Jounce Therapeutics, Inc.

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00:38 Thank you, operator. This is Eric Laub, Vice President of Investor Relations at Jounce Therapeutics.

Good morning and welcome to the Jounce Therapeutics third quarter twenty twenty one earnings conference call. This morning, we issued a press release, which outlines the topics that we plan to discuss today.

00:58 The release is available in the Investors & 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 CFO, Dr. Dmitri Wiederschain, will then discuss our discovery efforts.

And lastly, our CFO, Kim Drapkin, will review our third quarter financial results. We will then open the call for your questions.

01:40 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. 01:59 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 fourth, twenty twenty one, 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.

02:38 With that, I'll now turn the call over to Rich.

02:42 Thanks, Eric. Good morning and thank you for joining us today.

Jounce has had a very productive quarter as we 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 twenty twenty two 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.

03:10 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 JTX-8064, plus or minus pimivalimab, our own PD-1 inhibitor, in eight distinct cohorts across seven tumor types. 03:31 We continue to advance patient enrollment and our select study, which employs our stringent patient selection strategy and have continued our commitment to build our discovery pipeline.

We're having an exciting time in Jounce’s development and remain committed to progress new mechanisms that target different immune cell types within the tumor micro environment. 03:54 This is now evident in our myeloid and macrophage programs and our program licensed to Gilead, which targets T regulatory cells.

We also believe Jounce represents the next generation of immuno-oncology by unlocking a precision medicine approach through the continued execution of our translational and biomarker efforts. 04:15 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 divisions.

04:28 At beginning of this year, we an announced that enrollment had commenced in INNATE. The clinical study of JTX-8064, our highest priority program.

JTX-8064, an inhibitor of the macrophage checkpoint LILRB2, also known as ILT4 is being tested as a monotherapy and combination therapy along with pimivalimab or PD. 04:55 We move quickly through the necessary monotherapy and combinations therapy dose escalation for safety in all comers, cancer patients.

While establishing safety and PK PD to allow for dose selection. 05:09 We determined seven hundred milligrams as the preliminary recommended Phase 2 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.

05:30 We look forward to delivering further milestones with this program, and we reaffirm our belief that the myeloid and macrophage biology targeted by JTX-8064 via the LILRB2 mechanism, provides a new opportunity to bring benefit to patients, especially patients with PD-1 inhibitor resistant tumors. 05:51 As we previously mentioned, these patients tend to have few therapeutic options and representing 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 twenty twenty two. 06:11 Patient enrollment continues to advance in the SELECT study.

Our Phase 2 randomized is proof of concept trial of vopratelimab or ICOS Agonist, in combination with Pimi. The key feature of this study is the biomarker selection of patients utilizing TISvopra, an eighteen gene signature that includes genes relevant to both CD8 and CD4 T cell biology.

06:37 We believe from our own clinical data and from others that a rigorous patient selection strategy maybe critical to optimize the benefits of an ICOS agonist. We look forward to reporting clinical data on the select trial in twenty twenty two.

06:53 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 inflation points while continuing our robust novel discovery efforts, identifying and progressing new mechanisms have targeted reverse set and the immune cell types, within the tumor microenvironment. 07:16 With the goal of a new IND every twelve to eighteen months, we are on track to nominate another developed candidate.

In June, Jounce successfully opened the IND for GS-1811, formerly JTX-1811. And in August, the clinical study was initiated by Gilead.

07:36 We are extremely pleased to now have internally developed candidates in the clinic in the past five years. We remain fully committed and on track to achieve all the milestones set up for twenty twenty one.

From the clinic to our discovery efforts. 07:53 Before turning the call over with to Beth, I'd like to welcome back to Jounce, Jigar Raythatha.

In September, we announced that Jigar joined our board directors. His experience and skills are highly relevant and synergistic with the needs of our work.

As a former team member of Jounce, 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.

08:22 I'll now turn the call over to Beth to provide a clinical update. Beth?

