Good morning, everyone, and thank you for joining our third day of our Piper Sandler Healthcare Conference. Really excited to be featuring the team from Pliant Therapeutics here with us. We have quite a bit to cover over the next 25 minutes. Would love to get started, actually. I've been going in order of upcoming catalysts and chronological order as I start these fireside chats. And start off with PSC, actually. I think coming off of the AASLD meeting, which was two weeks ago, could you maybe capture what was the sentiment among docs who saw for the first time the PSC data? There were a lot of discussions on the results that they had seen for the first time. So if you could capture that, it would be really helpful for investors who didn't attend. Yeah, I think the key opinion leaders and also, excuse me, the PIs in the trial, we had quite a quite a few meetings over, obviously, at AASLD, and we had also advisory boards there. The sentiment was really very positive. Because I think, you know, first of all, they haven't been thinking about enriching trials the way we did. In the sense that most of the trials were enriched for patients with high ALP values. This was a bit of a different design, and also the fact that the drug was safe, showed an effect on, you know, fibrosis biomarkers and also the imaging. The MRI imaging was really, for them, an additional evidence of the treatment effect. Of course, there was the itch fewer events of cholangitis in the active arm compared to the placebo arm. So altogether, I think it really came out very nicely, and they're very, very excited about the program. Great. Also, there was a presentation at the late breaker session which was, to start with, very well attended. I think we went over time in just addressing all the questions because there was, you know, it it created definitely some, how would I say? A lot of interest. Great. Yeah, and, and as we were there, we saw the same enthusiasm, so thank you for capturing that. Team, you know, the next, the next readout now for us is to see the 320 mg dose group data that's expected in 1Q. I think a lot of investors are gonna expect that the data disclosure will be very similar than you did for the cohort you reported out in September. Is that fair, or will it have some measures that we didn't see or vice versa? So if you could just talk about the type of data that you're gonna have versus the initial data set. So the next readout will be the 12-week analysis of that 320 mg cohort. So this will be the apples-to-apples comparison with all the other doses. So you should expect to see exactly the same content, with the 320 mg dose being added. I think just pointing out also that, the way we did our design the placebo patients were embedded in each of those, the dose level in a 3:1 randomization ratio. So we'll have a few more placebo patients also, so that the placebo results might change slightly because of these seven more patients that will be there. Okay. And just to kind of level set so that investors don't forget, when you did an IPF and you showed the high dose, you came and you replotted the numbers, and so you showed us the values for. So that way we could see the, all dose cohorts plus the added placebo. So that, it seems that's gonna be. You guys are gonna be doing the same thing for PSC. That's right. Okay. Yeah. Then I think investors will remember that because of adding the additional placebo patients, the numbers of the MMRM may change a little bit, right? Like, could some numbers in the lower dose cohorts change a little bit or probably stay the same? Yeah, we don't have the same. Statistical. Yeah, exactly. MMRM, we have it as part of our statistical analysis plan for some of the biomarkers. But overall, we're not reporting MMRM for these types of readouts. Okay. For example, MRI is not MMRM, so it shouldn't affect it that way. Okay. But it could be that, for example, for the differences in terms of AEs and things like that, or, even the number of patients for the MRI findings for placebo it might change a little bit. Okay. I think the next question that a lot of investors are asking is, is like, and that will come up in your one-on-ones, is what do you want to see in this 300 larger, the 320 mg dose cohort across the biomarkers, like base as well as imaging? Yeah, I mean, primarily good safety like we've seen before, so that would be really important. I would say that if the 320 mg mg dose delivered results similar to the 160 mg dose which performed the best out of the lower doses we read out on, then that would really be a positive. Because we don't know how discriminate these circulating biomarkers are in terms of selecting a dose. Yeah. Right? So they... But, certainly, I think that, the evidence that we saw, that you could blunt the fibrosis production with FVC at 160, pretty much so. Something like that would be important, and if we get further reduction, that's great. Mm-hmm. Let's say the same results would be great as well. Okay. When you had a chance to discuss these results at the