ICE Bioscience Posters

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STING agonism has emerged as a promising therapeutic approach for cancer treatment via activation of the host antitumor immune response. Herein, we present a potent STING agonist BSP16 developed based on our STING agonist screening platform. It was demonstrated that BSP16 could effectively bind to STING protein and induce the active conformational transition of STING. In IRF reporter assay, BSP16 strongly activated STING signaling in both human and mouse cells with EC50 = 9.2 μM and 5.7 μM, respectively. The capability of BSP16 to activate STING pathway in vitro was also validated by its regulation of downstream gene transcription and protein expression. In addition, BSP16 had a favorable druggability, including good water solubility, good membrane permeability, good stability, no hERG toxicity, and no CYP3A4 inhibitory activity. In terms of the PK profiles, the exposure of BSP16 in vivo was excellent when administered intravenously and orally and the oral bioavailability of BSP16 was extremely high (F = 107%). Most importantly, BSP16 was proven to be effective in multiple syngeneic models, and in some cases, BSP16 could induce complete tumor regression and durable antitumor immune memory. Moreover, the synergistic antitumor effect of BSP16 combined with anti-PD-L1 therapy in the humanized mouse model of HCC827 lung cancer proved the potential benefits of BSP16 in combination with immune checkpoint inhibitors.

In summary, BSP16 is a promising STING agonist with outstanding in vitro and in vivo activities and favourable druggability, which makes it valuable for further development as a novel anticancer agent.