Jounce Therapeutics Inc (JNCE) 2020 Q4 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Jounce Therapeutics Fourth Quarter and Full Year 2020 Earnings Conference Call. (Operator Instructions) As a reminder, this conference is being recorded at the company's request.

I will now turn the call over to your host, Malin Deon, with Jounce Therapeutics. Please go ahead.

Thank you, operator. Good morning, and welcome to the Jounce Therapeutics Fourth Quarter and Full Year 2020 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 & Media section of our website at www.jouncetx.com. Speaking on today's call will be our CEO and President, Dr. Rich Murray, who will discuss our pipeline progress and key milestones for 2021; followed by our CMO, Dr. Beth Trehu, who will provide an update on our clinical activities; and lastly, our CFO, Kim Drapkin, will review our full year 2020 financial results and 2021 guidance. 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 provision 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, February 25, 2021, and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change.

With that, I will now turn the call over to Rich.

Thanks, Malin, and good morning, everyone. As we reflect on 2020, I'd like to note the meaningful progress Jounce has made to advance our growing discovery and development IO pipeline to align directly with the needs of cancer patients. Our new potential first-in-class programs and biomarker approaches are aimed at both PD-1 inhibitor-naive patients as well as the growing PD-1 inhibitor-experienced population. With 2 proof-of-concept studies actively enrolling patients, a sustainable and robust discovery effort, validated via an important out-license to a partner, and a strong balance sheet, we are entering 2021 with the potential to make significant positive impacts on the lives of cancer patients.

2020 saw the achievement of important clinical execution milestones for our highest priority program, JTX-8064, a LILRB2, also known as ILT4 inhibitor, as well as for vopratelimab, an ICOS agonist. In January, we announced that enrollment commenced in INNATE, our Phase I JTX-8064 clinical trial. The INNATE trial is designed to move quickly through the necessary dose escalation portion of the trial, leading directly to the opening of multiple tumor-specific expansion cohorts in the second half of the year. These expansion cohorts will include both JTX-8064 monotherapy as well as combination therapy with our own PD-1 inhibitor, JTX-4014.

In October 2020, we began enrolling biomarker-selected patients in SELECT, our Phase II proof-of-concept study of vopratelimab, also in combination with our PD-1 inhibitor, JTX-4014. Not only will the SELECT trial test the impact of vopra, we will also gain additional important single agent data for JTX-4014 in the new biomarker selection paradigm. We believe the TIS vopra biomarker will select more appropriate patients for both the CD8-mediated benefit of a PD-1 inhibitor as well as for the potential CD4-related benefit of vopra.

In addition, in October 2020, we licensed to Gilead the worldwide rights to JTX-1811, a potential first-in-class antibody, designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells. We continue to progress JTX-1811 to IND clearance, and we are on track for IND filing in the first half of 2021. On clearance of the IND, JTX-1811 will transfer to Gilead for clinical development and potential commercialization. In addition to the $85 million upfront and $35 million equity investment, Jounce has the potential to earn up to $685 million in milestones as well as royalties on worldwide sales. Although our primary goal is to retain and develop our wholly owned Jounce discovery programs, in this instance, we felt an out-license was the right deal at the right time. It's given us the financial flexibility to fund our 2 proof-of-concept studies and further progress our translational discovery engine and bring new candidates forward.

As we look to 2021, the significant unmet need faced by many cancer patients continues to be at the forefront of everything we do. Beth will take you through more details on our 2 POC studies, INNATE and SELECT, in a moment. But before turning the call over to her, I'd like to take this opportunity to reflect on what we believe it will take to bring meaningful and long-lasting benefit to cancer patients. As PD-1 inhibitors expand into earlier lines of therapy, including non-metastatic settings, the scope of the PD-1 inhibitor resistant market continues to grow. Unfortunately, most patients receiving a T cell checkpoint inhibitor as their first IO therapy will not benefit, highlighting the need for new treatment options.

