Greetings and welcome to the PureTech Health Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host, Allison Mead Talbot, Head of Communications. Thank you, Allison. You may begin. Thank you for joining PureTech's call to discuss the positive top-line results from our Phase 2b ELEVATE IPF trial. This presentation will be available at our investors' page of our website. I would like to remind you that during today's call, we may be making certain forward-looking statements. These statements are subject to various important risks, uncertainties, and assumptions that could cause our actual results to differ materially from our expectations, and we ask that you refer to our SEC filings for a complete discussion of these factors. You should not put undue reliance on any forward-looking statements. These forward-looking statements reflect our expectations as of the date of this call, and we undertake no obligation to revise or update any forward-looking statements or information except as required by law. Walking us through today's exciting results will be Dr. Bharatt Chowrira, Chief Executive Officer; Dr. Eric Elenko, Co-founder and President, and Dr. Cammie Graham, Vice President of Medical Affairs. Thank you, Allison. Welcome, everyone. Today is an important day in the pursuit of new treatments for people living with idiopathic pulmonary fibrosis, or IPF. As many of you know, IPF is a deadly, debilitating disease, and no new treatments have been approved in over 10 years. We could not be more pleased with the results from our Phase 2b ELEVATE trial of LYT-100, or deupirfenidone, in IPF, which exceeded our expectations. First and foremost, I would like to thank the courageous people living with IPF and their families for participating in the trial, as well as the investigators and study coordinators for their care and diligence in the execution of this trial. For those of you who are not familiar with IPF, it's a rare, progressive, and fatal disease involving scarring of the lungs, with a median survival of just two to five years. There are more than 230,000 people in the U.S. and EU five countries with IPF. There are two approved treatments for IPF, one of which is called deupirfenidone. Both approved treatments are effective, although they can cause challenging side effects, which means patients cannot fully benefit from these otherwise efficacious medicines because they are unable to stay on the treatment long enough or at the optimal dose to achieve good disease management. This trade-off between efficacy and tolerability means that most patients never start treatment, and those who do often take less than optimal dose or discontinue treatment altogether. And importantly, only one out of four people living with IPF in the United States are currently on treatment. This is largely due to these tolerability concerns. We are developing deupirfenidone to overcome these challenges. deupirfenidone is a deuterium-modified form of pirfenidone, which means we have strategically replaced three hydrogen atoms in the pirfenidone structure with three heavy hydrogen atoms, as shown in the figure. These changes are designed to retain the beneficial pharmacology and clinically validated efficacy of the molecule, but with a differentiated pharmacokinetic and tolerability profile. I'm delighted to share that deupirfenidone clearly demonstrated this favorable profile in our Phase 2b trial. The trial achieved its primary and key secondary endpoints, demonstrating remarkable efficacy and a favorable tolerability profile. These data support the progression of our program into a Phase 3 trial and highlight the potential for deupirfenidone to serve as a new standard of care treatment for IPF. I would now like to welcome Dr. Eric Elenko, our co-founder and President, and Dr. Cami Graham, our Vice President of Medical Affairs, to walk us through the results in detail. Thank you, Bharatt. This is a really exciting day, and I'm pleased to walk you through our unprecedented data. Let's start with our unique trial design. The Phase 2b trial was a randomized, double-blind, active, and placebo-controlled dose-ranging trial evaluating deupirfenidone at two dose levels three times a day, also known as TID, over 26 weeks in patients with IPF. Importantly, this was the first time that an investigational therapy has been evaluated alongside one of the two existing standard-of-care treatments. We over-enrolled the trial, and 257 participants were randomized 1:1:1:1 to receive deupirfenidone 550 mg, deupirfenidone 825 mg, pirfenidone 801 mg, which is the FDA-approved dose, or placebo TID for 26 weeks. ELEVATE was a global multicenter trial, and over a quarter of the participants were from the United States. Demographics of the trial generally reflected that of other IPF trials and was racially diverse. Before we dig into the results, I'd like to review our statistical approach. The primary endpoint was pre-specified to be evaluated using a Bayesian analysis. The Bayesian approach allowed for augmentation of the placebo arm of placebo data from a historical IPF trial. This approach enabled a more patient-centric clinical trial design by minimizing the number of trial participants exposed to placebo, a key consideration since IPF is progressive and fatal while delivering a robust placebo-controlled data set. We also pre-specified an analysis separate from the Bayesian approach that would allow us to calculate p-values, commonly known as the frequentist