FDA grants orphan drug designation to KT-253 for the treatment of patients with AML

On June 22, 2023, the U.S Food and Drug Administration (FDA) granted orphan drug designation to KT-253, a novel, highly potent, and selective MDM2 degrader, for the treatment of patients with acute myeloid leukemia (AML).¹ MDM2 is a regulator of the tumor suppressor p53, with overexpression of MDM2 implicated in AML. Small molecule inhibitors can stabilize and upregulate p53; however, this can create a feedback loop that increases MDM2 protein levels and subsequently decreases p53. Preclinical studies have demonstrated that KT-253 can counteract the MDM2 feedback loop and induce cancer cell death.¹

The safety, tolerability, pharmacokinetics, and clinical activity of KT-253 are currently being assessed in an open-label, multicenter, phase I study (NCT05775406) which began in March, 2023.¹ This phase I study includes patients with relapsed/refractory myeloid malignancies, such as AML, acute lymphocytic leukemia and lymphoma, and solid tumors, and will be used to determine the recommended phase II dose.¹