Great. Good morning, everyone. I'm Alex Thompson, Biotech Analyst here at Stifel. My pleasure to introduce this morning Keith and Greg from the Pliant Therapeutics team to have a fireside chat. So maybe I'll kick it over to Keith to do a quick overview of Pliant, and then we'll get into a Q&A.
Yeah, sure. Thanks for having us. Pliant is about a nine-year-old company. We were founded at UCSF by Third Rock. We're focused on rare fibrotic diseases. We're mainly small molecules and focused on integrin inhibitions to date. Over the course of the history of the company, we've developed four pipeline assets. Our lead asset is bexotegrast. It's a dual inhibitor of two integrins that are the drivers of fibrosis in the lungs and, in some cases, in the liver. So we're developing bexotegrast in IPF. We've passed our phase II-A data. We're in the process of executing our phase II-B, phase III seamless trial. That trial is currently enrolling. We expect it to be fully enrolled in the first quarter. We'll have data mid-2026. And then that trial will roll seamlessly into a phase III that'll start enrolling first quarter next year when enrollment's complete in the phase II-A .
We made a lot of progress. We've got a couple of early-stage assets, but really the focus for the company right now is on pulmonary fibrosis.
Great. Yeah. So maybe taking a step back, we've talked a little bit about bexotegrast and broadly the design rationale here going after TGF-β fibrosis, but upstream. So maybe Greg, do you want to talk a little bit about the design rationale there for bexotegrast?
Sure. So within the injured lung, αvβ6 and αvβ 1 are upregulated significantly, and it really is synonymous with fibrosis. So to selectively target TGF-β within the lung and avoid the systemic toxicity that's been associated with systemic inhibition, bexotegrast has the focus and the targeted approach to limit TGF-β within the lung, which is pathogenic in IPF, but maintain its important homeostatic function.
I guess then as we think about IPF as the lead indication here, what is the current state of the IPF market? What are the key unmet needs? What does the development landscape look like?
Yeah. So there are two approved therapies. Boehringer Ingelheim has Ofev, and Roche has Esbriet. These are drugs that have been on the market for about or since, I think, 2012 or thereabouts. Esbriet is generic now. Ofev will be generic, I think, next year. These are two drugs that have shown the ability to slow progression of IPF but not stabilize the disease. So they are only able to really slow down the disease. The issue with the two therapies is that they have serious tolerability issues. Ofev has some liver tox or liver issues. And also, the main thing with that is diarrhea. So it causes diarrhea in about 60% of patients. Similar with Esbriet, I think there are some GI issues there as well, as well as some other idiosyncratic AEs as well.
The problem with the space right now is that about half of patients who are diagnosed with IPF don't get treated because of the tolerability issues there. We think there's a huge unmet need. The market is around $4 billion today, even with the need that remains. We think there's a huge opportunity for a therapy or a group of therapies that could fill that gap with equivalent efficacy but with improved tolerability.
Yeah. And I guess to drill down a little bit more on the efficacy point, obviously the tolerability is a huge issue with these current therapies, but how well do they actually treat the disease?
Yeah. So the data that they showed in their registrational studies show that they slowed down the disease by about half. So whereas I think the placebo group was losing, was it 200 mL a year? The treated group was losing about 100 mL of volume in their lungs per year. So it's a quickly progressing disease. I think without treatment, the median survival is about three to five years. So you can imagine that you're extending mortality, excuse me, but not significantly.
Yep. Yep. So then jumping into your proof of concept work, the phase II-A trial, I mean, at a high level, can you talk about the key takeaways across the dose ranging work you did at 12 weeks?
Sure. So in INTEGRIS-IPF, in that 12-week study, we saw that there was a treatment effect in terms of change in FVC from baseline to week 12. That was supported not just in that one arm, but then we saw stabilization of radiographic fibrosis and a change in biomarkers. Then we actually began to see symptomatic differences between the groups. The totality of the data suggests that treatment effect is across several different lines of objective assessment. Certainly we're excited. Certainly there was a dose-dependent change, and we're carrying forward 160 and the 320 milligram to the current study, bexotegrast.
