Revolution Medicines at Needham Conference: Progress in Cancer Treatment

On Monday, 07 April 2025, Revolution Medicines (NASDAQ: RVMD) presented at the 24th Annual Needham Virtual Healthcare Conference. The company outlined its strategic focus on developing treatments for RAS-addicted cancers, showcasing optimism about its clinical trials and financial stability. However, challenges such as supply chain considerations and the regulatory environment were also discussed.

Key Takeaways

• Revolution Medicines is advancing clinical trials for RAS-addicted cancer treatments, focusing on pancreatic and non-small cell lung cancers.
• The company is financially stable, allowing it to withstand immediate market impacts and scale for commercial supply.
• Enrollment for the RESOLUTE 302 study is expected to complete by year-end, with results anticipated in 2026.
• Combination therapies, particularly RAS ON inhibitor doublets, are a key strategy to enhance treatment outcomes.
• Revolution Medicines maintains strong engagement with the FDA, ensuring regulatory compliance across its programs.

Financial Results

• Revolution Medicines reported a stable financial position, providing insulation from market fluctuations.
• The company is preparing for commercial supply, which may introduce future supply chain challenges.

Operational Updates

• RESOLUTE 302 Enrollment: Strong interest from patients and investigators, with U.S. and international site expansions. Completion expected by year-end, with trial readout in 2026.
• RMC-6236 (Doraxone Rasib): Initial efficacy in Phase 1/2 trials is promising, with median progression-free survival (PFS) over 8 months and overall survival (OS) over 14 months.
• RMC-9805 (Zolgensma Rasib): Active against G12D tumors, with strategic options for use and upcoming data readouts.
• RMC-6291 (Erileron Drasib): Low toxicity when combined with doraxone rasib, supporting potential combination therapies.

Future Outlook

• First-Line Pancreatic Cancer Trial: Initiation planned by year-end, comparing chemotherapy to diraxone rasib monotherapy and combination therapy.
• Combination Strategies: Focus on RAS ON inhibitor doublets to potentially reduce chemotherapy reliance.
• Platform Expansion: Exploring combinations with other mechanisms like pembrolizumab and EGFR antagonists.

Q&A Highlights

• Regulatory Environment: Strong relationship with the FDA, with ongoing engagement across multiple programs.
• Tariffs: Current insulation from tariffs due to financial stability, though some supply chain components are international.
• RESOLUTE Trial Interim Analyses: Designed for interim analyses based on overall survival events, with trial cessation upon efficacy.

In conclusion, Revolution Medicines remains committed to advancing its clinical programs and addressing the needs of patients with RAS-addicted cancers. For further details, refer to the full transcript below.

Full transcript - 24th Annual Needham Virtual Healthcare Conference:

Ami Fadia, Biotech Analyst, Needham: Good afternoon, everyone. Welcome to the next session with Revolution Medicines. I'm Ami Fadia, biotech analyst here at Needham. I have the pleasure to be hosting Mark Goldsmith, who is the chairman and CEO of the company. Mark, thank you for being here.

If you could just kick us off with some opening remarks, and, we can dive straight into q and a.

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Thanks, Ami. Really appreciate the opportunity to be here. This year is a very important one for RevMed, and we hope for patients as well. We have ambitious plans to advance this mission to bring revolutionary new medicines to patients living with RAS addictive cancers.

Ami Fadia, Biotech Analyst, Needham: Okay. Great. I wanted to just maybe open us up open the conversation with sort of a question that we've been getting just with, you know, the changes that have been going on in the, HHS and the FDA. Just from your vantage point, based on what we know so far, how should, you know, the industry be thinking about any changes that we should anticipate in terms of just the regulatory environment, and how are you guys thinking about that?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Right. Well, we don't have any control over that. The environment will evolve. You know, we have a very good relationship with the FDA and have been engaged with them across multiple assets and multiple programs, and we'll continue to do so. So far, we've continued to have, appropriate response times and and good engagement, and we hope that that will continue.

