Half Year 2023 PureTech Health PLC Earnings Call

Participants

Allison Mead Talbot; Head of Communications & IR; PureTech Health plc

Bharatt M. Chowrira; President, Secretary, Chief Business Finance & Operating Officer and Executive Director; PureTech Health plc

Daphne Zohar; Founder, CEO & Executive Director; PureTech Health plc

Eric Elenko; Chief Innovation & Strategy Officer; PureTech Health plc

Julie Krop; Chief Medical Officer; PureTech Health plc

Lucy-Emma Mary Sarah Codrington-Bartlett; Equity Analyst; Jefferies LLC, Research Division

Unidentified Analyst

Presentation

Operator

Greetings and welcome to the PureTech Health 2023 Half Year Results Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host, Allison Mead Talbot, Head of Communications. Thank you, Allison. You may begin your conference.

Allison Mead Talbot

Thank you for joining us today for PureTech's 2023 Half Year Results Webcast. Our half year report is made available this morning and will also be filed with the SEC today. This information is available on the Investors portion of our website at puretechhealth.com. PureTech is led by a proven and seasoned management team with significant experience in discovering and developing important new medicines, delivering them to market and maximizing shareholder value.
Today, I'm pleased to be joined by the senior team, including today's presenter, Daphne Zohar, Founder and Chief Executive Officer; and Bharatt Chowrira, President. Following the presentation, we will be joined by Eric Elenko, Chief Innovation Officer; and Julie Krop, Chief Medical Officer, who will all be available for questions.
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 important risks, uncertainties and assumptions that could cause our actual results to differ materially, and we ask that you refer to our half year 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 investors.puretechhealth.com and in our SEC filings.
I'll now turn the call over to Daphne Zohar, PureTech's Founder and Chief Executive Officer.

