Jounce Therapeutics, Inc.

Good morning, ladies and gentlemen, and welcome to the Johnson Therapeutics second quarter 2022 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 is being recorded at the company's request. I will now turn the call over to your host, Eric Laub, with Johnson Therapeutics.

Please go ahead. Thank you, Operator.

This is Eric Laub, Vice President of Investor Relations at Johnson Therapeutics. Good morning and welcome to the Jounce Therapeutics second quarter 2022 financial results 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 Wiederschein, will then discuss our discovery programs. And lastly, our CFO, Kim Drapkin, will review our second 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, August 4th, 2022 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'll now turn the call over to Rich.

Thanks, Eric. Good morning, and thank you for joining our call today. As disclosed in our press release this morning, we've made significant progress advancing our pipeline and look forward to sharing more details on our ongoing innate and select clinical trials today. We're encouraged by the important overall progress we've made in the second quarter and are pleased to announce that we've completed enrollment in select, tracking to report data later this year. As previously announced, we met the pre-specified expansion criteria in two of the seven innate combination cohorts enabling the continuation of enrollment from the first 10 patients to the full 29 patients in each. We're pleased with the pace of that continued enrollment. The remaining combination cohorts are either continuing patient enrollment to complete the first stage or waiting for patient data to mature. We persist in striving for a meaningful immunotherapy for patients who have few options. This is at the heart of our approach to novel mechanisms guided by biomarkers. Our plan is to submit clinical data abstracts for both innate and select to the ESMO Immuno-Oncology Congress 2022 being held from December 7th to 9th in Geneva, Switzerland. As we previously stated, our objective is to provide comprehensive datasets with as much follow-up in biomarker data as possible. Given the medical meeting submission deadlines, this venue makes the most sense to us to report these important clinical data. Beth will provide more details on our clinical studies in a few moments. Across the field, the use of PD-1 inhibitors continues to grow and expand into earlier lines of therapy, including non-metastatic settings. As a result, the size and scope of the PD-1 inhibitor resistant markets continues to increase. as there are more patients who are resistant to the therapy than benefit from it. Unfortunately, there are few alternatives for these patients in many tumor settings. We see this resistance as a fundamental scientific and medical problem that heads in the way of broader and more durable impact IO could have for cancer patients. As scientific evidence continues to point to the myeloid immune cell lineage, as being causal to at least some aspects of IO resistance, we have prioritized discovery work on the LIL-RB or ILT receptors. In a similar approach, T regulatory cells are thought to create immune suppressive barriers in the tumor microenvironment. We licensed our lead T regulatory cell program and antibody targeting CCR8 to Gilead. This antibody, the fourth brought through IND by Joust, is now called GS1811 and is being developed by Gilead. Under the license agreement, we're entitled to receive milestone payments from Gilead upon the achievement of specified clinical, regulatory, and sales milestones, along with tiered royalty payments. Our next potential internal clinical program, KTX1484, is an anti-LIL-RB4 or ILT3 program currently in IND-enabling studies. LIL-RB4 is expressed on immune-suppressive myeloid cells in the tumor microenvironment with both overlapping and distinct cell types and biology compared to LIL-RB2. Dmitri will provide more details on our discovery efforts and this program. On another note, we're sharing some internal promotion and changes to the board of directors. On the board front, Jigar Rathatha has replaced Perry Carson as chairman of the board. Perry has served as chair since April 2016 and remains on the board. I would like to recognize Perry's leadership, contributions, and commitment to Jounce during his time as chair. Perry was one of our first independent board members and was instrumental in building the board's strength and expertise. Thank you, Perry, and we look forward to your continued involvement. I'd also like to congratulate Jigar as the chair of the board. Jigar joined our board in 2021, is a former member of the child's management team, and has the relevant experience, knowledge, and understanding to step into the chair role at this important time. Internally, we've promoted two of our management team members to new roles. Hugh Cole is being promoted from Chief Business Officer and Head of Corporate Development to Chief Operating Officer. Dr. Haley Lakin is being promoted from SVP of Program and Portfolio Strategy to Chief Development Officer. Both Hugh and Haley are impactful leaders within Jounce, and we congratulate them on their respective promotions. We are eager to continue our robust clinical and discovery productivity across our pipelines. We're excited for what lies ahead at Jones as we work towards our key data readouts this year. Our current financial position enables our continued growth and execution beyond the proof of concept inflection points of innate and select, while continuing our robust novel discovery efforts, identifying and progressing new mechanisms to benefit cancer patients, particularly in the settings where patients have few therapeutic options. With that, I'll turn the call over to Beth to discuss our clinical pipeline in science in more detail.