We continue to believe that new mechanisms targeting different immune cells in the tumor microenvironment will be required to derive meaningful clinical benefit in the growing population of patients with PD-1 inhibitor resistant tumors. The need for novel approaches highlights the importance of our Translational Science Platform and our productive sustainable discovery engine, which has allowed us to generate targets beyond T cells, most notably, JTX-8064. JTX-8064 aims to convert immunosuppressive macrophages to an antitumor state and create a bridge between the INNATE and adaptive immune systems. This is something T cell checkpoint inhibitors cannot do alone, and it may result in the potential to reverse PD-1 inhibitor resistance.

More broadly, beyond JTX-8064, our discovery efforts are aimed at additional members of the LIL family of receptors as part of the dedicated strategy around the myeloid-based cells of the immune system. Beyond the LIL receptor family, we remain committed to addressing the needs of cancer patients through our early-stage discovery programs. Our discovery engine is built upon the capability to thoroughly investigate different cell types in the tumor microenvironment. In addition to myeloid cells, we believe stromal cells are another important target, with the potential to modify this environment and allow the immune system to become fully operational in the tumor.

Jounce has stayed true to its initial scientific mission of investigation, discovery and development of therapies that target different cell types in the tumor microenvironment, aided by a biomarker approach with the aim of enabling the immune system to fight tumors. We believe this approach will be necessary to reach new levels of therapeutic benefit generated by the immune system. I'd like to take a moment now to welcome the newest member of our Board of Directors, Dr. Luisa Salter-Cid, who was appointed earlier this month. Dr. Salter-Cid will further expand Jounce's immunology and IO expertise, and we look forward to her valuable contributions.

With that, I'll turn the call over to Beth to discuss our clinical pipeline and science in more detail.

Thanks, Rich, and good morning, everyone. We made great progress at Jounce in 2020, and I am very proud of the work our team has done to enable us to execute on our 2 ongoing proof-of-concept studies, INNATE and SELECT. These programs are key to our belief that novel mechanisms and biomarker strategies are necessary to bring clinical benefit to patients who do not optimally benefit from T cell checkpoint inhibitors. As Rich mentioned, our pipeline is well poised to address the significant unmet medical need of patients with tumors that are either sensitive or resistant to PD-1 inhibitors.

I would now like to provide more detail about our ongoing clinical trials, beginning with our highest priority program, JTX-8064, which is designed to reprogram immunosuppressive, or M2 macrophages, to immune stimulatory, or M1 macrophages, in order to enhance or restore antitumor immune activity. The mechanism of action is very different from other macrophage targeting therapies such as inhibition of CSF1R to deprive the myeloid lineage of a key growth factor and CD47 to improve macrophage-mediated phagocytosis of tumor cells.

JTX-8064 is a LILRB2 antagonist antibody, which we view as a macrophage checkpoint inhibitor with the potential to reverse PD-1 inhibitor resistance. A primary ligand of LILRB2 are HLA molecules, which are critical in the recognition of cells by the immune system, preventing our immune cells from destroying our own normal tissues. When LILRB2 binds to its ligand, which include HLA-G on tumor cells and HLA-A and B on immune cells, it induces an immunosuppressive state, similar to the effect of PD-1 binding to PD-L1. In preclinical studies, JTX-8064 interferes with the binding of LILRB2 to its ligand, resulting in an immune stimulatory state with production of pro-inflammatory cytokines, improved antigen presentation and T cell activation.

LILRB2 is expressed on cells in the innate immune system such as macrophages. We have evidence of the direct macrophage M2 to M1 conversion from in vitro studies in which JTX-8064 reprograms the cytokine production of macrophages from immunosuppressive cytokines such as IL-10 to immune stimulatory cytokines, such as TNF alpha. In addition, when JTX-8064 blocks the binding of LILRB2 to HLA-A and HLA-B on the macrophage itself, these critical parts of the antigen presenting machinery of the cell are now able to function again, resulting in improved antigen presentation and T cell activation.

LILRB2 is not expressed on T cells, which are members of the adaptive immune system. Importantly, we have shown that JTX-8064 treatment of cells derived from both peripheral blood and human tumors ex vivo results in T cell activation, providing evidence of JTX-8064's ability to create a bridge between the innate and adaptive immune systems. This biology, along with recently reported initial clinical data on another LILRB2 inhibitor, suggests the potential for JTX-8064 in combination with PD-1 inhibitors to reverse PD-1 inhibitor resistance as well as to further improve outcomes in PD-1 inhibitor sensitive tumors, thereby having the potential to provide clinical benefit to a wide range of cancer patients.

