Greetings and welcome to the PureTech Health 2024 Year End Financial Results Conference. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Allison Mead Talbot, Senior Vice President of Communications. Thank you, Allison. You may begin..

Thank you for joining us today for PureTech’s 2024 financial results webcast. Our annual report will be made available later today, portions of which will also be filed with our Form 20-F. This information is available on the Investors page of our website at puretechhealth.com.

PureTech is guided by a seasoned leadership team with a strong track record of translating scientific innovation into impactful medicines and long-term shareholder value.

Today, I am pleased to be joined by members of the senior team, including Bharatt Chowrira, Chief Executive Officer; Eric Elenko, Co-Founder and President; Chip Sherwood, General Counsel; and Michael Inbar, Chief Accounting Officer. I would like to remind you that during today’s call, we will be making certain forward-looking statements.

These statements are subject to various risks, uncertainties and assumptions that could cause our actual results to differ materially, and we ask that you refer to our annual report and our SEC filings for a complete discussion of these items.

We undertake no obligation to revise or update any forward-looking statements or information except as required by law. I also want to remind you that we will be referring to certain non-IFRS measures in this presentation.

The presentation of this non-IFRS financial information is not intended to be considered in isolation or as a substitute for financial information presented in accordance with IFRS.

A reconciliation of the IFRS to non-IFRS measures that we will be referring to today can be found in this presentation and is also available on our Investor Relations website at investor.puretechhealth.com and in our SEC filings. I will now turn the call over to Bharatt Chowrira, PureTech’s Chief Executive Officer..

our strong balance sheet; our wholly-owned programs; our equity stakes in our founded entities; future revenue stream from royalties and milestones; capital returns to shareholders; and most importantly, our exceptional team that’s driving the innovation forward.

Our capital-efficient R&D model has been tested and proven over the last decade, enabling us to protect our balance sheet while maintaining strategic flexibility in a volatile market environment.

PureTech offers a compelling investment opportunity, especially given the significant value disconnect where the diversified risk profile and the various components of value provide downside protection while the upside potential is really uncapped.

I remain confident in our ability to continue building value through disciplined execution and strategic agility. With that, I’d like to now turn the call over to our Co-Founder and President, Dr. Eric Elenko, who will walk us through our key programs and recent clinical progress.

Eric?.

Thank you, Bharatt. We’re very excited about the progress across our portfolio. And today, I’ll highlight our wholly-owned programs and the value they represent for both patients and shareholders. Let’s start with deupirfenidone, which we’re developing as a potential new treatment for IPF.

For those less familiar, IPF is a rare, progressive and fatal lung disease that affects more than 232,000 people in the U.S. and the EU 5 countries with a median survival of just 2 to 5 years after diagnosis.

Despite generating peak annual revenues in the billions of dollars, the current standard of care treatments only modestly slow lung function decline.

Their effectiveness is limited by tolerability challenges at higher doses, which creates a tolerability ceiling, preventing patients from reaching dosing levels that could more meaningfully improve outcomes. This leads to suboptimal efficacy, reduced patient uptake and a lack of adherence.

Importantly, in the U.S., only 1 in 4 people living with IPF has ever been treated with either FDA-approved therapeutic. There is an urgent need for better treatment options that can deliver meaningful disease management without compromising tolerability.

Our deupirfenidone program is deuterium-modified form of pirfenidone, a molecule that is strategically engineered to improve the stability of its bonds without changing the overall pharmacology.

With this targeted change, deupirfenidone retains the clinically validated efficacy of pirfenidone while offering a differentiated and more favorable tolerability profile. We believe deupirfenidone has the potential to become standard of care in IPF.

In our successful Phase 2b trial from which top line results were shared in December, deupirfenidone demonstrated the potential to stabilize lung function decline over at least 26 weeks without sacrificing tolerability.

Importantly, the deupirfenidone 825 milligrams 3 times a day or TID arm had an effect size compared to placebo that was 50% greater than that seen with pirfenidone.

Additionally, preliminary pharmacokinetic results indicate that deupirfenidone 825-milligram TID achieved about a 50% higher exposure than pirfenidone 801 milligrams TID, corresponding with the greater efficacy results demonstrated with deupirfenidone 825 milligrams TID.