Thanks, Rich. We are making great progress on our two proof-of-concept studies, and I am very pleased to be able to provide some updates on both trials for you this morning. Let's begin with the innate trial of JTX8064, our LIL-RB2 inhibitor. Last year, we completed the Phase I dose escalation for both monotherapy and combination with PIMI, selected 700 milligrams as the recommended phase two dose, and initiated the phase two expansion cohorts for both monotherapy and combination treatment in seven different indications. As a reminder, each of the expansion cohorts is a Simon two-stage design. For the combination cohorts, the first stage consists of 10 patients per cohort. Each cohort must meet pre-specified criteria based on radiographic response before resuming enrollment of the additional 19 patients for a total of 29 per combination cohort. Subsequent to this year's initial data readout, our goal is to demonstrate clinical proof of concept on the full set of 29 patients for each expansion cohort. To establish proof of concept, we require the response rate of JTX8064 in combination with our PD-1 inhibitor, PIMI, to be greater than what would be expected with a PD-1 inhibitor alone. The response rates for PD-1 inhibitor monotherapy are different for each innate indication and are all quite low, generally in the single digits. This reflects the high unmet need in patients who have failed a PD-1 inhibitor or have tumor types where PD-1 inhibitors alone have minimal impact. As previously announced, to date, we have met the expansion criteria in two of the seven combination cohorts. The indications that have met this pre-specified criteria and are currently enrolling up to 29 patients are third and fourth line PD-1 inhibitor-naive platinum-resistant ovarian cancer, and second and third line PD-1 inhibitor-resistant clear cell renal cell carcinoma. there is significant unmet medical need in both ovarian and renal cell carcinoma. Data from previously published studies with PD-1 inhibitors in PD-1 inhibitor naive ovarian cancer and PD-1 inhibitor experienced renal cell carcinoma have reported response rates of approximately 9% and 13%, respectively. In addition to response rate assessment, an important aspect of INATE is the evaluation of the correlation of pharmacodynamic and predictive biomarkers with efficacy. Analysis of potential predictive biomarkers may help us to understand the contribution of JTX8064 to clinical activity in these combination cohorts. There is a growing body of evidence that biomarkers expressed by immunosuppressive macrophages are a negative prognostic factor in many cancers regardless of treatment, and that high levels of tumor-associated macrophages relative to interferon gamma are a negative predictor of response to PD-1 inhibitors. If we observe an association of improved clinical outcomes with biomarkers typically linked to worse outcomes, particularly in the combination cohorts, it will help isolate the contribution of JTX8064 to clinical activity. Let me now take a few minutes to update you on the trial status. Enrollment is going well across innate. Enrollment of the full 29 patients in the ovarian cohort is nearing completion, and enrollment in the renal cohort is also going well. We have not yet met the point for expansion in the remaining combination cohorts. as they are either still enrolling up to 10 patients or have completed Stage 1 enrollment and we are awaiting patient data. In the ovarian cohorts, we prioritized enrollment in the combination cohort over the monotherapy cohort. As enrollment in the ovarian combo cohort is near completion, we will now shift our efforts to completing enrollment in the first stage of the monotherapy cohort. As Rich mentioned, We plan to submit an abstract to the December 2022 ESMO I-O meeting. The data will include all 31 phase one dose escalation patients, nine of whom were in combination, and at least 80 phase two combination treatment patients from the NAIT. We plan to present complete phase one monotherapy and combination dose escalation data, including the respective safety, PK, PD, biomarker, and preliminary efficacy data. Phase 2 data will include safety, preliminary efficacy based on RESIST 1.1, pharmacodynamics, and potential predictive biomarker correlation with efficacy within each cohort by prior PD-1 inhibitor history and in a cross-cohort analysis. Now, on to our other Phase 2 program, Bopratelemab, our ICOS agonist. in the SELECT trial, which is a randomized phase two proof of concept trial. We are pleased to have completed enrollment and are proud of the efforts of our team and the investigators have made to keep treating patients in Ukraine during these challenging times. In SELECT, we are studying two doses of Vopra in combination with PIMI compared to PIMI alone in biomarker selected patients with metastatic non-small cell lung cancer who are PD-1 inhibitor naive and have progressed on a platinum-based chemotherapy regimen. This trial seeks to address two important questions. One, will Vopra plus a PD-1 inhibitor in biomarker-selected patients result in greater activity than a PD-1 inhibitor alone? And two, which dose of Vopra should we choose for further development? The predictive biomarker selection of patients utilizes TIS-Vopra an RNA-based 18-gene signature that includes genes relevant to both PD-1 and ICOS biology. Only patients with a value above the biomarker threshold are enrolled, and the trial is designed to show the statistical superiority of OPRA plus our PD-1 inhibitor, PIMI, versus PIMI alone. The primary endpoint is the mean change from baseline in tumor size averaged over 9 and 18 weeks. And the secondary endpoints are the more common overall resist response rate, progression-free survival, overall survival, and duration of response, which represent all of the standard regulatory endpoints. All endpoints will be based on independent central radiology review. The doses we are exploring, 0.1 milligram per kilogram and 0.03 milligram per kilogram, demonstrated differentiated patterns of pulsatile target engagement in prior studies. The hypothesis we are testing is that the sustained target engagement required for antagonist antibodies is not ideal for an agonist molecule like BOPRA, and that a dose that results in a more pulsatile pattern of target engagement may be more efficacious than one with sustained target engagement. As Rich mentioned, we are on track to present the complete study data with an abstract submission to ESMO-IO. Since we will be reporting the complete study data this year, I would like to provide some guidance for expectations and interpretation of data from this randomized Phase II study. Our decisions regarding further development of VOPRA in combination with PIMI will be based on the totality of the data, including resist response rates. where there is strong benchmark data for PD-1 inhibitors. In this setting, response rates for PD-1 and PD-L1 inhibitors range from 14 to 20%, and we expect the response rate for PIMI alone to be similar to or better than this. The response rate for Vopra plus PIMI for at least one dose level will need to be meaningfully better than the response rate for pimi alone and supported by data from other endpoints. I would also like to mention that a manuscript on our first in human phase 1-2 iconic trial of BOPRA alone and with nivolumab, accompanied by a thoughtful editorial, was recently published in Clinical Cancer Research. I'd like to congratulate the team on this work. Our team has done an incredible job during unprecedented times executing on both clinical trials. I would like to take a moment to thank all the investigators, study teams, and especially the patients who put their trust in our medicines to make a difference in their lives. Without their bravery, we would not be able to advance these important medicines. We look forward to reporting on our continued progress this year. I will now turn the call over to Dimitri.