At the start of this year, we began enrollment in the INNATE Phase I clinical trial of JTX-8064 alone and in combination with our own PD-1 inhibitor, JTX-4014. Our trial is designed to progress quickly through dose escalation and demonstrate proof-of-concept in tumor-specific expansion cohorts. The expansion cohorts will address multiple different patient populations to identify the best and most rapid development path for JTX-8064. Indications will be selected based on a variety of factors, including biology, RNA signatures and the opportunity for differentiated development pathways. Additionally, an important part of our indication selection process involves an examination of the unmet need and opportunities across 3 major IO segments.

The first group is patients who are PD-1 inhibitor-experienced, whose tumors are now PD-1 inhibitor resistant. This represents a large and growing area of unmet need, in which a drug that reverses PD-1 inhibitor resistance, could make a great difference for patients since chemotherapy is the predominant and not very effective standard of care. Importantly, for Jounce, there are no approved PD-1 or PD-L1 inhibitors in this patient population, giving us the opportunity to develop 2 wholly owned Jounce products, JTX-8064 and JTX-4014 as a combination approach.

The second group is PD-1 inhibitor-naive patients who have tumors for which there are no PD-1 or PD-L1 inhibitors approved because they generally have not demonstrated much efficacy. If JTX-8064 can reverse this type of primary resistance, a combination with a PD-1 inhibitor could make immunotherapy a therapeutic option in this area of high unmet need. This also represents an opportunity for JTX-8064 plus JTX-4014 due to the lack of approved PD-1 inhibitors.

The third group is PD-1 inhibitor-naive patients who have tumors for which there are approved PD-1 or PD-L1 inhibitors, where some patients achieved durable clinical benefit, but there is still much room for improvement. Developing JTX-8064 in this setting would give us the opportunity to treat frontline patients in combination with PD-1 inhibitors. We plan to include all 3 groups of patients in our expansion cohorts as we explore the best opportunity for JTX-8064 to make a difference for patients with cancer.

As part of the trial, we will also be collecting data on a number of different pharmacodynamic and potential predictive biomarkers. The findings will help us guide further development and are an important part of Jounce's philosophy of providing the right immunotherapies for the right patients. As enrollment in INNATE continues, we will begin to guide on the timing of data readouts. We are pleased with the progress of the trial and completed enrollment in the first dose cohort in January. We also plan to present preclinical data on JTX-8064 at multiple scientific meetings this year.

I would now like to turn to an update on vopratelimab and our first biomarker patient selection trial, SELECT. The SELECT trial, which we initiated in October 2020, is currently enrolling approximately 75 immunotherapy-naive, second line non-small cell lung cancer patients, who will be selected using the predictive TIS vopra biomarker and randomized to vopra plus our PD-1 inhibitor, JTX-4014, versus JTX-4014 alone. TIS vopra is an 18-gene signature that includes genes relevant to both CD8 and CD4 T cell biology and has been optimized to predict for emergence of ICOS hi CD4 T cells in the peripheral blood, which have been associated with clinical benefits in patients treated with vopra plus or minus nivolumab.

We expected approximately 20% of second-line non-small cell lung cancer patients to be TIS vopra positive, and we are pleased that screening to-date has validated this projection. We are continuing to screen and enroll patients in SELECT, but we are experiencing COVID-19-related delays that are impacting patient enrollment. Given the challenges we are facing, we now anticipate reporting data from the SELECT trial in 2022. As Rich mentioned, 2021 is an important year of execution and key milestones for Jounce, building on our team's key accomplishments in 2020. We would not be where we are today without the dedication of our team, our valued investigators and, most importantly, the patients who put their trust in our drugs to make a difference in their lives. We look forward to continued progress in 2021 as we focus on trial enrollment and collection of high-quality clinical and biomarker data to guide our program.

Now I would like to turn the call over to Kim for a discussion of our year-end financial results. Kim?

Thanks, Beth, and good morning, everyone. As we reported in this morning's press release, we ended 2020 with cash, cash equivalents and investments, totaling $213.2 million compared to $170.4 million for 2019. The increase was primarily due to the receipt of $120 million in proceeds from the license and stock purchase agreements with Gilead and $14.5 million received during 2020 under our ATM program, offset by operating expenses incurred during the year.