08:26 Thanks, Rich good morning. I'm extremely pleased with 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 the point Rich made about cancer patients in need of better options. 08:47 Unfortunately, there are far too many patients still not benefiting from improved 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 JTX-8064 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. 09:20 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 and checkpoint inhibitors.

09:37 Turning first to JTX-8064, and our INNATE study. We believe the 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 PD-1 inhibitor resistant tumors.

By identifying and inhibiting key checkpoints of the innate immune system, new populations of T-cells can be tried and directed to the tumor, something T-cells alone cannot do. 10:11 For patients, this might mean a more comprehensive immune response and one that they overcome that significant barrier of treating PD-1 inhibitor resistance or non-responsiveness.

This substantial unmet need is why we consider JTX-8064 to be our highest priority program. JTX-8064 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.

10:47 As a reminder, the INNATE trial is divided in four parts. Part one, is JTX-8064 monotherapy dose escalation in all comers solid tumors.

Part two, JTX-8064 plus Pimi dose escalation in all comers solid tumors. Part three, JTX-8064 monotherapy expansion cohort in PD-1 naïve ovarian cancer.

Part four is JTX-8064 plus Pimi in seven tumor specific expansion cohorts. 11:26 As planned, we moved quickly to 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. 11:51 The expansion cohorts will steady JTX-8064 in three subsets of patients in order to identify the most rapid development paths for JTX-8064 alone or in combination with PD-1 inhibitors.

First, patients who progress 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.

12:22 Indications we have targeted for this patient population includes triple negative breast cancer, cutaneous squamous cell carcinoma, non-small cell lung cancer, and clear cell renal cell carcinoma. Second, PD-1 inhibitor naïve 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. 12:53 Indications, we have targeted for this patient population, include ovarian cancer and sarcoma.

Finally, PD-1 inhibitor naïve 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.

13:18 Earlier this year, we shared our translational approach to defining disease areas of interest for JTX-8064, based on analyses of the tumor microenvironment environment 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.

13:55 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 assignments two stage design with the potential to enroll up to twenty nine patients for combination cohorts and up to forty seven patients in the monotherapy cohort, if pre-specified criteria are met.

14:25 INNATE will also assess pharmacodynamic and potential predictive biomarkers to guide future development, aligning with Jounce’s 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 JTX-8064 as well.

14:50 Importantly, the combination expansion cohorts in INNATE allow us to potentially take two Jounce molecules, JTX-8064 and Pimi through to registration. Next year, we will guide on when and how we plan to release the data.

15:08 Now, turning to SELECT were screening and enrollment continue to progress well. SELECT is our Phase 2 randomized proof of concept trial of vopratelimab in combination with our own PD-1 inhibitor Pimi in approximately seventy five immunotherapy naïve non-small cell lung cancer patients, who will be selected using the predictive TISvopra biomarker and randomized to Vopra plus Pimi versus Pimi alone.

15:40 We expected approximately twenty percent of these second line non-small cell lung cancer patients to be TISvopra positive and screening to date continues to validate this projection. The essential feature of this study is a rigorous biomarker selection of patients utilizing TISvopra, an eighteen gene signature that includes genes predictive from both of PD-1 inhibitor response via CD8 cells, as well as the unique pharmacodynamic effect of Vopra via [Technical Difficulty] cells.

16:23 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 twenty twenty two.

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.

16:54 Our translational science biomarker approach became 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.

17:13 With that, I will now turn the call over to Dmitri to discuss our ongoing discovery efforts. Dmitri?

17:20 Thanks Beth. We focus on the utilization of our translational time platform to address the problems that patients with cancer are facing today.

Namely, resistance to T cell checkpoint inhibitor therapy. 17:35 We believe that our ability to dissect the tumor macro environment at the molecular level using immune cell type specific gene signatures will lead us to a target that may be important for overcoming resistance to checkpoint blockade.

17:44 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 are pursuing.