Thanks, Beth. We focused 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 at 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. The growing body of data points to suppressive myeloid cells, including tumor-associated macrophages, and their contribution to resistance to PD-1 or L1-directed therapies. JTX8064, which targets immunosuppressive macrophages and other myeloid cells in the TME, serves as an example of our patient-centric, biomarker-driven approach in discovery and through development. This approach is key to the value generating programs we are pursuing. We are very excited about our discovery activities and have announced our most recent advancement having selected JTX1484 as our newest development candidate. IND enabling studies are well underway and we continue to advance towards submitting an IND next year. JTX1484 binds to and inhibits LRB4 or ILT3, another LRB family member that is highly expressed on some of the key myeloid cells, including myeloid-derived suppressor cells and telogenic dendritic cells that orchestrate immune suppression in the TME, including resistance to checkpoint inhibitors. The LIL-RB4 target is distinct from other LIL-RB family members with respect to its ligand specificity as well as temporal and spatial pattern of expression on immune cells. Therefore, we see this program as complementary to our ongoing efforts to target LIL-RB2 with JTX8064. We have submitted two preclinical abstracts, one on JTX1484 and one on the LIL-RB family for consideration for this year's annual CITC meeting. We look forward to the opportunity to share this preclinical data. Additionally, our pipeline of monospecific LIL-RB-targeted antibodies is further strengthened by the ongoing efforts to develop potent and specific blockers of LIL-RB1, an inhibitory receptor that is expressed not only on myeloid cells but also on certain subsets of T and NK cells. Having these high-quality building blocks to target three important members of the LLRB family has enabled us to explore multi-targeted approaches preclinically by leveraging our knowledge and growing expertise in LLRB biology. We're confident that the LLRB family, as well as other targets that we're currently pursuing, represent attractive opportunities in immuno-oncology with the potential to improve upon and restore responsiveness to PD-1 or L1 inhibitors. In addition to our efforts in the little RB family, we continue to add to and diversify our discovery pipeline into other exciting areas of biology. I will now turn the call over to Kim for a discussion of our second quarter financial results.

