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'll be a question-and-answer session. 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 Morgan Healthcare Conference in January. Today, I'll review highlights of our company progress and lay out several important 2024 milestones for our pioneering RAS(ON) inhibitor pipeline, and Jack Anders will provide highlights of our financial results. 2023 was a transformative year for Revolution Medicine. First, we disclosed the preliminary clinical profiles of two unprecedented targeted RAS(ON) inhibitors, RMC-6236, a RAS(ON) multi-selective inhibitor, and RMC-6291, a RAS(ON) G12C-selective inhibitor as evaluated in Phase 1/1b trials in patients with RAS-mutated cancers. Initial safety, tolerability, and anti-tumor 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 RMC-9805, an oral covalent G12D selective inhibitor, our third distinguished RAS(ON) inhibitor in clinical development. As I'll summarize momentarily, this important progress with our first wave of RAS(ON) 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 RMC-6236 into its first pivotal trial. 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 JPMorgan conference, we disclosed that with ongoing follow-up since ESMO, the RMC-6236 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 across 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 began 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 RMC-6236. We began evaluating the impact of single agent RMC-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 began evaluating RMC-6236 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 RAS(ON) mutant selective inhibitors for late-stage development, RMC-6291, our G12C selective inhibitor, and RMC-9805, our G12D selective inhibitor. At the Triple Meeting in October, we reported preliminary results with RMC-6291 monotherapy supporting clinically meaningful differentiation at doses that were generally well-tolerated. Based on dose optimization work that has been completed, further study of RMC-6291 as a single agent continues at 200 milligrams bid. As a major next step for RMC-6291, we have initiated our first RAS(ON) inhibitor doublet trial with RMC-6236 in patients with advanced KRASG12C 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 RMC-6291 and a checkpoint inhibitor to assess the safety of this combination. For our G12D selective inhibitor, RMC-9805, we shared at the JP Morgan conference that oral bioavailability of RMC-9805 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 RAS(ON) 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-addicted 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 winddown 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 winddown 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. The 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 winddown 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 million and $520 million, which includes estimated non-cash stock-based compensation expense of $70 million to $80 million. The increase in expected GAAP 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 Revolution Medicine have ambitious plans to deliver on clear priorities for our pioneering RAS(ON) 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. Our first question comes from the line of Marc Frahm with TD Cowen. Your line is now open.

Hi, team, this is Ernie Rodriguez for Marc. 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? Thanks.

Hi, Ernie, thanks very much for your question. Primarily, what we're looking for is to validate safety. As you know, the biggest challenge so far in moving into first-line has been the combined hepatotoxicity signals, 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 just a quick 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 combine comfortably, as we have seen preclinically, if that carries through into patients, then it'll certainly be encouraging with regard to combining other mutant selective inhibitors with 6236, and of course, 9805 would be early on that list.

Thank you. Our next question comes from the line of Michael Smith with Guggenheim Partners. Your line is now open.

Hey, good afternoon. Thanks for taking my questions. Yes, Mark, I think we really appreciate the maturing Phase 1 data for 6236. I think you've made comments on how the data has been improving or changing over time now, but just curious if you could comment a bit more on how much more data do you need to support initiation of Phase 3 and also to fulfill project Optimus requirements before launching the pivotal studies as a monotherapy? Thanks so much.

Thank you, Michael. Appreciate the 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 actually making the go decision on those, we're looking 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, could you just help us understand the sequence of events? Will this all come at the same time? Is there some of the data might come before we see other data? Could you help us understand the cadence of data disclosed in the second half a bit better?

I wish I knew. I'd be able to tell you. 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; as the information becomes available and it is appropriate to disclose it, we will do so. Clearly, what people are most anxious to hear about is the timing and details regarding the go decision and the final plan for those pivotal trials. That is the most important event in the second half of the year. However, it is also true that other information will be coming out as we outlined in the milestones.

Thank you. Our next question comes from the line of Eric Joseph with JP 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.

Thank you, Eric. We appreciate your participation today. We are actively working with the FDA to finalize our trial design and will incorporate any relevant activity information into our discussions. We have pre-clinical data indicating that all tested mutant forms of RAS exhibit some level of sensitivity to RMC-6236. The emphasis on the G12X population stems from a large cell line analysis showing that this group demonstrated statistically greater sensitivity to 6236 compared to others; however, this data provided a quantitative rather than a binary measure, which led us to prioritize this group in our dose escalation study. Most of our available data focuses on the G12X group, but we are also looking to collect more information on additional genotypes, as you mentioned. If we can include that data in our final design strategy, we will definitely discuss it with the FDA.

Okay, great. Can you provide an update on the planned combination studies with 6236? Specifically, what are the necessary steps to initiate a frontline pancreatic combination study with chemotherapy? Are there specific chemotherapy regimens you are considering, like FOLFIRINOX or gem-paclitaxel? Additionally, aside from ensuring tolerability, what kind of efficacy signals would you expect to see in a combination setting to justify pursuing the frontline opportunity?