Ami Fadia, Biotech Analyst, Needham: Okay. And and just maybe more broadly with regards to, the tariffs, that, you know, are also kind of front and center. Obviously, RevMed is not kind of there yet, but just very high level initial thoughts on does this change how you think about supply chain down the line?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, I think the biggest impact right now, of course, is in the marketplace. That's pretty obvious to everybody. We're relatively insulated right now because of our stable financial position or strong financial position. From a supply point of view, we do have part of our supply chain that comes from outside The United States, and so that could be affected. I I don't think at the moment we are experiencing experiencing any significant impact.

We are, of course, scaling for commercial supply, and so at some point, that could come into play. But at the moment, I think it's the least of least of concerns.

Ami Fadia, Biotech Analyst, Needham: Yes. Absolutely. Okay. Well, let's let's start with RMC-six thousand February '30 '6 and the RESOLUTE three zero two study in second line PDAC monotherapy trial. Maybe if you can talk about how the study is enrolling and, if it's on track to complete by the end of the year as you've indicated?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Yes. We've seen, we've continued to see strong interest among patients and investigators. Enrollment at the, centers that have been activated has been, highly encouraging. We continue to expand the number of U. S.

Sites, and we now have a significant number of U. S. Sites and are also activating ex U. S. Sites, in The EU and in Japan.

We feel optimistic about the timelines we've laid out early in the year. We suggested that we should be able to complete enrollment, by the end of this year and to read out, the trial in 2026. Mhmm.

Ami Fadia, Biotech Analyst, Needham: And, you know, as you've been sort of making progress on the enrollment, what are you seeing, or what should we expect in terms of just, you know, representation across mutations relative to what we had in the phase one two study and also relative to what you're kind of you know, what we would expect in the real world setting?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, as you're alluding to, RAS addicted cancers come in a variety of of different genetic contexts. And so it's important that our trial, encompass all of those possibilities. There is a natural distribution in pancreatic cancer. Roughly eighty five percent of pancreatic cancer is associated with a mutation at position twelve. We call those G12X mutations.

And about fifteen percent are non G12x, and that's across the broad population. That's roughly what we saw in our trial, except when we actually focused on a particular subset for exploratory reasons. We would expect that enrollment in the RASLUT three zero two trial will roughly fall along these natural distribution lines in terms of representation by mutation type.

Ami Fadia, Biotech Analyst, Needham: Can you talk about kind of how you have powered or what assumptions have been made in terms of powering the study, just based on, some of the data that we've seen around PFS and OS from the phase one two study.

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Right. Well, the that study, as you know, showed a very encouraging estimate of the median PFS and OS when studied across the range of doses of a hundred and sixty milligrams to three hundred milligrams. We observed a median PFS of in the, you know, eight plus month range and and a median OS of in the fourteen plus month range for that broad group. The OS had not matured sufficiently at the three hundred milligram dose, which is the final dose for the study in the top dose in that range for us to have an estimate of the OS, but the median PFS was also in the the eight plus month range. So I don't have anything new to offer for that.

But in terms of how we, design the trial, we use our target product profile as the foundation for designing trials, including the powering. And in this particular case, it's also further informed by the PFS and OS estimates that we have from that hundred and sixty to three hundred milligram group. And so with these encouraging phase one results from the single arm trial, we do, believe that our phase three RESOLUTE trial is designed with robust power, and the ability to demonstrate clinically meaningful PFS and OS benefits.

Ami Fadia, Biotech Analyst, Needham: Does the RESOLUTE trial have any interim looks along the way? And, you know, is it just safety, or is there any other efficacy related interim looks as well?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Yes. It is designed with the possibility of of planned interim analyses. Of course, whether or not we end up having multiple analyses will just simply be determined by the results at at at the first analysis. And these analyses, one or more, will be event driven. It's based on the number of OS events that occur.

