Vicore Pharma Holding — Call Transcript 2026

Great, we'll kick it off. Hey, everybody. Thanks again for joining us at the Leerink Partners Global Healthcare Conference. My name is Roanna Ruiz. I am the senior biotech analyst here at Leerink, and really happy to host Vicore Pharma here with me. With me, I have Ahmed Mousa, the CEO, and we're really looking forward to getting to the discussion, thanks for joining us. Yeah, thanks for having us, Roanna. Yeah. For investors who may be new or revisiting your story, I'll start big picture and then start to drill down into the details. In terms of big picture, can you just recap, you know, what's been happening at Vicore? What are some of the recent updates? Moving to what are your future goals for this year and beyond? Absolutely. Vicore Pharma is a company that's working in the angiotensin II pathway, and specifically, we've focused in on activating a receptor called the AT2 receptor, which is an endogenous tissue repair fibrosis resolution system. It's also anti-inflammatory and vasodilatory. At Vicore, we believe this intervention can have broad impact in a number of fibrotic and inflammatory conditions, and we've been really focused on IPF. Really the, the theme as we've started out the year is strong focus on execution. We're running a relatively large phase II-B study in idiopathic pulmonary fibrosis, which is a disease with a super high unmet need, and a very attractive commercial profile. We're now approaching a conclusion of enrollment in the study, so we've guided towards enrollment, completion of enrollment of that study in the first half of this year. Certainly, we're paying a lot of attention to that and looking forward to reporting that milestone and moving forward from there. Yeah. Sounds great. I'll dig in a little bit on buloxibutid in terms of the mechanistic rationale. Can you talk a bit about how it's different from current antifibrotics in IPF like Nintedanib and Pirfenidone and those that are in the pipeline as well? Yeah. Generally speaking, pulmonary fibrosis, including IPF, is a disease where there's injury to the air sacs, injury to the epithelial layer of the alveolus, and that injury drives a number of disease processes, including fibrosis. Many of the mechanisms that have been advanced to date, including the current standard of care, are designed to block the fibrotic cascade, and that's not an invalid way to go after the disease, but we think it's relatively incomplete and relatively downstream. We've selected instead a mechanism of action that addresses the fundamental injury that is the starting point for the disease state. This mechanism of action that we're driving, basically, promotes epithelial repair so that we can both resolve the injury as well as the fibrosis that occurs after it. Yep. Can you just elaborate a bit on how you're thinking about the differences between being more downstream in the pathway, more upstream? What are some of the benefits or advantages there? Yeah. When you have this injury to the air sacs, it essentially is what causes, right, that those injured cells are then the ones that release these pro-fibrotic factors, including TGF-beta 1 and other pro-fibrotic cytokines. That's then what drives the fibrosis in the area around the air sacs called the interstitium. As that fibrosis builds up, it essentially disables the ability for oxygen to diffuse across the air sac into your pulmonary vasculature. In addition to that, the buildup of fibrosis starts to squeeze on the pulmonary vasculature so that actually, 40% of IPF patients ultimately develop pulmonary hypertension as well because of that vascular dysfunction. Essentially, the idea is that by repairing the injured cells, not only do you restore the health of the air sac of the alveolus, you also attenuate or stop that injury signal, that kind of pathological release of TGF beta 1, which is a huge contrast to the idea of blocking TGF beta 1 mediated signaling thereafter, which is, I would say, the approach that many of the other mechanisms take. The benefit is both twofold, right? If you're promoting repair, right, you're gonna be able to restore gas exchange capability and other elements of the disease that are not fibrosis. Even though we call this disease pulmonary fibrosis, it's not just about fibrosis, it's about that injury to the air sacs. That's something that's unique to our mechanism. In addition to that, right, the ability to address the fibrotic drive by stopping the signal at its source, we think can be much more potent and actually much more safe than trying to block it downstream. One of the challenges that we see with, you know, blocking TGF beta mediated signaling is that's actually an important signaling pathway for tissue hemostasis, right? You have fibrotic matrix in normal tissues. It's part of the scaffolding of your cells. If you really take a hammer and block TGF-beta 1 mediated signaling, you are liable to create toxicities, right? That's why I think there's been such a challenge with a number of therapies, both in the clinical development pipeline as well as in the standard of care, where threading that needle between getting some efficacy, but also essentially not too much so that you don't drive toxicities can be a huge challenge. This orthogonal repair approach, we think can be, you know, kind of driven without creating the same types of liabilities. One of the other nice things to put this mechanism into context is activating the AT2 receptor, is the other side of essentially blocking the AT1 receptor. The AT1 receptor is pro-inflammatory, pro-fibrotic, and hypertensive pathway, and this actually is the pathway that's blocked by ARBs. ARBs are AT1R antagonists. Of course, we know that ARBs and ACE inhibitors, which also block that pathway, have been both safe and well-tolerated, and many patients take them not only for hypertensive conditions, but also for fibrotic and inflammatory conditions. Just as that intervention point is used in a broad range of therapeutic areas effectively, we believe that so too can AT2 activation. Yep, I hear you. That's really interesting. Wanna also ask you a bit about the prior phase II-A, the AIR trial, and in IPF patients, what are some of the key takeaways that came out of that? What should investors be learning from that trial in terms of looking ahead for your program? Absolutely. I think the first thing to really note about this phase II-A study is it studied the drug's effect over nine months, which is quite unique for a phase II-A. Most programs in phase II-A development test only over 12 weeks, and while there's of course a practical component to this, you wanna see your signal quickly so that you can move forward, we don't necessarily believe that 12-week signals are representative of what would happen thereafter. When you have a build up of fibrotic material in IPF and this disease state, we believe that's a process that takes some amount of time, and of course, along with the fibrosis, there's always inflammation. One of the challenges with intervention points that can both impact fibrosis and inflammation, as is the case with the drugs and development in the clinical landscape as well as the standard of care, is if you're only looking over a short period of time and you're looking at this FVC endpoint, which is the main endpoint that companies in the space study, it's forced vital capacity, and essentially it's how many milliliters of lung capacity is in your lungs. If you reduce inflammation or swelling, you might be able to improve lung capacity over a short period of time, such as 12 weeks. If you haven't really stopped the pro-fibrotic drive, then it's going to overtake any benefits over time. That's why it's really nice to have studied our drug over a nine-month period of time, where we showed not only the ability to stabilize lung function, but actually to improve it over that period of time. That's something really unheard and unseen from before. While there are some features of our study, for example, it was an open-label study that you have to look carefully at, I think one of the really nice features is the length of the study. Yep. That's a really great segue. I was gonna ask you a bit about the fact that it was open-label, it was single arm. How do we extrapolate from the AIR trial to your other ongoing trial, the phase II-B ASPIRE trial? How do we think about that? Absolutely. I think the way you contextualize this phase II-A data set is a signal of disease modifying effect, right? I think that's what you can take away from this study, because there are a few points notwithstanding the fact that it's open-label. For example, pulmonary fibrosis patients or specifically IPF patients don't have stable lung function over a nine-month period. They don't have improved lung function, unfortunately, right? This is a disease where if you study a natural population with IPF, you would only see a single digit percentage of patients, 4%-9% having kind of a stable lung function over that period of time. When we see that 65% of the patients at 36 weeks in our phase II-A study have improvement in lung function, that's not the kind of thing that you can get to by chance. One of the other nice features is we have a great deal of confidence that we enrolled true IPF patients. We did central radiological reading from the top experts in the field and other measures to ensure that we were enrolling true IPF patients in the phase II-A setting. If you have IPF patients and you look at them over nine months and you're seeing this really nice signal of improvement, it's tough to explain it any other way than a signal of clinical activity. Of course, there are some different features in the phase II-B. For example, we'll now be allowing patients on background standard of care or not on standard of care to enroll in the study. I wouldn't divine an exact treatment effect out of the phase II-A, but that's something we can check for with the ongoing study. Mm-hmm. Yep. Anything else to note in the phase II-B trial design in terms of keeping an eye out, or how does it impact the potential future results? The phase II-B study is really set up as gold standard. It's relatively large in size. It's 360 patients. It positions the drug as one that can be used as a frontline therapy subsequently on top of standard of care or not on standard of care. We're allowing patients who are on Nintedanib standard of care, and actually nerandomilast was approved late last year. We're allowing patients on nerandomilast standard of care to enroll in the trial as well. The inclusion criteria are broad. They're materially similar to inclusion criteria that you would see in the TETON phase III studies, United Therapeutics phase III studies for IPF or other companies that are in the phase III stage studying drugs for pulmonary fibrosis. In addition to that, you know, the endpoint is 52-week change in lung function as measured by FVC, and this is the regulatory endpoint. We're already looking at the phase III endpoint in the phase II-B setting. Yep, yep. I know you recently expanded the size of the phase II-B, and can you talk a bit about, you know, what sites are being added? What's your level of confidence just expanding the trial, identifying efficacy signal, things like that? Anything we should know about safety checks, DSMB, stuff like that? Yeah, absolutely. You know, one of the things about IPF that's unfortunate is there's a fairly limited drug development landscape in the late stage. There's only a handful of therapies. Of course, since we designed the study in 2023, there have been a few readouts. One of those is nerandomilast, which is the newest drug that's now approved by BI. That drug has shown a 70-milliliter difference from the placebo group to the treatment arm in lung function at 52 weeks, that FVC difference. In addition to that, the TETON-2 study, so one of the two phase IIIs that United Therapeutics was running, read out last year as well and showed a 95 or 96 mL difference in lung function at 52 weeks. Prior to these readouts, we had powered our study basically with 80% power to detect a 126 mL difference in lung function at 52 weeks. Essentially, after we see these other readouts, which are positive and very well-received by both clinical communities and the investor community, you know, it became apparent that we did not need to set the bar quite that high. We actually added the patients in order to essentially provide for 80% power to detect about 97 milliliter difference in lung function between the Placebo arm and the treatment arm. Essentially, we're powered to have the best treatment effect of any IPF drug ever with this expanded trial. Yep. You also then asked about, in addition to the efficacy signal. Just increasing your conviction in the trial. Yeah. Just how are you thinking about the outcome, stuff like that. Yeah, absolutely. I think this reflects, you know, kind of our continued conviction in the study based on both the preclinical and the phase II-A data set. I think you'd also asked about kind of some of the safety checks. Safety exactly. So we're of course well underway in enrollment, well over half enrolled in the study. We've had a number of interactions with our independent Data Safety Monitoring Board and we've received no concerning feedback from them. Of course, in addition to that, we can observe the data set on a blinded basis and have seen nothing that's given us any concern as well. Yep. Yep. I think I might know part of this answer, but I think it might be helpful to clarify for investors. Coming out of the phase II-B, you know, what would you view as like a winning data set both on efficacy and safety tolerability, and excite you to keep moving forward with the program? Absolutely. I mean, in IPF, one of the unfortunate things is that the bar is relatively low because of the limited therapeutic landscape and because the desire here is to combine therapies, right? It's not a zero-sum game. For example, at only a 70 milliliter difference in lung function, as I mentioned, nerandomilast was very well received or is very well received by the clinical communities and that 95, 96 milliliter difference in lung function, that was very exciting both from an investor perspective and clinical perspective in terms of efficacy signals. Those are the types of efficacy signals that would really attract folks. Certainly, we're looking to see if we have effect in that level, and I think that would certainly support moving forward. Of course, we're hopeful that we can also have something that goes well beyond that, but