Turning to the P&L. Our license and collaboration revenue was $62.3 million for full year 2020 compared to $147.9 million for 2019. Revenue recognized during 2020 was related to our license agreement with Gilead. Revenue recognized during 2019 was related to a license fee and collaboration revenue under our former Celgene license and collaboration agreement. During 2020, we recorded $78.7 million in research and development expenses compared to $67.1 million for 2019. The increase in R&D expenses was primarily due to $7.9 million of increased clinical and regulatory expense, primarily attributable to the SELECT clinical trial, $3.2 million of increased manufacturing and IND-enabling expenses and $2.9 million of increased employee compensation costs. These increases were partially offset by decreased travel and lab consumable costs.

General and administrative expenses were $28.8 million for 2020 compared to $27.9 million for 2019. The increase in G&A expenses is primarily the result of increased employee compensation costs. Net loss for 2020 was $43.8 million or a basic and diluted net loss per share of $1.24 as compared to a net income of $56.8 million in 2019 or a basic net income per share of $1.72 and diluted net income per share of $1.66. Net loss for the full year 2020 was attributable to increased operating expenses, offset by $62.3 million of license revenue recognized under our agreement with Gilead.

Net income for the full year 2019 was primarily attributable to $147.9 million of revenue recognized under the Celgene license and collaboration agreements in the year. In 2020 and January '21, we sold a total of approximately 5.2 million shares, resulting in net proceeds of $44.7 million under our ATM offering. These sales were primarily block trades to biotechnology investors and resulted in the completion of the existing ATM. We reiterate our 2021 financial guidance we provided in January. We continue to expect gross cash burn on operating expenses and capital expenditures for the full year 2021 to be approximately $95 million to $110 million.

Given the strength of our balance sheet, we expect our existing cash, cash equivalents and investments, including the additional $30.2 million in funds received in January 2021 under our ATM program, to be sufficient to enable the funding of our operating expenses and capital expenditure requirements through Q2 2023. Additionally, we continue to have the flexibility to drive our innovative immunotherapy pipeline while efficiently executing against our strategic plans and goals.

With that, I'll hand the call to Rich for his final thoughts.

Thanks, Kim. On the heels of a strong 2020 of pipeline execution and corporate development, we're poised for an important year with the following key milestones: establish safety and recommended Phase II dose for JTX-8064 and open tumor-specific expansion cohorts in the second half of 2021; continue enrollment to enable reporting of preliminary efficacy and related biomarker data for vopra and JTX-4014 from the SELECT trial in 2022; continue IND-enabling activities for JTX-1811 and anticipate an IND clearance in 2021; and continue to advance our discovery pipeline of first-in-class programs with the goal of a new IND every 12 to 18 months. We look forward to updating you on our progress throughout the year.

Before I close, I'd like to take this opportunity to thank the investigators and Jounce employees, who, despite the challenges we all faced during the COVID-19 pandemic, remain dedicated to our mission of bringing new therapies and benefit to cancer patients. And most importantly, we extend our thanks to the patients, who we have had the privilege to treat.

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

(Operator Instructions) Our first question comes from Boris Peaker with Cowen.

So my first question is on 8064. I'm just curious, have you compared it to Merck's drug in preclinical development? And if yes, what are the differences that you observed between yours and Merck's drug?

Yes, I'll take that one. This is Rich. Yes. We have compared it in the following way. We've posted data in various presentations that we've been at. Merck has done that as well. So comparing those 2 different kind of releases of data from each company, respectively, 8064 is very potent, very specific inhibitor of LILRB2. Based on the existing data that we can compare in this way, we see similar properties we believe that kind of leads to the potential of read-through from the Merck data releases. And importantly, we view kind of the potential of kind of differentiation as we move forward as something, of course, we'll pay attention to. But like PD-1 approval landscape, we see many, many opportunities that are really dictated by clinical strategy and, of course, our biomarker implementation in the future as well.

Great. And my second question is, obviously, you're in dose escalation phase right now. I'm just curious based on your preclinical work, when do you anticipate to get to a therapeutically minimal effective dose at the current rate?