Daphne Zohar

Thank you, Allison. Welcome, everyone, and thank you for joining us today. I am delighted to review the important clinical and financial milestones achieved across both our Founded Entities and Wholly Owned Pipeline in the first half of 2023 and to discuss the exciting path forward.
Mission at PureTech is to give life to new classes of medicine that can then change the lives of patients with devastating diseases, and I'm extremely proud of what we have achieved for patients and the impact that we are having. PureTech's R&D engine has generated 27 therapeutics and therapeutic candidates. Two have gone from inception at PureTech through FDA clearance and the third, KarXT is expected to be filed for FDA approval in the third quarter of this year.
In addition to being extremely productive at creating new medicines, our track record of clinical success outperforms others in the biopharma industry. Let's direct our attention to the right of the slide, where you can see that our clinical success rate is around 6x higher than the industry average. This track record of productivity and clinical success is one that we are very proud of and continuing to replicate and scale across our portfolio with many more exciting new programs on the horizon.
Let's go through a case study of our approach with the KarXT program, which was invented by our team at PureTech. This is an important new medicine that, if approved, will be the first new mechanism for patients with schizophrenia in over 50 years. Schizophrenia is a devastating illness that is often diagnosed in young adulthood and affects 24 million people worldwide. Existing drugs have mixed efficacy and cause issues like significant weight gain, movement disorders and sedation. One of the components of KarXT, xanomeline, was shown to be highly effective for the treatment of psychosis and other symptoms of schizophrenia without these debilitating adverse events that have plagued other drugs, but it was sitting on a shelf at Eli Lilly due to GI tolerability issues that they and other pharma companies could not overcome with traditional chemistry approaches.
Our team at PureTech came up with the idea of coupling xanomeline with another drug that reduced the tolerability issues in the rest of the body. We conducted a key tolerability proof-of-concept experiment, and once we validated the concept, advanced this program through our Founded Entity, Karuna.
Karuna now read out 3 positive registration-enabling trials for KarXT and schizophrenia and has announced that it plans to file for approval with the FDA in the third quarter of this year. KarXT is also a great example of how our Founded Entities are able to generate value for our shareholders and of our capital efficiency. We allocated a total of $18.5 million to Karuna and the return on that cash has been almost 50x that without accounting for a recent $100 million upfront payment we received from Royalty Pharma in the first half of 2023. Karuna is around a $7 billion company now. We have taken $780 million in cash off the table so far, and we think there is the potential for a similar amount to be monetized over time.
The bar chart demonstrates this with the upper portion of the bar on the right, showing the value of our current equity holdings and potential remaining milestones from our Royalty deal. This is before accounting for 20% sublicense payments due to us on future partnering deals and milestone payments associated with our license agreement with Karuna. This is just one of the ways we are crystallizing the value of our innovation engine.
It's important to note that we have 5 other Founded Entities and at least 7 additional Wholly Owned programs that we believe have the potential for value on a similar scale to what I just described. I'm also really proud of the fact that due to both our model and our disciplined financial stewardship, we have not had to raise capital from the market or dilute our shareholders in almost 6 years, including during a time that was very challenging in the biotech sector at large. During this time, we've been creating an extremely exciting pipeline of therapeutic candidates that build on the same success pillars that created KarXT.
Our financial independence has allowed us to focus on what we do best, recognize value in potential new medicines when others don't yet see what we do and then rigorously validate and relentlessly prioritize programs with the highest probability of success. As such, we believe there is a significant amount of value that is yet to be realized in our pipeline, which we look forward to crystallizing for our shareholders. As we've shown, our Founded Entities are poised to bring back value to us in the form of equity, milestone payments, royalties and potential sublicense revenues. Let's talk about how the maturation of our Wholly Owned programs now gives us several pathways to realize their value as well. Now that we have developed these exciting programs, which we own 100% of, we plan to determine the best path for each one, whether it be through internal development, the creation of new Founded Entities, asset sales, partnering and/or royalty transactions.
And we will be guided by the optimal route to get these new medicines to patients and to generate the most value for our shareholders. We have many options available to us, and we are committed to maximizing shareholder returns while we make a difference for patients. We will be engaging with our shareholders in the coming weeks for feedback as we explore the exciting paths forward. As we look at the Wholly Owned programs, it's important to understand that we have been developing them based on a proven and successful strategy with a team that has consistently delivered results. Our strong R&D track record has been made possible in part due to our distinctive approach to drug development, which is underpinned by 3 key pillars. First, we identify an area with unmet patient need. We then identify compounds with validated human efficacy that have been hindered from reaching their full potential due to patients such as poor bioavailability or side effects. This brings us to our second pillar.
