you comment a little bit more about what's driving that and sort of where that lands from a dose perspective, if I recall correctly? It correlates with those. Yeah, absolutely. So yeah, you know, what we do know about this effect is it's certainly dose-dependent. So the higher you go in dose, the more hair loss you experience, both in terms of amount as well as the kind of prevalence, the number reported. So at the 100 mg dose, we had 16% of right participants report some hair loss. We do know also that it's reversible. So when you discontinue treatment, the hair comes back. Now, you know, we believe that ultimately this is an acceptable part of the TPP, given that IPF is such a fatal therapy and particularly one that affects in a greater proportion older men. But at the same time, the 50 mg dose, we believe, may be both effective and not include kind of that hair loss signal as part of its TPP. So that's one of the reasons why we're looking forward to investigating in the phase IIB a 50 mg twice daily dose. We might have the opportunity to, you know, sort of clear that from the drug, drug profile, although we ultimately think if we can't do that, it'll remain something that's manageable. Okay. That's helpful. And then with your recent deal in Japan, can you clarify just in terms of the support they're going to provide in terms of development, how that facilitates and how you're able to leverage that for your global program? Yeah, absolutely. So first of all, and kind of, you know, most near term, right, in terms of the global development, Nippon Shinyaku will contribute to the costs associated with non-clinical development, like activities that are necessary to advance the program, as well as CMC development work, so like process development work as we're preparing our Phase 3 and commercial drug substance and drug product. So we're really pleased to have Nippon Shinyaku's support for a portion of those kind of, right, let's call them overhead costs that are associated with the overall development of the program. So that for us is quite exciting, and that's what comes near term. And then I would say in the late stage development, as we move towards Phase 3, there's a, you know, both operational and overhead component in terms of Nippon Shinyaku's contribution to the clinical development of the program in Japan. And then in addition, of course, Nippon Shinyaku is quite excited to advance the program in Japan. And, you know, we'll be near term initiating activities to have discussions with the PMDA about, you know, the requirements associated for getting ready to be able to participate in global late stage development as well. Got it. Now, for the phase IIB trial that you're kicking off sort of mid-year, I know it's a 52-week endpoint. Are you going to be able to get an interim look at data at, say, 12 or 24 weeks? Anything investors should be looking for there as an opportunity for further clarity? Yeah, it's a great, it's a great question. We will be doing some futility analysis, and we'll talk a little bit more about that over time in the study. We will not be including, though, kind of an efficacy type interim. I think there are two reasons for that. One is just based on the modeling in terms of what becomes an informative interim based on the heterogeneity of the disease. We spent a bit of time looking at that. And I think there are significant risks associated with trying to define, you know, to gain insights based on 12- or 24-week data or even, you know, a small portion of 52-week data. That's kind of one topic. And then the second is that we'd like this phase IIB, you know, to be accepted by the FDA as one of two Phase 3s, you know, as one of the two Phase 3s to support the development or to ultimately, you know, permit us to hav e the engagement with the FDA to allow for only one Phase 3 to support approval of the drug. And I think in order to have that in the most productive way, avoiding an interim analysis is useful. Got it. No, appreciate it. And just for to make sure we've got it clear out there, current cash and milestones that you're able to achieve based on your current cash. Yeah, absolutely. So, you know, what's, what's very nice about a Nordic-based company, we have a very efficient cash burn. So we currently have a $50 million cash position. And then, of course, in addition, we just signed the Nippon Shinyaku deal, so that brings us up even further to that $60 million level. And that'll take us into 2026 in terms of the cash runway. So we have kind of a significant runway ahead of us and the ability to continue to, you know, to push forward on our programs, in particular, of course, the Phase 2b ASPIRE study. Okay. Looking to some of the questions that are coming in, what level of insight did Nippon Shinyaku have into the C21 program? Were they able to sort of see the raw data from the ongoing Phase 2, or what level of diligence were they able to conduct? Yeah, as is customary for any, you know, pharma transaction, Nippon Shinyaku got access to an extensive data room, you know, where they reviewed both clinical data in detail as well as CMC, regulatory, and all other aspects. We fielded over an extended period of time a large number of questions from the Nippon Shinyaku team who, you know, are quite experienced in this kind