Background：Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA damage response (DDR) and genome stability maintenance. PARP inhibitor is the first example of a targeted therapeutic exploiting synthetic lethality to kill DNA-repairing deficiency tumors (eg. BRCA1/2 mutation). Synthetic lethality arises when a combination of deficiencies in the expression of two or more genes leads to cell death, whereas a deficiency in only one of these genes does not. It can be exploited to develop targeted anticancer therapeutics using one or more targeted agents. Besides the single agent activity in ovarian, breast and prostate cancer, PARP inhibitors also show potential in novel combination therapies for different indications with a variaty of targeted anti-cancer agents and chemotherapies.
Description：IMPACT has built a broad DDR global pipeline of novel drug candidates generated by in-house discovery platform. IMP4297 was selected from two series of novel PARP inhibitors with better potency and selectivity. PCT patents have been filed and granted covering major markets. Preclinical studies of IMP4297 showed higher potency, more selective inhibition of BRCA mutant cells, and wider therapeutic window than the first approved PARP inhibitor olaparib. Early clinical data showed efficacy in BRCA mutation as well as non-BRCA mutation tumors with excellent safety profile and wide therapeutic window. See 2019 ASCO poster#3059 for more details. Impact is actively exploring IMP4297 monotherapy as well as combination therapy with other anti-cancer agents for different tumors to meet the urgent unmet medical needs.