Revolution Medicines, Inc.

Good day, and thank you for standing by. Welcome to Revolution Medicine's fourth quarter and full year 2023 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Erin Graves, Senior Director of Corporate Communications and Investor Relations.

Please go ahead. Thank you and welcome everyone to the fourth quarter and full year 2023 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer, and Jack Anders, our Chief Financial Officer. Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call. As we begin, I would like to note that our presentation will include statements regarding the current beliefs of the company with respect to our business that constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act. These statements are subject to a number of assumptions, risks, and uncertainties. Actual results may differ materially from these statements, and except as required by law, the company undertakes no obligation to revise or update any forward-looking statements. I encourage you to review the legal disclaimer in our corporate presentation and our earnings press release, as well as all of the company's filings with the SEC concerning these and other matters. With that, I will turn the call over to Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer.

Mark? Thanks, Erin. Good afternoon, everyone, and thank you for joining us. We will keep our prepared remarks brief today in light of the corporate presentation we provided at the J.P. Morgan Healthcare Conference in January. Today, I'll review highlights of our company progress and lay out several important 2024 milestones for our pioneering Rasson inhibitor pipeline. And Jack Anders will provide highlights of our financial results. 2023 was a transformative year for Revolution Medicines. First, we disclosed the preliminary clinical profiles of two unprecedented targeted Rasson inhibitors, RMC-6236 a RAS on multi-selective inhibitor, and RMC6291, a RAS on G12C selective inhibitor, as evaluated in Phase I 1B trials in patients with RAS-mutated cancers. Initial safety, tolerability, and antitumor activity data reported at the TRIPLE meeting and ESMO Congress showed that both investigational drugs have highly differentiated clinical profiles, suggesting substantial promise for patients, and supporting their continued development. We also announced in September that we had dosed our first patient in the phase 1 1B trial of RMC9805, an oral and covalent G12D selective inhibitor, our third distinguished Rason inhibitor in clinical development. As I'll summarize momentarily, this important progress with our first wave of Rason inhibitors provides significant momentum heading into this year's plans. and we believe serves as validation of the RAS on inhibitor platform and deep pipeline more broadly. Second, we ended 2023 with a particularly strong balance sheet bolstered by the EQRX acquisition that fuels our ambitious plans aiming to maximize clinical impact and drive shareholder value. With a strong pipeline and financial position, we have three strategic priorities for 2024. First, Building on strong clinical momentum with our boldest and most mature investigational drug with broad potential, our highest priority in 2024 is to propel single agent RMC6236 into its first pivotal trials. We are currently working toward the goal of launching randomized controlled trials against standard of care chemotherapy for patients with RAS mutated non-small cell lung cancer or pancreatic ductal adenocarcinoma. and we expect that these efforts will command the largest share of our resources this year. Encouragingly, at the J.P. Morgan Conference, we disclosed that with ongoing follow-up since ESMO, the RMC6236 safety profile had remained relatively stable, including at 300 milligrams per day, with relatively few dose interruptions or discontinuations. In the non-small cell lung cancer cohort, we reported favorable trends for aggregate objective response rate cross doses into the low to mid 40s range and that were trending even higher in the 300 milligram cohort. In the pancreatic ductal adenocarcinoma cohort, we reported favorable trends for aggregate ORR into the mid 20s and that were trending even higher in the 300 milligram cohort. We are now focused on the 300 milligram dose and below for both lung and pancreatic cancer and continue to follow these patients as we develop a more mature data set to determine progression-free survival, or PFS. We've begun preparing our regulatory packages for dose selection and monotherapy pivotal trials that we plan to initiate in the second half of 2024. Beyond advancing into late-stage development in second-line lung and pancreatic cancers, our second strategic priority for 2024 is to expand the reach of RMC6236. We've begun evaluating the impact of single agent 6236 in patients with tumors harboring RAS mutations beyond the G12X mutations that had been the focus of the dose escalation, mainly G13X and Q61X mutations. Likewise, we're studying 6236 in patients with tumor types beyond lung and pancreatic cancer, including colorectal cancer, melanoma, and gynecologic cancers. We anticipate disclosing initial clinical PK, safety, tolerability, and activity data from the genotype and tumor type cohorts in the second or third quarter of 2024. In addition, we've initiated combination drug cohorts to examine options for reaching into first-line treatment settings. For example, we've begun evaluating RMC6236 in combination with a checkpoint inhibitor, a combination that is likely required for advancing into first-line treatment for lung cancer. We anticipate disclosing initial data in the second half of 2024, with establishing safety of these combinations as the main focus. Our third priority for the year is to qualify our Ransom mutant selective inhibitors for late stage development, RMC6291, our G12C selective inhibitor, and RMC9805, our G12D selective inhibitor. At the triple meeting in October, we reported preliminary results with RMC6291 monotherapy supporting clinically meaningful differentiation at doses that were generally well tolerated. Based on dose optimization work that has been completed, further study of RMC6291 as a single agent continues at 200 milligrams BID. As a major next step for RMC6291, we have initiated our first RAS-on inhibitor doublet trial with RMC6236 in patients with advanced KRAS G12C mutated cancers. Patients are currently being treated in the dose escalation portion of the trial, and we anticipate disclosing initial clinical PK, safety, tolerability, and activity data in the second half of 2024. We've also begun treating patients with RMC6291 and a checkpoint inhibitor to assess the safety of this combination. For our G12D selective inhibitor, RMC9805, we shared at the JPMorgan conference that oral bioavailability of RMC9805 has been confirmed in patients. We've seen pharmacokinetics consistent with expectations from our preclinical data, including dose-dependent increases in plasma exposure on once-daily dosing. We've cleared several dose levels with good tolerability, and no dose-limiting toxicities have been reported thus far. We anticipate disclosing initial safety and activity data in the second half of 2024. Finally, these ambitious clinical development priorities for advancing our first wave of Rasson inhibitors are made possible by our strong balance sheet, which now includes approximately $1.1 billion of cash from the acquisition of EQRx that closed in November. With our compelling pipeline, innovation engine, and financial position, We aim to continue building and solidifying our position as an industry leader in developing targeted medicines for patients living with RAS-addictive cancers for many years to come. I'd like to now turn the call over to Jack Anders, our Chief Financial Officer, to provide the fourth quarter and full-year financial update.

