Good morning, everyone. Thank you for joining us for Pliant's presentation of top-line data from the INTEGRIS-IPF phase II clinical trial evaluating PLN-74809 in patients with IPF. The press release that we will be referencing today is available under the Investors and Media section of our corporate website. The slides accompanying this web presentation will be available in the same section of our website following the conclusion of this call. During today's call, we will be making forward-looking statements, including those related to the therapeutic potential of PLN-74809 and our plans for the future development of PLN-74809. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most public filings with the SEC, which are available at sec.gov. Pliant undertakes no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. Joining me today with prepared remarks are members of our management team, Dr. Bernard Coulie, President and Chief Executive Officer, Dr. Éric Lefebvre, Chief Medical Officer, Dr. Gregory Cosgrove, Vice President of Clinical Development, and Scott Turner, Senior Vice President and Head of Research. Pliant team members will be joined by Dr. Toby Maher, who is currently Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine at the University of Southern California. Dr. Maher is a trained pulmonologist who has spent the last 20 years specializing in the management of in the areas of pulmonary fibrosis and orphan interstitial lung diseases. Dr. Maher will be joining us for 45 minutes of this call. Please keep that in mind when it's time for the Q&A session. Dr. Keith Cummings, Pliant's Chief Financial Officer, will join us for the Q&A session. With that, let me turn the call over to Bernard. Thank you, Chris. Good morning, everybody, and thank you for joining us. It's a pleasure for my colleagues and myself to share with you today the exciting and very compelling data that we announced last night from our INTEGRIS-IPF phase II-A clinical trial of PLN-74809. Just as a reminder, PLN-74809 is an oral small molecule, dual selective inhibitor of α v β 6 and α v β 1 integrins that's currently in development for patients with IPF as well as Primary Sclerosing Cholangitis. Needless to say that the results from the INTEGRIS-IPF study have far exceeded our expectations. Before we dive into the data, I would like to take a step back to recognize something that many of you may know. The field of IPF drug development is a challenging one. At Pliant, we have built a solid foundation on science focused on interrogating the safety of our drug candidates and de-risking our clinical programs. This is evident in the multiple meticulous studies and trials we have conducted in the past years. From our live IPF patient tissue work, to our pSMAD biomarker studies, to the target engagement studies in IPF patients, I think we have built a compelling story, which leads us to the INTEGRIS phase II data we are presenting to you today. Our safety database is extensive. To date, PLN-74809 has been dosed to over 450 human participants, including healthy volunteers as well as patients with IPF or PSC with no safety concerns. In addition, we have successfully conducted chronic GLP tox studies with no safety issues arising. Turning now to yesterday's news. The achievement of a primary endpoint in a clinical trial is great news. When that trial is in IPF patients, it's really great news. When that 12-week IPF trial also shows dose-dependent improvements in forced vital capacity and Quantitative Lung Fibrosis, which were our exploratory endpoints, forced vital capacity being the current registrational endpoint in IPF versus placebo over 12 weeks of treatment, I think it's quite spectacular. We believe that today's data present a potential opportunity for a new treatment for what is a devastating disease for which there have been limited effective therapeutic options so far. Éric will begin with an overview of the INTEGRIS-IPF trial. Greg then will do a deep dive into the safety data. Éric will return to review the secondary endpoint of pharmacokinetics, and then Greg will discuss the exploratory endpoints of the trial. Scott will discuss the biomarker data, and then we will hear from Toby on his thoughts on these results before I conclude with next steps and closing thoughts. Thank you, Bernard. Good morning, everyone. Before I start on the summary of the results of the INTEGRIS-IPF study, I would like to remind the audience of the previous mechanistic work we had performed in the clinic with PLN-74809. We had looked at target engagement in IPF patients and had seen that PLN-74809 achieved dose-dependent and exposure-dependent changes in target engagement in the lungs of these patients, where the highest dose provided near saturation of α v β 6 in lung. We had also shown that PLN-74809 was able to reduce TGF-β activation in a dose-dependent manner. Now I'll turn to the study design and objectives of INTEGRIS-IPF. This was a multinational study which enrolled a total of 90 patients. There were three PLN-74809 dose groups, 40 mg, 80 mg, and 160 mg, which were dosed once daily. This was compared to placebo. We included patients that were either on or not on standard of care in our