Boris, this is Beth. I'll take that one. I think what we've said to date is that the study is designed to move as quickly as possible to dose -- to getting to a potentially therapeutic dose and expansion of the tumor-specific cohorts, which are designed to demonstrate proof-of-concept. And so if you think about a typical Phase I trial, sometimes it can take a year or even 1.5 years to get to that point, whereas we started enrollment and actually completed enrollment in the first dose cohort in January. And we are expecting and on track to open the expansion cohorts in the second half of this year. So I think that would say within 6 months from now, we expect to be at a dose that we think is potentially therapeutic, and that's when we would open expansion cohorts.

Our next question comes from Mike Ulz with Baird.

Maybe I could ask another one on 8064 and maybe a bit of a follow-up to Boris' question here. Just for the dose escalation, obviously, you're through the first cohort. I don't know if you can comment, but how many cohorts are you anticipating testing?

Yes. I think rather than getting into the specifics of the number of cohorts, I'll just reiterate. We expect to be through dose escalation and into our expansion cohorts by the second half of the year.

And will that just be for the monotherapy? Or will that be for both the monotherapy and the combination expansion?

Yes. We'll be initiating the cohorts for both monotherapy and combination in the second half of the year.

Got you. And then maybe just the last quick question for me. You seem pretty confident that you'll be in that position in the second half. And I guess just given what's happening with SELECT and COVID having some impact there and delaying things, is there any risk to those time lines at this point? Or what you're seeing is -- gives you enough confidence that you can hit that time line?

Yes. That's a great question, Mike. We are not currently experiencing any COVID-related delays for INNATE. You're right though, there's a lot of uncertainty. If we think we'll encounter delays, we'll let you know. But we believe with the number of sites, the enthusiasm of the investigators and the way that the trial is going so far, at this point, we feel comfortable saying that we'll be in those expansion cohorts the second part of the year.

Our next question comes from Arthur He with H.C. Wainwright.

Here is Arthur for RK. So I have 2 questions. One is regarding the 8064. I was just wondering if you guys could give us more color on the tumor type selection for the tumor-specific cohorts? Or we kind of still waiting for the data from the dose escalation study? And the second question regarding the 1811, the IND filing. So what other preparing you guys require to before filing IND?

Okay. So this is Beth. On the indications for INNATE, we will identify the tumor types that we've selected and the scientific rationale behind them midyear, this year at either a company-sponsored event such as an R&D Day or at a medical meeting.

Yes. And I can take the question for 1811. Yes. So we're in the kind of typical stretch of where we are in the IND-enabling process for monoclonal antibodies where the focus really is on ensuring the supply is produced, generated appropriately, all the analytical data is in shape and then compiling that into -- ultimately into the IND. So as is typical for an antibody, that's usually the rate limiting factor. So yes, we're comfortable with where we are. That's going well. And we're engaging with our colleagues at Gilead as we look to transfer that program.

Yes. And maybe I can just add that another important part of the IND is the clinical protocol, and we're working very closely with Gilead on that, and it's going very well.

(Operator Instructions) Our next question comes from Steve Seedhouse with Raymond James.

A couple of questions about 8064, just on the biomarker strategy first. Would this be something -- would you anticipate this being something as simple as just looking at HLA expression like HLA-G expression or even LILRB2 expression? Or are you thinking this will be like a TIS vopra-like RNA signature? Maybe if you could just talk about sort of what types of biomarkers you're exploring? And then relatedly, do you know if HLA-G or LILRB2 are overexpressed in PD-1 resistant patients? And then I have a quick follow-up.

Sure. So in terms of the biomarkers that we're exploring as potential predictive biomarkers, many of those were in the poster that we presented at SITC 2020, and they -- we were very pleased to see how well they correlated with the biology. So LILRB2 is one, HLA-A and B were included and also our proprietary tumor-associated macrophage signature. So for this first study, we will be exploring a broad panel of both gene signatures and also immunohistochemistry biomarkers. And once we sort of see how that plays out in terms of relationships with clinical data, that will help us to narrow down onto the predictive biomarkers that we think will be the best for the program. So I think we're in great shape. We have a number of different ones to test, and we'll be testing them retrospectively in this first study. But always with an eye to being able to identify something that we could test prospectively going forward. With respect to -- I'm sorry, I've forgotten your second question.

