Revolution Medicines, Inc.(RVMDW)Q2 2025 法說會逐字稿

Thank you, and welcome, everyone, to the second quarter 2025 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer; and Jack Anders, our Chief Financial Officer; Dr. Steve Kelsey, our President of R&D; Anthony Mancini, our Chief Global Commercialization Officer; and Peg Horn, our Chief Operating Officer, will join us for the Q&A portion of today's call. I'd like to inform you that certain statements we make 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-K and our quarterly reports on Form 10-Q that are filed with the U.S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended June 30, 2025, and recent corporate updates. The press release is available on the Investors section of our website at revmed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, our Chairman and Chief Executive Officer. Mark?

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. We have a compelling pipeline of 3 distinguished clinical stage RAS(ON) inhibitors. Daraxonrasib, a groundbreaking RAS(ON) multi-selective inhibitor; elironrasib, 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 RAS(ON) 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, daraxonrasib is our most advanced clinical program. We were pleased to announce recently that daraxonrasib received Breakthrough Therapy designation from the U.S. Food and Drug Administration in previously treated metastatic pancreatic cancer with KRAS G12 mutations. This designation underscores the large unmet medical needs for patients living with pancreatic cancer and the urgency of advancing development of daraxonrasib on behalf of patients. Towards this objective, we continue to make progress across our active and planned daraxonrasib registrational studies in pancreatic cancer. First, RASolute 302, our ongoing global Phase III 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 U.S. investigational sites to date, we are winding down enrollment in the U.S. while continuing to enroll patients outside the U.S. to ensure we have a reasonable geographic mix to support global registration. Second, we continue progressing toward initiating our first-line metastatic pancreatic cancer registrational trial, which we plan to conduct as a 3-arm trial comparing daraxonrasib or daraxonrasib plus chemotherapy to chemotherapy. Later this year, we expect to share the trial design and clinical combination data that informed this plan and to initiate the trial. Third, we also continue progressing towards a registrational trial with daraxonrasib as adjuvant treatment for patients with resectable PDAC. In 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 zoldonrasib is quite encouraging and suggest it is a remarkable inhibitor of this common cancer driver.

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 daraxonrasib, in combination with standard of care regimens and with other novel targeted agents. For example, for patients with pancreatic cancer carrying both a RAS mutation and deletion of MTAP, Tango Therapeutics announced that a first patient was dosed in a collaborative Phase I trial evaluating their PRMT5 inhibitor TNG 462 with either daraxonrasib or zoldonrasib. Such novel combinations have the potential to provide differentiated options for patients with these cancer genotypes. Moving to non-small cell lung cancer. RASolve 301, our Phase III trial of daraxonrasib in previously treated patients with RAS-mutant non-small cell lung cancer, continues enrolling patients in the U.S., and we are now activating trial sites in Europe and Japan as planned.

Evaluating daraxonrasib 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 daraxonrasib can be combined productively and tolerably with pembrolizumab with or without platinum-doublet chemotherapy. With these results in hand, we are 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 RAS(ON) mutant-selective inhibitors, elironrasib 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-cell lung cancer treated with elironrasib as monotherapy that showed a highly competitive profile including differentiated safety and tolerability along with a compelling objective response rate and progression-free survival.

We recently announced that elironrasib 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-1 and chemotherapy. This designation is a recognition of the significant unmet medical need and elironrasib'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 elironrasib with other inhibitors. In particular, the RAS(ON) inhibitor doublet of elironrasib and daraxonrasib was shown to exhibit significant antitumor activity in advanced non-small cell lung cancer patients who had progressed on treatment with a KRAS G12C(OFF) inhibitor. This observation mirrored similar findings that we had previously reported in patients with KRAS G12C colorectal cancer.

Third, we showed clinical evidence that elironrasib 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 elironrasib 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 zoldonrasib for patients with RAS G12D non-small cell lung cancer. We recently showed 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 registrational opportunities.

Fifth, we were pleased to announce recently a new clinical collaboration with Summit Therapeutics to evaluate combinations of Summit's ivonescimab, an advanced PD-1 VEGF bispecific antibody with each of daraxonrasib, elironrasib and zoldonrasib. This collaboration builds on promising initial clinical evidence we have reported indicating that daraxonrasib and elironrasib can deliver additive antitumor activity with an acceptable safety and tolerability profile when combined with a PD-1 antibody. The new cohorts will assess whether combinations with a next-generation PD-1 VEGF bispecific inhibitor can unlock further therapeutic impact. Beyond our first 3 clinical stage RAS(ON) inhibitors that are progressing nicely, the next asset we are preparing to enter clinical development is RMC-5127, a RAS(ON) G12V selective inhibitor. We expect this program to be clinic-ready later this year to support the planned initiation of a Phase I 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. 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 progress 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. 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 billion 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 and delivers innovative targeted therapies on behalf of patients worldwide living with RAS-addicted cancers. 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.