study, but it was stratified for use of standard of care or not. The number of patients on standard of care would be balanced across the groups. The primary and secondary endpoints of our study were PK safety, tolerability, and PK respectively. In terms of exploratory endpoints, we had change in forced vital capacity over 12 weeks, the high-resolution CT-based quantitative lung fibrosis imaging, patient-reported outcomes, and also selected effect on selected biomarkers. The summary of the results is the following: 74809 was well-tolerated over 12 weeks of treatment. Most treatment emergent adverse events were mild or moderate in severity. There were no discontinuations due to adverse events and no death or drug-related SAEs. 74809-treated patients experienced a 80% reduction in FVC decline over 12 weeks, so this was -15 mL in the pooled active groups. In contrast is placebo, which consisted mainly of patients on standard of care that showed a -74 mL decrease over that same time period. The treatment effect was evident with and without standard of care agents. We saw an improvement of approximately 25 mL in the 80 mg dose cohort. Importantly, we saw a clear dose-dependent reduction in the proportion of patients with percent predicted FVC decline of greater than or equal to 10%, which is a well-established predictor of death and disease progression in IPF. For the other exploratory endpoints, we saw dose-dependent anti-fibrotic effects based on QLF imaging, with no progression in the 160 mg group at week 12. Last, 74809 decreased serum biomarkers of collagen synthesis, which are PRO-C3 and PRO-C6, relative to placebo. We're excited about these encouraging findings, which provide confidence to advance 74809 forward in development. With that, I will pass it to Dr. Greg Cosgrove, who leads our IPF program. Thank you, Éric. The details of the study and operational aspects are illustrated here with 141 individuals screened, a relatively consistent screen value with other studies of just above 30%. We randomized 90 individuals, of which you see 67 to the active arm and 23 to the placebo arm. There are relatively small number of discontinuations in both arms of the study, and the safety and efficacy in intent-to-treat analyses are similar. Of note, the number of individuals on standard of care was approximately 80% and as an entire group, 50% approximately were on nintedanib and 50% on pirfenidone. The baseline characteristics of participants in the study were consistent throughout the different arms of the study. As you see, it is consistent with other IPF studies that it's male predominant. The age is appropriate, given the characteristics of the disease. The characteristics in terms of the time since diagnosis and the standard of care use are consistent throughout the different groups. Importantly, you see the duration of standard of care was consistent throughout the different arms as well. The physiologic characteristics, again, consistent throughout the different groups. We decided to assess an index of the disease severity with a GAP stage. You can see the proportion of individuals at GAP stage one and two were consistent throughout most populations. For the safety analyses, the adverse event rate was comparable through the different dose arms of PLN-74809 in the placebo group. There were no study drug-related serious treatment emergent adverse events related to drug. The withdrawal from study medication occurred only in the placebo group. Of note, there were no deaths related to an adverse event. As we broke down these adverse events and safety profiles from those with and without background therapy, you can see that the predominance of adverse events occurred in those on background therapy in contrast to those not on standard of care therapy. The most common treatment-emergent adverse event was diarrhea. Of note, this occurred in individuals on standard of care, with 12 of the 13 participants having diarrhea taking nintedanib. All but one event were mild to moderate in severity, and diarrhea was of note, recorded infrequently in our healthy volunteer study. To place this in context in terms of other studies in the IPF space, you can see that the rate of diarrhea is quite significantly larger in other studies of note in Ofev. If you see in monotherapy in our current study, there was no evidence of diarrhea, and the increased incidence occurred only in those on standard of care. In our study, there were no treatment-emergent serious adverse events related to study medication, and the serious adverse events that were reported were consistent with known features of the underlying disease of those individuals. In conclusion, regarding the safety evaluation, I believe we can confidently say that PLN-74809 is well-tolerated, and there was no dose relationship for the adverse events noted. There were no deaths or treatment-related serious adverse events, and no participants discontinued 74809 due to a treatment-emergent adverse event. As mentioned, the most frequent adverse event was diarrhea but only seen in individuals on standard of care. I will take it back, this is Éric to describe the pharmacokinetic analyses, which were our secondary endpoint. Based