Jounce Therapeutics, Inc.

Good morning, ladies and gentlemen, and welcome to the Jounce Therapeutics first quarter 2021 earnings conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded at the company's request. I will now turn the call over to your host, Malin Dion, with Jounce Therapeutics. Please go ahead. Thank you, Operator.

Thank you, Operator. Good morning, and welcome to the Jounce Therapeutics first quarter conference call. This morning, we issued a press release which outlines the topics that we plan to discuss today. The release is available in the Investors in Media section of our website at www.jouncetx.com. Speaking on today's call will be our CEO and President, Dr. Rich Murray, who will review our Pipeline Progress and Key Milestones, followed by our CSO, Dr. Dimitri Wiederschein, who will discuss our discovery efforts. Our CMO, Dr. Beth Trehu, will then provide an update on our clinical activities. And lastly, our CFO, Kim Trafkin, will review our first quarter financial results. We will then open the call for your questions. Before we begin, I would like to remind everyone that today's discussion will include statements about our future expectations, plans, and prospects, that constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including the risk factors discussed in our SEC filings. In addition, any forward-looking statements represent our views only as of today, May 4, 2021, and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. With that, I will now turn the call over to Rich.

Thanks, Malin, and good morning, everyone. Johnson's made meaningful progress at the start of 2021 as we continue to advance our two proof-of-concept studies, grow our discovery and development IO pipeline, and add to our strong balance sheet. We're at an exciting point in Johnson's development and remain committed to progressing new mechanisms that target different immune cell types in the tumor microenvironment. Our translational science platform and biomarker approach are integral to our commitment to bring the right therapy to the right patients. I'd like to take a few minutes to provide updates from the quarter. At the start of the year, we announced that enrollment commenced in N8, our phase one clinical trial of our highest priority program, JTX8064, a LIL-RB2, also known as ILT4, inhibitor. N8 is moving quickly through the necessary dose escalation portion of the trial towards the opening of eight tumor-specific expansion cohorts. We plan to include JTX8064 monotherapy as well as combination with our own PD-1 inhibitor, JTX4014, or an approved PD-1 inhibitor. JTX4014 will now be known as pimavelumab, or PIMI. We continue to believe that the myeloid and macrophage biology, harnessed by the potential effect of JTX8064 via the LIL-RB2 mechanism, provides a new opportunity to bring benefit to patients. Enrollment also continues in SELECT. our Phase II randomized proof-of-concept trial of Vopratilumab in combination with our PD-1 inhibitor, Phimi. The key feature of this study is the biomarker selection of patients utilizing TIS-Vopra, an 18-gene signature that includes genes relevant to both CD8 and CD4 T-cell biology. We believe it's clear from our own clinical data, as well as that of competitors, that a rigorous patient selection strategy may be critical to optimize the benefits of an ICOS agonist and a PD-1 inhibitor. We look forward to reporting clinical data from the SELECT trial in 2022. As Beth will mention in more detail, we're also pleased to present two trials in progress posters on both INAT and SELECT at the upcoming ASCO meeting in June. We continue to progress JTX1811 our potential first-in-class antibody designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells. We licensed the program to Gilead in 2020 and remain on track for the IND filing in the first half of this year. Beyond our development programs, we continue to make progress advancing our earlier stage pipeline. Our broad discovery pipeline includes multiple programs targeting diverse immune cell types and PD-1 or PD-L1 inhibitor resistance mechanisms. These are all active, targeted areas for our discovery engine, and we expect to see more valuable novel programs like JTX-8064 and JTX-1811 emerge from our efforts. Additionally, during the first quarter, we added more than $90 million to our ballot sheet through a follow-on offering and through the use of our now-completed ATM program. This capital infusion strengthens our balance sheet and gives us the runway to complete our key proof-of-concept studies while also driving new discovery programs forward. We remain excited for what lies ahead for Jones, with critical milestones laid out for the remainder of this year and beyond. To reiterate, we plan to evaluate safety and determine recommended Phase II dose for JTX8064 and open tumor-specific expansion cohorts in the second half of 2021. Continue enrollment to enable reporting of efficacy and related biomarker data for VOPRA and PIME from the select trial in 2022. Continue IND enabling activities for JTX1811 and anticipate an IND clearance in 2021. And continue to advance our discovery pipeline of potential first-in-class programs with the goal of a new IND every 12 to 18 months. I would like to take a moment now to welcome the newest member of our management team, Dr. Dimitri Wiederschein, who was appointed as Chief Scientific Officer in April. Dimitri has more than 15 years of pharmaceutical industry experience as a scientific leader and drug developer, and brings a broad knowledge of contemporary immuno-oncology approaches, tumor immunology, and cancer biology. His expertise with preclinical target discovery and first in human research will provide invaluable contributions in our work to deliver the right immunotherapies to the right patients. We're excited to have Dimitri on the Jounce team. With that, I'll turn the call over to Dimitri to say a few words.

