Revolution Medicines Q2 2025 Earnings Report

Revolution Medicines EPS Results

• Actual EPS: -$1.31
• Consensus EPS: -$0.94
• Beat/Miss: Missed by -$0.37
• One Year Ago EPS: -$0.81

Revolution Medicines Revenue Results

• Actual Revenue: N/A
• Expected Revenue: $0.50 million
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Revolution Medicines Announcement Details

• Quarter: Q2 2025
• Date: 8/6/2025
• Time: After Market Closes
• Conference Call Date: Wednesday, August 6, 2025
• Conference Call Time: 4:30PM ET

Revolution Medicines (NASDAQ:RVMD), a clinical-stage precision oncology company, develops novel targeted therapies for RAS-addicted cancers. The company's research and development pipeline comprises RAS(ON) inhibitors designed to be used as monotherapy in combination with other RAS(ON) inhibitors and/or in combination with RAS companion inhibitors or other therapeutic agents, and RAS companion inhibitors for combination treatment strategies. Its RAS(ON) inhibitors include RMC-6236 (multi), RMC-6291 (G12C), and RMC-9805 (G12D), which are in phase 1 clinical trial; and development candidates comprise RMC-5127 (G12V), RMC-0708 (Q61H), and RMC-8839 (G13C), as well as programs focused on G12R and other targets. The company's RAS companion inhibitors include RMC-4630 that is in phase 2 clinical trial; and RMC-5552, which is in phase 1 clinical trial. Revolution Medicines, Inc. was incorporated in 2014 and is headquartered in Redwood City, California.

Revolution Medicines Q2 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Breakthrough Therapy designation granted by FDA for Tiraxonrasib in previously treated metastatic pancreatic cancer, underscoring its potential to address a high unmet need.
• Positive Sentiment: RESLU-302 Phase 3 trial in second-line pancreatic ductal adenocarcinoma is enrolling globally, on track to complete this year with an OS-driven data readout expected in 2026.
• Positive Sentiment: Revolution Medicines secured a $2 billion financing commitment from Royalty Pharma through a mix of synthetic royalties and debt, providing non-dilutive capital to fuel its RAS inhibitor pipeline.
• Negative Sentiment: The company reported a net loss of $247.8 million for Q2 and updated 2025 GAAP net loss guidance to $1.03–1.09 billion, reflecting accelerated R&D and commercial expansion costs.
• Neutral Sentiment: New collaboration with Iambic leverages AI to integrate RevMed’s proprietary RAS data into predictive models, aiming to enhance lead discovery and optimization processes.

Presentation

[Operator]

Good day, and thank you for standing by. Welcome to the Revolution Medicine's Q2 twenty twenty five Earnings Conference Call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press 11 on your telephone.

[Operator]

You will then hear an automated message advising your hand is raised. To withdraw your question, please press 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Ryan A. C, SVP of Corporate Affairs. Please go ahead.

[Ryan Asay, SVP & Corporate Affairs at Revolution Medicines]

Thank you, and welcome, everyone, to the second quarter twenty twenty five earnings call. Joining me on today's call are Doctor. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer and Jack Anders, our Chief Financial Officer. Doctor. Steve Kelsey, our President of R and D Anthony Mancini, our Chief Global Commercialization Officer and Peg Horn, our Chief Operating Officer will join us for the Q and A portion of today's call.

[Ryan Asay, SVP & Corporate Affairs at Revolution Medicines]

I'd like to inform you that certain statements we made during this call will be forward looking. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10 ks and our quarterly reports on Form 10 Q that are filed with the U. S. Securities and Exchange Commission.

[Ryan Asay, SVP & Corporate Affairs at Revolution Medicines]

This afternoon, we released financial results for the quarter ended 06/30/2025, and recent corporate updates. The press release is available on the Investors section of our website at revmed dot com. With that, I'll turn the call over to Doctor. Mark Goldsmith, our Chairman and Chief Executive Officer. Mark?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thanks, Ryan. It's good to be with you this afternoon. Today, I'll highlight the progress we've made this quarter with a look ahead to the strategic priorities and milestones on the horizon for RevMed. I'll then pass the call over to Jack, who will provide a financial summary before I share closing remarks and open the call for questions and answers. At RevMed, we remain steadfast in our commitment to revolutionizing treatment for patients with RAS addicted cancers through the discovery, development, and global delivery of innovative targeted medicines.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We have a compelling pipeline of three distinguished clinical stage RasOn inhibitors. TiraxonRasib, a groundbreaking RasOn multi selective inhibitor, oleeronrasib, a differentiated G12C selective covalent inhibitor, and Zoldonrasib, a groundbreaking G12D selective covalent inhibitor for which a full report was published recently in Science describing the innovative chemistry, mechanism of action, and biological impact of this unique Ras9 inhibitor in preclinical cancer models. We are executing well and making meaningful progress in advancing all of these programs, which we believe have the potential to transform treatment for patients living with RAS driven cancers. Starting with our efforts in pancreatic cancer, diraxonrasib is our most advanced clinical program. We were pleased to announce recently that Diraxon Rasib received breakthrough therapy designation from the US Food and Drug Administration in previously treated metastatic pancreatic cancer with KRAS G12 mutations.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