Thank you for your question. I really appreciate your enthusiasm. It's exciting to see our focus on first-line therapies. There is, I believe, increasing interest in the first-line space with RMC-6236 based on the experiences of investigators so far. Perhaps Dr. Lin, our Chief Medical Officer, who is with us today, can share more about what we need to consider in deciding to design and launch such a trial.

Yes. Happy to do that, Mark. Hi. I think you did mention the two current regimens that are currently the standard of care. One is modified FOLFIRINOX, the other is gem-ABRAXANE, 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, gem-ABRAXANE typically response rate in the 20% to 30% range and then modified FOLFIRINOX in the 30% to 40% range, so that's really being secure 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, another metric.

Thank you. Our next question comes from the line of Jonathan Chang with Leerink 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 RMC-6236, what is your latest thinking on what a development path forward in second-line pancreatic cancer could look like? Would the Phase 3 primary endpoint of that study be OS or PFS? Thank you.

Thank you, Jonathan. Regarding the first question about capital allocation, we've clearly stated that our top strategic priority is to advance 6236 into pivotal trials for second-line pancreatic and lung cancer. This focus will significantly influence both our resource allocation and spending efforts. Additionally, for 2024, we have identified two more corporate priorities: expanding the reach of 6236, which will require sufficient capital and resources, and advancing our mutant selective inhibitors, 6291 and 9805, into late-stage development, which also necessitates capital. These priorities are distinctly highlighted for 2024. However, our budget is not limited to these initiatives, as we have earlier-stage programs and a strong discovery effort aimed at developing the next generation of RAS inhibitors. We will allocate resources based on these priorities while considering not just our immediate goals for 2024 but also building a strategy, data set, and asset pool that will sustain a commercial franchise from our earliest assets. We have a lot to invest in now, and while we may appear to have ample capital currently, there will be a point where that perception changes. Nonetheless, we are managing our resources according to a well-defined strategic plan.

Understood. And then just on the 6236 development path in pancreatic cancer.

The 6236 monotherapy second-line pancreatic cancer clinical trial design, Phase 3 design?

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

Yes, I think on the endpoint currently we're looking at is really a dual endpoint of PFS and overall survival OS.

Thank you. Our next question comes from the line of Ellie Merle with UBS. Your line is now open.

Thank you for taking my question. As we approach the initial KRAS combination data later this year, what would you view as positive results from the 6236 and 6291 combination? What specific aspects are you focusing on with this initial data? Thank you.

Thanks for joining us and for your question. The RAS doublet is indeed a unique aspect of Revolution Medicine's portfolio and strategy. Currently, we believe we are the only organization capable of exploring this combination, and the preclinical data strongly supports evaluating 6236 alongside 6291 in G12C cancers. However, we are uncertain how this will translate in humans. While we have insights from animal models, which typically represent short-term conditions and do not capture the complex evolution of human cancer, we anticipate potential benefits such as greater depth and durability of response, or increased response frequency, all of which are observable in preclinical studies. Establishing a direct connection to human outcomes is challenging. Thus, we will remain vigilant for early indicators that warrant further investigation and validation. The primary question we need to address first is the safety of this combination. So far, both components appear safe and well-tolerated, but we must confirm that their combination does not lead to adverse drug interactions or other issues that could undermine our strategy. After confirming safety, we will focus on identifying clinical activity signals, such as frequency of response, depth of response, or durability of response.

Great, thanks so much. And just a quick follow-up, I guess, which indications should we expect data on in the expansion cohorts from 6236 in 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.

Thank you for managing to include the third question. Regarding the data we plan to share later this year, let's begin with the pivotal trials. We are currently considering two separate trials for pancreatic cancer and lung cancer, each with its own data set that we expect to announce later this year as we reveal our plans moving forward. Additionally, you inquired about potential expansion cohorts beyond these cancers. We have identified several avenues for exploration. One focus is on different RAS genotypes beyond G12X, for which we aim to provide preliminary insights around mid-year, specifically in the Q2 to Q3 timeframe. Another area of interest is additional tumor types, including colorectal cancer, with updates expected in the second half of the year. Lastly, we are looking into combinations that may facilitate our entry into first-line therapies, including the 6236-6291 combination and combinations involving pembrolizumab. Wei also mentioned several other strategies that we might consider for initiating first-line treatment, particularly in pancreatic cancer alongside chemotherapy. A variety of developments are anticipated, and we expect to share significant updates in the latter half of this year. Would you like to ask any further questions?

Thank you. Our next question comes from the line of Ami Fadia with Needham and 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 right.

Yes. 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 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. 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 includes second, third, and potentially even some beyond that. People have had multiple different previous treatments. So our population probably isn't going to perform as well as the pure second-line population would perform. 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 comment 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. Just from a mechanistic perspective, I can understand if 6236 as a monotherapy makes sense in second-line, I understand the logic behind exploring a combination of that with pembro in first-line. But why would someone treat with 6291 plus pembro in first line, and then move to 6236 in second line? Just hypothetically.