on the sparse sampling we used in our study, the overall 74809 pharmacokinetics when we looked at total concentrations and unbound concentrations, which means free drug, were consistent with that of previous studies. The concentration of 74809 increased approximately proportionally with dose, and the proportion of free drug was 0.3%-0.5%, which is consistent with prior findings. We have data now to put into our population PK model that was derived to project PK parameters such as AUC24 and Cmax. I'll pass it back to Greg. The enthusiasm for our results are suggested in the current slide, which the change in FVC from baseline to 12 weeks demonstrates what we believe to be a dose-responsive relationship and treatment effect from the 40 mg, 80 mg, and then up to the 160 mg in contrast to placebo. Further exemplified as we move from the left upward panel across, you can see that effect is apparent in the pooled PLN-74809 group, and then subsequently begins to emerge in the 40 mg group. In the 80 mg, we see an inflection upwards or improvement beginning at eight weeks. In the 160 mg group, we see consistent separation of curves as we move forward. When we look at those on standard of care, we see a similar response. Then as we move forward to those not on standard of care, we again see a consistent, what we believe response therapy, notably in the 80 mg and 160 mg group, acknowledging the reduced number of participants not on standard of care. Additionally, we wanted to look at important features such as a change in the forced vital capacity percent predicted and a decline of greater than 10%, which is a clinically meaningful, and I would argue, a registrationally important change in FVC percent predicted. As you can see, and consistent with, the absolute change in FVC in mL, there is a decrease which appears to be dose responsive in the 80 mg and 160 mg cohort in contrast to placebo. To summarize, these forced vital capacity evaluations, we see that patients with 74809 experienced a benefit in terms of the change in FVC from baseline to 12 weeks, with a -15 mL for the pooled group compared to the placebo group of -74 mLs. This treatment effect is evident in both those on standard of care as well as off standard of care. If we look and focus on the 80 mg cohort, we see that improvement was approximately 25 mLs, so not simply a reduction of decline. This dose-dependent reduction in the proportion of individuals as we assessed with the percent predicted FVC, we believe is an important feature and further supports the absolute change in FVC. As we move forward to QLF, we noted a similar phenomenon and consistent change with that of the physiologic change in FVC in that we assessed the mean percent change in QLF extent or percent QLF from baseline to week 12. We see again evidence that would suggest a dose-responsive nature with the QLF, not progressing in contrast to placebo, in the 80 mg and then not progressing at all in the 160 mg cohort. To further assess and categorically evaluate individuals, you can see we can determine the minimal clinical important difference of 2%. If we assess greater than 2%, which would be worsening, -2% to 2%, which would be stable or less than -2%, suggest an improvement. As you can see in the 80 mg and 160 mg cohort, there appears to be a treatment effect in contrast to placebo. Each individual patient is further identified in the dot plot. These quantitative lung fibrosis data support that there is a dose-dependent anti-fibrotic effect based on QLF imaging. There was no progression in the 160 mg group at 12 weeks based on mean change from baseline. There were a higher proportion of participants who remained stable or improved in the 80 mg and 160 mg group compared to placebo. Scott? Great. Thank you. So here on this slide, what we're presenting are two biomarkers of a larger panel of biomarkers that will be evaluated in this study. But these biomarkers importantly reflect collagen synthesis that's ongoing in the IPF lung. On the left, it's highlighting PRO-C3, which is the propeptide of type three collagen, a fibrillar collagen that is a component of the excessive extracellular matrix that accumulates in the disease. What you can see very clearly is a dose responsive reduction in the synthesis of type three collagen at four and 12 weeks, with the highest reduction at 160 mg. On the right-hand side is PRO-C6, which is a basement membrane collagen, also secreted excessively in the IPF lung with consistent reductions across all doses at four and 12 weeks. These biomarkers are particularly interesting because they've previously been shown in large clinical studies to be elevated in IPF and also be further elevated in patients with progressive diseases. Thanks, Scott. It's my pleasure to now give Dr. Toby Maher the opportunity, sorry, to share his perspective on this data. Toby? Thanks. Yeah. Thank you very much for asking me to be part of the call, and congratulations on the results. I think just to go over them, the safety data I think looks very encouraging. As everybody I'm sure on the call knows, the two existing treatments that we have, nintedanib and pirfenidone, have considerable tolerability issues. We see significant drop-off