Just you know if the IHC-based biomarkers that you're including in that exploration, are they overexpressed in PD-1 resistant tumors?

Well, one thing we know is that one of the mechanisms of PD-1 inhibitor resistance is lack -- loss of HLA heterozygosity and also loss of beta-2 microglobulin, inability to present antigen. So we think that LILRB2 inhibitor such as JTX-8064 should help to address some of that. I'll let Rich add more on that.

Yes, yes. Some of that -- Steve, it's a good question, and we're really zeroing in on that. But some of the answers to that, stay tuned to the presentations that Beth was alluding to the scientific presentations. We'll have a lot more on biomarker data, characterization of different patient populations that we hope land in upcoming meetings.

Okay. Great. And then the last question I just had is, can you remind us if as we think about your LILRB2 and other ILT family member inhibitors in sort of emerging competitive landscape, I was hoping you can remind us. Are there any modifications or engineering to your antibody that are necessary to diminish or eliminate ADCC? And is that a feature that differs between some of these competitive antibodies? Is it relevant? Is it necessary? If you could just comment on that would be great.

Sure, sure. So I think the general emergence of these programs, we think they're likely to kind of continue is that, the Fcs will be disabled or minimized because really the -- for solid tumors because some of the biology is really heading towards straight up antagonism. We want to keep that receptor from binding from its ligand. Differing strategies will really be a completely different road to travel where there is potential in some heme malignancies where you may want to invoke some tumor cell specific targeting. That's not the way our molecule is built. Our molecule is built in a way that's similar to the design of Merck as far as we know, which is an IgG4. So we've minimized effector function. And so the kind of engineering that we foresee in the future is additional monospecific agents that are being brought forward that are highly selective to the different receptor families, the concept -- the potential of biospecifics, and, of course, the kind of the combination strategies that one would put into clinical trial design.

Our next question comes from Zegbeh Jallah with ROTH Capital Partners.

Just have a question on several of the different things you mentioned this morning. So the first is about vopra. I know you're not going to have data this year, but GSK did mention that they should have data from their program by midyear. So just kind of wanted to know how much read through should investors kind of take from what's happening with GSK? Is there any difference between the construct or anything like that, that should be accounted from there?

Yes. I'll let Rich address the differences between the molecules, and then I can say a few words about the clinical strategy.

Sure. Yes. I think there's a couple of levels of that. If we just look at the antibodies itself, we went with our preclinical data in terms of choosing our antibody, the binding sites, the Fc, and we chose IgG1 as our Fc. And that was explicitly chosen because that, I think everyone recognizes, gives you better signaling for an agonist antibody. So that IgG1 backbone is, in our opinion, the way to go for agonist activity.

What we've subsequently proven, of course, and derisked from our clinical data is that, that is associated with any cell depletion. That just simply doesn't occur. We've published that many, many times. So that's a difference. IgG1 in ours versus IgG4 in GSKs. We also believe just through kind of comparing data sets, preclinical data, that the binding sites may be a bit different as well. So our molecule, we believe, is a very highly potent engineered appropriately agonist to take forward. So just for a comparative standpoint, the molecules between GSK and Jounce for the ICOS agonists, our have some differences anywhere from nuances to things that could be more meaningful. I'm going to let Beth talk about the kind of the biomarkers and the clinical strategy and how we see that part of what could be read through.

Sure. So the data that we would expect them to be presenting this year would be in PD-1 experienced non-small cell lung cancer in combination with a PD-1 inhibitor, so very different from the trial that we did in PD-1 experienced non-small cell lung cancer. And then they're also going to be, we think, announcing whether their Phase II/III trial in frontline head and neck cancer will reach its gating criteria to move forward. So we look forward to seeing their data. But I think for us, we're using a biomarker selection strategy in our frontline -- I'm sorry, not frontline, but PD-1 inhibitor-naive non-small cell lung cancer study. And we're currently not studying head and neck cancer. So I think there are some similarities. It's obviously targeting the same thing. It's an agonist, but we've also taken a different approach with a biomarker and potentially also different dosing strategy. So there are enough differences that it's a little hard. It's not like what we've talked about with Merck 4830 and JTX-8064, where we think there's more similarities than differences. There may be some differences between our ICOS program and GSK's.