This designation underscores the large unmet medical needs for patients living with pancreatic cancer and the urgency of advancing development of doraxone rasid on behalf of patients. Toward this objective, we continue to make progress across our active and planned diraxonrasib registrational studies in pancreatic cancer. First, RESLU-three zero two, our ongoing global Phase three trial in patients with second line metastatic pancreatic ductal adenocarcinoma or PDAC has been enrolling well. And we expect to complete enrollment this year to enable an expected data readout in 2026. Notably, with robust contributions by US investigational sites to date, we are winding down enrollment in The US, while continuing to enroll patients outside The US to ensure we have a reasonable geographic mix to support global registration.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Second, we continue progressing toward initiating our first line metastatic pancreatic cancer registrational trial, which we plan to conduct as a three arm trial comparing diraxonrasib or diraxonrasib plus chemotherapy to chemotherapy. Later this year, we expect to share the trial design and clinical combination data that inform this plan and to initiate the trial. Third, we also continue progressing toward a registrational trial with doraxonrasib as adjuvant treatment for patients with resectable PDAC. And later this year, we expect to share the trial design and initiate this trial as well. For patients with pancreatic cancer specifically bearing a RAS G12D mutation, the clinical activity and tolerability profile we've reported for ZoltanRasib is quite encouraging and suggests it is remarkable inhibitor of this common cancer driver.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We continue to follow patients in the ongoing monotherapy trial and are currently studying several combination treatments, including as part of a Ras on inhibitor doublet with diraxonerasib in combination with standard of care regimens and with other novel targeted agents. For example, for patients with pancreatic cancers carrying both a RAS mutation and deletion of MTAP, Tango Therapeutics announced that a first patient was dosed in a collaborative phase one trial evaluating their PRMT5 inhibitor TNG462 with either diraxonrasib or zolturasib. Such novel combinations have the potential to provide differentiated options for patients with these cancer genotypes. Moving to non small cell lung cancer, RESOLUTE-three zero one, our Phase three trial of diraxonravsib in previously treated patients with RAS mutant non small cell lung cancer continues enrolling patients in The US. And we are now activating trial sites in Europe and Japan as planned.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Evaluating diraxonrasib in earlier lines of therapy for patients with non small cell lung cancer is also an area of strategic priority for RevMed. We recently showed clinical evidence that diraxonrasib can be combined productively and tolerably with pembrolizumab with or without platinum doublet chemotherapy. With these results in hand, we're working toward initiating a registrational trial in first line non small cell lung cancer in 2026 and expect to share the trial design in connection with the initiation. Clinical development efforts also continue across our RasOn mutant selective inhibitors, eleronrasib and zoldonrasib in patients with RAS G12C or G12D non small cell lung cancer respectively. First, we recently reported an updated clinical data set from patients with previously treated KRAS G12C non small cell lung cancer treated with oleuronrasib as monotherapy that showed a highly competitive profile, including differentiated safety and tolerability, along with a compelling objective response rate and progression free survival.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We recently announced that eleeron rasa was granted breakthrough therapy designation by the FDA for locally advanced or metastatic KRAS G12C non small cell lung cancer following prior systemic therapy, including anti PD-one and chemotherapy. This designation is a recognition of the significant unmet medical need oleuronrasib's potential to serve these patients. Currently there are no RAS targeted inhibitors with full FDA approval for treating patients with KRAS G12C non small cell lung cancer. Second, we also recently expanded the clinical evidence supporting the potential benefit of combining eleeronrasib with other inhibitors. In particular, the Ras on inhibitor doublet of eleeronrasib and diraxonrasib was shown to exhibit significant anti tumor activity in advanced non small cell lung cancer patients who had progressed on treatment with a KRAS G12C OFF inhibitor.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

This observation mirrored similar findings that we had previously reported in patients with KRAS G12C colorectal cancer. Third, we showed clinical evidence that oleuronarasib can be combined productively with pembrolizumab in first line non small cell lung cancer patients with an acceptable safety and tolerability profile. These findings suggest that eleeroniracib in various treatment configurations warrants evaluation in patients with RAS G12C non small cell lung cancer. And we continue work to prioritize among the multiple options for advancing development of this differentiated Ras on G12C inhibitor. Fourth, we continue to advance Zoldon Rasib for patients with RAS G12D non small cell lung cancer.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We recently shared promising data for patients with previously treated RAS G12D non small cell lung cancer. We are following these patients and enrolling an expansion cohort to generate a robust data set. We are also evaluating its potential in combination settings to inform potential registration opportunities. Fifth, we were pleased to announce recently a new clinical collaboration with Summit Therapeutics to evaluate combinations of Summit's ivonesumab and advanced PD-one VEGF bispecific antibody with each of diraxonrasib, belironrasib, and zoldonrasib. This collaboration builds on promising initial clinical evidence we have reported indicating that diraxonrasib and dalironrasib can deliver additive antitumor activity with an acceptable safety and tolerability profile when combined with a PD-one antibody.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

The new cohorts will assess whether combinations with the next generation PD-one VEGF bispecific inhibitor can unlock further therapeutic impact. Beyond our first three clinical stage RasOn inhibitors that are progressing nicely, the next asset we are preparing to enter clinical development is RMC-five thousand one twenty seven, a RasOn G12V selective inhibitor. We expect this program to be clinic ready later this year to support the planned initiation of a Phase one trial in 2026. And we continue investing to produce next generation assets to build on our momentum and support our commitment to creating the leading global RAS targeted franchise. Among these investments are collaborations that will enhance our discovery efforts.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

