Good morning, and welcome to the H.C. Wainwright 26th Annual Global Investment Conference. My name is Ed Arce. I'm one of the Senior Biotech Analyst here at H.C. Wainwright, and our next presenting company is Pliant Therapeutics. I'm very pleased to have with us two representatives from the company. To my far left is Keith Cummings. He's the Chief Financial Officer, and to my immediate left is Eric Lefebvre. He is the Chief Medical Officer. Keith and Eric, welcome. Thank you. Thank you so much. Appreciate you having us. Great to have you here. So, for those who may not be familiar with Pliant, perhaps we could just start by a brief overview of the company and your programs. Sure. Yeah, Pliant's been around for about nine years. We're focused on orphan fibrotic diseases. To date, we've been focused on integrin inhibition in the TGF-beta pathway with oral small molecule candidates. We've taken four candidates to IND so far, and our lead program is Bexotegrast, which we're testing in IPF, as well as we have data in PSC as well. Right. Great. So, before we get into the specific programs, four of which you've mentioned, maybe we could just briefly discuss your core platform technology with the oral small molecule integrins. Yeah. Sure. And the fibrotic pathways that come from that. Sure. Yeah, the company was founded on a set of compounds that were inhibitors of a specific integrin, alpha-v beta-1. Since then, we've built a best-in-class medicinal chemistry capability around sort of what we learned from that set of molecules, as well as a high-throughput screening platform. So what we can do is develop molecules very quickly with our chemistry, and we can screen against any of the 24 known integrins, so we can create and test molecules in a very efficient manner. To date, we have developed well over 10,000 molecules that we have in a library, and we can target any integrin out there to with inhibition, as well as, in some cases, activation. And from that, we've been able to pull molecules for specific, when targets have been discovered. For example, our oncology program sort of came out of that library. So that gives us a really efficient way to quickly develop drugs against new targets that we've identified. Great. So, let's dive in then with your lead Bexotegrast program, which is in idiopathic pulmonary fibrosis, as you mentioned. You've now completed readouts in your phase II-A in INTEGRIS-IPF study, both at 12 and 24 weeks. Maybe we could go over some of the key data, and in both functional and biomarkers with that study. Great. So our phase II-A trial was called INTEGRIS-IPF, and the trial was primarily a safety and tolerability study. That's what we had, you know, early designed it for, and then, but we also had included exploratory efficacy endpoints, such as FVC, the change in FVC. We also had assessments of radiological features of fibrosis. QLF was one of the markers we tested, and we also evaluated the effect on cough. We also evaluated effect on circulating biomarkers. We had four doses tested, going from 40 mg to 320 mg, and what we saw in our data, so that, patients were treated for at least 12 weeks, and that was compared to placebo, but in the top dose, the 320 mg, we had at least a 24-week duration, so we were able to look at longer-term safety and also the effects on FVC. So what we've reported is really good safety and tolerability, no dose relationship in terms of treatment emergent adverse events, and really no drug-related SAEs, which was also very important. This is, you know, the IPF population is an older population with quite a few comorbidities. So the fact that we have, you know, this clean safety profile was really a testament to Bexotegrast. And then, what was really exciting for us is the efficacy signals that we saw from this study, and we had seen basically further reduction in the FVC decline in a patient population that was predominantly using standard of care agents, such as Ofev and Esbriet. So 80% of our patients were using these drugs, but despite that, we had you know and further decreased the rate of the FVC decline by about 67%-80%. So it really suggests the stabilization of disease for us. What was really nice is to see these reciprocal changes in terms of less fibrosis, in terms of QLF, so the treatment groups for Bexotegrast had much less increase in QLF compared to placebo patients, and that was also manifested in the long-term evaluation of the 320 mg dose. We also saw an improvement in cough for that 320 mg dose. That was really quite exciting for us, but also for patients and physicians who treat this disease, because it's the number two symptom in IPF. Nothing to date, like, no therapies have really truly addressed cough. Right. And then, when we look at the circulating biomarkers, we had decreases in PRO-C3, which has been associated with more progression in IPF, and we also had reductions in integrin beta 6 levels, looking at circulating levels and really kind of serving as a PD marker for activity. So really exciting data from that study that really propelled us into the late-stage evaluation. Great. So, as those who may be familiar with IPF know, there are just two approved agents in the space right now, Nintedanib and Pirfenidone. Obviously, coming out of a phase II-A, there aren't any head-to-head studies yet, but in terms of looking at across, you know, agents, both the two that are approved as well as others that are in development, how do you see Bexotegrast comparing to that across those data points? Yeah, I can speak to the competitive landscape, the ones that are in development. Sure. Key ones that we're watching right now are the BI drug, the PDE4. They had an interesting phase II data where they showed a data not dissimilar from ours. They showed an increase at 12 weeks in FVC. There was some diarrhea associated with that mechanism, which, when you add that on to Nintedanib, is exacerbated, but that's a known issue with Nintedanib. Using those in combination may increase diarrhea. So we'll wait to see how that turns out in phase III, but we certainly hope that that drug works. The other one that's sort of ahead of us is BMS's LPAR1 that they're testing in IPF as well as PPF. They had modest effect in their phase two trial. They've doubled