of in these types of diseases. So it was nice to have the engagement with an experienced kind of partner in rare respiratory diseases and bring them on board. Great. And then one more, you know, there's obviously, as you noted, the IPF market is quite large. There are significant issues with current standard of care. What's the main pushback you're getting from in terms getting on the AIR results in terms of, say, the KOL or investor community? Yeah, absolutely. I think that, you know, the main questions that are asked about our phase IIa interim assessment are, you know, they break into three buckets. You know, one bucket is the notion that the study's open label and what does that mean? And could this be, you know, I think one question is like, could this be a placebo-ish effect? And actually, one interesting tack that we've done is we've just looked at all the other. There've been a number of other open label, you know, kind of IPF studies where different therapies have been tested. Nothing like this has been seen in an open label IPF study in terms of having patients, you know, kind of improve out to nine months. In fact, when you look at some of these open label IPF studies that have been conducted, including of like pirfenidone, you see that they kind of act as you would expect in a placebo-controlled study. So I think that's kind of one, you know, one, one piece of the puzzle. The second kind of question we're asked is there was a heavy Indian enrollment in the study. And, you know, that's because we were going after treatment naive patients to try to understand the drug and monotherapy safety efficacy as well as, you know, tolerability. And then the question gets asked, well, first, you know, are Indian IPF patients different? Of course, IPF is a very heterogeneous disease, but we've seen nothing that would suggest to us that South Asian IPF patients would be different than others. And then there's a question around kind of then what's ultimately the quality associated with the study given the heavy recruitment out of India. And I think the nice thing there is, you know, the company did a very good job in terms of having a central reader on the radiology scans. So there was one person in the United Kingdom who confirmed the diagnosis of IPF and allowed patients onto the study irrespective of where they were worldwide. And so that was a nice check to ensure that you're actually enrolling IPF patients. And the second piece of the puzzle then is on the quality of these FVC measurements and the spirometry. There the company did a good job using a well-respected company, same equipment at every site to do the spirometry measurements as well as what's called central overreading on the spirometry, which means that an automated system and then actually subsequently a human for this company would actually look at the spirometry curves and ensure that the spirometry was done correctly. Actually a patient at every site had to produce the same FVC value three times before it was kind of accepted as part of our data set. Then the third and final kind of question that we get around the Phase 2a data set is about dropouts, right? So enrolled kind of 52 patients, and then there were a number of dropouts as we went forward. First, I think that, you know, in terms of understanding why that happened, you know, during the first three months of the study, you know, that was conducted at the height of COVID in terms of the enrollment. We were asking patients to come back to clinical sites once every other week, which is pretty frequent for an IPF study. So, you know, that mix of things we think resulted in a lot of IPF patients who are older, less mobile, maybe they need family to take them to the hospital to drop out. That's kind of exactly what we saw in terms of the reason given for the dropouts. But the other thing then you ask is, of course, the question that gets asked is, okay, well, if you have a lot of dropouts, could those be the ones who weren't going to respond? And that could be impacting your data set? And, you know, the thing that we hear from key opinion leaders and clinicians when we talk to them about this is you can't really feel those modest changes in FVC, that 100 milliliter change in FVC over three months or even maybe less than that. So, you know, we've gotten a lot of skepticism as we've talked with our clinicians about whether that could be happening. And I think the second piece of the puzzle then is looking at the baseline characteristics of those who dropped out versus those who didn't. And there really is no difference. And so while we can actually generate, you know, a super responder signal by doing the analysis on our high-resolution CT scans, there's no signal associated with those who dropped out versus those who didn't. And so kind of taking that all together, you know, this is why we believe the data set represents a true clinical signal, notwithstanding some of the, you know, legitimate issues that people kind of raise around it as well. Right. So I think we are up on time. So Ahmed, thank you very much for the great presentation and discussion on the program. We had a big audience for this, so hope you have a great rest of the day and lots of good meetings. Wonderful. Thank you, Jeff, for the time, and appreciate it.