PureTech Health PLC (PRTC) 2020 Q4 法說會逐字稿

Greetings, and welcome to the PureTech Health 2020 Annual Report and Year-end Financial Results Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce your host, Allison Mead Talbot, Head of Communications. Thank you, Allison. You may begin.

Thank you for joining us today for PureTech's 2020 annual results webcast. We hope you've had a chance to review our press release, which was issued earlier this morning. Our annual report was made available this morning and also filed with our Form 20-F earlier 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 Daphne Zohar, Founder and Chief Executive Officer; Bharatt Chowrira, President and Chief of Business and Strategy; George Farmer, Chief Financial Officer; Eric Elenko, Chief Innovation Officer; Joe Bolen, Chief Scientific Officer; Steve Muniz, Chief Operating Officer; and Joep Muijrers, Chief of Portfolio Strategy.

I would like to remind you that during today's call, we will be making certain forward-looking statements and ask that you refer to our annual report and our SEC filings for a complete discussion of potential risks and uncertainties. I also want to remind you that we will be referring to certain non-IFRS measures in this presentation. A reconciliation of IFRS to non-IFRS measures, that I will be referring to today, can be found as an appendix to this presentation, which is available on the Investors section of our website at puretechhealth.com.

I will now turn the call over to Daphne Zohar, PureTech's Founder and Chief Executive Officer.

Thank you, Allison. We hope all of you and your families are keeping well. We are thankful to all the scientists and health care providers who have worked to make vaccines available, so we can look forward to seeing each other in person again soon.

We are grateful to be part of an industry that is dedicated to improving lives and inspired by our mission to give life to science by rapidly advancing scientific breakthroughs to patients. I am immensely proud of our team's accomplishments in 2020. It was a transformational year for PureTech with significant advances, important achievements and further validation of our unique model for developing new medicines.

I will start by highlighting our research and development engine. As a company that is focused on addressing major health needs, we are proud to have invented the underlying platforms and programs that have led to 26 potential new medicines for devastating diseases, including 15 that are clinical stage and 2 of which were taken from inception at PureTech through FDA and European regulatory clearances by our partners.

Our distinctive R&D model is built on collaboration with the world's leading experts around specific diseases bringing together cross-disciplinary perspectives and exploring multiple approaches to tackling that disease. Together, we identify, invent and advance scientific breakthroughs. This model has enabled us to consistently gain early access to breakthrough discoveries well before the rest of the world reads about them in major scientific journals.

Another important part of our process is to run key derisking experiments before advancing the programs. Our R&D focus has centered on the biology of the brain, immune, gut access, the crosstalk between those systems is gaining prominence across scientific disciplines. We are particularly excited about how this distinctive R&D engine has led to rapid advancement of our Wholly Owned Pipeline last year, with the initiation of multiple clinical studies evaluating these programs in a range of devastating diseases. We expect these programs, where we maintain 100% ownership, to be key value drivers for PureTech in the future.

Our founded entities, which you can see across the bottom of this slide, are the innovative programs that PureTech initiated and coinvented which are now advancing in independent entities. We hold sizable equity ownership in these 9 founded entities and continue to benefit from their growth as they expect to have many upcoming catalysts, and can serve as a potential source of nondilutive funding to us from events such as M&A transactions, IPOs and royalties.

In 2020, for example, we received $350.6 million from the sales of some of our equity and founded entities and an additional $118 million in the 2021 post period. We have a strong balance sheet, with $443.4 million in cash and cash equivalents at the PureTech level as of March 31. Our founded entities are also well capitalized, having raised over $1.2 billion over the last few years.

2020 was rich in accomplishments. As we look at the progress across our Wholly Owned Pipeline on the upper half of the slide, it's important to highlight that we initiated 4 clinical studies in 2020, one of which read out positively and t3 more that are ongoing. Our founded entities have also achieved many milestones in 2020, including the FDA clearance and European Marketing Authorization of Akili's EndeavorRx, the European Marketing Authorization of Gelesis Plenity and the initiation of Karuna's Phase III trial of KarXT for the potential treatment of acute psychosis in adults with schizophrenia.