rates in patients on treatment. I think in comparison to existing therapies, the data from this 12-week study would suggest that this is better tolerated than either of the existing treatments. To move to the efficacy analyses, I think there are some very encouraging signals there. First of all, if we just look at the placebo group, the placebo group behaves in the way we would expect an IPF placebo group to do so. They lose over 70 mL of FVC in the 12 weeks, and that's comparable to many other studies that we've seen published in studies that have been conducted in patients on background standard care. I think that reassures us that the placebo group is behaving realistically. Then if we look at the active treatment groups, we're seeing a reduction in the rate of FVC again, based both on the placebo in this study, but also on our historical understanding of how groups behave, to me suggests strongly that the drug is having an effective anti-fibrotic effect. If we move on to the more exploratory analyses, the QLF and the serum biomarkers with PRO-C3 and PRO-C6, again, although we understand less well how these measures behave in later phase studies, they are supportive of the FVC data in the sense that they're moving in the direction we would expect them to. I think for a phase II-A study, this provides a very compelling package of data to move forward with the compound. Thank you, Toby, for your insightful comments. As you heard today, the team and I are extremely pleased with these data and as they mark another step forward in Pliant development of PLN-74809 as an innovative approach to address the unmet need of the IPF patients. I want to leave you with a couple of conclusions, a program update, and next steps for the program. The results from the study obviously have exceeded our expectations, showing a favorable safety and tolerability profile and a treatment effect on both FVC and QLF. I think importantly, the fact that treatment effect was also observed on top of standard of care gives us confidence. That PLN-74809 has the potential to advance the treatment of IPF. We also recently completed enrollment in the 320 mg cohort of the INTEGRIS-IPF phase II-A trial. Interim data from this trial are anticipated in early 2023. Then finally, Pliant also intends on sharing today's data with the regulatory authorities in the near term to discuss the late-stage development plan for PLN-74809. Finally, we would like to thank our investigators and their study teams, as well as the members of the Pliant team for their dedication and support of the successful execution of this trial. More than that, special thanks to the INTEGRIS-IPF clinical trial participants, their families and support networks for helping us advance this promising program. Okay. With that, let's open the call to questions, Chris. The queue. Michelle, please go ahead and open up the queue to questions. If you'd like to ask a question, please press star then one. Our first question comes from Brian Abrahams with RBC. Your line is open. Good morning. Congratulations on the data, and thanks for taking my questions. My first one is for Dr. Maher, while he's still on. I was wondering if you could talk a little bit more about how these data overall fit in relative to other developmental IPF agents that you've seen with respect to the degree of promise. You know, might you expect potential improvements in FVC over time with an effective anti-fibrotic agent? And what would you be looking for here? What would you expect with even higher doses over longer durations with 809? And then I had a follow-up for the company. Thanks. Good questions. I think you know, realistically, I think we're expecting an effective anti-fibrotic to probably stabilize lung function and prevent FVC decline. I think there is a potential that drugs could lead to a sort of small but clinically important improvement over time. I doubt we're going to get a drug that's going to truly reverse established disease. I think aiming for stability and perhaps aiming for even a small improvement is realistic. Where does this sit in terms of other developments? As you'll know, there are some phase III programs ongoing. FibroGen have previously presented data with drugs suggesting some beneficial effects in phase II. Promedior, now taken over by Genentech, similarly, showed a reduction in the rate of decline in FVC over a 12-month study. Then more recently, BI in a 12-week study showed a PDE4 inhibitor appeared to prevent decline over 12 weeks. These data are at least comparable to those that have moved forward into phase III. You know, I'm sure everyone who's had any dealings with this field for a long time will know there have been a lot of failures. Success at this stage is certainly not a guarantee and only really a small number of drugs have proceeded. I think in the grand scheme, this is a very good result, and I think at least comparable to what to other programs that have moved forward to phase III. Got it. That's super helpful. This may be a question for management. In looking at the confidence intervals, it looks like they're relatively wide on FVC. Not surprising, you know, given the endpoint and the duration here. I'm just