approach, though we did not correct for multiplicity. Based on historical monotherapy development in IPF, a statistically significant effect was not anticipated between any individual arm versus placebo given the size of our Phase 2b trial. However, the magnitude of the efficacy demonstrated with deupirfenidone 825 mg TID was large enough to achieve a statistically significant p-value. Our efficacy calculations also utilized a random coefficient regression model with repeated measure, which is a standard statistical methodology. The primary endpoint of the trial was the rate of the decline on forced vital capacity or FVC over 26 weeks, comparing the full deupirfenidone arms versus placebo. FVC is the amount of air an individual can forcibly exhale from their lungs after taking a deep breath. It is the gold standard endpoint in clinical trials for IPF. Importantly, ELEVATE achieved its primary endpoint based on a pre-specified Bayesian analysis with a 98.5% posterior probability. This means there is a 98.5% probability that the full deupirfenidone arms were superior to placebo in slowing the rate of lung function decline in people with IPF, as measured by FVC at 26 weeks. The trial also achieved the key secondary endpoint, measuring the rate of lung function decline using forced vital capacity percent predicted, or FVCpp. While FVCpp and FVC are both measures of lung function, FVCpp accounts for the key patient characteristics, age, sex, height, and race, and therefore normalizes the results at the patient level. For example, a tall man will have a greater lung capacity than a petite woman, which is accounted for in the FVCpp analysis. On this important measure, there is a 99.6% probability that the full deupirfenidone arms were superior to placebo in slowing the rate of lung function decline. Now I'm going to show you the frequentist analysis for all four arms. The black bar represents placebo, the blue is deupirfenidone 550, the green is deupirfenidone 825, and the yellow is pirfenidone. The chart on the left shows that the rate of FVC decline at week 26 with deupirfenidone 825 mg was large enough to be statistically significant compared to placebo, with a p-value of 0.02. The same dose also demonstrated a robust treatment effect on FVCpp compared to placebo, as shown by the chart on the right, with a p-value of 0.01. I'd also like to note that the observed decline in FVC and FVCpp with placebo was consistent with the expected decline, indicating a rigorously executed trial. The results seen with deupirfenidone 825 TID are particularly striking, given that the reduction in lung function decline seen in this dose approached the level of natural decline seen in healthy adults over 60 years old for the same timeframe. This slide represents an analysis of the observed treatment effect of each active arm versus placebo. As you see, deupirfenidone demonstrated a dose-dependent effect, and the 825 mg dose had a robust treatment effect of 80.9%. deupirfenidone had a 54.1% treatment effect compared to placebo, which was in the high end of the expected range based on previously reported deupirfenidone clinical trial data. So to summarize, here are the four key takeaways on efficacy. We met our primary endpoint. We also met our key secondary endpoint. deupirfenidone 825 mg TID demonstrated a statistically significant difference from placebo on both efficacy endpoints, and preliminary data from our open-label extension study indicates durable effects. Remarkably, the rate of decline with deupirfenidone 825 mg TID approached the level of natural decline seen in healthy adults over 60 years old for the same timeframe. Now I'll turn it over to Cami, our Vice President of Medical Affairs, to walk us through the safety data. Thanks, Eric. I'd like to start off by saying that as a practicing physician, I know firsthand how hard it is to have patients struggle to tolerate a medication. So safety and tolerability are key considerations across everything we do at PureTech. Now, efficacy, which you just heard about from Eric, which in the context of IPF means slowing down the progression of lung function, is obviously very important to people living with this disease. But so is quality of life, including tolerability, and we carefully assessed the safety and tolerability of deupirfenidone in this study as well. In this trial, deupirfenidone demonstrated favorable tolerability with both doses that we tested. Now, as you can see from the table, when compared with the pirfenidone arm, the 825 mg arm of deupirfenidone had a lower percentage of patients reporting the key gastrointestinal-related adverse events of nausea, dyspepsia, diarrhea, constipation, and vomiting, although we did see an increase in abdominal pain compared to pirfenidone. This is context. The pirfenidone label was the 24% rate of abdominal pain. deupirfenidone's favorable profile is further validated by the fact that more than 90% of patients who completed the trial opted to enroll in an ongoing open-label extension study, and we're also seeing favorable preliminary data from this open-label extension. To date, the longest a patient has been on the 825 mg arm is 79 weeks. This suggests that deupirfenidone's favorable tolerability profile enables patients to stay on the drug longer. We intend to discuss all of these results with regulatory authorities and expect to share additional data from the trial at a future forum. I would now like to hand it back over to Bharatt. Thank you, Cammie. We are so proud of these data and the potential for deupirfenidone to change the way IPF is treated. To recap, we met our primary and the key secondary efficacy endpoints. Both doses of deupirfenidone demonstrated favorable tolerability. deupirfenidone 825 mg three times a day demonstrated a statistically significant difference from placebo, with a strong, consistent, and durable treatment effect that continues to be supported by our open-label extension trial. The decline in lung function seen with this dose as a monotherapy approached natural lung function decline expected in healthy older adults. We intend to discuss these results with the regulatory authorities and expect to share additional data from this trial at a future forum. 