Good morning, everybody. Good morning, everybody. I hope you're having a fantastic day three at the JP Morgan Healthcare Conference. My name is Pavna, and I'm an associate in the Healthcare Investment Banking team. Thank you for joining us for PureTech Health's presentation. We have with us the Chief Executive Officer, Bharatt Chowrira, PhD, JD. And in the audience, we also have Eric Elenko, co-founder and president. We'll leave time in the end for questions, but for now, over to you, Bharatt.
Great. Thank you, Pavna, and thank you to JP Morgan for inviting us to present here today. I want to welcome everyone who's here in the audience, as well as those of you who are following us on the webcast. So PureTech is moving into 2025 with great momentum on the backs of some amazing data that we announced at the end of last year before the holidays. So we'll be digging into some of that data from our phase IIb clinical trial with deupirfenidone in idiopathic pulmonary fibrosis, or IPF. These exciting results really capped off an amazing, incredible historic year for us, which, in addition to these clinical data, we also included three major events. One of our founded entities, Karuna Therapeutics, was acquired last year by Bristol-Myers Squibb for $14 billion. Subsequently, the lead program from Karuna was approved by the FDA.
This was called Cobenfy, which was invented at PureTech. This is a very landmark approval, and we believe it will help a lot of patients. We also, in 2024, launched a new company called Seaport Therapeutics, which is going to house the next wave of our CNS programs. And Seaport has attracted a lot of investor interest. They've raised about $325 million last year from top-tier investors. So all of this catalyst really translates to the fortification of our strong balance sheet and really strengthens our self-funded R&D model. I'm pleased to announce that we ended 2024 with $365 million to continue to fuel our programs and innovations. So when you look back, 2024 was truly a very remarkable year, especially when you look at the size of our company. And there's more to come.
So before I continue, I do want to remind everyone that during the presentation, we may be making some forward-looking statements. So please do refer to our SEC and other regulatory filings for up-to-date information. So for those of you who are new to this story, PureTech is a Boston-based clinical stage biotherapeutics company. We're a very unique company in a lot of different ways. So first and foremost, we have pioneered this hub-and-spoke R&D model, which fuels our innovation engine. Second, we have a de-risked R&D drug discovery approach centered around molecules with validated pharmacology that have not really lived up to the full potential in meeting the patient needs. And third, we have an impressive track record of success with this approach. One of the three aspects that drive our success is our de-risked approach to drug discovery.
Indeed, over 80% of clinical trials conducted by either PureTech or one or more of our founded entities over the last 15 years have been successful. And Cobenfy is our third FDA-approved product that originated from PureTech. So this success is really underpinned by three key factors. The first, and they're listed at the bottom of this slide here, first is to really identify significant patient need in a given disease. We then tackle that problem with either small molecules or biologics that have demonstrated some level of human efficacy, but for one reason or the other have been held back. So we then apply an innovative approach or a technology to overcome these challenges that have held them back so that they can live up to their full potential. And then we conduct really rigorous de-risking experiments with pre-specified thresholds for advancement.
Our disciplined and rigorous approach to R&D has really generated a robust portfolio of programs, and these are categorized in two different buckets, so the first category is our wholly owned pipeline, which is shown at the top of the slide here, and then at the bottom are the second category of programs that are housed in our founded entities, so we initially identified and discovered the programs and technologies and housed them in these individual founded entities, advanced them at PureTech through key validation and value inflection points before bringing in outside investments. These founded entities are a source of capital back to PureTech through our equity investments, as well as, in many cases, eligibility to receive milestones and royalties, because we're also co-inventors on a number of these programs.
Today, we're going to just focus on one of those wholly owned programs, deupirfenidone, and the truly remarkable data that we generated in IPF and announced at the end of last year. Those of you who are not familiar with IPF, it's a rare, progressive, and fatal disease characterized by scarring of the lungs. The median survival in IPF is just two to five years. It's really quite a devastating disease. There are two FDA-approved treatments for IPF, one of which is pirfenidone. Both of these treatments are effective, but they come with significant side effects and tolerability challenges. As a result, patients and providers must balance and have to choose whether the potential efficacy of these existing treatments outweighs the burden of the side effects and quality of life.
