Spesolimab (Anti-IL36R Antibody)

Spesolimab, also known as BI 655130, is a mouse-derived humanized IgG1k antibody against IL-36R (interleukin 36 receptor). IL-36 plays an important role in the immune system and Spesolimab is being investigated in palmoplantar pustulosis (PPP). Spesolimab was associated with a reduction in biomarkers associated with the innate, Th1/Th17 and neutrophil pathways. Interleukin-36 (IL-36) is not a single cytokine but a group of proinflammatory cytokines that belong to the IL-1 family and are expressed in epithelial barriers such as the skin, gut, and lungs. The IL-36 group consists of three ligand isoforms: IL-36alpha, IL-36beta and IL-36gamma, which are activated when the pro-protein forms are cleaved by neutrophil derived proteases. Signaling is initiated when IL-36 binds to the Interleukin 36 receptor (IL-36R), also known as IL-1RL2, and its co receptor IL-1 receptor accessory protein (IL-1RAP). This triggers a pro-inflammatory response predominantly through the NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. Dysregulated IL-36 signaling has been implicated in a variety of inflammatory diseases, most notably psoriasis where IL-36 is abundantly expressed in keratinocytes (KCs) on the skin. The field of IL-36-targeted therapies is rapidly evolving, spearheaded by the development of IL-36R antagonists. Spesolimab, FDA-approved for the treatment of generalized pustular psoriasis (GPP), is a humanized monoclonal antibody that blocks IL-36R, effectively inhibiting the activation of downstream inflammatory pathways.