Allakos Announces Publication Highlighting AK006 Mast Cell Inhibition

–  Data provide insights on the signaling pathways involved with AK006 mast cell inhibition –
– AK006 has a distinct mechanism of action that leads to broad inhibitory effects on mast cells –

SAN CARLOS, Calif., Feb. 12, 2024 (GLOBE NEWSWIRE) -- 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 the publication of new scientific results in Allergy.  The preclinical research found that AK006 (agonist Siglec-6 antibody) impacts mast cell function by interacting with multiple activating receptors and key signaling molecules.

The publication titled “Regulation of Mast Cells by Overlapping but Distinct Protein Interactions of Siglec-6 and Siglec-8” details efforts to identify proteins associated with Siglec-6 and Siglec-8 in mast cells and functionally characterize these protein interaction networks using ex vivo and in vivo models of mast cell activation. The data published today add to previously published preclinical data demonstrating that AK006 inhibits multiple modes of mast activation.

As detailed in the Allergy publication, proteomic profiling of mast cells revealed Siglec-6 and Siglec-8 interact with a large cluster of proteins involved in IgE and non-IgE-mediated mast cell activation, including the high affinity IgE receptor (FcεRI), IL-4 and IL-33 receptors, and intracellular kinases LYN and JAK1. Importantly, Siglec-6 was found to interact with multiple critical regulatory proteins that do not interact with Siglec-8, including stem cell factor (SCF) receptor KIT/CD117, different subunits of the FcεRI receptor and proteins modulating metabolic processes. These findings suggest Siglec-6 has a broader role in regulating mast cell function and may contribute to the increased inhibitory effects observed with AK006 in vitro and in vivo. 

The publication is both available on the Allergy website as well as Allakos Scientific Presentations page.

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-type lectins (Siglecs). Siglec-6 is expressed primarily on the surface of mature mast cells. Siglec-6 receptors contain 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 immunology and oncology.