Q4 2023 Revolution Medicines Inc Earnings Call

Participants

Erin Graves; Head of Corporate Communications and Investor Relations; Revolution Medicines Inc

Mark Goldsmith; President, CEO, Chairman; Revolution Medicines Inc

Jack Anders; Chief Financial Officer; Revolution Medicines Inc

Lin Wei; Chief Medical Officer; Revolution Medicines Inc

Ernie Rodriguez; Analyst; Cowen and Company

Michael Schmidt; Analyst; Guggenheim Securities, LLC

Eric Joseph; Analyst; J.P. Morgan Securities LLC

Jonathan Chang; Analyst; Leerink Partners LLC

Eliana Merle; Analyst; UBS Securities LLC

Ami Fadia; Analyst; Needham & Company Inc.

Jay Olson; Analyst; Oppenheimer & Co. Inc.

Laura Prendergast; Analyst; Raymond James & Associates, Inc.

Kelly Riza; Analyst; Stifel Nicolaus and Company, Incorporated

Presentation

Operator

Good day, and thank you for standing by. Welcome to Revolution Medicines fourth quarter and full year 2023 conference call. (Operator Instructions) Once 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.

Erin Graves

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 Medicines' 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 Medicines' Chairman and Chief Executive Officer. Mark?

Mark Goldsmith

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 JPMorgan 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 Medicines. First, we disclosed the preliminary clinical profiles of two unprecedented targeted RAS-ON inhibitors, RMC-6236, our RAS-ON multi selective inhibitor; and RMC-6291, our RAS-ON G12C-selective inhibitor.
As evaluated in Phase 1, 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 RMC-9805, an oral and 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 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 a larger 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 we're 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 we're 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 dataset 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 RMC-6236. 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 G61X 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 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 years 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 one as a single agent continues at 200 milligrams BID.
As a major next step for RMC-6291, we have initiated our first RAZ-ON inhibitor doublet trial with RMC-6236 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 RMC-6291 and a checkpoint inhibitor to assess the safety of this combination. For our G12D-selective inhibitor, RMC-9805, we shared at the JPMorgan 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.
With clear 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-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?

Jack Anders

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 nonrecurring 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; $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 million and $520 million, which includes estimated noncash stock-based compensation expense, $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.

Mark Goldsmith

Thank you, Jack. In summary, in 2024, we at Rev Med 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.

Question and Answer Session

Operator

Thank you. (Operator Instructions) Marc Frahm, TD Cowen.

Ernie Rodriguez

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

Mark Goldsmith

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 moving into first line has been up for all the RAS inhibitors has been combined hepatotoxicity signals. And while we have early reason to believe that it's just 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.

Ernie Rodriguez

Thank you. That's helpful. And then just a quick one. Will you remind me if you mentioned before -- I don't remember the potential or how are you thinking about the potential for combining 9805 with 6236?

Mark Goldsmith

Sure. We haven't said much about that other than we considered the 6291 plus 6236 combination to be a key test case. And if those combined comfortably as we have seen preclinically, if that carries through into patients, that it will certainly be encouraging with regard to combining other new selective inhibitors with 6236 and of course, 9805 would be early on that list.

Ernie Rodriguez

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

Operator

Michael Schmidt, Guggenheim Partners.

Michael Schmidt

Hey, good afternoon. Thanks for taking my questions. Mark, 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 in order to fulfill a project optimum requirements before launching the pivotal studies as a monotherapy? Thanks so much.

Mark Goldsmith

Thank you, Michael. I appreciate the question. 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 our 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 assessments or estimate that can come from more mature observation, which obviously we're developing now. And that really leads to finalization of the trial design, the 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.

Michael Schmidt

Okay, thanks. And then you've highlighted a number of potential data disclosures in the second half of this year, including additional monotherapy and also early combination data from all three of your programs. Can 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?

Mark Goldsmith

I wish I knew. I would 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 to set the information becomes available and as it becomes appropriate to disclose, it will 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 outlined in the milestones.

Michael Schmidt

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

Mark Goldsmith

Thank you.

Operator

Eric Joseph, JPMorgan.