Jack? Thank you, Mark. We are pleased to strengthen our balance sheet with the acquisition of EQRx. which added approximately $1.1 billion in net cash proceeds after estimated post-closing wind-down and transition costs. We ended the year with $1.85 billion in cash and investments, which is expected to fund planned operations into 2027 based on our current operating plan. Q4 and full-year 2023 financial results included $26.9 million in operating expenses associated with the wind-down of EQRX, which primarily consisted of non-recurring accounting charges associated with employee-related termination expenses and stock-based compensation expense resulting from the acceleration of EQRX equity awards in conjunction with the closing of the transaction. These were mostly one-time accounting charges specific to the close of the transaction in 2023 and are not expected to repeat in 2024. Collaboration revenue was $0.7 million for the fourth quarter of 2023 compared to $15.3 million for the prior year quarter, and $11.6 million for full year 2023 compared to $35.4 million for the prior year. Decrease in revenue was due to the termination of the company's collaboration agreement with Sanofi in 2023. Total operating expenses for the fourth quarter of 2023 increased to 180.7 million, largely driven by R&D expenses, which totaled 148.5 million. Total operating expenses for full year 2023 increased to 498.8 million, with R&D expenses increasing to $423.1 million. As noted earlier, our Q4 and full year 2023 operating expenses included $26.9 million in expenses associated with the wind down of EQRx. The remaining increase in total operating expenses for Q4 and full year 2023 was primarily due to an increase in clinical supply manufacturing and clinical trial expenses for our ongoing clinical development programs, increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation expense. Net loss for the fourth quarter of 2023 was $161.5 million, or $1.14 per share. For the full year, net loss was $436.4 million, or $3.86 per share. Turning to financial guidance for 2024, we expect full-year GAAP net loss to be between $480 and $520 million, which includes estimated non-cash stock-based compensation expense of $70 to $80 million. The increase in expected gap net loss for 2024 is a result of increased expenses associated with the progression of our ongoing clinical development programs. I'll now turn the call back over to Mark.

Thank you, Jack. In summary, in 2024, we at RevMed have ambitious plans to deliver on clear priorities for our pioneering Rason inhibitor portfolio, building on tremendous momentum coming out of 2023 and enabled by a strong balance sheet and a highly talented and motivated team. We remain committed to discovering, developing, and delivering innovative targeted therapies for patients living with RAS-addicted cancers. On behalf of our organization, I'd like to extend our deep appreciation to our patients, clinical investigators, scientific and business collaborators, advisors, and shareholders. This concludes our prepared remarks for today. and I'll now turn the call over to the operator for the Q&A session.