This includes our work with Aethon announced last year to discover novel bispecific antibodies that can complement RAS on inhibitors. We also recently announced a significant drug discovery collaboration with Iambic to use their cutting edge AI capabilities and generate customized models through training with our proprietary data. This work may be particularly impactful by enhancing our lead discovery and optimization processes directed against both current and new drug targets. This exciting collaboration brings together AI and our well validated drug discovery capability to help ensure that we continue building a highly impactful and sustainable pipeline. The progresses I've outlined today is enabled by a strong operational foundation and the capabilities, talent and financial wherewithal needed to scale the efforts to meet the ever growing opportunities afforded by our pipeline.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Our position of financial strength has been meaningfully bolstered by our recently announced partnership with Royalty Pharma. This partnership supplements our strong balance sheet by providing us with an additional $2,000,000,000 in committed capital through a highly flexible mix of synthetic royalty and debt instruments, which are available to us upon achievement of agreed upon milestones. This capital access gives us the firepower, autonomy, and strategic agility we need to advance our ambitious clinical development and commercialization plans. Importantly, it also provides the financial muscle behind the commitment we announced for RevMed to direct and execute independently on a global development and commercialization strategy for our promising RAS targeted portfolio. This financial strength, combined with our maturing pipeline and organizational capabilities, empower our intention to become a fully integrated global oncology company that discovers, develops, delivers innovative targeted therapies on behalf of patients worldwide living with RAS addicted cancers.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

I'd now like to turn the call over to Jack to provide more specifics on our Royalty Pharma partnership and summarize our second quarter results. Jack?

[Jack Anders, CFO at Revolution Medicines]

Thanks, Mark. Before turning to the second quarter financial results, I would like to review a few key highlights from our Royalty Pharma transaction. This funding arrangement provides for $2,000,000,000 in committed funding comprised of up to $1,250,000,000 in synthetic royalty on future sales of doraxonerasib and up to $750,000,000 in corporate debt. We have structured the funding arrangement to be flexible, with 1,250,000,000.00 or almost two thirds reserved as optional for RevMed and to be drawn at our election, subject to achievement of specific milestones. This innovative funding provides us with flexible access to $2,000,000,000 in committed capital at a competitive cost and without equity dilution to our shareholders or compromising control of our clinical assets.

[Jack Anders, CFO at Revolution Medicines]

We expect to use this financial flexibility as we progress our programs, as our cash flow and capital needs evolve, and as we continue optimizing our capital formation strategy as the company and portfolio mature. Additional details on our Royalty Pharma partnership can be found in our filings with the SEC. Moving to our financials. We ended the 2025 with $2,100,000,000 in cash and investments. This balance includes the receipt of the first royalty monetization tranche of $250,000,000 from our partnership with Royalty Pharma.

[Jack Anders, CFO at Revolution Medicines]

Turning to expenses. R and D expenses for the 2025 were $224,100,000 compared to $134,900,000 for the 2024. The increase in R and D expenses was primarily due to increases in our clinical trial related expenses and manufacturing expenses for our three clinical stage programs, with doraxonrasib being the largest driver of the increase given the program is in two Phase III trials. Personnel related expenses and stock based compensation expense also increased in 2025 due to additional headcount. G and A expenses for the 2025 were $40,600,000 compared to $21,700,000 for the 2024.

[Jack Anders, CFO at Revolution Medicines]

The increase in G and A expenses was primarily due to increases in personnel related expenses and stock based compensation expense associated with additional headcount and commercial preparation activities. Net loss for the 2025 was $247,800,000 compared to $133,200,000 for the 2024. The increase in net loss was primarily driven by higher operating expenses. With regard to the accounting for the Royalty Pharma transaction, the first $250,000,000 royalty monetization tranche we received in June was accounted for as a liability on our second quarter balance sheet. This liability will accrete or increase through interest expense on our income statement and future royalty payments we pay on net sales of doraxoneurasib will be applied against and reduce the liability balance on our balance sheet.

[Jack Anders, CFO at Revolution Medicines]

In the 2025, we recognized approximately $900,000 in non cash interest expense related to the transaction and expect this to grow for the remainder of the year. We are updating our 2025 financial guidance and expect projected full year 2025 GAAP net loss to be between $1,030,000,000 and $1,090,000,000 which includes estimated non cash stock based compensation expense of between $115,000,000 and $103,000,000 The increase in expected GAAP net loss is primarily the result of our decision to pursue global development and commercialization independently and increased expenses that result from our growing confidence related to our robust research, development and commercialization plans. That concludes the financial update. I'll now turn the call back over to Mark.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thank you, Jack. The Revolution Medicines Organization is determined to build the leading global targeted medicines franchise for patients living with RAS addicted cancers. We believe our strong financial condition and access to a large quantum of additional capital to fuel our expansive development and commercialization plans for our compelling portfolio of investigational drugs will empower us to establish new global standards of care for patients living with RAS addicted pancreatic, lung and colorectal cancers. Our momentum is made possible by the support of our patients and caregivers, clinical investigators, scientific and business collaborators, advisors and shareholders. I'd also like to recognize the continuing extraordinary efforts of RevMed employees whose tireless commitment to patients drives this progress.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

This concludes our prepared remarks, and I'll now turn the call over to the operator for the Q and A session.

[Operator]

Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 11 again. Please limit to one question and one follow-up question.

[Operator]

Please stand by while we compile the Q and A roster. Our first question comes from the line of Michael Schmidt with Guggenheim Securities. Your line is now open.

[Michael Schmidt, Senior MD & Equity Research Analyst - Biotechnology at Guggenheim Securities, LLC]

Hey, good afternoon. Thanks for taking my questions. And, yeah, nice to hear that the RAZALIL-three zero two study is winding down U. S. Sites.

