Revolution Medicines, Inc.

Welcome to the Revolution Medicine's Q4 2024 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 star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 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 Acy. Please go ahead.

Thank you, and welcome everyone to our fourth quarter 2024 earnings call. Joining me on today's call are Dr. Mark Goldsmith, our Chairman and Chief Executive Officer, and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of Research and Development, and Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call. 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 at the U.S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended December 31st, 2024, and recent corporate updates. The press release is available on the investor section of our website at revmed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer. Mark?

Thanks, Ryan. Good afternoon, and thank you for joining us. Today, I'll cover highlights of progress with our pioneering RAS on inhibitor pipeline and outline important priorities for 2025, as well as markers of progress we expect going forward as we pursue these priorities. Jack Anders will then summarize our financial results and provide a forward-looking financial view. Our mission at Revolution Medicines, one that we have pursued for much of our 10-year history, is to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development, and delivery of innovative targeted medicines. This mission is anchored in three pillars, discovery, development, and delivery. First, our innovative clinical stage RAS-on inhibitors have shown our discovery capabilities to be among the most productive in the industry. Our extensive original research in RAS biology and advances in our technology platform have given us critical know-how and a deep pipeline of proprietary assets we expect will enable us to continue raising the bar for what's possible in treating patients with RAS-addicted cancers. Second, our first-rate development capabilities have advanced multiple assets through first-in-human studies and progressed our lead program into late-stage development. We will continue strengthening these capabilities as we move into additional registrational studies across our portfolio and across a number of tumor settings and lines of therapy. Third, we are preparing to deliver our novel therapies to patients by building strong commercialization capabilities in support of a successful launch subject to regulatory approval for Deraxon RACID. Supporting our mission is an ambitious strategic roadmap for maximizing the impact our RACID inhibitor portfolio can have for patients living with RACID-indicted cancers. And our commitment to this level of ambition is reinforced by our track record of productivity and successful execution. We've been pioneers in the RAS space. Scientific innovation within RevMed has resulted in the first three clinical stage Rason inhibitors, a Rason multi-selective inhibitor, a Rason G12C selective inhibitor, and a Rason G12D selective inhibitor, each with a unique and promising clinical profile. Last month, we introduced the international non-proprietary or generic names for these three compounds. each of which is centered on the shared phrase, on RASIB, that alludes to the novel RASON mechanism of action for this new class of compounds. Dyraxon RASIB, or RMC-6236, our groundbreaking multi-selective RASON inhibitor, Eliron RASIB, or RMC-6291, our distinguished G12C-selective covalent inhibitor, and Zoldon RASIB, or RMC-9805, our innovative G12D-selective covalent inhibitor. In 2024, we built on our record of execution. We made substantial progress in advancing this portfolio of RAS-focused investigational drugs. We reported compelling monotherapy clinical data with our first wave of RAS-on inhibitors, particularly duraxone RASib in pancreatic ductal adenocarcinoma, or PDAC, and non-small cell lung cancer, and zoldone RASib in PDAC. We also reported initial evidence of two promising combination strategies. First, we reported initial clinical proof of concept for the first-of-its-kind RAS inhibitor doublet with a combination of iliron RASib with duraxone RASib. These data are highly encouraging and increased our confidence in the innovative RAS doublet concept more broadly. We've already completed dose escalation on a second RASon inhibitor doublet, zoldon RASib, combined with duraxone RASib. We will study both racon inhibitor doublets further as potentially compelling options for patients, particularly as we move into earlier lines of treatment. Second, we reported early safety and tolerability data for both duraxone racib in combination with pembrolizumab and eliron racib in combination with pembrolizumab, observations that are highly encouraging and potentially enable a path to develop therapies for first-line metastatic non-small cell lung cancer. In addition, we also entered discovery and clinical collaborations designed to expand the range of treatment strategies we can bring to bear for patients with RAS-addicted cancers. Such collaborations enable us to explore a range of combinations with inhibitors of novel targets, exemplified by a PRMT5 inhibitor under our agreement with Tango, and novel approaches such as bispecific antibodies under our agreement with Athon Therapeutics. We also formed collaborations with leading industry academia translational research partners, such as the Breakthrough Cancer Organization, that presents a valuable opportunity to uncover new patient-centric scientific insights to further inform our ongoing commitment to transformative science. Last year, we also made progress in building the organizational capabilities needed for us to drive the next stage of our strategic plan. In particular, we deepened our late-stage clinical development presence by launching our first phase three registrational trial, reaching commercial scale manufacturing of Durexan RASIV, and strengthening our organizational capabilities in preparation for a potential first regulatory approval. And we formed select partnerships to help us fulfill our tireless commitment to patients as we prepare to deliver our novel therapies to patients broadly. For example, to ensure that we keep patient needs at the forefront As we advance these medicines, we now have a relationship with Pancreatic Cancer Action Network, or PANCAN, a distinguished organization devoted to improving the lives of people living with pancreatic cancer. And we ended 2024 in an exceptionally strong financial position, allowing us to continue our ambitious patient-centric strategy. 