Okay, now I understand. So we're talking about, in KRASG12C cancers specifically. And 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 if we were able to succeed in developing 6291 plus pembro, or 6291 plus pembro and chemo, and that becomes a new standard of care for G12C patients in first-line lung, why would patients get 6236 with a second-line? Is that your question?

Yes, that's helpful. Thanks.

Yes. In that case, first of all, that's certainly one scenario we could develop it using a 6291 purely based regimen, plus either pembro mono for the poly or pembro plus chemo for all. There's another scenario where we could be developing 6291 plus 6236 plus pembro without chemo, right? That'd be another option. Just want to put that out there. But let's take what you put on the table, which is 6291 plus pembro with 6291 plus pembro plus chemo, if that became the standard of care in first-line, I think we still do believe that there could be scientific rationale for 6236 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 the RAS mutated tumor behaves in developing resistance against any G12C inhibitor. I think there's a wealth of data from sotorasib, adagrasib, and ivarasib. I think one really emerging sign is; number one, 80%, 90% of those tumors retain the original G12C mutation, they don't lose it. Number two, the vast majority of the resistant mutation involve 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 seemed to be the predominant mechanism and hence it goes along, I think, with how Mark is 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 could develop a G12D mutation to bypass the G12C, that 6236 can remain active. And furthermore, even if a patient were to activate a receptor tyrosine kinase, like EGFR, and the signal goes through a wild-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 data to support that for 6236 to remain the standard of care in the second-line setting, even if 6291 establishes itself as first-line treatment of choice.

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

That was very helpful.

Yes. If I could just go back to the first thing that Wei said, though, 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. It's not the only possible outcome, but that would be one way in which all those get rationalized. One shouldn't assume today that we will or would not move forward with the doublet of a PD1 plus either one of those agents. We'll see. We'll let the data tell us what makes sense to do.

Thank you. Our next question comes from the line of Alec Stranahan with Bank of America. Your line is now open.

Hey, guys, this is John on for Alec. 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 a press release or like an Investor Day, so any color on 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. Although our preference is to disclose such information in the context of peer-reviewed 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.

Thank you. Our next question comes from the line of Jay Olsen 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 your question. We've been consistent in our view that in the U.S., we see a significant opportunity for Revolution Medicine to establish its own franchise and leverage the RAS portfolio to create a strong leading position. Therefore, we are not particularly interested in sharing this with a partner and see no reason to do so at this time. Regarding opportunities outside the U.S., it's evident that the landscape is much more complex, making commercialization challenging. While we currently conduct development outside the U.S., pivotal late-stage global development requires a deep understanding of different country contexts, which can be supported by partnering with someone who already has that infrastructure. Additionally, we do not have any immediate plans for independent commercialization outside the U.S. Thus, the possibility of engaging an ex-U.S. partner in the future is open, and we would certainly consider it when the right opportunity arises and it aligns with our strategy.

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. Wei Lin is strong.

Yes, happy 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 anchors in our approach with tissue agnostic. Right now, we're actually rolling patients with colorectal cancer, melanoma, as well as gynecologic cancers, as well as other solid tumors, and obviously to be very much data-driven, but there's our aspiration given the broad activity we've seen frequently that this molecule could potentially help as many as 30% of patients with solid tumors with RAS mutations. So we certainly like to test that hypothesis to the fullest and then the data will drive our decision about how much of a tissue mass can be as far as.

Thank you. Our final question comes from the line of Laura Prendergast from Raymond James. Your line is now open.

Hey, guys, thanks for taking the questions, and look forward to seeing all these data updates later in the year. Just one for me. Curious, since you're running at the same time this Pan-RAS trial and then RAS selective clinical trials, have you got any feedback from trial investigators on how they make the decision on whether to enroll patients on the 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 got any insight there.

Yes, 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 that we can possibly support in these early-stage clinical trials where the size of the trial just is 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?

Yes, I think the business should reflect fairly well of what we see so far in terms of patient interest in our trial is a reflection on that.

Great. Very helpful. Thank you very much.

Thank you. Your final question comes from the line of Ben Burnett with Stifel. Your line is now open.

Hi, this is Kelly Reed 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.

Yes, thanks for your question. As we mentioned in January and reiterated here, we've seen favorable trends in the response rates. You're asking specifically about confirmation, I think generally what I can say is that most responses do confirm most of the responses that had been unconfirmed previously have been subsequently confirmed, except in those instances where somebody progressed in the interim or had to come off of drug and will never have the opportunity to confirm. So most of these do confirm. I'm not going to be able to give you specific confirmed rates today in part because these are ongoing trials, and so what happens is you're always enrolling new patients and getting unconfirmed responses while we're being asked about what's the confirmed response rate. So I'd say, you'll have to hang on and wait until later in the year when we'll try to give more precise information.

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.