[Michael Schmidt, Senior MD & Equity Research Analyst - Biotechnology at Guggenheim Securities, LLC]

Mark, could you comment on how you're tracking towards completing enrollment ex U. S. And perhaps, any comments on the rough geographic distribution of patients would be interesting, I think. And then a question on the planned first line PDX study, where you reaffirmed plans to run a three arm study here, and obviously a lot of interest in the chemotherapy combination where you're doing work still. Obviously, with the goal to optimize tolerability and I believe, maintaining dose intensity here, how important is potential clinical efficacy assessment for these chemotherapy combinations to support advancing one or perhaps more of these planned combinations into first line? Thanks so much.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thank you, Michael. Those were meaty questions. So the first question is about three zero two. It is making very good progress. I don't think we can share with you a breakdown of actual distribution.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

That, of course, continues to evolve. You know, as indicated, we're winding down the U. Enrollment. There continues to be enrollment outside The United States, and so the final numbers will ultimately be determined by that. But it's hard to give you much more information than that.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We're sort of like landing a baby jet on a moving aircraft carrier. There are a lot of parts that all have to synchronize to get to the finish line. It's looking very solid. We're in very good shape, and I think we'll be in a good position to share data in 2026. With regard to the three arm study and the chemo combination component, I think you asked sort of two subparts.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

One is, are we still studying it? And then the second was, what role does efficacy play as a parameter in that? Steve, do you want to comment on each of those questions? Are we still studying chemo combinations? And what role does efficacy play?

[Steve Kelsey, President - Research & Development at Revolution Medicines]

We are still studying the chemo combinations, but we're very close. We did promise that we would share the study design and the rationale behind that study design in 2025. We're getting closer to the end of 2025, so you can infer that we're pretty close to the end of the assessments that we need in order to inform the study design specifically.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

With regards to the efficacy assessments explicitly, of course, they will be important in informing the study design up to a point. The primary basis for the ongoing assessments that we have is obviously safety and tolerability. We are relying very heavily on the second line data that we have for doraxonerasib, which as we have previously reported, seems to exceed the outcomes for chemotherapy in first line pancreatic cancer. So that's already a fairly strong driver of our decision to move forwards with that study. But there will be some supplementary efficacy information for the analyses that we've done specifically in first line patients.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

And we will share that information when we share the study design as part of the rationale. I hope that we'll have a pretty comprehensive package and persuasive one for you at that time.

[Michael Schmidt, Senior MD & Equity Research Analyst - Biotechnology at Guggenheim Securities, LLC]

Very helpful. Thank you so much.

[Operator]

Thank you. Our next question comes from the line of Mark Fram with TD Cowen. Your line is now open.

[Marc Frahm, Biotechnology Equity Research Analyst at Cowen]

Hi. Thanks for taking my questions and mostly following on Michael's questions, hopefully as needy. Could you maybe characterize the chemotherapies you're zeroing in on and how closely you'd expect that to the chemo in the combination to resemble kind of a standard of care first line regimen versus maybe how much you've had to dose adjust to make things tolerable. And then on the guidance for data potentially being in 2026 for a second line trial, is that referring to the final analysis, or is that inclusive of where you're projecting all of the interims to occur as well?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Okay, thanks, Mark. Appreciate the questions. The first question remind me again had to do with chemotherapy Sure, I think

[Anthony Mancini, Chief Global Commercialization Officer at Revolution Medicines, Inc]

the regimens we're looking at.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Oh, the regimens, yeah. As we've indicated, I know we've talked about this with you before, that all of the dosing that we're looking at is well within standard practice. We're not pushing outside of that at all, nor do we think we're going to need to do that. So I think we're using very active doses. And within chemo, as we've discussed before, doses that are higher at the beginning of a treatment regimen often become lower.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

In fact, they typically become lower throughout the course of multiple cycles, simply because they started at MTD. So by definition, they're barely tolerable, they and get less and less tolerable over time. So I think we're well within that range, and that's my intention. The second question had to do with when we say a readout of data in 2026, what do we mean? Well, I mean, all we can really reference right now is the first analysis.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We can't really predict what would happen at that time. It all depends. That first analysis might be the final analysis. It might be an interim analysis. And there are potential additional analyses after that, but they're all event driven.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

And so we don't really control the timing, so it would be very hard to tell you all possible scenarios here.

[Marc Frahm, Biotechnology Equity Research Analyst at Cowen]

Okay, but it is the first interim that's likely in 'twenty six, given kind of current event rates and enrollment rates?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Well, we can't skip the first interim. The first analysis is always going be a first out analysis, and we do think there will be a report in 2026, and we're optimistic that we'll be able to deliver on that. You know, the enrollment has been very robust, as we're indicating here, and, you know, we're having to sort of slow some things down to allow other things to fill some slots. I don't think that enrollment's going to be an issue at all. We just then have to let the events and a reminder that this is an OS event driven readout, even though it will read all the endpoints, it's OS driven.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

And we can't really predict that, even though we have models that attempt to predict it, but we don't know, for sure. I think we're comfortable with twenty twenty six.

[Marc Frahm, Biotechnology Equity Research Analyst at Cowen]

Okay, thank you.

[Operator]

Thank you. Our next question comes from the line of Jonathan Chang with Leerink Partners. Your line is now open.

[Jonathan Chang, Senior MD & Senior Research Analyst at Leerink Partners]

Hi, guys. Thanks for taking my question. On the doraxonerasib combination data informing the frontline PDAC registrational study design, can you provide any additional color on what kind of data and how much data we can expect later this year? Thank you.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thanks, Jonathan. I think the best way to answer that, and Steve may want to add to this, is we are building a data set that allows us to make these decisions, And that's usually our standard. If it's sufficient information to guide our decision making, to give us confidence in moving forward, to spend significant capital and to commit patients to experimental arms in a trial, then we feel that that's sufficient to share with you. And that's all we can do to quantitate it at this point.