Thank you. As a reminder, to ask a question, you'll need to press star 11 on your telephone. To withdraw your question, please press star 11 again. Please wait for your name to be announced. We ask that you please limit your questions to one and one follow-up until all have had a chance to ask a question, after which we'll be able to answer any additional questions from you as time permits. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question comes from the line of Mark Fromm with TD Cowan. Your line is now open.

Hi, Tim. This is Ernie Rodriguez for Mark. Congrats on all the progress, and thanks for taking our questions. The question is on the combinations with PEMBRO for 6291 and 6236. What would you like to see on that early data in the combinations for you to feel comfortable to make a decision to move those combinations into pivotal development?

Hi, Ernie. Thanks very much for your question. Primarily, what we're looking for is to validate safety. As you know, the biggest challenge And while we have early reason to believe that this is less likely to happen with either 6236 or 6291 compared to the earlier compounds, that's something we just have to evaluate. And so that's really the main thing we'll be looking for is establishing a safety profile that can support moving into first line. Thank you.

That's helpful. And then the second one, do you remind me if You mentioned before, I don't remember, the potential or how you think about the potential for combining 9805 with 6236?

Sure. We haven't said much about that other than we considered the 6291 plus 6236 combination to be sort of a key test case. And if those combined, would be early on that list.

Got it. Thank you. Thanks again for taking our questions.

Thank you. One moment for our next question. Our next question comes from the line of Michael Schmidt with Guggenheim Partners. The line is now open.

Hey, good afternoon. Thanks for taking my questions. Yeah, Mark, we really appreciate the maturing phase one data for 6236. I think you've made comments on how the data has been improving or changing over time now. But I'm just curious if you could comment a bit more on, you know, how much more data do you need to support initiation of phase three and also to fulfill a project optimist requirements before launching the pivotal studies as a monotherapy? Thanks so much.

Thank you, Michael. Appreciate that question. Right, so the update that we provided in January that you're referring to had to do with response rates, and that information is helpful for guiding dose selection. And, of course, we're incorporating that updated information into our analyses and into packages for the FDA. So that's really for dose selection. I think for moving into the pivotal trials for a mature PFS assessment or estimate that can come from more mature observation, which obviously we're developing now. And that really leads to finalization of a trial design with statistical power and so on, and accompanying all that, of course, is FDA input. So I think those are the key elements for making a final go decision associated with each of those trials.

Okay, thanks. And then you've highlighted a number of potential data disclosures in the second half of this year, including additional monotherapy and then also early combination data from all three of your programs. Can you just help us understand the sequence of events? You know, will this all come at the same time? Is there some of the data that might come before we see other data? Could you help us understand the cadence of data disclosure in the second half a bit better?

I wish I knew. I'd be able to tell you. You know, we have some ideas about how things might roll out, but I think it's too early to really set out a schedule. We're not engineering it for a particular disclosure methodology. Just as the information becomes available and as it becomes appropriate to disclose it, we'll do so. I think clearly what people are most anxious to hear about is the timing, is a go decision and timing and details about the final plan for those pivotal trials. So that's clearly what we would highlight as the most important event in the second half of the year, but it is also true there will be other information coming out as we outline the milestones.

Great. Well, thanks so much, and congrats on the progress. Thank you.

Thank you. One moment for our next question. Our next question comes from the line of Eric Joseph with J.P. Morgan. Your line is now open.

Good evening. Thanks for taking the questions. Maybe just following up on Mike's question regarding regulatory buy-in and the finalization of the pivotal studies. Is visibility on sort of activity in the context of G12X and Q61 mutations needed at all to sort of get buy-in on the nested efficacy analysis as part of your proposed design? And then I have a follow-up to that question.

Okay, thanks, Eric. Thanks for joining us today. You know, clearly we're trying to make decisions in collaboration ultimately with the FDA about what to include in that final trial design, and to the extent that we have any activity information that can guide it, We'll include that information in conversations with the FDA. We do, of course, have preclinical data that suggests, that supports the notion that really all mutant forms of RAS, certainly all that we've ever tested, showed some degree of sensitivity to RMC6236, and the elevation of the G12X population, you might recall, came out of a large cell line panel that shows a statistically greater sensitivity of the G12X population of tumor lines to 6236 than the others, but did not distinguish them as yes versus no. It was more quantitative signal that highlighted them, and therefore we prioritized them in the dose escalation study. So the bulk of the data that we have is around the G12X group, but we are working to gather additional information that extends into these other genotypes, as you alluded to, and to the extent that we can include that in our final determination of what's the best design, we'll certainly discuss that with the FDA as well.