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 billion in committed funding comprised of up to $1.25 billion in synthetic royalty on future sales of daraxonrasib and up to $750 million in corporate debt. We have structured the funding arrangement to be flexible with $1.25 billion or almost 2/3 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 billion in committed capital at a competitive cost and without equity dilution to our shareholders or compromising control of our clinical assets. 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 second quarter of 2025 with $2.1 billion in cash and investments. This balance includes the receipt of the first royalty monetization tranche of $250 million from our partnership with Royalty Pharma. Turning to expenses. R&D expenses for the second quarter of 2025 were $224.1 million compared to $134.9 million for the second quarter of 2024. The increase in R&D expenses was primarily due to increases in our clinical trial-related expenses and manufacturing expenses for our 3 clinical stage programs with daraxonrasib being the largest driver of the increase, given the program is in 2 Phase III trials. Personnel-related expenses and stock-based compensation expense also increased in 2025 due to additional headcount. G&A expenses for the second quarter of 2025 were $40.6 million compared to $21.7 million for the second quarter of 2024.

The increase in G&A expenses was primarily due to increases in personnel-related expenses and stock-based compensation expense associated with additional head count and commercial preparation activities. Net loss for the second quarter of 2025 was $247.8 million compared to $133.2 million for the first quarter of 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 million royalty monetization tranche that 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 daraxonrasib will be applied against and reduce the liability balance on our balance sheet. In the second quarter of 2025, we recognized approximately $900,000 in noncash 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 $1.03 billion and $1.09 billion, which includes estimated noncash stock-based compensation expense of between $115 million and $130 million. 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.

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, advisers and shareholders. I'd also like to recognize the continuing extraordinary efforts of RevMed employees whose tireless commitment to patients drives this progress. This concludes our prepared remarks, and I'll now turn the call over to the operator for the Q&A session.

Our first question comes from Michael Schmidt with Guggenheim Securities.

Nice to hear that the RASolute 302 study is winding down U.S. sites. 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 PDAC study where you sort of reaffirmed plans to run a 3-arm study here and obviously, a lot of interest in the chemotherapy combination where you're doing work still. And obviously, with the goal to optimize tolerability and I believe maintaining dose intensity here, how important is potentially clinical efficacy assessment for these chemotherapy combinations to support advancing one or perhaps more of these planned combinations in the first line.

Thank you, Michael. Those were meaty questions. So the first question is about 302. It is making very good progress. I don't think we can share with you a breakdown of actual distribution. That, of course, continues to evolve. As indicated, we're winding down the U.S. enrollment, and 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. We're sort of like landing a Navy 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 3-arm study and the chemo combination component, I think you asked sort of 2 subparts. One is are we still studying it, and then the second was what role this efficacy play as a parameter in that. Steve, do you want to comment on each of those questions? Are we still studying the chemo combinations and what role does efficacy play?

We are still studying the chemotherapy combinations, and we promised to share the study design and the reasoning behind it in 2025. As we approach the end of 2025, we're nearing the completion of the assessments needed to inform the study design, particularly regarding efficacy, which is important. However, our ongoing assessments primarily focus on safety and tolerability. We are heavily relying on the second-line data for daraxonrasib, which reportedly shows better outcomes than chemotherapy for first-line pancreatic cancer. This strongly supports our decision to proceed with the study. There will also be additional efficacy information from our analysis of first-line patients, which we will share when we present the study designs and rationale. We aim to provide a comprehensive and compelling package at that time.

Our next question comes from the line of Marc Frahm with TD Cowen.

Following Michael's questions, could you describe the chemotherapies you are focusing on and how similar you expect the chemotherapy in the combination to be to a standard first-line regimen, versus how much you have had to adjust the doses for tolerability? Also, regarding the guidance for data potentially being available in 2026 for a second-line trial, does that refer to the final analysis, or does it include all the interim projections as well?

