IMSB301 cGAS Inhibitors
Autoimmune disease arises when the body’s natural defense system cannot distinguish between its own cells and foreign cells, resulting in the body mistakenly attacking normal cells. Preventing aberrant activation of the cGAS-STING pathway is crucial for maintaining immune homeostasis. If the cGAS-STING pathway is chronically activated by lack of regulation, it causes activation of the immune system and inflammation, resulting in autoimmune diseases.
Several enzymes (RNase H2, TREX1, and DNase II) regulate cGAS activation by controlling the basal level of cytosolic DNA. Mice deficient in these functional enzymes have been shown to develop profound autoimmune disease with inflammation and lethality in a cGAS- and STING-dependent manner, underscoring a critical role for the cGAS-STING pathway in the pathogenesis of autoimmune diseases.
Based on in vitro and in vivo potency, DMPK and safety-toxicity studies, we selected a potential best-in-class novel orally available cGAS inhibitor small molecule, IMSB301. We are evaluating IMSB301 in a Phase 1 randomized placebo-controlled, double-blinded clinical trial in healthy volunteer subjects. We plan to evaluate IMSB301 and other novel small molecule cGAS inhibitors for potential applications in a broad range of inflammatory and autoimmune diseases, including CNS diseases with profound unmet medical need.