Yep. And in terms of the patient population that you looked at, I think one of the questions here is thinking about a drug that could be used on top of standard of care. I guess can you talk about your rationale for studying bexotegrast on top of background therapy?
I think with two approved therapies, we understood it was more likely than not that patients would be on nintedanib or pirfenidone. But certainly, as Keith mentioned, a large proportion of patients wouldn't. So we allowed that. 80% of the individuals were on one of the two drugs, but 20% were not. And we saw a treatment effect in those on and off a background therapy. And it really opens the market, we think, because of the limited uptake in about only 50% of patients. And given its safety profile, we believe that's favorable moving forward to address the unmet need.
Then you were able to study the 320 milligram group out to 24 weeks. I guess patients were studied beyond 24 weeks as well. Can you talk about what you saw there and how that progressed over time?
So when we looked at the 320 versus their cohort placebo, we saw an increase in FVC and then a durable treatment response out to 24 weeks, suggesting that there's continued efficacy. And the safety profile went out to 40 weeks. So I think we're really further evidencing not only the favorable safety profile, but a durable treatment effect.
I think one of the questions coming out of INTEGRIS more broadly is just how variable FVC measures can be. I guess as you think in the totality of the data across the INTEGRIS study, what do you feel like is the most convincing as it relates to just the signal that you're seeing there?
I think it's what I mentioned before, that we saw a treatment effect not only in change in FVC, but objective assessment of radiographic fibrosis, which is done by centralized automated assessment. And that's compounded by what we see in the biomarkers. So it really is all of the different aspects of evidence of a treatment effect rather than just one marker. It's a constellation of four different ones, and they're all correlating in the same direction.
Yep. So then maybe turning towards BEACON-IPF. So this is seamless phase II, phase III. Can you talk about the design rationale here and how it compares to INTEGRIS, I guess, in terms of the patient population that you're enrolling?
From the patient population standpoint, we anticipate a similar group of individuals. We're targeting at least 30% not on background therapy, and that allows us to have within BEACON-IPF two independent, robust, rigorous, pivotal studies moving forward, a phase II-B and then a phase III study that allows us to literally accelerate development, but in a rigorous and robust manner, and perhaps get to NDA as quickly as possible.
Yep. And how much, as you think about running this seamless trial, how much time savings does that really equate to?
Yeah. So if you think about the time after your last patient in phase II-B, you've got a year of treatment. You've got time to get to data, and then you've got to ramp up your phase III. You save it at least two years there.
Yeah, because as soon as we enroll the last patient in phase II-B, the next patient will be in the phase III. So we lose zero time there.
Yep. And I guess digging into this a little bit more, FDA was not sort of open necessarily to enrolling the seamless design in the U.S. Can you talk a little about FDA interactions here and if that's progressing at all, if there's a possibility to expand the phase III in the U.S.?
Yeah, so I'll maybe jump in if you, Greg, but there have been a few important failures in this space. We had the Galapagos trial that went from a 23-patient phase II to a 1,500-patient phase III. We had the Biogen study that went from a fairly small phase II into a phase III, and then both those studies ended up having tox. I believe that FDA is fairly conservative in pulmonary fibrosis at the moment. They don't want to see a large number of patients enroll at the same time before having long-term safety data. That's been their issue. There's nothing with our program that is of a concern to them. I think it's just history and the disease indication. We haven't had that issue globally. Everywhere else in the world, we have the ability to run the seamless design.
Once we have future further safety data from the phase II-B, there's a good chance that the FDA will approve the phase III portion, but right now, they're a bit conservative on the safety side.
What does the cadence of interactions look like with the FDA in terms of what would the path forward look like there?
I guess one comment I'll make is when we met with them, they were encouraging us to design our phase II-B as a pivotal study, meaning there were certain statistical aspects that are required when a study is assessed for one of the two pivotal studies. So the interaction was, I would say, highly encouraging. They provided the appropriate guidance, and they were encouraging us to design our study in anticipation of valid data. It could serve as one of the two pivotals. So I took that as a very positive interaction.
