All right, all right. Welcome, everyone. Thanks for joining us for the Guggenheim Biotech Conference. I'm Vamil Divan, one of the biopharma analysts here. Pleased to have as our next company here, we have Vicore Pharma, and we have Ahmed Mousa, who's the CEO, joining us for this, fireside chat. So thanks so much, Ahmed, for joining us. Maybe just for a way to kind of kick it off, for people who maybe are less familiar with the story, just a little bit of overview on the Vicore story and sort of your developments to date, and then we'll dive deeper into the upcoming events. Yeah. No, thanks for having me, Vamil, and, so for background, Vicore's a historically Nordic, biotech company, based out of Stockholm, and, the, you know, kind of, deep know-how that the company's built over the years has been in understanding, the angiotensin II pathway, and in particular, modulating the angiotensin II type II receptor, which we think, is a really nice, upstream pathway that we can drive, for a number of potential indications, starting with idiopathic pulmonary fibrosis. Okay. So maybe just starting with the IPF side, and again, it's a tough disease. You know, a lot of companies have tried to go after it. We haven't seen a lot of great progress there, but maybe you can just talk about the condition, how is it currently managed, and what do you see as sort of the unmet need that Vicore is trying to address? Yeah, so IPF is a, you know, as you say, Vamil, a really tough disease. It has, you know, a cancer-like or honestly, a prognosis that can be tougher than a number of different cancer types, with three to five-year survival from diagnosis, and that's with the standard of care therapies. So there are two currently available therapies, pirfenidone and nintedanib. These drugs can slow the progression of the disease, but remains kind of a fatal one with that high unmet need. In addition, these drugs carry a pretty significant side effect or tolerability issues, in particular, GI side effects, nausea, diarrhea, vomiting. And these actually side effects are significant enough that, for example, in the United States, 75% of folks who are diagnosed with the disease choose not to initiate on standard of care and, typically, discontinue treatment within a mean time of 10 months as well. So really a tough disease with a very limited set of options currently available as a standard of care. But also the emerging standard of care pipeline, while it's great to see some developments there, also a very limited number of drugs in late-stage clinical development as well. And also drugs that to date, by and large, have shown either some tolerability issues and/or, you know, potential to have some efficacy for the disease, but not paradigm-changing in terms of making something, you know, kind of fatal into something that you can live with or being a bit more like a disease-modifying therapy. Okay. All All right, so it's a nice sort of framework. So now maybe you could talk a little bit about Vicore and the angiotensin path you guys are going after here. What's the rationale for this in IPF? So what drives your confidence here? Yeah, absolutely. I think that, you know, the company's hit on. You know, and I'm relatively new to the company, so I'm about four months in as a CEO and was really excited to join because I think the company's hit on exactly the right pathway to go after this type of disease. A number of therapies that have been developed unsuccessfully for IPF have sought to antagonize a downstream target. So, for example, trying to block, you know, the collagen deposition cascade by interfering with that one. And we think that's tough for such a profound pathological disease. And rather than going for downstream agonism, what Vicore goes for is upstream, downstream antagonism is kind of what others are working on. Vicore's going for upstream agonism, and I think there are a number of benefits to that. One is that we're taking this natural tissue repair system, this AT2 receptor that exists in the body, and supercharging it against the disease. And I think the second thing is that when you're talking about a tough disease, and you're trying to block, you need to dose your drug in a way where you're hitting, you know, kinda 100% target occupancy, as well as 24/7 target coverage. But in contrast to that, when you're activating this upstream pathway, you have an exaggerated PD effect, and you have the opportunity to, you know, kind of have this more, what we call, hit-and-run type of an effect, where you can activate the pathway, but you don't necessarily need to hit it 24/7, or have 100% target occupancy. And that's important for a heterogeneous disease like IPF, where every patient is a little bit different, has a different state of disease, and probably has different levels of target expression as well. Okay. So then maybe we can talk a little bit about the data that you've generated to date. So you had the phase II-A open-label data that you presented. Maybe just talk through that, you know, the study, the design, and sort of what you've seen to date, and then maybe a few specific follow-up questions that I think investment wondering about the data you've generated. Yeah, absolutely. So the company's running a phase II-A study. It's an open-label study that's enrolled 52 IPF patients. They are all treatment naive patients, so they've not taken the standard of care. And the study was designed to test our drug C21, so this AT2 receptor agonist in monotherapy in that patient population. And we studied it over a 9-month period, and were focused in on, in addition to, of course, safety and tolerability, the impact on lung function as measured by forced vital capacity. So that was the overall study design. Now, on the kind of, safety and tolerability, as well as the efficacy side, we reported interim data in May 2023 at, the American Thoracic Society, and that interim readout, on the safety and tolerability side reflected a really nice profile. So we reported the treatment- emergent adverse events and quite well-tolerated. We