European BioPharma team here at Jefferies. It's a pleasure today to be joined by the PureTech team. I think we're going to lead off with a quick presentation, and then we'll jump into some Q&A. If anyone has any questions, we can go into that. Otherwise, I've got plenty of things to be asking about anyway. Over to you, Bharatt. Thank you. Thank you, Ben, and thank you to the Jefferies team for inviting us to present here. It's really great to be here today. I'd like to welcome the people who are here in this room, as well as those of you who are following on the webcast. I'm really excited to share the PureTech story today, including the remarkable progress we are making with our lead program, deupirfenidone, for the treatment of idiopathic pulmonary fibrosis, or IPF, which is poised to enter phase three clinical development later this year. Before I proceed, I'd like to remind everyone that we may be making some forward-looking statements. Please do refer to our SEC and other regulatory filings for up-to-date information. Those of you who are not familiar with PureTech, we are a Boston-based clinical stage biotherapeutics company. We pioneered the hub-and-spoke R&D model, which enables us to efficiently fuel our innovation while maintaining a strong financial position. Our R&D approach is highly de-risked, focusing on molecules with validated pharmacology that have not really fully met the needs of the patients. This approach has yielded a strong track record of clinical and financial success, including several recent examples that are highlighted on this slide. In 2024, and thus far in 2025, we have delivered several milestones. Our most advanced program in our pipeline, deupirfenidone, our wholly owned program for IPF, has demonstrated unprecedented efficacy in a phase IIb study, positioning it, as we believe, a potential for a new standard of care. Just last month, we shared new data suggesting the durability of this treatment effect, and I am excited to touch upon that program a little later. Our LYT-200 program, it's our oncology program, continues to deliver positive results in acute myeloid leukemia, or AML, and solid tumors. We plan to house this program in a new founded entity called Gallop Oncology, and we're in the midst of seeking external funding to advance this program. The FDA approval in 2024 of COBENFY, which was invented at PureTech for the treatment of schizophrenia in adults, stands as a major validation for our R&D engine. These successes from our R&D hub-and-spoke model have also enabled us to maintain a very strong balance sheet. Our spokes, so we last reported about $339 million at the PureTech level as of March 31st. Our spokes, which we refer to as founded entities, serve as a source of capital back to us. These founded entities are well funded, mostly from third-party investors, which allows us to protect our balance sheet while maintaining the upside. In 2024 alone, for example, we generated approximately $327 million from our founded entity, equity holdings and milestone payments, which is a testament to the capital efficient model that we have. At the core of PureTech is a disciplined, innovation-driven R&D model built on three core principles: validated efficacy, clear patient benefit, and efficient de-risk development. We begin with drugs that have some level of human data or clinical signals, but have phase limitations. We then apply an innovative approach to science to overcome those limitations, unlocking the greater patient benefit and strong commercial potential. From there, we advance these programs through key de-risking milestones. If a program does not meet our predefined thresholds, we then reallocate resources towards programs that are more promising. This approach has delivered clinical success rate above 80% across our portfolio over the last 15 years and has led to three FDA approvals, including COBENFY that I mentioned earlier. With this approach, we have built a robust and strategically structured portfolio of therapeutic programs, which generally fall into two categories. There are our wholly owned programs, which are listed on the top portion of this slide, includes the LYT-100, our deupirfenidone, and our LYT-200 Gallop Oncology programs. At the bottom are listed our founded entities that are advanced through external investment after being identified and de-risked by PureTech through key value inflection points. Our unique hub-and-spoke R&D model that we pioneered offers significant upside across our programs, which have best-in-class potential. As shown on the left side of this slide, almost all of our current market cap is covered by the balance sheet, which means that most of everything else that we have in our portfolio, including our deupirfenidone program, which is entering phase three, we have LYT-200 program, which is our oncology program, poised to enter phase two next year, COBENFY, which we talked about royalties and milestones that we are eligible for, Seaport Therapeutics, equity holding in our new founded entity, which we launched last year, where we have not only equity, but also milestones and royalties, and so on. Most of our portfolio is not being recognized by the market, which represents a huge value disconnect. Our model also makes us one of the very few biotech companies, therefore, that can shield investors from downside risk with our strong track record of clinical success, which continues to fuel our high-value pipeline with exciting data that we've been announcing. We also have attractive pockets of value, as shown on this left side of this slide, a strong balance sheet of $339 million that