Allakos presents preclinical data on AK006 at AAAAI meeting

Allakos announced a poster presentation at the 2024 American Academy of Allergy, Asthma & Immunology Annual Meeting. The poster highlights preclinical data detailing AK006’s mechanism of action and ability to reduce MRGPRX2-induced skin inflammation. Inappropriate mast cell activation, via IgE-dependent and IgE-independent pathways, has been implicated in the pathogenesis of multiple inflammatory skin diseases. IgE-dependent mast cell activation has been identified as a pathogenic driver of chronic spontaneous urticaria and food allergy and agents which target this pathway have demonstrated therapeutic activity. More recently, mast cell activation through MRGPRX2, an IgE independent mast cell activation pathway, has been implicated in the pathogenesis of chronic spontaneous urticaria, atopic dermatitis and prurigo nodularis. AAAAI Presentation Details: The poster, titled: “MRGPRX2-Mediated Mast Cell Activation is a Shared Pathogenic Mechanism in Atopic Dermatitis and Prurigo Nodularis Patients that can be Inhibited by Siglec-6” was presented on Friday, February 23rd, key findings include: IgE-independent mast cell activation, via MRGPRX2, has been implicated in atopic dermatitis and prurigo nodularis disease pathogenesis Atopic dermatitis and prurigo nodularis skin lesions contain mast cells displaying signs of MRGPRX2 activation, as well as elevated and activated macrophages AK006 has a dual mechanism of action that inhibits mast cells and reduces mast cells via antibody dependent cellular phagocytosis in the presence of activated macrophages; In an MRGPRX2-induced skin inflammation model, AK006 reduced skin inflammation and reduced mast cells numbers via ADCP; By broadly inhibiting and reducing mast cells, AK006 has the potential to treat inflammatory skin diseases, such as atopic dermatitis, prurigo nodularis, and chronic spontaneous urticaria. The data presented Friday add to previous published preclinical data demonstrating that AK006 inhibits both IgE-dependent and IgE-independent mast cell activation and can reduce mast cell numbers at sites of inflammation where activated macrophages are found.