[Jonathan Chang, Senior MD & Senior Research Analyst at Leerink Partners]

Got it. Maybe just one follow-up on that then. Can you provide your latest thoughts on what you think the key considerations are as we think about which chemo regimen or regimens could be part of that frontline doraxone Rasa registrational study? Thank you.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Well, I think Steve may want to comment on it and reiterate that it's primarily a safety and dose intensity question. We can give you a little bit more color to that, but that's always been the question that we needed to resolve as we discussed starting back at the first conference of the year. Chemotherapy I'll just say one more thing, and then Steve can clarify it here. Chemotherapy is dosed at maximum tolerated dose. So anything you add to that may end up compromising not only the dosing of the chemotherapy but also the dosing of the active target agent as well.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

And since we believe generally continuous dosing is a very good idea for suppressing RASP pathway signaling and thereby suppressing inhibiting tumor growth, we need to optimize that. So that really is the main consideration, but maybe Steve can give you

[Steve Kelsey, President - Research & Development at Revolution Medicines]

That was the primary the primary consideration was the minimizing dose interruptions and maximizing the dose intensity of the RAS inhibitor. We fundamentally believe that pancreatic cancer is a RAS driven disease and that the best treatment you can deploy would be a RAS inhibitor. And so it's really important for us that the patients that are randomized to get the RAS inhibitor get the best chance on that RAS inhibitor, which means that the dose intensity has to be as high as possible interruptions need to be as infrequent and as short as possible. And chemotherapy, unfortunately, does a very good job of disrupting both of those things. So chemotherapy will cause toxicities that require dose interruptions of the RAS inhibitor and chemotherapy may result in other things happen that may ultimately reduce the dose intensity of the RAS inhibitor.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

Having said that, there are some critical constraints. We're not testing regimens that are unusual. We're not testing cytotoxic drugs that are not used in standard practice on a global basis. And we're not testing the schedules or doses of those drugs that are not used in standard practice on a global basis. So I think that, ultimately, we have a few constraints.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

This is going to be a global trial. We have consulted very widely across the major geographic areas that will be, participating in the study. And I think that we will come up with a solution that is, acceptable for everyone involved. As I say, once we've dotted the Is and crossed the Ts, we'll be very happy to share that information with you. We're just not quite ready right now to do that.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

For disclosure, but we are very optimistic about this, and we've repeated this plan multiple times now, and it will be the plan.

[Jonathan Chang, Senior MD & Senior Research Analyst at Leerink Partners]

Understood. Thank you.

[Operator]

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

[Ellie Merle, ED - Biotech Equity Research at UBS Group]

Hey, guys. Thanks so much for taking the question, and congrats on all the progress. Curious your perspective on RAF upregulation as a resistance mechanism and thoughts on RAF degradation versus inhibition, particularly in the G12D space? Thanks.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

Yeah, RAS amplification is a real issue. So firstly, let's start with, I don't think it matters whether it's all about G12D or not, frankly, because I think what I'm going to say is going to likely to be true for all of the major RAS mutations in probably all of the major tumors in which RAS is a cancer driver. But RAS amplification, that is amplification of the mutant allele, the actual KRAS G12D, if you like, for G12D driven tumors, is a major cause of escape from RAS inhibitors because the tumors really, really love RAS and they try everything they possibly can to continue to signal through RAS. If you give a mutant selective inhibitor, there are multiple other ways the tumor can escape But if you give a RAS multi inhibitor, a lot of those additional pathways are shut down and the tumor ultimately has to default to RAS amplification.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

The problem for the tumor is that mutant RAS amplification is unfavorable for the tumor. It takes a lot of energy for the tumor to do it. It takes quite a long time for the upregulation to become apparent and for the translation of the protein to actually overcome the RAS inhibitor. And there are also therapeutic ways where you can get on top of RAS amplification. If you double down on inhibition of the mutant RAS allele with, for instance, a RAS on doublet, which we have we're clinically testing right now, you can actually get over the mutant RAS allele amplification.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

So yes, we acknowledge that it's a problem. It seems to be more of a problem for RAS multi inhibition than it is for mutant selective inhibitors, and there are therapeutic ways of getting on top of it. And some of them we have in our discovery toolbox and we just haven't shared them publicly yet. With regards to degraders versus inhibitors, I don't think there's any evidence anywhere in the global literature for any oncology target that a degrader is better than an inhibitor. And, I think that the jury will remain out until the degrader companies generate clinical data that exceeds the efficacy and safety of inhibitors that we have currently in clinical development.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

So, can't comment more than that. I just don't see any precedent right now for the degrader technology being superior to, inhibitors.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Yaeli, thanks for that And just to highlight a point that Steve made, the tumor is a microcosm of natural selection. And so it's actually gratifying to see that these RAS addictive tumors go to such great lengths to overcome diraxone RAS. It's because it's such an effective inhibitor of RAS, and they're so dependent upon RAS. So I think it makes complete sense biologically. We believe it makes complete sense biologically and is a marker of how effective durexion really is on suppressing broadly the RAS pathway.

[Operator]

Thank you. Our next question comes from the line of Kelly Hsieh with Jefferies. Your line is now open.

[Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies]

Congrats on the progress, and thank you for taking my questions. For the frontline pancreatic cancer trial, as you guided, you will share the pivotal trial design later this year.

[Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies]

Curious, at this moment, if the trial design has been signed off by the regulatory agencies, could we assume no interim data from second line pivotal trial is needed in the data package for sign off based on the comments made from the opening remarks. Thank you.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Yeah, thank you, Kelly. We don't typically give sort of blow by blow updates on our interactions with the regulatory agencies. It ends up being much less helpful than one might hope for. So I can't really answer that specific question, but I think what's lost here a little bit is, although it's not yet transparent to our investors, to our analysts, we're actually making very good progress. The fact that we keep reiterating that we're going to be on timeline for initiating is an indicator of where we stand.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

But beyond that, we just can't give you any higher resolution insight into it. It's coming soon enough. Days go by quickly.

[Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies]

Okay, thanks.

[Operator]

Thank you. Our next question comes from the line of Andrea Newkirk with Goldman Sachs. Your line is now open.

[Andrea Newkirk, Biotechnolgy Equity Research at Goldman Sachs]

Good afternoon. Thanks for taking the question. Maybe just given the reiterated timelines here for expected enrollment completion for RESOLUTE, the top line data next year, launch to follow in 'twenty seven, just curious if you'd be willing to speak more on the extent to which you're already engaging in pre commercial activities and what learnings you're taking from Lumacraft or Krizate launches that you see to be applicable to the upcoming direct formacid launch in PDAC? Thanks so much.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thanks, Andrea. Just to clarify, don't think we've guided to commercial dates. We have guided to data in 2026. I'm not agreeing or disagreeing with that particular date, but just clarifying that we've not guided to anything about the commercial timeline. With that said, Anthony Mancini can give us his view of our commercialization program status.

[Anthony Mancini, Chief Global Commercialization Officer at Revolution Medicines, Inc]

Now, thanks for the question, Andrew. And thanks, Mark. I think, what I'll say is that launch readiness plans are progressing very well. We've, got a team of experienced and talented executives leading our commercialization team across MedAffairs, market access, marketing and sales, and they're deeply engaged in market shaping activities and planning and in KOL and advocacy organization engagement, and it's really building our operational capabilities and launch readiness activities. And an example of some of the market shaping work that's going on is our Expect RAS campaign that's focused on educating the community oncologists, primarily that RAS is a driver mutation in PDAC and over ninety percent of pancreatic cancers have RAS mutations.

[Anthony Mancini, Chief Global Commercialization Officer at Revolution Medicines, Inc]

We're continuing to add to that experience and talented team, you know, and starting to build our US Field Teams more broadly now. We're learning from some of the other launches, not just not just the G12 off inhibitors, and putting the right resources in the right place, building the best strategies and tactics and operational capabilities so that we bring direct on Rasa with urgency to patients when we get that opportunity, and we're confident in our ability to continue to hire the right talent with the right commercialization experience both in The US and internationally.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Yeah, thanks, Anthony. And maybe I could just add a comment, sort of observing it. As Anthony builds that organization, I think we're going to give this a really strong effort, and hopefully we'll have a terrific approval that will go with it and great label when the time comes.

[Operator]

Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

[Jay Olsen, Biotechnology Equity Research Analyst at Oppenheimer & Co. Inc.]

Hey, congrats on all the progress, and thanks for providing this update. We have a question about your Summit partnership. And since you're planning to combine ivonesumab with all three of your RasOn inhibitors, Can you just talk about how you're going to prioritize those three combinations, and especially with regards to which tumor types you would prioritize? And then I have a follow-up. Thank you.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thanks, Jay. Can't really give you much information about that. That's sort of an operational question more than anything. We continue with our commitment to pembrolizumab, as you know. We've talked about things that we'll continue to do with pembrolizumab, which is the really singular standard in first line lung cancer in particular, and also in other some other many other indications.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

But in parallel, we'll begin exploring how the bispecific antibody will behave jointly with these different agents. And I'm sure they'll be studied across a variety of solid tumors. You know, initially with dose escalations, we typically start with a wide net because we're trying to establish safety initially, and then over time, once we get past any safety questions, then we start focusing on very specific indications. Too hard today and in this context, and at this stage, to outline in any of those more specific paths beyond the dose escalation. But we're excited to be in the collaboration.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We think it takes essentially the most advanced VEGF PD-one bispecific antibody in the field with the richest pipeline of Ras thawing inhibitors and puts them together, and we think that's a very promising opportunity.

[Jay Olsen, Biotechnology Equity Research Analyst at Oppenheimer & Co. Inc.]

Okay, thank you for that. And then I guess as you look into the future, do you think the combination of ivanesemab plus diraxone rasid has the potential to be an ideal combination in first line non small cell lung cancer?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Ideal?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Ideal is a fairly big word. I don't know. There will always be things that we'll continue to try to improve upon whatever is the then standard. But I mean, stands a chance at becoming a new standard of giving having differentiated impact. In the meantime, while we're doing that work, bimezumab in other contexts will see more mature data as Summit and their partner elaborate that information, and so we'll get a better sense of how it performs relative to PD-one.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Initial information is encouraging, but it's hard for us to see into the future. This work for us is being done on the presumption that it will play out, and we're excited to see more options, more opportunities, more potential benefit for patients.

[Jay Olsen, Biotechnology Equity Research Analyst at Oppenheimer & Co. Inc.]

Excellent. We'll look forward to that. Thanks for taking the questions.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thank you.

[Operator]

Thank you. Our next question comes from the line of Ami Fadia with Needham and Company. Your line is now open.

[Poorna Kannan, Biotech Equity Research Associate at Needham & Company]

Hi. This is Puna on for Ami. Thank you for taking our question. Just wondering, for the data update that's expected in 2026 for RESIDU-three zero two, is there any scenario where, with the data update you could seek some sort of accelerated approval and what would that look like? And the second question is a follow-up on the SANET Therapeutics one.