liver meeting, did you get a feel for what the consensus were on which biomarkers the physicians were more relating to and getting more excited about versus others? Like, were there things that everybody was aligned and talked about, "Oh, wow, we saw ALP PRO-C3?" if you could just talk about, like, what were things that they pointed out to you that they were excited about? Yeah. ELF, for them, is certainly, very, very interesting because there's so much validation that's been done for ALF, and we know it's really can. R eally be a good prognostic biomarker in PSC, because EASL now recommends-... performing a yearly ELF test in PSC patients. Okay. So that's giving you the sense. They're also interested by PRO-C3 data but there's a little bit less data PRO-C3 compared to ELF. The other aspect, which was really an exploratory measure in our in our study, was the MRI contrast with the gadoxetate agent. Mm-hmm. They hadn't seen this type of data before. Still some, you know, curious about it how to completely interpret it. Mm-hmm. But at the same time, the key takeaway for that was that you continue to see a difference between active and placebo, and we should really think about this new technology. Mm-hmm. We'd want to know more about it. Okay. Is the ELF recommended on for an annual checkup just to see where you're progressing in fibrosis over time? Is that their tool? It's really for prognostic value. Okay. Exactly, and they also recommend, these also recommend a yearly Fibroscan or transient elastography. Yeah. So those are the two, that they recommend, just for, to prognosticate, basically and make sure that the patients are not going in, you know, more advanced clinical liver fibrosis. Is there, as you look at the guidelines, a lot of times we get this question is, you know, what change in these ELF PRO-C3 could alarm a physician to say, "Hey, I'm now thinking you could be at risk of, you know, worsening of fibrosis or potentially cirrhosis?" Like, what are those numbers? Yeah, PRO-C3 that's not really well known, but for ELF, there are some different categories. Mm-hmm. Right? So according to the threshold you have a low risk of fibrosis an indeterminate risk of fibrosis, and then a high risk of fibrosis. Mm-hmm. That's more helpful, I would say, because typically the way that these doctors will will look at the ELF test is looking at the category the patient was in when they started following them up, and then where they end up. Mm-hmm. So, for example, they increase in a category that's higher risk that usually requires more, evaluation and assessment, and potentially follow-up as well. Great. And then, team, obviously, after that data is available, a lot of clients are going to be interested in, is this the time when you start engaging with the agency, or would you want to wait for your 24-week data to then discuss next steps? So what will happen post the 1Q readout to start the process? Yeah, so we don't need to wait for the 24-week data for the 320 to really engage with the, FDA, because, in fact, the apples to apples comparison at 12 weeks is it's at 12 weeks. Yeah. Right? So then we have all we need there. So as soon as we get these data we'll write up a meeting package and engage with FDA, and we expect that to happen potentially midyear next year. And that would be about talking about the late-stage study design and, you know, the way we would think about the primary and secondary endpoints. Okay. Last time, it's funny because the way the data came out in IPF was in a similar format, right? You had the 320 mg dose group starting engaging with the FDA, and then you started mid this year, and we'll talk about Beacon. So is it fair to assume that time from the high dose cohort to starting to engage with the agency and then designing the pivotal study, sort of that sequence or that timeframe could be the same for PSC potentially? Or could it be a little longer just because, you know, it's PSC development is a little bit more... requires maybe a little bit more discussion with the agency? Yeah, I think in the ideal circumstances, I don't think there would be much of a difference in terms of timing. As we had it, the cadence with IPF versus PSC. I think that the bigger difference now, or the situation has changed in the sense that we are doing doing BEACON. Mm-hmm. That's really kind of the focus of the company and also in terms of allocation of resources. So, timing is not just execution or operational timing in PSC as it relates to 24-week readout, the interactions with the FDA, and all, all of those plans that we are kind of rolling out. It's also the availability of cash, right? Mm-hmm. And so for us, it will be critically important to at least have, I would say, three threshold issues solved before we engage in a phase III or a pivotal trial kind of program. First, the 320 data. Yeah. Eric can speak to that as well in terms of what we expect, but we think it will be a confirmation. Mm-hmm. We're pretty confident it will be a confirmation of what we have seen. Second, will be