This trade-off has really limited both the adoption of and the adherence to these two existing treatments. So importantly, in the U.S., only one out of four people with IPF are currently on either of these two treatments, which is quite remarkable given how deadly this disease is. So the vast majority of the patients are currently not on any treatment. So therefore, there is a tremendous need for better treatments so patients can achieve optimal disease management without having to compromise on tolerability. So we are developing deupirfenidone to overcome this challenge. So what you see on the left side of this slide here is a cartoon structure of one of the two approved treatments, pirfenidone. Our molecule, deupirfenidone, is on the right-hand side of this slide. It's a deuterium-modified form of pirfenidone.
This means we have strategically engineered the molecule to improve the stability of the bonds without changing the overall pharmacology of the molecule. With this targeted change, deupirfenidone retains the clinically validated efficacy of pirfenidone, but the differentiated and favorable tolerability profile really is quite impressive. So here are the data from our successful phase IIb clinical trial, which we believe positions deupirfenidone to serve as a new standard of care. The trial achieved its primary and key secondary endpoints, demonstrating remarkable efficacy and a favorable tolerability profile. Perhaps the most striking was the treatment effect seen with 825 milligrams three times a day, or TID dose. At that dose, the decline in lung function slows to a rate that approached the natural six-month decline that you typically see in older, healthy adults, 60 years and older. So this is quite unprecedented, especially for a monotherapy.
This dose also demonstrated a statistically significant difference from placebo with a strong, consistent, and durable effect that continues to be supported by the open-label extension study. deupirfenidone also showed a dose-dependent response with a key, which is quite key, that the FDA often looks for. With this strong data set, we are advancing deupirfenidone, and we're announcing here for the first time that we plan to initiate a phase III trial before the end of this year, of course, pending positive feedback from regulatory agencies. The design of the phase II trial is shown on this slide. The phase IIb trial was a randomized, double-blind, active, and placebo-controlled dose-ranging trial evaluating deupirfenidone at two doses over a 26-week period in IPF.
Importantly, this was the first time that an investigational drug has been evaluated over a six-month period alongside one of the two existing standard-of-care drugs in a company-sponsored trial, so we enrolled 257 participants who were randomized one-to-one-to-one-to-one to receive deupirfenidone 550 milligrams, deupirfenidone 825 milligrams, pirfenidone 801 milligrams, which is the FDA-approved dose, or placebo three times a day over a 26-week period. Just as a reference, the 550 milligram deupirfenidone roughly is equivalent to the exposure that you see with the FDA-approved dose of pirfenidone, and 825 milligrams of deupirfenidone provides 50%, approximately 50% more exposure compared to the FDA-approved dose of pirfenidone, so before we jump into the data, let's briefly walk through the two statistical analyses that we employed. The first is the Bayesian analysis, which allows for the borrowing of placebo from historic IPF trials.
This is a patient-centric approach to trial design because it minimizes the number of participants being exposed to placebo. And this is important to us because, given how deadly this disease is, this was a pre-specified analysis used to evaluate our primary endpoint. For completeness, we also pre-specified a second approach, which is a frequentist analysis, which evaluates only the data from the study, and we also get a p-value. We were pleased that both of these analyses gave us a very robust data set. Let's first look at the Bayesian analysis. The primary endpoint of the trial was the rate of decline of forced vital capacity or lung function, or FVC, over a 26-week period, comparing pooled arm of deupirfenidone versus placebo. The FVC is the amount of air an individual exhales from the lung after taking a deep breath.
This is the gold standard endpoint that the FDA uses for approving treatments in IPF. The trial achieved the primary endpoint, as seen in the graph on the left here in green. That's deupirfenidone pooled, the two pooled arms. And we achieved a 98.5% posterior probability. So this means that there is 98.5% probability that the pooled deupirfenidone arms were superior to placebo in slowing the rate of the lung function decline. And this was measured using the FVC at 26 weeks. So the rate of lung function decline in placebo, as shown in the black bar here, is around 110 mL over a six-month period, which is quite standard, what you would expect in an IPF patient.