2025 will be an important year for RevNet as we advance our strategy, aiming to maximize the impact we can have for patients with RAS-addicted cancers. I'd like to outline the highest current priorities that we anticipate could drive significant company transformation and value creation, and to identify some of the markers of progress to follow. Our first priority is to execute pivotal trials with Draxon RAS and monotherapy in patients with previously treated metastatic pancreatic cancer and non-small cell lung cancer. For the global phase three resolute 302 randomized controlled trial currently underway in patients with second line metastatic PDAC, enrollment is an important measure of progress. So far, we have seen very strong interest among patients and investigators with highly encouraging enrollment at the initial U.S. investigation centers, and we are actively opening new U.S. sites in line with our plan. With regulatory clearances in the EU and Japan in hand, we are also activating ex-US sites to support the global strategy. We currently anticipate substantially completing enrollment in the trial this year to enable an expected data readout in 2026. For non-small cell lung cancer, I'm pleased to confirm that activation of investigational sites is now ongoing in the phase three RESOLVE-301 randomized control trial, comparing duraxone RACIB to docetaxel in patients with previously treated metastatic RAS tumors. Our second priority is to advance Deraxon RASib into earlier-line randomized pivotal trials in patients with PDAC. We expect to initiate a trial in first-line metastatic disease, comparing a reference arm of patients treated by chemotherapy to two investigational arms, one with patients treated with Deraxon RASib monotherapy and one with patients treated with duraxanracib plus chemotherapy. Based on single-agent data and preliminary chemotherapy combination data, we are optimistic that both treatment arms containing duraxanracib have the potential to become important therapeutic options for patients living with metastatic pancreatic cancer. We plan to finalize the trial design later this year when we have sufficient safety and tolerability data from the currently ongoing duraxanracib plus chemotherapy safety cohorts. Of course, we'll need to align with the relevant regulatory authorities, including the US FDA, before we can initiate the global randomized case-free trial in patients with first-line metastatic PDAC. As a further step in our ambition to serve patients with earlier stage disease, I'm also very happy to share that we are actively designing a registrational trial with Deraxon RACIB as an adjuvant treatment, patients with resectable pancreatic cancer who have undergone surgery and perioperative therapy, often including chemotherapy. This population constitutes approximately 15% of newly diagnosed pancreatic cancer cases in the US each year. We expect to move quickly on developing this program in parallel with our work to finalize the pivotal trial in first-line metastatic disease mentioned earlier. We anticipate that both of these pivotal trials will be initiated in the second half of this year. Our third priority is to generate sufficient data to inform development priorities for the mutant selective inhibitors, Eliron RASIB and Zoldon RASIB, and prepare to initiate one or more pivotal trials, either as monotherapy or in a drug combination, and a number of options are under consideration. For example, we continue development of Zoldon RASIB, our innovative Rason G12D selective inhibitor for which the first in human clinical data including a favorable tolerability profile and encouraging anti-tumor activity in RAS G12d PDAC were reported at the triple meeting last quarter. A key marker of progress against this priority is generating additional clinical data that helps to qualify and prioritize these options, and we expect to share additional clinical safety and anti-tumor activity on this exciting compound in the second quarter of 2025. Another example is our ongoing efforts to identify and advance rational combination strategies with our Rasson inhibitors. We are data-driven in prioritizing among multiple combination options for advancing into earlier lines of therapy. As noted earlier, we have already provided initial encouraging safety and tolerability data for both Durexon Rassib and Eliron Rassib in combination with Pembrolizumab, thereby enabling potential combination paths to pivotal studies in first-line metastatic non-small-cell lung cancer where pembrolizumab is the global standard of care. We also provided initial encouraging data on the combination of aliron racib with daraxan racib in KRAS G12C colorectal cancer that provide initial validation of this innovative approach. We are actively enrolling and evaluating this racon inhibitor doublet in combination with pembrolizumab. That is, as a triplet regimen, in KRAS G12C non-cell lung cancer as a potential chemotherapy sparing first-line treatment. And a trial evaluating a doublet of zoldonracib with daraxanracib is currently in an expansion phase across a range of solid tumors at the anticipated single agent recommended phase two dose for each agent. We plan to evaluate emerging data for multiple ongoing studies to help us prioritize among the range of potential monotherapy and combination clinical development plan options. Based on this work, we expect to initiate one or more pivotal combination trials in 2026 that incorporate either Elir on RASIB or Zold on RASIB, likely based on a Rason inhibitor doublet, and anticipate sharing clinical data supporting these plans in the second or third quarter of this year. Our fourth priority is to regress our earlier stage pipeline, including advancing next-generation innovations from our highly productive discovery organization. In particular, we currently expect to advance RMC5127, a Rathon G12V selective inhibitor, to a clinic-ready stage this year. This will enable initiation of a first-in-human dose escalation phase one clinical trial in 2026 and a subsequent evaluation of a Rasson inhibitor doublet with Derax on Rassus. Based on a highly productive virtuous cycle between the preclinical and clinical sciences enabled uniquely by our platform and pipeline, we are excited about other promising next generation preclinical programs that will continue to be areas of investment for us to sustain our innovation pipeline beyond the current development stage assets. Finally, we are growing our commercial and operational capabilities and increasing pre-commercial activities in support of a potential launch. We've experienced and talented executives leading our commercial and medical affairs teams, and these groups have already begun expanding our visibility in key settings, including clinical conferences to reach leading oncology practitioners. It is clear that our presence and growing leadership role are being felt. We continue to expand key aspects of our organization to support a commercial launch by adding top talents, including our U.S. field teams. We expect to continue to partner with translational and clinical experts and leading patient advocacy organizations to complement our internal capabilities. We are resourcing our efforts to ensure that we have the best strategy, tactics, operational capabilities, and people to bring Durexone RACIB with urgency to patients with previously treated metastatic PDAC through a successful launch pending regulatory approvals. We see the U.S. as a core foundation and an important driver of potential long-term shareholder value. We are committed to retaining control of U.S. commercial rights as a main element of our current strategy. We also continue exploring strategies for serving patients outside the U.S., potentially including partnership opportunities to help us determine the best approach to ensure global access. We're excited about the continuing momentum and remarkable opportunity we have in front of us and look forward to reporting on markers of progress as we advance programs throughout the year. I'll now turn the call over to Jack Anders, our CFO, to summarize our fourth quarter financial results and forward-looking guidance. Jack?