curious, any impact you think outliers may have had on mean FVC changes and maybe how some of those threshold analyses and any other analyses you've done on medians, for instance, might normalize for that. I had one more quick follow-up on safety. Yeah. This is Éric. Thanks, Brian. We have seen some patients who did better and some patients that did worse across all the treatment groups, I think. When we look at, given the size of each of the groups, we've also looked at the median changes which were consistent with the means. We think really the treatment effects of 74809 was definitely present in the 80 mg and 160 mg dose groups, and it doesn't seem that outliers are explaining that. Got it. That's super helpful. Lastly, just real quick in terms of the diarrhea that you've seen, can you expand a little bit about on I guess the manageability and you know how persistent versus transient that is, and any PK interaction you've seen or might expect with nintedanib that might further explain it? Thanks. Thank you. We don't expect any interaction with nintedanib because 74809 does not have much DDI liability. It's mainly a substrate for different transporters and isoenzymes. What's interesting, of course, is that 74809 is a substrate for CYP3A4 and PGP, and so is nintedanib. We will be conducting a formal interaction study, but we have not seen any excess toxicity in terms of the groups. In terms of, we know that there's more diarrhea in the combination, but we also saw that this was manageable as some of these patients used loperamide to treat. The duration of diarrhea was variable. For some patients, it started later, some patients, it started earlier, in some patients, the mild diarrhea tended to persist. Importantly, none of the patients discontinued due to diarrhea. Thanks again and congrats again. Thank you. Our next question comes from Pete Stavropoulos with Cantor Fitzgerald. Your line is open. Good morning, and congratulations on this positive data. My first question is for Dr. Maher. Seeing this data that was presented and then sort of taking into account your clinical experience, you know, with the two approved agents for IPF, you know, how do you see 74809 fitting into the current landscape or treatment paradigm? The reason I ask is, you know, I've spoken to a number of treating physicians, you know, and many of them highlight the tolerability issues with the two approved agents, which leads to high discontinuation rates of treatment by patients. You know, when you think about 74809, where it sits mechanistically, you know, sort of above TGF-β activation and take into consideration tolerability profile, you know. How do you sort of see implementing treatment in newly diagnosed patients? That's a good question. You know, my strong suspicion with IPF, like many other complex diseases, is that ultimately successful treatment is gonna involve combination therapy. Having said that, you also allude to the issue of tolerability that we have with existing drugs. I think as I see it, existing therapies have made a huge difference to IPF patients. It's making them live longer. Despite that, they are still dying of respiratory failure. They're still progressing. Their disease is getting worse. They're ending up on oxygen. There remains a need for better treatment. I think for patients who are on this therapy, I suspect they would be put on to a second agent, to help ensure that they have disease stability. I think one of the sort of reassurances from this trial was done on background standard of care. The data would suggest that it can feasibly be used as part of a combination treatment. Secondarily, given the fact that sort of a third or more of patients end up discontinuing existing therapies because of tolerability issues, there is a huge need for sort of cleaner, much better-tolerated drugs. Again, although it's a phase II-A study, the early signal would suggest that perhaps this is such a drug where we would see far fewer side effects. In all likelihood, it would be an option for those patients who struggle with the current existing treatments. I think the final point of where would we be if we saw these data replicated in a phase III study. I think the current challenge we have is that the FDA have not really been allowing trial designs that would allow you to place a new treatment as automatic first-line therapy. I think if we fast-forward five or six years from now and imagine that this drug gets approved, then I suspect it would come into the market as an add-on treatment on top of existing standard of care and would be used as monotherapy in patients who are intolerant of both existing treatments. I think one would then want to design a phase IV program to try and position the drug as automatic first-line treatment. Thank you. Very helpful. Next question I have is, you know, when you look at slide 25 and 26, the 80 mg dose, you know, you sort of or actually across the doses, you know, you sort of see, you know, the change on versus off standard of care, you know, seems to be an inverted U-shaped dose response. Any reasons why? You know, is it mechanism of action, PK or just an artifact of a small N in the non-standard of care cohort? Thanks for