feedback from the FDA. Yeah. Is this a reasonable path to NDA? Mm-hmm. Right? Because now we are a frontrunner in PSC. Yeah. That means that we have are paving the way. Yeah. Nobody has ever succeeded in completing a phase III. And then thirdly is, you know, do we have the resources to execute on that program that we could agree with with the FDA? And that needs to come from additional capital. Mm-hmm. Obviously, we're not going to raise capital at this point in time for a PSC trial. Mm-hmm. We are actively looking at generating non-dilutive capital to potentially fund a pivotal or, you know, a registrational program in PSC. Obviously, we have our earlier stage programs in DMD and oncology that, you know, are progressing but they are definitely generating a lot of potential partnership interest where we could kind of find that additional non-dilutive capital also. But how challenging would it be to partner for PSC, but then keep IPF for yourself? Like, that's, that's always gonna be- It is, it's definitely challenging. Yeah. It's not impossible. Yeah. It's definitely challenging. I think a partnership for PSC is something that, became apparent with the data, right? Mm-hmm. I mean, to be quite honest, we didn't expect the PSC data, this, this to be this kind of positive right? Yeah. I mean, most of the analysts and investors were already happy if there was some. You know, if it was safe, Good signal. Some signal. Every signal points toward an antifibrotic effect, which for me, the key value of that is actually how it tells you something about the asset itself. Mm-hmm. Right? Partnership in PSC, there are creative solutions. Mm-hmm. But it's a challenge, right? Yeah. I mean, you don't want to end up in court for years because you split indications. A cross one single asset afterwards. Yeah. But with the PSC data, obviously, suddenly there was inbound interest, outbound interest coming inwards. In terms of, you know, companies that are specifically interested in PSC. Mm. And so we are looking at that and see what we can do. Without obviously diluting the value of the asset or jeopardizing it. Yeah. It's potential in IPF, and also kind of it has to have a win-win situation. F or the company as well, so. I think a lot of investors going into the data may wanna also figure out, and one key: would you be in a position, once you saw the next dose cohort, to kind of, in broad strokes, tell us about how you're thinking or how you're what type of a study you would potentially propose to the agency? Or should we just set the right expectations, say: "Guys, you're gonna get the data, we'll engage with the agency, and then we'll come back to you and tell you, like, what we negotiated." Or will you share potentially at the time of the top line, how you're thinking about your proposal to the FDA? I mean, I can, I can address some of that now. Yeah. I absolutely would- we would provide more details, but certainly there is a straight-to-phase III path in, in PSC. Yeah. Right? It's been done by Gilead and others. Yeah. So we would like to take that path because of the length of these trials. Mm-hmm. As you know, the Gilead and the Dr. Falk trials which were, which are. One was terminated, but the other one is still going on. It's a European program, so they have a two-year duration that's required by EMA and FDA. And so doing a phase IIb approach you know, what would you really win? Yeah. Would you lose a lot of time? Yeah. And then potentially carrying two doses into a phase III would make more sense, and that's the way we're thinking now. And certainly something we'll discuss with the regulators. And the other part of the story is that histology is the approvable endpoint surrogate endpoint, but the, there's an open door to consider noninvasive with histology as potentially composite endpoint. So that, that's the type of discussion we want to have with them as well. Yes. No, that's very helpful. Team, maybe now transitioning to Beacon. Could you maybe give us, you know, the study has begun enrollment across 150 sites, that's the target sites that you hope to activate. Could you kind of give us some thoughts how enrollment is progressing? You know, how is your work with your CRO and the enthusiasm that you see among the community? So I think a lot of investors are gonna try to track, because I think you guys have said enrollment within one year, Beacon started middle of the year, the middle of 2024, you would want to be done with enrollment. So based on what you see, how do we feel about achieving that? Well, you know, we haven't revised our guidance and we don't yet have enough runway in terms of enrollment to really predict exactly when that will, you know, the end of enrollment will happen. But we, we are still targeting a year from midyear this year, which would be midyear next year, right? Mm-hmm. I can tell you that sites are being activated on a daily basis so that, exercise is going really well. Mm-hmm. Sites, the sites are activated or screening. I would say there, there's quite a lot of enthusiasm