Thanks, Rich. I'm thrilled to join Jounce at such a pivotal moment in the company's journey to discover, develop, and commercialize important new immunotherapies. After many years of building the oncology and IO pipeline at Sanofi, my goal was to join a vibrant, science-oriented, and fast-paced organization that understands what it takes to succeed in IO, has resources to do so, and is ready and able to forward integrate the company. Coming from a large pharmaceutical company setting and seeing many biotech companies through business development activities, I believe Jounce is that place. With JTX 8064 and JTX 1811 as good examples, we hope to continue to create new important options for patients and value to Jounce shareholders. At our upcoming R&D day in late June, I look forward to sharing more about the exciting science behind our pipeline, translational work, and particularly the opportunities around the myeloid cell focus as exemplified by Lil R family. With that, I'll turn it over to Beth to discuss our clinical programs in more detail.

Thanks, Dimitri, and good morning, everyone. 2021 is a year of clinical execution for jouts. and we remain focused on our two ongoing proof-of-concept studies, INATE and SELECT. These trials are key to our belief that novel mechanisms and biomarker strategies are necessary to bring clinical benefit to patients who do not optimally benefit from T-cell checkpoint inhibitors. I would now like to provide more detail on both ongoing trials, beginning with JTX8064, a LIL-RB2 inhibitor. JTX8064 is designed to reprogram immunosuppressive or M2 macrophages to immune stimulatory or M1 macrophages to enhance or restore anti-tumor immune activity. We view JTX8064 as a macrophage checkpoint inhibitor with the potential to reverse PD-1 or PD-L1 inhibitor resistance as well as to further improve outcomes in PD-1 inhibitor-sensitive tumors, thereby having the potential to provide clinical benefit to a wide range of cancer patients. We are very pleased with the pace of enrollment in the innate trial. Our trial is designed to progress quickly through dose escalation and demonstrate proof of concept in expansion cohorts that will enroll patients with specific tumor types. These tumor types were selected based on a variety of factors, including macrophage biology, potentially predictive RNA signatures, and the opportunity for differentiated development pathways. An important part of our tumor selection process involves an examination of the unmet need and opportunities in both PD-1 inhibitor experienced and naive patients as we explore the best opportunity for JTX8064 to make a difference for patients with cancer. At last month's AACR conference, we presented data describing how expression profiles of LIL-RB2 mRNA, our proprietary tumor-associated macrophage, or TAM signature, and an interferon gamma signature were used to identify tumor types that may benefit most from JTX8064 treatment alone or in combination with PD-1 inhibitors. This data was used to inform the tumor types in expansion cohorts of the innate trial. We remain on track for the opening of eight expansion cohorts, one with JTX8064 monotherapy and seven in combination with PD-1 inhibitors. These planned expansion cohorts will study JTX8064 in three subsets of patients in order to identify the best and most rapid development paths for JTX8064 alone or in combination with PD-1 inhibitors. First, patients who have progressed on PD-1 inhibitors and may now be PD-1 inhibitor resistant. These patients have very few treatment options, and repeat immunotherapies have been largely unsuccessful. We believe that JTX8064 has the potential to restore responsiveness to PD-1 inhibitors and bring the durable benefits of immunotherapy to these patients. Second, PD-1 inhibitor naive patients with tumors that don't typically respond to PD-1 inhibitors. This is also an area of high unmet need in which T-cell directed immunotherapy has not had a significant impact. and we believe that JTX8064 alone or with a PD-1 inhibitor may make immunotherapy a viable option for these patients. Finally, PD-1 inhibitor naive patients with tumors for which PD-1 inhibitors are approved, but there is still much room for improvement. By combining a macrophage targeting agent with a T-cell directed therapy, we hope to improve clinical outcomes beyond what is achievable with PD-1 inhibitors alone. We will provide the details on tumor types and scientific rationale for the expansion cohorts in a trials-in-progress poster at ASCO. Once we have selected the dose and opened these expansion cohorts, we will provide guidance on the timing of data readouts. I would now like to turn to an update on Vopratelemab. and our first biomarker patient selection trial, SELECT. Screening and enrollment is on track to report data from the SELECT trial in 2022. As a reminder, we plan to enroll approximately 75 immunotherapy-naive second-line non-small-cell lung cancer patients who will be selected using the predictive TIS-VOPRA biomarker and randomized to VOPRA plus our PD-1 inhibitor, PIMI, versus PIMI alone. We believe the TIS-VOPRA biomarker will select more appropriate patients for both the CD8-mediated benefit of a PD-1 inhibitor, as well as for the potential CD4-related benefit of VOPRA. We expected approximately 20% of second-line non-small-cell lung cancer patients to be TIS-VOPRA-positive, and we are pleased that screening to date has validated this projection. Details of the select trial will be provided in a Trials in Progress poster at ASCO. Before closing, I would like to take a moment to thank our team, our investigators, and the patients whom we have the privilege to treat. Now more than ever, it is imperative to execute on our mission of delivering long-lasting benefit to cancer patients. We believe that our translational science, biomarker approach, and commitment to new mechanisms targeting different immune cells brings us closer to achieving this target. We look forward to our continued progress in 2021 and to delivering on our important upcoming milestones. I will now turn the call over to Kim for a discussion of our first quarter financial results.