We apply our proprietary insights and technologies to overcome these limitations and unlock the drug's benefit for patients. Our third pillar, efficient derisking, is achieved in 2 ways. We build on well-defined clinical and regulatory paths, and we also conduct what we call killer experiments early on. We believe in disciplined R&D and we quickly shut down programs that don't reach our prespecified thresholds for advancement. This allows us to pivot resources towards the programs with the highest probability of success. This has resulted in our exciting therapeutic development pipeline, which is positioned to change people's lives.
Let's talk through some of our key programs through the lens of these 3 pillars. Starting with LYT-100 for idiopathic pulmonary fibrosis, or IPF, the rare progressive and fatal disease with a real patient need. There are 2 FDA-approved treatments, but they cause significant side effects, which means patients cannot fully benefit from these medicines because they are unable to stay on treatment long enough or at the right dose. Because of this, approximately 3 out of 4 people living with IPF in the U.S. forego treatment with these otherwise efficacious medicines. Furthermore, clinical development in IPF has been met with challenges recently and several trials of drugs with novel but unproven mechanisms have been discontinued over the last 12 months. I want to highlight why we believe our program is different. Let's start by looking at pirfenidone, which is 1 of the 2 FDA-approved medicines for the treatment of IPF.
This is a drug that has been proven efficacious and has been shown to improve survival in these patients by approximately 3 years. That is really meaningful in a disease that has a median survival of 2 to 5 years. However, significant GI tolerability issues caused most patients to discontinue or reduce their dose, which ultimately limits pirfenidone's effectiveness. Even with these issues, combined sales of pirfenidone and nintedanib, the other drug approved in IPF or more than $4 billion in 2022, representing a significant market opportunity in IPF and other fibrotic lung diseases. Our candidate LYT-100 is a deuterated form of pirfenidone, which as you can see on this slide means we made selective substitutions in the molecule that improve metabolic stability, thereby reducing the side effects that have limited pirfenidone's usage.
Deuterium substitution maintains the important therapeutic properties of the drug, which allows patients to stay on therapy longer to achieve more optimal disease management. With this profile, we believe LYT-100 has the potential both to supplant the current standard of care treatments and to serve a larger market of patients who are unable to tolerate current therapies. Here are the results of a key experiment we conducted that demonstrates LYT-100's advantage.
On the left side of the slide are the results of our head-to-head trial with pirfenidone in healthy older adults. In this trial, LYT-100 reduced the number of GI-related side effects by 50% when compared to pirfenidone. The reduction in nausea is particularly meaningful because it affects the patient's quality of life and their ability to stay on the drug. We believe this profile may also allow higher dosing, which could improve overall efficacy.
Now for context, before we embarked on this study, we did what we always do. We spoke with the leading physicians in the field, and we asked them what results would be clinically meaningful. From those conversations, we set a bar of a 25% to 30% reduction in GI-related side effects. And what we achieved was nearly twice that. So we couldn't be more thrilled with these results. Building on these exciting results is our ongoing Phase IIb dose-ranging trial. This is a global study designed to evaluate the efficacy, tolerability and safety and dosing regimen of LYT-100 against placebo and to assess the relative efficacy of LYT-100 compared to pirfenidone.
As you can see from this slide, we were not required to evaluate LYT-100 on top of either standard of care treatment in this trial, highlighting another key differentiator and the strength of this mechanism. Importantly, we are investigating 2 doses of LYT-100, one with the same exposure as the currently approved dose of pirfenidone and another with a higher total drug exposure to see if higher exposure results in improved efficacy. In addition to our robust clinical data to date, we have a clear and well-defined regulatory path and are using the same end points that have supported past approvals. Based on regulatory feedback, we believe the compelling efficacy data from the ongoing Phase IIb dose-ranging trial, together with a Phase III trial could serve as the basis for us to file for FDA approval for the treatment of IPF in the U.S. LYT-100 also has the potential for therapeutic benefit in other indications, which you can see on this slide.
Beyond IPF, we are exploring its development in progressive fibrosing interstitial lung diseases, a group of lung diseases closely related to IPF with a clear development path along with other fibrotic conditions, where there is human data with pirfenidone suggestive of clinical benefit. We are also developing LYT-100 for medical countermeasures under the FDA Animal Rule, which allows for the approval of drugs based on well-controlled animal models. We may be eligible to receive a priority review voucher from the FDA for a medical countermeasure application upon approval.