Thank you, Marc, for the questions. The first question relates to chemotherapy regimens. We've previously discussed that all the dosing we are considering is well within standard practice, and we do not believe we will need to exceed that. We are utilizing effective doses, and as we've mentioned, doses tend to decrease over the course of treatment cycles, starting at the maximum tolerated dose which is barely manageable and tends to become less tolerable over time. We are intentionally staying within that range. The second question about the data readout in 2026 refers to our first analysis. At this point, we can't predict the outcomes. The first analysis could be final or interim, and there may be further analyses, but all are event-driven, making it difficult to specify the timing of various scenarios.

Okay. But it is the first interim that's likely in 2026, given kind of current event rates and enrollment rates.

Well, we can't skip the first interim. The first analysis is always going to be the first 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. The enrollment has been very robust as we're indicating here, and we're having to sort of slow some things down to allow other things to fill some slots. I don't think that enrollment is going to be an issue at all. We just then have to elect 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. 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 2026.

Our next question comes from the line of Jonathan Chang with Leerink Partners.

On the daraxonrasib combination data in forming the front-line 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?

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 and to give us confidence in moving forward to spend significant capital and to commit patients to experimental arms in the trial, then we feel that's sufficient to share with you. And that's all we can do to quantitate it at this point.

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 front-line daraxonrasib registrational study?

Well, I think Steve may want to comment on it and reiterate, but it's primarily 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, just to say one more thing, and then Steve can clarify here, chemotherapy is dosed at national-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 targeted agents as well. And since we believe generally continuous dosing is a very good idea for suppressing RAS 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...

The primary consideration was to minimize dose interruptions and maximize the dose intensity of the RAS inhibitor. We fundamentally believe that pancreatic cancers are RAS-driven diseases and that the best treatment would be a RAS inhibitor. It's crucial for us that the patients receiving the RAS inhibitor have the best possible chance, which means maintaining high dose intensity with infrequent and short interruptions. Unfortunately, chemotherapy disrupts both aspects effectively. It causes toxicities that necessitate dose interruptions of the RAS inhibitor and may lead to other issues that could lower the dose intensity. However, there are critical constraints; we are not testing unusual regimens or cytotoxic drugs outside of global standard practices, nor are we using non-standard schedules or doses. This will be a global trial, and we've consulted widely across key geographic areas involved. We are optimistic about finding a solution that works for everyone and will share more information once we finalize the details, although we are not ready to disclose specifics just yet. We have reiterated this plan multiple times, and it will be the course moving forward.

Our next question comes from the line of Ellie Merle with UBS.

Congrats on all the progress. Curious your perspective on RAS up-regulation as a resistance mechanism and thoughts on RAS degradation versus inhibition, particularly in the G12D space.

RAS amplification is a significant issue. To begin with, I believe it doesn't matter whether we discuss G12D specifically because what I'm about to say likely applies to all major RAS mutations across the primary tumors where RAS acts as a cancer driver. RAS amplification, specifically the amplification of the mutant allele such as KRAS G12D in G12D-driven tumors, is a major method by which tumors can escape RAS inhibitors. Tumors heavily rely on RAS and will do everything possible to keep signaling through it. When a mutant-selective inhibitor is administered, tumors can find multiple alternate pathways to reactivate RAS. However, when a RAS multi-inhibitor is given, many of those alternate pathways are inhibited, forcing the tumor to rely on RAS amplification. Although mutant RAS amplification is detrimental for the tumor, as it requires a lot of energy and time for the up-regulation to become noticeable and for the translated protein to counteract the RAS inhibitor, there are therapeutic strategies to address RAS amplification.

For example, intensifying the inhibition of the mutant RAS allele with a RAS(ON) doublet that we are currently testing clinically can help manage the amplification. We recognize this issue, noting it appears to pose more of a challenge for RAS multi-inhibition than for mutant-selective inhibitors. There are therapeutic approaches in our discovery toolkit that we have yet to disclose publicly. Regarding the comparison of degraders versus inhibitors, I see no evidence in the global literature indicating that a degrader outperforms an inhibitor for any oncology target. The situation will remain uncertain until degrader companies provide clinical data demonstrating efficacy and safety that surpasses current inhibitors in development. Therefore, I cannot provide further insights beyond stating that there is no current precedence for degrader technology being superior to inhibitors.

Ellie, I appreciate your question. To emphasize a point Steve mentioned, the tumor serves as a small-scale model of natural selection. It's actually encouraging to observe how these RAS-dependent tumors exert significant effort to counteract daraxonrasib. This is due to its potency as a RAS inhibitor and their strong reliance on RAS. We believe this biologically makes complete sense and serves as an indicator of how effectively daraxon suppresses the RAS pathway.

