Jounce Therapeutics, Inc.

Good day, ladies and gentlemen, and welcome to Jounce Therapeutics' third quarter 2021 earnings conference call. At this time, all participant lines are in a listen-only mode. Later, we'll conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference is being recorded at the company's request. I will now turn the call over to your host, Eric Laub, with Jounce Therapeutics. Please go ahead.

Thank you, operator. This is Eric Lau, Vice President of Investor Relations at Jounce Therapeutics. Good morning and welcome to the Jounce Therapeutics third quarter 2021 earnings 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 and media section of our website at www.jouncetx.com. Speaking on today's call will be our CEO and President, Dr. Richard Murray, who will review our pipeline progress and key milestones, followed by our CMO, Dr. Beth Trehu, who will provide an update on our clinical activities. Our CSO, Dr. Dimitri Vetershin, will then discuss our discovery efforts. And lastly, our CFO, Kim Drakken, will review our third 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 purpose of the safe harbor provisions under the Private Securities Litigation and 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 represents our views only as of today, November 4th, 2021, and should not be relied upon as representing our views 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'll now turn the call over to Rich.

Thanks, Eric. Good morning, and thank you for joining us today. Johnson's had a very productive quarter as we've made significant progress across all areas of the company. We continue to build momentum as we head into the new year with data expected in 2022 from two ongoing clinical studies, new candidates progressing from our active discovery efforts, and a cash runway that allows us to reach new inflection points. We are pleased to report that we are now actively recruiting patients in the monotherapy and combination therapy expansion portion of the innate study, testing JTX8064, plus or minus pimavalimab, our own PD-1 inhibitor, in eight distinct cohorts across seven tumor types. We continue to advance patient enrollment in our select study. which employs our stringent patient selection strategy and have continued our commitment to build our discovery pipeline. We're at an exciting time in Johnson's development and remain committed to progressing new mechanisms that target different immune cell types within the tumor microenvironment. This is now evident in our myeloid and macrophage programs and our program licensed to Gilead, which targets T regulatory cells. We also believe Johns represents the next generation of immuno-oncology by unlocking a precision medicine approach through the continued execution of our translational and biomarker efforts. Biomarker selection and targeting key checkpoints on different immune cell types not only differentiates us, but is integral to our mission to bring the right immunotherapy to the right patients. At the beginning of this year, we announced that enrollment had commenced in an eight. the clinical study of JTX8064, our highest priority program. JTX8064, an inhibitor of the macrophage checkpoint LIL-RB2, also known as ILT4, is being tested as a monotherapy and combination therapy along with primivalumab, or PIMI. We move quickly through the necessary monotherapy and combination therapy dose escalation for safety in all comorbid cancer patients. while establishing safety and PKPD to allow for dose selection. We determined 700 milligrams as the preliminary recommended phase two dose for the mono and combo expansion cohorts, and we recently announced enrollment for monotherapy and combination therapy expansion in well-defined patient populations in eight cohorts across seven tumor types. We look forward to delivering further milestones with this program and reaffirm our belief that the myeloid and macrophage biology targeted by GTF-8064 via the LLRB2 mechanism provides a new opportunity to bring benefit to patients, especially patients with PD-1 inhibitor-resistant tumors. As we've previously mentioned, these patients tend to have few therapeutic options and represent a growing patient population. due to primary or acquired resistance to prior PD-1 inhibitor treatment. We anticipate presenting the first clinical data from this program in 2022. Patient enrollment continues to advance in the SELECT study. Our Phase II randomized proof-of-concept trial of ovotelamab, our ICOS agonist, in combination with PIMI. The key feature of this study is the biomarker selection of patients utilizing TIS-VOCRA, an 18-gene signature that includes genes relevant to both CD8 and CD4 T-cell biology. We believe from our own clinical data and from others that a rigorous patient selection strategy may be critical to optimize the benefit of an ICOS agonist. We look forward to reporting clinical data from the select trial in 2022. We ended our quarter in a strong financial position and are situated to fund our two wholly-owned proof-of-concept studies, Innate and Select, to pass their reflection points while continuing our robust novel discovery efforts, identifying and progressing new mechanisms that target a diverse set of immune cell types within the tumor microenvironment. With a goal of a new IND every 12 to 18 months, we are on track to nominate another development candidate. In June, John successfully opened the IND for GS1811, formerly JTX1811. And in August, the clinical study was initiated by Gilead. We are extremely pleased to now have four internally developed candidates in the clinic in the past five years. We remain fully committed and on track to achieve all the milestones set out for 2021, from the clinic to our discovery efforts. Before turning the call over to Beth, I'd like to welcome back to Chounce, Jigar Raythapa. In September, we announced that Jigar joined our board of directors. His experience and skills are highly relevant and synergistic with the needs of our board. As a former team member of Chounce, Jigar has an intimate working knowledge of our science, as well as an understanding of what we are working to achieve. We look forward to his continued contributions now as a board member. I'll now turn the call over to Beth to provide a clinical update. Beth?

