Revolution Medicines(US:RVMD)2022-05-12 12:15Pipeline and Drug Candidates - Revolution Medicines is developing a deep pipeline of targeted therapies for RAS-addicted cancers, with the first two drug candidates expected to enter the clinic in 2022 [13] - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with potential against various RAS-addicted cancers, targeting approximately 137,000 new KRASG12X patients per year in the U S [19, 20] - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers, addressing approximately 29,000 new KRASG12C patients per year in the U S [38, 39] - RMC-9805 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG12D cancers, targeting approximately 55,000 new KRASG12D patients per year in the U S [59, 60] - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers, addressing approximately 3,000 new KRASG13C patients per year in the U S [69, 70] Preclinical Data and Activity - RMC-6236 demonstrated robust anti-tumor activity in cancer models, with 44% ORR (8/18) in NSCLC, 53% ORR (8/15) in PDAC, and 61% ORR (11/18) in CRC [24] - RMC-6291 showed superior outcomes in a mouse clinical trial with KRASG12C NSCLC models, achieving 72% ORR (18/25) and 92% DCR (23/25) [43] - Preclinical research indicates that RMC-6236 and RMC-6291 exhibit anti-tumor immunity in vivo and strong additivity with checkpoint inhibitors [29, 52] Clinical Development and Strategy - Revolution Medicines plans to initiate single-agent dose escalation for RMC-6236 in patients with cancers harboring KRASG12X mutations, focusing on NSCLC, pancreatic cancer, and CRC [36] - The company also intends to start single-agent dose escalation for RMC-6291 in KRASG12C tumors, including expansion cohorts in select populations like NSCLC [58] - RMC-4630, a RAS companion inhibitor, is undergoing clinical combination studies, including with sotorasib and adagrasib, to address resistance mechanisms in KRASG12C tumors [91, 93] Financial Status - As of March 31, 2022, Revolution Medicines had approximately $518 8 million in cash, cash equivalents, and marketable securities [125] - The company anticipates a GAAP net loss of $260 million to $290 million for 2022, including $35 million to $40 million in non-cash stock-based compensation expense [125, 126]