When a certain threshold number of OS events occurs, we're then able to to look at the data and and make a judgment about where where we are. Mhmm.

Ami Fadia, Biotech Analyst, Needham: So is there sort of a predefined plan where the trial may be stopped early for efficacy?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, the trial will be stopped when efficacy is reached. So whether that's early or late might be in the eyes of the beholder, but, that's what will that's what will determine it. And since it is OS driven, that is the decision to look and have an interim analysis is driven by a a defined minimum number of OS events, we can we can expect that we'll learn something from from that interim analysis. And if it's sufficient to declare the the study complete, then it'll be declared complete.

Ami Fadia, Biotech Analyst, Needham: Mhmm. Okay. I guess, you know, you've talked about kind of when you expect the trial to be completed, which is sort of by year end of this year. I think investors are, you know, trying to figure out when might we potentially get kind of the efficacy readout, particularly, you know, PFS or OS, actually. So maybe kind of talk about, when we might be able to get those readouts.

Would it end up being only in 2026?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, we believe the readout will be in 2026. I can't really give you any timing, with regard within that 2026 time frame, of course, at this stage. Enrollment is going well, but we have to see how the event rates actually, you know, show up. That's what the interim analysis will help us, will help us do. So, you know, there are a few things that have to go on mechanically.

Once we declare that we've crossed, an endpoint, there still has to be additional work done before one one is able to, conclude that conclusively. So there's some mechanics built into that, but I do expect we'll have a readout in 2026.

Ami Fadia, Biotech Analyst, Needham: Got it. And and you would read out through OS endpoint?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, the readout is PFS and OS. The FDA has made it publicly clear that they prefer to see OS as a decision, you know, as pancreatic cancer, and that that does make sense. And so we're looking for both PFS and OS. Okay. And as I said, again, the interim analyses are actually driven by OS events, not PFS events.

So, essentially, it's overpowered for PFS because the powering is driven off of OS.

Ami Fadia, Biotech Analyst, Needham: Got it. Okay. Understood. Let's talk about kind of the first line, trial that you're planning to initiate, sometime by the end of this year. Can you talk about the rationale for still studying r n t six two three six plus chemo regimen when the monotherapy has already demonstrated efficacy that's superior to chemo in first line?

And, you know, could there be, you know, added toxicity of, you know, the combining the two? And, you know, and then do you believe that there's synergistic benefit?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: So it is true that the draxone draxone rasib monotherapy demonstrated encouraging initial efficacy in the phase one two single arm study. Of course, that's not a comparative study. So event driven single arm studies, aren't consider sufficiently rigorous. You really have to have the second arm, to have something compare to compare to. On the other hand, the, the median PFS and median OS as we talked about earlier, we're so substantially beyond, what what's been well established with a wide variety of chemotherapy phase three trials that we do have confidence that doraxone rasib will be effective in first line as well as in second line that we've studied previously.

We do expect to initiate a first line pancreatic cancer trial comparing patients treated with chemotherapy to two investigational arms. One is Diraxone Rasib monotherapy, and the second is Diraxone Rasib plus chemotherapy, as you just indicated. Based on the monotherapy data in second line as well as preliminary chemo combination data, we're optimistic that both treatment arms containing diraxone have the potential to become important therapeutics, options. So your question is why have a chemo arm given that level of confidence around, monotherapy? And I think there really are two reasons.

One is there is some basis, albeit somewhat limited, but there is some basis for believing that a combination with chemotherapy may deliver increased efficacy over either agent alone. We don't know that with any high level of confidence, but there's some basis for it, particularly from a preclinical data. And there is even a mechanistic foundation for that potentially. Also importantly is that community oncologists, essentially all oncologists who take care of pancreatic cancer, are very familiar with chemo. They've come to rely on it.

