LAUSR

ABSTRACT Interleukin (IL)‐12 and IL‐23 share a common subunit (p40) and function in T‐helper (Th) 1 and Th17 immunity, respectively. Anti‐IL‐12/23p40 and specific anti‐IL‐23 antibodies are currently in clinical use for psoriasis and undergoing trials for autoimmune diseases. Since expression levels of the IL‐23 receptor are likely to be much lower than those of IL‐23, an anti‐IL‐23 receptor antibody might offer greater promise in inhibiting the IL‐23‐IL‐17 pathways involved in inflammatory disorders. To our knowledge, no anti‐IL‐23 receptor antibody has been trialed in clinical studies to date. This study describes the generation and characterization of AS2762900–00, a fully human monoclonal antibody against the IL‐23 receptor. AS2762900–00 bound both human and cynomolgus monkey IL‐23 receptors. AS2762900–00 showed potent inhibitory effects on IL‐23‐induced Kit‐225 cell proliferation compared to the existing anti‐IL‐12/23p40 antibody, ustekinumab. In a single dose administration pharmacodynamics study in cynomolgus monkeys, 1mg/kg of AS2762900–00 significantly inhibited (> 85%) IL‐23‐induced STAT3 phosphorylation in blood for up to 84 days. Therefore, AS2762900–00 represents a potent novel IL‐23‐IL‐17 pathway inhibitor with the potential to be developed into a new therapy for the treatment of autoimmune diseases.