China-based Simcere Pharmaceutical Group (HKG: 2096) has announced the first patient in (FPI) a clinical study for its SIM0237, a bispecific antibody (BsAb) targeting PD-L1 and IL-15 in advanced solid tumors. The global multi-center, open-label Phase I study is designed to assess the safety, efficacy, and pharmacokinetics/pharmacodynamics of the drug. The study is expected to enroll 192 cases and will commence simultaneously in China and the United States.
Drug Profile and Mechanism
SIM0237 is a PD-L1 monoclonal antibody (mAb) and inactivated IL-15/IL-15R α sushi fusion protein. It can block the PD-1/PD-L1 immunosuppressive pathway by binding to PD-L1 and activate the immune system through IL-15, playing a synergistic role in relieving immunosuppression and activating immune anti-tumor dual pathways. The inactivated IL-15 terminal of SIM0237 increases drug exposure and avoids over-activation and depletion of NK and CD8+ T cells.
Innovative Features
The fusion of inactivated IL-15 and PD-L1 antibodies extends the half-life of IL-15 and delivers it directly to the tumor microenvironment, reducing systemic exposure and toxicity. In addition, inactivated IL-15 can match the dose of PD-L1 to maximize the efficacy of PD-L1 antibodies. SIM0237 can bridge CD8+ T cells, NK cells, and PD-L1+ antigen-presenting cells, promoting the formation of immune synapses and enhancing the activation of effector cells to kill tumor cells.
Preclinical Findings
Preclinical studies have shown that SIM0237 demonstrated better efficacy than PD-L1 and IL-15 alone in mouse tumor models. This highlights the potential of SIM0237 to offer a more effective treatment option for patients with advanced solid tumors.
Significance of the Study
The initiation of the Phase I clinical trial for SIM0237 marks a significant milestone in the development of this innovative bispecific antibody. It underscores Simcere Pharmaceutical’s commitment to advancing novel therapies for cancer, potentially improving patient outcomes and quality of life.-Fineline Info & Tech