And even though it's really leaves a great deal of room for improvement, it's what they're used to providing and have some level of confidence in at least that they know what to expect when they treat with that. It is the current, standard of care, and, the ability to combine with something that physicians are familiar with is is something, that that makes sense, to provide. And then you could imagine the possibility that if both arms of that trial, are are successful, that that could create two paths, two options for treating patients, who who enter a physician's office.

Ami Fadia, Biotech Analyst, Needham: Mhmm. What are the gating factors, for really finalizing this trial design? And perhaps if you can share some initial thoughts around what chemo regimen, you will end up using, you know, in in in sort of in the combination arm. And would these be sort of at the same dose as what's currently being used in terms of the standard of care for today?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Right. So as I mentioned, we are optimistic that we have a path forward both as monotherapy and in a chemo, combination. We have been doing some studies, evaluating chemotherapy in combination with drexone rasib, and we're looking at both folfernox and gemmibraxane based combinations. But we haven't made a determine determination yet whether we'll have both types of regimens available or only a single regimen. We really need further follow-up on safety and tolerability from the patients who have been enrolled with doraxonerasib, plus chemotherapy.

Now within each of these chemotherapy types, there is a, well known, well understood range of doses and, schedules, that are considered acceptable. And indeed, most patients, even if they begin on the highest dose and the most aggressive schedule, most patients undergo some modification of that fairly early in the course of their treatment or at some point in the course of their treatment, such that very few patients actually get what you might call sort of simplistically full dose chemo, simply because it's it's difficult for patients to tolerate. There are many side effects. There are often hospitalizations, and there often are dose reductions or or decreases in the frequency of dosing. That's just very common with with, pancreatic cancer chemotherapy.

It's a harsh, set of regimens. Within the range of dose reductions, modifications that are widely accepted, I think we're optimistic that we can find, a combination that, carries with it typical chemotherapy induced, side effect profile, but not so profoundly that it drives patients into the hospital with life threatening side effects that require discontinuations of their anticancer treatment. That's really the fundamental, issue for us is to make sure that patients who should be on a doraxone rasib containing regimen, in a trial, that they are able to stay on doraxone for as much of that trial and for as continuously as possible because we believe it's the biologically active agent that really is affecting and inhibiting the cancer driver. And therefore, it would not be helpful to a patient to have unintended discontinuations or breaks in treatment with thraxol and rasib. So that's what we're working within this range of accepted doses and schedules, and we'll make a determination and then incorporate one or both of those regimens into our trial.

Ami Fadia, Biotech Analyst, Needham: Mhmm. Just going back to a comment that you made that, you know, a lot of the physicians in the community are sort of are used to or kind of as a general practice do use a lot of chemotherapy. But given the efficacy that was seen for daratumumab in second line as well as sort of the safety profile and the quality of life benefits, wouldn't it just be difficult to enroll or justify a chemo loan arm?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: No. I don't think so. You know, we have not yet, in a randomized controlled trial, proven, by head to head comparison that diraxone rasib is superior, to chemotherapy. I I think the data that we have shown from a single arm, very traditional first in human study are are highly encouraging. And I think everybody recognizes that from patients to investigators and and even to regulators.

But, ultimately, in our regime where we have a formal process by which a regulatory body makes a decision, it's actually mandatory that we provide a head to head comparison versus standard of care. And it's, scientifically sound, and it's the ethical thing to do, until the until that's been proven. So we will we will conduct the the head to head comparison, and we hope to generate the data that will then answer that question definitively and allow for regulatory action accordingly.

Ami Fadia, Biotech Analyst, Needham: Okay. That makes sense. You also announced earlier in the year that you intend to initiate a study in the adjuvant resectable PDAC cancer patients. The standard of care chemo in this setting, I believe, you know, varies a lot by physicians. How different are these patients from first line patients, and how different is the standard of care chemo regimen that's used in this setting versus the first line setting?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, I think the main difference, with patients in the adjuvant setting is that they'll they have no visible disease by CT scan. And while the likelihood is low for any given patients, there is curative potential by combining adjuvant therapy, by providing adjuvant therapy for these patients who have been surgically resected, as opposed to first line pancreatic patients who, even with chemotherapy under any of the observed and historical regimens that we use for pancreatic cancer, patients will unfortunately succumb to their disease eventually. So there is a difference between those. As to standard of care chemotherapy, there really is less of a standard of care when it comes to the adjuvant setting, But the the compounds that are used, the drugs that are used are are essentially the same drugs that are used in metastatic setting. Fofironox is the same.

