Revolution spreads its PRMT5 bet

Revolution Medicines already has a clinical collaboration with one PRMT5 player, Tango Therapeutics, but now it’s working with another, Bristol Myers Squibb. During Revolution’s fourth-quarter results call the group disclosed plans to test its pan-RAS inhibitor daraxonrasib in combination with navlimetostat, a molecule Bristol gained via its purchase of Mirati, in pancreatic cancer patients with a RAS mutation and MTAP deletion. This might be bad news for Tango, which is running a phase 1/2 study of its contender, vopimetostat, that includes combos with daraxonrasib or Revolution’s G12D-selective project zoldonrasib; initial data are due this year. Tango’s trial is in second-line MTAP-deleted and RAS-mutated pancreatic adenocarcinoma and non-small cell lung cancer; the group has already disclosed plans to take vopimetostat monotherapy into phase 3 in second-line pancreatic cancer. A first-line pivotal study is also in the works, depending on the combo results. Bristol’s navlimetostat, meanwhile, is already in two phase 2/3 trials: MountainTAP-29, plus Keytruda and chemo in first-line NSCLC; and MountainTAP-30, plus Abraxane and gemcitabine in first-line PDAC. MountainTAP-29, once expected to start in October, got going in January. Amgen, once the leader in PRMT5, is apparently still carrying out dose optimisation for its candidate, AMG 193.

PRMT5 inhibitors being combined with Revolution projects

Note: PRMT5 inhibitors being tested in MTAP-deleted cancers. Source: OncologyPipeline.