So far in the 2021 post period, Vor has completed a $203 million IPO, and Karuna has completed an approximately $270 million follow-on public offering. These 2 public founded entities are valued at a total of over $4.5 billion, and we have several other private founded entities who we believe also have substantial value potential.

In our Wholly Owned Pipeline, we created significant fundamental value and achieved a number of additional clinical and business milestones, towards our mission of developing transformational medicines for millions of people who have long struggled to find effective treatments. These milestones are highlighted in our annual report, and I'll touch on just a few of them here.

Our Wholly Owned Pipeline is focused on the lymphatic system and related immunology and is a major new driver of growth. We are now in multiple clinical trials and anticipate several upcoming milestones from these programs. The lymphatic system is a key component of brain, immune, gut and crosstalk and serves 3 essential functions. One function is maintaining fluid balance. Disruption of lymphatic flow can lead to lymphatic disorders like lymphedema, which we are pursuing and is intriguingly implicated in the development of neurodegenerative disease.

The lymphatic system is also a sort of super highway for immune cell trafficking and programming. It plays a role in absorbing dietary lipids. We are leveraging this third function to directly drug the immune system by oral administration of compounds directly into the lymphatic system, where immune cell education and circulation takes place.

On the next slide, we're going to start our step-through of our therapeutic development pipeline with LYT-100, which is a perfect case study for our research and development model. Unique insights and unpublished data from our collaborators and business network enabled us to identify LYT-100 and acquire the related IP. We then ran a study, which provided proof of concept for the tolerability of LYT-100, which we believe derisks the program. And we think that based on the data we have, that this could potentially be an important new therapeutic to treat a range of diseases.

We initially came to this program through our focus on lymphedema, a serious lymphatic flow disorder with no approved therapeutics. Lymphedema is a chronic and painful condition that affects 1 million people in the U.S. and is characterized by severe swelling in parts of the body due to the buildup of limb fluid inflammation and fibrosis.

Relationships with the world's leading lymphatic experts led us to unpublished preclinical data that showed that pirfenidone had activity in preclinical models of lymphedema. We combined this information with insights regarding the potential clinical differentiation of deupirfenidone, an oral containing deuterium-containing analog of pirfenidone. This led us to acquire deupirfenidone, which is what we now call LYT-100 from Teva Pharmaceuticals in 2019.

We have also in-licensed intellectual property from the Memorial Sloan Kettering Cancer Center for lymphedema. Since then, we have confirmed that LYT-100, like pirfenidone, is also active in those same preclinical models of lymphedema. Importantly, as typical for us, we ran a key proof-of-concept clinical study where we observed that LYT-100 has a favorable pharmacokinetic and tolerability profile.

Pirfenidone has been approved for the treatment of idiopathic pulmonary fibrosis, or IPF, a condition which is characterized by progressive irreversible scarring of the lungs. One of the current standard of care treatments for IPF is pirfenidone. The other drug is nintedanib.

While the current standard of care treatments are widely prescribed and efficacious, serious limitations particularly GI-related tolerability issues, affect treatment compliance and patient outcomes. In fact, in a post-marketing analysis that followed about 11,000 patients in real-world treatment settings since these drugs were approved back in 2014. Only approximately 25% actually started therapy and many ceased administration due to GI side effects such as vomiting and diarrhea. Nevertheless, both drugs combined sold almost $3 billion annually worldwide in 2019. So we think that there is a significant need here.

We think LYT-100 could overcome these limitations and potentially offer a new treatment option for IPF patients. So we believe there's an opportunity here for LYT-100 with its favorable tolerability profile, less frequent dosing and lower pill burden and also the ability to administer without regard to food. We are planning registration-enabling studies and expect to provide additional guidance regarding our regulatory strategy later this year. Importantly, in preclinical studies, LYT-100 retained the activity of pirfenidone, but demonstrated a differentiated safety and tolerability profile.