18:05 We are confident that the LILRB family represents attractive immuno-oncology targets with the potential to improve upon and restore responsiveness to PD-1 or L1 inhibitors. As disclosed earlier this year, we are rapidly advancing two additional LILRB family programs through discovery, one targeting LILRB1 and the other targeting LILRB4.

We are on track to nominate our next development candidate within the LILRB family. 18:38 In addition, we are now leveraging highly specific LILRB targeting building blocks to generate multi-targeted biologics that we're exploring preclinically.

Today, 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 are very proud of their work and I look forward to sharing updates on our productive discovery engine in the future. 19:10 I will now turn the call over to Kim for a discussion of our third quarter financial results.

Kim?

19:17 Thank you, Dmitri. As we reported in this morning's press release, cash, cash equivalents and investments as of September thirty, twenty twenty one increased two forty nine million dollars compared to two hundred and thirteen point two million dollars as of December thirty one, twenty twenty.

The September thirty, twenty twenty one cash balance includes the recognition of a twenty five million dollars milestone received from Gilead in the third quarter. 19:45 Turning to the P and L, no revenue was recognized during the third quarter twenty twenty one or twenty twenty.

During the third quarter of twenty twenty one, we incurred twenty three point three million dollars in research and development expenses compared to eighteen million dollars for the same period in twenty twenty. 20:03 The increase in R and 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.

20:19 General and administrative expenses were six point nine million dollars for the third quarter of twenty twenty one, compared seven point one million dollars for the same period in twenty twenty. The decrease in G and A expenses was primarily a result of decreased professional fees, offset by increases in other administrative costs.

20:40 Net loss for the third quarter of twenty twenty one was thirty point one million dollars, resulting in a basic and diluted net loss per share of zero point five nine dollars as compared to a net loss of twenty four point nine million dollars for the same period in twenty twenty, resulting in a basic and diluted net loss per share of zero point seven three dollars. 21:01 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 periods in twenty twenty.

21:15 We are narrowing our cash burn guidance and expect growth cash burn on operating expenses and capital expenditures for full year twenty twenty one to be approximately one hundred million dollars to one hundred and ten million dollars ending twenty twenty one with approximately two twenty million dollars. 21:32 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 twenty twenty three.

21:45 I'll now hand to Richard for some final words.

21:48 Thanks, Kim. A combination of our experienced team, innovative science, and financial resources puts us in a strong position to move beyond our net set of inflection points, and continue to execute our strategic plans.

Jounce continues to focus on patients first and we're proud out of the IO pipeline we're building to address the growing unmet medical need faced by cancer patients. 22:15 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 made across our pipeline.

Additionally, we’re fortunate in having 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 progress.

22:42 With that, we'd now like to open the call for your questions. Operator?

23:09 Great. Thank you very much and 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.

23:37 Thanks, Ted. This is Beth.

So, I 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 both for Pimi and 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.

24:09 We believe the data that we generate from this study will give all the information we need to design our randomized Phase 3 trial for our registration.

24:19 And do you see opportunities to, again, obviously it’s early and it will be data dependent, but to pursue this combination beyond loan?

24:31 Yes. Our belief as with 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 Vopra 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 CD4 T cell targeting agent.

25:05 Remember, in Select, we found that about twenty percent of the patients are TISvopra positive and we'll be looking across other tumor types. We have some data on the prevalence in those as well, but I think that's exciting that we're really honing in on the percentage of patient who are most likely to benefit as opposed to some other biomarker selection like PDL-1, which kind of eliminates the bottom twenty percent, we're really targeting the top twenty percent of patients who are most likely to benefit from this therapy.

25:44 Yeah. And then one other one, tried to take so much time and focus on SELECT and this mechanism for 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, are there other mechanisms that might make sense to add to this already co-stim and checkpoint inhibitor or stim inhibitor?

26:17 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 Vopra plus Pimi has been, as we've shown with Vopra and Nivo in the iconic trial and even with Vopra and [ipi] [ph], 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 JTX-8064.

27:08 And, yeah, just think for a 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 combinations. So, PD-1 on the T cells, you know we’re going up to the macrophages and we kind of continue to push that cell type specific biology that we think will lead to the best combinations.

