Tango Therapeutics, Inc. announced that the first patient has been dosed in the phase 1/2 trial of TNG462 in patients with MTAP-deleted solid tumors. TNG462 is a potentially best-in-class MTA-cooperative PRMT5 inhibitor previously granted Fast Track designation by the U.S. Food and Drug Administration. The TNG462 phase 1/2 clinical trial will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of TNG462 in solid tumors with MTAP deletions.

TNG908 and TNG462 are potent PRMT5 inhibitors that are selective for cancer cells with MTAP deletion. MTAP deletion causes accumulation of intracellular MTA, an inhibitory PRMT5 co-factor. TNG462 selectively binds to and inhibits PRMT5 in the presence of MTA, thus is selectively cytotoxic for cancer cells with MTAP deletion while sparing normal cells.

In preclinical studies, both TNG462 and TNG908 induced deep tumor regressions in preclinical models of multiple cancer types.