D1.444 - Dual Blockade of IL22 and IL23 with a bispecific antibody: A Promising Strategy for the Treatment of Psoriasis and Other Autoimmune Skin Disorders

Psoriasis and other chronic autoimmune skin diseases affect a large patient population, leading to substantial impairment in quality of life and imposing a significant socioeconomic burden. Although biologics targeting IL17 or IL23 have demonstrated robust efficacy in subsets of patients, unmet medical needs remain. Our study demonstrates that simultaneous inhibition of IL23 and the IL22 pathway produces a synergistic therapeutic effect in preclinical psoriasis models. Based on this rationale, we developed a bispecific antibody (bsAb) targeting both IL23 and IL22, aiming to establish a next-generation therapeutic approach for psoriasis and related autoimmune skin disorders.

Binding affinity and functional activity were assessed using in vitro affinity measurements and reporter assays. In vivo stability was evaluated in SD rats. Therapeutic efficacy was investigated in multiple mouse models of psoriasis. 

In an IL23–induced mouse skin inflammation model, blockade of either IL23 or IL22 significantly ameliorated inflammatory responses. In the imiquimod (IMQ)-induced psoriasis model, monotherapy with IL23- or IL22-targeting monoclonal antibodies (mAbs) effectively reduced disease severity, while combination treatment resulted in superior efficacy, demonstrating a clear synergistic effect. We subsequently engineered a bsAb capable of simultaneously binding and neutralizing both IL23 and IL22. This bsAb exhibited sub-nanomolar affinity to both targets and retained potent functional activity in vitro. Importantly, the bsAb showed robust therapeutic efficacy in psoriasis mouse models and favorable in vivo stability in SD rats.

These findings demonstrate that dual blockade of IL23 and IL22 using a bispecific antibody represents a compelling therapeutic strategy for psoriasis and other inflammatory skin diseases. The strong preclinical efficacy and favorable pharmacological properties support further clinical development of the IL23/IL22 bsAb as a promising next-generation biologic for patients with autoimmune skin disorders.