Yep. And so if this does not roll into a phase III in the U.S., at least until you have top-line data from the phase II-B in 2026, what does that mean for the phase III trial from a registrational perspective in the U.S.?
The phase III is a global study. It's representative of the U.S. population. We have sites in Europe, Asia, South America, Australia, Canada. It's a representative study. We're measuring a global endpoint. FVC is measured the same in every country. They use the same criteria. We don't see any issue with the trial being registrational in the U.S. If you look at the fact that we'll have two confirmatory studies, the phase II-B being one of them, that study will have a large portion of U.S. patients in it. We'll have a very good representation in the trial.
I think I asked this question in a fireside here last year, but I guess are we out of the woods on safety yet with αvβ6 ? I guess as it relates to DSMB interactions out of BEACON-IPF, what can you say about how those have been and how many patients do you have on drug for at least a year at this point?
Yeah. So we've been in over 700 patients. I mean, it goes up every day. In our phase II-A, we had patients out to 40 weeks in both the IPF and PSC studies. So count for both of those. We do have patients out to a year at this point in the BEACON-IPF study. I mean, the key AE that you look for in IPF is exacerbations, right? That's a very dangerous situation for patients to get into, and that's when you have an acute inflammation or exacerbation that can cause respiratory distress, and patients can die, and that's killed a lot of programs. We haven't seen any of that in our patients so far, so we feel like it's gone as well as it possibly could.
Obviously, we're going to be monitoring patients closely going forward, but we feel very good about safety based on the data we have to date.
Yeah. And you mentioned the DSMB. So at a regular prescribed interval, both in INTEGRIS-IPF, but also in BEACON-IPF, they evaluate the data. And we've received continually recommendations to continue without modification, which is essentially the safety profile is appropriate, and that has occurred in BEACON-IPF as well.
So in terms of timelines here, full enrollment is mentioned in Q1 , topline, middle of 2026. Can you talk about sort of the assumptions that have gone into those guidance timelines?
Yeah. It's complicated to run a global study. I mean, you have sites coming on board throughout. So you have sort of this ramp-up period. We're in that ramp-up period at this moment. I mean, it's not long until Q1. But I will tell you that our projections that we started with, we've been on or ahead of those projections for the entire study. We fully expect to be fully enrolled in the first quarter. It's a year-long study. And then you have a few weeks to get your database locked, get the data cleaned up, and get it ready to release. So mid-2026 is our guidance for data. It's probably a little bit conservative. We'll do everything we can to pull those timelines in. But we feel very good about where we're at from a projection standpoint.
Yep, so we kind of touched on the competitive landscape, I guess, a little bit in terms of the commercial landscape, but I think you alluded to this before too. It's just there's been a lot of challenges here from proof of concept to pivotal translation in this space, and I guess, I don't know, what are your perspectives on why that's been such a challenge in IPF so far?
Yeah. I mean, there's been a few recent failures that have really hurt the space. FibroGen was one. Galapagos was one. Biogen was another. If you look at each of these studies individually, the phase II studies were not run in the same way that the phase III were run, right? FibroGen used a different statistical analysis for their phase II study versus phase III. Galapagos had a very small phase II and went into phase III. And BI had they actually used a dose in their phase III they had never used before. So it's been tough. And the scuttlebutt on the street has been that the phase II are not predictive of phase III. Now we finally have a study from BI with their new PDE4.
They came out with a press release a few weeks ago that says that they actually have met their primary endpoint in their phase III. And we know from their phase II that they actually used the appropriate statistical analysis that is required in phase III. So they had a positive phase II. They ran a phase III that was very similar to the phase II, and it actually worked. So it's great to see that the quality of development can actually be successful. So we feel like we're in that same position. I mean, we had similar, although I think slightly superior data to their phase II data. We used the MMRM model for statistical analysis for our phase II, which is what is required for approval from the FDA. So we'll be using that same analysis in our phase II-B and phase III.