Thanks, Rich, and good morning. I'm extremely pleased at the progress and continued execution we have made in both our innate and select clinical trials. Before getting into detail on our ongoing proof of concept studies, I'd like to emphasize a point Rich made about cancer patients in need of better options. Unfortunately, there are far too many patients still not benefiting from approved T-cell-based IO therapies. With these patients in mind and our goal of bringing the right immunotherapy to the right patients, we are enthusiastic about the potential for JTX8064 as a macrophage checkpoint inhibitor to improve clinical outcomes in patients with both tumors that are sensitive and resistant to PD-1 or L1 inhibitors. Both the innate and select trials are consistent with 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. Turning first to JTX8064 and our innate study, we believe targeting immune cells such as macrophages has the potential to address the greatest unmet need in immuno-oncology and bring effective treatments to patients with TD1 inhibitor-resistant tumors. By identifying and inhibiting key checkpoints of the innate immune system, new populations of T cells can be primed and directed to the tumor, something T cells alone cannot do. For patients, this might mean a more comprehensive immune response, and one that may overcome that significant barrier of treating TB1 inhibitor resistance or non-responsiveness. This substantial unmet need is why we consider JTX8064 to be our highest priority program. JTX8064 aims to convert immunosuppressive macrophages to an anti-tumor state and create a bridge between the innate and the T-cell arms of the immune system. As a reminder, the innate trial is divided into four parts. Part one is JTX8064 monotherapy dose escalation in all comers solid tumors. Part two, JTX8064 plus PIMI dose escalation in all comers solid tumors. Part three, JTX8064 monotherapy expansion cohort in PD-1 naive ovarian cancer. Part four is JTX8064 plus PIMI in seven tumor-specific expansion cohorts. As planned, we moved quickly through the dose escalation of the innate study, and we are proud of the efforts our team made to accomplish this. With the dose escalation of both mono and combo completed, we are now enrolling patients in the important proof-of-concept portion of the innate monotherapy and combination expansion cohorts. The expansion cohorts will study JTX8064 in three subsets of patients in order to identify the most rapid development paths for JTX8064 alone or in combination with PD-1 inhibitors. First, patients who have progressed on PD-1 inhibitors and are now PD-1 inhibitor resistant. These patients have very few treatment options, and repeat immunotherapies have been largely unsuccessful. Indications we have targeted for this patient population include triple negative breast cancer, cutaneous squamous cell carcinoma, non-small cell lung cancer, and clear cell renal cell carcinoma. 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. Indications we have targeted for this patient population include ovarian cancer and sarcoma. Finally, PD-1 inhibitor-naive patients with tumors for which PD-1 inhibitors are approved, but there is still room for improvement. The indication we have targeted for this patient population is frontline head and neck squamous cell carcinoma. Earlier this year, we shared our translational approach to defining disease areas of interest for JTX8064 based on analyses of the tumor microenvironment across multiple tumor types. We have taken these disease areas of interest and defined specific indications to include in the expansion stage of Innate based on biology, unmet need, competitive differentiation, and consideration of PD-1 or L1 inhibitor sensitivity and resistance. We believe it is important to investigate this new and exciting mechanism in the three distinct patient populations mentioned previously. Proof of concept expansion cohorts in Innate Follow assignment two-stage design with the potential to enroll up to 29 patients per combination cohort and up to 47 patients in the monotherapy cohort if pre-specified criteria are met. And they will also assess pharmacodynamic and potential predictive biomarkers to guide future development, aligning with Jones' philosophy of developing the right immunotherapies for the right patients. As data emerges, we will have the opportunity to explore other indications and combinations with JTX8064 as well. Importantly, the combination expansion cohorts in ANAPE allow us to potentially take two Jones molecules, JTX8064 and PIMI, through to registration. Next year, we will guide on when and how we plan to release the data. Now turning to SELECT, where screening and enrollment continue to progress well. SELECT is our Phase II randomized proof-of-concept trial of Bopratelemab in combination with our own PD-1 inhibitor, PIMI, in approximately 75 immunotherapy-naive non-small-cell lung cancer patients who will be selected using the predictive TIS-BOPRA biomarker and randomized to BOPRA plus PIMI versus PIMI alone. We expected approximately 20% of these second-line non-small-cell lung cancer patients to be TIS-VOCRA positive, and screening to date continues to validate this projection. The essential feature of this study is a rigorous biomarker selection of patients utilizing TIS-VOCRA, an 18-gene signature that includes genes predictive for both of PD-1 inhibitor response via CD8 cells, as well as the unique pharmacodynamic effect of Vopra via CD4 cells. We believe this biomarker could represent a precision medicine approach in IO. We are pleased with how enrollment is progressing and are on track to share data in 2022. I would like to take a moment to thank our team at Jounce, our investigators, and the patients who we have the privilege to treat. Now more than ever, I believe it is imperative that we execute on our mission of delivering long-lasting benefit to cancer patients. 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 this year and next and to delivering on our important upcoming milestones. With that, I will now turn the call over to Dimitri to discuss our ongoing discovery efforts. Dimitri?