The trial also showed a key secondary endpoint measuring the rate of lung function decline using forced vital capacity percent predicted, or FVCPP, as seen on the right-hand side of this slide here. This analysis had 99.6% probability that the pooled deupirfenidone arms were superior to placebo in slowing the decline of lung function. For those who are not familiar with the FVC and FVCPP, they both measure lung function, but with FVCPP, it accounts for key patient characteristics such as age, sex, height, and race, and therefore, it normalizes the results at the patient level. For example, a 60-year-old, six-foot-tall male has a different lung capacity than a petite 80-year-old woman, so this difference is accounted for in the FVCPP analysis. Now turning our attention to the frequentist approach, what we see on this slide is the primary and the key secondary endpoints.
Let's focus on the green bar in each of the panels, which represents the 825 milligram TID dose. The left panel is the FVC data, and the right panel is the FVCPP data. What's really noteworthy is that at 825 milligram TID dose, deupirfenidone's efficacy was large enough to achieve a statistical significance versus placebo, as shown in the black bar. We achieved a p-value of 0.02 with FVC and 0.01 on FVCPP at six months. Importantly, the placebo behaved the way we expected it to behave, and the pirfenidone behaved as we expected. And so it is an indicator of a rigorously conducted trial. So these two graphs really stood out to us when we first saw the data. I mean, it's really exciting. Let's focus on the green line at the top of each of these two graphs. So the green line really represents 825 milligram TID dose.
As you can see here, the deupirfenidone 825 milligram curve is essentially a flat line, which means efficacy with 825 milligram is so strong that we're not seeing significant worsening of the lung function during that six-month period, which is quite impressive and I think a big deal with this data. This is the most striking data point from our phase II-B trial. deupirfenidone 825 milligram TID dose, as shown in the green in the middle there, slowed the decline in lung function to a level approaching the natural decline that you expect to see in healthy older adults, 60 years or older. This is quite a remarkable result, showing that this has never been seen before with a monotherapy with at least six months of treatment.
So many key opinion leaders that we actually previewed the data with were really excited, and they felt that this was one of the most impressive takeaways from our phase IIb trial, especially since this is the type of data that every new investigational therapy that's out being studied is trying to achieve. And most of them, to our knowledge, are being studied on top of the current standard of care, which is essentially a combination. So for us to see this kind of data with this monotherapy is a big deal. So we had great data. So how is the tolerability of deupirfenidone? We could not be more pleased that deupirfenidone also showed favorable tolerability at both doses evaluated. And most importantly, it has demonstrated the potential to offer patients enhanced efficacy at the higher dose without compromising tolerability.
deupirfenidone's favorable profile is further validated by the fact that more than 90% of the patients who completed six months of treatment also transferred over and enrolled into the open-label extension study that's currently ongoing. For the first time today, we are sharing some early preliminary data from the ongoing open-label extension study. I want to stress these are really preliminary data based on a small number of patients, as they are still continuing through the open-label extension after we finished this study, which was late last year. What is encouraging to see is that it supports both the durable treatment effects of deupirfenidone, also a favorable tolerability profile.
As of December 4, we had approximately 90% of those who enrolled in the open-label extension remained on treatment, and the treatment effect demonstrated by 825 milligram TID at 26 weeks was maintained to 52 weeks, and it's continuing. I'd also like to point out that as of December 4, we had at least one patient who had been on 825 milligram treatment for over a year and a half. Again, these are preliminary data, but they do reinforce our findings from part A that demonstrated the durable, consistent, strong effect of deupirfenidone, 825 milligrams TID, with a favorable tolerability profile. The open-label extension is going to continue, and we'll have more data to share with you in a future forum. So here are the key takeaways. We met our primary and key secondary endpoints. deupirfenidone had a favorable tolerability profile at both the doses that we studied.
Remarkably, the rate of decline of lung function with 825 milligram TID approached the level of natural decline seen in healthy adults over 60 years or older for the same time frame. We also saw a statistically significant difference from the placebo on both the efficacy endpoints with deupirfenidone, 800 milligram TID, and the preliminary data from our open-label extension study indicating a very durable effect. We intend to discuss these data with the regulatory authorities and, assuming and pending positive feedback, we expect to start the phase III study before the end of this year, so in addition to the initiation of phase III trial for deupirfenidone, we remain on track to have final data from the phase Ib from our other wholly-owned program, which is in oncology, LYT-200, for which the FDA recently awarded fast-track designation for the treatment of AML.