Results from single and multiple ascending dose studies enrolling healthy volunteers suggest that LYT-100 could be well tolerated at up to 1,000 milligrams twice per day, which we think provides comparable exposure to the 801 milligrams 3 times a day currently used for pirfenidone dosing. Note that in this study, LYT-100 was well tolerated at all doses, and all treatment-related adverse events were mild and transient with no discontinuations.

We are planning to initiate additional clinical studies in healthy volunteers to further evaluate the pharmacokinetic dosing and safety data generated thus far to help with the clinical development of LYT-100 across indications. Results from these studies are anticipated in 2021. In the next slide, we describe the results from one of several independent research surveys we conducted with physicians, patients and payers.

Study, pulmonologists were presented with a hypothetical profile of a drug, with an improved tolerability and dosing profile and similar efficacy compared to the standard of care in IPF. What was most striking was that the physicians indicated that they may prescribe such a drug to approximately 30% of their IPF patients on average based on this profile, even without seeing an improvement in efficacy relative to the standard of care.

Across the board, pulmonologist highlighted an unmet need for treatments with improved tolerability profiles, especially GI-related adverse events that often lead to dose reduction or discontinuation of treatment and poor disease management. Encouraged by this feedback, our major goal with LYT-100 is to supplant pirfenidone as a backbone standard of care for the treatment of IPF and potentially other progressive fibrosing interstitial lung diseases, or PF-ILDs.

ILDs encompass a group of over 200 distinct disorders, including IPF and effect about 0.25 million patients in the U.S. alone. Within ILDs, patients can develop PF-ILDs, in which there is a progressive deterioration in lung function and quality of life with an increase in early mortalities. PF-ILDs beyond IPF have a dearth of treatment options with nintedanib being the only approved drug for the broader umbrella of ILDs. The common biology that PF-ILDs share, a drug that is effective against IPF, also has the potential to treat other PF-ILDs.

We look forward to providing more detail on our regulatory strategy for this Phase III program in IPF and potentially other progressive fibrosing interstitial lung diseases later this year. In the meantime, we have 2 Phase II clinical trials that are underway, one of which is for long COVID-related pulmonary complications, which I will detail on the next slide.

The outcome of COVID-19 is not binary and surviving COVID-19 is not the end of the story. There is increasing evidence around the longer-term complications of COVID-19, which is referred to as Long COVID or post-acute COVID-19 syndrome, or PACS. Based on a recent study, up to 53% of patients recovering from mild-to-moderate and severe COVID-19 showed signs of lung fibrosis or scarring at 3 weeks post symptom onset. Many survivors continue to suffer from pulmonary complications, which are believed to be the result of continuous inflammation and fibrotic activity in the lungs.

Early in the pandemic, based on reports we were hearing within the pulmonologist community, we quickly decided to evaluate whether LYT-100 could be useful for treating these patients. I'm very proud that in just a few months, our team was able to initiate a global randomized placebo-controlled Phase II study to test the potential clinical benefit of LYT-100 with a primary endpoint of the 6-minute walk test. We're off to a great start and expect results from the study in the second half of this year.

Coming back to lymphedema. We launched a Phase II study late last year evaluating LYT-100 in patients with breast cancer-related upper limb secondary lymphedema shown on the next slide. The primary endpoint of our ongoing randomized placebo-controlled Phase IIa proof-of-concept trial is safety and tolerability, with secondary clinical efficacy, patient-reported outcomes and biomarker endpoints. We will also be looking for signals of improved lymphatic flow associated with LYT-100 treatment.

We expect results from this study originally targeted for the end of this year, now in the first half of next year based on some enrollment challenges driven by the COVID-19 pandemic.

In summary, the 2 Phase II studies with LYT-100 that were initiated towards the end of last year are progressing. One of these studies is targeting lung complications associated with Long COVID and another is a proof-of-concept trial enrolling women with breast cancer-related upper limb secondary lymphedema. And we are finalizing our plans for registration-enabling studies in IPF and potentially other PF-ILDs and expect to share additional guidance later this year.

