Science

Allakos is a leader in the fields of mast cell and eosinophil biology, and is focused on the central role these immune cells play in the pathogenesis of acute and chronic inflammatory conditions

The company’s lead drug candidate, lirentelimab (AK002), is an investigational therapeutic antibody that targets Siglec-8, an inhibitory receptor found on the surface of mast cells and eosinophils. By targeting Siglec-8, lirentelimab offers the potential to treat a broad range of serious, complex inflammatory diseases, some of which are shown on the graphic below.

Mast Cell and Eosinophil Biology

Mast cells and eosinophils are key drivers of inflammatory disease


 

Tissue mast cells and eosinophils are found at the internal/external interfaces of the body, in particular at mucosal surfaces, 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 are involved in both innate and adaptive immune responses, and participate in both acute and chronic inflammation. Because of the inflammatory mediators they release, and their ability to recruit and activate other immune cells through expression of chemokines and cytokines, mast cells and eosinophils 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 and eosinophils. Siglec-8 is an inhibitory receptor and studies have shown that engagement of the receptor results in inhibition of mast cells and apoptosis of eosinophils. Siglec-8 may provide an important inhibitory mechanism used by the body to regulate mast cell and eosinophil mediated inflammation.

Lirentelimab (AK002)

Lirentelimab is an investigational, non-fucosylated IgG1 monoclonal antibody targeting Siglec-8. By targeting Siglec-8, an inhibitory receptor, lirentelimab blocks multiple inflammatory pathways. In clinical and preclinical studies, binding of lirentelimab to Siglec-8 induces inhibition of mast cells, apoptosis of tissue eosinophils, and depletion of blood eosinophils by antibody dependent cellular cytotoxicity (ADCC). Lirentelimab is being developed in several mast cell and eosinophil driven diseases, and has demonstrated positive clinical activity in eosinophilic gastrointestinal diseases (EGIDs), chronic urticaria, severe allergic conjunctivitis, and indolent systemic mastocytosis (see Clinical).

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