We feel that we're in a very good position to replicate positive data.
Yeah. I guess assuming that they present data sometime next year, what are you going to be looking for out of that data set to give you more confidence in BEACON-IPF and moving forward?
Yeah. I mean, we don't know much about what their data looks like. I mean, they've only said that they hit their primary endpoint. We'll be looking closely at safety. I think the issue with the phase II data from the PDE4, and it's a known class effect, was diarrhea. So when you put a PDE4 on top of Ofev, which causes diarrhea itself, then you magnify that effect. So we'll be looking closely to see how they manage that. And hopefully, that was something that they could because we want that drug to be successful because patients really need another option. But that safety is going to be crucial, right? And I think it's important to see how the drug behaves off standard of care as well as on. So we need to see what both patient populations are doing.
They filed too, so potentially approval next year as well.
Yeah. I don't think they have filed yet.
Oh, they haven't?
They said they were going to. It's unclear what the timeline was, though. So we really don't know. Greg, do you have any thoughts?
No.
So then thinking about fibrotic lung disease more broadly, you've talked more recently about PPF as another adjacent potential indication for bexotegrast. Can you talk a little bit about why that makes sense and what a path forward might look like there?
Sure. So the pathophysiology in progressive pulmonary fibrosis as opposed to IPF, they're very similar. The difference is we generally know what causes other forms of pulmonary fibrosis. We don't know what causes IPF. But ultimately, it's TGF-β that drives the disease. We have done a lot of research around precision cut tissue slices from patients with different types of pulmonary fibrosis, scleroderma, rheumatoid arthritis, etc., and have shown that they have increased expression of αvβ6 and αvβ6 1. And that's what we would expect, right? Because TGF-β is actually what's the αvβ1 and αvβ6 are driving the TGF-β, which is driving the disease. So we feel like we should have a very good chance of having a similar effect in PPF that we do in IPF.
The two groups of individuals, patients with IPF and patients with PPF or progressive pulmonary fibrosis, their prognosis is similar. So once you have that progressive course, they almost overlap in terms of their survival curves. So it's an obvious group with tremendous unmet need. Certainly, for some individuals, they take advantage of nintedanib, which has been approved in PPF. But the same challenges are even, I would say, harder in that group because they're on underlying concomitant meds to, say, treat their rheumatoid arthritis that can cause diarrhea. So it really speaks to we need an effective therapy that also is tolerable because the inability to take any treatment limits its efficacy long-term, which is really unfortunate not only for patients with IPF, but patients with PPF.
Striking that balance in terms of identifying a medication that is effective potentially can improve symptoms, which is one of the biggest complaints that patients have, and is tolerable for a longer period of time really will afford the community the best treatments moving forward.
What does the regulatory path look like here?
It's a defined path. I mean, Ofev, nintedanib has actually been approved in PPF. It's clear. I mean, it's similar to IPF, I think. The path has been sort of laid out there. The important thing for PPF is that we can do a single study in PPF and potentially get approved in that indication. What we'd like to do is have the approvals, assuming we can get there, have approvals for IPF and PPF as close together as we can so we can actually pull all those patients in as early as possible.
Yep. So the other indication that you've done work on here is PSC, liver fibrosis. I guess can you talk at a high level of the rationale here and what the current state is of this program?
Yeah. So the physiology of PSC is interestingly similar to IPF. So it's a disease of the biliary tract, which is lined by epithelial cells. So in PSC, you have your cholangiocytes or your epithelial cells and your stellate cells, which are similar to your fibroblasts, overexpressing αvβ6 and αvβ 1, driving fibrosis and causing strictures of the bile ducts. So it was designed bexotegrast was sort of targeted at PSC from the start because of the design of the drug. So it makes a lot of sense to go into PSC. The issue that we've had is the path to registration is undefined in that indication. So that's been a struggle for the industry as a whole. I think no one's really been able to agree with the FDA on how to get a drug approved in PSC.