[Poorna Kannan, Biotech Equity Research Associate at Needham & Company]

Could you elaborate on how the combination of RasOn inhibitor with PD-one VEGF inhibitor can improve response or efficacy in RAS tumors? Thank you.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Sure. Yeah, so the first thanks for your question. The first question is, do we envision the possibility of an accelerated approval? I think we're kind of that might mix up a couple of different things. I mean, there's an accelerated approval pathway, which as my friend Steve Kelsey often points out is not often the most accelerated approval pathway.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

It's just called accelerated approval because you can submit a different data set. We're going to have a complete data set. That's the sort of whole point of the randomized control trial and the progress that's being made now, and we expect to have a package of data in 2026. So then the question is, how fast can they move on it, as opposed to will they will we pursue an accelerated approval path, I think, just to differentiate those. And we'll move as fast on it as we can, and we hope they'll move as fast on it as they can.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

But beyond that, I don't think we can speculate today about timing. We, of course, are preparing ourselves to move as absolutely as sufficiently as possible when we do open the envelope and see what the data show us. There won't be any hesitation on our part to move those data forward. We'll be well prepared for it. It'll be a well oiled machine.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

And hopefully by then we will also set things up with the FDA to maximize their ability to move as well. And I guess the other comment would be that the BTD does create some efficiencies or some speed in the review process that we'll take advantage of, and so that's a benefit of having the BTD in our hands. I think that's all I can probably say on that. Yeah. Okay.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

And then the bispecific what was the question on it? It was Oh, why was

[Poorna Kannan, Biotech Equity Research Associate at Needham & Company]

by the combo of dementia with an arrest here.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Yeah. Doctor. Wei Lin is with us, our chief medical officer. And maybe he wants to comment on PD-one with and without VEGF and why there's the possibility that it adds incremental value.

[Wei Lin, Chief Medical Officer at Revolution Medicines]

Yeah, sure. Thanks for the question. Thanks, Mark. Historically, if you reference back to, say, EGFR, RAS is a downstream node from EGFR, the combination of target therapy using EGFR cotoprotein plus VEGF, there's actually crosstalk between these pathways such that there's actually improvement in both response rate as well as progression free survival. There's been a number of trials actually demonstrated that.

[Wei Lin, Chief Medical Officer at Revolution Medicines]

Now, that has to prove itself in RAS, but at least that's in theory, there could be interaction between those two pathways that can enhance antitumor activity and potentially even translate to improved progression free survival. Yeah, and to add to that,

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

I mean, we've already demonstrated, albeit with a relatively early data set, but we've already demonstrated that the RAS inhibitors, both diraxone Rasib and elyron Rasib, in combination with an anti PD-one, do deliver greater punch, at least as determined by response rates.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We didn't present any durability data, and we've seen that many times in preclinical models. Particularly the RAS inhibitors are so effective at suppressing the RAS pathway that they reverse some of the local immunosuppressive effects that occur inside a RAS driven tumor, and that makes them more sensitive to the impact of an anti PD-one antibody when it unleashes the immune response. So that additivity, we think, is already there. Whether the VEGF itself contributes the VEGF antagonist contributes to RAS driven signaling versus just tumor growth, I don't think we can dissect that out.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

But it's a reasonable bet that if the bispecific antibody is superior to the monospecific PD-one antibody, then when you combine it with RAS, it will be superior to the monospecific PD-one antibody combined with the RAS inhibitor. That just makes sense, but it'll have to be experimental to show.

[Poorna Kannan, Biotech Equity Research Associate at Needham & Company]

Great. Thank you so much.

[Operator]

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

[Alec Stranahan, VP - Equity Research at Bank of America]

Hey, guys. Thanks for taking our questions, and congrats from me on the updates as well. First on Zolgensma and Aliron Rasib, are there any particular data points you're waiting on before pushing these into additional studies? And when do you expect to have the information in hand to make that decision? And second, the iambic collaboration, how do you see your in house data as maybe synergizing with their platform?

[Alec Stranahan, VP - Equity Research at Bank of America]

And what kind of conclusions do you think you'll be able to draw leveraging their AI technology that, I guess, you wouldn't have been able to make on your own? Thank you.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Thanks a lot, Alex. ZOLD ON and ELEER ON, you're looking for sort of what data packet will impact our decision making. Well, we have those studies really already underway, and they've been well described. And we've, in some cases, shown relatively small early data sets that are quite encouraging. And we believe those data sets but of course, we continue to follow patients to make sure that there aren't latent tolerability or safety signals, so that's one of the things we do.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We often expand them to make sure we have enough data to convince the FDA or regulatory bodies and so on. So there are quite a number of things, and there are so many different options there that it would be very difficult for us to sort of lay out a complete delineation of every study and exactly which data will be coming when and what would make the difference. So therefore we've simply not described it except when we think we're close to something where we can have a meaningful guidance about when something's going to happen. I think both Zolon and Leron are doing very well, and they do create some fantastic opportunities for us. And you can bet we're working on those.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

We'll just ask for patience until we're ready to give more complete stories about them. With regard to iambic, yeah, I think basically it comes down to this for us. We have tens of thousands of tri complex inhibitors that have been carefully crafted by our amazing chemistry group with feedback and input from our cancer biology organization. That creates a massive data set around you could call it simply SAR, but it's a massive data set. Now our chemists are very familiar with it because they've made all of those compounds, but it's a lot of information to keep in your head and to be able to access sort of on a moment's notice.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