27:32 Makes a lot of sense. Thanks for all the time.

27:43 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 2 dose?

27:54 Sure. So, this is a classic inhibitory monoclonal antibody.

And so, the recommended Phase 2 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 seven hundred milligrams, which is the dose we're taking forward, patients will have full receptor occupancy through the entire three week dosing cycle.

28:29 We actually saw full receptor occupancy and the requisite PK data at three hundred milligrams every three weeks, but we really wanted to optimize both the percentage of patients who would have full receptor occupancy given potential inter patient differences and also optimize the amount of receptor occupancy in the tumors, which may be different from what you see in the peripheral blood. 28:55 So, the choice of the dose was not based on any clinical data other than PK and receptor occupancy, and of course, safety.

29:07 Got it. Okay.

And maybe on the SELECT study, can you remind us again how the TIS for biomarker works and specifically I'm just thinking, how can we scale up from the clinical scale to a commercial scale market?

29:23 Sure. So, it's currently it's 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 a commercial use and also make it easier for patients and physicians. So, that's in the works, but you know, but NanoString platform is something that's pretty widespread and so, we believe that it's very feasible to take this forward as a companion diagnostic.

Do you want to add anything Rich?

30:02 Yes, I think Boris, that's all kind of dated accordingly in pace with the clinical data. So, the next, as we're using it now, the clinic that kind of next step to really take that forward, coordinated with the next step in clinical would then be moving into that more commercial realm of how to use the biomarker.

30:22 Great. Thank you for taking my questions.

30:26 Welcome.

30:35 Good morning. Thank you.

As you guys know the Phase 1 data for Merck before inhibitor was recently published, 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 any of your expansion cohort choices or your hypotheses regarding the mechanism? Thanks.

30:58 Thanks, Steve. I think in general, the Merck data has 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 it's not identical to the biology that we're following. And I think we were very pleased to see it published.

31:27 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.

Dmitri, if you want to say something about the biomarker?

31:56 Yeah. Thanks Beth.

I think as Beth mentioned Merck Publication is largely consistent with our hypothesis around LILRB2. As we disclosed and mentioned during our R and D day a few months ago, CD-163 is a marker of immunosuppressive macrophages, and it is a negative prognostic market in many cancers.

32:21 I think that’s very consistent with the Merck messaging in their manuscript. And we've also shown that the ratio of the LILRB2 specifically to the interferon gamma signature, which is tumor inflammation, could be a negative predictor of response to PD-1 inhibitors and again, I think that's very consistent was what Merck has shown.

32:46 We're looking forward to analyzing biomarker data from INNATE where we have many opportunities to assess potential predictive biomarkers. We will be looking at them individually, as well as the relationship to each other and correlate that with clinical efficacy.

33:03 Yes. Maybe I'll just mentioned that when we do report those data from the expansion cohorts and INNATE, we will have the potential predictive biomarker and the pharmacodynamic biomarker data included with the clinical data.

33:22 Great. Thank you.

33:35 Hi guys. Thanks for the question.

This is Tiffany on for Cory. Just one on INNATE, how has trial enrollment gone across your expansion cohorts or certain cohorts enrolling faster than others are pretty similar across the board?

33:49 Thanks for the question. Yes, we're very pleased with enrollment.

We expected each cohort to have different enrollment rates based on 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.

34:29 Great. Thanks for taking our questions.

On the dose for the INNATE study, I think you've previously said, you would be exploring potentially a higher dose of eighty sixty four, any update on that and why you might be looking at a higher dose beyond seven hundred mix?

34:46 Thanks, Colleen. In our dose escalation, we went up to twelve hundred milligrams every three weeks.

And we've completed that. We've completed dose escalation for both monotherapy and combination, twelve hundred was the highest dose we planned to test.

We've completed that, it was safe. 35:06 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, we're very happy with seven hundred milligrams that's the dose that that we're taking forward in the expansion cohorts.