the question. This is Éric. We believe it's really a question of small Ns. And because of course the study was not powered to look at the efficacy endpoint. These were exploratory, but we think these could likely change with larger populations and certainly longer duration. But what we do think is really strong is the dose response that we see in the categorical assessment of FVC. So that's the percent predicted of greater or equal to 10%, where there's the fewest amount of patients progressing are the ones that are on the 160 mg dose. And that's certainly consistent what we saw in terms of benefits that we're seeing in terms of the QLF. Together, I think this gives us good confidence that there is a dose response which we have seen in previous studies as well, that were mechanistic and also on our preclinical evaluation. We'll just have to be, you know, really for myself, we know that the drug is active and it has an effect on FVC and QLF. We have everything we need to give the confidence to advance the program. Then as we design our phase II-B study, obviously this one will be powered adequately to be able to tease out the dose response. You know, along those lines, you know, when you think about a registrational study and, you know, you do look at the responder analysis, you know, it seems to reduce some of the potential compounding effects of the sample size. You know, when you think about a longer term study, you know, would it be just a change versus baseline in FVC with regards to the primary endpoint, or would you and possibly the agencies be interested in responder analysis? Can it be approvable beyond just the absolute change? Yeah. Both are important. The change in mL, the actual change in mL, is expected to be the primary endpoint, given that that's been used for the other approved agents. The other agents have also evaluated the 10% predicted FVC change, because it is part of the clinical outcomes evaluation. We will be providing data or evaluating both these endpoints as we move forward. All right. Thank you for taking my questions and, congratulations once again. Our next question comes from Ed Arce with H.C. Wainwright. Your line is open. Hi. Good morning. Thanks for taking my questions, and let me add my congrats on this positive data readout. First question for me, wondering if you could discuss, and this is for company management, the thoughts around dose selection. Clearly you have the 320 dose cohort coming up early next year, but from what you have, you know, 80 mg clearly has an absolute improvement in FVC, while with 160 mg you have no progression in QLF. Just wondering if you could discuss your thought process and the criteria by which you would ultimately select one or two for the next study. I have a couple follow-ups. Thanks, Ed. So we have certainly from this study results now really you know really good reasons to consider the 80 mg and the 160 mg as part of phase II-B evaluation. What will be interesting for us as we anticipate the results or wait for the results of the 320 mg cohort is it will tell us you know do we continue to see this favorable safety profile being manifested? Can we see even further changes in terms of FVC? Also the categorical assessment of FVC and QLF because all these measures will be part of the evaluation at 320 mg. Based on this information, then this is gonna be really important to see whether, you know, the 320 mg dose could be included, should be considered in late stage development. But right now, we have enough data, positive data to really have interactions with regulators later this year to discuss the study design that we intend to pursue in late stage. Basically the results of the 320 mg cohorts will help us inform the dose selection, but will not be needed to be able to advance the program because we have great confidence in the results that we have today. Right. Éric, the next question is, would you necessarily expect an incremental improvement in response with the 320 mg dose cohort, given that you saw, at least on the absolute FVC measurement, a stronger response on the 80 mg versus the 160 mg? It's gonna be interesting to see that. I mean, obviously 12 weeks is a great finding to see these changes that we've seen in our study now at 12 weeks. Certainly we're very excited about these results. The 320 mg dose group will go out to a longer treatment duration, which is supported by the availability of the preclinical safety studies. You know, we'll have treatment that will be administered for at least six months and up to a year. That's gonna give us additional confidence on how we know the projection of the curve, how we continue to see whether these, for example, improvements are stabilizing really throughout the 24-week period and longer. I think for us, you know, we would be, I think, maybe we'll be well served by looking at these data to really see, you know, to really further support the dose response we're seeing in the categorical change and also in the QLF. As we are coming up on the hour and have several callers in the queue, please limit yourselves to one question. Our next question comes from Ritu Baral with Cowen. Your line is open. Hi, guys. Thanks for fitting me in while