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.

牛皮癣是高度流行的炎症性皮肤病。斑块状牛皮癣是最常见的牛皮癣类型，白介素（IL）-23 / IL-17轴在疾病进展中起关键作用。在本文中，我们描述了IBI112，一种正在开发的高效抗IL-23单克隆抗体，可有效中和IL-23的亚基IL23p19，以消除IL-23与其受体的结合并阻断下游信号转导和激活剂转录3（STAT3）磷酸化。具体而言，IBI112阻断了IL-23诱导的脾细胞下游IL-17的产生。此外，在连续hIL-23注射攻击的牛皮癣样表皮增生小鼠模型中，IBI112给药可降低皮肤厚度。IBI112在咪喹莫特（IMQ）诱导的牛皮癣模型中，在控制疾病进展中显示出与抗IL-1R抗体的协同作用。而且，在人-FcRn敲入小鼠和食蟹猴中，与野生型IgG1版本相比，IBI112的Fc片段中存在突变，观察到延长的半衰期。食蟹猴高剂量给药后，IBI112的耐受性良好。总之，我们开发了延长半衰期的抗IL-23p19单克隆抗体IBI112，可在两种牛皮癣小鼠模型中有效中和IL-23，阻断IL-23诱导的IL-17产生并减轻疾病症状。 。食蟹猴高剂量给药后，IBI112的耐受性良好。总之，我们开发了延长半衰期的抗IL-23p19单克隆抗体IBI112，可在两种牛皮癣小鼠模型中有效中和IL-23，阻断IL-23诱导的IL-17产生并减轻疾病症状。 。食蟹猴高剂量给药后，IBI112的耐受性良好。总之，我们开发了延长半衰期的抗IL-23p19单克隆抗体IBI112，可在两种牛皮癣小鼠模型中有效中和IL-23，阻断IL-23诱导的IL-17产生并减轻疾病症状。 。