Good morning. My name is Peter Welford. I'm one of the European pharma and biotech analysts at Jefferies in London. It's my great pleasure to be hosting the next company in this track, which is PureTech Health. Here from the company, we have the CEO of PureTech, Bharatt Chowrira, and we also have Eric Elenko down there as well, of the management team, who's here for the Q&A as well. With that, though, pass over to Bharatt, who's going to give some few opening remarks and slides, and then we'll go to the Q&A. Thank you very much.
Thank you, Peter, and thank you to the Jefferies team for inviting us. Welcome to everyone in this room, as well as those viewing our webcast. Today I'm really excited about sharing the PureTech story with you today, including how we are poised to scale and continue the momentum that we've been building with our pioneering hub-and-spoke R&D model. We'll tell you more about it, including, you know, the recent success of our KarXT program with Karuna Therapeutics and its acquisition by Bristol Myers Squibb. Before I start, I'd like to remind everyone about some forward-looking statements that we may be making, and so I really encourage you guys to review our regulatory filings for the up-to-date information.
So with that, our mission at PureTech, for those of you who are not familiar with PureTech, is, you know, to give life to new classes of medicine, to change lives of patients with devastating diseases. We deliver on this mission through our de-risked hub-and-spoke R&D model, which I'll discuss in detail shortly. I'm also very proud of our track record of clinical success using this hub-and-spoke R&D approach, which has resulted in 80% of our clinical trials that have been either run by PureTech or our founded entities being successful. So we are delivering on this mission with a promising pipeline of new medicines, which was built using the hub-and-spoke R&D model that PureTech pioneered.
Our hub is our core group of people and capabilities that enable us to identify, develop new medicines, some of which we advance through our founded entities. There are many advantages to this model, and I'd like to highlight at least three of them. It is a risk-mitigated approach. It's highly capital efficient, and it's catalyst rich, and it's an evergreen model, which is self-funding, and I'll tell you more about what we mean by that. The first advantage is that we don't have a binary risk. 'Cause we have a diversified portfolio with multiple quality shots on goal, that we don't take the binary risk associated with the conventional biotech.
This gives us the flexibility to prioritize the programs with the greatest probability of success, and this has resulted in our R&D engine generating 29 therapeutics and therapeutic candidates to date. Two of these programs have gone from inception at PureTech through to FDA clearance, and the third, KarXT, has been filed with the FDA for approval, with the PDUFA date later this year. This model is highly capital efficient, which is the second major attribute of our R&D approach. By housing our programs in founded entities, we are able to share the risks and R&D costs with third parties, such as external investors. Our founded entities, for example, have raised over $3.8 billion to date, 96% of which have come from third parties.
So our model is highly productive and extremely capital efficient, and over the past six years, we have demonstrated the third advantage, which is that it is evergreen self-funding model. Our portfolio is catalyst rich, both clinically and financially, so we have not had to raise capital or dilute our shareholders in over six years. Karuna is a great case study for us of this model, which was recently acquired by Bristol Myers Squibb for $14 billion, and this was a company that we founded and helped advance. So we can talk more about that case study. This model also enables us to consistently maintain a strong balance sheet with the $573 million in PureTech level cash and cash equivalents and short-term investment that was reported in March 31, 2024.
Which we allocate and deploy strategically to maximize patient benefit as well as shareholder returns. So a little bit about our approach in a little more detail. So our portfolio is underpinned by our de-risked and scalable R&D approach. We start with drugs that have validated pharmacology or targets that were previously held back from advancing due to key limitations. We create de-risk programs through killer experiments and by leveraging our scientific network and R&D expertise to unlock their full potential. We then take these medicines forward internally until a value inflection point is achieved, at which point, you know, we have the optionality to spin it out into funded entities and bring in outside investors.
