Good afternoon, everyone, welcome back to Oppenheimer's 36th Annual Healthcare Conference. I'm Jeff Jones, one of the biotech analysts on the team here, and I'm delighted to welcome from Pliant Therapeutics, Bernard Coulie and Keith Cummings, CEO and CFO respectively. Gentlemen, welcome, and, of course, since you're on the East Coast, or on the West Coast, I hope you've got better weather than we do out here. Yes. So, well- Thanks 2025 was really a major year of transition for you guys at Pliant. Bernard, why don't you give us just a little bit of a feel for how you're positioning the story today? Obviously transitioning to oncology, but why don't you just give an introduction? Absolutely, thanks for having us, Jeff. Very much appreciated. As you know, of course, we are an integrin small molecule platform company. Over the past 10 years, we have developed a library of small molecules and a biology platform that helped us to kind of really elucidate the role of these different receptors in different disease systems and indications. Our initial focus was, of course, on fibrosis. With, you know, stopping the program last year, we obviously had to kind of rethink how to kind of continue the company. I think there was no better way than to focus again on that integrin platform. While doing that, we have and are in the process of developing a pipeline of products that are all based on that unique integrin targeting small molecule platform. Our most advanced program is PLN-101095, which is a dual αvβ8, αvβ1 integrin small molecule blocker, not for fibrosis, but, as you mentioned, in oncology. We had a readout of our initial phase I, which was a safety PK type of study in all comers, patients refractory to immune checkpoint inhibitors, solid tumors, that showed very encouraging data. Although the study wasn't designed to kind of really look for clinical responses, we saw a number of very interesting data, both related to clinical response as well as to a number of biomarker readouts. We will, of course, dig into this in more detail. Furthermore, we have earlier stage programs, again, based on our integrin platform, I would like to mention specifically a targeted drug delivery platform that we are started to build. This is based on siRNA molecules that are linked to our small molecule integrin, or integrin binding small molecules, basically serving as warheads to deliver a payload to cells, this is in a very specific and very selective manner. The reason we can do this is because, of course, we mastered at chemistry as it relates to designing small molecules that are very selective to certain integrin receptors. We do know, from a biology perspective, the expression patterns of specific cell types as it relates to specific integrins. For example, we can deliver siRNA in a highly selective manner to, let's say, muscle cells or adipocytes without touching any other tissue. We have built this platform. We have products that are moving forward. All the initial work was done in murine models. Right now we are kind of confirming what we have seen in terms of targeted delivery of these siRNAs with concomitant knockdown of a target gene, therapeutic gene, in non-human primates. We anticipate to have data later this year, probably around towards the end of the second quarter, as we are dosing the non-human primates as we speak. I think those are kind of the key kind of new areas of focus, but all based on that same platform that we have been building for the past 10 years. Okay. Would it be fair to say that you're spending less time, or you've shifted away from exploring business development and licensing, which was maybe the message shortly after the IPF transition? Yes, this was, of course. I mean, we haven't shifted away from that entirely. Let me make that very clear. We continue to evaluate external opportunities, external assets, for potential in-licensing or acquisition. Clinical stage assets, mostly small molecules or antibodies in a relatively broad spectrum of indications, and that hasn't changed, so I would argue cardiometabolic, pulmonary, I&I in general, but also of course, oncology, as long as there is a complementarity to our existing oncology program. The oncology program right now, based on the data we have generated, late last year, is kind of moving forward. If there is anything else we can add to that, to strengthen that pipeline and to increase shareholder value, we will definitely do that. Okay we haven't moved away from that entirely. All right. Why don't we dig into 1095, and talk about this as a program, in the data you've put out relatively recently. The target, αvβ8, αvβ1, can you talk about the role of those integrins in checkpoint resistance and maybe set the stage with the TGF-β pathway there? Absolutely. PLN-101095, just to make that clear, is a small molecule, so it's orally administered one, twice daily. In response to immune activity, sustained immune activity, tumors will express both αvβ8 and αvβ1. They will utilize this basically to mediate activation of TGF-β. TGF-β is being activated by these two integrins. In the tumor microenvironment, αvβ1s or ex receptors are expressed on CAFs, so on cancer-associated fibroblasts. While