ONC201 (benzyl-benzylmethyl-imipridone)
ONC201 is the founding member of the imipridone class. The compound exhibits attractive drug-like chemical and physical characteristics: excellent chemical stability, high aqueous solubility at low pH, and high lipophilicity at physiological pH. These attributes enable oral bioavailability that achieves therapeutic concentrations and wide distribution throughout the body to target tissues, including brain, bone marrow and lymph nodes. ONC201 has excellent activity in preclinical models of advanced cancers that no longer respond to standard-of-care treatments. The antitumor activity of ONC201 is achieved without any signs of toxicity, which is likely caused by the ability of ONC201 to target DRD2 with a high degree of selectivity and a rapid dissociation rate. Furthermore, decades of clinical experience with selective GPCR antagonists for indications outside of oncology have proven that drugs which target this superfamily are generally well tolerated, unlike most cancer therapies. Clinical trials have demonstrated the exceptional clinical safety of ONC201 along with a therapeutic pharmacokinetic (PK) profile, induction of pharmacodynamic (PD) markers, and early efficacy signals in a number of different types of cancer, including acute myeloid leukemia, non-Hodgkin’s lymphoma, prostate and endometrial cancers.