Now let's turn to our CNS programs, LYT-300 and LYT-310, which were developed from our proprietary Glyph technology platform. Our Glyph technology is designed to enable oral administration of certain drugs that previously could not be given orally because the liver breaks them down before [that] drug is absorbed into the body. The technology capitalizes is on the way the body naturally absorbs lipids directly into the lymphatics. This approach has the potential to enable the drug to bypass the liver, thus maximizing the therapeutic potential of efficacious drugs whose widespread adoption had been limited by their lack of oral bioavailability. We have been advancing this platform, which has been published in a number of scientific journals and forums.
LYT-300, an oral prodrug of allopregnanolone is another example of how we take an existing efficacious therapy held back by factors that limited its commercial use and apply novel approaches to address those limitations and unlock the full potential of the therapeutic. Allopregnanolone has demonstrated benefit in a range of central nervous system conditions, but it's limited oral bioavailability, which means it can only be administered via IV has hindered its broad therapeutic use. This limitation is critical because of the evidence that allopregnanolone has therapeutic potential for anxiety and certain mood disorders, areas of serious patient need where standard of care treatments can have mixed efficacy, delayed onset of action and poor tolerability. Patients are in need of better treatment options, and we think LYT-300 can potentially make a difference.
Using our Glyph technology platform, LYT-300 retains the activity and potency of endogenous allopregnanolone in a more convenient oral form. LYT-300 is a markedly differentiated approach from other attempts by the industry to synthesize orally bioavailable chemical analogs of allopregnanolone. As such, it may also enable greater potency and a differentiated safety profile. Here are the results that give us reason to believe that LYT-300 could have a truly meaningful impact on patients.
In our multipart Phase I trial, we demonstrated oral bioavailability with LYT-300 that is ninefold greater than what third parties have published with orally administered allopregnanolone. This builds on what we've previously demonstrated in preclinical work and serves as additional validation of our Glyph platform technology.
In the same trial, LYT-300 also achieved blood levels of allopregnanolone at or above those shown to be associated with therapeutic effect, and it demonstrated a favorable safety profile and evidence of GABA A receptor target engagement in healthy volunteers, confirming that the oral prodrug is metabolized into active allopregnanolone. We initiated a Phase IIa trial of LYT-300 in healthy volunteers using a clinical model of anxiety in June, and we expect results by the end of this year.
Beyond anxiety and mood disorders, we're also pursuing development of LYT-300 for a rare condition called Fragile X-associated Tremor/Ataxia Syndrome or FXTAS. FXTAS is a rare and late onset condition characterized by cognitive decline, tremors in the hands and balance problems. There is no treatment approved for this condition, but an exploratory open-label trial showed signals of pharmacological benefit in a small number of patients with IV-administered allopregnanolone.
Earlier this month, we announced that we've been awarded up to $11.4 million from the U.S. Department of Defense to pursue FXTAS. We have an active grant writing program across our pipeline, which continually brings a substantial nondilutive funding. The DoD grant will support a Phase II trial of LYT-300 in collaboration with the researchers at the University of California, Davis.
Another CNS medicine generated from our Glyph platform is LYT-310, our oral cannabidiol prodrug, which is being advanced for the potential treatment of epilepsies and other neurological indications. CBD has validated activity in seizure disorders and like allopregnanolone has issues that have limited its broad use. Available therapies do not adequately serve patients and the only FDA-approved CBD treatment has poor oral bioavailability and tolerability challenges such as nausea, stomach pain, sleepiness and mood changes that impact patients' quality of life. Furthermore, the current approved CBD-based product has significant formulation and scalability limitations.
Let's take a look at the right side of the slide, illustrating the potential for LYT-310 to improve upon the current standard of care. As you can see on the left, the currency CBD treatment requires a larger volume of a sesame oil-based formulation, limiting its use to a small subset of rare pediatric epilepsies. Using our Glyph technology, we believe that LYT-310 has the potential to expand the therapeutic application of CBD across a much wider range of age groups and indications, most notably given its oral dosing, streamlined manufacturing process and potential to reduce the GI issues and liver toxicity associated with the currently approved CBD treatment.
In addition to LYT-300 and LYT-310, our Glyph platform continues to demonstrate great potential across a range of therapeutics. The platform has produced 3 additional preclinical CNS programs, as you can see on this slide, and we look forward to sharing more about these in due course. As we look out across the remainder of this year, we anticipate several major catalysts across our wholly-owned therapeutic candidates, including LYT-200, which is currently in 2 studies in patients with advanced solid tumors or leukemia. And the list of catalysts is growing. Our Founded Entities have also had a productive 2023 so far with significant commercial and clinical momentum, the details of which can be found in our half year report made available this morning.
I would now like to invite Bharatt Chowrira, our President, to provide a recap of our 2023 half year financial results that were announced earlier this morning and to make some closing comments.