around the results. Mm-hmm. There have been some really key differentiators for our program, including great safety. Yeah. I mean, that's what the PIs and IPF leaders are telling us, and certainly they understand the mechanism of TGF-β inhibiting TGF-β as a way to inhibit fibrosis. So I think those two things make it really easy for them to think about the trial. Mm-hmm. Yeah, we're getting quite a lot of engagement, and I think so we should be able to deliver on our goals. Great. Just in the last couple weeks, we've seen quite a bit of surprises on the management, on execution, on pivotal studies and important studies. It has created quite a bit of fear. Could you maybe talk about what you do with your team in regards to oversight? Like, I hate to say this, but micromanaging—like, what is the level of managing your CRO and your engagement there? Because I think this is gonna be a very important topic for various- You absolutely have to be on top of your CRO. Yeah. I mean, that's even the best CRO, right? Yeah. So, you have to communicate the sense of urgency what you're expecting as well. Yeah. These are things that, you know, we're very comfortable with, and certainly Bernard can speak about a recent hire also, that we've had to really help with with that aspect specifically. But, yeah, so we have, you know, in terms of even the data integrity piece we really will have real-time review of FVC data that comes in a blinded way. Wow! Okay. But to look at whether we need to retrain some of the sites, because there's too much variability there. Mm-hmm. You know, that hasn't happened yet. But we're gonna put all the measures in place, so we really have the best data coming in you know, to the database. Yeah. I think we saw, we see execution of the trial as the. That's kind of the next thing for us. Mm-hmm. I think to a large extent, bexotegrast has been de-risked from safety perspective. Yeah. We seem to have an efficacy signal in two different indications, so I'm less worried about that. Yeah. It relates to the phase II B readout. So execution is key. One has to realize our two main competitors are large pharma. Yeah. We are the only biotech company still in that stage of IPF Mm-hmm -development. So we have to get our act together. Mm-hmm. And long before all of- Yeah This happened, not that I knew that this was going to happen, but, I mean, we working with one of the top- Mm-hmm CROs in the space, just in clinical development space. But we were able to attract talent from outside, Minnie Kuo- Mm-hmm -who joined us as Chief Development Officer, and she was responsible for- Mm-hmm -all development at, Tir. Mm-hmm. and was also part of the Oleta team, the Hep C team at- Mm-hmm -Gilead. Right. I mean, talking about- Yeah -uh, flawlessly- Yeah -executed- Yeah -clinical trials- Yeah at top speed. Yeah. That's, that's her, right? And so bringing her in and then really kind of building- Mm-hmm -a clinical operations group, or further expanding our clinical operations group, has been critical. Mm. So we don't kind of... I don't truly believe in a completely outsourced model- Yeah -where you have- Yeah One person overseeing. Got it -a massive- Yeah -design, massive study. Yeah. I think that's part of the issue- Yeah Right? I mean, of course, CROs will make mistakes. Yeah and are sloppy, but you also have to have Mm-hmm -over oversight, and we have a big team actually, covering all the different- Yeah geographical areas that we are, you know, are doing or executing our study in, so. Great. No, that's helpful. The other question also comes up as the study continues, is discontinuations, how they're monitored. So if you could talk about, are you blinded? Do you get notified if discontinuations occur? If discontinuations occurred, you know, what happens with the data? You know? Yeah. Yeah. So the first part, we have language in our protocol- Mm-hmm -that, requires investigators to let us- Mm-hmm know in a short order if any of their patients- Yeah -have temporary- Mm-hmm -interrupt, temporarily, in interrupted drug or, just- Yeah -a discontinued drug. And advise the, you know, the sponsor- Yeah the medical monitor, so we can have a conversation Mm-hmm with that PI about what was the issue. Yeah -right? Right. That's something we want to track very carefully. Mm-hmm. Because we have covered. We've put enough buffer in our- Mm-hmm sample size to account for Mm-hmm the typical type of discontinuation. Mm-hmm rates you see in IPF trials. But we want to do better than that Mm-hmm -because we know that every patient we keep in- Yeah -and maybe, you know, you have two examples of the in our IPF study, the- Mm-hmm phase II study, patients discontinuing for mild diarrhea. Yeah. Right. Why? Yeah. You know, why weren't they- Yeah -restartled? Right. Those things we want to avoid at all costs. Yeah. In terms of the... what we do with the missing data, they're just missing, right? Yeah. In terms of there's no imputation assumption- Yeah -in the MMRM. Okay. The data for these patients up to a certain Mm-hmm up to the point