Revolution Medicines, Inc.

Good day, ladies and gentlemen, and welcome to the Revolution Medicine's third quarter fiscal 2021 financial results conference call and webcast. At this time, all participants are in listen-only mode. Following management prepared remarks, we will hold a Q&A session. To ask a question at that time, please press the star followed by the number one on your touchstone phone. Please be advised that today's conference call is being recorded. If anyone has a difficulty hearing the conference, please press star zero for operator assistance. I would now like to hand the conference over to Peg Horn, Revolution's Chief Operating Officer, for opening remarks. Peg, you may begin.

Good afternoon, everyone, and thank you all for joining us today. Joining me on today's call are Dr. Mark Goldsmith, Revolution's Chairman and Chief Executive Officer, Dr. Steve Kelsey, the company's President of R&D, and Jack Anders, our Senior Vice President of Finance and our Principal Accounting Officer. As we begin, I'd like to caution you that our presentation today will contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act regarding the current beliefs of the company with respect to our business. 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 we are presenting today, as well as all of the company's filings with the SEC concerning these and other matters. During this presentation, we will be referring to a few slides from our corporate presentation. The entire presentation was posted on our website immediately prior to this call. With that, I will turn the call over to Dr. Mark Goldsmith, Revolutions Chairman and Chief Executive Officer. Mark.

