Revolution Medicines, Inc.

Good day, and thank you for standing by. Welcome to Revolution Medicine's fourth quarter and full year 2023 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'll 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, Erin Graves, Senior Director of Corporate Communications and Investor Relations.

Please go ahead. Thank you and welcome everyone to the fourth quarter and full year 2023 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. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call. As we begin, I would like to note that our presentation will include statements regarding the current beliefs of the company with respect to our business that constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act. These statements are subject to a number of assumptions, risks, and uncertainties. Actual results may differ materially from these statements, and except as required by law, the company undertakes no obligation to revise or update any forward-looking statements. I encourage you to review the legal disclaimer in our corporate presentation and our earnings press release, as well as all of the company's filings with the SEC concerning these and other matters. With that, I will turn the call over to Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer.

Mark? Thanks, Erin. Good afternoon, everyone, and thank you for joining us. We will keep our prepared remarks brief today in light of the corporate presentation we provided at the J.P. Morgan Healthcare Conference in January. Today, I'll review highlights of our company progress and lay out several important 2024 milestones for our pioneering Rasson inhibitor pipeline. And Jack Anders will provide highlights of our financial results. 2023 was a transformative year for Revolution Medicines. First, we disclosed the preliminary clinical profiles of two unprecedented targeted Rasson inhibitors, RMC-6236 a RAS on multi-selective inhibitor, and RMC6291, a RAS on G12C selective inhibitor, as evaluated in Phase I 1B trials in patients with RAS-mutated cancers. Initial safety, tolerability, and antitumor activity data reported at the TRIPLE meeting and ESMO Congress showed that both investigational drugs have highly differentiated clinical profiles, suggesting substantial promise for patients, and supporting their continued development. We also announced in September that we had dosed our first patient in the phase 1 1B trial of RMC9805, an oral and covalent G12D selective inhibitor, our third distinguished Rason inhibitor in clinical development. As I'll summarize momentarily, this important progress with our first wave of Rason inhibitors provides significant momentum heading into this year's plans. and we believe serves as validation of the RAS on inhibitor platform and deep pipeline more broadly. Second, we ended 2023 with a particularly strong balance sheet bolstered by the EQRX acquisition that fuels our ambitious plans aiming to maximize clinical impact and drive shareholder value. With a strong pipeline and financial position, we have three strategic priorities for 2024. First, Building on strong clinical momentum with our boldest and most mature investigational drug with broad potential, our highest priority in 2024 is to propel single agent RMC6236 into its first pivotal trials. We are currently working toward the goal of launching randomized controlled trials against standard of care chemotherapy for patients with RAS mutated non-small cell lung cancer or pancreatic ductal adenocarcinoma. and we expect that these efforts will command the largest share of our resources this year. Encouragingly, at the J.P. Morgan Conference, we disclosed that with ongoing follow-up since ESMO, the RMC6236 safety profile had remained relatively stable, including at 300 milligrams per day, with relatively few dose interruptions or discontinuations. In the non-small cell lung cancer cohort, we reported favorable trends for aggregate objective response rate cross doses into the low to mid 40s range and that were trending even higher in the 300 milligram cohort. In the pancreatic ductal adenocarcinoma cohort, we reported favorable trends for aggregate ORR into the mid 20s and that were trending even higher in the 300 milligram cohort. We are now focused on the 300 milligram dose and below for both lung and pancreatic cancer and continue to follow these patients as we develop a more mature data set to determine progression-free survival, or PFS. We've begun preparing our regulatory packages for dose selection and monotherapy pivotal trials that we plan to initiate in the second half of 2024. Beyond advancing into late-stage development in second-line lung and pancreatic cancers, our second strategic priority for 2024 is to expand the reach of RMC6236. We've begun evaluating the impact of single agent 6236 in patients with tumors harboring RAS mutations beyond the G12X mutations that had been the focus of the dose escalation, mainly G13X and Q61X mutations. Likewise, we're studying 6236 in patients with tumor types beyond lung and pancreatic cancer, including colorectal cancer, melanoma, and gynecologic cancers. We anticipate disclosing initial clinical PK, safety, tolerability, and activity data from the genotype and tumor type cohorts in the second or third quarter of 2024. In addition, we've initiated combination drug cohorts to examine options for reaching into first-line treatment settings. For example, we've begun evaluating RMC6236 in combination with a checkpoint inhibitor, a combination that is likely required for advancing into first-line treatment for lung cancer. We anticipate disclosing initial data in the second half of 2024, with establishing safety of these combinations as the main focus. Our third priority for the year is to qualify our Ransom mutant selective inhibitors for late stage development, RMC6291, our G12C selective inhibitor, and RMC9805, our G12D selective inhibitor. At the triple meeting in October, we reported preliminary results with RMC6291 monotherapy supporting clinically meaningful differentiation at doses that were generally well tolerated. Based on dose optimization work that has been completed, further study of RMC6291 as a single agent continues at 200 milligrams BID. As a major next step for RMC6291, we have initiated our first RAS-on inhibitor doublet trial with RMC6236 in patients with advanced KRAS G12C mutated cancers. Patients are currently being treated in the dose escalation portion of the trial, and we anticipate disclosing initial clinical PK, safety, tolerability, and activity data in the second half of 2024. We've also begun treating patients with RMC6291 and a checkpoint inhibitor to assess the safety of this combination. For our G12D selective inhibitor, RMC9805, we shared at the JPMorgan conference that oral bioavailability of RMC9805 has been confirmed in patients. We've seen pharmacokinetics consistent with expectations from our preclinical data, including dose-dependent increases in plasma exposure on once-daily dosing. We've cleared several dose levels with good tolerability, and no dose-limiting toxicities have been reported thus far. We anticipate disclosing initial safety and activity data in the second half of 2024. Finally, these ambitious clinical development priorities for advancing our first wave of Rasson inhibitors are made possible by our strong balance sheet, which now includes approximately $1.1 billion of cash from the acquisition of EQRx that closed in November. With our compelling pipeline, innovation engine, and financial position, We aim to continue building and solidifying our position as an industry leader in developing targeted medicines for patients living with RAS-addictive cancers for many years to come. I'd like to now turn the call over to Jack Anders, our Chief Financial Officer, to provide the fourth quarter and full-year financial update.