ZL-1503: A bispecific antibody targeting inflammatory and pruritogenic pathways with a prolonged serum half-life and sustained activity in non-human primates
Recommended Citation
Zhang L, Yan S, Dai X, Wan B, Ye Q, Peng W, Ge Y, Li W, Fang X, Li S, Wen Z, Tan X, Du H, Qi B, Wang L, Huang P, Stein Gold LF, Charuworn P, Liu L. ZL-1503: A bispecific antibody targeting inflammatory and pruritogenic pathways with a prolonged serum half-life and sustained activity in non-human primates. Alcohol Clin Exp Res 2025; 49.
Document Type
Conference Proceeding
Publication Date
12-25-2025
Publication Title
Alcohol Clin Exp Res
Abstract
Background: The “itch-scratch-inflammation” cycle drives atopic dermatitis (AD) development and persistence. Targeting IL-13 and IL-31 signaling disrupts this cycle and has been clinically validated. ZL-1503, a bispecific antibody with an extended serum half-life, effectively inhibits IL-13 and IL-31 signaling in vitro and in vivo in rodent studies. Method: ZL-1503 was evaluated in a pilot study with three non-human primates (NHP) to assess its long-term effects on IL-31-mediated scratching and IL-13-induced pSTAT6. Baseline scratching was established with IL-31 injection prior to ZL-1503 dosing. Results: An intravenous single dose of ZL-1503 completely inhibited IL-13-mediated pSTAT6 and IL-31-induced scratching for at least 76 days in all three animals. Two out of the three animals exhibited prolonged IL-13-mediated pSTAT6 inhibition for over 118 days, and one out of the 3 animals sustained IL-31-induced scratching inhibition for over 115 days. Pharmacokinetic (PK) analysis of serum samples collected during the study revealed that ZL-1503 exhibited slow clearance, ranging from 1.42 to 2.52 mL/day/kg. ZL-1503 serum exposures correlated very closely with the PD responses. Additionally, in vitro studies showed that binding to one target did not affect ZL-1503's blocking effects on the other target. These findings demonstrate strong PK/PD relationships of ZL-1503 in blocking IL-13 and IL-31 in the NHP model. Conclusion: ZL-1503 exhibited sustained inhibition of inflammatory and pruritogenic pathways in NHP, supporting its progression to IND-enabling studies as a potential treatment for moderate-to-severe AD, and other IL-13 and IL-31-driven diseases.
Volume
49