let's see. Yep. Yep. Just to double click on that, I noticed some companies distinguish between what's really exciting regulatory wise in terms of being able to go forward, eventually get approval and what's exciting clinically. Yeah. Could you break that out in terms of what you think would be really clinically meaningful, will be great regulatory wise, or is it applicable for both? I think it really is applicable for both. When we talk with a number of folks in the clinical community, they're actually quite excited by nerandomilast. You know, one of the key reasons for that is even though the effect on lung function appears to be modest, especially compared to the current standard of care, it's a gentler drug. It still causes gastrointestinal side effects, the feedback from clinicians and some of the data that BI's put out to date from their phase III trial reflect that it's a milder GI profile than, for example, the Nintedanib standard of care therapy. I would certainly say, you know, especially with buloxibutid's tolerability profile in development to date, even at that level, that would be quite exciting, I think, to a clinical community. I think again, we have hopefully with our phase II-A data set the opportunity to look for things beyond that as well. Yep. Yep. I hear you. In the phase II-B, anything that you're watching out for potentially on the safety signal side or anything to consider given you are going after like a pretty novel pathway? Absolutely. What we've observed in phase II-A development to date is a tolerability signal, which is mild to moderate hair loss or hair thinning. It was observed in 19% of patients in the phase II-A study, and it's tracking similarly in the blinded data set. We believe this is ultimately a manageable side effect given that IPF is a disease of older individuals and generally of older men. It is a dose dependent side effect, we are testing both the same dose as we tested in the phase II-A as well as a half dose, 50 milligrams, twice daily. Hopefully there'll be an opportunity to potentially mitigate or eliminate that side effect if the 50 milligram dose is also efficacious. Beyond that, as you say, this is a relatively new mechanism of action. It's actually not really been studied in significant clinical development to date outside of Vicore's efforts. Vicore has made significant efforts, in the advancement of buloxibutid. Of course, we have our phase II-A data set where we studied this drug in IPF patients over nine months, and we did not observe any treatment related serious adverse event, for example. This is a mechanism in the angiotensin II pathway, so we look carefully at the hemodynamics, for example, hypertensive or hypotensive effects, and we've not observed any signals like that as well. Actually, ultimately, buloxibutid's been exposed before this phase II-B study in over 350 patients, and we've observed a tolerability profile and a safety profile similar to what I've you know, expressed nothing significant. We do of course, see that hair loss effect that I mentioned. Yep. Yep. To put this in context, what are you hearing from physicians in terms of the current trade-offs that they have to make in terms of prescribing today's available agents in IPF to patients on, trying to get them the best efficacy, but also helping manage the tolerability issues with current antifibrotics? Like, what is that like in terms of the baseline here? Because the standard of care therapies are so limited in efficacy, for example, they have not really shown significant mortality benefit signals, although they show that difference in lung function. I would say that we've heard from a number of clinicians that they prioritize tolerability, older patient population, a lot of comorbidities, and it might be one of the reasons why, at least when you look historically before the approval of nerandomilast, only a minority of patients even initiate standard of care in the United States, actually only about 25%. That might be because, when patients and physicians think about what the tolerability profile is for this standard of care therapies, they just opt to, for example, wait and see. One of the challenges, though, is the decline in lung function is not necessarily a linear path. Sometimes you kind of go off a little bit of a cliff, unfortunately, with an IPF exacerbation, and then it can become, for example, too late to start a therapy. I would say that drugs with a better tolerability profile certainly be very attractive. I also think one of the reasons why there's a big hesitation and a prioritization of tolerability is there's not much benefit trade-off, right? The mortality signals are not really significant in terms of what they've shown in development to date as well. Yep. I hear you. With your program. Thinking ahead, let's say everything works out, your program's approved in IPF, like, where would you see it layering into the treatment paradigm? Like, are you thinking monotherapy, maybe combination therapy use? Like, how would physicians want to start to use it, and then how could it integrate more into the treatment paradigm? Absolutely. I mean, how we want to position the therapy is that you could take it as a frontline and that you could choose to take it on top of the available standard of care, or you could choose to take it alone. For example, if you have the discussion with the clinicians and, you know, you as a patient become comfortable with the tolerability profile of the standard of care, then you can add that on to what buloxibutid would offer. You could also choose to then take it alone if you wanna avoid it. I would say that's pretty consistent with how our study's enrolling. We're about 60% of patients enrolled to date are on a background standard of care, largely an imatinib, and then about 40% are not on standard of care, and that's actually about equally split between patients who have never taken a standard of care therapy, and then the other half are patients who started or attempted to take the standard of care but didn't tolerate the side effect profile, so have discontinued use. Yep. I hear you. Just broader in terms of the IPF landscape, like, where do you see the field moving towards in the future, especially if buloxibutid is available and prescribers just getting more comfortable, maybe guideline changes happening? Like, where do you see the field moving and knowing that what's coming in the pipeline too? Yeah, absolutely. I mean, I certainly think that there'll be a significant effort, because this is such a tough disease, to combine therapies. Right, like, there will be, you know, I think a clinician push if it's possible to put two drugs together and patients can tolerate that to do it. I think also, you know, you see it in the pulmonary hypertension space, you know, the ability to even then attempt triplet therapy. I would say the landscape is currently not mature enough to think about what goes first, what goes second, and, you know, for Vicore, that's a little bit of a flexibility benefit because then we can position as that frontline therapy. Of course, as the landscape matures, there might be some thinking about, okay, what, you know, kind of mechanisms might be best to go first, and then what might be best to go later? I would say conceptually, because we have this epithelial repair mechanism of action, it makes a lot of sense for, you know, this one to be a frontline, and also because it's relatively well-tolerated, compared to the broader landscape, should be an easy one for people to take at the outset. Yep. I hear you. Just thinking beyond IPF, are there any other fibrotic or inflammatory lung conditions that may be appealing with this mechanism, possibly maybe differentiating in that space? Are you starting to think about that? Absolutely. Mm. Certainly high on our list are the other pulmonary fibrosis indications, right? Like progressive pulmonary fibrosis, which share a lot of commonalities. Many companies that pursue and attain a clinical signal in IPF move to expand into those spaces. In addition to that, we think this mechanism of action makes a lot of sense in pulmonary hypertension. We've certainly generated a really nice translational data set using the classical pulmonary hypertension models and shown a very strong effect in those settings too. Certainly, this is a highly conserved and relatively upstream mechanism of action, so we actually even are thinking for the future for buloxibutid or potentially actually for some of our follow-on molecules that are in the preclinical landscape or in preclinical pipeline to think about fibrotic and inflammatory conditions in other organs as well. Interesting. Okay, great. Still staying future looking for a sec, in terms of a possible phase III and executing on that and thinking about BD partnerships, et cetera, like, a lot of options could lie before you. How are you thinking if everything works out for your phase II-B and moving forward and possible strategic partnerships that may come in beyond that in terms of optionality? Yeah, absolutely. First, we think it's quite feasible for the team that we've built, to scale to develop the drug in the phase III setting. Our phase II-B, which our team's really executed well on to date, is 360 patients. The TETON studies, phase III studies, for example, are 590 or so patients. We think that there's a feasible way to scale up into a phase III setting. In addition to that, because IPF is a larger rare disease, but it is a rare disease, we believe that it's quite feasible also to build out the right size sales force in the United States to be able to commercialize the therapy as well. In addition to that, of course, we're, you know, it's quite nice to see that there's a lot of pharma interest in IPF as a therapeutic area. I certainly think that that will be an option that we can consider as well. Certainly we're excited and have a vision to be able to push this forward on our own. Yep. I wanted to ask also a landscape question. Like, how would you frame your program against some of the other IPF mechanisms that are being explored today in the clinic, in terms of what's coming up? Like, I know there's some companies focusing on the LPA1 mechanism as well, and data sets coming later this year, like BMS has a phase III reading out. Well, I know it's not apples to apples, but how would you possibly cross compare or think about extrapolating from competitive data sets to your program? Yeah, absolutely. I think first of all, conceptually, these mechanisms of action, again, are in that space of trying to block the fibrotic cascade. You know, what basically TGF-beta 1 and other pro-fibrotic cytokines bring. The LPA1 mechanism of action is quite different from that perspective in our view. I would also say that's consistent with the clinical data sets that have been shown with this mechanism of action to date. We're talking about therapies that have the potential to have effect, but more in the zone of slowing the decline of lung function incrementally. BMS, of course, has put out, you know, phase II, phase II data set for their mechanism of action, where they do show that ability to incrementally slow the decline of lung function. Certainly it can have a place in the broader landscape. You can try combining this with other therapies. We think that, you know, the buloxibutid mechanism of action is distinct both because it acts on the epithelial side, so it acts on this injury, which we haven't actually seen any therapy to date in the clinic that's shown kind of data in a phase II setting or beyond, with that type of an effect. Of course, that corresponds to what we've seen, at least initially, as this signal of improvement in lung function as well. Yep. Sounds great. Also want to throw in a question. How are you feeling about current cash position, executing against all your goals? You know, what are you most excited or looking forward to coming up? What's nice to see is that we're well capitalized, about $130 million cash position as of year-end, and that provides us with sufficient capital to have this clinical readout in mid-2027, with an additional year of Opex thereafter, as well. We're really excited to complete enrollment in the first half of this year, hopefully, report out those results. We're certainly gonna be excited to be at the American Thoracic Society, which is the key conference, in this space in May, and have some interesting, kind of, complementary data sets that we'll be putting out at that conference as well. We'll also, of course, in later in the year, report out on a futility analysis that we're conducting after about 30% of patients have completed the one-year treatment period. A few milestones coming up later this year that we're really looking forward to. Yeah, definitely. On the futility analysis, is there a sort of bar you're looking to beat, or is it just a simple futility analysis? Can you just refresh us on the assumptions there? We've constructed the futility analysis as one that doesn't cost alpha, it's a simple kind of yes/no, and it'll be evaluated by the DSMB according to kind of pre-specified criteria, which we'll talk a little bit more about in the future. Of course, we'll keep the folks updated as we get closer to that, both in terms of what the assumptions are as well as once we have that ultimate futility analysis result. Yep. Super interesting. In the last couple minutes, I'll ask a bigger picture question again. What do you think investors in your conversations recently most underappreciate about the Vicore story, in terms of, you know, what should people be looking out for? I mean, I think that there are a few things. I think it's the consistency of the mechanism and what it's supposed to do. Even when you look at these medical textbooks, you know, the AT2 receptor, the angiotensin II pathway as part of the renin-angiotensin system is known. The role of this receptor is tissue repair, fibrosis resolution, anti-inflammatory, vasodilatory effect. We see that it does that in a really broad range of preclinical data sets. Then we see in a clinical data set over nine months, the ability then for this drug to actually translate that broad efficacy into an improvement in lung function. I think it's a very nice thread from principle to preclinical to clinical and quite an orthogonal approach to others. We're really excited to see this phase II-B result. Yeah. That sounds great. Looking forward to the data. Yeah. Thank you. Thanks so much for joining me, Ahmed. We are now at time. I'll have to close the call. Thank you, Roanna. Yep. Thanks.