Gem Abraxane is modified a bit typically in the adjuvant setting. It's usually gemcitabine plus capecitabine plus a nab paclitaxel. That's the preferred regimen because that was a regimen that was first used and approved in the in the adjuvant setting. In Japan, there is a five f u based regimen called s one. It's an oral five f u based regimen, that's used for adjuvant chemotherapy based on Japanese trial, but it's still five FU based.

So these regimens are pretty similar to the treatments that are used in the metastatic setting. And as a matter of just general principle, proof of concept clinical proof of concept that's achieved in the meta metastatic setting, is widely accepted as proof of concept for the adjuvant setting. And that means, that it is possible to proceed right away with the experimental treatment into the adjuvant setting. And in fact, both the historical fulphiranox and gemcitabine adjuvant trials that I mentioned, were initiated after POC was achieved in the metastatic setting. It's a very conventional approach.

Mhmm.

Ami Fadia, Biotech Analyst, Needham: So I guess from a trial design perspective, what what all do you need to determine sort of internally to really figure out how you you know? What are patients gonna get in the in the in the various arms?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Right. We we believe we have the data needed. There really is nothing that we need to generate at this point to help inform that that planning. So we are currently actively designing, a registrational adjuvant trial with Draxonrasib, in these resectable patients, and we expect to move quickly on developing this program. It does take some time to develop a protocol even though one might think that once you know what you wanna do, you can just move forward.

It takes time to do this thoroughly and and properly, and we use advisory boards. And then ultimately, we have to engage with the regulatory agency, But we expect to initiate the adjuvant study sometime in 2025, and we also expect to initiate the first line metastatic study as well.

Ami Fadia, Biotech Analyst, Needham: And and just to follow-up there, would the standard of care or sort of the the competitor arm be physician choice chemo, or would you need to pick?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Stay tuned. That's that's that's something that we'll be able to just talk about when we have the design. I can it's not not constructive for me to get out in front of that design. Let's let us get through our work of designing that trial, and then we can describe what the design is. Okay.

Ami Fadia, Biotech Analyst, Needham: Alright. Sounds good. So maybe we can shift gears to, Zolgensma Rasib, which is RMC nine eight zero five, which is your Rasgon, G 12 d. I guess you're gonna be presenting some data, that's coming up, at a at a meeting soon. But maybe if you can just step back, and and maybe, you know, what is sort of the potential role of this drug which targets g drug d in PDAC as you think about kind of a paradigm shift, from doraxoneuracive monotherapy or chemotherapy with chemo?

So how does sort of this drug kind of play a role with this changing paradigm that you're developing in?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, things are are moving rapidly, and I think zolonaracid is going to play an important role. It is a compelling compound based on the initial tolerability profile, which we reported just a few months ago in pancreatic cancer. It's also clearly very active against g twelve d tumors, which gives us a range of strategic options. We're still in the early stages of understanding exactly its clinical profile and its potential. And as you pointed out, we'll share some new clinical data in non small cell lung cancer at at at AACR coming up.

So we believe an important part of the strategy for our mutant selective inhibitors may be in combination strategies, including a RasOn inhibitor doublet combination with doraxonrasib, combinations with existing standard of care such as pembro and chemotherapy, combinations with other targeted and or novel agents such as EGFR antibodies and PRMT five inhibitors. I think the fundamental point I'd wanna make here is that we haven't cured a lot of pancreatic cancers yet. We have an exciting set of compounds pipeline in the clinic and additional things coming behind it that will make a difference, we believe, for patients, but we haven't cured pancreatic cancers yet. And I think it's just too early for us to declare victory. We're I like to say we're maybe in the second inning of this, of this baseball game, and, we have some momentum, but we're gonna continue going until we've made a real difference.