Okay, great. And maybe just a follow-up on plant combination studies with 1636. Specifically, can you talk about what the getting steps are to starting a Frontline pancreatic combination study with chemo. Is there a particular chemo regimen you're looking to combine with, you know, between either fulfirinox or gempaclitaxel? And, you know, beyond adequate tolerability, is there an efficacy signal that you'd want to see in a combination study to warrant pursuit of a frontline opportunity?

Yeah, thanks for that question. I really appreciate your enthusiasm. You're moving us to first-line.

It's terrific.

You know, there is, I think, growing interest in the first-line space with HARPC 6236, given what investigators have experienced so far. Maybe Dr. Lin, our chief medical officer who's joining us today, can comment on what we're looking for to help us make the decision about launching and designing and launching such a trial.

Yeah, how do you do that, Mark? Hi. I think you did mention the two current regimens that are currently at the center of care. One is MoFi for Viranox. The other is Gemabraxane. And both are in wide clinical use. So we would be exploring the combination with both of these regimens in an early phase study. And the benchmark for those are Gembraxane typically has a response rate in a 20% to 30% range, and then modafinilferanox in a 30% to 40% range. So that's really being superior to either one of these would enable us to really move forward into a first-line setting. Obviously, that's just the response rate. Ultimately, we'd like to provide survival benefit, and so PFS would be another metric we'd be looking at.

Okay, great. Thanks again for taking the question.

Thank you. And our next question comes from the line of Jonathan Chang with Lering Partners. Your line is now open.

Hi, guys. Thanks for taking my questions. First question, with an enviable year-end cap balance of about $1.85 billion, can you discuss your high-level thought process around how one spends that capital effectively within the context of all the moving parts in your pipeline? And then second question, On RMC6236, what is your latest thinking on what a development path forward in second-line pancreatic cancer could look like?

Would the Phase III primary endpoint of that study be OS or PFS? Thank you. Thanks, Jonathan.

I think on the first question, which was capital allocation, given all the competing opportunities that we have, you know, I think we've been pretty clear One strategic priority is to advance 6236 into pivotal trials in second line pancreatic and lung cancer. And no question that from our bandwidth perspective and even direct spending that supports it, that the allocation of capital is made accordingly. So that's going to take the lion's share of our effort. So then beyond that, we've identified these two additional corporate priorities for 2024, which is to expand the reach of 6236, and you've heard the various ways in which we're doing that, and that requires a certain amount of capital and a certain amount of bandwidth, and then qualifying our mutant selective inhibitors 6291 and 9805 to advance into late-stage development. That requires a certain amount of capital, too. So those are clearly kind of ring-fenced, and elevated in priority for 2024. That doesn't account for the entire budget, of course, because we have programs that go beyond those assets. Those are earlier stage programs, either defined development stage assets, of which we have several that we've identified and talked about, and then we have a robust discovery effort that leverages years of accumulated know-how to build out second, you know, later generation grants, inhibitors, and so on. So, you know, we're going to continue to allocate according to those priorities, but we are thinking about not just the near term. So when we're making these investments in 2024, we have to meet our 2024 goals, but we also are trying to build our strategy, our data set, and our asset, you know, pool that would sustain and protect a franchise once we're able to create a commercial franchise from the earliest assets that move forward. So lots of things to invest in. It seems like we have a lot of capital today. At some point, it won't feel like that much capital, but we're managing according to a very strategic plan.

Understood. And then just on the 6236,

development path in pancreatic cancer?

The 6336 monotherapy second line pancreatic cancer clinical trial design.

Yeah, exactly, exactly. And what is your latest thinking on what that primary endpoint could look like? Thank you.

Well, I think, yes, I think we can Lynn can comment most directly on that.

Yeah. I think that an endpoint currently we're looking at is really a dual endpoint of PFS and global survival OS.

Thank you.

One moment for our next question, please. Our next question comes from the line of Ellie Merrill with UBS. Your line is now open.