Speaker 2: Great, we'll kick it off. Hey, everybody. Thanks again for joining us at the Leerink Partners Global Healthcare Conference. My name is Roanna Ruiz. I am the senior biotech analyst here at Leerink, and really happy to host Vicore Pharma here with me. With me, I have Ahmed Mousa, the CEO, and we're really looking forward to getting to the discussion, thanks for joining us. Great, we'll kick it off. great we'll kick it off Hey, everybody. hey everybody Thanks again for joining us at the Leerink Partners Global Healthcare Conference. thanks again for joining us at the leerink partners global healthcare conference My name is Roanna Ruiz. my name is roanna ruiz I am the senior biotech analyst here at Leerink, and really happy to host Vicore Pharma here with me. i am the senior biotech analyst here at leerink and really happy to host vicore pharma here with me With me, I have Ahmed Mousa, the CEO, and we're really looking forward to getting to the discussion, thanks for joining us. with me i have ahmed mousa the ceo and we're really looking forward to getting to the discussion thanks for joining us

Speaker 1: Yeah, thanks for having us, Roanna. Yeah, thanks for having us, Roanna. yeah thanks for having us roanna

Speaker 2: Yeah. For investors who may be new or revisiting your story, I'll start big picture and then start to drill down into the details. In terms of big picture, can you just recap, you know, what's been happening at Vicore? What are some of the recent updates? Moving to what are your future goals for this year and beyond? Yeah. yeah For investors who may be new or revisiting your story, I'll start big picture and then start to drill down into the details. for investors who may be new or revisiting your story i'll start big picture and then start to drill down into the details In terms of big picture, can you just recap, you know, what's been happening at Vicore? in terms of big picture can you just recap you know what's been happening at vicore What are some of the recent updates? what are some of the recent updates Moving to what are your future goals for this year and beyond? moving to what are your future goals for this year and beyond

Speaker 1: Absolutely. Vicore Pharma is a company that's working in the angiotensin II pathway, and specifically, we've focused in on activating a receptor called the AT2 receptor, which is an endogenous tissue repair fibrosis resolution system. It's also anti-inflammatory and vasodilatory. At Vicore, we believe this intervention can have broad impact in a number of fibrotic and inflammatory conditions, and we've been really focused on IPF. Really the, the theme as we've started out the year is strong focus on execution. We're running a relatively large phase II-B study in idiopathic pulmonary fibrosis, which is a disease with a super high unmet need, and a very attractive commercial profile. Absolutely. absolutely Vicore Pharma is a company that's working in the angiotensin II pathway, and specifically, we've focused in on activating a receptor called the AT2 receptor, which is an endogenous tissue repair fibrosis resolution system. vicore pharma is a company that's working in the angiotensin ii pathway and specifically we've focused in on activating a receptor called the at2 receptor which is an endogenous tissue repair fibrosis resolution system It's also anti-inflammatory and vasodilatory. it's also anti-inflammatory and vasodilatory At Vicore, we believe this intervention can have broad impact in a number of fibrotic and inflammatory conditions, and we've been really focused on IPF. at vicore we believe this intervention can have broad impact in a number of fibrotic and inflammatory conditions and we've been really focused on ipf Really the, the theme as we've started out the year is strong focus on execution. really the the theme as we've started out the year is strong focus on execution We're running a relatively large phase II-B study in idiopathic pulmonary fibrosis, which is a disease with a super high unmet need, and a very attractive commercial profile. we're running a relatively large phase ii-b study in idiopathic pulmonary fibrosis which is a disease with a super high unmet need and a very attractive commercial profile We're now approaching a conclusion of enrollment in the study, so we've guided towards enrollment, completion of enrollment of that study in the first half of this year. Certainly, we're paying a lot of attention to that and looking forward to reporting that milestone and moving forward from there. We're now approaching a conclusion of enrollment in the study, so we've guided towards enrollment, completion of enrollment of that study in the first half of this year. we're now approaching a conclusion of enrollment in the study so we've guided towards enrollment completion of enrollment of that study in the first half of this year Certainly, we're paying a lot of attention to that and looking forward to reporting that milestone and moving forward from there. certainly we're paying a lot of attention to that and looking forward to reporting that milestone and moving forward from there

Speaker 2: Yeah. Sounds great. I'll dig in a little bit on buloxibutid in terms of the mechanistic rationale. Can you talk a bit about how it's different from current antifibrotics in IPF like Nintedanib and Pirfenidone and those that are in the pipeline as well? Yeah. yeah Sounds great. sounds great I'll dig in a little bit on buloxibutid in terms of the mechanistic rationale. i'll dig in a little bit on buloxibutid in terms of the mechanistic rationale Can you talk a bit about how it's different from current antifibrotics in IPF like Nintedanib and Pirfenidone and those that are in the pipeline as well? can you talk a bit about how it's different from current antifibrotics in ipf like nintedanib and pirfenidone and those that are in the pipeline as well

Speaker 1: Yeah. Generally speaking, pulmonary fibrosis, including IPF, is a disease where there's injury to the air sacs, injury to the epithelial layer of the alveolus, and that injury drives a number of disease processes, including fibrosis. Many of the mechanisms that have been advanced to date, including the current standard of care, are designed to block the fibrotic cascade, and that's not an invalid way to go after the disease, but we think it's relatively incomplete and relatively downstream. We've selected instead a mechanism of action that addresses the fundamental injury that is the starting point for the disease state. This mechanism of action that we're driving, basically, promotes epithelial repair so that we can both resolve the injury as well as the fibrosis that occurs after it. Yeah. yeah Generally speaking, pulmonary fibrosis, including IPF, is a disease where there's injury to the air sacs, injury to the epithelial layer of the alveolus, and that injury drives a number of disease processes, including fibrosis. generally speaking pulmonary fibrosis including ipf is a disease where there's injury to the air sacs injury to the epithelial layer of the alveolus and that injury drives a number of disease processes including fibrosis Many of the mechanisms that have been advanced to date, including the current standard of care, are designed to block the fibrotic cascade, and that's not an invalid way to go after the disease, but we think it's relatively incomplete and relatively downstream. many of the mechanisms that have been advanced to date including the current standard of care are designed to block the fibrotic cascade and that's not an invalid way to go after the disease but we think it's relatively incomplete and relatively downstream We've selected instead a mechanism of action that addresses the fundamental injury that is the starting point for the disease state. we've selected instead a mechanism of action that addresses the fundamental injury that is the starting point for the disease state This mechanism of action that we're driving, basically, promotes epithelial repair so that we can both resolve the injury as well as the fibrosis that occurs after it. this mechanism of action that we're driving basically promotes epithelial repair so that we can both resolve the injury as well as the fibrosis that occurs after it

Speaker 2: Yep. Can you just elaborate a bit on how you're thinking about the differences between being more downstream in the pathway, more upstream? What are some of the benefits or advantages there? Yep. yep Can you just elaborate a bit on how you're thinking about the differences between being more downstream in the pathway, more upstream? can you just elaborate a bit on how you're thinking about the differences between being more downstream in the pathway more upstream What are some of the benefits or advantages there? what are some of the benefits or advantages there

Speaker 1: Yeah. When you have this injury to the air sacs, it essentially is what causes, right, that those injured cells are then the ones that release these pro-fibrotic factors, including TGF-beta 1 and other pro-fibrotic cytokines. That's then what drives the fibrosis in the area around the air sacs called the interstitium. As that fibrosis builds up, it essentially disables the ability for oxygen to diffuse across the air sac into your pulmonary vasculature. In addition to that, the buildup of fibrosis starts to squeeze on the pulmonary vasculature so that actually, 40% of IPF patients ultimately develop pulmonary hypertension as well because of that vascular dysfunction. Yeah. yeah When you have this injury to the air sacs, it essentially is what causes, right, that those injured cells are then the ones that release these pro-fibrotic factors, including TGF-beta 1 and other pro-fibrotic cytokines. when you have this injury to the air sacs it essentially is what causes right that those injured cells are then the ones that release these pro-fibrotic factors including tgf-beta 1 and other pro-fibrotic cytokines That's then what drives the fibrosis in the area around the air sacs called the interstitium. that's then what drives the fibrosis in the area around the air sacs called the interstitium As that fibrosis builds up, it essentially disables the ability for oxygen to diffuse across the air sac into your pulmonary vasculature. as that fibrosis builds up it essentially disables the ability for oxygen to diffuse across the air sac into your pulmonary vasculature In addition to that, the buildup of fibrosis starts to squeeze on the pulmonary vasculature so that actually, 40% of IPF patients ultimately develop pulmonary hypertension as well because of that vascular dysfunction. in addition to that the buildup of fibrosis starts to squeeze on the pulmonary vasculature so that actually 40% of ipf patients ultimately develop pulmonary hypertension as well because of that vascular dysfunction Essentially, the idea is that by repairing the injured cells, not only do you restore the health of the air sac of the alveolus, you also attenuate or stop that injury signal, that kind of pathological release of TGF beta 1, which is a huge contrast to the idea of blocking TGF beta 1 mediated signaling thereafter, which is, I would say, the approach that many of the other mechanisms take. The benefit is both twofold, right? If you're promoting repair, right, you're gonna be able to restore gas exchange capability and other elements of the disease that are not fibrosis. Even though we call this disease pulmonary fibrosis, it's not just about fibrosis, it's about that injury to the air sacs. That's something that's unique to our mechanism. Essentially, the idea is that by repairing the injured cells, not only do you restore the health of the air sac of the alveolus, you also attenuate or stop that injury signal, that kind of pathological release of TGF beta 1, which is a huge contrast to the idea of blocking TGF beta 1 mediated signaling thereafter, which is, I would say, the approach that many of the other mechanisms take. essentially the idea is that by repairing the injured cells not only do you restore the health of the air sac of the alveolus you also attenuate or stop that injury signal that kind of pathological release of tgf beta 1 which is a huge contrast to the idea of blocking tgf beta 1 mediated signaling thereafter which is i would say the approach that many of the other mechanisms take The benefit is both twofold, right? the benefit is both twofold right If you're promoting repair, right, you're gonna be able to restore gas exchange capability and other elements of the disease that are not fibrosis. if you're promoting repair right you're gonna be able to restore gas exchange capability and other elements of the disease that are not fibrosis Even though we call this disease pulmonary fibrosis, it's not just about fibrosis, it's about that injury to the air sacs. even though we call this disease pulmonary fibrosis it's not just about fibrosis it's about that injury to the air sacs That's something that's unique to our mechanism. that's something that's unique to our mechanism In addition to that, right, the ability to address the fibrotic drive by stopping the signal at its source, we think can be much more potent and actually much more safe than trying to block it downstream. One of the challenges that we see with, you know, blocking TGF beta mediated signaling is that's actually an important signaling pathway for tissue hemostasis, right? You have fibrotic matrix in normal tissues. It's part of the scaffolding of your cells. If you really take a hammer and block TGF-beta 1 mediated signaling, you are liable to create toxicities, right? In addition to that, right, the ability to address the fibrotic drive by stopping the signal at its source, we think can be much more potent and actually much more safe than trying to block it downstream. in addition to that right the ability to address the fibrotic drive by stopping the signal at its source we think can be much more potent and actually much more safe than trying to block it downstream One of the challenges that we see with, you know, blocking TGF beta mediated signaling is that's actually an important signaling pathway for tissue hemostasis, right? one of the challenges that we see with you know blocking tgf beta mediated signaling is that's actually an important signaling pathway for tissue hemostasis right You have fibrotic matrix in normal tissues. you have fibrotic matrix in normal tissues It's part of the scaffolding of your cells. it's part of the scaffolding of your cells If you really take a hammer and block TGF-beta 1 mediated signaling, you are liable to create toxicities, right? if you really take a hammer and block tgf-beta 1 mediated signaling you are liable to create toxicities right That's why I think there's been such a challenge with a number of therapies, both in the clinical development pipeline as well as in the standard of care, where threading that needle between getting some efficacy, but also essentially not too much so that you don't drive toxicities can be a huge challenge. This orthogonal repair approach, we think can be, you know, kind of driven without creating the same types of liabilities. One of the other nice things to put this mechanism into context is activating the AT2 receptor, is the other side of essentially blocking the AT1 receptor. The AT1 receptor is pro-inflammatory, pro-fibrotic, and hypertensive pathway, and this actually is the pathway that's blocked by ARBs. ARBs are AT1R antagonists. That's why I think there's been such a challenge with a number of therapies, both in the clinical development pipeline as well as in the standard of care, where threading that needle between getting some efficacy, but also essentially not too much so that you don't drive toxicities can be a huge challenge. that's why i think there's been such a challenge with a number of therapies both in the clinical development pipeline as well as in the standard of care where threading that needle between getting some efficacy but also essentially not too much so that you don't drive toxicities can be a huge challenge This orthogonal repair approach, we think can be, you know, kind of driven without creating the same types of liabilities. this orthogonal repair approach we think can be you know kind of driven without creating the same types of liabilities One of the other nice things to put this mechanism into context is activating the AT2 receptor, is the other side of essentially blocking the AT1 receptor. one of the other nice things to put this mechanism into context is activating the at2 receptor is the other side of essentially blocking the at1 receptor The AT1 receptor is pro-inflammatory, pro-fibrotic, and hypertensive pathway, and this actually is the pathway that's blocked by ARBs. the at1 receptor is pro-inflammatory pro-fibrotic and hypertensive pathway and this actually is the pathway that's blocked by arbs ARBs are AT1R antagonists. arbs are at1r antagonists Of course, we know that ARBs and ACE inhibitors, which also block that pathway, have been both safe and well-tolerated, and many patients take them not only for hypertensive conditions, but also for fibrotic and inflammatory conditions. Just as that intervention point is used in a broad range of therapeutic areas effectively, we believe that so too can AT2 activation. Of course, we know that ARBs and ACE inhibitors, which also block that pathway, have been both safe and well-tolerated, and many patients take them not only for hypertensive conditions, but also for fibrotic and inflammatory conditions. of course we know that arbs and ace inhibitors which also block that pathway have been both safe and well-tolerated and many patients take them not only for hypertensive conditions but also for fibrotic and inflammatory conditions Just as that intervention point is used in a broad range of therapeutic areas effectively, we believe that so too can AT2 activation. just as that intervention point is used in a broad range of therapeutic areas effectively we believe that so too can at2 activation