Thanks, Beth. We focus on the utilization of our translational science platform to address the problems that patients with cancer are facing today, namely resistance to T-cell checkpoint inhibitor therapy. We believe that our ability to dissect the tumor microenvironment the molecular level using immune cell type specific gene signatures will lead us to targets that may be important for overcoming resistance to checkpoint blockade. JTX 8064 serves as an example of our integrated biomarker approach from discovery through development. This approach is key to the value generating programs we offer soon. We are confident that the little RV family represents attractive immune oncology targets with the potential to improve upon and restore responsiveness to P1 or L1 inhibitors. As disclosed earlier this year, we're rapidly advancing two additional little RV family programs through discovery, one targeting little RV1 and the other targeting little RV4. We are on track to nominate our next development candidate within the little RV family. In addition, we're now leveraging highly specific LIL-RB targeting building blocks to generate multi-targeted biologics that we're exploring preclinically. To date, our discovery efforts have been very successful and value-generating. Our scientists and broader research teams are steadfast in their commitment to bring novel therapies to patients in need. We're very proud of their work. and I look forward to sharing updates on our productive discovery engine in the future. I will now turn the call over to Kim for a discussion of our third quarter financial results. Kim?

Thank you, Dimitri. As we reported in this morning's press release, cash, cash equivalents, and investments as of September 30, 2021 increased $249 million compared to $213.2 million as of December 31, 2020. The September 30, 2021 cash balance includes the recognition of a $25 million milestone received from Gilead in the third quarter. Turning to the P&L, no revenue was recognized during the third quarter of 2021 or 2020. During the third quarter of 2021, we incurred $23.3 million in research and development expenses compared to $18 million for the same period in 2020. The increase in R&D expenses was due to increased clinical and regulatory expenses for innate and select manufacturing activities performed for our development programs and increased payroll and stock-based compensation expenses. General and administrative expenses were $6.9 million for the third quarter of 2021 compared to $7.1 million for the same period in 2020. The decrease in G&A expenses was primarily a result of decreased professional fees offset by increases in other administrative costs. Net loss for the third quarter of 2021 was 30.1 million, resulting in a basic and diluted net loss per share of 59 cents as compared to a net loss of 24.9 million for the same period in 2020, resulting in a basic and diluted net loss per share of 73 cents. The increase in net loss is attributable to increased operating expenses, and the decrease in the net loss per share is attributable to an increased number of shares outstanding as compared to the same period in 2020. We are narrowing our cash burn guidance and expect growth cash burn on operating expenses and capital expenditures for the full year 2021 to be approximately $100 million to $110 million ending 2021 with approximately 220 million. We 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 third quarter of 2023. I'll now hand it to Rich for some final words.