αvβ8 is expressed on tumor cells as well as on regulatory T cells. What happens is TGF-β gets activated, and basically through that activation, it will reduce the or will induce immune suppression, leading to a reduced immune response of the tumor, whether it's by the patient's own immune system or a checkpoint inhibitor. By blocking that conversion, by blocking these integrins, we will block the conversion of latent to active TGF-β, thereby reducing the TGF-β tone in the tumor microenvironment and basically taking away that immune suppression that basically escaping from the immune response and reestablishing a immune sensitive environment as such. What will happen is TGF-β gets reduced, interferon gamma will increase again, and hence, checkpoint inhibitors or the patient's own immune system may attack the tumor again. That's basically the whole principle behind this. This is, I mean, well-established biology. This is not something that we all figured out ourselves. This has been around, and of course, the role of TGF-β in cancer therapy has been studied extensively. I think one of the key issues with TGF-β inhibition, systemically, is tolerability and safety, even in patients with, you know, cancer. Our approach, again, is very tumor specific. It doesn't suppress TGF-β systemically. It only suppresses there where the receptors are expressed, notably in the tumor microenvironment. All right. Given you're effectively reestablishing the immune sensitivity of these tumors, we should be thinking about this as not single-agent activity, but essentially reestablishing activity of immune checkpoint inhibitors. Would that be right? That's the basis, right? I think that I would consider that as the basis, and that's what we have shown so far. However, interestingly enough, I mean, the design of the phase I study was basically 14 days of a lead-in period with in a monotherapy setting with PLN-101095, after which, in our case, Pembrolizumab, as the checkpoint inhibitor, was introduced. What we see in those 14 days, although it's too short to see a clinical response, obviously, in terms of tumor size reduction, what we do see are significant changes, very significant changes in the number of biomarkers, notably interferon gamma, in those patients that would respond to reintroduction of Pembrolizumab. What we see from a biomarker perspective in patients that are responders, meaning that there is a resetting of their immune sensitivity, is 3-12-fold increase of interferon gamma over 14 days, between baseline and 14 days later, which lasts for about 28 days, after which it starts to decline. We do see an interesting signal in a monotherapy setting, not just in combination. We did see clear evidence for monotherapy efficacy in a number of different animal models. Taken together, we definitely plan to evaluate our drug also in a monotherapy setting, albeit not right now. In terms of next phase of development, we are initiating a phase Ib dose expansion study, that will be first patient in probably second quarter, no, definitely in second quarter, of this year. That will be in combination with Pembrolizumab. Based on those initial response results, we will identify an indication where we feel like we can kind of try to evaluate monotherapy as well. Okay. In the phase 1a, I guess. You saw some responses across non-small cell melanoma, cholangiocarcinoma. For that, for your next trial, are you going to limit the enrollment to those tumor groups, or how are you thinking about, you know, selecting patients for those tumors or for the trial? We will, I mean, more detail will follow during our in our fourth quarter financial update. High level, what I can give you is basically we will limit the number of indications, but actually still wanting to make sure that we don't miss anything. We will have a cohort with small, non-small cell lung cancer, because obviously we saw the effect there. We do see amongst the responders we have evaluated in our phase I, initial phase I, we see that all responders had a tumor mutation burden that was high at inclusion. We will include that also as a separate cohort, and that will be a number of different tumor types that will be studied, then more detail will follow. We have 1/3 cohort, which will be renal cell carcinoma, and that's again based on αvβ8 expression profiles, as well as previous data with other anti-TGF-β approaches showing a clear effect in that tumor type. Yeah. That's kind of the overall design, and as I mentioned, we, I mean, all the preparations have started, and we anticipate to have our phase Ib first patient in second quarter this year. It's probably, I mean, we've talked a bit about the mechanism of action here, and as you noted, the renal data, which, you know, has some validation around based on what AbbVie's doing. It's probably worth highlighting, some of the other validation that's been generated, not necessarily this, αvβ8, and αvβ1, but the TGF-β pathway in some of these tumors. What are the findings we're seeing? Where does that give you confidence, and how does that help you in thinking about the design of the next steps? What we have seen in general, I mean, from a competitor perspective, there are αvβ8 