Revolution in the next KRAS battleground

With Revolution Medicines initiating dosing in the first-in-human study of its KRAS G12D inhibitor RMC-9805, the industry pipeline now comprises six clinical-stage projects with this modality. If the KRAS G12C space, now featuring the approved drugs Lumakras from Amgen and Krazati from Mirati, fast became crowded, then that targeting KRAS G12D-driven tumours might follow suit, given that G12D is said to be the most common driver of RAS-addicted human cancers. Revolution’s phase 1 study is enrolling patients with G12D-driven cancers, and is designed to inform the phase 2 dose; the company, which recently acquired EQRX for the latter’s cash balance, is also developing projects targeting various other KRAS mutations, in addition to assets with companion mechanisms including SHP2 and SOS1. The competition, meanwhile, includes Mirati’s MRTX1133 and Astellas’s degrader project ASP3082, as well as engineered T-cell receptor approaches at the NCI (this had been in Kite’s pipeline, so Gilead presumably has some rights over it), Medigene and the private companies Affini-T and Anocca.

KRAS G12D inhibitor pipeline

Note: *comprises clinical and selected preclinical projects only. Source: OncologyPipeline.