Abstract 1399: Discovery and development of PARP inhibitor senaparib

Abstract Poly (ADP-ribose) polymerase (PARP) is a key enzyme for DNA repair. PARP inhibitors have been shown to be effective against cancers with DNA repair defects, such as with BRCA1 or BRCA2 mutations. Several PARP inhibitors, including olaparib, rucaparib, niraparib, talazoparib, fluzoparib and pamiparib have been approved for the treatment of several types of cancer. In this presentation, we will report our discovery and development of senaparib (IMP4297) as a potent PARP inhibitor. We will present studies led to the identification of senaparib as a clinical candidate, as well as IND enabling in vitro and in vivo characterization of senaparib. Preclinical data indicated that senaparib had a wide therapeutic window (single agent effective dose of 2.5-21 mg/kg QD, in a BRCA1 mutated MDA-MB-436 human breast cancer xenograft model), which was confirmed in clinical studies (effective dose of 20-120 mg QD, and no DLT was found up to 150 mg QD). Senaparib is currently in several phase I/II, phase II and phase III clinical studies for the treatment of multiple tumor types either as single agent or in combination with temozolomide (TMZ). The most advanced study of senaparib is a phase III study as maintenance therapy in platinum-sensitive advanced ovarian cancer patients following first-line chemotherapy (ClinicalTrials.gov Identifier: NCT04169997). Citation Format: Sui Xiong Cai, Ning Ma, Xiaozhu Wang, Yangzhen Jiang, Mingchuan Guo, Chih-Yi Hsieh, Ye Edward Tian. Discovery and development of PARP inhibitor senaparib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1399.