do not have the GI side effect signal associated with the standard of care therapies. There were no drug-related, serious adverse events in the therapy. There was some reported hair loss at 16% of the population in the phase II-A study, that we reported on the interim. We ultimately think this is, manageable because IPF is predominantly a disease of older men, in addition to being, one that's, you know, currently fatal. So we think that's a manageable side effect, but that is one thing we see in the side effect profile. But then what's really nice is on the efficacy side of things, you know, what we see in this 9-month study is initially over 12-16 weeks, a stabilization of lung function, as measured by the FVC, the forced vital capacity, followed by a period of improvement in the lung function out to the nine months of the study. And that's quite something that's quite kind of excellent and different from the standard of care, as well as the emerging standard of care. So that's, that's really got us excited, and that interim data set was enough for the company to also initiate the preparations for the phase II-B development. We'll actually will both report out on the final phase II-A data in the first half of this year, as well as initiate the phase II-B study, that I'm happy to talk more about, later on. Yeah. Okay, so I get. That was one thing we've talked about, is just the fact that was first, the disease was stable for a little bit of time, and then showed improvement after that. Now, just is there anything specific to the mechanism or how this works that might explain why you see the initial stabilization and then improvement? Yeah, absolutely. Maybe I'll take a little step back and talk a little bit more about the mechanism of action in general. So you have this peptide, angiotensin II, that's naturally released in the body, and the two main receptors that it activates are the AT1R and the AT2R. The AT1R is a system that's actually pro-fibrotic, pro-inflammatory, and hypertensive. It drives an increase in blood pressure. And then that actually AT1 receptor is quite broadly expressed in the body in a constitutive state. So you normally have a lot of AT1 receptor expression. And so then the angiotensin II pathway, actually, when it releases that peptide, it naturally actually results in a lot of that kind of fibrotic phenotype, that hypertensive phenotype, and that's the reason why ACE inhibitors have been developed and angiotensin receptor blockers. In contrast, this AT2 receptor, actually, it does the opposite. It is anti-inflammatory, anti-fibrotic, and vasodilatory, and it exists in the body to resolve the fibrosis and inflammation associated with the AT1 receptor. And because of that, it's actually very selectively expressed, both in tissues and in time. So it tends to be upregulated, this AT2 receptor, and expressed after there's an AT1R signal for some period of time, or when there's otherwise some injury or insult to the tissues or the body. So it kind of is upregulated when the body feels it's needed. And that, and that actually is interesting thing is that one of the actually very few organs then, where you actually see AT2 receptor expressed in a basal state, is actually the lung, and we think that's quite interesting. We think that's because you always, you know, have some inhalation of virus or bacteria, and so there's always a little bit of maybe fibrosis and inflammation, immune response to that, that needs to be resolved over time. But the general idea is that we can harness this natural tissue repair system, this AT2 receptor, and put it in overdrive against the disease. And, you know, one of the things that we think we're driving when we activate this pathway are kind of three main mechanisms that we think are driving the clinical effect that I just talked about. One of those is the AT2 receptor is highly expressed on a precursor cell in the alveolus, called an alveolar epithelial type two cell, and these are a very important cell type. They produce surfactant proteins, and surfactant proteins are very important in the lung because they maintain kind of the shape of the alveolus, allow you to continue to breathe through it, and prevent alveolar collapse due to surface tension of water in the lung. And actually, it's known in IPF that even before fibrosis buildup causes a decline in the lung function, there's pre-fibrotic alveolar collapse due to the loss of surfactant production, and this causes some impact on the lung function. So, that's kind of one of the things that we'd highlight that our mechanism is able to do. We act as a survival signal to these alveolar epithelial type two cells, allowing them to continue to produce surfactant. And then a second thing that we do is we allow them to continue to differentiate into gas exchange cells for the alveolus, this alveolar epithelial type one cell. And then the other two pieces of the mechanism that we'd highlight for this upstream pathway is an inhibitory impact on TGF-beta1, as well as an inhibition of something called the epithelial to mesenchymal transition. And what this is, is in the disease state that is IPF, the precursor alveolar epithelial type two cells, they actually start differentiating into fibroblasts and then myofibroblasts, which are the cell type that drive collagen deposition, as well as the fibrotic process. And so our drug candidate will also inhibit that process, basically preventing the creation of the cell type that drives this collagen deposition. Okay, and I guess your kind of question was then how does this ultimately relate to the clinical- Yeah. You know, data set? And, you know, I think it's interesting to see this stabilization period followed by this improvement, and that's consistent with, I would say, this more durable mechanism of action that's slowly resolving the fibrosis over time. And so the expectation isn't that our drug will have a quick-shot, anti-inflammatory type of effect as the dominant mechanism of action, but rather resolve the fibrosis over a more extended