Eric Joseph

Hi, 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 activity in the context of G12X and Q61 mutations -- needed at all get buy-in on the nested efficacy analysis as part of your proposed design. And then I have a follow-up to that question.

Mark Goldsmith

Okay. Thanks, Eric. Thanks for joining us today. Clearly, we are trying to make decisions and 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 graphs. Certainly all that we've ever tested, showed some degree of sensitivity to RMC-6236.
And the elevation of the G12X population, you might recall, came out of a large cell line panel that shows that 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 a quantitative signal that highlighted them and therefore, we prioritize 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.

Eric Joseph

Okay. Great. And maybe just a follow-up on the planned combination studies with 6236. Specifically, can you talk about what the gating steps are to starting a front-line pancreatic combination study with chemo? Is there a particular chemo regimen you're looking to combine with between either FOLFIRINOX or jiM paclitaxel and beyond adequate tolerability, is there an efficacy signal that you'd want to see in a combination setting to warrant to pursue the frontline opportunity?

Mark Goldsmith

Yeah. Thanks for that question. I really appreciate your enthusiasm, you're moving us to first line. (laughter) Terrific. There is, I think, growing interest in the first line space with our 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 the -- designing and launching such a trial.

Lin Wei

Yeah, how do you do that, Mark. Hi -- I think you did mention the two current regiments that are currently at the standard of care. One is FOLFIRINOX and other is Gem-Abraxane. And both are in wide clinical use. So we would be exploring the combination with both of these regimens in early phase studies and even -- the benchmark for those are -- Gem-Abraxane typically response rate in a 20% to 30% range. And then FOLFIRINOX will turn off in the 30% to 40% range. So that's really being superior to -- either one of these would enable us to really move forward (technical difficulty) first line setting. Obviously, that said, the response rate is -- (technical difficulty) like to provide survival benefit and so PFS will be another matter we'll be working on.

Eric Joseph

Okay, great. Thanks again for taking the question.

Operator

Jonathan Chang, Leerink Partners.

Jonathan Chang

Hi, guys. Thanks for taking my questions. First question; with an enviable year-end cash 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 the development path forward in second-line pancreatic cancer could look like with the Phase 3 primary endpoint of that study BOS or PFS? Thank you.

Mark Goldsmith

Thanks, Jonathan. I think on the first question, which was capital allocation, given all the competing opportunities that we have, I think we've been pretty clear about this, that our number-one strategic priority is to advance 6236 into pivotal trials in second line pancreatic and lung cancer. And no question from our bandwidth perspective and even direct spending that supports 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 has expanded 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 a qualifying our mutant selective inhibitor 6291 and 9805 to advance into late-stage development that requires a certain amount of capital too.
So those are clearly 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 -- later generation graph inhibitors and so on.
So 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 from our strategy, our data set, and our asset pool that would sustain and protect the franchise. Once we're able to create a commercial franchise from the first -- 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.

Jonathan Chang

Understood. And then just on that 6236-development path in pancreatic cancer?

Mark Goldsmith

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

Jonathan Chang

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

Mark Goldsmith

Well, I think we can clarify what we've stated so far than anything else -- just that based on conversations with the FDA, we'll update in the second half of the year, but I think Wei Lin can comment more strictly on that.

Lin Wei

Yeah, I think on the endpoint front, we are looking is that -- Q end, PFS and overall survival OS.

Operator

Eli Merle, UBS.

Eliana Merle

Hey guys, thanks so much for taking my question. Just heading into the initial K-RAS 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.

Mark Goldsmith

Okay. Thanks for joining us, and thanks for your question. Yeah, the RAS doublet is really another differentiating angle of Rev Med's portfolio of strategy. I think at the moment, we are really the only organization that could attempt such a combination. And the preclinical data are strongly supportive and do support evaluating 6236 in combination with 6291 in G12C cancers.
But what we don't know is exactly how that will play out translationally in humans. We know in the animal models, which are generally relatively short-term models and don't have the same evolution characteristics as a true human cancer, heterogeneous human cancer, we know what that looks like. It can look like both increased depth of response and the 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 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 a safe combination. Is it safe and tolerated? 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 drug interactions or other manifestations that could compromise the strategy going forward.
And then after that, we'll be thinking about looking for the clinical activity signal that I just alluded to, whether it's frequency response, depth of response, or durability of response.