Bharatt M. Chowrira

Thank you, Daphne. I'm pleased to report that PureTech's cash position remains very strong due to our unique business model, strong track record and commitment to financial discipline. At the PureTech level, we ended June 2023 with cash and cash equivalents of $348.5 million compared to cash, cash equivalents and short-term investments of $339.5 million at the end of 2022.
On a consolidated basis, our cash and cash equivalents were $350.5 million at the end of June 2023 compared to cash, cash equivalents and short-term investments of $350.1 million at the end of 2022. The cash and cash equivalents as of end of June 2023 include the proceeds from the Royalty Pharma transaction for the sale of future royalties of KarXT that we entered into in March 2023. Based on our existing financial assets, we expect to have operational runway into the first quarter of 2026.
Our revenues are mostly driven by upfront and milestone-based payments from collaborations as well as grants and are expected to continue to fluctuate from year-to-year. On a consolidated basis, our revenues in the first 6 months of 2023 was [$1 million] compared to $7 million in the first 6 months of 2022. We reported operating expenses of $79.3 million for the first 6 months of 2023 compared to $108.2 million in the first 6 months of 2022, reflecting a decrease in operating expenses, largely due to a decrease in R&D expenses, which is primarily driven by deconsolidation of one of our Founded Entities, Vedanta in the first quarter of 2023 as well as program selection and prioritization.
On a consolidated basis, we reported a net loss of $25.6 million for the first 6 months of 2023 compared to a net loss of $23.5 million for the first 6 months of 2022. The increase in net loss is partially due to the equity method accounting related to our investments in associates and an increase in tax provision mainly due to the Royalty Pharma transaction. These are largely offset by a higher gain recorded on the deconsolidation of a subsidiary, and the decrease mentioned above in operating expenses. This has been an exceedingly strong period across both our Wholly Owned Pipeline and our Founded Entities. While others in this sector has struggled, we have grown financially stronger and have continued to build an important pipeline of new medicines that are positioned to change people's lives.
As always, we are grateful to our skilled and dedicated team who continue to shepherd this important work forward, and we look forward to another exciting period ahead as we work to change the lives of patients with devastating diseases.
We'd like to thank all of the patients and clinicians who are participating in our clinical trials. We are humbled to be involved in your journey. We're grateful to our network of shareholders, advisers and other stakeholders for your confidence in our team and vision. Thank you for joining us today.
And I'm pleased to invite our Chief Innovation Officer, Dr. Eric Elenko and our Chief Medical Officer, Dr. Julie Krop, to join Daphne and me for the Q&A portion of this call.

Question and Answer Session

Operator

(Operator Instructions) Our first question, it's a written question comes from Miles Dixon from Peel Hunt, and it reads, (inaudible) that there were greater focus on the capital returns priority moving forward. Was this intended? And if so, if there were to be another significant capital event, would you also consider being more aggressive with capital deployment as well as the potential shareholder returns?

Daphne Zohar

Thank you. And thanks, Miles, for the question. We -- that was indeed intentional. We believe that we've been able to generate a significant amount of capital through our Founded Entities and monetization events. And we believe that with our Founded Entities and our Wholly Owned programs, which are quite advanced, we have many opportunities for generating additional potential monetization events. And as we do so, we plan to consider with our shareholders and our Board, but the idea is that we look forward to driving more returns back to our shareholders. Thank you for that question.

Operator

Our second question also comes from Miles, and it reads, you have described $575 million raised from Founded Entities in the first half of 2023 and $3.8 billion since 2018. How should we think about this over the next 5 to 6 years? Do you think you might be able to achieve a similar amount of value creation?

Daphne Zohar

So I think that there's a few ways to look at the advancements and success that we have achieved with both the Founded Entities and the Wholly Owned programs. Obviously, the first and most important is clinical and regulatory advancement and bringing these new medicines to patients. And I think that one of the things we're incredibly proud of is our clinical track record. The second is, obviously, what you just noted, being able to attract capital so that those Founded Entities, for example, can execute on their plans, and we've been able to do that as well without diluting our shareholders.
So absolutely, we think that there are many opportunities for us to create value. And one of the markers of that value is the amount of fundraising that has happened on the Founded Entity level. But I think it also speaks to the independence of those entities and the fact that they're actually bringing value back to us as opposed to having them be a drain on our resources. Thank you very much for that question.
And I think we're going to go to Tom Smith from Leerink next, correct?

Operator

Yes, that's correct. Tom Smith, your line is now open. Please go ahead.

Unidentified Analyst

This is [Nat Charoensook] on for Tom Smith. Congrats on the progress. A few questions from us. So the first is, (inaudible) the enrollment progress of the IPF study of LYT-100, what are the strategies you have implemented to accelerate the enrollment and how [quickly] are they? And second, with the recent approval of zuranolone in PPD and (inaudible) MDD, how does it impact your strategy for LYT-300 development in neurological indications?