we announced at the end of first quarter, which has enabled us to fund our R&D operations. We are a self-funded evergreen type of a model, which has enabled us for the last seven years, we haven't had to raise money in the public markets, and we are self-funded from that perspective. In a volatile market environment, such as we are experiencing now, the resilience and differentiation are going to be key. We believe that our scientific and operational strengths, track record of success, and strong balance sheet, combined with our commitment for advancing impactful programs like deupirfenidone, make PureTech a compelling, we believe, opportunity for new investors, especially given this huge value disconnect that we currently have. Today, I'll just highlight one of those exciting programs that we have, deupirfenidone. For those not familiar with IPF, it's a rare progressive fatal lung disease that affects more than 232,000 people in the U.S. and most major European countries. The median survival after diagnosis is just two to five years. Despite generating annual revenue in the billions of dollars, the current standard of care treatment, there are two of them, two drugs that are approved, only modestly slow lung function decline in people with IPF. Why is that? Their effectiveness is really limited by the tolerability challenges at higher doses, which creates an efficacy ceiling. This prevents patients from reaching dose levels because of their poor tolerability to improve the outcomes, which leads to suboptimal efficacy, reduced patient uptake, and lack of adherence. As a result, only about one in four patients in the U.S. have ever been treated with an FDA-approved therapeutic. To further highlight the unmet need in IPF, this slide illustrates this urgent need for better therapies. Currently approved antifibrotics are efficacious, but patients continue to see a significant decline in their lung function. We believe that the next generation of IPF treatment must deliver meaningful disease management without compromising tolerability. I could not be more proud of the progress we are making with deupirfenidone to address this major gap in efficacy. The key takeaways from our successful phase II- B ELEVATE IPF trial. In the phase II- B trial, deupirfenidone 825 mg three times a day, or TID, slowed lung function decline as measured by forced vital capacity, or FVC, to -21.5 mL over a 26-week period, compared to -112.5 mL for placebo. This represents a robust treatment effect versus placebo of 80.9%, which was approximately 50% greater than what we have shown with deupirfenidone in our study. Importantly, when we look at the pharmacokinetic data from this study, it correlated very nicely with the increased efficacy we saw with deupirfenidone. The deupirfenidone 825 mg TID arm achieved approximately 50% higher exposure than deupirfenidone. This is meaningful because it roughly corresponds with approximately 50% greater efficacy that we demonstrated with deupirfenidone. More importantly, there was no increase in adverse events with increased drug exposure with deupirfenidone, which is really important because higher exposure did not necessarily mean that you had a higher AE profile. For context, when you look at the lung function decline, the rate of decline we saw with deupirfenidone, which is shown in the middle column there in green, is similar to what is expected in older healthy adults who do not have IPF. All of us lose lung function as we get older. That is shown, that is the average physiological lung function decline on the right-hand side of this slide. These results demonstrate the level of lung function preservation that has not been seen in IPF trials over at least six months treatment duration. This is, we think, is a really big deal. A lot of the key opinion leaders we have spoken to are really excited about this level of efficacy we are seeing with deupirfenidone. Just last month, we presented more compelling data at the American Thoracic Society Conference, ATS, from our ongoing open-label extension study. As of May, a total of 101 patients had received at least 52 weeks of treatment with either dose of deupirfenidone. Those in the deupirfenidone 825 mg TID arm experienced a decline in FVC of -32.8 mL over a one-year period. That is shown on the green line on this slide here. That green line overlaps with the yellow range that is shown on the slide, which depicts the natural lung function decline you see in healthy older adults who do not have IPF. This once again reinforces the potential for deupirfenidone to preserve lung function in people with IPF. We believe that this has the potential to be the new standard of care in IPF and gives us a lot of confidence as we are progressing into a phase III trial. We intend to have a dialogue with the regulatory agencies, including FDA, before the end of the third quarter of 2025 to align on the potential registration pathway with the goal of initiating a phase III trial by the end of this year. We expect to provide additional detail later this year. We are really excited about this program. Beyond deupirfenidone, we are excited about what lies ahead for PureTech, as shown on this slide. With a robust portfolio and a track record of clinical and financial success, we are really well positioned for another transformative year at PureTech. With that, I'd like to welcome Dr. Eric Elenko to join me for this fireside chat. Thank you, Ben. Appreciate it. Thank you. Inviting us. Look, there are a few questions I'd like to get through. I want to start more on the business level, and then I think we'll touch on IPF as well, given