Overview
Eosinophils and mast cells are immune cells that are involved in acute and chronic inflammation and play an important role in a large number of allergic, inflammatory and proliferative diseases, some of which are shown on the chart below.
Allakos is a leader in the field of mast cell and eosinophil biology, focused on the central role these immune cells play in the pathology of acute and chronic inflammation
The company is developing a therapeutic antibody that targets Siglec-8, an inhibitory receptor found on the surface of mast cells and eosinophils. Antibodies against Siglec-8 offer the potential to treat a broad range of serious diseases.
Eosinophils and Mast Cell Biology
Eosinophils and mast cells are found in tissues at the internal/external interfaces of the body, in particular at mucosal surfaces and surrounding blood vessels and peripheral nerves. They produce a broad range of inflammatory mediators including vasoactive amines, bioactive lipids, proteases, cytokines and chemokines. As a result, they can participate in both acute and chronic inflammation and couple innate and adaptive immune responses. Because of their anatomical location and inflammatory ability, eosinophils and mast cells are key drivers in a number of diseases including gastrointestinal, ophthalmic, dermatologic, respiratory, and proliferative diseases.
Siglec-8
Siglec-8 is a member of the family of cell surface receptors called Sialic acid-binding immunoglobulin-type lectins (Siglecs). Siglec-8 is found selectively on the surface of mast cells, eosinophils, and at a low level on basophils. Siglec-8 is an inhibitory receptor and studies have shown that engagement of the receptor results in apoptosis of eosinophils and inhibition of mast cells. The Siglec-8 receptor may provide an important inhibitory mechanism used by the body to regulate mast cell and eosinophil mediated inflammation.
AK002
AK002 is a non-fucosylated IgG1 monoclonal antibody targeting Siglec-8. In preclinical and clinical studies, binding of AK002 to Siglec-8 induces apoptosis of eosinophils and inhibition of mast cells. AK002 is being developed in several diseases (see Pipeline)