I’m also pleased to share for the first time today, that as of March 14, 2025, 140 patients have continued in the open-label extension and 85 patients have received at least 52 weeks of treatment with deupirfenidone.

Preliminary data from those receiving deupirfenidone 25 milligrams TID indicate the significant slowing of lung function decline observed in Part A of the trial has been sustained through 52 weeks of treatment, supporting the durability of the treatment effect with this dose and its potential to stabilize lung function decline over time.

Detailed OLE results will be presented at an upcoming scientific forum. These results are unprecedented, especially for a monotherapy. And to our knowledge, this is an achievement unmatched by any other investigational IPF therapeutic to-date. Based on the strength of our data, deupirfenidone has the potential to offer benefits to 3 patient segments.

The subgroup of those currently on treatment, those who discontinued due to side effects and those who never start treatment at all with currently available options.

By demonstrating a meaningful improvement in lung function decline over 6 months and the potential for stabilization without compromising tolerability, deupirfenidone has the potential to become a next-generation IPF treatment by pushing for levels of efficacy that have not been possible for the past 10-plus years and reach far more patients than today’s therapies, and to do so in a way that supports sustained disease management.

We believe deupirfenidone represents a sizable commercial opportunity with a total addressable market or TAM that continues to expand.

The IPF market size was valued at approximately $5 billion in 2024 with increased disease awareness, early diagnosis and the availability of new treatment options, the market is expected to grow to nearly $10 billion a year by 2033.

With its highly differentiated efficacy and safety profile, deupirfenidone has blockbuster commercial potential in IPF with additional upside in other interstitial lung diseases, or ILDs, such as progressive pulmonary fibrosis or PPF, while significantly enhancing patient impact. There remains a clear need for better treatment options in IPF.

And based on the data to date, we believe deupirfenidone has potential to become a next-generation standard of care. We will present additional details from the Phase 2b data at the American Thoracic Society International Conference this May.

We also intend to discuss these results with the FDA before the end of the third quarter of 2025 to align on a potential registration pathway with the goal of initiating a Phase 3 trial by the end of the year. We anticipate providing further guidance later this year following the finalization of the trial design and FDA interactions.

The next program I’ll highlight today is LYT-200, our wholly-owned oncology program being advanced by our founded entity, Gallop Oncology.

We’re taking a differentiated approach to cancer treatment by targeting the pro-tumor mechanisms of galectin-9 in acute myeloid leukemia, or AML, and high-risk myelodysplastic syndrome, or MDS, and head and neck cancers.

The FDA has granted Orphan and Fast Track designation for LYT-200 in AML as well as Fast Track designation in head and neck cancers, reinforcing the urgency and potential impact of this program.

Both preclinical and human data underscored the importance of galectin-9 as a potent oncogenic driver and immunosuppressive protein, with LYT-200 demonstrating direct cytotoxic, anti-leukemic effects through multiple mechanisms as well as antitumor activity. We’re very encouraged by the clinical data we’ve generated to date across our LYT-200 trials.

On the left of this slide is new interim data from our ongoing Phase 1b trial in AML and high-risk MDS, evaluating LYT-200 as a monotherapy in combination with venetoclax and hypomethylating agents.

At a high level, LYT-200 has shown a favorable tolerability profile across both arms and all dose levels with no dose-limiting toxicities as well as evidence of clinical efficacy, hematological improvement and sustained disease management.

We last shared a detailed update on this trial at the American Society of Hematology Annual Meeting in December, noting that the combination arm had achieved 2 complete responses at that time. Today, I’m pleased to share that as of April 28, we have seen 4 additional complete responses in this arm, bringing the total to 6.

I want to remind you that this trial is being conducted in a heavily pretreated relapsed/refractory AML/MDS population, whose time to progression tends to be less than 1 month and whose overall survival averages 1.7 to 2.4 months with standard of care therapy.

We’re very pleased with the data generated to date in this indication, which is in desperate need of innovation. And we look forward to sharing top line results from this trial in the third quarter of this year. On the right of the slide is something we’re also sharing for the first time today.

Top line data from the recently completed Phase 1b trial in relapsed/refractory solid tumors, including head and neck cancers. This study evaluated LYT-200, both as a monotherapy and in combination with tislelizumab and across all cohorts, LYT-200 demonstrated a favorable safety profile, along with disease control and early signs of efficacy.

