Allakos Presents Preclinical Data Highlighting Inhibition of MRGPRX2-Mediated Mast Cell Activation with AK006 at AAAAI 2024
27 Feb 2024
ImmunotherapyAACR
– Atopic dermatitis and prurigo nodularis skin lesions show evidence of MRGPRX2 mast cell activation and activated macrophages –
– AK006 inhibited mast cell activation and reduced mast cell numbers in an MRGPRX2-induced skin inflammation model –
Feb. 26, 2024 -- Allakos Inc. (Nasdaq: ALLK), a clinical-stage biotechnology company developing therapeutics that target immunomodulatory receptors present on immune effector cells involved in allergy, inflammatory and proliferative diseases, today announced a poster presentation at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) 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 (ADCP) 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.
About AK006
AK006 is a humanized IgG1 monoclonal antibody which activates the inhibitory receptor Siglec-6. Siglec-6 is a member of the family of cell surface receptors called Sialic acid-binding immunoglobulin-like lectins (Siglecs). Siglec-6 is expressed primarily on the surface of mature mast cells. Siglec-6 contains intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) which, when activated, recruit phosphatases that work to oppose activating signals driven by kinase signaling cascades. Because of this opposition to multiple activation pathways, AK006 has the potential to inhibit multiple modes of mast cell activation and has demonstrated preclinical inhibition of mast cell activation by IgE and through MRGPRX2 and KIT receptors. ITIM bearing receptors have important roles in regulating the immune system and therapeutics targeting ITIM bearing receptors, such as PD-1 and Siglec-10, have demonstrated therapeutic activity in oncology and immunology.
AK006 appears to drive deep mast cell inhibition and, in addition to its inhibitory activity, can reduce mast cell numbers via antibody-dependent cellular phagocytosis in the presence of activated macrophages. AK006 is currently being tested in a Phase 1 study in healthy volunteers and will begin dosing in early 2Q 2024 in patients with chronic spontaneous urticaria. Results from the Phase 1 study are expected throughout 2024.
About Allakos
Allakos is a clinical stage biotechnology company developing therapeutics that target immunomodulatory receptors present on immune effector cells involved in allergy, inflammatory and proliferative diseases. Activating these immunomodulatory receptors allows for the direct targeting of cells involved in disease pathogenesis and, in the setting of allergy and inflammation, has the potential to result in broad inhibition of inflammatory cells. The Company’s most advanced antibody in ongoing clinical development is AK006. AK006 targets Siglec-6, an inhibitory receptor expressed on mast cells. Mast cells are widely distributed in the body and play a central role in the inflammatory response. Inappropriately activated mast cells have been identified as key drivers in a number of severe diseases affecting the gastrointestinal tract, eyes, skin, lungs and other organs. In preclinical studies, AK006 appears to provide deep mast cell inhibition and, in addition to its inhibitory activity, reduce mast cell numbers. For more information, please visit the Company’s website at www.allakos.com.
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