Thank you, Dimitri. As we reported in this morning's press release, cash, cash equivalents, and investments as of June 30th, 2022 were $162.3 million compared to $220.2 million as of December 31st, 2021. The decrease was due to cash burn from operating expenses incurred during the period. Turning to the P&L. No revenue was recognized during the second quarter of 2022 compared to $25.4 million of revenue recognized during the second quarter of 2021. The 2021 revenue was comprised of a $25 million clinical development and regulatory milestone for FDA clearance of the IND for GF1811 and $0.4 million related to non-cash revenue for the performance of research and transition services, both under the Gilead License Agreement. During the second quarter of 2022, we incurred $26.2 million in research and development expenses compared to $22.1 million for the same period in 2021. The increase in R&D expenses was due to increased manufacturing activities performed, increased clinical and regulatory expenses for innate, and increased payroll and lab supplies. General and administrative expenses were relatively flat at 7.5 million for the second quarter of 2022, compared to 7.3 million for the same period in 2021. Net loss for the second quarter of 2022 was 33.5 million, resulting in a basic and diluted net loss per share of 65 cents, as compared to a net loss of 4 million for the same period in 2021, resulting in a basic and diluted net loss per share of 8 cents. The increase in net loss is attributable to increased operating expenses and no revenue recognized under the license agreement with Gilead in the second quarter of 2022. Given current market conditions, both in our sector and more broadly, we are making an effort to decrease our cash burn and extend our runway. While we continue to invest in both our clinical and discovery programs, we have identified areas in which we can continue to create value but also decrease expenses. As a result of these efforts, our cash on hand now provides runway into the first quarter of 2024. Based on our current operating and development plans, we now expect to be on the lower end of our growth cash burn guidance for the full year 2022 of approximately 115 to 130 million. I'll now hand it back to Rich for some final words.

Thanks, Kim. The combination of our clinical execution, innovative science, and financial resources enables us to move beyond our next set of inflection points slated for this year. We're looking forward to this year's CITSE and ESMO IEO meetings to be a busy time for us. As Beth and Dimitri described, we're working hard to build an IEO pipeline which looks to address the growing unmet need faced by cancer patients. I'd like to personally thank all of our hardworking employees who bring their enthusiasm to work every day to make these programs possible. We're privileged to be working on this mission together at Jounce and are fortunate to have such dedicated employees, collaborators, and clinical investigators. We look forward to updating you on the programs as the year progresses. With that, we'd now like to open the call for your questions. Operator?

