Tango Therapeutics presented preclinical data for TNG‑456, a next‑generation PRMT5 inhibitor engineered to cooperate with MTAP-deleted tumors and showing strong antitumor activity in glioma and brain-metastatic models. The compound demonstrated tumor regressions in in vitro and in vivo assays, supporting further development in brain‑tropic cancers. The data highlight a selective mechanism of action for tumors with specific metabolic contexts (MTAP loss), underscoring precision oncology strategies that match epigenetic inhibitors to tumor genotype. For drug developers: brain-penetrant PRMT5 inhibitors pose formulation and PK/PD challenges; the preclinical package aims to justify clinical candidate selection for CNS indications.