Our next question comes from the line of Kelly Shi with Jefferies.

Congrats on the progress. For the front-line pancreatic cancer trial, as you guided, you will share the pivotal trial design later this year, curious, at this moment, if the trial design has been signed off by the regulatory agencies. Could we assume no interim data from the second-line pivotal trial is needed in the data package based on the comments made from the opening remarks.

Yes. 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 and analysts, we're actually making very good progress. The fact that we keep reiterating that we're going to be on a timely line for initiating is an indicator of where we stand. But beyond that, we just can't give you any higher resolution insight into it. It's coming soon enough, days go by quickly.

Our next question comes from the line of Andrea Newkirk with Goldman Sachs.

Maybe just given the reiterated timelines here for expected enrollment completion for RASolute, the top line data next year, launch to follow in '27. 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 Lumakras or Krazati launches that you see to be applicable to the upcoming daraxonrasib launch in PDAC.

Thanks, Andrea. I want to clarify that we have not provided guidance on commercial dates. We have indicated that data will be available in 2026, and I'm not taking a position on that specific date, but I want to emphasize that we have not provided any guidance on the commercial timeline. With that in mind, Anthony Mancini can share his perspective on the current status of our commercialization program.

Thanks for the question, Andrea, 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 med affairs, market access, marketing and sales, and they're deeply engaged in market-shaping activities and planning in KOL and advocacy organization engagement and in really building our operational capabilities and launch readiness activities. 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 of oncologists primarily that RAS is a driver mutation in PDAC, and over 90% of pancreatic cancers have RAS mutations. We're continuing to add to that experienced and talented team and starting to build our U.S. field teams more broadly now. We're learning from some of the other launches, 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 daraxonrasib 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 U.S. and internationally.

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 us a really strong effort. And hopefully, we'll have a terrific approval that will go with and great label when the time comes.

Our next question comes from the line of Jay Olson with Oppenheimer.

Congrats on all the progress. We have a question about your Summit partnership. And since you're planning to combine ivonescimab with all 3 of your RAS(ON) inhibitors, can you just talk about how you're going to prioritize those 3 combinations and especially with regards to which tumor types you would prioritize? And then I have a follow-on.

Thank you, Jay. I can't provide much detail on that since it's more of an operational question. We remain committed to pembrolizumab, having discussed our ongoing plans for it, especially its role in first-line lung cancer and other indications. At the same time, we will start examining the performance of the bispecific antibody in combination with these different agents, which we expect to study across various solid tumors. We will begin with dose escalations, starting broadly as we focus on establishing safety. Once we have addressed any safety concerns, we will narrow our attention to specific indications. It's too early to define these pathways beyond the dose escalation phase. However, we are enthusiastic about our collaboration, as it combines the most advanced VEGF PD-1 bispecific antibody with the most comprehensive pipeline of RAS(ON) inhibitors, presenting a promising opportunity.

Okay. And then I guess, as you look into the future, do you think the combination of ivonescimab plus daraxonrasib has the potential to be an ideal combination in first-line non-small cell lung cancer?

Ideal is a significant term; I'm not certain. There will always be aspects we will strive to enhance beyond the current standard. However, there is potential for it to establish a new standard with a distinct impact. In the interim, as we progress, we will observe more mature data regarding ivonescimab from Summit and their partner, which will provide a clearer understanding of its performance compared to PD-1. The initial findings are promising, but predicting future outcomes is challenging for us. Our efforts are based on the assumption that it will yield positive results, and we are eager to explore more options and opportunities that could benefit patients.

Our next question comes from the line of Ami Fadia with Needham & Company.

This is Poonam on for Ami. Just wondering for the data update that's expected in 2026 for RASolute 302, 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 Summit Therapeutics one. Could you elaborate on how the combination of RAS(ON) inhibitor with PD-1 VEGF inhibitor can improve response or efficacy in RAS tumors?

Thank you for your question. Regarding the possibility of accelerated approval, it’s important to clarify that while there is a pathway for accelerated approval, it doesn’t always guarantee a faster process. The term refers to the ability to submit a different data set for review. We are committed to providing a complete data set, as is the goal of the randomized controlled trial currently in progress. We expect to have this data package ready in 2026. The question then becomes how quickly the review can proceed rather than whether we will seek accelerated approval. We plan to move as quickly as possible and are preparing ourselves accordingly. Once we have the data, we will proceed without hesitation, and we aim to have processes in place to ensure an efficient review by the FDA. Additionally, having Breakthrough Therapy Designation will help streamline the review process, which is an advantage for us. That’s about all I can share at this moment. Now, regarding the bispecific question...