Speaker 2: Yep, I hear you. That's really interesting. Wanna also ask you a bit about the prior phase II-A, the AIR trial, and in IPF patients, what are some of the key takeaways that came out of that? What should investors be learning from that trial in terms of looking ahead for your program? Yep, I hear you. yep i hear you That's really interesting. that's really interesting Wanna also ask you a bit about the prior phase II-A, the AIR trial, and in IPF patients, what are some of the key takeaways that came out of that? wanna also ask you a bit about the prior phase ii-a the air trial and in ipf patients what are some of the key takeaways that came out of that What should investors be learning from that trial in terms of looking ahead for your program? what should investors be learning from that trial in terms of looking ahead for your program

Speaker 1: Absolutely. I think the first thing to really note about this phase II-A study is it studied the drug's effect over nine months, which is quite unique for a phase II-A. Most programs in phase II-A development test only over 12 weeks, and while there's of course a practical component to this, you wanna see your signal quickly so that you can move forward, we don't necessarily believe that 12-week signals are representative of what would happen thereafter. When you have a build up of fibrotic material in IPF and this disease state, we believe that's a process that takes some amount of time, and of course, along with the fibrosis, there's always inflammation. Absolutely. absolutely I think the first thing to really note about this phase II-A study is it studied the drug's effect over nine months, which is quite unique for a phase II-A. i think the first thing to really note about this phase ii-a study is it studied the drug's effect over nine months which is quite unique for a phase ii-a Most programs in phase II-A development test only over 12 weeks, and while there's of course a practical component to this, you wanna see your signal quickly so that you can move forward, we don't necessarily believe that 12-week signals are representative of what would happen thereafter. most programs in phase ii-a development test only over 12 weeks and while there's of course a practical component to this you wanna see your signal quickly so that you can move forward we don't necessarily believe that 12-week signals are representative of what would happen thereafter When you have a build up of fibrotic material in IPF and this disease state, we believe that's a process that takes some amount of time, and of course, along with the fibrosis, there's always inflammation. when you have a build up of fibrotic material in ipf and this disease state we believe that's a process that takes some amount of time and of course along with the fibrosis there's always inflammation One of the challenges with intervention points that can both impact fibrosis and inflammation, as is the case with the drugs and development in the clinical landscape as well as the standard of care, is if you're only looking over a short period of time and you're looking at this FVC endpoint, which is the main endpoint that companies in the space study, it's forced vital capacity, and essentially it's how many milliliters of lung capacity is in your lungs. If you reduce inflammation or swelling, you might be able to improve lung capacity over a short period of time, such as 12 weeks. If you haven't really stopped the pro-fibrotic drive, then it's going to overtake any benefits over time. One of the challenges with intervention points that can both impact fibrosis and inflammation, as is the case with the drugs and development in the clinical landscape as well as the standard of care, is if you're only looking over a short period of time and you're looking at this FVC endpoint, which is the main endpoint that companies in the space study, it's forced vital capacity, and essentially it's how many milliliters of lung capacity is in your lungs. one of the challenges with intervention points that can both impact fibrosis and inflammation as is the case with the drugs and development in the clinical landscape as well as the standard of care is if you're only looking over a short period of time and you're looking at this fvc endpoint which is the main endpoint that companies in the space study it's forced vital capacity and essentially it's how many milliliters of lung capacity is in your lungs If you reduce inflammation or swelling, you might be able to improve lung capacity over a short period of time, such as 12 weeks. if you reduce inflammation or swelling you might be able to improve lung capacity over a short period of time such as 12 weeks If you haven't really stopped the pro-fibrotic drive, then it's going to overtake any benefits over time. if you haven't really stopped the pro-fibrotic drive then it's going to overtake any benefits over time That's why it's really nice to have studied our drug over a nine-month period of time, where we showed not only the ability to stabilize lung function, but actually to improve it over that period of time. That's something really unheard and unseen from before. While there are some features of our study, for example, it was an open-label study that you have to look carefully at, I think one of the really nice features is the length of the study. That's why it's really nice to have studied our drug over a nine-month period of time, where we showed not only the ability to stabilize lung function, but actually to improve it over that period of time. that's why it's really nice to have studied our drug over a nine-month period of time where we showed not only the ability to stabilize lung function but actually to improve it over that period of time That's something really unheard and unseen from before. that's something really unheard and unseen from before While there are some features of our study, for example, it was an open-label study that you have to look carefully at, I think one of the really nice features is the length of the study. while there are some features of our study for example it was an open-label study that you have to look carefully at i think one of the really nice features is the length of the study

Speaker 2: Yep. That's a really great segue. I was gonna ask you a bit about the fact that it was open-label, it was single arm. How do we extrapolate from the AIR trial to your other ongoing trial, the phase II-B ASPIRE trial? How do we think about that? Yep. yep That's a really great segue. that's a really great segue I was gonna ask you a bit about the fact that it was open-label, it was single arm. i was gonna ask you a bit about the fact that it was open-label it was single arm How do we extrapolate from the AIR trial to your other ongoing trial, the phase II-B ASPIRE trial? how do we extrapolate from the air trial to your other ongoing trial the phase ii-b aspire trial How do we think about that? how do we think about that

Speaker 1: Absolutely. I think the way you contextualize this phase II-A data set is a signal of disease modifying effect, right? I think that's what you can take away from this study, because there are a few points notwithstanding the fact that it's open-label. For example, pulmonary fibrosis patients or specifically IPF patients don't have stable lung function over a nine-month period. They don't have improved lung function, unfortunately, right? This is a disease where if you study a natural population with IPF, you would only see a single digit percentage of patients, 4%-9% having kind of a stable lung function over that period of time. Absolutely. absolutely I think the way you contextualize this phase II-A data set is a signal of disease modifying effect, right? i think the way you contextualize this phase ii-a data set is a signal of disease modifying effect right I think that's what you can take away from this study, because there are a few points notwithstanding the fact that it's open-label. i think that's what you can take away from this study because there are a few points notwithstanding the fact that it's open-label For example, pulmonary fibrosis patients or specifically IPF patients don't have stable lung function over a nine-month period. for example pulmonary fibrosis patients or specifically ipf patients don't have stable lung function over a nine-month period They don't have improved lung function, unfortunately, right? they don't have improved lung function unfortunately right This is a disease where if you study a natural population with IPF, you would only see a single digit percentage of patients, 4%- 9% having kind of a stable lung function over that period of time. this is a disease where if you study a natural population with ipf you would only see a single digit percentage of patients 4%- 9% having kind of a stable lung function over that period of time When we see that 65% of the patients at 36 weeks in our phase II-A study have improvement in lung function, that's not the kind of thing that you can get to by chance. One of the other nice features is we have a great deal of confidence that we enrolled true IPF patients. We did central radiological reading from the top experts in the field and other measures to ensure that we were enrolling true IPF patients in the phase II-A setting. If you have IPF patients and you look at them over nine months and you're seeing this really nice signal of improvement, it's tough to explain it any other way than a signal of clinical activity. Of course, there are some different features in the phase II-B. When we see that 65% of the patients at 36 weeks in our phase II-A study have improvement in lung function, that's not the kind of thing that you can get to by chance. when we see that 65% of the patients at 36 weeks in our phase ii-a study have improvement in lung function that's not the kind of thing that you can get to by chance One of the other nice features is we have a great deal of confidence that we enrolled true IPF patients. one of the other nice features is we have a great deal of confidence that we enrolled true ipf patients We did central radiological reading from the top experts in the field and other measures to ensure that we were enrolling true IPF patients in the phase II-A setting. we did central radiological reading from the top experts in the field and other measures to ensure that we were enrolling true ipf patients in the phase ii-a setting If you have IPF patients and you look at them over nine months and you're seeing this really nice signal of improvement, it's tough to explain it any other way than a signal of clinical activity. if you have ipf patients and you look at them over nine months and you're seeing this really nice signal of improvement it's tough to explain it any other way than a signal of clinical activity Of course, there are some different features in the phase II-B. of course there are some different features in the phase ii-b For example, we'll now be allowing patients on background standard of care or not on standard of care to enroll in the study. I wouldn't divine an exact treatment effect out of the phase II-A, but that's something we can check for with the ongoing study. For example, we'll now be allowing patients on background standard of care or not on standard of care to enroll in the study. for example we'll now be allowing patients on background standard of care or not on standard of care to enroll in the study I wouldn't divine an exact treatment effect out of the phase II-A, but that's something we can check for with the ongoing study. i wouldn't divine an exact treatment effect out of the phase ii-a but that's something we can check for with the ongoing study