Together, these data highlight the broad potential of LYT-200 across both hematological malignancies and solid tumors. As we look ahead, we expect 2025 to be another catalyst-rich year across our wholly-owned and founded entity programs, including the Phase 3 initiation of deupirfenidone in IPF and Phase 1b readout of LYT-200 in AML to name a few.

We are proud that our efficient and proven hub-and-spoke model has enabled us to maintain a strong financial position even in a volatile market environment as we remain steadfast in our mission to deliver life-changing medicines. With that, I’ll turn it back to Bharatt for a recap of our 2024 financial results and closing remarks..

Thanks, Eric. I’m pleased to report that PureTech’s cash position remains strong, reflecting our business model, track record of clinical success and commitment to financial discipline. At the PureTech level, we ended 2024 with cash, cash equivalents and short-term investments of $366.8 million compared to $326 million at the end of 2023.

On a consolidated basis, our cash, cash equivalents and short-term investments were $367.3 million at the end of 2024 compared to $327.1 million at the end of 2023. At the PureTech level, as of March 31, 2025, we held unaudited cash, cash equivalents and short-term investments of $339.1 million.

On a consolidated basis, our cash, cash equivalents and short-term investments were $339.5 million. Based on our existing financial assets as of December 31, 2024, we expect our operational runway into at least 2027.

Our revenues are mostly driven by milestone-based payments and royalties from license agreements as well as grants and are expected to continue to fluctuate from year-to-year. On a consolidated basis, our revenue in 2024 was $4.8 million compared to $3.3 million in 2023.

We reported a lower 2024 operating loss of $136.1 million compared to $146.2 million in 2023.

This was largely due to a decrease in R&D expenses driven by the completion of deupirfenidone Phase 2b clinical trial, development of Glyph platform candidates now being advanced by our founded entity, Seaport Therapeutics as well as deconsolidation of Seaport.

The decrease in R&D expenses is partially offset by an increase in G&A expenses that was largely driven by non-cash stock-based compensation expenses for new stock awards granted to founders, directors, executives and employees of Seaport Therapeutics in 2024 prior to its deconsolidation.

On a consolidated basis, we reported a net income of $27.8 million for 2024 compared to a net loss of $66.6 million for 2023. This was largely due to a $151.8 million gain that was recognized upon the deconsolidation of Seaport, coupled with the decrease in the operating loss driven by the decrease in R&D expenses mentioned earlier.

I am pleased that our balance sheet remains strong. We are committed to maintaining financial discipline by allocating capital efficiently to high-impact programs while actively pursuing external funding opportunities.

This measured approach allows us to protect our balance sheet and preserve strategic flexibility even in today’s volatile market environment. In closing, I’d like to thank the patients, caregivers, advocates, clinicians and partners. We are deeply grateful for the engagement, participation and belief you have placed in us and our team.

I would also like to extend a sincere thank you to every member of the PureTech team, including our Board of Directors and Advisors for their invaluable contributions to our work and culture. What we have accomplished together is both rare and highly meaningful.

Finally, I’d like to thank our shareholders for continuing to support our journey to bring new classes of medicines to patients in need. We value our recent and continued engagement and your feedback as we remain steadfast in our commitment to maximizing positive patient impact and value for shareholders.

Your trust and support have been essential to our journey, especially over the past year as I stepped into the role of the CEO. I am proud of the progress we have made and we remain focused on advancing our science to improve the lives of the patients. Thank you. And we will now take your questions..

Thank you. [Operator Instructions] Our first question is from Miles Dixon of Peel Hunt. Miles, your line is now open. Please go ahead..

Good morning Bharatt, Eric. Thank you so much. I have got a few. Maybe we can take them one by one. But let’s start with, let’s call it KarXT rather than COBENFY.

But can you tell us a little bit about what you – what your understanding is of how sales have started, please, with BMS?.

Thank you, Miles. I appreciate you joining the call. Yes. So, as you know, COBENFY was approved last year by the U.S. FDA for the treatment of schizophrenia in adults. And so BMS, who acquired Karuna has launched this product in the U.S., I believe in the last quarter of 2024.