Dr. Maher is still on. Hi, Dr. Maher. Great to speak to you again after so long. I wanted to ask your opinion about the mechanism and target engagement and whether you think that we're past the window of concern that was, I guess, first identified with the Biogen program toxicity. The mechanism, and target engagement, and whether you think that we're past the window of concern that was, I guess, first identified with the Biogen program toxicity around, α v β 6. I guess any additional details around that one, event of IPF that did not resolve, at the 160 milligram dose on the slide. Thanks. Hi, Ritu. It's been a long time since the days of [Persantin]. I think in terms of mechanism of action, you know, we've always recognized that TGF-β is a very important and integral part of disease pathogenesis in IPF. But at the same time, targeting TGF-β has been constrained by the knowledge that it plays important homeostatic roles both in the lung and in other organs. The targeting of the integrins, particularly α v β 6, has sort of looked like the most attractive route to damping down TGF-β activation without interfering too much with homeostatic mechanisms. I think as you allude to with Biogen, particularly in the phase sort of I-B, II-A data that they presented, they certainly did seem to see a sort of dose response that suggested a negative effect when they had their maximal effect on TGF-β activation. I guess that's always been in the back of people's minds as a concern when it comes to the safety of this sort of approach. I think, you know, that will remain a safety concern going into phase III. Pliant's teams have done a huge amount of work, not just with this data, but with other data they've generated to try and alleviate concerns about the safety of this approach. For me, that data has all been very reassuring. I think it's worth recognizing that this trial that we've heard about today is several times larger than the early Biogen trials, where they were already beginning to see a negative signal. For me, I think there's a lot of reassurance there that this is a pathway which can, with the right approach, be blocked safely. As I said, I think it's a very important pathway in the pathogenesis of IPF. Importantly, it's not a pathway that is particularly inhibited by either of the existing treatments. It really makes this drug complementary to existing treatments. Our next question comes from Yasmeen Rahimi with Piper Sandler. Your line is open. Good morning, team, and congratulations on the excellent data. Two questions for Dr. Maher. Thank you for being with us this morning. The first one is, can you maybe comment on sort of, you know, expectation when we think about translating this data into a larger study? You know, we have seen a number of failures when investigators run short studies in small populations. Given the totality and the comprehensiveness of the data that Pliant has generated, how confident can we be, you know, as they will be running, you know, a phase II-B study of a longer duration, more patients per arm, several doses. If you could just comment on that and what evidence we have, that would be one. The second one is, would love to hear your thoughts on the data on the QLF that the company presented. What does this data mean to you in terms of establishing its antifibrotic effect, and how widely used is this measure currently in the clinic? Thank you again for taking my question. Thank you. I think to answer your first question, you know, the best example of a failure after promising early phase data is the sort of recent experience with Galapagos. I think that the difference between what Pliant has done and Galapagos has done is enormous. While I was involved with the Galapagos program, it must be remembered that their first trial and the trial that led to the development of their phase III program was really a 23-patient study with only seven in placebo, and designed as a target engagement study with a single dose. Essentially because the company were cash rich, they took the opportunity to move that forward very rapidly into phase III without doing any further enabling studies, without doing any dose ranging phase II-B studies. I think with the data, we're a million miles away from that. Pliant has, you know, done lots of target engagement, so we know the drug is hitting the target in the lung. They have, with this phase II-A study, tested a number of doses, and have got the associated PK data, et cetera. I think in terms of following a logical developmental pathway, Pliant has really sort of ticked all the boxes. For me, I think we can be in a much more confident position with this drug than we ever were with Galapagos drug. I think you know, if we compare perhaps for success, it'd be similar to the pathway that was taken with nintedanib originally with dose ranging early phase studies. I think you know, acknowledging that phase II-A doesn't guarantee success at II-B or phase III, I still think we have reason to be confident based on this data. Your second question, which of course slipped my mind while I talk. That was the QLF. Sorry, Toby. QLF. The QLF. Yeah, QLF. Right. Thank you. Thank you, Éric. Yeah. I think, as I see it, the