Jounce Therapeutics Inc (JNCE) 2020 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Jounce Therapeutics Third Quarter 2020 Earnings Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded at the company's request. I will now turn the call over to your host, Malin Deon, with Jounce Therapeutics. Please go ahead.

Thank you, Operator. Good morning and welcome to the Jounce Therapeutics Third Quarter Conference Call. This morning we issued a press release which outlines the topics that we plan to discuss today. The release is available in the Investors & 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 progress and key milestones; followed by our CMO, Dr. Beth Trehu, who will provide an update on our clinical activities. Lastly, our CFO, Kim Drapkin, will review our third quarter financial results. We will then open the call for your questions.

Before we begin, I would like to remind everyone that today's discussion will include statements about our future expectations, plans, and prospects that constitute forward-looking statements for the 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, November 6, 2020, 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 you all know, we provided an update on our vopra program earlier this week and mentioned important pipeline prioritization changes. I'm pleased to share more detail on this with you today. This strategic shift reflects our view of the unmet medical needs defined by patients' responsiveness to current IO therapy, and further emphasizes our vision of bringing meaningful and long-lasting impact to cancer patients.

When thinking about the impact of IO, we believe the landscape can be broken down into 2 distinct patient populations. One, patients with PD-1 inhibitor-sensitive tumors; and two, patients with PD-1 inhibitor-resistant tumors. Both have significant and unmet medical need, represent large and growing market opportunities, but may differ in how to bring -- best bring forward long-lasting therapeutic benefit, the hallmark benefit of IO.

IO therapies in solid tumors to date have had the most significant impact on certain patients within an overall PD-1 inhibitor-sensitive tumor types such as non-small cell lung cancer or melanoma. But unfortunately, at the individual patient level, it's still a minority of patients that benefit from checkpoint therapy. Patients with PD-1 inhibitor-resistant tumors can either present as resistant from the outset or develop resistance over time after initially receiving benefit. Overall, patients in the PD-1 inhibitor-resistant tumors are the most difficult to treat, and chemo is still largely the standard of care.

Given the increased use of PD-1 inhibitors in front-line metastatic disease, and the fact that most patients will initially or ultimately progress, the scope of the PD-1 inhibitor-resistant market continues to grow. To better progress our immunotherapies to meet the needs of cancer patients, we think about our current pipeline in reference to these 2 patient populations as follows, for the patients with PD-1 inhibitor-sensitive tumors, we believe a biomarker-driven approach and combination of PD-1 inhibitor and novel mechanism have the best chance to benefit patients beyond today's current regimens. Our vopra SELECT trial predictive biomarker study, and separately, our JTX-8064 macrophage program targeting LILRB2 or ILT4, a new mechanism, position us well to address the patients in this PD-1 inhibitor-sensitive population.

For the patients with PD-1 inhibitor-resistant tumors, whether primary or acquired, we believe novel mechanisms and approaches will be needed. In this context JTX-8064 is a novel program to convert immunosuppressive macrophages to an anti-tumor state and we believe could be an important mechanism for these patients.

Our early discovery programs also focused on novel mechanisms to address this patient population. By viewing our pipeline and biomarker approach through this lens, we can prioritize our resources and design our studies to address each of these distinct patient populations. I would now like to take a few minutes to provide updates from the quarter.

Earlier this week, we announced that an early look at the interim data from EMERGE did not meet pre-specified criteria for expansion of the study. Based on this interim data readout, we will not be expanding patient enrollment in EMERGE. Our focus in the PD-1 inhibitor-resistant population will shift to a strategy of targeting other immune cell types, in addition to T-cells, beginning with our JTX-8064, our LILRB2 program. As we discussed on the vopra call update, we will continue to follow the overall survival of the EMERGE patients still on study and monitor biomarkers.