Yes, of course. Thank you for the question, Mark. Looking back historically, for example, with EGFR, where RAS is a downstream factor, the combination of targeted therapy using the EGFR prototype alongside VEGF shows communication between these pathways, resulting in improvements in both response rates and progression-free survival. Several trials have proven this. While it still needs to be validated in RAS, there is a theoretical possibility that these two pathways may interact to enhance antitumor activity and potentially lead to better progression-free survival.

Yes. To add to that, we've shown, even with our preliminary data, that the combination of RAS inhibitors, daraxonrasib and elironrasib with the anti-PD-1, leads to greater observed response rates. We haven't presented any durability data yet. In preclinical models, these RAS(ON) inhibitors effectively suppress the RAS pathway, which can reverse some local immunosuppressive effects seen in RAS-driven tumors, making them more responsive to anti-PD-1 antibodies when the immune response is activated. We believe this additivity is already present. It's difficult to determine the exact contribution of the VEGF antagonist to RAS-driven signaling versus tumor growth, but it’s reasonable to infer that if the bispecific antibody outperforms the monospecific PD-1 antibody, then combining it with RAS will likely surpass the results of the monospecific PD-1 antibody combined with the RAS inhibitor. This is logical, but it will need to be tested.

Our next question comes from the line of Alec Stranahan with Bank of America.

Congrats from me on the updates as well. First on zoldonrasib and elironrasib, 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, on the Iambic collaboration, how do you see your in-house data as synergizing with their platform? 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, Alec. Regarding Zoldon and Eliron, you're interested in what data will influence our decision-making. We already have studies in progress that have been well described, and in some instances, we've presented early data sets that are promising. We believe in these data sets but continue to monitor patients for any hidden tolerability or safety issues. It’s part of our approach to expand studies to gather enough information to convince the FDA and other regulatory bodies. There are numerous factors at play, making it challenging to provide a comprehensive outline of every study and the specific data timelines. Therefore, we haven’t detailed this unless we’re close to sharing something significant. Both Zoldon and Eliron are performing well and present exciting opportunities for us. We appreciate your patience as we prepare to share more complete information. As for Iambic, we have a vast collection of tri-complex inhibitors crafted by our excellent chemistry team, supported by input from our cancer-biology group.

This creates an extensive data set around structure-activity relationships. Our chemists are very familiar with this data, but it can be overwhelming to manage. AI, however, can quickly access and process all this information. The idea is to leverage AI to extract valuable insights from our massive data set, which consists of millions of data points across various parameters. This will assist chemists in deciding which compounds are worth synthesizing. Iambic has developed their NeuralPLexer technology, which has proven effective and has allowed them to rapidly create their own molecule and development candidates. This isn’t directly connected to RAS, but it does validate the power of their technology. Both teams agree that incorporating our proprietary data into their AI model might yield insights that enhance efficiency for RAS and non-RAS targets. We aim for a range of goals, from modest to highly ambitious, and we will assess the outcomes as we progress. Meanwhile, we are definitely investing in our own internal AI capabilities, which is an integral part of our growing strategy to enhance our proficiency in this area.

Our next question comes from the line of Peter Lawson with Barclays.

Just a follow-up on the commercial build out and how large the U.S. field team be and kind of what milestones do you want to hit over the next 12 months as regards to the build-out?

Yes. 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's sort of somewhat strategic and competitive information, but Anthony, give it a try.

Thanks, Mark, and thanks, Peter, for the question. We have initiated the build-out of our U.S. 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. And it's really been impressive to see the caliber of talent that continues to be really interested in making our mission come true, and that's the goal. So all I'll say to fulfill Mark's point earlier is that we're really pleased with the field build, and we're really pleased with our progress on launch readiness so far.

Yes, I would like to add that Tango might reference a figure around 30%, and we don’t disagree with that. It’s challenging to pinpoint that exactly, but they likely have the most insight since they’ve done the research. They would also highlight that other tumor types exhibit MTAP deletion, although these are less common locations for RAS mutations, which is why we don’t focus on them as much in our considerations. Therefore, I concur with Steve's observations.

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

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

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