Hey, guys. Thanks so much for taking the question. Just heading into the initial KRAS combo data later this year, I guess, what would you consider good data from this, from the 6236, 6291 combo, and what are you focused on from this initial data? Thanks.

Okay. Thanks for joining us, and thanks for your question. Yeah, the RAS doublet is really kind of another differentiating angle of RevMed's portfolio and strategy. I think, at the moment, we're really and the preclinical data strongly supported and do support evaluating 6236 in combination with 6291 in G12C cancers. What we don't know is exactly how that will play out translationally in humans. We know what that looks like, and it can look like increased depth of response and increased durability of response or increased frequency of response. So really everything you can measure, you can see in the preclinical studies, but it's very hard to try to tie a direct line from those into the human studies. So I think a fair amount of this will be keeping our eyes wide open and looking for early signals that we then want to chase down and have to validate further. But I do think the very first question is simply, is it a safe combination? Is it safe and tolerated? And the two components of that seem to be safe and well tolerated to date. But putting the two together, we just need to verify first that that doesn't create any out and looking for the clinical activity signal that I just alluded to, whether it's frequency response, depth of response, or durability response.

Great. Thanks so much. And just a quick follow-up. I guess, which indication should we expect data on in the expansion cohorts from 6236 and the data update later this year? And then more broadly, I guess, in the CRC cohort, what are you looking to see to make a go, no-go decision thinking longer term for a potential pivotal study start there? Thanks.

Okay, I think you managed to squeeze in at least the third question. Nicely done. So in terms of the data that we've committed to communicating later this year, trials under contemplation here, pancreatic cancer and lung cancer. And so there's a data set associated with each of those. And I think those would be sort of headline data sets to come out later in the year as we announce plans, go-forward plans. But then I think you were asking about going beyond pancreatic cancer and lung cancer. Expansion cohorts. Expansion cohorts that go beyond pancreatic and lung cancer. We've indicated that there are several different directions for those. One is different RAS genotypes beyond G12X, and we've indicated we'll provide some preliminary view of that sometime in the mid-year range. I think we said Q2 to Q3 timeframe. The second is tumor types beyond lung and pancreatic some information on that in the second half of the year. And then third is combinations that help us to begin to enable optionality for going into first line and the 6236-6291 combination we just spoke about and then combinations of 6236 with PEMBRO, 6291 with PEMBRO and then Wei alluded with chemotherapy. So there's a wide range of things that are going to happen. A good number of those we could read out in the second half of this year.

Yes, did you want to follow up on that?

Thank you. Our next question comes from the line of Amy Fadea with Needham & Company. Your line is now open.

Hi, good evening. Thanks for taking my question. I've got one follow-up and a question just on the PDAC data that you'll be presenting from the ongoing study data this year in second line. Could you tell us what you see as the bar in terms of PFS that you would like to see? And with regards to your program or what you're pursuing in first line, You're developing 6236 in second line, or at least you're planning to initiate a pivotal study there. What is the clinical rationale or the hypothesis in terms of what would be the right combination partner with PEMBRO plus minus chemo, whether it would be 6236 or 6291? If you could sort of share your thinking there, that would be helpful. Thanks.

Let me comment on the first question, and then I might ask you to repeat the second question, because I'm not sure that I completely tracked it. Your question was in second line PDAC, what is the bar that would compel us to move forward from a PFS perspective? That's what you're asking? Yeah, I don't think we've really specified a particular number. Of course, we have our own internal benchmarks, but we've not publicly discussed those no-go, no-go decisions. But we're clearly looking to be superior to second-line chemotherapy, and we know what median PFS is in virtually every second-line study that's ever been done. You know, it's really around three to three-and-a-half months at best in true second-line patients. Keep in mind, our population is not truly second-line. Our population is second, third, and potentially even some beyond that. People have had multiple different... But nonetheless, we've said what we're trying to do with our current patient population is to be superior to the well-accepted benchmark for second line. But how much superior, I think, is a question that goes beyond what we've commented on today. If you want to repeat your second question, then we can figure out who's the best person to comment on that.

Sure. You know, just from a mechanistic perspective, I can understand, you know, if 6236 as a monotherapy makes sense in second line, I understand the logic behind exploring a combination of that with PEMRO in first line. But why would someone treat with 6291 plus PEMRO in first line and then move to 6236 in second line? Just hypothetically.