period of time. Okay, and a couple of last questions on the phase II-A. So one, you mentioned hair loss was one of the side effects that you guys have seen. Maybe just talk about overall the safety profile and the number of dropouts, and sort of what percentage of patients do you expect to have when you show the final data in the first half of this year? And then second question that sometimes come up is just the geographic distribution of patients, because it was pretty heavily patients from India in this trial. So just how it was designed, why that was the case, and any concerns about that being reproducible to a broader population? Yep. No, both great questions. So on the kind of dropout question, I think, you know, we have basically in our interim data set, reported data out to nine months for 19 individuals, and we'll expect to have about 28 individuals out to nine months of data when we report the final phase II-A data set, which does mean that we did have dropouts in the study. The dropouts were predominantly in the first three months of the nine-month study. And we think that's, you know... The reason for that, we think, is because in the first three months of the study, we asked patients to come back to clinical sites every other week, and that first three months of the study was also dominantly during like the height of COVID. So we believe that the combination of asking patients to return quite often to the clinical sites as well as COVID, you know, for an older patient population that can be less mobile, you know, made it tougher for them and drove some of those dropouts. And that was also attributed, you know, when we directly kind of right got the reasons for the dropouts. I think the question then on folks' mind is, okay, well, are these dropouts individuals who would have otherwise had a much more negative, you know, profile or would not have had kind of this clinical result? We looked at that from two angles. You know, one is we talked a little bit with clinicians about whether patients feel progression of the disease over periods of time, like three months. The answer, generally speaking, that we get back from the clinical community is no. So you can't really feel a, for example, 100 milliliter decline or improvement in FVC based on our discussions with clinicians. So that's kind of one piece on the dropouts. And the second piece is, what's interesting is when we look at the baseline characteristics of our patient population, we have the ability to understand who improved most and link that back to the baseline characteristics. And when you look at the baseline characteristics of the dropouts versus those who remained on the study, there is no real difference that we can identify. So that's maybe on the dropout side of things. The second question you ask is, "Okay, you guys enrolled a lot in India. Why did you do that? You know, does that make the data more or less reproducible?" I think in terms of the why, you know, when we were trying to go for a treatment-naive population, as well as a monotherapy study, to really understand how the drug works by itself, safety and efficacy-wise in IPF patients before moving forward, that can be a little bit challenging to do. So countries like India can be useful geographies to test the drug in a monotherapy setting in a treatment-naive population. That's tougher in other countries, and that's one of the reasons why we had a heavier Indian population. But then the second question is reproducibility. So I think I'd segment reproducibility into two buckets. One is, okay, well, how confident are you in the quality of the study in terms of what was done in India? And then the second question is, are Indian IPF patients different? Mm-hmm. On the kind of quality aspect, what's nice is we had central reading with a kind of U.K. radiologist who specializes in reviewing the high-resolution CT scans for IPF patients. That central reading meant that every patient had to go through one reader in the U.K. to confirm that these were truly IPF patients, because that's kind of one of the key questions when you go into different geographies, making sure that you really are enrolling patients that suffer from this, from this disease. So that we did, I think, a nice job of... Then the second question is, okay, are you measuring the spirometry, the FVC, in a robust way? And there, I think also we did a good job. We brought in a well-respected company that uses the same equipment at each site and actually does what's called central overread on the spirometry, which means they look at the different inhalation curves and exhalation curves from each of the patients at each of the clinical sites and can kind of, you know, ask patients to repeat things when it's necessary or ask them to come back when it's necessary. And we had to basically, in order to accept a FVC measurement to include in our data set, have the patient reproduce it at least three times. So in that sense, I think that there was good central oversight around the study inclusion and the measurement of the FVC. Then in terms of the IPF patient population in India versus other countries, we've looked closely at this and, you know, IPF is a heterogeneous disease, but within that heterogeneity, we've seen nothing that points us in the direction that an Indian or South Asian IPF patient would be different from the broader global population. Okay. Okay, great. So maybe let's shift into the phase II-B, as you said, I think, starting this half. So maybe you can just walk through sort of how you've thought about the study design, the population you're targeting here? What's the goals in that? Yeah, absolutely. So the phase II-B design is really designed to be as robust as possible and to give as much as possible a definitive answer on the efficacy of this of this molecule. So it's going to be a global placebo-controlled study. We're going to include multiple doses, the 100 mg twice daily dose that we investigated in phase II-A, as well as a lower 50 mg twice daily dose. We will be looking at a one-year