Thanks, Beth, and good morning, everyone. As we reported in this morning's press release, cash equivalents and investments as of March 31st, 2021 increased to $271.3 million compared to $213.2 million as of December 31st, 2020. This increase was primarily due to the $90.8 million in aggregate net proceeds from sales under our follow-on public offering and our ATM offset by operating costs incurred during the period. Turning to the P&L, we recognized $1.5 million in license revenue during the first quarter of 2021, which was comprised of non-cash revenue related to research and transition services performed under our license agreement with Gilead. No revenue was recognized during the same period in 2020. During the first quarter of 2021, we incurred $20.5 million in research and development expenses compared to $19.6 million for the same period in 2020. The increase in R&D expenses was due to increased expenses for manufacturing and IND-enabling activities performed for our development program, offset by decreased clinical and regulatory costs attributable to reduced spending on BOPRA. General and administrative expenses were $7.6 million for the first quarter of 2021 compared to $7.5 million for the same period in 2020. The increase in G&A expenses was primarily the result of increased stock-based compensation expense. Net loss for the first quarter of 2021 was $26.5 million, resulting in a basic and diluted net loss per share of 58 cents as compared to a net loss of 26.4 million for the same period in 2020, resulting in a basic and diluted net loss per share of 78 cents. We are reiterating our financial guidance and continue to expect gross cash burn on operating expenses and capital expenditures for the full year 2021 to be approximately 95 million to 110 million. We have always maintained a strong balance sheet and expect our existing cash, cash equivalents, and investments to be sufficient to enable the funding of our operating expenses and capital expenditure requirements through the second quarter of 2023. The combination of our experienced team, financial resources, and innovative science puts us in a strong position to move beyond our next set of inflection points and continue to execute against our strategic plans and goals. Jounce continues to focus on patients first, and we are proud of the I-O pipeline we are building to address the growing unmet medical need faced by cancer patients. We look forward to updating you on our progress as the year progresses. With that, we would now like to open the call for your questions. Operator?

Thank you. Ladies and gentlemen, to ask a question, you will need to press the start and the one key on your touchtone telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. And our first question coming from the line of Steve Seedhouse with Raymond James. Your line is open.

Good morning. This is Ryan Deschner on for Steve. I just wanted to ask, are you guys seeing any surprises so far in ILT4-treated patients with respect to the pharmacology of the molecule? Or is it, excuse me, translating to humans as expected?

Thanks for the question. We don't usually report on data from ongoing clinical trials. All I can tell you is, as I said, enrollment's going very well. And I think, you know, as we've said, we think our molecule is more similar than different to Merck's molecules. So, you know, we would expect something similar to what they saw in their Phase I study.

Okay. And maybe real quick. Can you talk about the stopping criteria for Select and when the interim analysis is expected?

Yeah, there isn't an interim analysis in Select. Our expectation is to complete the study and report data in 2022. Okay, thank you very much.

You're welcome.

And our next question coming from the line of .