And they recently announced their first quarter sales, which according to their announcement, it is going quite well. The sales ramp has gone quite well. They, I think generated about $27 million in the first quarter, which currently, it’s around 40% to 50% – yes, around 48% above the average analyst estimate. So, it’s a good sign.

It’s getting a lot of attention and traction and momentum. So, we will continue to monitor and watch that growth as BMS launches this product across the U.S..

Great. Thank you. And then sticking on the same subject, you have obviously got quite a complicated but potentially profitable load of economics in there, whether it would be the sublicense and royalty payments with BMS, but also the milestones with Royalty Pharma.

I wonder can you give us any more color on what the – what may happen, for instance, with BMS with the sublicense agreement and what the milestone structure might be with royalty? Is it too simplistic for me to imagine that those milestones may fall due at $500 million, $1.5 billion and $2 billion – sorry, $500 million, $1 billion, $1.5 billion, for instance, before they revert? Thank you..

Yes. So, as you mentioned, the COBENFY was invented at Puretech. So, we licensed that to Karuna. And as part of that license, we were eligible for a 3% royalty on product sales. So, we monetized that 3% royalty with Royalty Pharma. We received $100 million upfront. We are eligible for up to another $400 million in milestones.

Most of those milestones are sales threshold related. And there are a few smaller milestones on approvals. We received a small milestone on the approval of COBENFY in the U.S. There is another small milestone due for a second indication when that happens. But most of the remaining up to $400 million milestones are sales threshold achievement driven.

We have not broken that down into different layers for obvious reasons, Royalty Pharma, and we have a confidentiality related to those tiers of milestones. So, we are not able to disclose any more specifics in terms of those tiers of milestones. In addition to those milestones, we are eligible for 2% royalty above the sales of $2 billion for COBENFY.

And so that – depending on when those sales ramp set, we should start seeing that 2% royalty above $2 billion from the sales of COBENFY. In addition, we have small milestones from Bristol-Myers Squibb as they advance the program through other indications. And so we have those small milestones due to us.

And if they sublicense the COBENFY in other countries, we are eligible for a small sublicense income. But we believe that given BMS’ global footprint, we are unlikely to actually expect – I don’t think we expect BMS to sublicense this in other parts of the world.

So, primarily, it’s small milestones on development milestones as well as Royalty Pharma milestones based on the monetization of the royalty..

Got it. Thank you. And presumably the lower the sublicense income, the higher the potential royalty payment from BMS, if they do commercialize it elsewhere, but if I could move on maybe to LYT-100, you obviously had some brilliant trial data last year.

But you have indicated the potential trial costs might be beyond that of your balance sheet, which is why you are looking to partner. But can you just break down for me a little bit what it is about that potential trial? Is it the scope, the timeline that means that it’s going to be more than your typical respiratory trial? Thank you..

Yes. Thank you for that, Miles. So, it’s a combination of the two. So, when you look at LYT-100 that we are advancing for idiopathic pulmonary fibrosis or IPF. When you look at historical Phase 3 trials that people have run, other companies have run in this space, they are generally a 52-week study.

It’s a 1-year treatment study, which is – takes around 2 years to enroll a Phase 3 study in IPF, depending on the size of the study and the number of patients required in that study and depending on the trial design.

But historically, that’s sort of what we have seen is a 1-year treatment that takes about 2 years to 3 years to read out – top line results to read out. So, we are looking at from the start of the study, 3-year duration for the top line results to be announced. And the most recent example is Boehringer Ingelheim, who ran a Phase 3 study.

They had about 400 patients per arm, and they had, I think two or three arms. And so you can imagine the size of that study. I am not saying that, that’s the trial design we are going to follow, but that is an example of the Phase 3 study that the FDA has required BI to run. We will of course have a discussion with the FDA.

We will discuss our Phase 2b data with the FDA in the third quarter of this year, and we will reach alignment with them regarding the trial design. And we will have a better sense for what the study design and the scope of the study and the duration of that study could look like, and so we will be able to provide better guidance.

But our goal is to – coming out of those discussions, is to try and initiate a Phase 3 study before the end of this year..

Great. Thank you. Yes, I think Boehringer’s was 400 locations, incredible. But lastly, if I can just ask one more on Seaport, obviously, now a kind of arm’s length company, if you like, but you are a significant shareholder. They raised a huge amount of money.