Speaker 2: Mm-hmm. Yep. Anything else to note in the phase II-B trial design in terms of keeping an eye out, or how does it impact the potential future results? Mm-hmm. mm-hmm Yep. yep Anything else to note in the phase II-B trial design in terms of keeping an eye out, or how does it impact the potential future results? anything else to note in the phase ii-b trial design in terms of keeping an eye out or how does it impact the potential future results

Speaker 1: The phase II-B study is really set up as gold standard. It's relatively large in size. It's 360 patients. It positions the drug as one that can be used as a frontline therapy subsequently on top of standard of care or not on standard of care. We're allowing patients who are on Nintedanib standard of care, and actually nerandomilast was approved late last year. We're allowing patients on nerandomilast standard of care to enroll in the trial as well. The inclusion criteria are broad. They're materially similar to inclusion criteria that you would see in the TETON phase III studies, United Therapeutics phase III studies for IPF or other companies that are in the phase III stage studying drugs for pulmonary fibrosis. The phase II-B study is really set up as gold standard. the phase ii-b study is really set up as gold standard It's relatively large in size. it's relatively large in size It's 360 patients. it's 360 patients It positions the drug as one that can be used as a frontline therapy subsequently on top of standard of care or not on standard of care. it positions the drug as one that can be used as a frontline therapy subsequently on top of standard of care or not on standard of care We're allowing patients who are on Nintedanib standard of care, and actually nerandomilast was approved late last year. we're allowing patients who are on nintedanib standard of care and actually nerandomilast was approved late last year We're allowing patients on nerandomilast standard of care to enroll in the trial as well. we're allowing patients on nerandomilast standard of care to enroll in the trial as well The inclusion criteria are broad. the inclusion criteria are broad They're materially similar to inclusion criteria that you would see in the TETON phase III studies, United Therapeutics phase III studies for IPF or other companies that are in the phase III stage studying drugs for pulmonary fibrosis. they're materially similar to inclusion criteria that you would see in the teton phase iii studies united therapeutics phase iii studies for ipf or other companies that are in the phase iii stage studying drugs for pulmonary fibrosis In addition to that, you know, the endpoint is 52-week change in lung function as measured by FVC, and this is the regulatory endpoint. We're already looking at the phase III endpoint in the phase II-B setting. In addition to that, you know, the endpoint is 52-week change in lung function as measured by FVC, and this is the regulatory endpoint. in addition to that you know the endpoint is 52-week change in lung function as measured by fvc and this is the regulatory endpoint We're already looking at the phase III endpoint in the phase II-B setting. we're already looking at the phase iii endpoint in the phase ii-b setting

Speaker 2: Yep, yep. I know you recently expanded the size of the phase II-B, and can you talk a bit about, you know, what sites are being added? What's your level of confidence just expanding the trial, identifying efficacy signal, things like that? Anything we should know about safety checks, DSMB, stuff like that? Yep, yep. yep yep I know you recently expanded the size of the phase II-B, and can you talk a bit about, you know, what sites are being added? i know you recently expanded the size of the phase ii-b and can you talk a bit about you know what sites are being added What's your level of confidence just expanding the trial, identifying efficacy signal, things like that? what's your level of confidence just expanding the trial identifying efficacy signal things like that Anything we should know about safety checks, DSMB, stuff like that? anything we should know about safety checks dsmb stuff like that

Speaker 1: Yeah, absolutely. You know, one of the things about IPF that's unfortunate is there's a fairly limited drug development landscape in the late stage. There's only a handful of therapies. Of course, since we designed the study in 2023, there have been a few readouts. One of those is nerandomilast, which is the newest drug that's now approved by BI. That drug has shown a 70-milliliter difference from the placebo group to the treatment arm in lung function at 52 weeks, that FVC difference. Yeah, absolutely. yeah absolutely You know, one of the things about IPF that's unfortunate is there's a fairly limited drug development landscape in the late stage. you know one of the things about ipf that's unfortunate is there's a fairly limited drug development landscape in the late stage There's only a handful of therapies. there's only a handful of therapies Of course, since we designed the study in 2023, there have been a few readouts. of course since we designed the study in 2023 there have been a few readouts One of those is nerandomilast, which is the newest drug that's now approved by BI. one of those is nerandomilast which is the newest drug that's now approved by bi That drug has shown a 70-milliliter difference from the placebo group to the treatment arm in lung function at 52 weeks, that FVC difference. that drug has shown a 70-milliliter difference from the placebo group to the treatment arm in lung function at 52 weeks that fvc difference In addition to that, the TETON-2 study, so one of the two phase IIIs that United Therapeutics was running, read out last year as well and showed a 95 or 96 mL difference in lung function at 52 weeks. Prior to these readouts, we had powered our study basically with 80% power to detect a 126 mL difference in lung function at 52 weeks. Essentially, after we see these other readouts, which are positive and very well-received by both clinical communities and the investor community, you know, it became apparent that we did not need to set the bar quite that high. In addition to that, the TETON-2 study, so one of the two phase IIIs that United Therapeutics was running, read out last year as well and showed a 95 or 96 mL difference in lung function at 52 weeks. in addition to that the teton-2 study so one of the two phase iiis that united therapeutics was running read out last year as well and showed a 95 or 96 ml difference in lung function at 52 weeks Prior to these readouts, we had powered our study basically with 80% power to detect a 126 mL difference in lung function at 52 weeks. prior to these readouts we had powered our study basically with 80% power to detect a 126 ml difference in lung function at 52 weeks Essentially, after we see these other readouts, which are positive and very well-received by both clinical communities and the investor community, you know, it became apparent that we did not need to set the bar quite that high. essentially after we see these other readouts which are positive and very well-received by both clinical communities and the investor community you know it became apparent that we did not need to set the bar quite that high We actually added the patients in order to essentially provide for 80% power to detect about 97 milliliter difference in lung function between the Placebo arm and the treatment arm. Essentially, we're powered to have the best treatment effect of any IPF drug ever with this expanded trial. We actually added the patients in order to essentially provide for 80% power to detect about 97 milliliter difference in lung function between the Placebo arm and the treatment arm. we actually added the patients in order to essentially provide for 80% power to detect about 97 milliliter difference in lung function between the placebo arm and the treatment arm Essentially, we're powered to have the best treatment effect of any IPF drug ever with this expanded trial. essentially we're powered to have the best treatment effect of any ipf drug ever with this expanded trial

Speaker 2: Yep. Yep. yep

Speaker 1: You also then asked about, in addition to the efficacy signal. You also then asked about, in addition to the efficacy signal. you also then asked about in addition to the efficacy signal

Speaker 2: Just increasing your conviction in the trial. Just increasing your conviction in the trial. just increasing your conviction in the trial

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Just how are you thinking about the outcome, stuff like that. Just how are you thinking about the outcome, stuff like that. just how are you thinking about the outcome stuff like that

Speaker 1: Yeah, absolutely. I think this reflects, you know, kind of our continued conviction in the study based on both the preclinical and the phase II-A data set. I think you'd also asked about kind of some of the safety checks. Yeah, absolutely. yeah absolutely I think this reflects, you know, kind of our continued conviction in the study based on both the preclinical and the phase II-A data set. i think this reflects you know kind of our continued conviction in the study based on both the preclinical and the phase ii-a data set I think you'd also asked about kind of some of the safety checks. i think you'd also asked about kind of some of the safety checks

Speaker 2: Safety Safety safety

Speaker 1: exactly. So we're of course well underway in enrollment, well over half enrolled in the study. We've had a number of interactions with our independent Data Safety Monitoring Board and we've received no concerning feedback from them. Of course, in addition to that, we can observe the data set on a blinded basis and have seen nothing that's given us any concern as well. exactly. exactly So we're of course well underway in enrollment, well over half enrolled in the study. so we're of course well underway in enrollment well over half enrolled in the study We've had a number of interactions with our independent Data Safety Monitoring Board and we've received no concerning feedback from them. we've had a number of interactions with our independent data safety monitoring board and we've received no concerning feedback from them Of course, in addition to that, we can observe the data set on a blinded basis and have seen nothing that's given us any concern as well. of course in addition to that we can observe the data set on a blinded basis and have seen nothing that's given us any concern as well

Speaker 2: Yep. Yep. I think I might know part of this answer, but I think it might be helpful to clarify for investors. Coming out of the phase II-B, you know, what would you view as like a winning data set both on efficacy and safety tolerability, and excite you to keep moving forward with the program? Yep. yep Yep. yep I think I might know part of this answer, but I think it might be helpful to clarify for investors. i think i might know part of this answer but i think it might be helpful to clarify for investors Coming out of the phase II-B, you know, what would you view as like a winning data set both on efficacy and safety tolerability, and excite you to keep moving forward with the program? coming out of the phase ii-b you know what would you view as like a winning data set both on efficacy and safety tolerability and excite you to keep moving forward with the program

Speaker 1: Absolutely. I mean, in IPF, one of the unfortunate things is that the bar is relatively low because of the limited therapeutic landscape and because the desire here is to combine therapies, right? It's not a zero-sum game. For example, at only a 70 milliliter difference in lung function, as I mentioned, nerandomilast was very well received or is very well received by the clinical communities and that 95, 96 milliliter difference in lung function, that was very exciting both from an investor perspective and clinical perspective in terms of efficacy signals. Those are the types of efficacy signals that would really attract folks. Certainly, we're looking to see if we have effect in that level, and I think that would certainly support moving forward. Absolutely. absolutely I mean, in IPF, one of the unfortunate things is that the bar is relatively low because of the limited therapeutic landscape and because the desire here is to combine therapies, right? i mean in ipf one of the unfortunate things is that the bar is relatively low because of the limited therapeutic landscape and because the desire here is to combine therapies right It's not a zero-sum game. it's not a zero-sum game For example, at only a 70 milliliter difference in lung function, as I mentioned, nerandomilast was very well received or is very well received by the clinical communities and that 95, 96 milliliter difference in lung function, that was very exciting both from an investor perspective and clinical perspective in terms of efficacy signals. for example at only a 70 milliliter difference in lung function as i mentioned nerandomilast was very well received or is very well received by the clinical communities and that 95 96 milliliter difference in lung function that was very exciting both from an investor perspective and clinical perspective in terms of efficacy signals Those are the types of efficacy signals that would really attract folks. those are the types of efficacy signals that would really attract folks Certainly, we're looking to see if we have effect in that level, and I think that would certainly support moving forward. certainly we're looking to see if we have effect in that level and i think that would certainly support moving forward Of course, we're hopeful that we can also have something that goes well beyond that, but let's see. Of course, we're hopeful that we can also have something that goes well beyond that, but let's see. of course we're hopeful that we can also have something that goes well beyond that but let's see