Beyond LYT-100, another clinical stage wholly-owned program is LYT-200. We began dosing patients at the end of last year with LYT-200, our novel fully human monoclonal antibody targeting galectin-9, a foundational immuno-suppressor that is upregulated in difficult-to-treat cancers, like pancreatic and other solid tumors that are unresponsive to checkpoint inhibitor therapies.

Preclinical results showed that LYT-200 has potential for single agent efficacy as well as in combination with anti-PD-1 therapy and chemotherapy. Treatment with LYT-200 led to inhibition of tumor growth and increased survival in a preclinical pancreatic cancer model, where other immuno-oncology agents like anti-PD-1s don't work.

Using human-cultured organoids derived from 20 individual tumors across various tumor types, we've also seen very robust and reproducible activation of intratumoral T-cells when incubated with LYT-200. We have advanced LYT-200 in the first portion of a Phase I/II clinical study, with top line data expected from Stage 1 of the study in Q4 of this year. The first part of the study is designed to evaluate the safety and tolerability of LYT-200 in patients with relapsed/refractory metastatic cancer with the aim of identifying a recommended Phase II dose.

Our most recent candidate nomination for our Wholly Owned Pipeline is LYT-300. LYT-300 is an oral form of a natural neurosteroid called allopregnanolone, an IV version of which is approved by the FDA and available in the U.S. a brexanolone or ZULRESSO. Brexanolone is administered as a 60-hour IV infusion. which has greatly limited its usage in postpartum depression disorder and would likely be a limitation for other indications.

In preclinical studies thus far, including nonhuman primates, we have seen oral bioavailability with LYT-300 and plasma exposures that suggest therapeutically relevant human plasma levels may be achieved. Based on these promising data, we expect to initiate a Phase I trial with LYT-300 by the end of this year. This oral form of natural allopregnanolone is developed using our proprietary Glyph technology, which you can see on the next slide.

The Glyph technology platform is designed to allow for lymphatic targeting and avoidance of first pass metabolism. We believe an orally administered allopregnanolone has therapeutic potential across a wide range of neurological conditions like seizures, sleep and neuropsychiatric disorders. We have 2 other lymphatic research platforms, which include Orasome, our oral biotherapeutics platform, which along with Glyph, leverages absorption of dietary lipids to traffic therapeutics via the lymphatic system and our meningeal lymphatics discovery research program for treating neurodegenerative diseases.

In summary, as you look across our Wholly Owned Pipeline and our founded entities, we believe this is going to be another exceedingly catalyst-rich year, which includes multiple value drivers across our Wholly Owned Pipeline and our founded entities, including at least 10 expected clinical study initiations and 9 expected readouts.

I would now like to welcome George Farmer, PureTech's Chief Financial Officer, to the call, so he can provide a recap of our 2020 financial results that were announced earlier this morning.

Thank you, Daphne. As the newest member of PureTech's management team, I am very pleased to note that PureTech has never been in a stronger financial position than it is today. At the PureTech level, we ended the first quarter of 2021 with cash and cash equivalents of $443.4 million compared to our balance of $349.4 million at the end of 2020 and $120.6 million at the end of 2019. This difference includes proceeds from our sales of shares in our founded entities in 2020 as well as $118 million of proceeds from sales of an additional stake in February this year.

Backed by the strong financial position, we are pleased to report that we are extending our cash runway guidance by 1 year into the first quarter of 2025. This assumption is based off of conservative budget projections and excludes potential, nondilutive capital inflows from possible monetization of positions in our founded entities, future strategic partnerships, possible equity financings or grant funding.

On a consolidated basis, our cash and cash equivalents amounted to $486.5 million at the end of the first quarter of 2021 compared with $403.9 million at the end of 2020 and $162.4 million at the end of 2019.