We're also -- we also announced that enrollment commenced in our SELECT study. We look forward to reporting preliminary efficacy data from the SELECT trial in late 2021. We also expect to begin enrollment in our Phase I dose-escalation study of JTX-8064 by year-end. We're also pleased to announce that supporting pre-clinical biomarker data for JTX-8064 will be presented at next week's 2020 Citi annual meeting.

In September, Jounce and Gilead announced a license agreement for the worldwide rights for JTX-1811, our potential first-in-class antibody designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells. After clearing the HSR process the Gilead transaction closed in October of 2020. We believe this out-license further validates our pipeline and ability to generate value from our Translational Science Platform. In connection with the closing, we received an $85 million upfront license fee, and Gilead invested $35 million in Jounce stock. We continue to progress JTX-1811 to IND clearance, and we are on track for IND filing in the first half of 2021.

Beyond our development programs, we continue to make progress advancing our early-stage pipeline, despite the challenges presented by the COVID-19 pandemic. Our broad discovery pipeline includes multiple programs targeting myeloid cells, stromal cells and other PD-1 inhibitor-resistance mechanisms. These are all active targeted areas for our discovery engine, and we expect to see more valuable novel programs, like JTX-8064 and JTX-1811, emerge through our efforts.

Before turning the call over to Beth to go into more detail on our programs. I'd like to take a moment to acknowledge and thank Dr. Bob Tepper, a long-time member of our Board of Directors. Due to professional commitments at Third Rock Ventures, Bob is stepping down from his Board role at Jounce. We sincerely thank Bob for his contributions and leadership as he has been an integral part of the Jounce team since our inception.

I'll now turn the call over to Beth to discuss our clinical activities in more detail.

Thanks, Rich, and good morning, everyone. We have made great progress at Jounce this quarter, and I'm very proud of the work our team has done to enable us to initiate our next clinical study, SELECT. Despite the challenging times we live in, we continue to execute new trials and stay focused on our overarching goal of helping cancer patients. We are on track to begin enrollment, before year-end, in our first clinical trial with JTX-8064, our exciting new macrophage program. With the upcoming JTX-8064 trial initiation, we are set up for multiple clinical readouts in 2021 and beyond.

I would now like to provide more detail about our ongoing and soon-to-be-initiated clinical programs.

The SELECT trial, which we recently initiated, will enroll approximately 75 immunotherapy-naive second-line non-small cell lung cancer patients, who will be selected using the predictive TIS vopra biomarker, and randomized to vopra plus our PD-1 inhibitor, JTX-4014, versus JTX-4014 alone. TIS vopra is and 18-gene signature that includes genes relevant to both CD8 and CD4 T cell biology. The CD8-related genes contribute potential predictive value for PD-1 inhibitors, while the CD4-related genes are indicative of the presence of activated and, therefore, ICOS hi CD4 T cells, which are required for the activity of vopra. The threshold for the biomarker has been optimized to predict for emergence of ICOs hi CD4 T cells in the peripheral blood, which have been associated with clinical benefit in patients treated with vopra plus or minus nivolumab. We believe that the TIS vopra biomarker is ideal for patient selection in the SELECT randomized trial, due to its potential predictive value for both vopra and PD-1 inhibitors. We expect approximately 20% of second-line non-small cell lung cancer patients to be eligible for the trial based on TIS vopra and are pleased with the rate of patient screening to date.

SELECT is powered to demonstrate the superiority of vopra plus JTX-4014 to JTX-4014 alone. The primary endpoint is mean percent change from baseline tumor size of all measurable existing and new lesions averaged over 9 and 18 weeks, which was chosen for 2 reasons. First, several publications have indicated that percent change from baseline in tumor size at early time points may be an early predictor of overall survival for chemo and other types of cancer therapy, potentially better than RECIST overall response rate. This may be especially true with IO therapy in which durable tumor reductions that do not meet RECIST response criteria may still result in meaningful clinical benefit and improved survival.