Our model has been incredibly productive, and we are very fortunate to have a strong balance sheet, which enables us to continue our mission for patients and also provides optionality to maximize shareholder value through various avenues, such as improving liquidity and evaluating further capital returns based on future monetization events. So I want to spend a few minutes just highlighting a couple of our programs that are wholly owned, and I will spend more time talking about them during the fireside chat. Our most advanced program is LYT-100, which is a deupirfenidone, which we are advancing for idiopathic pulmonary fibrosis. So for those of you who are not familiar with IPF, it's a rare, progressive, fatal lung disease with median survival of 3-5 years.
There are two approved, FDA treatments, FDA-approved treatments, but they cause significant side effects, which has resulted in only about 25% of IPF patients in the U.S. taking either of these two standard care drugs. Which leaves about 75% of the patients who are untreated, primarily due to tolerability issues associated with both of these drugs. We have demonstrated favorable tolerability data in over 400 people to date, including a crossover trial with pirfenidone to demonstrate the favorable profile of LYT-100. Based on these data, to date, LYT-100 actually presents two potential ways for us to have improved patient outcomes.
The 500 mg TID dosing that we're advancing in phase IIb clinical trials could translate into improved safety profile compared to pirfenidone, which has the same potential to significantly improve patient compliance, as well as achieve more durable efficacy. The second way for us to improve patient outcomes is, you know, our 825 mg TID dosing regimen, which could translate into better efficacy compared to pirfenidone, which has the potential for patients to remain, maintain more lung function over time. We believe that LYT-100 has the potential to replace the current standard of care treatments, both as a first-line therapy, as well as preferred backbone therapy in combination treatments in the future. And we look forward to announcing the data from our ongoing phase IIb study in Q4 of this year. Our second program is LYT-200.
It's the anti-galectin-9, fully human, monoclonal antibody for hematological malignancies and localized, and metastatic solid tumors. We believe this has the potential, to, you know, alleviate immunosuppression, not just in cancer, but also in other disease states. Earlier in the year, LYT-200 received Orphan Drug Designation for the treatment of AML, and Fast Track designation for the treatment of head and neck cancers. We shared some initial positive results from the ongoing phase Ib clinical trials in December, which were promising. We reported on three dose escalation cohorts from the clinical trial, evaluating LYT-200 as a single agent in relapsed to refractory AML and MDS patients. In a heavily pretreated patient population, the early data is encouraging. It demonstrates a favorable safety and tolerability profile, with no dose-limiting toxicities identified.
In addition, we also saw some early signals of potential clinical activity. Additional data from this study are expected to be presented in a scientific forum later this year. On the solid tumor front, we have a combination study going on with LYT-200 in combination with a checkpoint inhibitor, tislelizumab, which is supplied by BeiGene. So LYT-200 demonstrated a favorable safety profile in all the cohorts, and we are beginning to see some disease control and suggestions of antitumor activity. We expect to share additional data this year at a cancer conference. So we are quite excited about this treatment potential for LYT-200 in both hematological malignancies as well as in solid tumors.
And finally, I wanted to quickly touch on some of the exciting value-driving catalyst ahead for us in 2024 and look forward to discussing some of those programs in detail during our chat, fireside chat today. If there are programs we don't get to today, but you're interested in learning more, please feel free to reach out to us through our investor relations webpage, and we'd be happy to provide more information. With that, you know, I have my colleague, co-founder, and president, Dr. Eric Elenko, with me on this fireside chat with Peter, and I'll hand it back to Peter.
That's great. Thank you. Let's start off just in terms of. You talked about, you know, value drivers and monetizing value. Can we just talk about, for starters, Karuna? Because I appreciate obviously that that's been phenomenally successful in terms of realizing cash proceeds. But you've still got some economics there. So can you just talk about the Royalty Pharma deal that you did there, how we should think about, I guess, that in terms of future, the way in which you think about royalties in the future? And what, perhaps, I guess, just explain what the terms of that are in terms of what upside you could get.
Yeah. So we entered into a partnership with Royalty Pharma, where we monetized our 3% royalty that we are eligible for under a license agreement with Karuna Therapeutics for KarXT, and we received $100 million upfront and an additional eligible for additional up to about $400 million in milestones based on certain regulatory and commercial milestone achievement. In addition, the deal was structured in such a way that when the annual sales hit $2 billion, you know, we are eligible to receive 2% of that royalty back, you know, on net sales above $2 billion. So we believe there is significant upside potential that continues to, you know, be important for us going forward, even after this acquisition by BMS.
