TNG456 + abemaciclib

TNG456 + abemaciclib is an investigational combination therapy being evaluated for the treatment of advanced or metastatic solid tumors with MTAP (methylthioadenosine phosphorylase) loss, including glioblastoma. TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor that selectively targets PRMT5 in MTAP-deleted cancers and demonstrates high potency and selectivity in preclinical studies. Abemaciclib is an approved small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), marketed as Verzenio, primarily used for HR-positive, HER2-negative breast cancer. The rationale for combining these agents stems from the frequent co-deletion of CDKN2A and MTAP in certain cancers and observed synergy between PRMT5 inhibition and CDK4/6 inhibition in preclinical models. The combination aims to exploit synthetic lethality to improve outcomes for patients with limited treatment options[1][2][3][7][9].