Speaker 2: Yep. Yep. Just to double click on that, I noticed some companies distinguish between what's really exciting regulatory wise in terms of being able to go forward, eventually get approval and what's exciting clinically. Yep. yep Yep. yep Just to double click on that, I noticed some companies distinguish between what's really exciting regulatory wise in terms of being able to go forward, eventually get approval and what's exciting clinically. just to double click on that i noticed some companies distinguish between what's really exciting regulatory wise in terms of being able to go forward eventually get approval and what's exciting clinically

Speaker 1: Yeah. Yeah. yeah

Speaker 2: Could you break that out in terms of what you think would be really clinically meaningful, will be great regulatory wise, or is it applicable for both? Could you break that out in terms of what you think would be really clinically meaningful, will be great regulatory wise, or is it applicable for both? could you break that out in terms of what you think would be really clinically meaningful will be great regulatory wise or is it applicable for both

Speaker 1: I think it really is applicable for both. When we talk with a number of folks in the clinical community, they're actually quite excited by nerandomilast. You know, one of the key reasons for that is even though the effect on lung function appears to be modest, especially compared to the current standard of care, it's a gentler drug. It still causes gastrointestinal side effects, the feedback from clinicians and some of the data that BI's put out to date from their phase III trial reflect that it's a milder GI profile than, for example, the Nintedanib standard of care therapy. I would certainly say, you know, especially with buloxibutid's tolerability profile in development to date, even at that level, that would be quite exciting, I think, to a clinical community. I think it really is applicable for both. i think it really is applicable for both When we talk with a number of folks in the clinical community, they're actually quite excited by nerandomilast. when we talk with a number of folks in the clinical community they're actually quite excited by nerandomilast You know, one of the key reasons for that is even though the effect on lung function appears to be modest, especially compared to the current standard of care, it's a gentler drug. you know one of the key reasons for that is even though the effect on lung function appears to be modest especially compared to the current standard of care it's a gentler drug It still causes gastrointestinal side effects, the feedback from clinicians and some of the data that BI's put out to date from their phase III trial reflect that it's a milder GI profile than, for example, the Nintedanib standard of care therapy. it still causes gastrointestinal side effects the feedback from clinicians and some of the data that bi's put out to date from their phase iii trial reflect that it's a milder gi profile than for example the nintedanib standard of care therapy I would certainly say, you know, especially with buloxibutid's tolerability profile in development to date, even at that level, that would be quite exciting, I think, to a clinical community. i would certainly say you know especially with buloxibutid's tolerability profile in development to date even at that level that would be quite exciting i think to a clinical community I think again, we have hopefully with our phase II-A data set the opportunity to look for things beyond that as well. I think again, we have hopefully with our phase II-A data set the opportunity to look for things beyond that as well. i think again we have hopefully with our phase ii-a data set the opportunity to look for things beyond that as well

Speaker 2: Yep. Yep. I hear you. In the phase II-B, anything that you're watching out for potentially on the safety signal side or anything to consider given you are going after like a pretty novel pathway? Yep. yep Yep. yep I hear you. i hear you In the phase II-B , anything that you're watching out for potentially on the safety signal side or anything to consider given you are going after like a pretty novel pathway? in the phase ii-b anything that you're watching out for potentially on the safety signal side or anything to consider given you are going after like a pretty novel pathway

Speaker 1: Absolutely. What we've observed in phase II-A development to date is a tolerability signal, which is mild to moderate hair loss or hair thinning. It was observed in 19% of patients in the phase II-A study, and it's tracking similarly in the blinded data set. We believe this is ultimately a manageable side effect given that IPF is a disease of older individuals and generally of older men. It is a dose dependent side effect, we are testing both the same dose as we tested in the phase II-A as well as a half dose, 50 milligrams, twice daily. Hopefully there'll be an opportunity to potentially mitigate or eliminate that side effect if the 50 milligram dose is also efficacious. Absolutely. absolutely What we've observed in phase II-A development to date is a tolerability signal, which is mild to moderate hair loss or hair thinning. what we've observed in phase ii-a development to date is a tolerability signal which is mild to moderate hair loss or hair thinning It was observed in 19% of patients in the phase II-A study, and it's tracking similarly in the blinded data set. it was observed in 19% of patients in the phase ii-a study and it's tracking similarly in the blinded data set We believe this is ultimately a manageable side effect given that IPF is a disease of older individuals and generally of older men. we believe this is ultimately a manageable side effect given that ipf is a disease of older individuals and generally of older men It is a dose dependent side effect, we are testing both the same dose as we tested in the phase II-A as well as a half dose, 50 milligrams, twice daily. it is a dose dependent side effect we are testing both the same dose as we tested in the phase ii-a as well as a half dose 50 milligrams twice daily Hopefully there'll be an opportunity to potentially mitigate or eliminate that side effect if the 50 milligram dose is also efficacious. hopefully there'll be an opportunity to potentially mitigate or eliminate that side effect if the 50 milligram dose is also efficacious Beyond that, as you say, this is a relatively new mechanism of action. It's actually not really been studied in significant clinical development to date outside of Vicore's efforts. Vicore has made significant efforts, in the advancement of buloxibutid. Of course, we have our phase II-A data set where we studied this drug in IPF patients over nine months, and we did not observe any treatment related serious adverse event, for example. This is a mechanism in the angiotensin II pathway, so we look carefully at the hemodynamics, for example, hypertensive or hypotensive effects, and we've not observed any signals like that as well. Beyond that, as you say, this is a relatively new mechanism of action. beyond that as you say this is a relatively new mechanism of action It's actually not really been studied in significant clinical development to date outside of Vicore's efforts. it's actually not really been studied in significant clinical development to date outside of vicore's efforts Vicore has made significant efforts, in the advancement of buloxibutid. vicore has made significant efforts in the advancement of buloxibutid Of course, we have our phase II-A data set where we studied this drug in IPF patients over nine months, and we did not observe any treatment related serious adverse event, for example. of course we have our phase ii-a data set where we studied this drug in ipf patients over nine months and we did not observe any treatment related serious adverse event for example This is a mechanism in the angiotensin II pathway, so we look carefully at the hemodynamics, for example, hypertensive or hypotensive effects, and we've not observed any signals like that as well. this is a mechanism in the angiotensin ii pathway so we look carefully at the hemodynamics for example hypertensive or hypotensive effects and we've not observed any signals like that as well Actually, ultimately, buloxibutid's been exposed before this phase II-B study in over 350 patients, and we've observed a tolerability profile and a safety profile similar to what I've you know, expressed nothing significant. We do of course, see that hair loss effect that I mentioned. Actually, ultimately, buloxibutid's been exposed before this phase II-B study in over 350 patients, and we've observed a tolerability profile and a safety profile similar to what I've you know, expressed nothing significant. actually ultimately buloxibutid's been exposed before this phase ii-b study in over 350 patients and we've observed a tolerability profile and a safety profile similar to what i've you know expressed nothing significant We do of course, see that hair loss effect that I mentioned. we do of course see that hair loss effect that i mentioned

Speaker 2: Yep. Yep. To put this in context, what are you hearing from physicians in terms of the current trade-offs that they have to make in terms of prescribing today's available agents in IPF to patients on, trying to get them the best efficacy, but also helping manage the tolerability issues with current antifibrotics? Like, what is that like in terms of the baseline here? Yep. yep Yep. yep To put this in context, what are you hearing from physicians in terms of the current trade-offs that they have to make in terms of prescribing today's available agents in IPF to patients on, trying to get them the best efficacy, but also helping manage the tolerability issues with current antifibrotics? to put this in context what are you hearing from physicians in terms of the current trade-offs that they have to make in terms of prescribing today's available agents in ipf to patients on trying to get them the best efficacy but also helping manage the tolerability issues with current antifibrotics Like, what is that like in terms of the baseline here? like what is that like in terms of the baseline here

Speaker 1: Because the standard of care therapies are so limited in efficacy, for example, they have not really shown significant mortality benefit signals, although they show that difference in lung function. I would say that we've heard from a number of clinicians that they prioritize tolerability, older patient population, a lot of comorbidities, and it might be one of the reasons why, at least when you look historically before the approval of nerandomilast, only a minority of patients even initiate standard of care in the United States, actually only about 25%. That might be because, when patients and physicians think about what the tolerability profile is for this standard of care therapies, they just opt to, for example, wait and see. One of the challenges, though, is the decline in lung function is not necessarily a linear path. Because the standard of care therapies are so limited in efficacy, for example, they have not really shown significant mortality benefit signals, although they show that difference in lung function. because the standard of care therapies are so limited in efficacy for example they have not really shown significant mortality benefit signals although they show that difference in lung function I would say that we've heard from a number of clinicians that they prioritize tolerability, older patient population, a lot of comorbidities, and it might be one of the reasons why, at least when you look historically before the approval of nerandomilast, only a minority of patients even initiate standard of care in the United States, actually only about 25%. i would say that we've heard from a number of clinicians that they prioritize tolerability older patient population a lot of comorbidities and it might be one of the reasons why at least when you look historically before the approval of nerandomilast only a minority of patients even initiate standard of care in the united states actually only about 25% That might be because, when patients and physicians think about what the tolerability profile is for this standard of care therapies, they just opt to, for example, wait and see. that might be because when patients and physicians think about what the tolerability profile is for this standard of care therapies they just opt to for example wait and see One of the challenges, though, is the decline in lung function is not necessarily a linear path. one of the challenges though is the decline in lung function is not necessarily a linear path Sometimes you kind of go off a little bit of a cliff, unfortunately, with an IPF exacerbation, and then it can become, for example, too late to start a therapy. I would say that drugs with a better tolerability profile certainly be very attractive. I also think one of the reasons why there's a big hesitation and a prioritization of tolerability is there's not much benefit trade-off, right? The mortality signals are not really significant in terms of what they've shown in development to date as well. Sometimes you kind of go off a little bit of a cliff, unfortunately, with an IPF exacerbation, and then it can become, for example, too late to start a therapy. sometimes you kind of go off a little bit of a cliff unfortunately with an ipf exacerbation and then it can become for example too late to start a therapy I would say that drugs with a better tolerability profile certainly be very attractive. i would say that drugs with a better tolerability profile certainly be very attractive I also think one of the reasons why there's a big hesitation and a prioritization of tolerability is there's not much benefit trade-off, right? i also think one of the reasons why there's a big hesitation and a prioritization of tolerability is there's not much benefit trade-off right The mortality signals are not really significant in terms of what they've shown in development to date as well. the mortality signals are not really significant in terms of what they've shown in development to date as well

