Tango Therapeutics disclosed preclinical efficacy of TNG-456, a selective MTA-cooperative PRMT5 inhibitor, demonstrating antitumor activity in glioma and brain-metastatic tumor models. The program targets PRMT5 dependency in tumors with MTAP deletions and brain-tropic biology, positioning TNG-456 for indications that require CNS penetration. Preclinical brain activity differentiates the candidate amid a crowded PRMT5 space and supports planned clinical progression for gliomas and metastatic NSCLC with brain spread. Developers will need to translate pharmacology and safety into clinical dosing regimens given PRMT5 biology’s systemic effects.