QLF data is sort of supportive of the FVC data. QLF, and again, I'm sure most people on the line have a reasonable understanding of this, but essentially QLF is a computerized algorithm for trying to interpret change in imaging, unlike FVC, where we have a clear understanding of what FVC change means over time in terms of survival and what slowing of FVC change means. With QLF, we perhaps have a broad understanding that preventing change in fibrosis severity on imaging is a good thing. We are still learning how to quantify that, and we're still learning how to interpret what any amount of given change means. On the QLF data alone, I think it's very hard to understand exactly how that might translate into a phase III study outcome. For me, the fact that the data are heading in the same direction as the FVC is very reassuring. I think the same is true of the serum biomarker data. We don't really understand what given change means, but from what we do know, changing things in the right direction is a positive. For me, it's all supportive of the FVC data, and I probably wouldn't try and extrapolate it further than that. Our next question. Thank you. Sorry, I think we'll be losing Dr. Toby Maher at this stage. Well, thanks for having me on the line, guys, and congratulations again on the data. Thanks, Toby. Thank you. Thank you. Our next question comes from Jeff Jones with Oppenheimer. Your line is open. Thank you, operator, and congrats again to the team on the excellent data. Thanks for taking the question. I guess, two questions for the team. As we look forward, are there other secondary endpoints such as cough or IPF symptom scores we should be thinking about to help differentiate the product? Will you look at things like that in your phase II-B ahead of the phase III? Then in terms of timing around the phase II-B, you've mentioned going to the FDA in the short term ahead of the 320 mg data. Of course, the 320 mg has the long-term readout as well. What are you thinking in terms of timing to start the phase II-B in the context of having data around the 320 mg? I'll halt there. Thank you. To address the first question, we will include patient-reported outcome measures as part of the phase II-B evaluation and also phase III, because these have traditionally been used and certainly we know that they're important to you know, the payers and what have you, and also to see if whether we can see some benefits from that perspective. We will definitely be including that. In terms of our regulatory interactions, as I mentioned before, really you know, we have the data now in terms of the strong efficacy signal that we see with a favorable safety to meet with the agency. What we wanna be talking about is really the strong arm of our late-stage development plan, where we really want to take the most robust but also most expeditious path to NDA. This will require some discussion with the regulators in terms of what you know, how they feel comfortable about our plan. That's the reason their feedback will really help inform when phase II-B can start. You know, I think that's all I'll say for now, but certainly these regulatory interactions will be needed to determine the start of phase II-B. Our next question comes from Thomas Shrader with BTIG. Your line is open. Good morning. Let me add my congratulations. Just a quick question on who your monotherapy patients were. Were they all people who couldn't handle standard of care, or were some of them treatment naive? There's a hint that some of your best treatment effects are in those patients. Do you think they'll try to get more patients just on your drug? Thank you. Yeah. The protocol allowed individuals to participate, whether they were on or off standard of care. These individuals would have been treatment naive for at least three months, whether or not they previously were on treatment or not. We don't have those data readily available, but suffice it to say that they experienced the treatment benefit was in the absence of standard of care. Which in total was approximately 20% in our study, but we will evaluate them in our advanced phase program as we did in the phase II. Yeah. Maybe just to add some color to that, we definitely are, you know, we'll be planning to include approximately 30% of patients not on standard of care as part of our phase II-B evaluation. We'll certainly be, you know, adding the information whether they were pre-treated and had to discontinue or whether they're truly naive. This is information that we will have for late-stage studies. Our next question comes from Joseph Stringer with Needham & Company. Your line is open. Joseph, if your telephone is muted, please unmute. Joseph Stringer, your line is open. There are no further questions at this time. I'd like to turn the call back over to Chris Keenan. Thank you, Michelle. On behalf of my executive team and all of my fellow Pliant colleagues, thank you for joining us this morning. This is certainly a great day for Pliant and potentially for patients with IPF. My team and I look forward to sharing updates from across the Pliant portfolio in the near future. Have a good day, everybody. This concludes the conference call. You may now disconnect.