Yes. Maybe I can jump on to one more point there that is a little bit of, I think, learnings along the way here across immunotherapy, not just channels, is that as you go after those kind of T cell-T cell mechanism combos, we really think the IO-naive, PD-1-naive patient populations are the way to go. And our biomarker strategy is really looking to pull together the patients that we think are most appropriate for both the PD-1 effect as well as the effect of vopra, which we can measure through its pharmacodynamic activity and relationship to benefit. So I think our kind of biomarker strategy, as Beth alluded to, is also very kind of distinguishing for us. We think in that kind of space, you really, really want to find the right patients with the kind of multiple T cell mechanisms.

And then just a follow-up on 8064. Any comments on why enrollment might be going so well? And then are we likely to see any kind of data from that program before the end of the year?

Sure. So we worked with great investigators. We spend a lot of time talking about the science of the program, and I think they really believe in this mechanism. So also, patients are always looking forward to opportunities for novel IO therapy. So as I said, we're very pleased with how things are going to date. We've traditionally been able to enroll our Phase I clinical trials pretty quickly. I think for those reasons, we work very closely with the sites. We have a very hands-on approach. In terms of data, so we'll provide guidance in the second half of the year once we've opened the expansion cohorts on when you can expect to see data.

And then I'm actually just going to merge the next 2. The first one is about 1811. Just kind of wanted to know if you're going to get any kind of milestone payment once you transfer over the IND to Gilead? And then a follow-up to that is just also how much leeway you're going to have in terms of data updates on that program? Or it's just really going to just be driven by Gilead at that point?

And then lastly, Rich, you talked extensively about the [press on those] pipeline. So just want to know, are you going to nominate anything from the program from the pipeline this year? And then if you are, is it going to be one of the myeloid or the stromal targeted agents? And then I know this is quite long. But also, you talked a lot about targeting different cell types. So I'm just wondering, again, are you guys going to explore additional combinations beyond the PD-1 combos and things like that?

Sure. Zegbeh, thanks for your questions. This is Kim. I'll start on the Gilead, and then I'll hand it over to Rich, and he can give you some more information on your discovery-related questions. So in terms of the Gilead milestones, we're not at liberty to disclose when and if we'll achieve any milestones. But importantly, the $685 million in milestones that we have the opportunity to earn, $510 million of those are development and regulatory. So we were happy with the negotiation of that and the opportunity to earn milestones in the more near-term as opposed to being completely back-loaded. And just keep in mind also, all of our financial projections, like our cash going through Q2 2023, do not include the earning of any milestones. That would extend our runway even further. And when and if we earn a milestone, we will announce it at that time. And I'll turn it over to Rich for your other questions.

Sure. Yes. So Zegbeh, I may have missed the question, but you asked about new candidates. And yes, we're very excited about how things are going in discovery. We're quite active in kind of the myeloid-related space. So macrophages, LILRB2 with JTX-8064. There are other family members of the LIL family that invoke more dendritic cell biology or NK cell biology. We really think that kind of optimizing the therapeutic benefit from these different myeloid cell types is something that fits well with then combo with a PD-1 inhibitor. So kind of some of the lead discovery programs are kind of in and around that space. Stromal biology, we think, is kind of a next wave as well. So I'd rather not pinpoint a specific molecule at this point. The -- usually, when we get to kind of a development candidate, which is meeting a certain criteria for us, is when we announce that. And we're on track to do that. I may have missed a question.

I think the last one. You kind of hit on. It was just combos beyond PD-1 combo, maybe combining some of your other agents in your pipeline?

Yes. This is Beth. I can comment on that. So I think, as you know, we're really driven by the biology and really focus on rational combinations. So this is definitely an area we're continuing to explore for JTX-8064, as we've spoken about macrophage rich tumors are of interest for us. And there are published data showing that macrophage infiltration may increase after some chemotherapies or radiation therapies. So we're continuing to explore a breadth of combo opportunities for JTX-8064 because we really think it's a program with a lot of potential to make a difference for patients.

Thank you. Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may now disconnect. Have a good day.