their dose for phase III, and I'm not quite sure what the status of that phase III is, but we know that they're enrolling it now, so we'll wait to see that. They did have a small issue with hypotension, which is an issue in older patients. Mm-hmm. They've had to dose reduce in some cases, but nonetheless, they're moving forward. We'll be watching that one closely. Another one that's moving into phase III is United Therapeutics Tyvaso, which is a pulmonary hypertension drug. They had interesting phase II data as well. They showed a modest effect on six-minute walk. That's an inhaled drug, so it's difficult for patients to tolerate who have a cough and who can be stimulated to cough by an inhaled drug. So again, that's a bit more of a niche application in the space. But those are the three ones that are sort of head-to-head and ahead of us, and we're watching closely. As far as our profile, I think our favorable tolerability profile and the effect size that we've shown today puts us in a very good competitive position relative to those molecules. Right. Great. Thanks, Keith. Next, I want to move on to another study, a smaller study that you did, and a rather novel marker utilizing positron emission tomography or PET to look at the collagen in the lung. I'm wondering if you could describe the design of that study and the importance of your findings from it, in particular, the potential to reverse fibrosis. Yeah, this was certainly a very exciting results from that study, as you mentioned, and these data were just presented a few days ago at ERS as a late breaker. What we wanted to see is whether our drug could inhibit collagen deposition, type one collagen deposition, using this PET probe, and Sydney Montesi at Mass General had assessed this probe in a non-interventional way, so no therapies had been ever tested. We were the first drug that was ever using this technology to look for treatment effects, and we used the 160 mg dose for that study. We compared it to placebo. It was a small study. 10 patients were enrolled in a two-to-one randomization. They were treated for 12 weeks, again, predominantly in patients using standard of care agents. And we were able to show a reduction in the PET signal for SUV with twelve weeks treatment of Bexotegrast at 160 mg. We saw an increase on placebo patients. We saw that the differences between active and placebo were very marked in terms of the subpleural areas of the lung, where IPF is generally. I mean, that's where it starts. So that was even more exciting. And then we also were able to see an improvement in FVC with a 160 mg dose. We were able to see also a reduction in cough. These patients had more cough than the patients in our INTEGRIS-IPF study, and we were able to show a marked reduction over the treatment period. And last, we had the biomarkers like PRO-C3 and integrin beta six again going down. Right. So quite exciting. And we also looked at correlations. We presented this at ATS whether the changes in collagen were also associated with the improvement in FVC, and they were correlated both with the FVC and the reduction in cough severity. So quite exciting for the field because this is truly novel. This is the first, as I mentioned, first ever trial that's been done in an interventional setting. And certainly looking forward to, it further builds our confidence on the antifibrotic mechanism. Right. And you mentioned the ERS International Congress. I think today is the last day, so you've just reported that data. You mentioned the PET data. Is there any other presentations that you'd like to point out? Yeah, we had another late breaker, which was looking at the effects of Bexotegrast on precision-cut tissue slices from explanted lungs of patients with other types, non-IPF ILDs, and interstitial lung diseases. We see that Bexotegrast again really in terms of, you know, testing Bexotegrast against the positive control, which is ALK5. In addition, we saw that the effect of Bexotegrast was also seen in these different diseases as well. Right. And I mean, that's really interesting because we know that alpha v beta 6, so one of the targets of bexotegrast, has been shown to be a highly predictive biomarker in terms of disease progression, both in ILD and also in IPF. So these are recent publications from the last two years. So we really do believe that there's an opportunity also for bexotegrast outside of IPF in these, for example, progressive pulmonary fibrosis, which is an indication that's been pursued by BI and also BMS and others. The broader space of interstitial lung diseases, as you mentioned, ILD, there's several potential indications there, right? Yes. There's basically, you know, you can think about rheumatoid arthritis-associated ILD, systemic sclerosis ILD, and also hypersensitivity pneumonitis. So there's quite a few of those, and there's a way to be able to. Some of these diseases are more stable, but some have a more progressive phenotype. And these are the subgroups of these different diseases of patients that are more likely to progress similar to IPF. Right. Yeah, makes sense. Okay, so now, of course, you are enrolling your pivotal seamless phase II-B/III study called BEACON-IPF, and are on track to complete enrollment in the first quarter of next year, with data in mid-2026. Perhaps we can discuss the design of that particular trial, and go through the primary and secondary endpoints. Right. So they, I mean, two independent studies under one master protocol in this seamless phase II-B/III. Both, so there's a phase II-B dose ranging part and the phase III. And there's continuous enrollment, and which really saves about two years in development timelines. That's what's really attractive about this study design. So as soon as we finish the enrollment of the phase II-B part, which is 360 patients, moving forward, we're enrolling phase III patients. So we've done is we're testing 160 mg and 320 mg compared to placebo in a one-to-one-to-one randomization ratio. We'll have the approvable endpoint as the primary endpoint, which is the absolute change in FVC, and looking at secondary endpoints such as disease progression, and also QLF, we'll be testing in that trial. 