Good day, and thank you for standing by. Welcome to the Revolution Medicines Q2 2025 Earnings Conference Call. 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 Asay, SVP of Corporate Affairs. Please go ahead.

Thank you, and welcome, everyone, to the second quarter 2025 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines' Chairman and Chief Executive Officer; 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 three 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 the 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 three-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 dataset from patients with previously treated KRAS G12C non-small 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 three 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 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 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 three clinical stage programs with daraxonrasib 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&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 headcount 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 the line of 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 three-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 three-arm study and the chemo combination component, I think you asked sort of two subparts. 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 the chemo combinations and what role does efficacy play?

We are still studying the chemotherapy combinations and have promised to share the study design and the rationale behind it in 2025. As we approach the end of 2025, it's clear that we are nearing the conclusion of the necessary assessments to inform the study design. Specifically, the efficacy assessments will play an important role in this process. However, the primary focus of our ongoing evaluations remains on safety and tolerability. We are heavily relying on the second-line data for daraxonrasib, which appears to outperform chemotherapy outcomes in first-line pancreatic cancer. This has strongly influenced our decision to proceed with the study. Additionally, we will provide supplementary efficacy information gathered from first-line patients when we release the study designs and rationale, and we aim to present a comprehensive and persuasive package at that time.

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

Following on Michael's questions, could you characterize the chemotherapies you're focusing on and how closely you expect the chemotherapy in the combination to resemble a standard first-line regimen, as well as how much you've had to adjust the doses to make them tolerable? Additionally, regarding the guidance for data possibly being available in 2026 for a second-line trial, does this refer to the final analysis, or does it include projections for all interim analyses as well?

Thank you, Marc, for the questions. The first question is about chemotherapy regimens. As we have mentioned before, all the dosing we are considering is within standard practice; we are not exceeding those limits, nor do we anticipate needing to. We are utilizing active doses, and as we have discussed, initial doses in a treatment regimen are typically higher and tend to decrease over multiple cycles because they begin at the maximum tolerated dose. By nature, these initial doses are at the edge of tolerability and become less manageable over time. Thus, we are intentionally staying within that acceptable range. The second question pertains to what we mean by a readout of data in 2026. Currently, we can only refer to the first analysis. It is difficult to predict what will happen at that point since the first analysis could be the final one, or it might be an interim analysis, with additional analyses potentially following, all of which are event-driven. Therefore, it’s challenging to outline all the possible 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 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 informing 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 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 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, just to say one more thing, and then Steve can clarify here, chemotherapy is dosed at the 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 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 driven by RAS mutations and that the most effective treatment would be a RAS inhibitor. It is essential for us that patients who are randomized to receive the RAS inhibitor have the best opportunity to succeed with it, which means keeping the dose intensity as high as possible and minimizing any interruptions. Unfortunately, chemotherapy tends to disrupt both aspects as it causes toxicities that necessitate dose interruptions of the RAS inhibitor and may lead to factors that can reduce the dose intensity of the RAS inhibitor. However, there are some important constraints. We are not evaluating regimens that are uncommon or using cytotoxic drugs not employed in standard global practice, nor are we testing dosing schedules that fall outside of standard practices. Ultimately, we have a few limitations in place. This will be a global trial, and we have consulted extensively across major geographical areas that will be involved in this study. We are optimistic about finding a solution that meets the expectations of all parties involved. Once we finalize the details, we will be happy to share that information with you, but right now, we’re not quite ready for disclosure, though we remain optimistic as we have reiterated this plan multiple times, and it will be our approach.

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 concern. Firstly, I don't believe it's crucial to differentiate between G12D and other major RAS mutations because my comments apply broadly to all significant tumors driven by RAS. RAS amplification, specifically the increase of the mutant KRAS G12D in tumors where G12D is the driver, plays a key role in resistance to RAS inhibitors. Tumors are highly reliant on RAS and will make every effort to maintain signaling through it. When a selective inhibitor targeting the mutant variant is administered, tumors have various mechanisms to evade it, including reactivating RAS. However, using a multi-inhibitor approach can block many of those escape routes, leading the tumor to resort to RAS amplification. This is detrimental for the tumor as it requires significant energy and time for the up-regulation to become effective enough to counter the RAS inhibitor. There are also strategies that can effectively address RAS amplification. For example, employing a RAS(ON) doublet, which we are currently testing, targets the mutant RAS allele amplification. We recognize it's a challenge, especially with multi-inhibitors compared to selective inhibitors, but there are therapeutic approaches to manage it, some of which we have in development that we haven't disclosed yet. Regarding degraders versus inhibitors, I haven't seen any evidence in the literature suggesting that degraders are more effective than inhibitors for any oncology target. The effectiveness of degraders compared to our current inhibitors will need to be validated through clinical data from the degrader companies. At this point, I don't see any evidence indicating that degrader technology is superior to inhibitors.

Ellie, thanks for that question. I want to emphasize a point Steve made: the tumor represents a small-scale example of natural selection. It's encouraging to see how these RAS-dependent tumors strive to overcome daraxonrasib. This reaction occurs because daraxonrasib is such a potent RAS inhibitor, and the tumors rely heavily on RAS. Biologically, this makes complete sense, and we believe it demonstrates how effective daraxon is at broadly suppressing 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 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, 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. 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 haven't provided guidance on commercial dates. We are expecting data in 2026, and while I'm not confirming or denying that date, I want to emphasize that we haven't suggested any details regarding the commercial timeline. With that in mind, Anthony Mancini can share his perspective on the 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 medical affairs, market access, marketing, and sales, and they're deeply engaged in market-shaping activities and planning and 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 community 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 three of your RAS(ON) inhibitors, can you just talk about how you're going to prioritize those three combinations and especially regarding which tumor types you would prioritize? And then I have a follow-on.