Ladies and gentlemen, if you have a question or a comment at this time, please press star 1-1 on your telephone keypad. We'll pause for a moment while we compile our Q&A roster.

Our first question comes from Edward Tennoff with Piper Stanley. Your line is open. Great. Hi, thanks. Good morning, everybody.

Congrats on all the progress. Looking forward to the data in the fall here. So two quick questions, if I may, on your LittleRB franchise. I'm really trying to understand sort of how the profiles differentiate between LittleRB2 and LittleRB1. And, you know, is this something where ultimately you may have a future combination or are these really expressed differentially? Thanks for explaining.

Thanks for the question. That's a great question. That's something that we're actively working on and addressing in the labs. We believe that LIL-RB1, 2, and 4 have differentiated expression profiles. They are expressed on different types of immune cells in the two microenvironment. More importantly, we do believe that they have both overlapping but also distinct biological functions. And we're looking forward to presenting some of these data at the CITC meeting where we submitted an abstract for just a few days ago. Clearly, we see plenty of opportunities for combination of our highly potent and specific LIL-RB1, 2, and 4 blockers in a clinical setting. But also, as we pointed out, we have an active effort on blue larvae multi-targeted approaches using innovative biological scaffolds. Thanks for the question.

One moment for our next question. Our next question comes from Boris Peeker with Cowan. Your line is open.

Great. My first question is on an aid. When will you hear from ESMO to confirm that you're included in the meeting? And part of that is, can you help us interpret how we should be interpreting the ESMO data update?

So the, hi Boris, this is Beth. The abstract submission date is September 27th. So, you know, usually the, I think the abstracts will be published on December 1st. So we don't usually announce that abstract has been submitted, but that's sort of the timeframe. So we'll be submitting the end of September. And then the meeting is December 6th through 9th.

Got it. So we could see from the publication of abstracts on December 1st whether you're included or not, just to be clear.

Correct.

Got it. And in terms of interpreting the data, can you help us understand I guess there's both for the cohorts, the two cohorts in ovarian and clear cell that you've brought up. And what about the other five cohorts that aren't fully enrolled?

Sure. So the data we will present will include patients from every cohort. There obviously will be more patients from the ovarian and renal cell cohorts, although I don't expect we'll have full 18-week data on everybody from those cohorts. But our goal, and one of the reasons we decided to submit to ESMO IO, our goal is to have as robust a data set as possible. So we'll be presenting the data by cohort, even for the cohorts that have not gone beyond 10 patients. We'll be presenting the data by whether, you know, breaking it down by the PD-1 experienced patients, the ones that are resistant, or the PD-1 inhibitor naive patients, and then also looking at a cross-cohort analysis. And an important part of the data presentation will be the correlation or association with various potential predictive biomarkers.

Great. Thank you very much for taking my question.

You're welcome.

One moment for our next question. Our next question is Steven Seathouse with Raymond James.

Thank you. Good morning. Thanks for taking the question. First, I just want to ask, so the response criteria where you are looking for greater response than what you would expect for PD-L1 inhibitor alone, I just wanted to be specific there. So the expectation is 9%, for instance. in third or fourth line ovarian, does that mean you'd only require one response? Or in that case, are you looking for two before you enroll the stage two?

So thanks, Steve. We haven't talked about our criteria for moving from stage one to stage two. In ovarian, we're in, you know, almost complete with the 29 patients. And so really the best way to think about it is what we need to see in the 29 patients and the the final proof of concept data we think we'll have in early 2023. But, you know, with that data, we would need to see a response greater than, you know, meaningfully greater than 9% in the ovarian cancer patients and greater than 13% in the renal cell carcinoma patients. I think it's also helpful to understand not just the benchmark for PD-1 inhibitors, but also for standard of care. So in these patients, the standard of care for ovarian cancer response rates range from 4% to 14%. And in renal cell carcinoma for this patient population, the standard of care would deliver about 17%. Okay.

