Allakos Inc. 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 andSiglec-8 in mast cells and effectively characterize these protein interaction networks using ex vivo and in vivo models of mast cell activation.

The data published 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 (FceRI), IL-4 and IL-33 receptors, and intracellular kinases LYN and JAK1. 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. 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 (ADCP) 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 Second Quarter 2024 in patients with chronic spontaneous urticaria.

Results from the Phase 1 study are expected throughout 2024.