Speaker 2: Yep. I hear you. With your program. Thinking ahead, let's say everything works out, your program's approved in IPF, like, where would you see it layering into the treatment paradigm? Like, are you thinking monotherapy, maybe combination therapy use? Like, how would physicians want to start to use it, and then how could it integrate more into the treatment paradigm? Yep. yep I hear you. i hear you With your program. Thinking ahead, let's say everything works out, your program's approved in IPF, like, where would you see it layering into the treatment paradigm? with your program. thinking ahead let's say everything works out your program's approved in ipf like where would you see it layering into the treatment paradigm Like, are you thinking monotherapy, maybe combination therapy use? like are you thinking monotherapy maybe combination therapy use Like, how would physicians want to start to use it, and then how could it integrate more into the treatment paradigm? like how would physicians want to start to use it and then how could it integrate more into the treatment paradigm

Speaker 1: Absolutely. I mean, how we want to position the therapy is that you could take it as a frontline and that you could choose to take it on top of the available standard of care, or you could choose to take it alone. For example, if you have the discussion with the clinicians and, you know, you as a patient become comfortable with the tolerability profile of the standard of care, then you can add that on to what buloxibutid would offer. You could also choose to then take it alone if you wanna avoid it. I would say that's pretty consistent with how our study's enrolling. Absolutely. absolutely I mean, how we want to position the therapy is that you could take it as a frontline and that you could choose to take it on top of the available standard of care, or you could choose to take it alone. i mean how we want to position the therapy is that you could take it as a frontline and that you could choose to take it on top of the available standard of care or you could choose to take it alone For example, if you have the discussion with the clinicians and, you know, you as a patient become comfortable with the tolerability profile of the standard of care, then you can add that on to what buloxibutid would offer. for example if you have the discussion with the clinicians and you know you as a patient become comfortable with the tolerability profile of the standard of care then you can add that on to what buloxibutid would offer You could also choose to then take it alone if you wanna avoid it. you could also choose to then take it alone if you wanna avoid it I would say that's pretty consistent with how our study's enrolling. i would say that's pretty consistent with how our study's enrolling We're about 60% of patients enrolled to date are on a background standard of care, largely an imatinib, and then about 40% are not on standard of care, and that's actually about equally split between patients who have never taken a standard of care therapy, and then the other half are patients who started or attempted to take the standard of care but didn't tolerate the side effect profile, so have discontinued use. We're about 60% of patients enrolled to date are on a background standard of care, largely an imatinib, and then about 40% are not on standard of care, and that's actually about equally split between patients who have never taken a standard of care therapy, and then the other half are patients who started or attempted to take the standard of care but didn't tolerate the side effect profile, so have discontinued use. we're about 60% of patients enrolled to date are on a background standard of care largely an imatinib and then about 40% are not on standard of care and that's actually about equally split between patients who have never taken a standard of care therapy and then the other half are patients who started or attempted to take the standard of care but didn't tolerate the side effect profile so have discontinued use

Speaker 2: Yep. I hear you. Just broader in terms of the IPF landscape, like, where do you see the field moving towards in the future, especially if buloxibutid is available and prescribers just getting more comfortable, maybe guideline changes happening? Like, where do you see the field moving and knowing that what's coming in the pipeline too? Yep. yep I hear you. i hear you Just broader in terms of the IPF landscape, like, where do you see the field moving towards in the future, especially if buloxibutid is available and prescribers just getting more comfortable, maybe guideline changes happening? just broader in terms of the ipf landscape like where do you see the field moving towards in the future especially if buloxibutid is available and prescribers just getting more comfortable maybe guideline changes happening Like, where do you see the field moving and knowing that what's coming in the pipeline too? like where do you see the field moving and knowing that what's coming in the pipeline too

Speaker 1: Yeah, absolutely. I mean, I certainly think that there'll be a significant effort, because this is such a tough disease, to combine therapies. Right, like, there will be, you know, I think a clinician push if it's possible to put two drugs together and patients can tolerate that to do it. I think also, you know, you see it in the pulmonary hypertension space, you know, the ability to even then attempt triplet therapy. I would say the landscape is currently not mature enough to think about what goes first, what goes second, and, you know, for Vicore, that's a little bit of a flexibility benefit because then we can position as that frontline therapy. Yeah, absolutely. yeah absolutely I mean, I certainly think that there'll be a significant effort, because this is such a tough disease, to combine therapies. i mean i certainly think that there'll be a significant effort because this is such a tough disease to combine therapies Right, like, there will be, you know, I think a clinician push if it's possible to put two drugs together and patients can tolerate that to do it. right like there will be you know i think a clinician push if it's possible to put two drugs together and patients can tolerate that to do it I think also, you know, you see it in the pulmonary hypertension space, you know, the ability to even then attempt triplet therapy. i think also you know you see it in the pulmonary hypertension space you know the ability to even then attempt triplet therapy I would say the landscape is currently not mature enough to think about what goes first, what goes second, and, you know, for Vicore, that's a little bit of a flexibility benefit because then we can position as that frontline therapy. i would say the landscape is currently not mature enough to think about what goes first what goes second and you know for vicore that's a little bit of a flexibility benefit because then we can position as that frontline therapy Of course, as the landscape matures, there might be some thinking about, okay, what, you know, kind of mechanisms might be best to go first, and then what might be best to go later? I would say conceptually, because we have this epithelial repair mechanism of action, it makes a lot of sense for, you know, this one to be a frontline, and also because it's relatively well-tolerated, compared to the broader landscape, should be an easy one for people to take at the outset. Of course, as the landscape matures, there might be some thinking about, okay, what, you know, kind of mechanisms might be best to go first, and then what might be best to go later? of course as the landscape matures there might be some thinking about okay what you know kind of mechanisms might be best to go first and then what might be best to go later I would say conceptually, because we have this epithelial repair mechanism of action, it makes a lot of sense for, you know, this one to be a frontline, and also because it's relatively well-tolerated, compared to the broader landscape, should be an easy one for people to take at the outset. i would say conceptually because we have this epithelial repair mechanism of action it makes a lot of sense for you know this one to be a frontline and also because it's relatively well-tolerated compared to the broader landscape should be an easy one for people to take at the outset

Speaker 2: Yep. I hear you. Just thinking beyond IPF, are there any other fibrotic or inflammatory lung conditions that may be appealing with this mechanism, possibly maybe differentiating in that space? Are you starting to think about that? Yep. yep I hear you. i hear you Just thinking beyond IPF, are there any other fibrotic or inflammatory lung conditions that may be appealing with this mechanism, possibly maybe differentiating in that space? just thinking beyond ipf are there any other fibrotic or inflammatory lung conditions that may be appealing with this mechanism possibly maybe differentiating in that space Are you starting to think about that? are you starting to think about that

Speaker 1: Absolutely. Absolutely. absolutely

Speaker 2: Mm. Mm. mm

Speaker 1: Certainly high on our list are the other pulmonary fibrosis indications, right? Like progressive pulmonary fibrosis, which share a lot of commonalities. Many companies that pursue and attain a clinical signal in IPF move to expand into those spaces. In addition to that, we think this mechanism of action makes a lot of sense in pulmonary hypertension. We've certainly generated a really nice translational data set using the classical pulmonary hypertension models and shown a very strong effect in those settings too. Certainly, this is a highly conserved and relatively upstream mechanism of action, so we actually even are thinking for the future for buloxibutid or potentially actually for some of our follow-on molecules that are in the preclinical landscape or in preclinical pipeline to think about fibrotic and inflammatory conditions in other organs as well. Certainly high on our list are the other pulmonary fibrosis indications, right? certainly high on our list are the other pulmonary fibrosis indications right Like progressive pulmonary fibrosis, which share a lot of commonalities. like progressive pulmonary fibrosis which share a lot of commonalities Many companies that pursue and attain a clinical signal in IPF move to expand into those spaces. many companies that pursue and attain a clinical signal in ipf move to expand into those spaces In addition to that, we think this mechanism of action makes a lot of sense in pulmonary hypertension. in addition to that we think this mechanism of action makes a lot of sense in pulmonary hypertension We've certainly generated a really nice translational data set using the classical pulmonary hypertension models and shown a very strong effect in those settings too. we've certainly generated a really nice translational data set using the classical pulmonary hypertension models and shown a very strong effect in those settings too Certainly, this is a highly conserved and relatively upstream mechanism of action, so we actually even are thinking for the future for buloxibutid or potentially actually for some of our follow-on molecules that are in the preclinical landscape or in preclinical pipeline to think about fibrotic and inflammatory conditions in other organs as well. certainly this is a highly conserved and relatively upstream mechanism of action so we actually even are thinking for the future for buloxibutid or potentially actually for some of our follow-on molecules that are in the preclinical landscape or in preclinical pipeline to think about fibrotic and inflammatory conditions in other organs as well

Speaker 2: Interesting. Okay, great. Still staying future looking for a sec, in terms of a possible phase III and executing on that and thinking about BD partnerships, et cetera, like, a lot of options could lie before you. How are you thinking if everything works out for your phase II-B and moving forward and possible strategic partnerships that may come in beyond that in terms of optionality? Interesting. interesting Okay, great. okay great Still staying future looking for a sec, in terms of a possible phase III and executing on that and thinking about BD partnerships, et cetera, like, a lot of options could lie before you. still staying future looking for a sec in terms of a possible phase iii and executing on that and thinking about bd partnerships et cetera like a lot of options could lie before you How are you thinking if everything works out for your phase II-B and moving forward and possible strategic partnerships that may come in beyond that in terms of optionality? how are you thinking if everything works out for your phase ii-b and moving forward and possible strategic partnerships that may come in beyond that in terms of optionality

Speaker 1: Yeah, absolutely. First, we think it's quite feasible for the team that we've built, to scale to develop the drug in the phase III setting. Our phase II-B, which our team's really executed well on to date, is 360 patients. The TETON studies, phase III studies, for example, are 590 or so patients. We think that there's a feasible way to scale up into a phase III setting. In addition to that, because IPF is a larger rare disease, but it is a rare disease, we believe that it's quite feasible also to build out the right size sales force in the United States to be able to commercialize the therapy as well. Yeah, absolutely. yeah absolutely First, we think it's quite feasible for the team that we've built, to scale to develop the drug in the phase III setting. first we think it's quite feasible for the team that we've built to scale to develop the drug in the phase iii setting Our phase II-B, which our team's really executed well on to date, is 360 patients. our phase ii-b which our team's really executed well on to date is 360 patients The TETON studies, phase III studies, for example, are 590 or so patients. the teton studies phase iii studies for example are 590 or so patients We think that there's a feasible way to scale up into a phase III setting. we think that there's a feasible way to scale up into a phase iii setting In addition to that, because IPF is a larger rare disease, but it is a rare disease, we believe that it's quite feasible also to build out the right size sales force in the United States to be able to commercialize the therapy as well. in addition to that because ipf is a larger rare disease but it is a rare disease we believe that it's quite feasible also to build out the right size sales force in the united states to be able to commercialize the therapy as well In addition to that, of course, we're, you know, it's quite nice to see that there's a lot of pharma interest in IPF as a therapeutic area. I certainly think that that will be an option that we can consider as well. Certainly we're excited and have a vision to be able to push this forward on our own. In addition to that, of course, we're, you know, it's quite nice to see that there's a lot of pharma interest in IPF as a therapeutic area. in addition to that of course we're you know it's quite nice to see that there's a lot of pharma interest in ipf as a therapeutic area I certainly think that that will be an option that we can consider as well. i certainly think that that will be an option that we can consider as well Certainly we're excited and have a vision to be able to push this forward on our own. certainly we're excited and have a vision to be able to push this forward on our own

