Revolution Medicines, Inc.

Good day. My name is Christy, and I'll be your conference facilitator today. Welcome to the Revolution Medicine Second Quarter 2022 Earnings Conference Call. Today's call is being recorded. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a question-and-answer session. To ask a question at that time, please press star, then the number 1 on your telephone keypad. If anyone has difficulty hearing the conference, please press star zero for operator assistance. I would now like to hand the conference over to David Errington, Revolution Medicine's SVP of Investor Relations and Corporate Affairs, for opening remarks. David, you may begin.

Thank you, and welcome, everyone, to our second quarter earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer, Dr. Steve Kelsey, the company's President, Research and Development, and Jack Anders, our SVP of Finance and Principal Accounting 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 Medicines 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 Senior Vice President of Finance, Jack Andrews, will provide highlights of our financial results. In the second quarter of 2022, Revolution Medicines continued building strong momentum in the discovery and development of innovative medicines on behalf of patients with a wide range of RAS-addicted cancers, which represent 30% of all human cancers. We are advancing a deep and cohesive portfolio of RAS-targeted therapeutics, led by our development stage RAS-on inhibitors. Recently, we reported significant progress across our pipeline, setting us up for an exciting period as our assets progress over the next 12 to 18 months. 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 advanced the first two drug candidates from our highly innovative RAS-on inhibitor portfolio into clinical development. In June, we began dosing patients in a Phase I 1b trial, evaluating RMC6236. our oral RAS multi-on inhibitor in patients with tumors bearing various KRAS G12D mutations. The first patient treated with this drug candidate has advanced pancreatic cancer bearing the common KRAS G12D mutation. RMC6236, a bold compound that we have shown preclinically, inhibits a wide range of RAS proteins that can drive cancer, is the first development candidate from our broad collection of RAS-on inhibitors to enter clinical development. And this step marks a significant milestone in our efforts to serve the unmet needs of patients with RAS-addicted cancers. Additionally, I'm pleased to report that study site activation is underway for a phase one 1B trial of our second oral RAS-on inhibitor drug candidate, RMC6291. And shortly, this study will begin dosing patients who have tumors harboring the KRAS G12C variant. Unlike RMC6236, RMC6291 is designed as a highly selective covalent inhibitor of the activated or RAS-on state of the KRAS G12C variant that is common in lung and colorectal cancer. We have previously reported extensive preclinical data demonstrating its differentiated and promising anti-tumor profile. RMC-6291 is the first of a robust series of mutant-selective RAS-on inhibitors that we intend to bring into the clinic. Our third RAS-on inhibitor drug candidate, RMC-9805, remains on track toward our goal of beginning clinical evaluation in mid-2023. We believe that RMC-9805 is the first oral covalent inhibitor of KRAS-G12D, the most common RAS variant causing human cancer. particularly pancreatic, colorectal, and lung cancers. Based on their preclinical profiles, we believe that, in aggregate, 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. Second, in support of our goal to develop optimal treatment strategies directed to RAS-addicted cancers, we continue clinical evaluation of two class-leading RAS companion inhibitors, our SHIP2 inhibitor, RMC4630, and our mTORC1 selective inhibitor, RMC5552, both of which have shown clinical evidence of anti-tumor activity. These RAS companion inhibitors are designed to be deployed primarily as combination agents with direct RAS inhibitors. Our clinical collaborator, Amgen, recently reported encouraging preliminary evidence from its phase 1B code break 101 clinical study, suggesting promising and durable benefit from combining RMC4630 with its KRAS G12C inhibitor, Sotiracid, particularly in second-line treatment of patients with non-small cell lung cancer who are KRAS G12C inhibitor naive. We continue enrolling patients into our phase 2 study of this combination, RMC4630-03, in patients with KRAS-G12C non-small cell lung cancer. Additionally, Sanofi is now recruiting patients in its Phase I-II dose escalation and expansion study, evaluating RMC4630 in combination with adagracid in patients with previously treated lung cancer bearing a KRAS-G12C mutation. Further, 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 focus for 2022 and 2023. In July, we successfully completed an 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. Following this productive financing in the remainder of 2022 and 2023, The company will take a disciplined approach to ensure successful and timely execution of the multiple development stage activities currently underway or planned. Our top priority is to deliver on important milestones during this time. In this period, we intend to concentrate our development resources on our three most advanced RAS-on inhibitors, RMC6236, 6291, and 9805, and two clinical stage RAS companion inhibitors, RMC4630 and 5552. Importantly, we maintain our strong commitment to research activities that provide critical scientific insights to support our ongoing development activities and that also leverage our proven RAS inhibition engine to generate exciting new mutant-selective RAS-on inhibitors with distinct profiles. We expect to nominate our next RAS-on inhibitor development candidate in the second half of 2022, which will join a planned second wave of drug candidates, including RMC 8839, which we anticipate to begin clinical development after 2023. With this R&D strategy and our current cash, cash equivalents, and marketable securities extending operating runway through 2024, we expect to deliver on important milestones. In our Rasa on inhibitor portfolio, upcoming milestones are as follows. to provide evidence of first-in-class single agent activity for RMC6236 in 2023, to announce dosing of the first patient in a monotherapy dose escalation study of RMC6291 in the second half of 2022, and provide preliminary evidence of superior activity in 2023, and to announce dosing of the first patient in a monotherapy dose escalation study of RMC9805 in mid-2023. In our RAS companion inhibitor portfolio, upcoming milestones are as follows. To provide top-line data from the 4630-03 study of 4630 plus sotiracid in 2023. And to dispose 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 pipeline and R&D efforts have entered an exciting and important phase. The first wave of RAS-on inhibitors, which includes three differentiated drug candidates, has advanced significantly, with RMC-6236 now dosing patients, RMC-6291 preparing to begin dosing patients shortly, and RMC-9805 continuing progress toward the clinic. Our differentiated RAS companion inhibitors have shown evidence of single-agent clinical activity along the path towards strategic combinations with direct RAS inhibitors. And the first clinical evidence has now emerged in support of RMC4630 as a RAS companion inhibitor combined with a RAS inhibitor. As we intensify efforts to progress these assets to significant milestones in the coming period, we are also continuing to make a significant investment, pipeline expansion activities based on our productive RAS innovation engine. Building on this exciting company momentum, I'll now turn to Jack Anders, our Senior Vice President of Finance, to provide a financial update. Jack?