PRT1419 (MCL1 inhibitor). PRT1419 is Prelude’s third clinical candidate. PRT1419 is designed to be a potent and selective inhibitor of the anti-apoptotic protein, MCL1. MCL1 has been shown to have a critical role in promoting cancer cell survival and is frequently found to be amplified or overexpressed in both solid tumors and hematologic cancers. Inhibition of MCL1 expression and/or function is therefore of considerable therapeutic interest in cancer. Small molecule MCL1 inhibitors have been shown to be efficacious as monotherapy in preclinical models of multiple myeloma, acute myeloid leukemia and lymphoma. PRT1419 demonstrated potent and selective inhibition of MCL1 in vitro and in vivo that resulted in tumor regressions in preclinical models of hematologic malignancies following once weekly oral dosing.
PRT1419 is currently in the dose-escalation phase of a Phase 1 clinical trial in high risk myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin’s lymphoma and multiple myeloma patients, with expansion cohorts planned in combination with azacitidine or venetoclax in patients with myelodysplastic syndrome or acute myeloid leukemia.
The Company’s earlier stage programs include PRT2527, a CDK9 inhibitor, and PRT-SCA2, a SMARCA2 protein degrader.