Thank you. This is RK from . I have a couple of questions. Beth, you know, regarding the innate study, which is going to have about seven different combinations, between AD64 and a PD-1 inhibitor, and in the press release you have that it could be either 4014 or an approved PD-1 inhibitor. How would you, you know, what is the criteria in deciding which expansion cohort will get what PD-1 inhibitor?

Sure, that's a great question. As I mentioned, we'll have a trials in progress poster at ASCO. That's where we will introduce the specific tumor types that we're including in the study. And then later in June, we expect to have an R&D day, and that's when we'll get into a little bit more detail. We'll describe which PD-1 inhibitor in which cohort, the scientific rationale for each cohort, more detail about the lines of therapy and that kind of thing for each cohort. Stay tuned. We'll be providing detail on all of that very soon.

Sure. And then just to follow up within that trial itself, you know, you were talking about the three subgroups of patients that you're going to be investigating. My question is more on the PD-1 naive subset and also the PD-1 naive but minimal to poor response subgroup. Within those subgroups, I don't know if it is too early in the expansion cohort, but would you think about how to sequence the combination? Or that is not a question now. You just want to go ahead and just do a straight combination and then think about sequencing the drugs later. Okay.

Yeah, we believe giving them on the same day makes sense. Merck certainly saw very encouraging data in their study where the drugs were given on the same day. So we obviously, as you know, we collect a lot of pharmacodynamic biomarkers in our study as well as the potential predictive biomarkers. So we certainly will be analyzing our PK and our receptor occupancy data and and the PK of the companion molecules throughout the study to see if there's any suggestion that we would need to do sequencing. But maybe I'll ask Rich to comment on that as well. Rich, I think you're on mute.

Yeah, thanks, Beth. Sorry about that. Okay, yeah, thanks for that question. Just to follow up on Beth's a little bit, I think as we continue to study the mechanism, you know, we really believe that there's kind of the simultaneous action of these antibodies. And, of course, they'll be on board in terms of dosing, you know, throughout the dosing cycle. So, you know, we'll still pursue the mechanistic kind of underpinnings of what we see, but I think all that work really translates into dosing molecules on the same day.

And that being said, they're both inhibitors. So, you know, once you achieve that concentration that maintains, you know, inhibition of binding to the ligand, at that point, I don't know that sequencing really becomes that relevant.

So we'll see. Yeah. One last question for me before I step back into the queue. Beyond 8064 and 4014 and obviously 1811 will be moving on into the hands of Gilead come second half. Thinking about early stage pipeline, I understand you'll talk more in June in your R&D day, but with Jones' experience of bringing novel molecules to the forefront, what sort of molecules should we expect that you could be unveiling later in the year?

Yeah, sure. I think what we'll give, as Dimitri alluded to, in late June is, you know, the kind of direction of where we anticipate new programs to come from. You know, we've been stating we're very interested in the myeloid-related cell biology. You know, LIL-RB2 in 8064 is our first example. But there are other little family members, other mechanisms associated with overall myeloid cell function that we think are very important areas to pursue. So we'll provide a bit of depth on that, and Dimitri has hit the ground running here, and we'll provide that update in late June. And then we'll stick to our kind of pattern of how we identify specific molecules once we're at the stage of a development candidate then we will kind of announce that kind of progression as things move into the IND-enabling stages. So stay tuned. A lot of focus on the myeloid cell biology. We're very excited about that. And, again, stay tuned for late June on that one.

Thank you, Rich, and the team. Thank you. Sure. Thanks.

Our next question coming from the line of Colleen Cussey with Bayer, DLN is open.

Hi, good morning. Thanks so much for taking our questions. Is there any update you can provide on how many escalation dosing cohorts you've cleared? And then for the ASCO update, can we expect any safety data from the NIH study, or will that just be focused almost on the trial design?

Yeah, hi, Colleen. It's Beth. So in terms of the dose escalation cohorts, I think what's important is we are still on track to open the expansion cohorts, both monotherapy and combination, in the second half of the year. So other than that, I'm not going to go into detail on those, but we're doing really well. We're on track. We will be opening expansion cohorts in the second half of the year. And regarding the Trials in Progress poster, ASCO does not allow inclusion of any data in these posters. They really have to be strictly a description of the scientific rationale, the study design, that kind of thing.

