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
June 2022 Disease State

The Economic Burden of Eosinophilic Gastritis and Eosinophilic Enteritis in the United States

Advances in Therapy

May 2022 Clinical

Determination of Optimal Eosinophil Thresholds for Diagnosis of Eosinophilic Gastritis and Duodenitis: A Pooled Analysis of 4 Prospective Adult Studies

Digestive Disease Week (DDW)

April 2022 Clinical

Lirentelimab for Severe and Chronic Forms of Allergic Conjunctivitis

Journal of Allergy and Clinical Immunology (JACI)

February 2022 Preclinical

Mast Cells are Locally Activated and Respond to MRGPRX2 Stimulation in Atopic Dermatitis Ex Vivo Skin Biopsies

American Academy of Allergy Asthma & Immunology (AAAAI) Annual Meeting

January 2022 Preclinical

The Inhibitory Receptor Siglec-8 Interacts with FcεRI and Globally Inhibits Intracellular Signaling in Primary Mast Cells Upon Activation

Frontiers in Immunology

January 2022 Clinical

An Open-Label, Proof-of-Concept Study of Lirentelimab for Antihistamine-Resistant Chronic Spontaneous and Inducible Urticaria

Journal of Allergy and Clinical Immunology (JACI)

November 2021 Preclinical

Mast Cell Activation is Associated With Post-Acute COVID-19 Syndrome

Allergy

October 2021 Disease State

Peripheral Eosinophils, Total IgE, and Atopy in Newly Identified Patients with Gastroduodenal Eosinophilia

American College of Allergy, Asthma, & Immunology (ACAAI)

October 2021 Disease State

High Discovery Rate of Eosinophilic Gastritis and/or Duodenitis Among Patients with Chronic Unexplained Gastrointestinal Symptoms

American College of Gastroenterology (ACG)

October 2021 Clinical

Patients With Eosinophilic Esophagitis and Gastrointestinal Symptoms May Have Eosinophilic Gastritis and/or Duodenitis, Not Associated With Peak Esophageal Eosinophil Count

American College of Gastroenterology (ACG)

October 2021 Clinical

Safety and Efficacy of Long-Term Treatment With Lirentelimab, a Monoclonal Antibody Against Siglec-8, in Patients With Eosinophilic Gastritis and/or Duodenitis

American College of Gastroenterology (ACG)

October 2021 Clinical

Similar Efficacy of Lirentelimab in Patients With New vs Established Diagnoses of Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial

American College of Gastroenterology (ACG)

October 2021 Clinical

Systematic Collection of Biopsies and Quantification of Eosinophils in Multiple High-Power Fields is Required for Diagnosis of Eosinophilic Gastritis and/or Duodenitis

American College of Gastroenterology (ACG)

October 2021 Clinical

General Pathologists Did Not Routinely Evaluate Gastric or Duodenal Eosinophilia

American College of Gastroenterology (ACG)

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