molecules of the month

Ziftomenib (KO-539) is an oral menin-MLL1 protein-protein interaction inhibitor being developed for acute myeloid leukemia (AML) by Kura Oncology. This Sep. ’22 Molecule of the Month inhibits the protein–protein interaction between menin and mixed lineage leukemia (MLL) fusion proteins, an interaction that drives many leukemias. Early data from an ongoing Ph. I/II clinical trials for acute leukemias are very promising, including a response in 6/8 patients and two complete responses in heavily pre-treated patients. A partial clinical hold that was placed on the trial in November 2021 due to a patient death was subsequently lifted, which was likely associated with differentiation syndrome, a known tissue-damage adverse event related to agents that cause the differentiation of leukemic blasts. The differentiation syndrome…