Thanks for clarifying. That was my misunderstanding about the stages where you're looking for that specific response rate. So the other thing you commented on, just the enrollment in the mono versus combo ovarian I just want to make sure I understand that right. I know you commented, but so are you enrolling the full stage one and stage two for combo and then pivoting to prioritizing enrollment in the mono or is there some sort of support there?

Sure. So what happened, the monotherapy ovarian cohort opened in August, right? So that started enrolling. When we opened the combo ovarian cohort, you know, the investigators tended to prioritize that. So we decided to prioritize the ovarian combo. It met the criteria to move from 10 to 29 patients. We're now almost finished with enrollment of the full 29 patients. And so once that's complete, then we will really focus on trying to complete enrollment in the first stage of the monotherapy cohort.

Makes sense. Okay, thank you.

clarify the response criteria for expanding enrollment from 10 to 29 is that confirmed resist response or is something else yeah so we haven't we haven't shared those criteria they were internal criteria that that we use we really think it's important to focus on our success criteria for a full set of 29 patients you know there's so much with with really small data sets and that things can be quite misleading. So we really want to make sure we're focusing on the responses in the 29 patients. And those will be based on confirmed resist responses, yes.

Thank you, Beth.

Appreciate it.

You're welcome.

One moment for our next question. Our next question, David Dye with SMBC. Your line is open.

Hey, great. Thanks for taking my questions, and congrats on the progress. This first question is just around AD64. Could you clarify... Could you clarify if any of the indication has stopped enrollment because it has not met the prespective response criteria?

No, all the cohorts are still open and could potentially expand. Some have completed enrollment of the first 10 patients, and we're just waiting for data to mature. And then some have not completed the first 10 patients yet. We have not closed any cohort.

Got it. I see. That's helpful. So the second question is just around the your innate signature HEMA for AD64. What we saw from your slides before was that venous cell carcinoma has high innate immune signature, whereas the ovarian cancer has medium to low levels of the innate signature. So could you help us understand a little bit more about the biomarker hypothesis based on the fact that you're enrolling additional patients for ovarian and venous cell carcinoma?

Sure. So first of all, for that heat map, I think all of the tumors that we selected are actually what we would consider high. So ovarian may look a little lower than renal cell in terms of the intensity on the heat map, but it is also a tumor that has high levels of the gene signatures that we were using for selection of indications, which were LIL-RB2, our tumor-associated macrophage signature, and an interferon gamma signature. In terms of the predictive biomarkers that we're going to be looking at, these have all been pre-specified. We'll be analyzing all of the clinical data in its association with this panel of biomarkers. And these include both gene signatures and IHC. The ones we've talked about have been things like LIL-RB2 itself, some of its ligands, The LLRB2 or TAM to interferon gamma ratio, which, as I've mentioned, is a poor predictor for PD-1 inhibitor response. And then things like CD163, which is an IHC marker for tumor-associated macrophages. So I think the general theme is high levels of immunosuppressive macrophages generally predict poor outcomes for patients, either with regular standard of care or with PD-1 inhibitors. And so if we see benefit in the patients who have high levels of those, you know, which would suggest that JTX8064 is contributing to the efficacy and help to isolate the effect in a combination with a PD-1 inhibitor.

That's helpful to think about. You're welcome. One moment for our next question. Our next question comes from Swamp with HCW.

Your line is open.

Thank you. Good morning, folks. Thanks for taking the question. Richard, when you first started talking about LRB2, the big players were just Merck and yourself. But over time, you know, we have seen additional players come into the LLRB space. I do understand that, you know, you have three molecules within that in development. But I'm just trying to understand how strategically, how are you thinking to maintain that leadership within the LLRB space? And do you plan to bring additional molecules or try to move these molecules, which are currently in preclinical and clinical stages, a little bit faster than your competition?

