Stapokibart (CM310) targets IL-4Rα for the treatment of type 2 inflammation

  • iScience. 2024 Aug 13;27(9):110721. doi: 10.1016/j.isci.2024.110721.
Wei Liu  1 ,  Yan Zhao  2 ,  Yanyun He  1 ,  Xinyu Yan  1 ,  Juntao Yu  1 ,  Qin Song  1 ,  Libo Zhang  1 ,  Bohan Dong  3 ,  Gang Xu  1 ,  Changyu Wang  1 ,  Jianzhong Zhang  2 ,  Bo Chen  1
Affiliations
  • 1. Research and Development Department, Keymed Biosciences (Chengdu) Limited, Chengdu 610000, China.
  • 2. Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
  • 3. Tallulah Falls School, Georgia, GA 30573, USA.
PMID: 39262798 DOI: 10.1016/j.isci.2024.110721
Abstract

Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab. Epitope mapping revealed that stapokibart bound to distinct sites on IL-4Rα compared to dupilumab. In vitro assays showed that stapokibart was comparable or numerically superior in blocking IL-4Rα-mediated signaling compared to dupilumab. In vivo studies further demonstrated that stapokibart effectively inhibited the progression of type 2 inflammation. Pharmacokinetic studies revealed a circulating half-life of approximately 298-351 h in cynomolgus monkeys and 55-142 h in rats for stapokibart. Toxicity studies indicated a favorable safety profile in cynomolgus monkeys and rats. The preclinical evaluation of stapokibart supports its clinical development.

Keywords
Drugs; Immunology.
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