Thanks, Kim. In combination of our experienced team, innovative science, and financial resources, puts us in a strong position to move beyond our next set of inflection points and continue to execute our strategic plans. Johns continues to focus on patients first, and we're proud of the IL pipeline we're building to address the growing unmet medical need faced by cancer patients. Before closing, I'd like to take a moment to recognize the efforts our team makes every day and congratulate them on our fourth IND and all the advances we've made across our pipeline. Additionally, we're fortunate to have such dedicated collaborators and clinical investigators that are true partners in our mission. We have an exciting upcoming year with important clinical data expected, and we look forward to updating you on our programs. With that, we'd now like to open the call for your questions. Operator?

Thank you. To ask a question, you would need to press star then one on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Ted Tinoff with Piper Sandler. Your line is now open.

Great. Thank you very much. Appreciate the update. So much going on and appreciating innate data next year. I wanted to ask my question on select and just get a sense for expectations around timing and sort of what you see as the bogey there and what potential next steps could be for ICoS PD-1 combo. Thanks.

Thanks, Ted. This is Beth. I'll reiterate, as we've said, we'll have data on SELECT next year, and it will be the final study data, the primary endpoint, and all the secondary endpoints of the combo with BOPRA-PIMI and the PIMI alone arm. And as you may recall, this study was designed to be a proof of concept, but our intention is that the next study to follow this one will be a registration study if the data supports that. We believe the data that we generate from this study will give us all the information we need to design our randomized phase three trial for registration.

And do you see opportunities to, again, obviously it's early and it will be data dependent, but to pursue this combination beyond lung?

Yes. Our belief, as with, you know, IO agents in general, is The data from one tumor type can be very informative for other tumor types, and we believe that this combination of GOPRA plus PIMI plus the biomarker is something that could be applied broadly across tumor types where PD-1 inhibitors are used, but there's room for improvement with better patient selection and the addition of a CD4 T-cell targeting agent. And remember, in Select, we found that about 20% of the patients are TISPO prepositive. And, you know, we'll be looking across other tumor types. We have some data on the prevalence in those as well. But I think that's, you know, exciting that we're really honing in on the percentage of patients who are most likely to benefit as opposed to some other biomarker selection like PD-L1. which kind of eliminates the bottom 20%, we're really targeting the top 20% of patients who are most likely to benefit from this therapy.

Yeah, and one other one, sorry to take so much time and focus on select and this mechanism for a moment, but is there a potential, too, for triple combination therapy? I know that's kind of moving the ball further down the field, but as you guys evaluate all the data, and this is even before the select data readout, you know, are there other mechanisms that might make sense to add to this already co-STEM and checkpoint inhibitor or STEM and inhibitor?