2024 has been a historic year for PureTech, with several major milestones achieved across our pipeline and portfolio, as highlighted on this slide. These results build on our track record of developing impactful new therapies to address tremendous patient need. I would like to thank all of my PureTech colleagues for their extraordinary efforts in achieving this important milestone. This success is a result of your unwavering commitment, expertise, and teamwork, and it represents a critical step forward for patients who are counting on us. The Elevate trial marks a significant milestone for PureTech as our first fully-owned program advancing into late-stage development. These results further reinforce our proven ability to advance potentially transformative medicines rooted in validated pharmacology. With this achievement, we are well-positioned to drive continued innovation, growth, and meaningful impact for patients. We will now take questions. Thank you. If you would like to ask a question, please press star one on your telephone keypad now. If you would like to withdraw your question, please press star two. Our first question comes from Ben Jackson at Jefferies. Please go ahead. Great. Thank you for the question. If we just start with the safety data that we've just seen, obviously very impressive, but on the abdominal pain side of things, is this perhaps something that we're seeing because it's a more mild form of the other events that are occurring, or is there any kind of explanation that you have to why we're seeing an elevated rate in the trial? I obviously understand that when you compare it to the label itself, it's slightly different. But any kind of explanation around why that rate is increased would be of use to us. And then secondly, if I may just squeeze another one in, if we're looking at the relative efficacy of the lower deupirfenidone dose versus the standard of care, we were obviously expecting after Phase 1 that that was going to be similar on an efficacy standpoint. What would perhaps be the reason, or potentially this is something that we have to wait for PK data from, that they did not perform relatively equally in this study? Any thoughts there at all? Thank you, Ben. So let me address your first question. Maybe I can have Cami address the first question, and then I'll follow up with the efficacy question. Yeah, sure. So the abdominal pain percentage is different. We've looked into it. There's no signal, no cause for any concern. And we're continuing to dig into all of these numbers. But for right now, we don't have any cause that there's a signal there. Regarding the efficacy question, so our goal with deupirfenidone has always been to offer better efficacy, whether through improved tolerability or by increasing the dose relative to pirfenidone. So deupirfenidone 550 mg three times a day clearly showed evidence of efficacy versus placebo as a monotherapy with a favorable tolerability profile at six months. So the ELEVATE is a dose-finding trial, and we are pleased that it has established dose-dependent efficacy, which is important from a clinical and regulatory perspective. We also see clearly a differentiated product with the 825 mg three-times-a-day dose that demonstrated unprecedented efficacy. You may recall we picked the deupirfenidone 550 mg three-times-a-day dose based on our Phase 1 clinical trial PK data in healthy adults. So today we are sharing top-line results, and we do not have the PK data from this trial. When we have this information, we will be sharing that additional insight in the future forums. Clearly, 550 dose was efficacious when compared to placebo, and 825 really had unprecedented efficacy data showing and demonstrating a really good dose response. Because this was a dose-ranging study, trying to look at what is the optimal dose we want to move forward in a future study, we actually have accomplished that. Very clear. Thank you. And if I just may really quickly just follow up with two more. One, could you just remind me how the dosing worked here? Was it a fixed dosing in the sense that patients weren't able to delay or pause treatment or therapy if they struggled with tolerability? And then the second one, just on potential timing for detailed data. Obviously, I think something that we've been discussing here with people is potentially for ATS in May. Is that perhaps too early, or is that potentially feasible, albeit not looking for confirmation of when you're looking to submit for? Thank you. The second part of the question, so I know we do plan to present the data at a major conference in 2025, and we'll provide that information as we get closer to those conferences. Regarding your first question, I'll