Our revenues are mostly driven by upfront and milestone-based payments from collaborations and are expected to continue to fluctuate from year-to-year. On a consolidated basis, our revenues in 2020 were $11.8 million compared with $9.8 million in 2019, primarily driven by cash generated through collaboration.

Our 2020 operating loss decreased to $119.5 million from $135.4 million in 2019, largely due to the deconsolidation of Karuna, Gelesis and Vor from our financials in 2019. If you exclude the performance of the noncontrolled founded entity segment of our 2019 results, than on a like-for-like year-over-year comparison basis, our operating loss actually increased $10.1 million or 8.5% from a loss of $109.4 million in 2019 to a loss of $119.5 million in 2020, driven by our continued strategic investment in our Wholly Owned program. This included R&D expenses for our Wholly Owned programs increasing to $41.6 million in 2020 and $26 million in 2019 due to excellent progress in our clinical and preclinical development programs.

On a consolidated basis, we reported a positive net income of $4.6 million for 2020 compared with $366.1 million for 2019. This accounting difference was driven mainly by noncash fair value gains related to the deconsolidation of Karuna, Gelesis and Vor in 2019.

During the past calendar year, our founded entities raised an aggregate sum of $247.8 million, 99.6% of which came from third-party investors. Our founded entities also raised an additional $473.2 million subsequent to the reporting period, all of which was contributed by third-party investors.

Lastly, we are pleased to have listed our American depository shares on NASDAQ in November 2020 through a direct listing. And due to our strong cash position was not coincident with the capital raise. This listing broadens our access to the U.S. capital markets, if needed. This has been an incredible year for PureTech, and I'm very proud to be part of this company since joining earlier this year. We have a lot to look forward to over the ensuing months and beyond.

I will now turn the call back over to Daphne.

Thank you, George. I would like to thank the entire PureTech team on their resilience this year as we accomplished historic milestones as an organization while navigating remote working and the emotional strain of a global pandemic. I would also like to extend my gratitude to our tremendous Board and Research and Development Committee for their wise counsel and strategic oversight.

We are fortunate to have a dedicated team and outstanding scientific collaborators who are committed to developing highly differentiated medicines for patients in dire need of better options. To our shareholders, thank you for your continued vision and the trust that you place in our team. Above all, we thank the patients, volunteers and clinicians working alongside us in our clinical trials. We are humbled and inspired by your courage. You make possible the medical advances of the future. We look forward to another transformational year, focused on giving life to science and making a difference for patients together.

Thank you, everyone. We will now take questions.

(Operator Instructions) Our first question comes from Amy Walker of Peel Hunt.

Congratulations team. I have 3 questions. I'll ask them individually, if I could, please. The first one, Daphne is, I think you mentioned now that there are at least 2 assets in clinical trials for the consequences of COVID-19 infections and their lingering effects in patients. And I wondered if you could talk to how confident you are around the recruitment criteria given the characterization of the disease and the long-term effect still seems to be evolving? And is there any concern that the potential heterogeneity of the patients might make that a slightly riskier indication than some of the others that are in the clinic at the moment? And how should we think about that? That's the first question.

Okay. Thank you, Amy. It's good to hear from you. So I will let Eric answer that question in more detail. There are some similarities between the Long COVID-related respiratory complications and what we've seen in other viruses like SARS Classic and MERS, and we've also done some things to make the patient population more homogenous. I'll ask Eric to add any additional thoughts to that.

And Amy, I think you were referring to LYT-100 and also to the Akili cognitive trial. So we think really key here is recruiting patients and having inclusion and exclusion criteria that reflect the particular symptoms that the patients are experiencing. So in the case of LYT-100, we're aiming at patients who have continued respiratory complaints and respiratory symptoms, which really would reflect ongoing inflammation and the sort of fibrosis in those patients. And that's really what we've seen as Daphne was saying with the SARS experience.

And so what we are doing is not only looking at the emerging data with regards to COVID, but also to the past precedent that other respiratory complications from viral disease have presented and have really tried to hone in on a patient population that's reflective of what is most likely the underlying pathology of inflammation and fibrosis. And so there are a number of things we're doing there in terms of things like requiring to look for involvement of the lungs, requiring them to have a certain level of dyspnea. So really to hone in on the right population.