Great. That makes sense. That's helpful. Thank you. And in light of the interesting data that you guys presented at AACR, can you comment on how you're thinking of incorporating potential biomarkers into the expansion cohorts of the N8 study? I guess could some of those expansion cohorts potentially use biomarkers as a screening criteria, or will that still be more exploratory?

Sure, that's a great question. So at this point, in all the expansion cohorts, we're collecting both archival tumor tissue and a fresh biopsy pretreatment. And we will be screening those for a whole panel of potential predictive biomarkers that include both RNA signatures, some of which we've commented on in our prior posters, and also some IHC. So we have... I think we're in a great position because we have a number of these biomarkers that we've already identified, so we're going to be testing them retrospectively, looking back at the samples and doing analyses to see if they correlate with clinical outcomes. If we see something that looks like it correlates, the next step would be to either enrich or select. So I would say what you could look at these expansion cohorts now is the hypothesis generating, and then the next stage would be something where we would either enrich or select with whichever one of those biomarkers looks the most promising. Rich, did you want to add anything?

Yeah, yeah. Just as a reminder that biomarkers that Beth is speaking to, That really is a kind of a collected set of what we think are the appropriate either PD or potentially predictive biomarkers that have come directly from our mechanistic and tumor-related work within jobs. So we kind of serve up that set that we think are worthy of being tested, coordinated to the trial, as Beth mentioned. And should we find those correlations with clinical data, then we move to the next stage.

Great. That's really helpful. And if I can just add one more quick one. Are there any other potential combination regimens that you think could be interesting with AD64 beyond PD-1?

Sure. And, you know, that's something that I think you know, Colleen, even after we're in the clinic, our research teams are still very, very active on the same, you know, program. So that's an active area of investigation. Thank you for that question.

Great, thank you.

Our next question coming from the line of BORA's speaker with Colin Ylanis-Holtman.

Great, thanks for taking my question. My first one is on 8064. You mentioned that your drug is relatively similar to Merck's drug. Just wondering if you could also maybe compare in terms of the patients you're enrolling in the innate studies, how that may differ from the patients that Merck is enrolling in their initial studies.

Sure, Boris. Hi, Scott. So in the dose escalation phase, like Merck, we're enrolling all comers, no specific tumor types, no kind of enrichment or selection. So I would say the dose escalation parts of the study are probably very similar. Then we are doing these expansion cohorts in specific tumor types, and we're being very specific there, down to the line of therapy, the type of prior therapies, allowed for each of those. Merck is also doing expansion cohorts in their study. They opened nine expansion cohorts in January of 2020, and we don't know as much about those as we know about the dose escalation patients. What I can say is in the dose escalation, we will have far fewer patients than Merck did. because we were able to leverage some of their data and reduce the amount of dose escalation cohorts. However, once we get into the expansion cohorts, those are really dictated by the specific eligibility for each cohort. Merck has theirs. We have ours. So unless we do cohorts that are in exactly the same patient population, I would expect them to be potentially different. And I'll finish just by saying, Since the molecules do appear to be quite similar, we believe that the way that we can differentiate is through the tumor types that we're exploring as well as our biomarker strategy. Gotcha.

Maybe speaking about biomarker, switching to Vopra, for the TIS-Vopra biomarker, what clinical development would you have to do in order to get the diagnostic test for the biomarker approved?

Sure. When you develop a drug that's with a companion diagnostic, the companion diagnostic is actually developed by the company that makes the biomarker. But it's a very collaborative process. This is done on the nanostring platform, so it's a well-recognized process. And, you know, we know what the development takes. There's a whole path through a different part of the FDA. that's, you know, well mapped out. So if that's what we do going forward, there's no particular extra complications there. We know what we need to do to take that forward. Rich, did you want to add anything?

Yeah, yeah, maybe just add to kind of on the business side of that, you know, there are kind of different stages of investment that one would take in the kind of journey to get to a companion diagnostics. So clearly we're at the clinical stage. We're, you know, running the assay in a manner that's consistent and appropriate with that. But we'll be able to, you know, stage gate our investment on that kind of path, which would then go to the next stage, I'm sure the data warrant, of, you know, kind of readiness for, you know, starting on the route to readiness for commercialization of that biomarker and assay.

Great. Thank you very much for taking my questions.

You're welcome.

Our next question coming from the line of Nick Abbott with Wells Fargo Securities. Your line is open.

