ZL-1503: A Bispecific Antibody Targeting IL-13 and IL-31Rα Sustains Suppression of Pruritus and Atopic Disease in Non-Human Primates 2305220

Abstract

Abstract Introduction IL-13 and IL-31 are key mediators in atopic diseases. IL-13 promotes type 2 inflammation and tissue changes, while IL-31 drives pruritus and amplifies local immune responses. Their combined effects worsen disease, highlighting the need for dual-targeted treatments. ZL-1503 is a bispecific antibody with extended half-life that blocks both IL-13 and IL-31Rα signaling. Methods In the pruritus model, cynomolgus monkeys (n = 16) received a single IV dose of ZL-1503 (0, 0.3, 3, or 10 mg/kg; n = 4/group). IL-31-mediated scratching and IL-13-induced pSTAT6 were monitored for 112 days. Serum samples were collected for PK analysis. In the atopic disease (asthma/allergic rhinitis) model, cynomolgus monkeys (n = 9; 3/group) were divided into: naive, disease (Ascaris suum challenge), and treatment groups (ZL-1503 10 mg/kg IV + antigen). Results In the pruritus model, a dose dependent effect of ZL-1503 was observed in both the magnitude and duration of the response, including inhibition of IL-31-mediated scratching and IL-13-mediated pSTAT6, during a 112-day observation period following ZL-1503 treatment. PK analysis demonstrated a strong PK/PD correlation. In the atopic disease model, ZL-1503 significantly improved airway resistance (RAW, p < 0.001) and dynamic compliance (Cdyn, p < 0.01), and reduced nasal rubbing (p < 0.001) and sneezing frequency (p < 0.0001) compared with disease-induced, untreated animals. Conclusion ZL-1503 strongly inhibited IL-13/IL-31 pathways in primates and showed significant effects across atopic conditions in NHP models. These findings support its development for human trials targeting moderate-to-severe atopic dermatitis and other IL-13/IL-31 driven diseases. Funding Source n/a Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)