Second, using percent change from baseline as a continuous variable rather than categorical RECIST response criteria creates an opportunity to establish statistical significance with a smaller sample size, which we felt was appropriate for this proof of concept study. We are also measuring and will report on all the traditional efficacy endpoints as well, including overall response rate, 9 months and median progression-free survival, disease control rate, duration of response and overall survival. Safety and biomarkers will also be part of the final study data.

I would now like to turn to JTX-8064, our lead macrophage program. JTX-8064 is a LILRB2 or ILT4 antagonist antibody, which we view as a macrophage checkpoint inhibitor designed to reprogram immunosuppressive M2 macrophages to immune-stimulatory M1 macrophages. When LILRB2 binds to its ligands, which include HLA-G on tumor cells and HLA-A and B on immune cells, it induces an immunosuppressive state analogous to the effect of PD-1 binding to PD-L1 on T cells.

Like the PD-1, PD-L1 interaction, the LILRB2-HLA-G interaction plays a role in maternal fetal tolerance, a fundamental immunosuppressive biology. JTX-8064 interferes with the binding of LILRB2 to all of its ligands, resulting in an immune stimulatory state with production of pro-inflammatory cytokines, improved antigen presentation and T-cell activation. This biology suggests the potential, to overcome PD-1 inhibitor resistance.

The first clinical data on another LILRB2 inhibitor suggesting safety and preliminary signs of efficacy in heavily pre-treated PD-1-experienced patients was recently presented at ESMO 2020. We are excited about the potential for JTX-8064 to benefit this difficult-to-treat patient population and expect to be the second clinical program for this target when we begin patient enrollment by the end of 2020.

Our upcoming clinical study with JTX-8064 will be a dose-escalation study with monotherapy, and in combination with our own PD-1 inhibitor, JTX-4014. Our trial is designed to demonstrate proof of concept early, with multiple tumor-specific expansion cohorts at a pre-defined target dose. These expansion cohorts will include both JTX-8064 monotherapy and combination with JTX-4014 and both PD-1 inhibitor-sensitive and resistant patients.

At the SITC meeting next week, we will have a poster providing preliminary information on our approach to predictive biomarkers and indication selection for JTX-8064. We will provide more specifics on the trial design after enrollment commences. And in 2021, we will begin to guide on when readouts will be available on the Phase I study of JTX-8064.

Before I close, I would like to highlight the opportunities that we now have to combine drugs from our own pipeline with the inclusion of JTX-4014 in both SELECT and the JTX-8064 Phase I study. JTX-4014 has all the pre-clinical characteristics of a typical PD-1 inhibitor and demonstrated a 17% RECIST response rate in heavily pre-treated patients in a small Phase I study, with a preliminary safety profile similar to approved PD-1 inhibitors. Of note, the patients enrolled in our Phase I trial of JTX-4014 who were required to be PD-1 inhibitor naive, we're more challenging to treat then patients enrolled in the first clinical trials of PD-1 inhibitors, as patients with all the typically IO responsive tumors in which PD-1 and PD-L1 inhibitors are approved were excluded. We, therefore, expect JTX-4014 to contribute similar efficacy to approved PD-1 inhibitors in our combination studies.

We are excited to be initiating studies with approaches beyond T cell-focused therapies and to potentially make a difference in the lives of patients not currently served by today's approved therapies. Our team has always done a great job on execution, which has Jounce well-positioned to be an IO leader with multiple clinical programs across novel areas of biology, and with the potential to improve outcomes.

Now I would like to turn the call over to Kim, who will provide a financial update.

Thanks, Beth, and good morning, everyone. As we reported in this morning's press release, cash, cash equivalents and investments as of September 30, 2020, totaled $105.3 million compared to $170.4 million as of December 31, 2019. The decrease was primarily due to operating costs incurred during the period. Not included in the September 30, 2020, cash balance is the $120 million we received upon the closing of the Gilead agreement in October 2020.

This additional capital provides us with a strong balance sheet.