Beyond these two programs, we have a diversified portfolio, and we are expecting to deliver another momentous year. When you look across on this slide, our founded entities, they are poised to provide additional milestones for us this year, and we maintain substantial equity in a number of these founded entities, in addition to milestones and royalties on a number of these programs, so with this strong foundation, we are really poised to achieve even greater progress in the year ahead and to further our mission to advance and serve the patients in most need, so with that, I'd like to invite my colleague, Dr. Eric Elenko, to join me on the stage here to answer any questions, so thank you.
Thank you, Bharatt. Maybe a question for me to kick us off. When you think about the market for deupirfenidone, are you mostly going to focus on the 75% that are currently not getting access to treatment, or would you be looking at the 25% that is currently served by the standard of care?
Yeah. So thank you for the question. So right now, as I mentioned, only one out of four patients are currently on either of these two standard of care drugs. And so 75% of the patients are currently not being treated. And also, when you talk to the pulmonologists, they'll tell you that they, in fact, do not want to prescribe either of these two treatments until the patient has really progressed quite far in their IPF. So if there is a way for us to come up with a treatment to allow these patients to stay on the drug longer and be able to get the optimal disease management, and with our 825 milligram data to actually have better disease management, then I think it opens it up for opportunities to not only serve the existing 25%, but also expand into that 75% who are currently not on treatment.
Another opportunity that's really important also is that this one potentially could allow the physicians to start prescribing earlier in the disease process, as opposed to currently the practice being wait until much later.
When you sort of think about the market for IPF, it's highly genericized. So how do you feel about bringing a new therapy into this market? And also, when you think about deupirfenidone, it's a small molecule with a deuterium molecule. How do you feel about sort of protecting yourself from generics?
Yeah. Good points. So currently, I think pirfenidone is generic. And I think nintedanib is the other standard of care drug that probably will go generic in a couple of years. So when we do enter the market, there will be at least two generics. But what we have seen from a year of generic pirfenidone is that the number of scripts have not gone up very dramatically. So it's not the cost that is holding the usage of these two treatments back. It's really the tolerability. Just because something is generic doesn't mean suddenly people start using it or being prescribed. So that's one aspect. So we think coming in with a superior product with a more favorable tolerability profile, we think, will be an attractive treatment option. In terms of the intellectual property, there's good precedence for deuterated molecules.
So far, the FDA has approved four products that are deuterated, and you get composition of matter patent, as well as some additional patents, including some new patents that we have filed on the doses that will extend, give us a long period of exclusivity, so we should have pretty good intellectual property coverage for this.
Yep. Go ahead. Could you wait for the mic, please? Sorry. Thank you.
Oh, I think it's for the webcast.
I appreciate it.
Great. Thanks. I guess what I was wondering about is, from an MOA point of view, have you thought I'm sure you have, but what are your kind of insights into how making a change from hydrogen to deuterium is translating into this kind of improved efficacy and safety that you've been seeing so far?
Yeah. It's a good point. So I have a lot of history with deuterium modified compounds. So the first compound that we worked on, which is currently in the market now, it was the first deuterium modified drug that was approved. It's called Austedo or deutetrabenazine for movement disorders. And so the whole point about deuterium modification is you are essentially replacing a regular hydrogen with heavy hydrogen. So structurally, you're not changing the molecule too much, but you require more energy to break a carbon-deuterium bond versus a carbon-hydrogen bond. So that translates that stability of the bonds translates into a differentiated metabolic profile and differentiated pharmacokinetic profile, which then translates into that you can get the same exposure at a lower dose. And that seems to also translate into better tolerability of the drug.
Yeah. So that makes a lot of sense from a chemistry point of view. As you mentioned before, the issue with the SOC in IPF is a lot of tolerability issues, all the side effects that people end up discontinuing. So maybe it could be related to the MOA of the SOC. Maybe it could be related to, as you mentioned, how they're metabolized. If it is a consequence of how it's metabolized, then OK, probably I can understand how maybe the deuteration may improve that. But if it's an MOA issue, it looks like the deuteration should still maintain the same MOA. But yeah, it's interesting. I think I have to think about it some more as well.
Yeah. I'll start, and then I'll have Eric please feel free to comment. So the first part of that is that pirfenidone, when it was being developed, they did see a dose response. So when they reduced the dose by 50% from the approved dose, they got half the efficacy. But they could never actually go higher than the FDA-approved dose of 801 milligrams three times a day because patients couldn't tolerate that drug, primarily because of safety tolerability. So with a deuterium modified deupirfenidone, we are able to actually increase the exposure because it's better tolerated. We couldn't have gone 50% more exposure if it was not very well tolerated. And so we are now able to show that you can actually get better efficacy if you increase the dose. And we are approaching that ceiling because we are normalizing the lung function to healthy older adults.
