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.