Turning to the P&L. During the third quarter of 2020, we incurred $18 million in research and development expenses compared to $15.1 million for the same period in 2019. The increase in R&D expenses was due to IND-enabling costs for JTX-1811, external clinical and regulatory costs associated with the SELECT clinical trial and increased employee compensation costs, partially offset by decreased lab consumables and travel expenses.

General and administrative expenses were $7.1 million for the third quarter of 2020 compared to $6.5 million for the same period in 2019. The increase in general and administrative expenses was primarily due to increased employee compensation costs, partially offset by decreased facility expense.

Net loss for the third quarter of 2020 was $24.9 million, or a net loss per basic and diluted share of $0.73 as compared to a net income of $98.9 million for the same period in 2019, or a net income per basic share of $2.99 and net income per diluted share of $2.90. The increase in net loss was primarily attributable to no license and collaboration revenue in the third quarter 2020 and the increase in operating expenses.

We are reiterating our financial guidance and continue to expect gross cash burn on operating expenses and capital expenditures for the full year 2020 to be approximately $80 million to $95 million.

In closing, we continue to have the flexibility to drive our innovative immunotherapy pipeline while efficiently executing against our strategic plans and goals. We expect our existing cash, cash equivalents and investments to be sufficient to enable the funding of our operating expenses and capital expenditure requirements into 2023.

I will now turn the call back to Rich for final remarks.

Thanks, Kim. In conclusion, Jounce is on track to achieve the milestones we set for 2020. And importantly, by year-end, we also plan to initiate the Phase I trial of JTX-8064, our LILRB2 program.

With the recent closure of our deal with Gilead, we are also well capitalized with a cash runway into 2023. This will allow us to continue to fund our high-quality discovery engine while executing on multiple clinical trials and advancing our wholly-owned pipeline. With multiple clinical programs, 2021 is poised to be a strong year of execution and results, including filing the IND for JTX-1811 in the first half of 2021 and transitioning the program to Gilead to begin clinical studies; executing across multiple clinical trials, including SELECT, with the data readout in late 2021; and later this year, initiating the Phase I JTX-8064 trial, and continuing to work on advancing multiple new targets from our discovery pipeline for patients in the PD-1 inhibitor-sensitive and resistant populations.

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

(Operator Instructions) Our first question comes from the line of Mike Ulz from Baird.

Just on 8064, you mentioned the potential biomarker to select patients and you'll have some more details at SITC so I'm not sure how much you're willing to comment at this point, but should we be thinking of something similar to a TIS vopra where you're kind of looking at gene signatures?

So yes, it's a little too early for me to comment on that. I think what you'll see at SITC is our approach to exploring biomarkers using human histoculture, which are slices of human tumor that we actually can evaluate. And you'll see sort of some -- also the process that we go through to try to understand indication -- potential indications and sort of pair that with where potential biomarkers might be taking us, but we're not giving any details at this point.

As you know, Mike, we usually incorporate multiple potential predictive biomarkers and pharmacodynamic biomarkers into our studies. So it will really depend on the data that comes out of this first study that will let us know if there is a good predictive biomarker to take forward.

Got it. And then maybe just sticking with 8064, and maybe you guys can just comment on the competitive landscape. And I realize it's early, but are there any differentiating features of 8064 -- or should we be also thinking about just the strategy in terms of the path forward, maybe that's a way to differentiate from one of the other products out there?

Sure, I'll take that one, Mike. As we look at the kind of the binding of the inhibitory antibodies to the targets, our view is that appropriate kind of potency, specificity binding antibodies to LILRB2 are going to be more similar than they are different. And part of that is really due to the nature of these receptors is a -- a little group of these receptors in humans. The binding, they're all very, very similar to each other.

So with that being said, there's maybe 2 things to point out. So we think the differentiation is really going to be in how we take forward different indications, different lines of therapy, perhaps guided by the biomarkers as Beth referred to. So as we see the SITC poster next week, one could envision that being a tool leading us to a differentiated path in the clinical programs.