And then Akili is -- I think was the second call you were alluding to, which is they're using AKL-T01 and testing that as a treatment for patients with cognitive dysfunction on COVID-19. And again, the idea there really is to hone in on patients who have a particular complaint, in this case, the cognitive complaint.

That's very helpful. My second question is around the great anecdotal sort of statistics actually that you mentioned in the press release around the soft launch of Plenity. And I wondered if we could get some insight from you on the gating factors for PureTech to monetize that residual stake in Gelesis now? Is it about waiting for further demonstration of strong uptake in the main launch? How do we think about that monetization pathway for Gelesis and Plenity given what you've seen so far?

Thanks, Amy. So we're really excited about what we're seeing so far with the Plenity launch. And as with all of our founded entities, we're in really fortunate position that we have such a strong cash position that we're not, at this point, under pressure to do monetization and can really think about optimal times to do that with different founded entities.

So I think there are several ways that it could play out with any of these founded entities, but also with Gelesis and those include -- first of all, we have royalties from the sale of products. So that's really exciting. Secondly, there's opportunities always that these companies could be acquired and then, of course, public offerings and then subsequent growth and monetization of our stake over time. But it's not that we're immediately thinking about monetizing everything. We really want to create the most value for our shareholders over time, and some of that might be in the near term and some of it might be in the longer term.

Okay. And then just my last one is probably for George, I guess. Are you able to give a little bit of guidance on your R&D spend for 2021? And maybe even directionally for next year, given the visibility that you have at this stage on the various trial programs and how those are progressing? And then I'll let others ask.

Thanks, Amy. So I'll just -- go ahead, George.

Well, sorry, Daphne. Yes, thanks for your question, Amy. Yes. So we've reported our Q1 cash of $443 million at the end -- of the end of first quarter. We've guided now that, that cash will extend to the first quarter of 2025. We haven't given any guidance beyond that. But you can expect a continuous ramp in R&D expenses as our pipeline matures.

Our next question comes from Ted Tenthoff of Piper Sandler.

Great. And congrats on the progress. It really has been quite a year. Firstly, just back to the Long COVID study again. Remind us on what the endpoints are and really how you're trying to assess benefit in these post-COVID patients? And then with respect to IPF, what should we be thinking about in terms of size of a potential registrational study? How do you engage the regulatory agencies yet? Appreciate the color.

Thanks, Ted. Good to hear from you. So I will let Eric answer in more detail in a second on the Long COVID study. The primary endpoint is the 6-minute walk test, and he can say some more about some of the other endpoints that we're looking at. And one thing I wanted to note about Long COVID and lymphedema is that while we think that these are really important conditions, and we're very excited to be able to put something forward that could help patients, these are novel indications. And on the other hand, as you pointed out IPF is an area where we know a lot about the efficacy profile of pirfenidone, for example.

So we're really excited to be putting forward these novel indications, and we're also comforted by the fact that we have a path forward with IPF. So we think we have several ways that we could potentially benefit patients here.

Yes, appreciate it.

Regarding the size of study and IPF -- yes. Okay. Thank you so much for the question by the way, Ted. And then regarding the size of the study in IPF, we're not yet ready to provide guidance on that. We are engaging both with regulatory authorities. But also importantly, with some of the leading experts who ran the past IPS study for the existing drugs that are currently available for patients as well as the broader studies (inaudible) studies for PF-ILD. So we're spending a lot of time really figuring out the ideal trial design, both with the experts and also with regulatory authorities, and we'll be able to say more later this year.

Eric, do you want to comment any more on the endpoints for the Long COVID study?

Yes, Daphne. I think you said it quite well, right? The primary endpoint is 6-minute walk test. The only thing I'll add is that we're also looking at patient-reported outcomes, primarily around respiratory function given that really is the focus. We will have one patient referring outcome, which is SF-36, which is more of a global scale in terms of how patients are feeling. So it will both be a physical functioning test as well as patient reported outcome.