dosing period, and we will also be looking at the you know kind of primary endpoint being the change in forced vital capacity over that one-year period. And so in that sense, it's the same as a phase III endpoint in this disease state. Actually, our objective, if we hopefully have a positive readout in this phase II-B study, is to engage with the FDA to hopefully have this be one of the two studies that can support approval of the program, rather than having to conduct two phase III studies. So that's certainly something that's on our mind. In terms of the study powering, we'll include 270 patients in the study, 90 per arm, placebo, 100 mg dose, 50 mg dose. And that patient number is designed to detect a 125 mL change in FVC from baseline at 52 weeks. Essentially, what we're trying to do is power the study to detect stabilization of lung function out to 52 weeks. And so while it's really nice that we've seen these improvements in the FVC in our phase II-A study, that's actually not necessary to have a really exciting therapy, given the standard of care and emerging standard of care. And so our kind of, you know, powering will be for stabilization, and we'll see how that goes. Okay, and sorry if I missed this, but in terms of the background therapy here, is it still naive, or are you gonna have add-on to- It's a good question. We'll allow patients who are on the nintedanib standard of care, which is, for example, in the United States, the dominant standard of care therapy. We did some drug-drug interaction work and confirmed that we would be good to go in terms of combining with nintedanib. There are some DDI risks associated with combinations with the other standard of care therapy, pirfenidone, so we'll leave that out for the phase II-B study. Okay. And just mechanistically, again, does it make sense? Do you, do you expect to see a better response for patients who are on, the standard care already, or, or how are you thinking about the impact of combination versus use on its own? Yeah, so the nintedanib has a TKI, tyrosine kinase inhibition mechanism of action, which is different from ours, so we would see the potential, you know, for additive effects. So, it'll be interesting to study that in the phase II-B and to see how that develops. Okay. And then, you have another product that last year was stopped, I think because of the blood pressure increases, C106, and I think it's a somewhat similar mechanism to C21. So maybe you can talk about the similarities, differences, and what this means, if anything, for C21. Yeah, absolutely. So if you recall, I was talking a little bit about this angiotensin II pathway, and there's this AT1R and this AT2R, and our drugs are designed to selectively activate AT2R. But because they do the opposite of each other, they are structurally similar, there is a ratio of AT2R to AT1R selectivity. So actually, our clinical drug candidate, C21, that we're continuing to advance, has a 3,000:1 selectivity ratio of AT2R to AT1R activation. Based on preclinical studies, we were advancing a follow-on molecule for other indications, the C106 that you mentioned, that has actually a much lower selectivity ratio. It actually has a 1:500 AT2R to AT1R selectivity ratio. Based on our preclinical experiments, we still did not believe it would drive a AT1R activation in a way that would have a clinical impact, based on the dose-doses that we were going for, but ultimately, it did. And that was manifest then in our phase I study with a modest increase in blood pressure. But that ultimately remains, let's say, unacceptable from the perspective of the patient population and the potential diseases that we're trying to go after. So it was a useful, it was a useful set of, you know, kind of studies in the sense that it now gives us a much better understanding of the translatability of different experiments, preclinical to clinical, and that'll, I think, help us a lot as we push forward on further follow-on molecules that we can hopefully more efficiently advance. Ultimately, though, C21, the lead molecule, you know, remains for us quite exciting, and we've actually studied it now in more than 300 individuals and have not seen a blood pressure signal there. So we remain, confident that from that perspective, that molecule can continue to advance. Okay, and then maybe just obviously, the focus here, IPF, starting phase II-B. Are there sort of, indications where you've seen a potential for this mechanism to have an impact? Yeah. So, you know, we'd really love to, over time, use, you know, kind of IPF data and our signal here as a springboard for other indications. You know, there are a number of potential indications that you can, develop this drug for, given its kind of upstream nature. We, we like the lung as the starting point, given, as I mentioned, you already have the basal expression, and then it's further upregulated in the disease state. So we really like pulmonary hypertension, pulmonary arterial hypertension, as a group of, diseases that we think we can also have disease-modifying potential, in the, in those types of indications as well. Okay, maybe just in the last minute or two here, just give people a sense of the financial side. So what the current cash position and your cash runway? Yeah, absolutely. So current cash position is about SEK 50 million, and we've guided that that takes us into 2026. And so that's great to have, and I think it's a product of the nice kind of efficient burn in for a European biotech company. In addition to that, you know, we probably will need additional capital in order to ultimately read out on the study, have the additional runway, as well as, you know, do the phase III enabling CMC work. But what's nice is we both have the time and flexibility to decide when to do that, and we also believe that there are, you know, potential non-dilutive approaches to obtain capital to support continued development as well. Okay. Out of interest of time, I think we'll leave it there. Thanks so much for joining us. Yeah, thank you, Vamil. Appreciate it. Thanks.