Yeah, sure. Okay, this is Rich. I can take that one. As we look at the little family, as Dimitri mentioned just a few moments ago, There are overlapping similarities in mechanisms, but importantly also distinctions. In addition to the distinction of function that we can characterize, there are different ligands. So there's a different way to kind of stimulate the immunosuppressive effect through those receptors. So as we kind of elucidate that biology linked to different ligands, that can start to direct us to what we think are smart combination types of first lab experiments, as well leading to clinic, as well as indications. So we think, as with many immunotherapies, there's always an opportunity in lines of therapies and different indications that we think could really allow us to be very assertive in one area and create a leadership position. As Bethann mentioned, the biomarker analysis is going to be quite important for us as well. If in some places, in some circumstances, a biomarker becomes important or necessary, we think that's also really an opportunity for differentiation for our molecules. One final note that Dimitri alluded to is we believe the myeloid cell system is quite important in creating immunosuppressive barriers. So while we've spoken much about the LIL-RB receptors, we have other myeloid targets in hand. And so there's a way to really go after that cell lineage, we think, through our highly specific monotherapy agents as well as constructed bispecific agents. that we think really go after that cell type that may be creating such a barrier for the immune system.

Thanks for that. One additional question. Any update you can give us on the CCR8 molecule that Gilead is developing in terms of data expectations over the next 6 to 12 months?

Yeah, I can take that one as well, RK. So when we filed the IND and opened that IND, we were quite pleased with how that was taken up by Gilead. You know, for us, we really can't comment, you know, from their progress internally. That would really be more of a direct question for them. But, you know, we were certainly pleased when Gilead had their R&D day, what's now called GS 1811, was part of that whole presentation. And so we're happy with the way that is moving forward. And, of course, that allows for a potential for milestones coming down the road, which are not included in our current financial forecast.

Thanks, Richard. Thanks for taking my question.

One moment for our next question. Our next question comes from Nick Abbott with Wells Fargo.

Your line is open.

Hey, morning. Thanks for taking my question. It's rather early here on the West Coast. I'm going to ask a silly question first, which is just on the cash runway, Rich, is this the corporate jet that's going? What are you doing to extend the cash runway? Are some programs not going to move ahead as fast as they were? Just maybe a little bit of clarity on that, please.

Yeah, sure, Nick. I think, you know, generally speaking, I think, you know, I think everyone, given the state of the markets, is looking very hard at this. And so what we've done is to maintain the value generation kind of swim lanes, if you will, of key programs, but also adjust our timing. And as our timing adjusts, we can look at, you know, what we planned versus what we're, you know, seeing in the actuals. So I will mention we've worked really hard across the company to look at that very hard. You know, we are within the range that we originally gave at the lower end of the range, which we're happy to report today. Kim can comment on this as well.

Sure. So to specifically answer your question, Nick, it's not the private jet. We've never had that. And also, importantly, we've not cut any programs. We've really just tried to take a hard look. think about the market conditions, think about ways in which we can extend our runway. And as with any financial forecast, as you get closer and you know your doses, your timing, things like that, you're able to refine it. And we just took a really hard look at it, just given the conditions, and feel good about where we are.

Okay, thanks. And then maybe just sort of going back to, we've had several questions on 8064. And truly, what is this meaningful increase? Is it Beth, is it 2x, 3x the ORI you expect to see, you know, with PD-1 monotherapy or standard of care? You already have cohorts that have been enriched of potentially responsive patients. So, you know, you could argue you really need to see a pretty high bar of efficacy, and that needs to be backed up by correlative science that supports why you're seeing activity. So maybe if you can just give me your thoughts on, you know, what you're thinking in terms of what you need to see, and then, you know, if it's how important is duration of response, i.e., I mean, would you be ready to make a decision on a registration trial designed by early 23, or do you need to see how these responses play out over time? And that decision may be second half of 23. Thanks.