The other comment I'll make is that LILRB2 is one of this group of inhibitory receptors, primarily on the myeloid cells, and so there are kind of broader strategies that we have in discovery around that whole family. We think this is a group of receptors that have really kind of been under the radar screen in terms of their potential for immunotherapy, but that would be more of a layout of the pipeline in the future.

Our next question comes from the line of Jim Birchenough from Wells Fargo Securities.

It's Nick on for Jim this morning. First, has the 8064 IND being filed? Or can you tell us when it will be filed?

Yes. So we don't usually comment on that, Nick. All I can tell you is that we're on track to start enrolling patients before the end of the year.

Okay. Fair enough. [2020], thank you. And then, just going back to TIS vopra, can you talk about the logistics of TIS vopra and does it present any challenge for recruiting patients in what must be a very highly competitive space?

Sure. So we've actually been really, really pleased by the investigator engagement and enthusiasm about the study, and about their -- the screening that's going on. So basically patients sign a pre-screening consent form that allows their tissue to be submitted for screening. And then their physician is informed about whether they are TIS vopra-positive or not. At that point, they complete the rest of the screening for the study. For every clinical trial, there's a screening period, and that they have to past the eligibility criteria and have certain labs checked for eligibility.

The turnaround times for the test is a week or less so we have not found that to be a barrier. As I said, there seems to be a lot of enthusiasm. The investigators are doing a lot screening. And we've also opened the pre-screening even to sites that aren't actually actively going to enroll patients in the trial but have been identified as referral sites for some of the trial sites. So recognizing that when you have a predictive biomarker, it always does pose a challenge to enrollment. But we've put a lot of measures in place that we believe will help to mitigate that.

And then maybe just following up on that. So is this on the archival tissue? Or is this on fresh tissue? And do you think that matters?

Yes, that's a great question. So because these are PD-1 inhibitor-naive patients who have only had their front-line chemotherapy. And as you know, even if people respond to chemotherapy, they usually progress rather quickly. We didn't feel it was necessary to get fresh tumor biopsies, so we're using archival tumor. But in most cases, it will be less than a year before they get screened for this study. So we felt that that was sufficient.

Our next question comes from the line of Cory Kasimov from JPMorgan.

This is Gavin on for Cory. Actually, I had a follow-up from the last question on TIS vopra. Is there any reason to suggest that -- I mean you said that 20% of the lung cancer patients are eligible for the trial. Is there any reason to believe that there is geographic differences in the patient population for TIS vopra? And then also, does first-line chemo have an impact on the expression of TIS vopra to your knowledge?

Sure. So we don't have any reason to believe there would be a geographic difference. Lung cancer, the primary risk factor for lung cancer is smoking no matter where you live. And so we don't believe there's any reason for there to be a geographic difference.

With respect to your second question, which was -- sorry, I just blanked. What was your second question, Gavin?

The potential impact of first-line chemo...

Oh, of chemo. Sure. Sure.

Or other first-line regimen such as EGFR treatment?

Sure. These patients are only allowed to have had a platinum-containing regimen, not targeted therapy, so we don't expect the targeted therapy to have any impact. If anything, chemotherapy has -- there have been reports suggesting that chemotherapy may make tumors a little bit more hot, but we don't have any direct data on the difference between totally treatment-naive and chemo-treated tumors regarding TIS vopra, but we don't have any reason to believe that it would have a significant impact on that.

Our next question comes from the line of Steve Seedhouse from Raymond James.

Just regarding the primary end point of SELECT, can you maybe comment on the powering assumptions there, basically what tumor size reduction Delta it's powered for, and what is the power?

And then, I wanted to clarify the detail regarding using this as a continuous variable from week 9 to 18, I think you said. Can you maybe just clarify how many tumor measurements patients were actually having, and at what time points?

