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

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

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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