Speaker 2: Yep. I wanted to ask also a landscape question. Like, how would you frame your program against some of the other IPF mechanisms that are being explored today in the clinic, in terms of what's coming up? Like, I know there's some companies focusing on the LPA1 mechanism as well, and data sets coming later this year, like BMS has a phase III reading out. Well, I know it's not apples to apples, but how would you possibly cross compare or think about extrapolating from competitive data sets to your program? Yep. yep I wanted to ask also a landscape question. i wanted to ask also a landscape question Like, how would you frame your program against some of the other IPF mechanisms that are being explored today in the clinic, in terms of what's coming up? like how would you frame your program against some of the other ipf mechanisms that are being explored today in the clinic in terms of what's coming up Like, I know there's some companies focusing on the LPA1 mechanism as well, and data sets coming later this year, like BMS has a phase III reading out. like i know there's some companies focusing on the lpa1 mechanism as well and data sets coming later this year like bms has a phase iii reading out Well, I know it's not apples to apples, but how would you possibly cross compare or think about extrapolating from competitive data sets to your program? well i know it's not apples to apples but how would you possibly cross compare or think about extrapolating from competitive data sets to your program

Speaker 1: Yeah, absolutely. I think first of all, conceptually, these mechanisms of action, again, are in that space of trying to block the fibrotic cascade. You know, what basically TGF-beta 1 and other pro-fibrotic cytokines bring. The LPA1 mechanism of action is quite different from that perspective in our view. I would also say that's consistent with the clinical data sets that have been shown with this mechanism of action to date. We're talking about therapies that have the potential to have effect, but more in the zone of slowing the decline of lung function incrementally. BMS, of course, has put out, you know, phase II, phase II data set for their mechanism of action, where they do show that ability to incrementally slow the decline of lung function. Yeah, absolutely. yeah absolutely I think first of all, conceptually, these mechanisms of action, again, are in that space of trying to block the fibrotic cascade. i think first of all conceptually these mechanisms of action again are in that space of trying to block the fibrotic cascade You know, what basically TGF-beta 1 and other pro-fibrotic cytokines bring. you know what basically tgf-beta 1 and other pro-fibrotic cytokines bring The LPA1 mechanism of action is quite different from that perspective in our view. the lpa1 mechanism of action is quite different from that perspective in our view I would also say that's consistent with the clinical data sets that have been shown with this mechanism of action to date. i would also say that's consistent with the clinical data sets that have been shown with this mechanism of action to date We're talking about therapies that have the potential to have effect, but more in the zone of slowing the decline of lung function incrementally. we're talking about therapies that have the potential to have effect but more in the zone of slowing the decline of lung function incrementally BMS, of course, has put out, you know, phase II, phase II data set for their mechanism of action, where they do show that ability to incrementally slow the decline of lung function. bms of course has put out you know phase ii phase ii data set for their mechanism of action where they do show that ability to incrementally slow the decline of lung function Certainly it can have a place in the broader landscape. You can try combining this with other therapies. We think that, you know, the buloxibutid mechanism of action is distinct both because it acts on the epithelial side, so it acts on this injury, which we haven't actually seen any therapy to date in the clinic that's shown kind of data in a phase II setting or beyond, with that type of an effect. Of course, that corresponds to what we've seen, at least initially, as this signal of improvement in lung function as well. Certainly it can have a place in the broader landscape. certainly it can have a place in the broader landscape You can try combining this with other therapies. you can try combining this with other therapies We think that, you know, the buloxibutid mechanism of action is distinct both because it acts on the epithelial side, so it acts on this injury, which we haven't actually seen any therapy to date in the clinic that's shown kind of data in a phase II setting or beyond, with that type of an effect. we think that you know the buloxibutid mechanism of action is distinct both because it acts on the epithelial side so it acts on this injury which we haven't actually seen any therapy to date in the clinic that's shown kind of data in a phase ii setting or beyond with that type of an effect Of course, that corresponds to what we've seen, at least initially, as this signal of improvement in lung function as well. of course that corresponds to what we've seen at least initially as this signal of improvement in lung function as well

Speaker 2: Yep. Sounds great. Also want to throw in a question. How are you feeling about current cash position, executing against all your goals? You know, what are you most excited or looking forward to coming up? Yep. yep Sounds great. sounds great Also want to throw in a question. also want to throw in a question How are you feeling about current cash position, executing against all your goals? how are you feeling about current cash position executing against all your goals You know, what are you most excited or looking forward to coming up? you know what are you most excited or looking forward to coming up

Speaker 1: What's nice to see is that we're well capitalized, about $130 million cash position as of year-end, and that provides us with sufficient capital to have this clinical readout in mid-2027, with an additional year of Opex thereafter, as well. We're really excited to complete enrollment in the first half of this year, hopefully, report out those results. We're certainly gonna be excited to be at the American Thoracic Society, which is the key conference, in this space in May, and have some interesting, kind of, complementary data sets that we'll be putting out at that conference as well. What's nice to see is that we're well capitalized, about $130 million cash position as of year-end, and that provides us with sufficient capital to have this clinical readout in mid-2027, with an additional year of Opex thereafter, as well. what's nice to see is that we're well capitalized about $130 million cash position as of year-end and that provides us with sufficient capital to have this clinical readout in mid-2027 with an additional year of opex thereafter as well We're really excited to complete enrollment in the first half of this year, hopefully, report out those results. we're really excited to complete enrollment in the first half of this year hopefully report out those results We're certainly gonna be excited to be at the American Thoracic Society, which is the key conference, in this space in May, and have some interesting, kind of, complementary data sets that we'll be putting out at that conference as well. we're certainly gonna be excited to be at the american thoracic society which is the key conference in this space in may and have some interesting kind of complementary data sets that we'll be putting out at that conference as well We'll also, of course, in later in the year, report out on a futility analysis that we're conducting after about 30% of patients have completed the one-year treatment period. A few milestones coming up later this year that we're really looking forward to. We'll also, of course, in later in the year, report out on a futility analysis that we're conducting after about 30% of patients have completed the one-year treatment period. we'll also of course in later in the year report out on a futility analysis that we're conducting after about 30% of patients have completed the one-year treatment period A few milestones coming up later this year that we're really looking forward to. a few milestones coming up later this year that we're really looking forward to

Speaker 2: Yeah, definitely. On the futility analysis, is there a sort of bar you're looking to beat, or is it just a simple futility analysis? Can you just refresh us on the assumptions there? Yeah, definitely. yeah definitely On the futility analysis, is there a sort of bar you're looking to beat, or is it just a simple futility analysis? on the futility analysis is there a sort of bar you're looking to beat or is it just a simple futility analysis Can you just refresh us on the assumptions there? can you just refresh us on the assumptions there

Speaker 1: We've constructed the futility analysis as one that doesn't cost alpha, it's a simple kind of yes/no, and it'll be evaluated by the DSMB according to kind of pre-specified criteria, which we'll talk a little bit more about in the future. Of course, we'll keep the folks updated as we get closer to that, both in terms of what the assumptions are as well as once we have that ultimate futility analysis result. We've constructed the futility analysis as one that doesn't cost alpha, it's a simple kind of yes/no, and it'll be evaluated by the DSMB according to kind of pre-specified criteria, which we'll talk a little bit more about in the future. we've constructed the futility analysis as one that doesn't cost alpha it's a simple kind of yes/no and it'll be evaluated by the dsmb according to kind of pre-specified criteria which we'll talk a little bit more about in the future Of course, we'll keep the folks updated as we get closer to that, both in terms of what the assumptions are as well as once we have that ultimate futility analysis result. of course we'll keep the folks updated as we get closer to that both in terms of what the assumptions are as well as once we have that ultimate futility analysis result

Speaker 2: Yep. Super interesting. In the last couple minutes, I'll ask a bigger picture question again. What do you think investors in your conversations recently most underappreciate about the Vicore story, in terms of, you know, what should people be looking out for? Yep. yep Super interesting. super interesting In the last couple minutes, I'll ask a bigger picture question again. in the last couple minutes i'll ask a bigger picture question again What do you think investors in your conversations recently most underappreciate about the Vicore story, in terms of, you know, what should people be looking out for? what do you think investors in your conversations recently most underappreciate about the vicore story in terms of you know what should people be looking out for

Speaker 1: I mean, I think that there are a few things. I think it's the consistency of the mechanism and what it's supposed to do. Even when you look at these medical textbooks, you know, the AT2 receptor, the angiotensin II pathway as part of the renin-angiotensin system is known. The role of this receptor is tissue repair, fibrosis resolution, anti-inflammatory, vasodilatory effect. We see that it does that in a really broad range of preclinical data sets. Then we see in a clinical data set over nine months, the ability then for this drug to actually translate that broad efficacy into an improvement in lung function. I think it's a very nice thread from principle to preclinical to clinical and quite an orthogonal approach to others. We're really excited to see this phase II-B result. I mean, I think that there are a few things. i mean i think that there are a few things I think it's the consistency of the mechanism and what it's supposed to do. i think it's the consistency of the mechanism and what it's supposed to do Even when you look at these medical textbooks, you know, the AT2 receptor, the angiotensin II pathway as part of the renin-angiotensin system is known. even when you look at these medical textbooks you know the at2 receptor the angiotensin ii pathway as part of the renin-angiotensin system is known The role of this receptor is tissue repair, fibrosis resolution, anti-inflammatory, vasodilatory effect. the role of this receptor is tissue repair fibrosis resolution anti-inflammatory vasodilatory effect We see that it does that in a really broad range of preclinical data sets. we see that it does that in a really broad range of preclinical data sets Then we see in a clinical data set over nine months, the ability then for this drug to actually translate that broad efficacy into an improvement in lung function. then we see in a clinical data set over nine months the ability then for this drug to actually translate that broad efficacy into an improvement in lung function I think it's a very nice thread from principle to preclinical to clinical and quite an orthogonal approach to others. i think it's a very nice thread from principle to preclinical to clinical and quite an orthogonal approach to others We're really excited to see this phase II-B result. we're really excited to see this phase ii-b result

Speaker 2: Yeah. That sounds great. Looking forward to the data. Yeah. yeah That sounds great. that sounds great Looking forward to the data. looking forward to the data

Speaker 1: Yeah. Thank you. Yeah. yeah Thank you. thank you

Speaker 2: Thanks so much for joining me, Ahmed. We are now at time. I'll have to close the call. Thanks so much for joining me, Ahmed. thanks so much for joining me ahmed We are now at time. we are now at time I'll have to close the call. i'll have to close the call

Speaker 1: Thank you, Roanna. Thank you, Roanna. thank you roanna

Speaker 2: Yep. Thanks. Yep. yep Thanks. thanks