Sure. That's a great question, Nick. Thank you. So, first of all, yes, duration of response is very important. That's obviously one of the differentiators for immunotherapy is that the responses tend to last longer than they do with chemotherapy. So that will be an important part of our decision making. I guess the way to think about it is we need to see response rates high enough in these single arm cohorts to give us the confidence to move forward. I think the next step would be a randomized study, whether it's a phase three study or phase two, three study. you know, depends on the data and how clear the, you know, and how rapid we think the path can be. Also what the, you know, degree of unmet need is. And so I think it really is, we have to see a response rate that's high enough for us to have confidence to go ahead and start a randomized study.

Okay, terrific. Thanks, Beth. And then I think that maybe last time we talked a little bit about CMC. I know you're putting A lot of effort, you know, there's a lot of drug product required here, so you're putting a lot of effort into that. Can you just give us an update on where you are in terms of being able to manufacture products, registration quality, quantity?

Yeah, sure. I can take that one, Nick. Thanks for that. Yeah, you know, we've... reflective of all of our programs as we kind of zero in on the doses necessary We are always looking to create processes that are done in a proactive way such that they can be very scalable and very controlled. So we've not taken the approach to, you know, fly into phase one and then create kind of an issue as you might want to expand that. So we've got a lot of experience in our CMC group, people who have been through the drill many a time. And so these processes from productivity to scalability are done in a very proactive way. That is, you know, reflective of a study, of course, you feel the benefit of that, in a study that has many different cohorts, and we're looking to see how many of those cohorts might move ahead. Of course, you have to be ready for that since there's, you know, at least a year-plus kind of lead time if you want to flip the switch. So really what it is is a kind of early productivity and kind of manufacturability analysis that goes into everything we do quite early so that it becomes predictable as we scale.

Thanks, Rich. So just integrating, you know, your response to Beth's then, what do you think the earliest is you'd be able to move ahead on a registration trial? towards the end of next year?

Yeah, I think, as I mentioned, Nick, you know, the next step will be randomized trials. And, you know, based on the data next year, we would plan to start randomized trials. And the data, you know, we think that the final POC data will be in the early 2023. and that's what would trigger randomized trials.

Yeah, and maybe, Nick, just a quick comment back to the CMC question. That won't be a gating factor for us. It will really be the clinical data that will be driving that.

Okay, great. And then the last one really is just on sort of a two-parter, really. Obviously, you know, Merck has a co-formulation of Hembro, and I keep forgetting the number, you know, that four-number formula. You know, you have PIMI, obviously AB64. Are you looking to co-formulate? There was a question earlier on competitive landscape. You're in a very good position here. And then, you know, as this program hopefully expands broadly next year, what are your thoughts on partnership and, you know, given current valuations and potential valuation in this program, what sort of collaborative structure makes sense at this time?

Yeah, so the way we look at that, you know, currently, Nick, is that we believe the, you know, combinations of the two are very quite manageable for us. And, you know, we're using PIMI for other things as well. So we'll continue, you know, we'll continue on that track certainly for the moment. I mean, having said that, we are looking at, you know, very rationally designed types of bispecific kind of partners as well. You know, on the going to the partnership side of your question, I mean, we're really looking to, depending on the data, move forward as rapidly as possible. Now, certainly there could be scenarios that might indicate, you know, Jounce could take programs forward further and, you know, with our analytics built around that of building more value, as well as perhaps the types of partnerships that might need or be well served to happen sooner. So based on just the realities of taking multiple types of cohorts forward. So that really dictates the data outplay, the number of cohorts, That really kind of moves the sliding on the scale as to how we're thinking about partnerships. But inherent in all of those is that we really want to create and maximize the value for Johnson and shareholders.

Okay. Thanks, Rich. That's it for me.

And I'm not showing any further questions at this time, so this does conclude today's conference. You may all disconnect and have a wonderful day.