Daphne Zohar

So the first question was regarding our enrollment progress in IPF for LYT-100. So I'm pleased to say that we've seen a very nice uptick in enrollment and we're feeling very good about the measures that were put in place, which we talked about, I think it was in the annual results. So I will invite Julie Krop, our Chief Medical Officer, to say a little bit more about some of the measures that we put in place. But overall, we're very pleased with the uptick in enrollment in IPF. So go ahead, Julie.

Julie Krop

Yes. Thanks for the question. I think we talked about on the last half yearly call that we have put in a number of different initiatives and as Daphne was saying, I think a lot of those initiatives we've put in are really paying off. Some of them were to go to additional countries where there are less approvals in place for standard of care medications. So that's one thing we've done that I think has really helped. We've been working closely with patient advocacy groups and [RPIs] to get referrals from various sources, including patient support groups and other novel approaches that we've come up with. And I think all of those things have really put us in a really nice position right now with our enrollment, and we're on target for completing again, the top line results in 2024.

Daphne Zohar

Thanks so much, Julie. And the second part of your question had to do with the zuranolone approval for PPD and the setback they had around MDD, I believe, and whether that's affected our thinking about LYT-300 for PPD. So first of all, we're very happy that there's a new treatment option for patients with PPD. In light of the 2 approved PPD treatments on the market, we believe that there are other depression-related indications that have greater patient needs than PPD. So within the context of mood disorders, we are in the process of prioritizing what would be the best path forward for depression. We're extremely excited about this program. And in addition to depression-related indications, we're also pursuing anxiety. I will just see -- and also we've recently received a grant for FXTAS , which is a rare disease. So let me invite Eric Elenko, our Chief Innovation Officer, to see if he would like to comment further on this question.

Eric Elenko

Yes. I think the results from the ongoing Phase IIa proof-of-concept trial in healthy volunteers, which uses a validated clinical model of anxiety, which we're expecting results of -- by year-end this year. Alongside our completed Phase I results are going to inform potential future development plans [in] additional indications. And we're in the process of prioritizing which additional indications to pursue with regard to new disorders as Daphne was saying. And while we're conducting this indication prioritization exercise, we're no longer guiding to the initiation of the Phase IIa POC in PPD as Daphne was indicating, but of course, we're continuing to pursue our plans in FXTAS, for which we received the grant.
Overall, we're very excited about the LYT-300 program, which leverages our Glyph platform, given its ability to retain the potency of endogenous allopregnanolone and in a more convenient oral form and potentially enable us to unlock the therapeutic potential of allopregnanolone across a range of neurological and neuropsychiatric conditions.

Daphne Zohar

Yes. And that's a really important point. LYT-300 is a natural neurosteroid, where zuranolone is a synthetic analog. Therefore, the pharmacology of the 2 compounds, including the AEs could be different. And as Eric noted in our Phase I study, LYT-300 was safe, generally safe and well tolerated, and we're continuing to conduct relevant studies, which we think is an opportunity to further differentiate LYT-300 from zuranolone based on, for example, tolerability profile among other things.

Unidentified Analyst

And one more question, if I may.

Daphne Zohar

Sure.

Unidentified Analyst

So with the current cash and cash runway into the first quarter '26, do you plan to license any new assets or initiate any additional internal program?

Daphne Zohar

Yes. So we actually are really excited about the productivity of the Glyph platform. And we've noted in the results briefly, but we're excited to say more about in addition to 300 and 310, we have 3 more CNS programs coming from the Glyph platform. So -- and that's what we see in front of us, but we believe it's incredibly productive platform. And we continuously look externally to see what's out there and whether there are programs that were intrigued by. But I have to say right now, we're prioritizing some of the things coming out of our Glyph platform internally just because we think that they (inaudible) bar is really high to bring in anything external compared to the programs that we have in front of us.
So we'll say more about these programs as they progress towards the clinic, but you could think of them as preclinical stage, some of them are late discovery, but we have candidates close to selection in that case.