that they were in the trial Mm-hmm will be used in the model. Yeah. But after that, they- Yeah Don't have any data to provide in the model. Mm-hmm so they, they can't influence the model. Got it. So it will be, and we're doing that exactly like you, we did for INTEGRIS-IPF. Yeah and we will do for late stage as well, right? Right. For phase III. And team, I think a lot of clients are starting to also pay attention for the competitive landscape in IPF. Mm. They understand you're the only biotech in this space and, with a very promising study. How do you, how do you think the competitive space will play out? And as of right now, based on the data that you have, what is the product profile? Yeah. I think to, to Éric's point, the feedback we got from KOLs and our clinical investigators- Mm-hmm. This is an easy drug. Mm-hmm. It has no side effects. Yeah. Safety, I mean, tolerability profile- Mm-hmm Looks really great once daily dosing. Yeah. I think those are kind of the key, key aspects here. It works at least based on our phase IIa data. Yeah. The competitors, the two main competitors, are Boehringer Ingelheim with a PDE4B inhibitor. Yeah. That's a known mechanism in COPD. It's anti-inflammatory- Mm-hmm But has no antifibrotic activity. Mm-hmm that we are aware of. Yeah. There's no evidence- Yeah that this actually does Right have an antifibrotic activity. So let's see how that- Mm-hmm 52-week trial plays out. Yeah. Right. Of course, Boehringer may not be a scientific- Mm-hmm Or clinical threat, but could be a commercial threat. Yeah. Right? I mean, they're really big in the- Yeah IPF space, so we better kind of, you know, we shouldn't be dismissive of that. Mm-hmm. The key issue with that drug is diarrhea. Mm-hmm. That was already generating quite a high dropout rate in their phase IIa- Mm-hmm after 12 weeks only- Mm-hmm at the high dose. So they're running now a two-dose phase III, have fully enrolled that study. Mm-hmm. Let's see how that tolerability issue- Mm-hmm Kind of plays out, because it's on top of standard of care. Yeah. Right? And there- Yeah You have the same thing with their own- Yeah -you know, approved drug. BMS, so Bristol has a ALK1 blocker- Mm-hmm -that's antifibrotic. Mm-hmm. We know that's a relevant mechanism. Yeah. Yeah. I think based on the data we have seen, they've published, they show that at ATS, it has a modest effect- Mm-hmm on top of standard of care. Yeah. Where we saw a very clear effect- Yeah -on top of standard of care. That was a -month trial, 200+ patients. Mm-hmm. I think that's a very relevant size in order to be predictive- Mm-hmm for what, what the outcome of a phase III would look like. From a timing perspective, they are just initiating- Yeah -their phase III. So it is- Mm-hmm ... I anticipate their phase III data and our phase IIb data may- Yeah come around the same time. Same time, yeah. Those are the key ones. But, you know, don't forget, we don't have any drug-drug interaction issues. Mm-hmm. Yeah. If need be, they can be combined- Yeah -mechanistically- Mm-hmm Definitely with the BMS drug, it makes sense. Mm-hmm to combine an ALK blocker with, you know Mm-hmm an integrin blocker, as we have. So ultimately, the market will be orals. Mm-hmm. New orals- Yeah. with better safety tolerability profiles than what we have now, and we anticipate, based on Mm-hmm market research, we have found that that will be about Mm-hmm -at least 60% of the total IPF market. No, very helpful. Given that we're coming to the end of the year, a lot of investors wonder, right, Pliant has had a phenomenal year in terms of execution and data. So then raises the question, why, why own now, right? Like, what is, what and we talked about the PSC readouts, we talked about enrollment. So, you know, like, if somebody. You were gonna get that. Why should I buy the stock today? You know, like, not just wait for maybe- To be- A quarter or two quarters. Yeah. Yeah. I mean, why buy now? I think, there will be more catalyst in- Mm-hmm in the coming years, in the coming year, for sure, before even we have the phase IIb data. Yeah. We have our Oncology Program, DMD Program. The platform itself- Mm-hmm is of great interest. Yeah. I anticipate there will be more BD to happen. Yeah. Right? And so partnerships obviously are something that we are exploring, as I said, around oncology, DMD, and even platform. So yeah, I mean, there is definitely a lot of interest in the lead asset- Yeah to partner at this point in time. It's something that we, you know, have been reluctant to do because we don't want to dilute- Yeah the value of the asset. Ultimately, what our investors, potential partners- Mm-hmm are looking for, actually, the data we have Yeah Seem to be enough. Yeah. But I think going to phase IIb data will be critically important because I think that will be the true- Yeah -value creator, at least for the bexotegrast assets. No, that's wonderful. Well, the 25 minutes flew by. It's been a pleasure hosting you. Just want to say thank you on behalf of all, all of us here at Piper Sandler.