35:27 Got it. That's helpful.

Thank you. And then still on the dose for the INNATE study, remind us what the doses for Pimi that you're using and how that compares to the dose you're using in the SELECT study?

35:37 Sure. The dose of Pimi is five hundred milligrams every three weeks, which was the, we had two different recommended Phase two doses for Pimi either five hundred every three weeks or a thousand every six weeks.

And since JTX-8064 is given every three weeks, we're using the five hundred milligram dose.

36:01 Got it. Thank you.

And then last question for the INNATE update next year, would that – do you expect that that would include both dose escalation and early dose expansion data?

36:14 Correct. Correct.

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

36:41 Great. Thanks for taking the questions.

37:01 Hi. Thanks for taking my question.

I just have two quick ones. The first one is just about the combo arms in the INNATE study, just wanted to get a sense of the competitiveness of those different arms and think the key one that we’ve been getting questions about is about your PD-1 inhibitor.

And I 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 are thinking about is competitive then relative to other PD-1?

37:33 So, Pimi was originally studied in a Phase 1 dose escalation trial. We had no dose-limiting toxicities that doses was quite very similar to other PD-1 inhibitors, and importantly, we had a seventeen percent response rate in all comers tumors that by definition could not have a – PD-1 inhibitors because the patients had to PD-1 inhibitor naïve and had to have failed all available therapy.

38:05 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 INNATE trial, and we're very pleased that we're able to use Pimi in every of the expansion cohorts, including frontline head and neck cancer.

So, 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 wholly-owned drugs approved at the end.

38:47 Thanks Beth. And then just a last one year.

It's just about SELECT, of all model you still view it as a call option, but there's still a lot of good signs back in this as you mentioned, you know the biomarker strategy is novel and very exciting. And so, for folks that are interesting, understanding a bit more about the outlook of this program, can you just comment a little bit on 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 stronger conviction around this program and the data readout?

39:27 Yeah. I could take that one Zegbeh.

I think the most important thing in describing the biomarker that we're applying, TISvopra, 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 cut out point and where clinical benefit was observed, we can kind of identify those patients from the retrospective analysis.

39:56 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.

40:07 So, for us, it is an example of one of the most and one of the more stringent biomarker selections. Where currently immunotherapy to date, that really hasn't been the case, there has 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 the precision medicine approach in oncology.

So that's the path we're taking. It’s driven by science and our clinical data.

40:39 Thanks Rich. 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?

40:57 Yeah. From all the data that, as Rich was talking about that we generated retrospectively, this biomarker seems to have the best sensitivity – this thresholds seems to have the best sensitivity and specificity.

And also from a practical point, finding twenty percent of patients is a lot better than finding four percent of patients that can be really challenging. 41:23 So, we've been extremely pleased that the screening data from the SELECT trial has continued to really be spot on, but twenty percent of patients being TISvopra positive, which we think is really – it gives us that really finding the tough group of patients most likely to benefit, but in a way that's actually clinically manageable.

41:48 Doctors and patients are willing to do the screening knowing they have a one in five chance of being eligible based on the biomarker. So, it's worked up very well.

42:02 Thanks Beth, really appreciate. And I think folks glad to know that you guys heard 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.

42:16 Yeah.

42:28 Thank you. Good morning, Rich and Beth.

Most of my questions have been asked, but just want to try to understand how the data releases are going to work in twenty twenty two, especially in the combination cohorts, the expansion towards that you recently initiated? With eight different studies going on in seven different indications, would you be releasing data cohort wise or would you want to wait till all of these cohorts – the data from all the cohorts are available to release?

43:20 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 Yes, along with biomarker data.

43:40 Fantastic. And 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 would 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 will sequence these things?

44:15 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 combinations.

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 will do the development in a way that gets us the early possible approval for JTX-8064, but also serves the greatest number of patients.

So, it will really be determined as we look at the data.

45:07 Thank you. Thank you, Beth.

Thanks, Rich. Talk to you soon.

45:11 Sure.

45:12 Thank you.