Ami Fadia, Biotech Analyst, Needham: Mhmm. Just as you sort of talked about the, kind of a RAS on doublet, as as a concept. Now would you consider, especially in the PDAC setting, given some earlier comments around kind of the how entrenched the use of chemo is in in in this space. Would you consider a RAS on doublet with chemo, or would that be the time point to explore a RAS on doublet without chemo?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Right. There are a variety of possibilities. We certainly believe that a Rasmon inhibitor doublet, by which we we mean a mutant selective Rasmon inhibitor combined with a RAS multi inhibitor like doraxonerasib, that those are among the most, exciting combination options. And we've seen in pre preclinical models that we've shown now in several settings, that combining a multi selective and a mutant selective inhibitor, it increases the target occupancy of the mutant form of RAS, and it drives significant antitumor activity that can exceed that seen with either agent alone in a particular in a particular model. We've also demonstrated that doraxone rasib suppresses many of the known RASP pathway resistance mechanisms that have been shown to emerge in patients who are treated with a mutant selective RASP inhibitor, particularly the g twelve c inhibitors for which we now have a lot of publicly known, you know, experience.

And then early evidence of translation of this preclinical data into the clinic have been observed as we reported in December with the combination of diraxone rasib plus elyron Rasib, our g twelve c selective inhibitor, where we observed highly encouraging combinatorial activity, which increases our confidence in the concept of the innovative Ras on inhibitor doublet more broadly. So that's really the context for our enthusiasm for this two RasOn inhibitor approach or the doublet approach. And with respect to the combination of diraxone Rasib plus Zoltan Rasib in particular, since that's what we're talking about here, We have completed dose escalation in patients at the anticipated single agent recommended phase two dose for each drug, and we plan to study these RAS on inhibitor doublets further in patients, and we'll continue to observe antitumor effects and safety, particularly as we move towards earlier lines of treatment. And now would we combine a doublet of RAS on inhibitors with chemotherapy? That seems unlikely.

I think the goal there would be to use the RasOn inhibitor doublet to spare patients of chemotherapy and to push the chemotherapy option down to the next the next treatment arm. So you can imagine if we're introducing a doublet of RAS inhibitors in a frontline setting, well, now we've saved patients from having to take chemotherapy, preserve that chemotherapy to be available for second or or third line use. And that's really where we could start to stack up potential potentially stack up OS benefit.

Ami Fadia, Biotech Analyst, Needham: Okay. That's helpful. You've indicated that you're studying zolonrasib in several combinations for which you're gonna share, additional data, perhaps in second and third quarter of this year. How do you think about how much synergistic benefit you need to see to pick a particular combination and move that forward? What is sort of that bar without, you know, having to see enough durability of effect as well.

Right? Or would you need to wait to get the duration durability data?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Okay. Now I understand your question. Yeah. I I don't think we typically would be able to use durability as the indicator for moving to accommodation in the clinic because that really can add a year or two to these studies. And it's just too urgent that we get these into patients and and move things towards towards registration.

With something like doraxone rasib, we've already established significant durability with the caveat I mentioned that that's from single arm studies in lung and pancreatic cancer. And so those are not formally sufficient to declare proof. But it is quite encouraging. And so if we're adding a mutant selective inhibitor on top of that and if we see an objective response rate benefit, I think it's very likely from there that that would translate into greater long term benefit. That's certainly what we've seen in the preclinical models where combining two RASM inhibitors can result in in really highly durable antitumor benefit in animals.