AI has no problem with that. It accesses all of that information iteratively very, very quickly. And so the notion here is that we always just get more firepower out of processing that information, that multidimensional information, which accounts to undoubtedly many millions of data points, if not even a larger scale than that. It's very large data sets across many different parameters, and it can process those and give us give the chemist a hand in helping to prioritize which things that are worth synthesizing and which things aren't. And iambic in particular has used has built their neural plexor technology to facilitate this, and they've done it on a particular scale for a particular set of goals and actually created very quickly their own lead molecule and then development candidates to take into the clinic that's not related to RASP per se, but they it sort of validated the effectiveness of their technology.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

So they have their own uses for it, but they and we agreed that feeding that AI model or updating the AI model by incorporating our proprietary data may deliver insights that the model can predict for us or produce for us that can make it more efficient. That could be applied to RAS targets, that could be applied to non RAS targets. We have everything from modest ambition goals to very high ambition goals, and we'll see as we prosecute this to what degree it delivers. And in the meantime, we are for sure investing in our own internal AI capabilities. This is a very nice component of an overall strategy that's growing here with regard to the use of machine learning essentially largely, but also more broadly AI to make us even better at something that our organization is already pretty good at.

[Alec Stranahan, VP - Equity Research at Bank of America]

Thank you.

[Operator]

Thank you. Our next question comes from the line of Peter Lawson with Barclays. Your line is now open.

[Peter Lawson, MD - US Biotech Equity Analyst at Barclays Capital]

Great. Thank you. Thanks for the updates. Just a follow-up on the commercial build out, kind of how large the US field team be and kind of what milestones do you want to hit over the next twelve months as regards to the build out?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Yeah, hi Peter, thanks for the question. I'm going to hand you over to Anthony, who may be somewhat disappointing for you on this particular point, that sort of somewhat strategic and competitive information, and we give it a try.

[Anthony Mancini, Chief Global Commercialization Officer at Revolution Medicines, Inc]

Thanks, Mark, and thanks Peter for the question. We have initiated the build out of our US field team. In fact, we already have parts of the field team in place. We have an MSL team and we have a thought leader liaison team already in place. And we've started to build the rest of our team, including our access and sales leadership.

[Anthony Mancini, Chief Global Commercialization Officer at Revolution Medicines, Inc]

And it's really been impressive to see the caliber of talent that continues to be really interested in, you know, making, you know, making our mission come true. And that's, that's the goal. So all I'll say to fulfill Mark's point earlier is that we're, we're really feel, we're really pleased with the field build. And we're really pleased with our progress on launch readiness so far.

[Peter Lawson, MD - US Biotech Equity Analyst at Barclays Capital]

Okay, thank you so much. Realize it's difficult to talk through those. And then on the PRMT-five combo, kind of what tumor types are you prioritizing? Whether it's lung versus pancreatic or broader MTAP deletion?

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Steve, do want to comment on that?

[Steve Kelsey, President - Research & Development at Revolution Medicines]

Well, firstly, the current study that's ongoing is being sponsored by Tango, not by Revolution Medicines. But the overlap between MTAP deletion, which creates the susceptibility to the RMT5 inhibition and RAS mutation is largely pancreatic cancer. So the focus there is mainly on pancreatic cancer. There's about, as you know, almost pretty much all pancreatic cancer is RAS driven, about ninety two percent of it is frankly RAS mutated. And somewhere between, depending on geography, somewhere around twenty percent to twenty five percent I would say would have some form of NTAP deletion or loss of function.

[Steve Kelsey, President - Research & Development at Revolution Medicines]

So it turns out that around between twenty percent and twenty five percent of pancreatic cancer have both, and that would be the target population for the combination largely. Are some RAS mutant lung cancers that also have NTAP deletion, but the numbers are a little bit smaller there.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

Yeah, if I could add, I think that Tango I think they might use the number of thirty percent, something like that. And we're not disagreeing with that. It's hard to nail that down. They probably have the most information since they study that. And there are, I'm sure they would also be quick to point out, there are other tumor types in which MTAP solution occurs, but they're less commonly sites for which RAS mutations occur, so we don't capture them in our thinking so much. So I agree with Steve's points.

[Peter Lawson, MD - US Biotech Equity Analyst at Barclays Capital]

Great. Thank you so much.

[Operator]

Thank you. I'm showing no further questions at this time. I would now like to turn it back to Mark Goldsmith for closing remarks.

[Mark Goldsmith, CEO, President & Chairman at Revolution Medicines]

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

[Operator]

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Participants

Executives

• Ryan Asay, SVP & Corporate Affairs
• Mark Goldsmith, CEO, President & Chairman
• Jack Anders, CFO
• Steve Kelsey, President - Research & Development
• Anthony Mancini, Chief Global Commercialization Officer
• Wei Lin, Chief Medical Officer

Analysts

• Michael Schmidt, Senior MD & Equity Research Analyst - Biotechnology at Guggenheim Securities, LLC
• Marc Frahm, Biotechnology Equity Research Analyst at Cowen
• Jonathan Chang, Senior MD & Senior Research Analyst at Leerink Partners
• Ellie Merle, ED - Biotech Equity Research at UBS Group
• Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies
• Andrea Newkirk, Biotechnolgy Equity Research at Goldman Sachs
• Jay Olsen, Biotechnology Equity Research Analyst at Oppenheimer & Co. Inc.
• Poorna Kannan, Biotech Equity Research Associate at Needham & Company
• Alec Stranahan, VP - Equity Research at Bank of America
• Peter Lawson, MD - US Biotech Equity Analyst at Barclays Capital