Yeah, that's a great question, Ted. I think the first part of the answer to that question is the safety of the combination of BOPRA plus PINDI is, you know, has been, you know, as we've shown with Vopra and Nevo in the ICONIC trial, and even with Vopra and IPI in eMERGE, Vopra does not add any toxicity to checkpoint inhibitors, so that certainly opens up the possibility for taking those two drugs together and adding additional drugs. As with everything we do, any new combinations would be very, very science-driven And the same goes for any additional combinations that we may consider with JTX8064.

Yeah, I just make a quick comment. I think part of that question also is very much all the different cell types in the tumor environment that we think really lead to the logical combination. So PD-1 on the T cells, you know, we're going up to the macrophages. And, you know, we kind of continue to push that cell type specific biology that we think will lead to the best combinations.

Makes a lot of sense. Thanks for all the time.

Our next question comes from the line of Boris Peeker with Cowan. Your line is now open.

Great. My first question is on 8064. I'm just curious, did you see a dose response or how did you establish the recommended phase two dose?

Sure. So this is a classic inhibitory monoclonal antibody. And so the recommended phase two dose or the dose that we're using for continued development is based on receptor occupancy and PK. And so using the data from both of those assays, we're able to determine that at 700 milligrams, which is the dose we're taking forward, patients will have full receptor occupancy through the entire three-week dosing cycle. we actually saw full receptor occupancy and the requisite PK data at 300 milligrams every three weeks. But we really wanted to optimize both the percentage of patients who would have full receptor occupancy given potential interpatient differences and also optimize the amount of receptor occupancy in the tumors, which may be different from what you see in the peripheral blood. So the choice of the dose was not based on any clinical data other than PK and receptor occupancy and, of course, safety.

Got it. Okay. And maybe on the select study, can you remind us again how the TIS work for biomarker works? And specifically, I'm just thinking how it can be scaled up from the clinical scale to a commercial scale market.

Sure. So it's currently an 18 gene RNA signature. It's done on the NanoString platform, but you have asked a very important question and something that we're spending a lot of time and effort on is how to make this something that is scalable for commercial use and also make it easier for patients and physicians. So that's in the works, but you know, the nanostream platform is something that's pretty widespread, and so we believe that it's, you know, very feasible to take this forward as a companion diagnostic. Do you want to add anything, Rick?

Yeah, I think, Boris, you know, that's all kind of gated accordingly and in pace with the clinical data. So the next As we're using it now in the clinic, that kind of next step to really take that forward, coordinated with the next step in clinical, would then be, you know, moving into that, you know, more commercial realm of how to use the biomarker.

Great. Thank you for taking my questions. You're welcome.

Our next question comes from the line of Stephen Siebhaus with Raymond James. Your line is now open.

Good morning. Thank you. As you guys know, the phase one data for Merck's IL-C4 inhibitor was recently published, and I know you look closely at that paper. But I just wanted to ask if you could share your thoughts on the data in that paper and what either supports or contradicts, you know, any of your expansion cohort choices or your hypotheses regarding the mechanism.

Thanks. Thanks, Steve. I think in general, the Merck data as published in the recent paper, is completely supportive of our approach. We believe the kind of biology that they're following in terms of the tumor types that they're exploring and the data that they saw really is very similar, if not identical, to the biology that we're following. And I think we were very pleased to see it published. We're really encouraged by the data that they've shared. We remain super excited about this mechanism. And I think in particular, their data continues to reinforce that this is a mechanism that may reverse PD-1 inhibitor resistance and be able to increase the number of patients who can benefit beyond those who just respond to PD-1 inhibitors. Dimitri, do you want to say something about the biomarker?

Yeah, thanks, Beth. I think, as Beth mentioned, with our hypothesis around LRB2. As we disclosed and mentioned during our R&D day a few months ago, CD163 is a marker of immunosuppressive macrophages, and it is a negative prognostic marker in many cancers. I think that's very consistent with the Merck messaging in their manuscript. And we've also shown that the ratio of LRB2 specifically to the interferon gamma signature, which is the marker of tumor inflammation, could be a negative predictor of response to PD-1 inhibitors. And again, I think that's very consistent with what Mark has shown. You know, we're looking forward to analyzing biomarker data from INATE, where we have many opportunities to assess potential predictive biomarkers. We'll be looking at them individually as well as in relation to each other and correlating that with clinical efforts.

