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).

Scientific Presentations

Publications & Presentations

Date Focus Title of Publication
March 2021 Preclinical

Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody 

Front. Immunol.

January 2021 Clinical

Diagnostic Delay in Patients with Eosinophilic Gastritis and/or Duodenitis: A Population-Based Study

The Journal of Allergy and Clinical Immunology: In Practice

November 2020 Preclinical

Discovery, Function, and Therapeutic Targeting of Siglec-8

Cells

October 2020 Clinical

Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis

New England Journal of Medicine

June 2020 Preclinical

An anti‐siglec‐8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells

Clinical & Experimental Allergy

August 2020 Preclinical

A monoclonal antibody to Siglec-8 suppresses non-allergic airway inflammation and inhibits IgE-independent mast cell activation

Mucosal Immunology

June 2020 Preclinical

An anti‐siglec‐8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells

Clinical & Experimental Allergy

June 2020 Clinical

Treatment of Severe Allergic Conjunctivitis with AK002 Indicated Improvement of Ocular Signs and Symptoms and Reduction of Severity of Comorbid Atopic Diseases in a Phase 1b Open-Label Study

European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting

June 2020 Preclinical

A Siglec-8 Antibody Reduces Substance P-induced Inflammation by Inhibiting MRGPR-mediated Mast Cell Activation

European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting

See More Presentations