have Eric maybe comment on the dosing. Hi. Great to speak with you. So the way the dosing worked is patients titrated up, and then if they couldn't tolerate the drug, they were allowed to titrate down. And I appreciate the question because it gets to the really important point that the 825 dose also includes the 550 dose. And so that's why we were happy to see going back to what Bharatt said, that the 550 dose clearly had activity and clearly was differentiating from placebo. Yeah. Very clear. Thank you very much for the questions and the time to answer. Thanks, Ben. Our next question is from Faisal Khurshid at Leerink Partners. Please go ahead. Hey, good morning, guys. Congratulations on this nice update. First question I had is, how should we think about the relative tolerability of the 825-mg dose compared to pirfenidone? At this point, would you characterize this as similar tolerability or potentially improved relative to pirfenidone? Yeah. Thanks, Faisal. Maybe Cammie, you can comment on that? Sure. Thanks for the question. So we were looking for a dose of deupirfenidone that showed improved efficacy without sacrificing tolerability. And we focused on those key GI adverse events in that go-no-go decision-making because the pulmonologists treating IPF and people living with IPF had described these as the major challenges they faced. So evaluating safety and tolerability is complex, but so far, in totality, deupirfenidone 825 mg had similar to better tolerability than pirfenidone across the board. And that's what enabled us to see the efficacy that we described. Got it. That's helpful. And then I realize it might be premature to ask this question, but I just want to get the initial sense of how should investors be thinking about the potential path forward here? And in particular, I think people would be curious to understand, at this point, are you thinking you might have to run a head-to-head superiority study versus pirfenidone, or what would that potentially look like? Yeah, Faisal. So these data are really impressive, and we intend to discuss the outcome from this trial as well as the next steps with the FDA. And based on the strength of these results and our intention to pursue a 505(b)(2) pathway, it is possible that we may only need one additional trial before we see the full. Got it. Thank you. Thanks, Faisal. Our next question comes from Leolie Telford-Cooke at Peel Hunt. Please go ahead. Hi. So I'm going to be cheeky and ask the three. Firstly, does the data coming from this trial change how you think about strategy or partnering options for deupirfenidone? The second one is you're doing an open-label extension. How long are you planning on running the open-label extension? And then thirdly, in your kind of early thoughts, your opinions, what would be the most important dose for a potential Phase 3? Would it be the lower dose in minimizing adverse events or going with the higher efficacy of the higher dose? Yeah. So first part of your question, these results from the Phase 3 trial really provide us with significant optionality for future development of deupirfenidone. I mean, these options include, and we've said this previously, include continued development at PureTech through a variety of funding mechanisms, including project or royalty financing, partnerships with other companies, and as well as equity financing or a combination of these different options. So this really gives us a broad range of options that we can explore in parallel, guided by the optimal route to bring this potentially what we believe is transformational treatment rapidly to patients and generate value for our shareholders. With regards to the open-label extension study, I mean, maybe Eric, you want to comment on that? Sure. Thanks for that question. We're really happy to see such a high percentage of people who completed the randomized portion of the study went into the open-label extension study. We see the OLE, or open-label extension study, having value both from a patient perspective given the data that we saw, which of course is our goal, is to be able to help patients, as well as from a scientific perspective, so right now, we're going to continue the open-label extension, and then I think the third question that I'll go ahead and address here is around the dose, so the 825 dose showed the greatest efficacy, and the nice thing is that was done without sacrificing tolerability, so we were able to have a dose of the drug and data that showed an impressive effect, but we still had favorable tolerability here. I think this really goes to the earlier question, which is around how the drug was dosed and, of course, how the drug might be dosed. That really goes to the idea of titration. Someone getting 825 could end up going through a 550 dose and then, of course, could have then the option of titrating down. We're not providing any formal guidance about Phase 3 design in terms of specificity, but I think the data clearly point to the 825 dose really having that nice balance of efficacy and tolerability. Fabulous. Thank you. Very clear. Thank you. This now concludes the Q&A session, and I will hand the call back to Bharatt for any closing remarks. Thank you, everyone, for joining us today. On behalf of the PureTech board and the team here at PureTech, I would like to wish everyone a happy holiday season and a safe and healthy New Year. Thank you. This concludes today's conference call. Thank you all very much for joining.