And imaging and other biomarkers as well.

Our next question comes from Thomas Smith of SVB Leerink.

Congrats team on all the progress. Just a couple of questions on the Wholly Owned programs. For LYT-100, can you talk a little bit about the early enrollment trends in the lymphedema study and maybe some of the actions you are taking to mitigate some of the COVID-related challenges here? And then unlike 200 you guided to top line data from the first part of the study in Q4, can you walk us through your expectations here? And I guess, how you intend to communicate these results to The Street? Can we expect a top line release? Or should we be looking toward a medical meeting presentation like ESMO or SITC later in the year?

Yes. Thanks so much, Tom. These are great questions from all of you. So for the lymphedema study, I would put it in the realm of typical things that are going on with COVID sort of as a background and just sort of typical delays. So we think that we look forward to moving forward with the study and being able to share more updates as we move forward.

With regard to LYT-200, I think that what we're aiming for is probably around a conference would probably be the time that we would be reporting results. I don't know if Eric or George want to say more about what we'd be looking for here. But it is a study that's looking primarily at safety. Obviously, we're in patients. So we may learn more about some early efficacy signals, and that would be extremely exciting if that were to happen. But we are primarily looking at safety.

Eric or George, do you want to say anything more about LYT-200?

All right.

Yes. I mean, I -- please go ahead. Eric, please go ahead.

Okay. Sure. Yes. So the trial is a Phase I study, a very typical Phase I study with the new agent. We're looking for safety and tolerability in heavily pretreated patients with solid tumor disease. As Daphne mentioned, we're aiming for a medical conference at the end of the year to present the results.

Our next question comes from Philippa Gardner of Jefferies.

A couple of questions, if I could, please. First of all, maybe sort of from a higher level view. When you look at your Wholly Owned Pipeline, you've got a pretty nice balance across various stages. But I imagine that looking at the lymphatic system must be -- there must be very rich opportunities out there. And so given your cash balance, how are you thinking about sort of expanding the pipeline? Are you looking at bringing in sort of earlier-stage stuff or you may be thinking about later-stage opportunities that could be used to sort of bulk out the pipeline in various places?

And then my second question also on the internal pipeline is just given we recently had some data on LYT-210 AACR. I was wondering if you could just kind of walk us through what you presented there?

Great. Thank you very much,. So regarding the growth of our pipeline, we have 3 exciting research platforms that we think will see -- continue to see the pipeline. And so if we were to bring in any external programs, those would probably be later stage. And I will invite Bharatt to comment briefly on some of the earlier-stage platforms that we have. And then with regard to, I will ask Eric to say a little bit more about the recent poster at AACR. So maybe Eric can go first with the poster and then Bharatt with the pipeline.

Sure. The poster was on LYT-210, which is really against immunosuppressive gamma delta-1 T cells. These are cells that are immunosuppressive and therefore. And what you see is these cells up-regulated and present in a number of different solid tumors.

And what the folks are talked about is the antibody that we created, 210, which is a human IgG1, that is specific to both human and monkey Delta 1. That's important from a development point of view to be able to move it into the clinic because that allows for preclinical toxicology testing of the type that would be needed for filing and going and doing IND-enabling studies.

And then also, we showed high specificity and affinity to Delta-1. And the high specificity is important that it's again Delta-1 and not Delta-2. And also that this antibody combined across Delta-1 and gamma chain pairs given that Delta-1, 2 compare with more than 1 type of gamma chain. And then we also showed the Delta 1 antibodies can induce the therapeutically desired type of B cell killing, which is important again as we think about this as a potential therapeutic agent. And finally, there was data using patient-derived (inaudible) for multiple cancer types, showing that achieve T-cell activation. And Daphne was discussing for 200 some of the data that we had for these types of [PDOTT] experiment.

Thanks, Eric.

Great.

Bharatt?