Sure, sure. So I'll answer the second question first. So they will have their CT scans, obviously, pre-treatment and, then at 9 weeks and then at 18 weeks. And so because IO sometimes can take a little bit longer, responses deepen over time, we felt it was important to include the 18-week scan data, but we felt that averaging the 2 would give us kind of the best estimate of the tumor response to treatment.

We're not really stating right now what exactly the target difference is. But at some point, we will -- we'll talk about that more. I think what's important is that we have a sample size that with our assumptions would be sufficient to demonstrate statistical superiority. If at some point, if we look at the data and it's certainly heading in the right direction but we were wrong about our assumptions, particularly about the response rate to the PD-1 inhibitor or the tumor shrinkage with the PD-1 inhibitor, we do have an opportunity to do a onetime sample size readjustment.

Got it. And I think I know the answer to this, but maybe just to clarify on the call here. The -- this is not sequence treatment, this is treating with the PD-1 inhibitor in combination.

Correct.

So at both the 9- and 18-week time points, everyone will have received the same cumulative dose of PD-1 inhibitor, correct?

Correct.

Okay.

Correct. That's correct.

Okay. And then just on the LILRB2, it seems like, just through our conversations over the past week, that this is really becoming a focus for investors. There's a lot happening in this field. I'm just curious if it's possible, I know you don't know for sure, you haven't even started the study, but is it possible that data from that Phase I study could be sort of the next new clinical data you have even before the end of 2021 when you've guided SELECT data would be available?

Yes, it's still a little too early to say, Steve. We will definitely provide more detail about the study design after we announced that we've started enrollment. And then once we get a sense of how things are progressing, we'll guide to when we would have data. But right now, it's a little bit too early to say.

Okay. I appreciate that. And then, just lastly, the -- curious in the wake of the EMERGE readout that you reported. Are there any future plans to pursue vopra plus CTLA-4 inhibitor or have you more or less moved on past that hypothesis and focused on PD-1 combination through SELECT? Or, obviously, GSK is moving ahead in head and neck, maybe that's an avenue. Just curious your thoughts there.

Sure. So we're always following the science. So we certainly will look at the data as it matures and always be looking for things that we think make sense. However, as we've stated, really, if you look at all of the things that have failed when they're just another T cell-based mechanism adding on to a PD-1 inhibitor or whatever you add to a PD-1 inhibitor in the -- in the PD-1 resistant space, it really -- we think it makes sense to start looking at a completely different mechanism of action in combination probably with PD-1 inhibitors. And the data that was presented recently looked really encouraging in PD-1-experienced patients, and therefore, since we have JTX-8064 and that target looks like even just biologically like it could help to restore or to overcome PD-1 inhibitor resistance, that really I think is a bigger focus for us right now. Also the safety profile looks really good as well. So right now, that's where we're going to focus our efforts on the PD-1-experienced patient population. And I don't know, Rich, if you wanted to add anything to that.

Yes, I think that's right, Beth. I think maybe, Steve, the way to think about it is, we think it's the right decision to not continue the enrollment as EMERGE was originally designed. We are going to follow the OS. We are going to follow the biomarkers. But as Beth stated that the science is really leading us, at least in the PD-1-resistant population, to these other types of mechanisms that get you beyond T cells as well as a T cell combo.

Next question comes from the line of Arthur He from H.C. Wainwright.

I just had a quick one on the 1811 program. So could you remind us what else you guys need to be done before the -- you file the IND?

Sure. I can take that one. Primarily, like any monoclonal antibody program, it's really the CMC path and the manufacturing and analytical work around the drug manufacturer that is usually on that kind of tail-end of the timing for the IND. So we're progressing that. As we've mentioned, it's our role in this deal to get the IND filed and opened, but we're primarily in those kind of last phases of making sure we have material ready to go.

Our next question comes from the line of segment of Zegbeh Jallah from ROTH Capital Markets.