And I guess can you just outline, you know, what other royalties do you still, you know, potentially could you still be eligible for in the future?
Yes. So, the total royalty is 3% on net sales.
Oh, sorry, I'm thinking. Sorry, I'm thinking beyond KarXT, beyond Karuna. Can you just outline, I guess, thinking about the, the business model you have, you said, in terms of.
Yeah, not from Karuna, right?
No.
Yeah, right. Okay. So, so we recently, for example, you know, we spun out Seaport Therapeutics, which is a group of CNS-focused assets that we had advanced internally with into clinical validation. And so, that new founded entity, you know, was recently. We recently raised about $100 million in Series A financing with some really good investors, and as part of that transaction, we retained, you know, we licensed our assets to Karuna, sorry, to Seaport, for advancing these programs. And, you know, as they advance and, you know, with regulatory and commercial, we are eligible for milestones similar to Karuna and also to royalties on product sales.
Unlike Karuna, which is a single asset, we have multiple assets under Seaport that would also, you know, potentially generate future milestones and royalties.
And then thinking about capital allocation, you know, perhaps you could just talk about your capital allocation policy. And in particular, you know, what drove the decision to do the recent GBP 100 million tender offer as well?
Yeah. So, you know, our business model, which is our Hub-and-Spoke R&D model, which biotech pioneered, has been very successful. You know, we've been able to generate tremendous amount of value from that R&D engine through the success of, you know, the programs through our founded entities. And as and when we, you know, that has enabled us to, you know, build a very strong balance sheet on an ongoing basis, you know. And so, at last reported, we had about $573 million in cash that would get us to at least a runway of 2027.
And so the way we think about the capital allocation is that, you know, with our strong balance sheet, we want to continue to, you know, maintain at least three years of operating cash. We want to be able to support our ongoing internal programs. We want to be helpful and support our founded entities to the extent they need our support, as well as to fund our, you know, ongoing new innovation engine. And so that's, you know, initially, that's how we think about the capital allocation. In addition, we're also committed to generating shareholder value, and one way to, you know, you know, translate our success to the shareholders is through return of capital. And we've started doing that.
You know, we completed a $50 million share buyback, which we completed last year, and more recently, we announced another $100 million in tender offer. So in the aggregate, we would have returned $150 million to the shareholders, and we'll continue to evaluate, you know, with our Board, future, you know, potential capital returns from future monetizations. And looking into, as I laid out, you know, the different components of our capital allocation, you know, after that, we would then return some of those capital back to the shareholders.
And then, idiopathic pulmonary fibrosis, or IPF, you know, it's a, it's a challenging indication. There's been, you know, a lot of efforts across the industry to do this. Can you talk a little bit about. You've got your phase IIb ELEVATE results coming up towards the end of the year. Can you talk about how we should be looking at those results? You know, is the aim to potentially look for better efficacy than we see with pirfenidone and Esbriet? Is it more on the safety, or what should be our focus when we get to those results at the end of the year?
Yeah, it's a really. You know, we're excited about that program, and, you know, we expect to announce the top-line results from the ongoing phase II study. I'll invite my colleague, Eric, to comment more on, you know, the trial that's currently ongoing and how we think about the profile, you know, and what this can do for IPF patients.
Yeah, I think the challenge for new mechanism of action drugs in IPF has been the I part, idiopathic, right? If people don't really understand the fundamental pathophysiology of the disease, that's really been a problem that drugs that have new mechanisms have encountered. In our case, LYT-100 or deupirfenidone is deuterium- substituted form of pirfenidone, which has shown efficacy but has had challenges when it comes to adverse events, particularly GI adverse events. And we've previously actually shown in a crossover study in healthy older adults, the ability to really reduce those problematic adverse events. So in our phase IIb study, we have two different doses of LYT-100 as Bharatt outlined. One gives the same exposure as pirfenidone, and there we're gonna be looking for a reduction in adverse events.