Operator

Our next question comes from Lucy Codrington from Jefferies.

Lucy-Emma Mary Sarah Codrington-Bartlett

Just with regards to the capital return and strategy with this more robust returns, is the plan still to keep 3 years cash on hand as (inaudible). Secondly, just on the LYT-300, the clinical model data that we should get towards the end of the year. What can we expect from that trial? And how should we interpret the results (inaudible) a healthy volunteer study? And then finally, when you talked about value creation for the internal pipeline, I guess what are the factors you might consider when deciding whether to continue to develop something internally versus creating a Founded Entity? And if you were going to go down a partner [or sale route], is there a particular stage of development that you'd like to get to first?

Daphne Zohar

Yes. So your first and your third questions are somewhat interrelated, in that one of the -- so first of all, yes, we are continuing to guide to the first quarter of 2026 in terms of our runway. And we think that there's 2 factors that could enable us to more aggressively return capital to our shareholders. The first of those is potential future monetization events, some of which could come from the Founded Entities, but some of which could also come from the Wholly Owned programs. And I think one of the points that we wanted to emphasize is that we now have 7 Wholly Owned programs that we've been nurturing through this time period in addition to the Founded Entities, so one example, obviously, we've been able to demonstrate is the Karuna monetization, and we've taken about $780 million off the table there.
We think we have the potential over time to have a similar amount coming from just Karuna, but then we have these other Founded Entities and these Wholly Owned programs. And I think that as we look across them, we believe that there is a significant amount of value that is not clarified yet for our shareholders. And we look forward to crystallizing and clarifying that value for our shareholders. And one way to do that, for example, would be to put certain of these Wholly Owned programs into Founded Entities and other might be through partnering or royalty transactions or things like that, which would do a number -- a couple of other things. One, it would provide a reference value on some of these assets that are currently, I think, maybe our shareholders might not know how to value at this point. The second is if some of the programs are advancing together with outside capital, then that will actually free up more capital again for potential returns to our shareholders.
So we are not saying that we will not continue to advance programs internally. But now that some of these programs are out of the stage that they could be providing value back to us. We are looking at every possible way that we're going to get these to patients as quickly as possible and really have an impact on patients' lives, but also at how are we going to create across the pipeline and portfolio the most value for our shareholders. I think -- and then the second question you had was on the (inaudible) model that we're running for LYT-300, and this is a clinically validated model of anxiety in healthy volunteers. So you could look at this as an exploratory study on some level, but maybe Eric might want to say some more about that and what we'd hope to see and what that could teach us with regard to anxiety. Eric, you might also (inaudible) talk a little bit about the anxiety data so far with this particular mechanism.

Eric Elenko

Sure. And in terms of allopregnanolone, where generally there's preclinical animal data indicating the potential to have a therapeutic effect in anxiety. And then also in the context of postpartum depression using a really accepted scale for anxiety and anxiety can be a component of postpartum depression. Those 2 will often go together. What was observed for allopregnanolone was a fact on anxiety in that scale, which is an accepted scale. Given the known pharmacology and promise in anxiety, really the goal of this study is to show proof of concept for LYT-300 activity in anxiety disorders.
And placing healthy volunteers in a situation that simulates anxiety really is a way of efficiently determining the pharmacological activity of an agent, in this case, of course, LYT-300. The trial is double-blind, placebo-controlled. And so it's one that coming out of, we can have confidence that if we see activity that it's a real effect of the agent.

Operator

Our next question comes from Edward Thomason from Liberum, and it reads, sorry if I missed, but what indications will you be looking at for LYT-510? And secondly, safety is a priority for LYT-200, but what other data might we get to see from LYT-200 in AML later this year?

Daphne Zohar

Yes. Let me start with the LYT-200. So yes, this is primarily looking at safety, but we hope to also see some potential signals of efficacy and we could say some more about that, but maybe I'll invite Julie to comment on what we'd hope to see.