Eliana Merle

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

Mark Goldsmith

Okay. I think you managed to squeeze (technical difficulty) (laughter) -- the third question (technical difficulty). So in terms of the data that we've committed to communicating later this year, let's just start with the pivotal trials. There are two separate trials on the 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 headline datasets to come out later in the year as we announced plans to move into go-forward plans.
But then I think you were asking about going beyond pancreatic cancer and lung cancer, and expansion cohorts that go beyond pancreatic and lung cancer. We've indicated that there's several different directions for those. One is different RAS genotypes beyond G12X, and we've indicated we'll provide some preliminary view that sometime in the midyear range, I think we said Q2 to Q3 timeframe.
The second is tumor types beyond lung and pancreatic cancer. And that includes colorectal cancer. We've indicated we'll provide 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 6236, 6291 combination we just spoke about, and then combinations of 6236 with pembro, 6291 with pembro, and then some -- way alluded to a few other things that one would consider for ultimately moving into first line, particularly pancreatic cancer with chemotherapy.
So lot -- there's a wide range of things that are going to happen. A good number of those we could readout in the second half of this year.

Eliana Merle

Great, Thanks.

Mark Goldsmith

Yes, did you have -- did you want to follow up on that?

Operator

Ami Fadia, Needham & Company.

Ami Fadia

Hi, good evening. Thanks for taking my question. A quick one follow-up and a question just on the PDAQ 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 regard to your program or what you're pursuing in first line, you're developing 6236 in second line or if you're planning to initiate a pivotal study there? What is the clinical rationale or the hypothesis in terms of what will be the right combination partner with pembro plus minus chemo, whether it would be 6236 or 6291 -- if you could share your thinking there, that would be helpful. Thanks.

Mark Goldsmith

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 got it. Your question was in second line PDAQ, what is the bar that would compel us to move forward from a PFS perspective? That's what you're asking?

Ami Fadia

That's right.

Mark Goldsmith

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 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 3 to 3.5 months at best in true second-line patients.
Keep in mind, our population is not truly second-line, our population for the second and third and potentially even some beyond that, people had multiple different previous treatments. So our population probably isn't quite performed as well as the pure second-line population would perform. But nonetheless, we've said what we're trying to do with our current patients' population. It is to be superior to well accepted benchmark for second line. And 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.

Ami Fadia

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 the 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 the second line -- just hypothetically?

Mark Goldsmith

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?

Ami Fadia

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

Mark Goldsmith

Ah. Okay. Now I understand. So we're talking about in KRAS G12C cancers, specifically -- talking about (multiple speakers) lung cancer. And your question was, if we combined 6236 with 6291 in first line -- no? I'm not following it. So maybe you can interpret the question. I can answer it.

Lin Wei

Let me interpret your question. So I think what I'm hearing you saying is, if we were able to succeed in developing 6291 plus pembro, or 6291 plus pembro and chemo, and that becomes the new standard of care for G12C patients in first line lung, why would patients get 6236 with second line? Is that your question?

Ami Fadia

Yeah, that's helpful. Thanks.

Lin Wei

(multiple speakers) I'll take a stab at. That's certainly one scenario we could develop it using a 6291 -- pure truly based regimen plus either pembro-mono or the PD-L1 high, or pembro plus chemo, or (technical difficulty). There's another scenario where we could be developing 6291 plus 6236 plus pembro without chemo. That'll be another option, just want to put that out there. But let's take the -- when you put on the table, which is 6291 plus pembro -- 6291 plus pembro plus chemo. If that became the standard of care in first line, we still do believe that there could be some rationale for 6236 to remain as an option in the second-line setting.
And the reason is following: I think it really has to do with the way that the KRAS addicted tumor behaves in (technical difficulty) resistance against any G12C inhibitor. I think there's wealth of data from [sorboRASes, adecRASes, and tiboRASes].
I think one -- through the emerging sight is, number one, 90% of those tumors retained or compete 12D 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 risking or reactivating the RAS seem to be the predominant mechanism mentioned. It goes along, I think up with (technical difficulty) describing these tumors as RAS addicted.
I think the fact that they are addicted means that they're really relying on turning that tumor pathway back home in RAS and hence the broad spectrum activity of 6236 involving not only other RAS mutations that can potentially cover. So if timo T12 and TCOD mutation to bypass the G12C, that 6236 can remain active.
And furthermore, even if the patient or two activate the receptor tyrosine 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's still rely on provide rationale.
Obviously, we need to generate prognosis data to support that -- for 6236 to remains the standard of care in the second-line setting, even if 6291 establish itself as a first line treatment of choice.

