RXC008

RXC008 is a first-in-class, orally administered, gastrointestinal (GI)-restricted pan-ROCK (Rho Associated Coiled-Coil Containing Protein Kinase) inhibitor developed for the treatment of fibrostenotic Crohn’s disease. It is a highly potent and selective small molecule designed to act locally at sites of fibrosis in the GI tract, minimizing systemic exposure and thus avoiding cardiovascular side effects associated with systemic ROCK inhibition. RXC008 inhibits both ROCK1 and ROCK2 isoforms with nanomolar potency, suppressing pro-fibrotic pathways such as TGFβ-stimulated alpha smooth muscle actin expression in human intestinal fibroblasts. Preclinical studies have demonstrated strong anti-fibrotic effects in multiple animal models of inflammatory bowel disease. The drug degrades rapidly if absorbed into the bloodstream via enzyme-mediated metabolism by paraoxonase enzymes, ensuring its action remains localized to the GI tract. Phase 1 clinical trials in healthy volunteers have been completed; Phase 2 trials are planned for initiation in 2025[1][2][4][5][6].