Target

AIR645 antagonizes the action of the IL-4 receptor alpha chain (IL-4Ralpha) protein necessary for the biological activities of the T helper cell type 2 (Th2) cytokines IL-4 and IL-13. IL-4 and IL-13 are strongly linked to asthma pathogenesis. IL-4 mediates Th2 cell maturation, leading to the production of a state of allergy and accumulation of inflammatory cells within the airways. IL-13 shares some of the activities of IL-4 and also governs bronchoconstriction of the airways, fibrotic responses of lung tissue to damage resulting from chronic inflammation and plays a key role in the contribution of the airway surface cells to the inflammatory process present in asthma.

Genetic variations in IL-4Ralpha are associated with allergy and asthma, as well as asthma exacerbations, implicating IL-4Ralpha as an important regulator of these conditions. Experimental genetic studies in mice demonstrate that IL-4Ralpha is required for allergen-induced pulmonary inflammation, bronchoconstriction and overproduction of mucus in the airways. Clinical studies show beneficial effects of pharmacologic inhibition of IL-4, IL-13 or both cytokines together in patients with asthma. This approach has demonstrated clinical efficacy in patients with mild or moderate asthma following local aerosol or systemic drug administration. These studies provide clinical validation of the significance of IL-4 and IL-13 in allergy and asthma.