But can you just give me a bit of a flavor for what’s going on? How is the funding going in Seaport? I know that we have seen some early safety data on SPT-300, but have they got everything they need? Thank you..

Yes. So, they are a private company. So, there is a limited amount of information that they have shared regarding the timing and progress of their programs internally. But what we have previously disclosed is that the lead program, LYT-300 is advancing towards a Phase 2b study initiation in major depressive disorder, and they are on track for that.

So, they haven’t provided any more guidance in terms of the timing of that study. They also have a second study that’s initiating Phase 1 clinical study, which is in SPT-320, which is a Glyph version of agomelatine, and they are studying that for generalized anxiety disorder. And so they expect to start that study sometime this year.

But beyond that, we have not provided any additional guidance. And they have a third program, which is slightly behind – further behind in preclinical. And so they are well funded. They raised $325 million across two venture rounds. So, they are well capitalized.

And so they should be able to execute on these programs in the – for the foreseeable future..

Thank you, Bharatt. Thank you..

Thanks Miles..

Our next question comes from Faisal Khurshid from Leerink Partners. Your line is now open. Please go ahead..

Hey guys. Thank you so much for taking the questions.

I just want to ask, as you think about the path forward for LYT-100, like what could those potential paths look like? And how are you thinking about retaining upside in the program?.

Yes. Thanks Faisal and thanks for your question. So, we see – we are very bullish on LYT-100, or deupirfenidone. Based on the unprecedented data from Phase 2b that we announced in December, we have built quite a lot of momentum around this program.

And the key opinion leaders we have spoken to are really excited about the data especially the ability of deupirfenidone to potentially stabilize lung function is we believe it’s a really big deal for this indication. And so we are committed to advancing this forward.

And so we have looked at a number of different approaches to try and bring together the funding necessary to advance this into Phase 3. So, one of them is, of course what we have historically done, which is to house the program into a new founded entity and bring in external capital like venture round.

So, part of the funding required for Phase 3, we believe would come from such an equity financing from external sources. And similar to what we have done with Karuna and most recently with Seaport Therapeutics.

In addition, we are also speaking to people who provide what we call project financing or synthetic royalty type financing where these firms actually lend you the money to run the Phase 3 study at risk. And if the study is successful, then they would get some back-end economics in return for that.

And so this is a very common way of funding some of the large Phase 3 studies. So, another portion of the Phase 3 funding required would come potentially from a project financing. And then a third approach we are also looking at in parallel is speaking to potential strategic pharma companies for regional rights. So, we would potentially keep the U.S.

rights and then license out outside the U.S. and then use some of those upfront proceeds to then also provide funding for the Phase 3. So, this could be a combination of these three, and maybe there are other ways to bring in some additional funding to advance this program into Phase 3. So, that’s sort of how we are looking at it.

And how do we maintain the upside is primarily through equity ownership as well as because we have generated significant amount of intellectual property around this program over the years that we would be eligible for milestones and royalties as the programs would move forward, very similar to what we have done with Karuna and Seaport..

Got it. Great. And the other thing I want to ask about, so you mentioned kind of like the – your perceived value disconnect between the stock price and just the value of your cash and like the KarXT economics.

Can you talk a little bit more about like how you are thinking about that, and what the potential options could look like to sort of rectify that?.

Yes. So, we shared the frustration of our shareholders in terms of the value disconnect. We have been looking at different ways to try and address this. So, we have a range of options that we can look at. We have looked at – in the past, we have done share buybacks. We did a $50 million share buyback.

We – last year, in 2024, we did a $100 million tender offer. And so we continue to evaluate other potential opportunities to try and unlock the value.

And most recently, there was an announcement that was – that we had to put out prematurely because of some media speculation about some discussions with private equity firm to potentially explore ways to take the company private.

And so we are looking at a number of those opportunities and the Board and the management team regularly evaluate those opportunities on an ongoing basis, and we will continue to do that and try.

And our focus in 2025 is going to be not only in executing and advancing our pipeline programs and portfolio, but also spend a lot of time trying to figure out how to bridge this value disconnect..

Got it. Thanks for taking the questions..

Thank you. In the interest of time, we unfortunately have to conclude this Q&A. You may now disconnect your lines..