Revolution Medicines, Inc.

Good day and thank you for standing by. Welcome to the Revolution Medicines Q2 2024 earnings conference call. At this time, our participants are in listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you need to press star one one on your telephone. You would then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 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 Acey, Senior Vice President of Corporate Affairs. Please go ahead.

Thank you, and welcome everyone to the second quarter 2024 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer, and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our president of R&D, and Dr. Wei Lin, our chief medical officer, will join us for the Q&A portion of today's call. I'll note 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 30th, 2024, and recent corporate updates. This press release is available on the investor section of our website at resmed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicine's Chairman and CEO. Mark?

Thanks, Ryan. It's good to be with you this afternoon. Given our recent webcast in which we provided an update on our clinical progress in pancreatic cancer, we will keep our remarks relatively brief today. I'll share a quick summary of the data we presented last month, highlight recent progress we've made across the rest of our pipeline, and discuss several corporate updates. I'll then turn the call over to Jack, who will provide highlights of our financial results before we open the line for questions. We have made meaningful progress with our pioneering Rason inhibitor pipeline, notably preparing RMC6236, our Rason multi-selective inhibitor, to move into its first pivotal monotherapy studies in common difficult-to-treat cancers driven by oncogenic RAS variants. We kicked off the second half of the year with an important clinical milestone for RMC6236. We disclosed recent data from the RMC6236-001 trial, showing compelling preliminary progression-free survival and overall survival for patients with metastatic pancreatic cancer receiving RMC6236 monotherapy. These data have increased our confidence in the promise of this program and reinforce our commitment to initiate our first registrational study this year. I'll take a few minutes to walk through some of the key findings from the pancreatic cancer results we shared last month. The full detail of these results can be found on the investor section of our website at redmed.com. The data with a May 11th, 2024 cutoff date reflects patients with previously treated pancreatic cancer across the RMC6236 160 milligram to 300 milligram daily dose cohorts. The safety findings were promising. The most common adverse events are believed to be on target and associated with the inhibition of wild type RAS in normal tissue. Most adverse events were low grade. with approximately 22% of patients experiencing a grade three or higher treatment-related adverse event. The most common treatment-related adverse events observed were rash and gastrointestinal-related toxicities. There were no discontinuations due to treatment-related adverse events, and dose modifications of any kind occurred in only 28% of patients. The anti-tumor durability data were quite compelling as well. Historical progression-free survival benchmarks in pancreatic cancer are poor overall and deteriorate with advancing lines of therapy. In a progression-free survival analysis of second-line patients, which is consistent with the patient population we plan to evaluate in our phase three study, we observed an initial median progression-free survival of 8.1 months in patients with KRAS G12X tumors and 7.6 months in patients with RAS mutated tumors broadly. While these data continue to mature with longer patient follow-up, these preliminary findings compare favorably to standard of care in this patient population. We also showed an early interim look at overall survival in these patients. As of the cutoff date, the median overall survival had not been reached for patients with either KRAS G12X mutations or other RAS mutations, And importantly, the lower bound of the 95% confidence interval for the median overall survival estimate is above the standard of care benchmark for median overall survival in second-line metastatic pancreatic cancer. As we noted in July, while early overall survival estimates represent a relatively immature data set, in the context of the strong progression-free survival data, we believe these observations provide a meaningful complement to the overall efficacy story of RMC6236 in metastatic pancreatic cancer. We anticipate that these two measures, progression-free survival and overall survival, will be dual primary endpoints in our planned phase three study. Additional metrics and more detail regarding these data can be found on our website. Given the strength of these data and based on initial feedback from the Food and Drug Administration, including alignment around high-level study design and the selection of 300 milligrams as our go-forward dose for pancreatic cancer, we plan to initiate our first global, registrational Phase III study this year. This Phase III study, called RASALUTE302, will