Thanks, Jay. I can't provide much detail on that as it's more of an operational question. We remain committed to pembrolizumab, which we have discussed as a standard treatment for first-line lung cancer and several other indications. Simultaneously, we will start investigating how the bispecific antibody interacts with these different agents, and I am confident they will be evaluated across various solid tumors. We usually begin with dose escalations to establish safety, and once any safety concerns are addressed, we will then zero in on specific indications. It’s too early at this stage to outline more specific paths beyond the dose escalation, but we are excited about the collaboration. We believe combining the most advanced VEGF PD-1 bispecific antibody with a rich pipeline of RAS(ON) inhibitors presents 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, and while there will always be areas for improvement relative to the current standard, there is a possibility that it could establish a new benchmark with a unique impact. In the meantime, as we continue our efforts, we expect to see more advanced data on ivonescimab from Summit and their partner, which will give us a clearer understanding of its performance compared to PD-1. The preliminary data is promising, but future predictions are challenging. Our work is based on the assumption that these developments will be favorable, and we are looking forward to more options and opportunities that could potentially 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 an accelerated approval, I want to clarify that there's an accelerated approval pathway, which, as often mentioned, isn't always the quickest option. It's labeled as such because it allows for the submission of a different data set. However, we will have a complete data set, as that is the purpose of the randomized controlled trial, and we anticipate having this data compiled by 2026. The real question is how quickly the review process can proceed, rather than whether we will pursue an accelerated approval path. We will act as swiftly as possible, and we hope the review process will be expedited too. However, we cannot speculate on the timing at this stage. We are preparing thoroughly to respond promptly once we analyze the data. We will be ready to advance the data without delay. Additionally, we aim to optimize our interactions with the FDA to facilitate a smoother review. The breakthrough designation does enhance some efficiencies in the review process, which we plan to leverage, providing us with a competitive advantage. That covers most of what I can share for now.

Yes, sure. Thanks for the question. Historically, if you look back at EGFR, from which RAS derives, the combination of targeted therapy using the EGFR prototype along with VEGF shows that there is interaction between these pathways which leads to improvement in both response rates and progression-free survival. Several trials have demonstrated this. While it still needs to be validated in RAS, there is a theoretical possibility that these two pathways could interact to enhance antitumor activity and potentially improve progression-free survival.

Yes. To add to that, we've demonstrated, although with relatively early data, that the RAS inhibitors daraxonrasib and elironrasib, when used in combination with anti-PD-1, can achieve greater response rates. We haven't presented any durability data, but we've seen in preclinical models that RAS(ON) inhibitors effectively suppress the RAS pathway and reverse some of the local immunosuppressive effects within RAS-driven tumors, making them more responsive to anti-PD-1 antibodies that activate the immune response. We believe this additivity is already evident. While we cannot distinctly separate the contributions of the VEGF antagonist to RAS-driven signaling versus tumor growth, it is reasonable to assume that if the bispecific antibody is more effective than the monospecific PD-1 antibody, then its combination with RAS will outperform the combination of the monospecific PD-1 antibody with the RAS inhibitor. This seems logical, but will require experimentation.

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 maybe 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, we have studies already in progress, and we have shared some early data that is encouraging. We are continuing to track patients to identify any potential safety or tolerability issues. We often expand the scope of our studies to ensure we have sufficient data to satisfy the FDA and other regulatory bodies. There are many variables involved, making it challenging to provide a thorough outline of each study and the timing of data releases. Therefore, we generally hold off on sharing details unless we are close to providing meaningful updates. Both Zoldon and Eliron are performing well and present excellent opportunities for us. We appreciate your patience as we work toward providing a more detailed update. As for Iambic, we have developed tens of thousands of tri-complex inhibitors with our talented chemistry team, creating a substantial dataset that our chemists are well-acquainted with. However, managing this wealth of information is complex. AI can efficiently access and process this multi-dimensional data, which encompasses millions of data points. This capability can assist chemists in prioritizing which compounds to synthesize. Iambic has utilized their NeuralPLexer technology effectively to develop their own molecules and candidates for clinical trials. While this isn't directly related to RAS, it underscores the effectiveness of their technology. We believe that enhancing their AI model with our proprietary data could yield valuable insights to improve its predictive capabilities for both RAS and non-RAS targets. We have a range of goals, from modest to highly ambitious, and will see how this effort unfolds as we proceed. In the meantime, we are investing in our in-house AI capabilities. This is an important part of our broader strategy to enhance our expertise through machine learning and AI as we continue to excel in our field.

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 may have mentioned a figure around 30%, and we are in agreement with that. It's difficult to pinpoint an exact number, and they likely have the most comprehensive data since they've conducted detailed studies. I'm sure they would also emphasize that there are other tumor types where MTAP deletion occurs, but these are less frequently associated with RAS mutations, so we don't focus on them as much. I share Steve's views on this.

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.