specific programs. That's one set of data. We know that there are earlier stage programs from Genentech. There is a program in phase Ib or II from Pfizer, and some others, and those are all antibodies. By the way, I think one has to be very careful in terms of extrapolating data from those studies to what we are doing, because I think the fact that we have a small molecule and that it covers αvβ1 as well, makes it quite differentiated from those programs. I think one has to be, again, careful about extrapolating. The anti-GARP program from AbbVie kind of closely relates to our program in terms of GARP being the chaperone protein that provides TGF-β or that offers, kind of basically presents TGF-β to αvβ8. Obviously, there or in later stage development, in, in a pretty kind of wide range of different indications, so that helps us to kind of select indications as well. There is a whole group of programs that are directly TGF-β targeted. Most of them are TGF-β traps, combined often bispecifics, combined with, let's say, a PD-1 or a PDL-1. There's a whole bunch of phase I programs there. I think, Incyte and Hengrui have, like, later stage programs there, phase II, phase III. Then again, you have other bispecifics outside of the PD-1, combined with TGF-β, such as EGFR, Bicara, VEGF, et cetera, et cetera. All of those programs basically provide, I would say, a certain rationale to kind of target specific tumor types where we think that TGF-β is relevant, because the key driver of TGF-β activation in all cases are these two integrins, notably alpha V beta eight and alpha V beta one. Selecting indications is based on other programs, as well as our internal data in terms of alpha V beta eight expression in certain tumor types that we have. We kind of skipped over it, but would you highlight what you actually showed in your phase I? What's gotten you excited for moving forward? Then I'd like to talk a little bit about the interferon gamma as a biomarker. Absolutely. We treated in total 16 patients in our phase I over five different dose levels, so five cohorts ranging from 250 mg twice daily to all the way up to 2,000 mg or 2 g twice daily. From 1,000 mg BID on, we started to see responses. In total, we had four clinical responders, three partial and one complete responder. That was the cholangiocarcinoma, and you mentioned before, melanoma, non-small cell, and head and neck cancer. Those were the four different tumor types that where we saw a clear response. The average duration at the time of analysis, so towards the end of November, early December, was 15 months. And those patients, three, at least three out of four patients, continued to be responders. More data, by the way, I want to make sure that that's understood. The full data set will be presented in the very near term at a scientific conference, so you will see all the data up to a later time point, of course. In terms of average tumor size reduction, it was 71% in those four responders, so the ORR was 40% in secondary non-refractory, sorry, secondary refractory, at that dose of 1,000 mg BID or higher. From a safety perspective, the drug was well-tolerated. I mentioned before, anti-TGF-β has its kind of, you know, potential significant safety and tolerability issues. We never saw anything of that. Most common. reported side effect was mild to moderate rash in about half of the patients, which is probably a combined effect or driven by both a combination of pembro and PLN-101095. To your point, we saw a very significant increase in interferon gamma during the monotherapy phase of the study. The first 14 days, where we had only monotherapy with our drug, and we saw this three to 30 or 12 x increase in interferon gamma between baseline and 14 days of treatment in all the responders. The question is, of course, is this potentially an early predictor of treatment response? In our phase 1b study, we're going to continue to evaluate that, although it will be a very unbiased approach. We're not going to select patients based on their initial response as it relates to interferon gamma increase. We want to make sure that we expand the number of patients, measure interferon gamma over two weeks, and see, you know, if we can confirm an increase being related to a response, and no increase related to probably no response, right? That's kind of the idea behind that. This could be a predictive biomarker, which ultimately, thinking phase II or phase III controlled studies, where you would use this to kind of basically select patients. Mm-hmm -responders- Yeah -and kind of try to increase your response rate to its maximum using this biomarker. Was there any correlation with rash in the interferon gamma response? Nope, we didn't see that. Interesting. Nope. Okay. As we think about the rest of the year for you guys, 2026, what are the key updates we should be keeping an eye on? The key updates, I mean, first, as it relates to our lead program, will be just clinical execution, right? I mean, getting those centers up. The plan is to have first patient in the second quarter of this year. We would like to have most of the clinical sites open by the end of the year, and having a significant portion of patients across