revumenib + TDI-11055

Revumenib + TDI-11055 is an investigational all-oral epigenetic combination regimen for acute leukemias characterized by KMT2A rearrangements or NPM1 mutations, pairing a menin–KMT2A interaction inhibitor with an ENL YEATS domain inhibitor. Revumenib is a small-molecule inhibitor of the menin–lysine methyltransferase 2A (KMT2A, formerly MLL) interaction that disrupts menin-dependent oncogenic transcription programs and is clinically active in relapsed or refractory KMT2A-rearranged and NPM1-mutant acute leukemias.[11] TDI-11055 is a potent, selective, orally bioavailable inhibitor of the acyl-lysine reader ENL (eleven-nineteen leukemia, MLLT1) YEATS domain that displaces ENL/AF9 from chromatin, impairs transcriptional elongation, downregulates HOX/MEIS/MYC-driven gene expression programs, and induces differentiation in MLL-rearranged and NPM1-mutant AML models.[4][2][13] Together, this combination is designed to co-target complementary components of the KMT2A/ENL-dependent transcriptional machinery to more profoundly suppress leukemogenic transcriptional complexes and overcome resistance in molecularly defined subsets of AML and related acute leukemias, although its development remains preclinical and exploratory.