And then we also have a higher dose, and the idea of having a higher dose is that could achieve greater efficacy. Now, both adverse events, so, as well as a higher dose in the end, are both related to efficacy. The reason is, if you look at patients, about half of them end up dose-reducing or discontinuing on pirfenidone. And so by allowing patients to experience fewer adverse events, what that could ultimately translate into is staying on the drug longer, and of course, staying on the drug longer could ultimately result in greater benefit.
That's clear. And perhaps if we just think then beyond the Phase IIb ELEVATE results, you know, assuming they're successful, and they show what we hope, then what's the path forward then to get this drug to market, perhaps? 'Cause I think it's perhaps not the usual route.
Yeah, so the ultimate design of our pivotal study will depend on the data that we see in the IIb, both in terms of powering as well as thinking about the dose that we're gonna take forward. Now, we do know, based on what the FDA has historically required, some of the typical features one would see in an IPF trial. So, for instance, in our IIb, we're using forced vital capacity, FVC, as a primary endpoint. We'd imagine using that also, and historically, these trials have been 12-month studies, so 12 months dosing per patient.
Okay. So let's move on to then Seaport Therapeutics. This was recently, I guess, created, if you want to call it, the entity, and obviously to house the Glyph platform. Can you just talk a bit about what drove that decision, and perhaps, you know, what is the real benefit of the Glyph platform? I mean, what does it bring for drugs?
Certainly. I'll, you know, start off, and then Eric, feel free to, you know, jump in. So we launched Seaport recently with a $100 million Series A financing, with some three really, you know, well-known biotech investors, you know, ARCH Ventures, Sofinnova, and Third Rock. The reason we decided to, you know, create and launch this founded entity was because we had been building this portfolio of really attractive, exciting, you know, CNS, you know, molecules based on our Glyph platform, which, you know, Eric can talk more about. And we had generated some clinical data that validated the platform, and in a phase IIa study.
We felt that, you know, there were enough, you know, programs in that CNS-focused pipeline; it required a dedicated effort to try and, you know, advance these programs rapidly and to bring in some really good investors to, you know, share in that, you know, in that process. We ended up, you know, spinning that out with, you know, Dr. Steven Paul, who was the former CEO at Karuna, you know, wanted to join this effort, and he's the Chair, and then Daphne Zohar, who is the Founder and CEO of PureTech, then transitioned to run Seaport, which is, you know, gonna, we believe, generate, you know, significant future upside value for PureTech, and so we're quite excited about that.
I don't know if in last 2 minutes you can talk about the Glyph platform, Eric?
Yeah. So, what Glyph allows is the creation of prodrugs that are absorbed essentially like dietary lipids. So they go through the lymphatic system, and as a result, they avoid first-pass metabolism by the liver. And the advantage of that is, being able to take drugs and make them orally bioavailable or take drugs and circumvent issues with hepatotoxicity when high first-pass metabolism are the cause of the underlying issues. And so what you see is, once again, a model of taking drugs which have known pharmacology, have some sort of issue holding them back, and by applying this technology and creating these prodrugs, really allowing these drugs to, realize their full potential and be utilized, in a way that maximizes benefit in the clinic.
And then we've got a minute left, so perhaps brief Gallop Oncology. That was also recently founded a similar time to LYT-200. Can you just talk a little about what is the path, I guess, to follow a similar path for Gallop in terms of potentially a Series A, I guess, and making that an independent entity?
Yeah. So Gallop, you know, we're quite excited about. You know, it's currently in two clinical trials, one for head and neck cancer, in combination with tislelizumab, and then in AML, MDS, in a single agent as well as in combination with standard of care. And so we're gonna let the data mature some more, which we later this year, probably later in the second half of this year, and based on that data package, then we will evaluate, you know, how best to move that forward and bring in, you know, additional investors from outside, so.
That's clear. We've run out of time. Thank you all very much for your attendance. Thank you, obviously, mostly Bharatt and Eric, for joining me here. With that, we'll close the session. The next company will start shortly. Thank you.