52-week duration, at least 30% of patients will not be on background therapy because we really think that our drug has the potential to be used in first line. Right. So we want to start generating that evidence. And so the 52-week duration, as soon as we get the phase II-B data. So initially, the phase III part of the protocol will enroll at two doses, but as soon as we have a dose identified from the phase II-B results, then the non-selected dose will go open to an open-label safety study. And then the two, the selected dose and the placebo will continue to enroll. So and they have the same endpoints, same eligibility criteria, and really, both trials are designed as to be serving as pivotal studies, so they could serve as the registration for IPF. Right. And of course, you've gone forward with the two top doses, which reflects obviously not only optimizing the efficacy, but the very clean safety profile as well. Yes, that's right. Okay, so then maybe we should move to the next program in PSC. I believe in July, you reported your 24- week results in your top dose, 320 mg in the INTEGRIS-PSC program or study, which is a phase II-A as well. What was the key data that you reported recently, earlier this summer? And maybe talk through your understanding of the predictive power of some of these biomarkers that you reported data on. Yeah, so I think, you know, what was exciting about the latest data release is that we continue to see the treatment effects manifested, and that was for the 320 mf dose at 24 weeks. So it was a very similar study design as INTEGRIS-IPF. Right In terms of the doses and the duration. But so we saw decrease or improvements or stabilization of transient elastography or FibroScan results, in contrast to an increase on placebo. We also had MR-based imaging, where we saw that the treatment group with bexotegrast we had a contrast agent that was eliminated through the bile, and we saw a reduction in the time to arrival to the bile duct, the common bile duct, in that study, which suggests there's potentially an effect on cholestasis. And that was really further supported by the fact that patients on bexo had stabilization of their ELF level. We continue to see increases on placebo, and then we also saw less itch in these patients. So really suggesting that not, not only the drug and, and I forgot to mention the fibrosis biomarkers, PRO-C3 and ELF, we reported on that as well. So we have evidence that this drug has anti-fibrotic properties, a clean safety in this vulnerable patient population, but also potentially can help address cholestasis, potentially by relieving the, you know, the strictures in the, the biliary tree. So very exciting data, but currently there's no biomarker that the regulatory agencies see as acceptable as a primary endpoint. So there's, there's more work to do on that front. But certainly for us, it was really great, great early data for our trial, and then, you know, the next steps, I think, maybe Keith can. Yeah, I mean, as Eric mentioned, the FDA's given little guidance to us on a phase III endpoint. I mean, they've agreed to, in theory, to a phase II-B design, but we don't know what would be expected in phase III, so, it's difficult to chart a course in PSC at the moment. Where we actually see value creation for the company is in the progressive pulmonary fibrosis, ILD indications that you guys were just talking about. Okay. So we will look to expand Bexotegrast into those indications as soon as possible. And we think that's for, you know, the capital that we have and the value creation that we see, especially with what we've seen in IPF so far. We think that's where we can take Bexotegrast and be most successful in the near term. Okay. So. But we'd certainly look at ways to take Bexotegrast forward in PSC as well. Right. But we don't have that plan. Yeah, so I know it was rather an important win, not just for Pliant, but for the greater PSC space, that the FDA indicated they would be willing, in a phase II-B or phase III, to move beyond biopsy. Mm. Right? And giving the opportunity to move forward with biomarkers. But sounds like the specific biomarker or set of biomarkers hasn't yet been decided. That's right. Okay. All right. So, we'll perhaps move to next programs. I know you have two more. Mm That are earlier stage. Maybe we can discuss where those are right now. Sure. Yeah, so our oncology program is in phase I. We're in our third cohort out of five in our ascending dose trial. Going well. I think we'll, we've guided to having data late this year, early next year. That just depends on, you know, how that trial is dosed out, where, what, what dose cohort we stop at, and where we, you know, where we expand, et cetera. Late this year, early next year, we should have phase 1 data there. Okay. And then, the second program is the DMD program. We had the CTA approved earlier this year, and that for DMD. We're free to launch a phase 1, but we are investigating that molecule for additional indications that it may be applicable in. And we're waiting to launch the phase 1 until we know exactly what biomarkers we wanna look at, in case there are other indications outside of DMD and even outside muscle, where we could have an effect. Right. So we think that that's an exciting program. I mean, it could have broader applications than what we originally thought. So we're being diligent there before we start phase I. Certainly, your platform gives you plenty of options to pursue. Maybe just one final question, and that is your current cash balance, your runway and which milestones are covered by that runway? Sure. Yeah, we finished the quarter, second quarter with close to $440 million of cash. We have capital through 2026, so we will certainly be able to read out our phase II-B BEACON trial with cash to spare, cushion on the runway there. That'll also get us, you know, obviously, the phase I oncology data that'll come out, as I mentioned. And we'll likely have some additional news flow, whether it's BD or other forms, within that time period as well. But right now, we're heads down, focused on executing on BEACON and making sure that we bring that data in on time, so that we maximize, you know, our efficiency and our capital usage. Fantastic. Keith, Eric, thank you so much for your perspectives. Really appreciate it. Thank you. Sure. Thanks, Ed. Thanks.