1. Academic Validation
  2. IBI112, a selective anti-IL23p19 monoclonal antibody, displays high efficacy in IL-23-induced psoriasiform dermatitis

IBI112, a selective anti-IL23p19 monoclonal antibody, displays high efficacy in IL-23-induced psoriasiform dermatitis

  • Int Immunopharmacol. 2020 Dec;89(Pt B):107008. doi: 10.1016/j.intimp.2020.107008.
Li Li 1 Zhihai Wu 1 Min Wu 1 Xuan Qiu 1 Yue Wu 1 Zhihui Kuang 1 Li Wang 1 Ta Sun 1 Yang Liu 1 Shuai Yi 1 Hua Jing 1 Shuaixiang Zhou 1 Bingliang Chen 1 Dongdong Wu 1 Weiwei Wu 2 Junjian Liu 3
Affiliations

Affiliations

  • 1 Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou 215123, Jiangsu, China.
  • 2 Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou 215123, Jiangsu, China. Electronic address: weiwei.wu@innoventbio.com.
  • 3 Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou 215123, Jiangsu, China. Electronic address: junjian.liu@innoventbio.com.
Abstract

Psoriasis is a highly prevalent inflammatory skin disease. Plaque psoriasis is the most common type of psoriasis, and the interleukin (IL)-23/IL-17 axis plays a key role in disease progression. In this article, we describe IBI112, a highly potent anti-IL-23 monoclonal antibody under clinical development, which efficiently neutralizes IL23p19, a subunit of IL-23, to abrogate IL-23 binding to its receptor and block downstream signal transducer and activator of transcription 3 (STAT3) phosphorylation. Specifically, IBI112 blocked IL-23 induced downstream IL-17 production from splenocytes. In addition, IBI112 administration reduced skin thickness in a psoriasis-like epidermal hyperplasia mouse model challenged by continuous hIL-23 injection. IBI112 showed synergism with an anti-IL-1R antibody in controlling disease progression in an imiquimod (IMQ) -induced psoriasis model. Moreover, with mutations in Fc fragment of IBI112, extended half-life was observed when compared to the wild-type IgG1 version in both human-FcRn-knock-in mice and cynomolgus monkeys. IBI112 was well tolerated after high dose administration in cynomolgus monkeys. In summary, we have developed an extended half-life, anti-IL-23p19 monoclonal antibody, IBI112, which efficiently neutralized IL-23, blocked IL-23-induced IL-17 production, and alleviated disease symptoms in two mouse models of psoriasis.

Keywords

Half-life extension; IBI112; IL-17; IL23p19; Psoriasis.

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