Mark Goldsmith

So you got yourself a very scholarly answer. But I just wanted to circle back --

Ami Fadia

That was very helpful.

Mark Goldsmith

If I could just go back to the first thing that Wei said, that was -- it's really important, might have gotten 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 of that would be one way in which all those get rationalized. One shouldn't assume today that we will or will not move forward with the topline of a PD-1 plus either one of those agents. We'll let the data tell us what makes sense to do.

Ami Fadia

That makes sense. Thanks.

Operator

Alec Stranahan, Bank of America.

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 expect a press release or like Investor Day? So any color on that? That would be great if you can share.

Mark Goldsmith

Thanks, John. Hard to answer that question because there's so many different datasets 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 were submitted long ahead of when we might have the information. So we'll pick a forum for each of the disclosures, that's suited to make sure that we're not holding on to data that investors need to know about.

Okay. Thank you for the color.

Operator

Jay Olson, Oppenheimer.

Jay Olson

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 US and outside the US?

Mark Goldsmith

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 US, we really believe this is a serious opportunity for Rev Med to build its own franchise and to use these brand's 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 US, 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 do development outside the US. We already do development outside the US, but doing pivotal late-stage global development typically takes a real appreciation of the nuances and different country 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-US partner or partners could be in the offering for us at some point in the future, we were 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.

Jay Olson

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?

Mark Goldsmith

Dr. Wei Lin is probably (laughter) that question.

Lin Wei

Yeah. (technical difficulty) 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 serve as an anchor in our approach to tissue diagnostics. Right now, we're actually enrolling patients with colorectal cancer, melanoma, as well as oncotic myopic cancers, as well as other solid tumors. And obviously it'll be very much data driven, but it's our aspiration given the broad activity we've seen preclinically that this molecule could potentially help on 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 that data will drive our decision about how much of the tissue mass can be aspired.

Jay Olson

Okay, great. Thanks again for taking the questions.

Operator

(Operator Instructions) Laura Prendergast, Raymond James.

Laura Prendergast

Yeah, thanks for taking the questions and look forward to seeing all these data updates later in the year. Just one for me. I am curious if you are running at the same time this pembro 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 pembro trial or RAS-selective trial, assuming that you probably have some trials going on at the same location. I'm just curious if you've got any insight there.

Mark Goldsmith

I'll just make a general comment. In most of the indications we're talking about, the need for these compounds is so high. Therefore, 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 near-term issues associated with that. But maybe Wei wants to comment further about when we're into pivotal trials, and how might that affect, if any.

Lin Wei

Yeah. I think that (technical difficulty) should reflect fairly well what we see so far in terms of down accruing patients and that they were addressing, I think just really highlighting this is an unusual situation that is the biggest driver in all oncology and that fight while -- (technical difficulty) really unlocks a huge unmet need. So all the patients coming in interest in our trial is a reflection of that.

Laura Prendergast

That's very helpful. Thank you very much.

Operator

Ben Burnett, Stifel.

Kelly Riza

Great. This is [Kelly Riza] 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 PDAQ are trending post-ESMO? Thank you.

Mark Goldsmith

Thanks for your question. As we mentioned in January and reiterated here, we have 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 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 all 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 till later in the year when we'll trying to give more precise information.

Kelly Riza

Okay. Thank you very much.

Operator

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

Mark Goldsmith

Well, thank you, operator, and thank you, everyone, for participating today, and for your continued support of Revolution Medicines.

Operator

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