So I don't know if, Eric, you want to comment?
No. I mean, I think that's a good summary. Ultimately, the way we look at all these questions is that these are empirical questions. And the data was very clear from the study, which is we were able to go up on dose. We were able to see greater efficacy. And as Bharatt was outlining, that was without sacrificing tolerability.
Maybe a question from me on LYT-200. You did briefly touch upon the upcoming milestones. What can you give us an insight into about the AML target population you're looking at?
Eric, do you want to take that?
Yeah. So initially, the trial that we're running right now is relapse refractory. So these are individuals who, unfortunately, have not been able to get a response to standard of care treatment or were not eligible and progressed in their disease. And so that's the population we're currently testing in the phase Ib trial, as Bharatt indicated, that we're going to have top-line data by third quarter. We also released data and presented that in poster format recently at the ASH conference. And we anticipate that being the therapeutic line that we continue to pursue. But as is typical in oncology, one tends to move up in terms of relapse refractory and then going towards a broader patient population.
Yeah. Congrats on the fast-track designation. And I'm sure we have a lot to look forward to in Q3. Maybe a question more about thinking about your internal programs you've shown quite a bit of success with deupirfenidone and LYT-200. How do you think about sort of your internal program pipeline? And are you focusing on these two, or do you have work going on with others?
Yeah. Absolutely. So we continue to innovate. We have an innovation engine. And it's really centered around the process that Bharatt outlined, which is doing innovation in a very systematic manner, starting from scratch, looking at problems and trying to solve those problems. And then a third pillar really is this idea of going into areas, in particular, where there's some type of validated pharmacology. There's evidence about mechanism or a particular drug working in people. And I think that really goes to the philosophy of we think that empirical evidence in human beings is the most important aspect in terms of relying on data, but having a drug where that drug is held back by some issue. We talked about Cobenfy. We didn't have a chance to talk about our most recent founded entity, Seaport Therapeutics, and now deupirfenidone.
What they all have in common is there are three different approaches to allow compounds to really reach their full potential and therefore have the ability to help patients. So that general philosophy is one that we continue to apply as we think about new programs.
Thanks for that insight into Seaport, and sort of I'm going to ask a question which feels like who's your favorite child, but can you tell us more about some of your founded entities and something that you're very excited about?
Yeah. So I'm happy to take that. So Eric mentioned Seaport, which is our most recent one. But we have a number of other founded entities that are really doing some leading-edge programs, advancing leading-edge programs. So Vedanta, for example, is our best-in-class, we think, microbiome company. They are currently in two major clinical trials. One is a phase III trial in C. difficile infection. And the second product is in ulcerative colitis. So they'll have data from their phase IIB study in UC later this year. And then I think the phase III study in C. diff will be sometime next year. And they're advancing that. Really exciting company. We own substantial equity ownership in that company. We also have another company that we founded, Vor, which is an AML. It's a cell therapy approach, very elegant way of using gene editing and cell therapy to address AML.
And they announced some early data from their clinical studies. They will have more data to announce later this year. So yeah, some really amazing and exciting companies in our portfolio.
Any questions from the room? I have another one for you. Obviously, you have a very strong cash position, but a lot of things going on with both deupirfenidone and 200. Can you tell us a little more about your capital allocation strategy?
Yeah, so we have a real pedigree track record of capital discipline. We have been self-funded. Our founded entities have been quite successful, and our R&D engine has been quite successful in really generating high-value programs, and we are able to monetize some of those equity positions as well as milestones and royalty from some of those programs to reinvest back into PureTech to advance some of these programs from our engine, and so we are self-funded. We haven't had to raise money in the last six years from the equity markets. That is really quite a testament to the success that we've had, and so we'll continue to harness that going forward, and we currently are not looking to raise any money.
That was super helpful. Thank you so much, Bharatt and Eric. If you have any closing remarks, please go ahead.
Thank you for joining us today. And we look forward to sharing more exciting data during the course of the year. And so stay tuned.
Congratulations. Thank you.