Good afternoon and thank you for joining us. We're very pleased to report that during this quarter, Revolution Medicines continued building momentum with our targeted therapeutics pipeline, advancing our mission to improve treatments on behalf of patients with a wide range of RAS-addicted cancers representing some 30% of all cancer patients. Our ambition is first to serve the significant unmet needs that remain for patients with KRAS G12C-bearing tumors despite first-generation targeted inhibitors coming online, and second, to deliver first-in-class or best-in-class solutions to benefit even larger numbers of patients with cancers driven by other RAS variants beyond KRAS G12C. RevMed continues making excellent progress reinforcing our belief that the company's innovative and integrated asset portfolio can drive rational mechanism-based combination treatments for the benefit of patients with diverse RAS-addicted cancers. Today, rather than providing a comprehensive overview of RevMed's entire pipeline, I would like to take you through a few highlights of several recent significant scientific presentations made by our R&D organization. As a reminder, represented on slide five of our November corporate slide deck, our primary R&D strategy is to advance our emerging RAS-on inhibitors to suppress RAS cancer drivers through innovative compounds with superior potential, deriving from their unique mechanisms of action and highly differentiated chemical and pharmacologic profiles. I'll update you on these exciting programs momentarily. We also recognize that RAS-addicted cancers are often supported and sustained by various cooperating proteins and cell regulatory pathways that limit the rate or durability of initial responses to targeted therapies. To defeat these oncogenic contributors, we are advancing our collection of high-quality targeted RAS companion inhibitors to deploy in combination with targeted RAS inhibitors in order to enhance clinical benefit. I'll touch on progress we've made in this part of our portfolio as well. RMC6291 is our potent, oral, and selective tricomplex inhibitor of KRAS G12C On with an exciting preclinical profile designed to address persistent unmet needs for patients with cancers driven by KRAS G12C. Shown in slide 8 is 6291's high potency and selectivity for KRAS G12C tumor cells and its favorable comparison to leading members of the KRAS G12C OFF inhibitor class. As shown on slide 9, our scientists recently disclosed data from a mouse clinical trial that was run with 19 KRAS G12C bearing non-small cell lung cancer models to compare the impact of RMC6291 head-to-head, in vivo, with a representative of the KRAS G12C off-inhibitor class. Consistent with findings we've reported in the past from previous experiments in individual tumor models, 6291 performed very well in this larger survey, showing broad antitumor benefit, evidenced by shrinking many tumors, inducing many regressions, including CRs, and demonstrating an overall response rate of 68% in this tumor set. The results of this study as shown on the previous slide and here on slide 10 point to specific advantages in terms of rate, depth, and or durability of response in the preclinical setting and establish an exciting best-in-class thesis for RMC6291 that we look forward to testing in the clinic. Additional data were presented just this week that extended the evaluation of 6291 into gastrointestinal cancers. Slide 11 shows a mouse clinical trial with 13 KRAS G12C-bearing colorectal cancers, demonstrating an objective response rate of 31% and disease control rate of 54%. Further, 6291 showed compelling durability of effect and delayed resistance development. Overall, these findings provide a broad foundation for our best-in-class thesis for RMC6291 that we expect to assess in the clinic. The company remains on track to submit an investigational new drug or IMD application for RMC6291 in the first half of 2022. I'd also like to highlight recent findings with RMC6236 are first-in-class oral RAS selective RAS multi-on inhibitor designed to treat cancers driven by a variety of KRAS mutations, including those that have emerged in patients following treatment with KRAS G12C off inhibitors. As shown on slide 15, our recently reported findings showed significant, broad, and durable activity of RMC6236 in vivo against numerous RAS-addicted tumor models driven by diverse RAS or RAS pathway mutations. In particular, as shown on the right, 6236 drove significant tumor shrinkage across multiple non-small cell lung cancer models with various mutations at the G12 position in KRAS, including G12D, G12V, and G12C. In addition, slide 16, shows a deeper dive specifically into the performance of 6236 in preclinical models of pancreatic cancer with mutations at KRAS position G12. This updated mouse clinical trial data set shows an objective response rate for RMC6236 of 57% across tumors with G12V, G12D, or G12R mutations with nearly complete disease control and sustained antitumor benefits. Likewise, data disclosed this week, as represented in slide 17, show significant antitumor benefit of 6236 across colorectal cancer models carrying either KRAS G12V or KRAS G12D in vivo, characterized by regressions, encouraging disease control, and highly durable antitumor effects. Overall, these data represent a very large and strong body of preclinical evidence that is a robust foundation for advancing RMC6236 to the clinic. The company remains on track to submit an IND for RMC6236 in the first half of 2022 to enable clinical evaluation for patients with these common, serious, and poorly served cancers. In addition to progressing 6291 and 6236 through IND-enabling programs, our RAS innovation platform enables the generation of additional new mutant-selective inhibitors of diverse oncogenic RAS mutants. As examples, on slide 23, which was initially disclosed last quarter, we described breakthrough work on crafting unprecedented potent RAS-on inhibitors that use highly mutant-selective covalent attachments to the KRAS G13C or KRAS G12D variants, respectively. Building on this important progress in drug discovery, recently we reported initial in vivo evaluation of two representative covalent KRAS G12D inhibitors labeled in slide 24 as RM036 and RM037. Both compounds administered orally drove deep regressions in this KRAS G12D dependent pancreatic cancer model, achieving CRs in nearly all animals. With this momentum, we remain on track to select a third development candidate from our lead optimization pipeline to advance into development by the end of this year. We will likely provide an update on this at an investor conference in early Q1. We also expect additional mutant selective RasOn inhibitors to mature out of our ongoing RasOn programs in the coming 12 to 24 months. The second key element of our R&D portfolio is developing targeted RAS companion inhibitors to counter other proteins and biochemical pathways that often cooperate with RAS mutants in driving or sustaining tumors. Today, I'll focus on certain aspects of our SHIP2 inhibitor, RMC4630, which we are developing in partnership with Sanofi, our global development and commercialization partner for SHIP2 inhibitors. RMC4630 is being evaluated in multiple combination studies with approved or late-stage drugs in development. Amgen's CodeBreak 101C study continues evaluating RMC4630 in combination with Sotiracib across multiple KRAS G12C-bearing tumor types. To date, this combination has demonstrated acceptable tolerability. RMC-4630-03 is a new study we announced in August evaluating the efficacy, safety, and tolerability and pharmacokinetics of RMC-4630 in combination with Sotiracib specifically in subjects with advanced lung cancer bearing the KRAS G12C mutation with or without additional mutations. Revolution Medicines is sponsoring the RMC-4630-03 study under its global partnership with Sanofi and conducting the trial in collaboration with Amgen. This study is now recruiting. In addition, under its global partnership with RevMed, Sanofi plans to sponsor a combination study evaluating 4630 in combination with Mirati's KRAS G12C inhibitor, Adagracid, to expand the evaluation of the potential benefit of adding this SHIP2 inhibitor to the KRAS G12C OFF inhibitor class. and we also anticipating evaluating 4630 in combination with RAS on inhibitor assets from our own portfolio as these progress. Finally, the TCD16210 study sponsored by Sanofi continues evaluating 4630 in combination with pembrolizumab, a PD-1 inhibitor, and Sanofi is planning an expansion cohort with this combination in first line PD-L1 positive lung cancer. With these prepared comments, I have tried to convey the status of our development stage assets represented by exciting and robust new data sets that suggest large clinical opportunities ahead for us to address in a wide range of RAS-addicted cancers. Further, our pipeline continues to grow with highly distinctive new assets deriving from our RAS cancer innovation engine, including multiple targeted RAS-on inhibitors and RAS companion inhibitors as we pursue science-driven strategies to outsmart RAS-addicted cancers. Please take the opportunity to review the full corporate slide deck that you can download from our investor relations website. I'll now turn to Jack Anders to report on our financial condition.