evaluate RMC6236 as a second-line therapy for patients with metastatic pancreatic cancer. Of course, while we are excited to initiate this study shortly on behalf of patients, Our ambitions for RMC6236 go well beyond second-line pancreatic cancer as we explore or plan to explore other tumor types and earlier lines of therapy. Data from the non-small cell lung cancer portion of the RMC6236 monotherapy study continue to mature. In the fourth quarter, we expect to provide updated safety and anti-tumor activity, including durability data, and to initiate a second registrational study evaluating RMC6236 monotherapy for patients with previously treated non-small cell lung cancer. The strength of the data we've presented also enhances our commitment to expand the reach of RMC6236 into earlier lines of therapy, including first-line metastatic, locally advanced unresectable, and resectable disease. Exploratory studies evaluating RMC6236 in combination with current standard of care chemotherapy in first-line pancreatic cancer and colorectal cancer are currently enrolling and will yield important insights that should inform dosing paradigms for potential first-line registrational paths. This area remains a significant focus for RevMed. Another important combination study in progress is evaluating RMC6236 with pembrolizumab, with or without chemotherapy, in patients with advanced RAS-mutated non-small cell lung cancer. We expect to report initial data for this combination in the fourth quarter of 2024. While there is substantial focus and investment in RMC6236 as our most advanced RAS-on inhibitor in the clinic, we also continue to prioritize investment in qualifying our first two RAS-on mutant selective inhibitors RMC6291, our G12C selective inhibitor, and RMC9805, our G12D selective inhibitor, for late-stage development. First, we continue to make progress in our combination studies with the goal of moving RMC6291 into early lines of therapy for patients with RAS G12C tumors. The RAS-on inhibitor doublet of RMC6291 in combination with RMC6236 in patients with KRAS G12C solid tumors, primarily non-small cell lung cancer, is a vanguard study of this sort of combination regimen. This study is ongoing and we expect to share initial data in the fourth quarter of this year. Another combination approach with KRAS G12C non-small cell lung cancer is RMC6291 with pembrolizumab with or without chemotherapy. A study of this combination is ongoing and we anticipate disclosing initial data for RMC6291 with pembrolizumab in the first half of 2025. Second, the first in human monotherapy study of RMC9805, a Rason G12 Deselective Inhibitor, continues to enroll well. Dose optimization is ongoing, and we are on track to share initial safety, tolerability, and antitumor activity in the fourth quarter. Overall, we have a busy and exciting road ahead with the anticipated initiation of two RMC6236 monotherapy registrational studies, a number of important exploratory combination study data updates, and additional data maturation that may validate the potential to advance two clinical stage RAS on mutant selective inhibitors into late stage development. In addition to advancing our studies, we are also preparing the organization for the next phase of growth. We are pleased to announce that we have appointed Frank Clyburn to our board of directors. Frank is a distinguished commercial pharmaceutical leader who brings a wealth of experience to help Revolution Medicines advance toward late-stage clinical development and pre-launch commercial readiness. Notably, he was instrumental in building Merck's modern oncology business, leading the successful global launch and commercialization of Merck's Keytruda to create the dominant immuno-oncology franchise. His insights and experience will be invaluable as we move forward. We've also made several strategic leadership hires across medical affairs, research and development, program management, and corporate affairs to help scale our organization as we move closer to becoming a fully integrated commercial organization. In particular, I'd like to highlight two individuals who have joined RevMed's senior leadership team. First, Ryan Acy, who is hosting today's call, brings extensive business experience in the biopharmaceutical industry to his new role as our senior vice president for corporate affairs. Second, Dr. Mary Pinder-Shank has joined the organization as our senior vice president and head of medical affairs. In addition to being a well-respected board-certified medical oncologist, Dr. Pindershank brings extensive US and global medical affairs leadership experience to RevMed. I'm highly confident in the strength of our team and the collective depth and breadth of experience we can apply to this transformative stage of the company. We continue to build the capabilities needed to drive the long-term sustainable growth of our business. This team, along with our robust pipeline of innovative programs and one of the most productive drug discovery organizations in the industry, position us well for what lies ahead. Now I'd like to turn the call over to Jack Anders, our Chief Financial Officer, to provide a financial update. Jack?