Core Insights - Revolution Medicines, Inc. has published a peer-reviewed research paper in Science detailing the discovery and development of zoldonrasib (RMC-9805), a selective covalent inhibitor targeting RAS(ON) G12D mutations in cancers [1][3] Group 1: Drug Development and Mechanism - Zoldonrasib targets RAS G12D mutations, which are prevalent in various cancers, including 92% of pancreatic ductal adenocarcinoma, 50% of colorectal cancer, and 30% of non-small cell lung cancer [2] - The drug employs a novel mechanism as a tri-complex inhibitor, successfully forming covalent bonds with RAS(ON) G12D proteins by utilizing a unique protein-protein interface [2][3] - Preclinical data indicate that zoldonrasib can drive significant tumor regressions in models with KRAS G12D mutations, showcasing its therapeutic potential [2][3] Group 2: Clinical Trials and Future Prospects - Zoldonrasib is currently in clinical trials, including a Phase 1 study (RMC-9805-001) evaluating its efficacy in patients with advanced solid tumors harboring KRAS G12D mutations [4] - Results from the NSCLC and PDAC studies have been presented at notable cancer research meetings, indicating ongoing evaluation and interest in the drug's performance [4] - The company is also developing additional RAS(ON) inhibitors, including daraxonrasib (RMC-6236) and elironrasib (RMC-6291), with plans for RMC-5127 (G12V-selective) to enter clinical development next [5]