Just had one quick one here. Beth, I think on the last call you provided some commentary around Merck's effort with their ILT4 program, that kind of give you guys some confidence. I was just wondering in terms of your clinical strategy moving forward, how it somewhat differs or compares to what Merck is doing? And then they also recently announced the partnership with NGM where they're dual-targeting ILT4 and ILT2 antibody. So just wondering, based on your knowledge, what you think you would expect from a dual-targeted agent versus a single ILT4-targeted antibody.

Sure, I'll address the first one and then -- and turn it over to Rich. So as I've said, we plan to demonstrate proof of concept as quickly as possible, but also we recognize that we do need to differentiate from Merck. So I think our trial is really designed to do that, to look, as I mentioned, at both monotherapy and combination with our own PD-1 inhibitor, look at PD-1 inhibitor-sensitive and resistant patients and certainly, include some cohorts that are differentiated from what Merck is doing.

Rich, would you like to speak to the bispecific?

Sure. Yes, sure. Sure. So first, I think it's important that we don't want to comment too much on that. I mean that's what we heard about from a press release rather than a scientific presentation. But the nature of the entire family of the low receptors, we think, is very, very interesting biology. And if you -- you need to have specificity for what you're targeting. Beyond that, there are commonalities between LILRB1 and LILRB2 and some distinctions.

So I think there is kind of a growing opportunity to look at these features that might be in common, as well as distinct. So for example, LILRB1, seems to be expressed on NK cells. So that's different for LILRB1. So that whole family, we believe, is going to be a very interesting one, and it could be kind of central in the myeloid kind of non-adaptive cell kind of realm, but it's really hard for us to comment beyond that generality given we haven't seen any data on that.

And actually, just one quick follow-up here for Kim. Kim, you mentioned that your current cash balances include, I think, the $120 million that you received from Gilead. And so I was just wondering if your cash runway does include that.

Thanks, Zegbeh. Yes, when thinking about the cash we have into 2023, that does include the upfront of $85 million from Gilead as well as the $35 million equity investment. What it does not include are any potential milestones that we may earn in the future under the Gilead deal. And you may recall that of the $685 million in potential milestones, $510 million of those are development and regulatory. So we were pleased that there are earlier-stage milestones and our hope is that we will earn these and the runway will be even further, but we do not include milestones in our projections.

Kim, and I suppose another follow-up here, but just confirming after the IND-enabling settings you're handing over the program to Gilead, who will take over, are you anticipating having to pay for any of the research in these or anything after that?

No, it's a complete out-license and so our expenses basically end on the development side as soon as we file the IND, and then Gilead takes it from there and they are responsible to develop and pay for the future developments.

That's really good considering the milestones that you could get. I appreciate it.

Thanks, Zegbeh.

Our last question comes from the line of Jim Birchenough from Wells Fargo Securities.

Just a question on the SELECT trial, the listing on ClinicalTrials.gov has 2 dose levels of vopra. Can you just elaborate on that, please?

Sure. After we analyzed all the data from the ICONIC trial, where we had patients dosed at 0.3 mg per kg every 3 weeks, which resulted in sustained target engagement or binding of vopra to ICOS all the time, we determined based on some reports in the literature and then also some additional pre-clinical data that for an agonist molecule such as vopra, it's probably better to have more pulsatile target engagement, so pulsatile dosing and target engagement.

So in the SELECT trial, as in the EMERGE trial, we are looking at 2 different doses with what we believe will be differentiated patterns of target engagement. So 1 dose is 0.1 mg per kg and the other 0.3 mg per kg, both given every 6 weeks. And although the 0.1 per kg data in the EMERGE trial actually looked better than the [0.3], we don't really have sufficient data to make a decision at this point about which dose is preferable. So we're continuing to explore both doses in the SELECT trial. And the final analysis will look at the 2 dose levels combined, and then individually compared to JTX-4014 alone.

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.

Thank you.

You're welcome.