Julie Krop

Yes. Thanks for the question. So this obviously is as Daphne said, a early-stage safety and tolerability primarily study, but we will be looking at surrogate exploratory, I should say, markers of efficacy, including transfusion rates in these patients, obviously, looking for blast in the periphery and in the bone marrow and really overall survival. This is a very [sick] patient population. And so we would hope to see patients staying on drug for some period of time. And overall, seen an improvement in their survival. So I think this was -- this could be a very interesting study, and we're excited to read out the results.

Daphne Zohar

Thank you, Julie. And regarding 510, the indication that we are looking at is ulcerative colitis, but I will say that for -- across our entire pipeline, we're continually looking at which programs are the most promising. And so several of the new Glyph programs are sort of surpassing 510 right now and moving ahead kind of in line before 510 towards clinical development. So ulcerative colitis is the indication, but we are not fully going forward with that at this point because there are some other programs that we're prioritizing. So hopefully, that answers your question.
Do we have any other questions?

Operator

Yes. Our next question comes from Miles Dixon from Peel Hunt again. And his first question reads, given the recent Gelesis merger agreement and your strategy to build the Wholly Owned Pipeline, can we expect to see over the midterm, all Founded Entities move towards 100% or 0% equity ownership, excluding any benefits from royalties and milestones? The second question from Miles reads, is there a rate limiting step when developing ideas for PRTC to pursue? Or do the team continue to see lots of options to prosecute on? Can you give us a steer as to how many ideas per year the group consider and the drop-off rate as due diligence go-to-market strategy is completed?

Daphne Zohar

Yes. So I'll start with the first question. I think, generally, just wondering whether we look to develop these programs as Wholly Owned or as Founded Entities. And I think the question was whether we want to move towards 100% or 0% ownership. And I think the way to think about this is that we start with 100% ownership, and we -- there are going to be some programs that we continue to hold 100% ownership of and other programs that we feel would be more quickly advanced with -- through a Founded Entity and in which case, those Founded Entities over time would be a source of value back to us. So over time, the ownership would go down if it's a Founded Entity.
And I'd say that in addition to equity, there's also the possibility of doing partnerships and including considering partnering an entire asset with a large pharmaceutical partner or selling royalties, whether they be our royalties in a program or whether we create royalties and actually monetize those, they're called synthetic royalties. So we think there's multiple ways that we can look at advancing the pipeline and there's not a set formula around that. It's really how are we going to create the most value, how are we going to get these new medicines to patients.
In terms of the rate limiting step, as we're developing ideas for PureTech, I think what we have is an embarrassment of (inaudible) that we have some really powerful platforms. We have an amazingly talented team and the ability to prosecute these because we have cash. And so for us, the key rate-limiting step is making sure that we are being really tough on our own assumptions and that we're not advancing any program unless we have full belief in it, and we really think it's going to generate value for us. We have, I think, in many ways, an enviable position because we have choices. So we're not just advancing one binary program. And therefore, we can be very honest with ourselves about how we feel about a program. So no, I think that no rate limiting step. I don't know if Eric would like to comment on the number of programs we see or the number of new ideas that we sort through each year before selecting which will advance. Eric, did you want to comment on that?

Eric Elenko

I mean I think you said it really well, Daphne. We have quite a few opportunities in front of us. And particularly, the Glyph platform has been very productive, and we think has the potential to continue to be quite productive in terms of new ideas. I don't think we're guiding on the number of candidates we're going to bring into the clinic a year at this point. But probably the best guide here is looking at the historic way we've advanced candidates coming out of Glyph and that's 300 and 310, and you've seen those going about one a year, but we do have a lot of opportunity that we see in front of us in terms of that platform.

Daphne Zohar

So I just would say that one of the things that I'm so grateful for is this team that I work with. Bharatt, Eric, Julie and just an amazing group of people that are fully committed to doing what's best for patients and our shareholders. And it's just a pleasure to work with everyone, a tremendous amount of progress in this first half of the year and really excited to talk to our shareholders about our plans going forward and meeting with many of you over the next few weeks. So thank you to everyone for your support, and we really appreciate the time today, and we wish you all a good last weekend of summer and look forward to seeing you soon. Thank you, everyone.