HRS-5041 + HRS-1167

HRS-5041 + HRS-1167 is an investigational oral combination therapy under clinical development for the treatment of advanced prostate cancer and potentially other solid tumors. HRS-5041 is a Proteolysis Targeting Chimera (PROTAC) designed to selectively degrade the androgen receptor (AR), a central driver in prostate cancer progression. HRS-1167 (also known as M9466) is a next-generation, highly selective, small molecule inhibitor of Poly (ADP-ribose) Polymerase 1 (PARP1), exhibiting over 600-fold selectivity for PARP1 over PARP2 to minimize hematological toxicity. HRS-1167 operates via catalytic inhibition of PARP1-mediated DNA repair (PARylation) and by promoting cytotoxic PARP-DNA trapping, thereby exploiting synthetic lethality in tumors with homologous recombination deficiency (HRD), such as those harboring BRCA1/2 mutations. The combination aims to provide a synergistic blockade of two critical pathways: androgen receptor signaling and DNA damage repair. Both molecules are being developed primarily by Jiangsu Hengrui Medicine and associated subsidiaries, with HRS-1167 co-developed globally with Merck KGaA (EMD Serono). The combination is being evaluated in phase 1 and 2 trials for advanced and metastatic castration-resistant prostate cancer, with disease extension potential in other solid tumors including ovarian cancer.