three different cohorts enrolled. We will provide continuous updates on that, of course. Secondly, we will provide a first, I would say, look at the non-human primate and other data that we have generated with our targeted drug delivery platform. That is still preclinical, of course, non-human primates will be a key data set that will decide or will kind of be determining whether or not this is a viable program. If so, we obviously will go full steam ahead and try to get this to the clinic as soon as possible. The other update, you know, potentially could relate to acquisition or in-licensing of a potential asset. As I mentioned before, we continue to do so. In terms of evaluating assets, if something comes our way that makes a lot of sense and we can afford it, we would definitely provide an update on that as well. Okay. In terms of the drug delivery platform with siRNA, is this something you would need to partner with an external source for the siRNAs, for the payload, if you will? Or are you thinking about this as an engine for internal R&D, or is it more of a partnering, external partnering type approach? I do see it as an internal effort to continue and to kind of build our pipeline further, s iRNA, as such, access to siRNA is these days, it's not too difficult, right? It's more or less a commodity. Delivery is key. The siRNA itself, basically, we use contract manufacturing to get siRNAs against specific targets. What is key is choosing the right target and making sure you have selective delivery to the cell types that are of interest from an indication perspective. Right now, we have shown that at least in murine models for muscle and adipocytes, those will be the first ones that we will focus on, but potentially expanding to other cell types, other tissue types as such. I don't see it as immediately as a partnering, how would I say? Asset or a partnerable asset. Of course, it's always partnerable, but I would like to kind of continue development if we can confirm what is. W ell, you know, what we have seen before in mice, now in monkeys as well. I'm pretty sure that once we start looking for those data, and showing those data, that there will be interest. I would be surprised if that's not the case, so. Okay. Can you remind us, although you report out in a few weeks, cash runway, and then what's in those runway assumptions? Yeah, Jeff, we finished third quarter with about if you pro forma for the payoff of our loan facility, we had about $211 million cash. We'll be reporting in a couple of weeks, new cash level. You know, burn was dramatically decreased in the fourth quarter. We have cash into the second half of 2028, at least, at this point. That includes the full, aggressive development of the oncology asset, as well as full speed ahead on the platform. We're doing everything, moving everything forward aggressively with that runway. All right. Okay, anything else that I'm missing or that you guys would like to flag? Of course, you know, this being ahead of your, you know, full year-end update. No, I think, I mean, we covered everything, and thanks for providing us the opportunity to do so, Jeff. I think maybe one thing, Keith clearly alluded to a significant reduction in burn. Obviously, we restructured the company to a much smaller footprint. What was key, what is key, is that we kept our development capabilities. I mean, our DevOps team has shown to be extremely capable and efficient, I would say, in terms of running large, multinational, multicenter studies in IPF, notably, I mean, global studies. This will be key to kind of deliver also in our oncology program from a enrollment and a timeline perspective. The executive team is here to lead the company and to lead the programs towards these very important value drivers and catalysts. Last but not least, we also kept core medicinal chemistry and core integrin biology capabilities to kind of drive that earlier stage program or programs, and notably the one that I mentioned before, the targeted siRNA delivery. We have those capabilities in-house to a large extent. Smaller footprint, but the core folks to really kind of move forward our pipeline are still here. All right. Well, guys. Yeah, it's a good point. Let me just add one more thing- Yeah -on the, on the runway. You know, that development capability is going to come into play, crucially for us. We expect we'll have data from the oncology program at some point next year. Even with our aggressive development, we have probably a year of cash post post our initial data reading from the phase Ib. Yeah. So. All right. Well, guys, really appreciate the update, and, you know, it's been a tough story sort of, you know, over the last year and a half, but you've always had this oncology asset that's been interesting and what is really a, a validated pathway. Seeing the phase 1 data, certainly helps give folks comfort that there's a path forward here in oncology, and it's a matter of time and execution, and obviously looking forward to the deeper dataset, when you guys release that. I think I am up on questions, so I'll say thank you very much, and hope that you have some great meetings through the day. Operator, with that, you can take us clear.