it's very relevant. This hub-and-spoke model is very unique to PureTech. What is it about it that you think offers an attractive offering to investors? How are you thinking about that hub-and-spoke model going forward on more of a forward-looking basis? Yeah. This hub-and-spoke R&D model that we pioneered, it's a really unique opportunity for us to, one, diversify our portfolio where we don't have to depend on any one program, success or failure of one program to drive value. We have multiple, what we call in hockey analogy, multiple quality shots on goals. It also provides potential investors an opportunity to really de-risk some of the investment when you look at. In the hub-and-spoke where we look at, we start these programs from de novo, from scratch at PureTech. We do the early de-risking experiments at PureTech and through key value inflection points. We spin them out as a wholly owned subsidiary where we end up owning 100% of each one of these programs. We bring in external investors into that. That, again, diversifies our exposure in terms of having to invest into multiple programs all by ourselves at PureTech. We have outside investors, but we maintain enough sufficient level of equity ownership, as well as because we are inventors in a number of these programs, we also have other economics like the milestones and royalties on the products. This gives us the de-risking as well as potential for upside. Corona is a great example of that for us. That's been our biggest success so far where we put in, we started that program, and Eric is a lead inventor on COBENFY. We started that at PureTech. We took it through the major de-risking through phase one. We put in, all said, about $18 million into that. Then we brought in outside investors, took them public. Overall, so far, we have been able to generate $1.1 billion from our $18 million investment. We were able to reinvest that into our pipeline. We also have now milestones and royalties from that. It is an ongoing revenue stream potential as well. That is a huge success for us and a great example of the validation of our hub-and-spoke model. Yeah, that makes sense. And look, as you said, you've earned a considerable amount from that Karuna stake over time. I'm interested to kind of know how that deal with Royalty Pharma is set up now that it's passed over to there. And is there potential for setting up similar deals like that in the future? Yeah, certainly. So when you look at the COBENFY, we had 3% royalty on COBENFY. We sold that to Royalty Pharma for $100 million upfront. We were eligible for another $400 million in milestones based on achievement of certain sales thresholds. We also are eligible for 2% royalty when the sales cross $2 billion in a given year. And Royalty Pharma keeps 1%. There is this potential. Depending on the analysts' estimates, COBENFY is expected to do somewhere between $5 billion-$10 billion in annual sales. We see that in the future as a potential revenue stream for us. Similarly, we have set up Seaport Therapeutics last year where we were inventors on a number of their programs and the platform. When Seaport advances their pipeline programs, we are eligible for milestones and royalties in a similar range as COBENFY. In addition to equity ownership, we own about 36.9% in that company. Makes sense. Look, you've got wholly owned assets and you've got these founded entities. What is the trigger point for switching it to either a founded entity or keeping it wholly owned? How are you thinking about the balance going forward? Yeah. It is on a case by case. It depends. In schizophrenia, when we decided to spin out Karuna, we believed that a dedicated effort would be required and a significant amount of funding would be required to advance COBENFY through clinical trials and potential launch. There we felt that we had added enough de-risking and value that we could then spin that out, keep a lot of the economics. We spun that out after phase I. In terms of deupirfenidone, we believe that it is a rare indication that a small company like PureTech could take it quite far in development and still be able to retain a lot of the value. We took that program through phase II- B. We are gearing up for phase III now. We are looking at different ways to decide whether to spin that out, similar to Karuna, and bring in outside investors or find other sources of non-dilutive funding for us to take it forward. Very clear. Eric, perhaps one for you here. We've had a little look at the data package for the IPF drug. I'm really interested to hear from you. What is it exactly that underscores the confidence that this is going to be something that is meaningful to these patients after into phase three? What are the key takeaways from that ATS presentation for you? Sure. There were a few aspects of the trial that we thought were exciting and, as Bharatt indicated, getting positive feedback from the key opinion leaders. If you look, it was a four-arm trial. Placebo, pirfenidone at the highest commercially approved dose, and then two different doses of deupirfenidone. The placebo behaved the way one would expect placebo to behave in a six-month study. Pirfenidone was about half of placebo, a little bit more, but really in the range of what one would expect. That really shows what people refer to as good assay sensitivity. In other words, there was good clinical trial conduct. If you look, we had a dose-dependent effect between the two different doses of deupirfenidone. Our highest dose, the 825 mg three times a day, was in a range of lung function decline as measured by FVC, which is a gold standard measure