Yes. So in terms of the pipeline, right, I mean, so as Daphne mentioned, we continue to look at programs that we can advance ourselves in our Wholly Owned Pipeline, either organically through our 3 different platforms that we currently have working on in discovery research, and it has -- one of them has already yielded a clinical candidate, which is LYT-300, it's the oral allopregnanolone, which we hope to bring to file IND later this year. And that is exciting because that's the first program coming out of the lymphatic targeting technology, what we call the Glyph platform. And that also can generate multiple other potential product opportunities in the future, which we are actively exploring.

And then the Orasome platform, which is our oral biotherapeutics technology platform, that also we expect to have some preclinical proof-of-concept data later this year. And depending on the data from that platform, that could then generate significant number of potential product candidates in the future. And to complement that, we also have active sourcing efforts going on, which Eric and his team were heading, where we continuously look at opportunities that we could potentially bring in either preclinical or clinical stage programs that would complement our immunology focus for the Wholly Owned Pipeline. So that's the combination of internal efforts as well as potential to in-license programs and so on a more opportunistic basis.

Our next question comes from Alistair Campbell of Liberum.

Just first question, please, just on LYT-200. I think you shared with me earlier in the year some really intriguing data from Nature Communications basically pointing to an interaction between (inaudible) and PD-1. With that sort of emerging sort of proof-of-concept data in mind, are you aware of other people now sort of focusing a bit more on (inaudible) as a mechanism? And maybe sort of is that beginning to gather attention in terms of people approaching you to maybe think about combination studies further down the line? Or what do you sort of think about that?

And then my second question is just on Vor, which obviously was a successful IPO. I realize you're obviously locked in for a period of time, but with sort of Karuna in mind, presumably given your current financing situation, there's clearly no rush to think about selling this stake. So I just wonder when you look at this, when you think a bit like with Karuna, there are clinical catalyst further down the line you want to hold on for because you still see significant upside in valuation?

Thank you so much, Alistair. It's good to hear from you. So regarding Vor and some of the other founded entities, I think that we do believe that there's a lot of potential growth in these founded entities, and we try to balance the upside potential with our own plans for growth internally. And right now, we're very enthusiastic about the growth potential of both of those entities. And I think what has driven sort of the monetization in the past, the original one was really just to take a little bit of money off the table, obviously, after having seen so much growth and value. And other considerations have been in the past related to our ability to drive forward internal programs that we're really excited about.

So it's kind of a balance, and that's why it's hard to say specifically what our plans will be. But we would just like to reiterate that nobody should think that we -- anything we've done in the past is a signal that we don't have confidence in the upcoming growth with these founded entities.

So -- and with regards to LYT-200 and PD-1, that was really intriguing. I'll have George, maybe say a little bit more about that. And just on a high level, we are the most advanced. So in terms of other programs in this stage, we are the most advanced. But we -- obviously, are seeing more excitement around this as additional data becomes available, particularly the PD-1. So we are, of course, this is becoming more sort of high interest to outside group. But we are really the leader in moving this approach forward.

George, do you want to say anything about at length on PD-1 and that (inaudible) came out?

Sure. Alistair. Yes, so you're referring to the Nature Communications publication that was -- came out in February, showing that galectin-9 was actually a ligand for PD-1, which is really quite intriguing, especially given now that this would be the third ligand that has been identified to be associated with PD-1, the others being PD-L1 and L2 and PD-L1 certainly being clinically validated.

So -- yes, we find that data particularly compelling. I mean right now, the data is just preclinical, and the consequences of that interaction, again, have been dissected preclinically. Ultimately, it depends on how the anti-galectin-9 approach works in the clinic. And as Daphne mentioned, we're at the forefront of this. We'll get our Phase I results by the end of the year, which, again, the trial is designed for safety and tolerability, but who knows? We may see some clinical activity, and we think that, that would -- if that's true, I think that -- we think that, that could spur a lot of interest in...

That concludes the Q&A portion of this webcast. Thank you for your time today.