And so you have talked to the FDA about what the potential next steps would be. What are your considerations about moving forward with doing a broader dose ranging study?
Yeah. I mean, what we saw in phase II in PSC was very encouraging. We looked at a number of measures similar to what we did in IPF, a number of measures across the liver. Most interesting, I think, was the MRI data where we showed sort of the hepatocytes were more healthy. They were taking up contrast faster, and they were moving bile to the common bile duct faster. So that implies that potentially we were relieving some of the strictures with bexotegrast, and that improvement continued from 12 weeks to 24 weeks, so patients continue to get better over that time period. So we really think the drug has a very good chance of working there, so we went to the FDA with a plan for a phase II-B trial, and they agreed on non-invasive endpoints for a trial there.
Problem is they haven't commented on a phase III endpoint, so we feel that going into a phase II-B at the moment would be a high-risk endeavor because we would be unclear if that would de-risk the phase III actually for us, and given our current resources, we feel like the better proposition is to focus on IPF and PPF because there we have a very defined path to approval.
And then beyond bexotegrast, you also have a development pipeline. I guess, can you talk about the status of both your muscular dystrophy program and your solid tumor programs and sort of what the path forward looks like for potentially executing on partnership discussions and outlicensing?
Yeah. So the furthest along is oncology. So that's an αvβ8 , αvβ 1 dual inhibitor targeting TGF-β in the tumor microenvironment. So the idea there is to remove the anti-inflammatory effect of TGF-β in the tumor microenvironment and allow the immune system to take over and allow checkpoint inhibitors to actually have an effect on the tumor. We are in phase I. We've completed enrollment of our third cohort of patients in that phase I. We expect to have data in the first quarter or early next year. And once we have that data, so that'll be PK safety in mono as well as in combination with Pembro. We'll have some biomarkers for activity. Probably not a lot of response data because it's a small phase I trial.
But once we have that set of data, PK, PD safety, we will likely have conversations around that program. We're not an oncology company. We have the expertise to build these integrated inhibitors. So that's how this sort of started. But yeah, this will ultimately be a partner program, and we'll have those discussions next year. Now, the DMD program, this is an α 7 β 1 allosteric agonist. So this augments a compensatory mechanism for the lack of dystrophin in DMD patients or muscular dystrophy patients in general. We've cleared the CTA in Australia for that study. So we're free to start a phase I whenever we like. We are currently running some experiments in-house to determine if we could potentially expand that program outside of muscle.
So we're going to collect the data from these experiments, determine the path forward there because before we run a phase I, we'd like to make sure that we're measuring the right thing in phase I, right?
What do you mean by outside of muscle?
We're not ready to talk about that. We're still running experiments, but different organ systems. We think α7β1 could be active in other parts of the body outside of muscle, so more to come there, we hope, but if not, then we will focus on DMD with that asset. Ultimately, that will be a partnerable asset as well, so once we have the full picture of where we think that program can be effective, then we'll likely have conversations there as well.
And how would you characterize strategic interests in these programs at this point? Are you just not ready to have those conversations, or are the people poking around?
For the oncology program, we would like to have the data, right? So before we partner that because this is meant to be a combination with the checkpoint inhibitor. So we'd like to have some safety data and PK data in combination with the checkpoint inhibitor before we have those conversations because we feel like that unlocks value there. Interest is significant. I mean, we have had a number of conversations around that molecule. DMD, similar. We feel that in that space, you really have to have a specialized expertise around DMD to be successful there. So we want to see that in the right hands. And we've had preliminary conversations around that. So we'll hope for something to come out of it.
And I guess final question here. Can you talk about your cash position, your runway, and what's embedded in those assumptions?
Yeah. So we finished the quarter with $406 million. We're funded through 2026 and into the front end of 2027. That gets us probably three quarters or so past our phase II-B data in IPF. The assumptions around that are that we do have the phase III plan, obviously. We're not planning to.