Good morning. Thanks for taking our questions. And, Dimitri, welcome to the team. I look forward to meeting you virtually later on in the year. A couple of questions for me. First, on SELECT, can you remind us if there's a correlation between the TIS and VOPR signature and any oncogenic drivers in lungs? I'm just sort of thinking of maybe that control. Obviously, you have one variable, which is it's in TISBO for positive patients, for which we don't know what a PD-1 inhibitor will do in that subset of patients. But then on top of that, I'm wondering what spectrum of different oncogenic drivers you might expect to see.

Yeah, I think I can take that one there. You know, I think we don't have a TIS-VOPRA-related kind of correlation to specific oncogenic drivers. However, we know, of course, that there are oncogenic drivers in these patients, and they will, you know, follow that route to a specific therapy should they have the right kind of, you know, kind of the right kind of driver mutation and such. But as we look at that kind of potential overlap with TISVOPRA, TISVOPRA is really telling us much more kind of the state of activation of the CD8 cells and we believe the CD4 cells. So that's really kind of the uniqueness about this biomarker. We're kind of getting both angles on that, CD8 and CD4. And then, you know, whether that kind of overlaps with, you know, mutations or not, we think the TIS-VOPR score makes the patients more likely to be benefiting from this combo therapy. So we don't have that kind of direct correlation to the oncogenic drivers. Of course, if those patients have those drivers, they will be going down the route of a particular line of therapy for that particular drug.

Yeah, that's right. In addition... Yeah, in addition, Nick, we actually exclude patients with EGFR mutations, that being the biggest class of oncogenic drivers that generally patients with those mutations don't do as well with PD-1 inhibitors. So we're excluding them. And then, as Rich mentioned, the patients with other drivers would be likely to go down a different path of therapy targeting the mutations.

Mm-hmm. Yeah, I think we'll also learn, Nick, as we get these larger data sets from all the patients enrolled, how all these things kind of overlap or not with each other. So that kind of data will emerge as the data set fills out.

Okay, thanks. And then on AD64 for that PD-L1 experience set of tumors, Do you think there's a difference in the role of, you know, myeloid cells in the settings of primary or acquired resistance to PD-L1 inhibitor? And how do you think about studying both those populations potentially in the expansion cohort to the NAIT?

Yeah, I think that's a great question. I'm not sure there's enough data right now to know the difference between which cell types are playing a primary role in primary and acquired resistance, and that's why we're planning to study those two groups of patients. So the patients who have failed a PD-1 inhibitor, you could say some of them might be primary, some of them might be secondary, and we'll certainly be collecting that data. And then the tumor types that are PD-1-naive, that where PD-1 inhibitors aren't approved, you could think of those as kind of primary PD-1 resistance. So we think it's important to look at both, and we'll be analyzing the data based on what kind of resistance they have.

Perfect. Thank you very much.

You're welcome. Our next question coming from the line of Zeped Chalda with Roth Capital. Your line is open.

Good morning, guys. Thanks for taking my question. The first one here is just on the enrollment for Select.

I know you can't say much, but I was just wondering if you're finding second-line IV naive patients as easily as you thought you would by going XUS. And then another follow-up to that is that, I mean, I know that there's not too much that can be done, but I was just wondering if you could perhaps while we wait for this data, look at accruable tissues from tissue banks to learn a little bit more about the TIS blood pressure signature, because I believe most of the original analysis was done based on tissues from the ICONIC study.

Yeah, that's a great question, Segba. We also worked with NanoString to get some additional TIS data, but to your point, first of all, We did have some setbacks related to COVID. I really think that COVID impact is really the only negative impact on the study. In terms of the screening rate, we're quite happy with that. And also, we've been very pleased that, as we predicted, 20% of these patients are TISPO prepositive. So that was our prediction based on prior analyses, and that's what we're seeing in the study. So the patients are definitely there. There are a lot of places where patients don't have access to PD-1 inhibitors. We have to screen, you know, five patients to find one. But that's actually not too bad when you think about the rates of some of the other target, you know, the biomarkers for targeted therapies, which are in the single digits.

Thank you.

And just another follow-up question. Yeah, sorry, Zach, but maybe to the other part of your question. You know, there is TIS data available, and thus we can kind of dial in the TIS-VOPRA, you know, specific cutoff point in other types of tumors as well. So kind of, you know, more to come on that in terms of the science, but it's not unlike the sense you get. Certain tumor types are more highly infiltrated, have more activated immune cells. Other tumor types are down the other end of the spectrum. and may not have that. So that's kind of the way to think about TISVOPRO.