And maybe I'll just mention that when we do report the data from the expansion cohorts in innate, we will have the potential predictive biomarker and the pharmacodynamic biomarker data included with the clinical data.

Great. Thank you.

Our next question comes from the line of Corey Kasimov with J.P. Morgan. Your line is now open.

Hi, guys. Thanks for the question. This is Tiffany on for Corey. Just one on innate. How has trial enrollment gone across your eight expansion cohorts? Are certain cohorts enrolling faster than others or pretty similar across the board?

Thanks for the question. Yeah, we're very pleased with enrollment. You know, we expected each cohort to have different enrollment rates based on the, you know, the prevalence of the tumor type, and we built all of those assumptions into our site selection and our program timelines. So as of now, things are going well.

Thanks. Our next question comes from the line of Colleen Cussey with Bayard. Your line is now open.

Great. Thanks so much for taking our questions. On the dose for the innate study, I think you previously said you would be exploring potentially a higher dose of AD64. Any update on that and why you might be looking at a higher dose beyond 700 mg?

Oh, thanks, Colleen. Yeah, in our dose escalation, we went up to 1,200 mg every three weeks. And we've completed that. We've completed dose escalation. for both monotherapy and combination. 1,200 was the highest dose we planned to test. We've completed that. It was safe. So the purpose of doing that is really just to give us that information about the safety profile of the drug at a higher dose than the one we've chosen to take forward. But at this time, you know, we're very happy with 700 milligrams as the dose that we're taking forward in the expansion cohorts.

Got it. That's helpful. Thank you. And then still on the dose for the NEA study, remind us what the dose is for PIMI that you're using and how that compares to the dose you're using in the select study.

Sure. The dose of PIMI is 500 milligrams every three weeks, which was the, we had two different recommended phase two doses for PIMI, either 500 every three weeks or 1,000 every six weeks. And since JTX 8064 is given every three weeks, we're using the 500 milligram dose.

Got it, thank you. And then last question, for the innate update next year, do you expect that that would include both dose escalation and early dose expansion data?

Correct, correct. Our goal is to really have a presentation of as meaningful data as possible, and so that would include the dose escalation data also preliminary data from the expansion cohorts with at least 18 weeks of data on patients and all of the predictive and pharmacodynamic biomarker data.

Great. Thanks for taking our questions. You're welcome. As a reminder to ask a question, you would need to press star then 1 on your telephone. Our next question comes from the line, Azik Bajala with Roth Capital Partners. Your line is now open.

Hi. Thanks for taking my question. I just have two quick ones. The first one is just about the crumble-downs in the innate study. I just wanted to get a sense of the competitiveness of those different arms. And I think the key one that we've been getting questions about is about your PD-1 inhibitor. And I know, you know, you've gone through the data on this, but a lot of folks are still curious about the efficacy and safety. So can you just comment on that and how you're thinking about its competitiveness relative to other PD-1s?

So PIMI was originally studied in a phase one dose escalation trial. We had no dose-limiting toxicities. The doses, you know, it was quite safe, very similar to other PD-1 inhibitors. And importantly, we had a 17% response rate in all comers, tumors that by definition could not have approved PD-1 inhibitors because the patients had to be PD-1 inhibitor naive and had to have failed all available therapies. So we were very pleased with both the efficacy and safety of PIMI. And as you know, we're using it in the select trial and the innate trial. And we're very pleased that we're able to use PIMI in every one of the expansion cohorts, including frontline head and neck cancer. So, you know, it's a big advantage for us to be able to use our own PD-1 inhibitor and both from a cost perspective and flexibility perspective for doing the clinical trial, but it also gives us the potential to actually get two jounce wholly owned drugs approved, you know, at the end.