Ah, so your question is in pancreatic cancer, If you received RMC-6236 as part of a first-line regimen, why would you continue, why would you repeat 6236 as part of a second-line regimen? Is that what you're asking?

Well, or why would you start with 6291, which is more targeted, you know, as a first-line treatment, and then move to 6236, which is broader?

Ah, okay. Now I understand. So we're talking about KRAS G12C cancers. specifically. You're talking about lung cancer. And your question was, if we combine 6236 with 6291 in first line? No? I'm not following it. So maybe you can interpret the question and you can answer it.

Let me interpret your question. So I think what I'm hearing you say is that if we were able to succeed in developing 6291 plus PEMBRO where 6291 plus PEMBRO and chemo, and that becomes a new standard care for T12C patients in first-line lung, why would patients get 6236 with a second line? Is that your question?

Yeah, yeah, that's helpful. Thanks.

Yeah, so I can go ahead. Now I have some thoughts on it. Okay. Yeah, I'll take a stab at it. I mean, that's certainly one scenario we could develop it using a 6291 purely based regimen plus either PEMBRO mono for the PD-L1 high or PEMBRO plus chemo for all patients. There's another scenario where we could be developing 6291 plus 6236 plus PEMBRO without key chemo, right? That would be another option. Just want to put that out there. But let's take what you put on the table, which is 6-9-1 plus PEMBRO with 6-9-1 plus PEMBRO plus chemo. If that became the standard care in first line, I think we still do believe that there could be scientific rationale for 6-2-3-6 to remain as an option in the second line setting. And the reason is the following. I think it really has to do with the way that a RAS-indicted tumor behaves in developing resistance against any G12C inhibitor. I think there's a wealth of data from sotiracib, adagracib, and diviracib. I think one really emerging sign is, number one, 89% of those tumors retain original G12C mutation. They don't lose it. Number two, the vast majority of the resistant mutation involves some type of either another RAS mutation or another mutation in the RAS pathway to reactivate the RAS pathway. So what we call a RAS rescue mechanism. So rescuing or reactivating the RAS seems to be the predominant mechanism, and hence it goes along, I think, with how Mark's really describing these tumors as RAS-addicted. I think the fact that they're addicted means that they are really relying on turning the tumor pathway back on in RAS. And hence, the broad-spectrum activity of 6236 involving not only other RAS mutations that can potentially cover, so if a tumor would develop a GCOD mutation to bypass the GCOC, that 6236 can remain active And furthermore, even if the patient were to activate a receptor-targeting kinase like EGFR and the signal goes through a well-type RAS, that 6236 can also cover. So there are so many resistant mutations that are well-characterized for the current G12C inhibitors that potentially 6236 can be active against. So I think it still provides rationale. Obviously, we need to generate clinical data to support that. 446236 remains the standard care in the set-line setting, even if 6291 establishes itself as a first-line treatment choice.

So you got yourself a very scholarly answer to that question. I just want to circle back to the first thing.

That was very helpful.

Yeah, if I could just go back to the first thing that Wei said, it's really important. It might have gone by a little bit quickly. which is that although we're testing 6291 plus PEMBRO, and we're also evaluating 6236 plus PEMBRO, we're also evaluating 6291 plus 6236, and all three of those are a way of triangulating potentially on a triplet combination of 6291 plus 6236 plus PEMBRO, which would be, as Wei said, a chemo-free regimen for first line. It's not the only outcome of that. either one of those agents. We'll see. We'll let the data tell us what makes sense to do.

That makes sense. Thanks.

Thank you. One moment for our next question. Our next question comes from the line of Alex Stranahan with Bank of America. Your line is now open.

Hey, guys. This is John. I'm on for Alex. Thanks for taking our question. Just a quick one from us. In terms of second half data updates, what could be the venue that we would be expecting? Would it be like a medical conference, or should we just be expecting like a press release or like an yesterday? Any color on that, that would be great if you can share it.

Thanks, John. Hard to answer that question because there's so many different data sets that we've listed there that could come out in the second half of the year. medical conferences. It's not always up to us. It just depends on the timing and availability. Often these things require abstracts that are submitted long ahead of when we might have the information. So we'll pick a forum for each of the disclosures that suits it to make sure that we're not holding on to data that investors need to know about.

Okay. Thank you for the call out.

Thank you. One moment for our next question. And our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Oh, hey. Congrats on the progress, and thank you for taking the question. As you look ahead to the potential for multiple pivotal trials, can you just talk about how you're thinking about partnering opportunities both in the U.S. and outside the U.S.? ?

