On August 20, 2025, Simcere Zaiming, an innovative oncology company and a subsidiary of Simcere Pharmaceutical Group (2096.HK), announced that SIM0508, an anticancer candidate targeting DNA polymerase theta (Polθ), has received a new IND approval from the National Medical Products Administration (NMPA) for the combination use with olaparib in patients with advanced solid tumors in clinical trials.
SIM0508, independently developed by Simcere, represents the latest advance in cancer therapy, particularly leveraging the concept of “synthetic lethality”. It is the first Polθ inhibitor approved for clinical development in China. The compound has received IND approvals in both China and the United States and is currently being investigated in Phase I clinical trials.
This molecule selectively impedes DNA break repair in HRD tumor cells by inhibiting Polθ activity. When combining with PARP inhibitors such as olaparib, SIM0508 enhances tumor cell sensitivity to PARP inhibition, resulting in a significant synergistic effect. This is expected to enable more precise treatments for certain tumor types, while minimizing damage to normal cells.
Early clinical studies have shown that SIM0508 is safe and well tolerated, with no significant hematologic toxicity observed. These findings indicate that combining SIM0508 with a PARP inhibitor or a chemotherapy will carry a low risk of additive hematologic toxicity, which provides a new therapeutic option for a variety of HRD solid tumors. Relevant research data will be presented at an upcoming academic conference.