Thanks, Beth. And then just the last one here is just about select. For our model, we still view it as a call option, but, you know, there's still a lot of good signs backing this. And as you mentioned, you know, the biomarker strategy is novel and very exciting. And so for folks who are interested in understanding a bit more about the outlook of this program, can you just comment a little bit on, you know, what you're thinking about in terms of the uniqueness of this approach and if there's anything else that you've seen more recently or that you've done internally more recently to give you a stronger conviction around this program and the data readout?

Yeah, I can take that one, Zegba. I think the most important thing in describing the biomarker that we're applying to Svoboda is that we're learning from clinical data. And so for us, being able to kind of follow and show retrospectively that, we can pick up this biomarker, this cutoff point, and where clinical benefit was observed, we can kind of identify those patients from the retrospective analysis. So I think that's kind of really the driver for us. It's really following the science, following the clinical data that puts us in a position to really bring that right immunotherapy to the right patients. So for us, it's an example of one of the more stringent biomarker selections We're currently in immunotherapy to date. That really hasn't been the case. There's been cases of removing a small percentage of patients, but a really rigorous selection, we think, is, you know, follows the lines of the logic of a precision medicine approach in oncology. So that's the path we're taking. It's driven by the science and our clinical data.

Thanks, Rich. And, Sarah, just a quick follow-up. I think, you know, key to this would be the threshold that's been set. And so I was just wondering if you can just comment again on your conviction around whether or not you did select the right threshold for your biomarker.

Yeah, from all the data that, as Rich was talking about, that we generated retrospectively, this biomarker seemed to have the best sensitivity. Sorry, this threshold seemed to have the best sensitivity and specificity. And also from a practical point, you know, finding 20% of patients is a lot better than finding, you know, 4% of patients. That can be really challenging. So we've been extremely pleased that the screening data from the select trial has continued to really be spot on with 20% of patients being TISPO for positive, which we think is really, it gives us that, you know, really finding the top group of patients most likely to benefit, but in a way that's actually clinically manageable. You know, doctors and patients are willing to do the screening knowing they have a one in five chance of, you know, of being eligible based on the biomarker. So it's worked out very well.

Thanks, Beth. Really appreciate it. And I think folks are glad to know that, you know, you guys are on the side of caution in terms of picking patients most likely to respond as opposed to trying to get a bigger part of the market.

Thank you. Our last question comes from the line of Swayampakulla Ramakant with HC Wainwright. Your line is now open.

Thank you. Good morning, Rich and Beth. Most of my questions have been asked, but I just want to try to understand how the data releases are going to work in 2022. especially in the combination cohorts, the expansion cohorts that you recently initiated. With eight different studies going on and seven different indications, would you be releasing data cohort-wise, or would you want to wait until all of these cohorts the data from all the cohorts are available to release.

Yeah, our goal is to present, as I said, a meaningful body of data, and we think that means data across multiple cohorts. So that's what you can expect. It will be data across multiple cohorts and, yeah, along with biomarker data.

Fantastic. You're looking at ovarian cancer both as a monotherapy and a combination therapy. I'm just trying to understand, let's say if the data is good on both fronts, how could you rationalize which way to go or you plan to do a late-stage study as both monotherapy and combination therapy? I'm just trying to figure out how you sequence these things.

Sure, that's a good question. It was important for us to have a cohort of monotherapy. Eventually, we expect this, as with all immunotherapy, is most likely to be used in combination. The monotherapy is helpful for proof of concept, but also because if there is sufficient data there that could support a registration, that's always the fastest path to market. So we'll look at the data and we'll do the development in a way that gets us the earliest possible approval for JTX-8064, but also serves the greatest number of patients. So You know, it will really be determined as we look at the data.

Thank you. Thank you, Beth. Thanks, Rich. Talk to you soon. Sure. Thank you.

Thank you. There are no further questions. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.