MCL1, a highly regulated member of the BCL2 family, is frequently found to be amplified or overexpressed in both solid tumors and hematologic cancers. It is induced by a wide range of survival signals and rapidly downregulated during apoptosis. Inhibition of MCL1 expression and/or function is therefore of considerable therapeutic interest in cancer, as it is thought to mediate cancer cell survival in myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin’s lymphoma, and multiple myeloma. Small molecule MCL1 inhibitors have been shown to be efficacious as monotherapy in preclinical models of multiple myeloma, acute myeloid leukemia, CLL, and lymphoma.
Prelude is developing PRT1419, which is designed to be a potent and selective inhibitor of MCL1. An intravenous formulation (IV) is being evaluated in patients with hematological malignancies. Prelude has prioritized development of the IV formulation, which has demonstrated a desirable pharmacokinetic, pharmacodynamic and safety profile with potential for differentiation from competitor compounds in development.