that, as Bharatt was outlining, is in that range of physiological decline associated with someone without IPF. What we saw with the open-label extension study, individuals who started on that 825 dose in the randomized part that was double-blinded and then continued into the open-label extension, that response was durable. That is really what we think lends deupirfenidone to really become the standard of care and really has shown data as a monotherapy that has not been shown previously. This really all correlates with the PK data that Bharatt was presenting. You get about 50% more exposure. You get about 50% more efficacy. It is known, and there are a few different groups that have presented data that really shows that pirfenidone itself is a drug where more is more. You get greater drug on board. You get greater exposure. You get greater efficacy. The problem has always been that no one was able to dose up higher because there was a ceiling reached because of adverse events, which, as we got greater exposure, we were able to do without increasing the adverse events compared to pirfenidone. That makes sense. Look, you weren't the only IPF drug presented at ATS. Could you give us a little bit of a sense about what you're seeing as part of the competitor Boehringer Ingelheim's program? What underscores the confidence that you've still got an asset here that should be differentiated? Sure. First of all, we're really happy that there's potential for new therapy for patients and people living with IPF. This is a devastating disease. Patients who are on standard of care still experience 100% mortality. It is important for the field that this drug represents an advance. While we can't comment specifically on another company's data and drug, what we can say with confidence is if you look at the data that we have and that we are in a range of lung function decline that represents the lung function decline associated with older adults without IPF, and that as a monotherapy, that really represents what people want to see. When we talk to key opinion leaders, talk to practicing physicians, talk to patients, number one is efficacy in terms of need, and specifically stabilization of lung function and getting to the same level as someone who does not have the disease. We are aware of the data that is out there and continue to believe that deupirfenidone has potential to be best in class and standard of care if we are able to reproduce what we saw in ELEVATE. Look forward to the results and getting on with the trial, I guess. Another area that we've seen some bubbling interest in has been the Seaport platform. I appreciate this has been established by PureTech already. Could you talk to us a little bit about the Glyph platform? What promise does that hold? You're looking primarily at CNS, but does it have potential translatable ability elsewhere as well in other indications? Yeah. Certainly, I can start. And then, Eric, please feel free to jump in. Yeah, Seaport Therapeutics is a company that we launched last year to advance programs in depression, anxiety, and related indications. We were able to attract a significant amount of investor interest. We raised, combined across two rounds of private financing, $325 million into Seaport Therapeutics. They have three programs in their pipeline currently in development. The lead program is going to enter phase II- B studies in depression. They have a second program entering phase one in general anxiety disorder and a third program behind it. They have a pipeline of really exciting programs in depression and anxiety-related indications. The key there was, as you mentioned, the Glyph platform. This was a technology that we originally identified at Monash University in Australia. A professor there was really looking at how to create pro-drugs of small molecules that have the ability to bypass the first-pass metabolism in the body. That has a number of potential applications in that it improves the oral bioavailability of molecules that otherwise are not orally administerable. It also bypasses the first-pass metabolism. It helps with some of the liver tox issues that a number of small molecule drugs have. We looked at a portfolio of these molecules over the period of about four or five years at PureTech. We had reached a point with the lead program where we had some de-risking in humans before we decided, OK, it requires a concentrated, dedicated effort. Also, the capital required to advance all of these programs forward would be significant. We decided to spin that out into a new founded entity. Initial programs are all focused on CNS-related applications. The opportunity set is quite broad. They can be applied to any small molecule across indications that have a first-pass metabolism issue that can be overcome with this approach. It is really exciting. I do not know if Eric wanted to add to that. It's a good summary. The platform, because it's based on the idea of bypassing first-pass metabolism, really does have a number of applications. In the context of Seaport, having that concentration on CNS and psychiatry really made sense. Just those trials really require a certain set of expertise. That's nice when that expertise can be concentrated. There are just some really phenomenal people involved in that company in terms of knowing how to conduct those types of trials. Very clear. Look, that takes us to the end of time. Thank you so much for joining us here at the Jefferies Conference. If anyone has any questions, please feel free to reach out to myself or the team. We will be here to help. Enjoy the rest of your day. Thank you. Great. Thank you.