Zai Lab’s interleukin (IL)-13/IL-31R bispecific antibody performed well in a pilot preclinical study presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 in Glasgow, Scotland.
ZL-1503 showed a favorable preclinical safety profile, prolonged half-life. and durable suppression of both inflammatory and pruritogenic pathways, supporting its advancement to Investigational New Drug (IND)-enabling studies. Zai Lab plans to file an IND for ZL-1503 for moderate-to-severe atopic dermatitis (AD) by the end of 2025.
ZL-1503 was evaluated in a pilot preclinical study in non-human primates to assess its long-term effects on IL-31-mediated scratching and IL-13-induced signaling (pSTAT6).
Key study results include:
- An intravenous single dose of ZL-1503 (10mg/kg, iv) completely inhibited IL-13-mediated IL-13-induced signaling (pSTAT6) and IL-31-induced scratching for at least 76 days in all preclinical subjects.
- Two out of three subjects exhibited prolonged IL-13-mediated pSTAT6 inhibition for over 118 days, and one out of three subjects sustained IL-31-induced scratching inhibition for over 133 days.
- Pharmacokinetic (PK) analysis of serum samples collected during the study revealed that ZL-1503 exhibited slow clearance, correlating closely pharmacodynamic (PD) responses, demonstrating strong PK/PD relationships in blocking IL-13 and IL-31 pathways in the preclinical model.
- ZL-1503 was well tolerated following weekly IV dosing up to 150mg/kg.
- Additionally, in vitro studies showed that binding to one target did not affect ZL-1503’s blocking effects on the other target.