Thank you. Very helpful. And then just a follow-up here regarding your comment about, you know, multiple cohorts from 8064. Just curious because I got excited when you said multiple cohorts. I was thinking multiple shots on goal year. But in terms of, you know, the cohorts, I know you can't say too much now because you have the child in progress posted. But from a risk perspective, I was just curious, you know, how much are you pushing the envelope with some of the cohorts in terms of, you know, how much, you know, you really think you have data to support it versus the others where it's just like one of the middle things that people typically do with cohort expansions? Sure.

So I think actually all of the cohorts are really grounded in the science. So I think they all have an equal potential to, you know, to show good results. And then what we've done is, you know, as we've described, of those seven combination cohorts, some of them are in the PD-1, you know, experience, some of them are PD-1 naive, and, you know, some of them are in tumor types that respond to PD-1, some are in tumor types that typically don't. So I think we've got a really good distribution, and the goal is to really cast a wide net, but all based on the science. All of these are absolutely rooted in the science, and then they're just exploring different settings in which that mechanism might work.

Thank you. And I think this is related to a follow-up question as well, just trying to understand what cells might work, you know, and things like that, what cells might drive resistance and things like that. So I think sometimes you do have to go really large. I was just wondering if you're going to be doing such large studies in the future because you're just trying to, you know, like you said, cast a wide net. Is that what we're going to expect from your other programs, you know, just really huge studies? And then just so I can hop off, follow up here. you guys seem to still be the only one that's focused on, you know, really going after novel biomarkers. So a follow-up to Boris's question is just how complex is the biomarker strategy, you know, from a development and what you anticipate from a commercialization perspective? Because I'm just wondering why, you know, not a lot of people are still, you know, actively pursuing novel biomarkers beyond the ones that we typically know, like PD1s.

Sure. So I think PD-L1 is a good example of where a biomarker made a huge difference. It's really what catapulted Pembrolizumab or Keytruda forward. You know, if the data is strong enough without a biomarker, that's fine. I mean, if a large percentage of your patients respond and do well, then you don't need a biomarker. We just think it's really important to incorporate it early on in case you you really do need it to find the patients that benefit. And obviously you don't want to treat people with something that's not going to provide benefit to them. So you want to find the right patients, you know, the right therapy for the right patients. Rich, did you want to add to that?

Yeah, maybe another way to think about this is the biomarkers that we now take for, you know, as being relatively common, we're all directed at PD-1 inhibitors, CD8 cell biology, T cell activation and such. And as you know, many of our discovery programs are pointed at different immune cell types. And so there's, you know, a set of biomarkers that may be, you know, become more established for the myeloid cells and for the macrophages and perhaps other cell types. So I think that's perhaps the way to see this kind of, you know, cascade of biomarkers. They link to certain cell types and behaviors and biology of the different cell types.

And then in terms of the clinical development program, Zygma, for a molecule like this, it is possible that, you know, it could be active in multiple different tumor types if you look at the PD-1 inhibitors. So this could develop into a very large development program, yes. I mean, we're planting the seeds in, you know, in all these different cohorts now. There are additional things that we might want to look at in the future. We could expand these within the study. We could do additional studies in these tumor types. I think we're planting the seeds for a potentially very large development program.

Thanks, guys, and congrats again on the progress.

Thank you. Thanks.

And as a reminder, ladies and gentlemen, to ask a question, please press star 1. And our next question coming from the lineup, Ted Tenthoff with Piper Sandler, ULNS Open.

Great. Thank you very much. So quick question. I'm very much looking forward to the post-dart ask as well as the R&D. I think that's going to be a great update. Is the plan with respect to the 8064 or innate expansion studies to do signal finding, and would those cohorts be able to be expanded on success and potentially inform registrational paths?

Great question, Ted. Yes, these are initially for signal finding, but each expansion cohort is actually designed as a Simon two stage design. So we have particular triggers that would lead to further expansions. And, you know, if we see encouraging data, then the next step to see if they could potentially become registration trials would obviously be discussion with FDA. but we do think some of them may have that potential if the data is strong enough.

Great. And I like the new name, PIMI.

Did you have another question?

No, I was just saying I like the new name for the PD1, PIMI.

Oh, PIMI. Yes.

Thanks, guys.

Okay, thank you.

That's all the time we have for our question and answer session today. Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may now disconnect. Have a good day.