Revolution Medicines, Inc.

Good day, and thank you for standing by. Welcome to Revolution Medicine's third quarter 2022 earnings webcast. At this time, all participants are on 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 1-1 on your telephone. You will then hear an automated message advising your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Peg Horn, Revolution Medicines Chief Operating Officer for opening remarks. Peggy, you may begin.

Thank you and welcome everyone to our third quarter earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer. Dr. Steve Kelsey, the company's president, research and development, and Jack Anders, our chief financial officer. 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 slide of our corporate presentation or the 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?

Good afternoon, and thank you for joining us. Today, I'll provide an update on our corporate progress, and our Chief Financial Officer, Jack Andrews, will provide highlights of our financial results. In the third quarter, Revolution Medicine's continued advancing our pipeline of groundbreaking Rason inhibitors on behalf of patients with a wide range of RAS-addicted cancers, which represent 30% of all human cancers. We are building momentum with our RAS-on inhibitor pipeline, having now advanced two RAS-on inhibitor development candidates into Phase 1, 1B dose escalation trials. With the transition of these RAS-on inhibitors into early clinical development, we now have four compounds from our cohesive portfolio of RAS cancer-targeted therapeutics in human studies. This progress across our pipeline sets up an exciting and potentially data-rich 2023. I'll now review a number of key achievements that reflect this recent progress regarding our pipeline of RAS-on inhibitors and RAS-companion inhibitors. First, we have entered the arena by advancing clinical development the first two drug candidates from our highly innovative Ras-on inhibitor portfolio. In a Phase I 1B trial evaluating RMC6236, our oral Ras multi-on inhibitor, investigators are dosing patients who have tumors harboring various common KRAS G12 cancer mutations, which may include KRAS G12D, KRAS G12V, and KRAS G12R. We believe RMC-6236 is the first oral direct RAS inhibitor to be deployed against tumors harboring any of these prevalent RAS cancer drivers and marks a significant step in our effort to serve the unmet needs of patients with RAS-addicted cancers. In a Phase 1-1B trial of our oral KRAS G12C-ON inhibitor, RMC-6291, investigators are dosing patients who have tumors harboring the KRAS G12C cancer variant. We have previously reported extensive pre-clinical data demonstrating the differentiated and promising antitumor profile of this highly selective covalent inhibitor of the activated or RAS-on state of the KRAS G12C variant found in lung and gastrointestinal cancers. RMC6291 is the first of a series of mutant-selective RAS-on inhibitors that we intend to bring into the clinic. Next up is our oral covalent inhibitor KRAS G12D, the most common RAS cancer variant causing human cancer, RMC9805. IND enabling work remains on track toward our goal of beginning clinical evaluation in mid-23. This first wave of RAS on inhibitor drug candidates, RMC6236, 6291, and 9805, has the potential to help serve the vast majority of patients with RAS-addicted cancers. And our portfolio contains additional RAS inhibitors lining up behind this first wave. In parallel, we continue a clinical evaluation of two class-leading RAS companion inhibitors, our shift inhibitor RMC4630 and our mTORC1 selective inhibitor RMC5552. both of which have shown clinical evidence of antigen activity. These RAS-companied inhibitors are designed to be deployed primarily as a combination of agents with direct RAS inhibitors. In the third quarter, our clinical collaborator, Amgen, reported encouraging preliminary evidence from its Phase 1b code break 101 clinical study, suggesting promising and durable benefit from combining RMC4630 with Amgen's KRAS G12C inhibitor, Sotiracib, particularly in second-line treatment of patients with non-small-cell lung cancer who were KRAS G12C inhibitor naive. We continue enrolling patients into our Phase II study of this combination, RMC463003, in patients with KRAS G12C non-small-cell lung cancer. Ultimately, we expect to evaluate our RAS companion inhibitors in combination with our own RAS-on inhibitors in the future. Now I'll shift to our corporate progress and comment on our priorities for the remainder of 2022 and 23. In the quarter, we completed a follow-on equity financing, raising gross proceeds of $265 million to strengthen the company's balance sheet and overall financial position to support the continued development and expansion of our product pipeline. With this strong financing behind us, we are focused on timely execution of the multiple development stage activities currently underway, and our highest priority is to deliver on important clinical milestones in the coming year. We continue deploying our development resources primarily in support of our three most advanced RAS-on inhibitors, RMC-6236, 6291, and 9805, and two clinical stage RAS companion inhibitors, RMC-4630 and 5552. Despite this growing clinical pipeline, we continue our strong commitment to research activities that provide critical scientific insights to support ongoing development activities and that also leverage our proven RAS innovation engine to generate exciting new mutant selective RAS-on inhibitors with distinct profiles. We expect to nominate our next RAS-on inhibitor development candidate by the end of the year, which will join a planned second wave of additional RAS-on inhibitor drug candidates, including our KRAS G13C inhibitor RMC8839. We anticipate advancing assets from this collection into development after 2023. With this R&D strategy supported by current cash, cash equivalents, and marketable securities extending operating runway through 2024, we are positioned to deliver on important milestones. In our RAS-on inhibitor portfolio, upcoming milestones are as follows, to provide evidence of first-in-class single-agent activity for RMC6236 in 2023, to provide preliminary evidence of superior activity for RMC6291 in 2023 with this clinical profile potentially indicated by tolerability safety and or anti-tumor effects, and to announce dosing of the first patient in a monotherapy dose escalation study of RMC9805 in mid-23. In our RAS companion inhibitor portfolio, upcoming milestones are as follows. To provide top line data from the 463003 study of RMC4630 plus sotiracib in the second half of 23, and to disclose additional evidence of single agent activity for RMC5552 in 2023. In summary, we remain deeply committed to our science-driven approach to treating patients with RAS-addicted cancers, and our development stage pipeline and research efforts have entered an exciting and important phase. Our first wave of RAS-on inhibitors, which includes three distinct and highly differentiated drug candidates, has advanced significantly, with patients now being dosed with RMC-6236 or 6291 and RMC-9805 continuing its progress toward the clinic. Our differentiated RAS companion inhibitors, RMC4630 and 5552, have each shown evidence of single-agent clinical activity along the path towards strategic combinations with direct RAS inhibitors, and initial clinical evidence has now emerged in support of RMC4630 as a RAS companion inhibitor used in combination with a direct RAS inhibitor. As we intensify efforts to progress these assets to significant milestones in the coming period, we also continue to make a significant investment in pipeline expansion activities based on our productive RAS innovation engine. Building on this strong company momentum, I'll now turn to Jack Anders, our Chief Financial Officer, to provide a financial update. Jack?