In fact, in in many cases, no recurrences. So I I think the concept is well established and we can use faster markers of antitumor activity like like response rates in the in the right context, just as we did with the colorectal cancer study where we took two agents, drexone rasib and leron rasib, either of which alone was going to have a single digit response rate. But when we combine them, we saw twenty five percent response rate in patients with very advanced colorectal cancer. I think that's sufficient to encourage us to move forward.

Ami Fadia, Biotech Analyst, Needham: Yep. Okay. So why don't we move shift gears to your Rasgon g twelve c inhibitor, which is erileron drasib or RMC six two nine one. These are all tongue twisters too for me. You showed that the combination of six two nine one and six two three six with pembro was well tolerated.

What is the next step here in terms of exploring the clinical development path forward in first line lung?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Yeah. Well, we're very excited about, Alir on Rasib. It's sort of been behind you know, a little bit behind the scenes since it was first disclosed back in 2023. We think it's a very exciting compound, and we're pursuing a variety of combination approaches for first line lung cancer, particularly for G12C positive lung cancer. As you mentioned, the dominant standard of care in first line lung cancer includes pembrolizumab, so combining with pembro and the ability to do that safely is important.

As you indicated, both doraxone rasib and eylere on rasib so far, we've seen very encouraging signs and very little evidence of additive toxicity. We also, as you indicated, have seen encouraging signs in the colorectal context that putting two RAS on inhibitors together can achieve something that neither alone can achieve, which leads us to the concept of combining two RasOn inhibitors with pembro. And we think we've essentially already demonstrated the safety and tolerability of that, at least with a limited dataset. We don't really have much of a concern, but it is a good idea. And I think the regulators and investigators would expect to see some evidence that the triplet does not, know, incur or carry with it some significant adverse events liability.

So we certainly are studying, you know, that triplet combination. I think we're moving, towards towards our first line strategy both for g twelve c lung cancer, which is really a subset of the total of lung cancer, of RAS lung cancer. It's about twelve percent of the thirty percent of lung cancer that is a RAS driven tumor. The other eighteen percent would not benefit from Eliran, but but could benefit from doraxonerasib. And so we're moving forward in in thinking that all through and as the the data mature, but more importantly, as our as our trial design work proceeds, we'll be able to share information about that.

Ami Fadia, Biotech Analyst, Needham: So maybe just stepping back, and you obviously have a very deep pipeline and kind of just the things that we've talked about. But, you know, kind of stepping back as we think about the RAS ON platform, how do you think about potentially combining that with other mechanisms beyond just RAS ON?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Well, other mechanisms directed towards RAS or other other drugs like pembrolizumab and PRMT five inhibitors and EGFR antagonists, all of the above?

Ami Fadia, Biotech Analyst, Needham: All of the above?

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Yeah. I think all of the above could be interesting. And I think we have a lot of dialogue, a lot of conversations underway with parties that have other compounds that they're evaluating or that have already been proven and are part of standard of care. We don't really need to have a big conversation about cetuximab combining with rasn inhibitor in colorectal cancer. That's just something we're now, you know, testing.

We've announced that we're testing through a collaboration with Tango Therapeutics. We're providing them doraxonerasib, and they're going to test it in combination with their PRMT five inhibitor. Our own RAS inhibitors combining combining with pembrolizumab, these are all options. And to the extent that the preclinical data or known clinical data provide good justification for moving something into the clinic as a combination strategy, we'll do so. And as my allusion to being only in the second inning of this baseball game means that there's a lot that we don't know yet as to which of these are the highest priority, from an endgame perspective.

And so we make judgments, and we'll move a lot of things in parallel into the clinic and and then make judgments based on what we see.

Ami Fadia, Biotech Analyst, Needham: Okay. Alright. Those are questions I had. Thank you so much. I really appreciate you taking the time to be with us today and to all our listeners for joining.

Mark Goldsmith, Chairman and CEO, Revolution Medicines: Thank you, Ami. I appreciate it.

Ami Fadia, Biotech Analyst, Needham: Thank you. Have a good day.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.