IL-4Rα and IL-31

Class

tetravalent ("2+2") bispecific antibody targeting IL-4Rα and IL-31, Fc half-life extended

Pathway

addresses both the Th2 inflammatory pathway (via IL-4Rα) and the itch-scratch cycle (via IL-31)

IL-4Rα is a receptor subunit shared by two type 2 cytokines, IL-4 and IL-13, which are central drivers of Th2-type inflammation, a pattern of immune signaling associated with allergic and atopic diseases. Blocking IL-4Rα prevents both cytokines from activating their downstream signaling, dampening the inflammatory cascade responsible for skin barrier disruption, mucus overproduction, and eosinophilic inflammation seen in conditions such as atopic dermatitis and asthma. IL-31 is a separate cytokine, produced largely by Th2 cells, that acts directly on sensory nerve endings in the skin and is considered a principal molecular trigger of itch in atopic and other pruritic skin diseases. Because chronic itch leads to scratching that further damages the skin barrier and reinforces inflammation, itch is not merely a symptom but part of the disease process itself. Combining neutralization of IL-4Rα and IL-31 in a single tetravalent bispecific antibody allows one molecule to address both the inflammatory and pruritic axes of the same disease, rather than requiring two separate injectable agents. This dual-pathway targeting is particularly relevant in chronic inflammatory skin diseases, where inflammation and the itch-scratch cycle sustain one another.