Hi, Jay. Thanks for joining us, and thanks for your question. I think, again, we've been pretty consistent about this, which is that in the U.S., we really believe this is a serious opportunity for RevMed to build its own franchise and to use the RASP portfolio to create a very strong and leading franchise. So I don't think we're particularly keen on sharing any of that with a partner, and I don't think there's any reason to do so, at least as we see things today. Outside the U.S., it's pretty clear that we don't have much opportunity there. That's a much more complex context in which to think about commercializing. We can't do development outside the U.S. We already do development outside the U.S., but doing pivotal, late-stage global development typically takes a real amount settings and different geographies. So that can be done. That can be enhanced by working with a partner that already has that infrastructure. And then, of course, commercialization per se is not something that we have any near-term plan to pursue on our own. So I think it's pretty clear that an ex-U.S. partner or partners could be in the offing for us at some point in the future. We're open to that possibility. And when the right opportunity presents itself and it makes sense for us to do it, I'm sure we would do so.

Super helpful. Thank you very much. And if I could ask one follow-up. As you look ahead to the potential tumor agnostic setting for 6236, can you just talk about the regulatory path that you're thinking about there?

Dr. Weyland is talking about that question. Yeah, I have to address that. I think we already presented probably activity in non-small cell lung cancer as well as pancreatic cancer. So those are probably going to be served as anchor in our approach to tissue diagnostic. Right now, we're actually rolling patients with colorectal cancer, melanoma, as well as gonoclastic cancers, as well as other cell tumor. And obviously, to be very much data-driven, broad activity we've seen recently that this molecule could potentially help as many as 30% of patients with solid tumor with RAS mutations. So we should like to test that hypothesis to the fullest, and then the data will drive our decision about how much of the tissue mass can be inspired.

Okay, great. Thanks again for taking the questions.

Thank you. As a reminder, to ask a question, you'll need to press star 1-1, and please wait for your name to be announced. Our next question comes from the line of Laura Prendergast from Raymond James. The line is now open.

Hey, guys. Thanks for taking the questions, and I look forward to seeing all these data updates later in the year. Just one for me. I'm curious, since you're running, you know, at the same time, this PAN-RAS trial and then RAS-selective clinical trials, Have you gotten any feedback from trial investigators on how they make the decision on whether to enroll patients on a PAN-RAS trial or a RAS-selective trial? Assuming that you probably have some trials going on at the same locations, I'm just curious if you've gotten any insight there.

Yeah, I'll just make a general comment. In most of the indications we're talking about, the need for these compounds is so high that there are more patients than we can possibly just as inherently limited. So I don't think there's really any sort of near-term issue associated with that, but maybe Wei wants to comment further about when you're into pivotal trials, how might that affect, if any?

Yeah, I think that the physical health should reflect really well what we've seen so far in terms of, you know, queen patients and men who are aggressive, I think. just really highlight this is a usual situation. This is the biggest driver in all of oncology. And then by enabling this, it really unlocks a huge amount of need. So all the patients coming in interested in our trial is reflection of that.

Great. Very helpful.

Thank you very much. Thank you. One moment for our final question, please. Our final question comes from the line of Ben Burnett with Stiefel. Your line is now open.

Hi, this is Kaylee Reza on for Ben Burnett. Thanks for taking our questions. I just had one quick question about RMC 6236. I was wondering if you could give us any additional color on how the confirmed response rates for non-small cell lung and PDAC are trending post-ESMO. Thank you.

Yeah, thanks for your question. You know, as we mentioned in January and reiterated here, we've seen favorable trends in the response rates. You're asking specifically about confirmation, and I think generally what I can say is that most responses do confirm. Most of the responses that have been unconfirmed previously have been subsequently confirmed, except in those instances where somebody progressed always enrolling new patients and getting unconfirmed responses while we're being asked about what's the confirmed response rate. So I say you'll have to hang on and wait until later in the year when we'll try to give more precise information.

Okay. Thank you very much. Thank you. I'm currently showing no further questions in the queue at this time. I'd like to hand the conference back over to Dr. Mark Goldsmith for closing comments.

Well, thank you, Operator, and thank you, everyone, for participating today and for your continued support of Revolution Medicine.

This concludes today's conference call. Thank you for your participation. You may now disconnect, everyone. Have a wonderful day.