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.

Lirentelimab (AK002) is an investigational therapeutics antibody that targets Siglec-8, an inhibitory receptor found on the surface of mast cells and eosinophils.  AK006 is an investigational antibody that target’s Siglec-6, an inhibitory receptor expressed selectively on mast cells.  Mast cells and eosinophils, two types of white blood cells that are widely distributed in the body and play a central role in the inflammatory response. Inappropriately activated mast cells and eosinophils have been identified as key drivers in a number of severe diseases affecting the gastrointestinal tract, eyes, skin, lungs and other organs.

Mast Cells and Eosinophils

Effector cells central to initiating and maintaining inflammatory responses 

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.

Siglec-6

Siglec-6 is a member of the family of cell surface receptors called Sialic acid-binding immunoglobulin-type lectins (Siglecs). Siglec-6 is found selectively on the surface of mast cells.  Siglec-6 is an inhibitory receptor and studies have shown that engagement of the receptor results in both deep inhibition of mast cells as well as reduction in mast cell numbers. Siglec-6 may provide an important inhibitory mechanism used by the body to regulate mast cell mediated inflammation.

Lirentelimab (AK002)

Lirentelimab is an investigational, 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.

AK006

AK006 is an investigational, monoclonal antibody targeting Siglec-6.  By targeting Siglec-6, an inhibitory receptor AK006 blocks multiple inflammatory pathways.  In preclinical studies, binding of AK006 to Siglec-6 reduces mast cell numbers and inhibits mast cell activity, including the ability to inhibit c-KIT activation.  We plan to begin human studies with AK006 in the first half of 2023.

Scientific Presentations

Publications & Presentations

Date Focus Title of Publication
November 2022 Preclinical

Discovery of an Agnostic Siglec-6 Antibody That Inhibits and Reduces Human Mast Cells

Communications Biology

November 2022 Preclinical

Antibody Blockade of the Immunoinhibitory Receptor Siglec-10 Polarizes Tumor-associated Myeloid Cells and Promotes Anti-tumor Immunity

Society for Immunotherapy of Cancer (SITC)

October 2022 Clinical

Results from KRYPTOS, a Phase 2/3 Study of Lirentelimab (AK002) in Adults and Adolescents with EoE

American College of Gastroenterology (ACG)

October 2022 Clinical

Lirentelimab (AK002) Safety and Efficacy in Patients with Higher Eosinophil Thresholds: Supplementary Analysis of Phase 2/3 EoE KRYPTOS Trial

American College of Gastroenterology (ACG)

July 2022 Preclinical

Siglec-6 Interacts with KIT/CD117, Recruits Shp Phosphatases and Inhibits SCF-Mediated Inflammation

Mast Cell and Basophil Research Network (EMBRN) Annual Meeting

July 2022 Clinical

Lirentelimab Reduces Levels of Inflammatory Cytokines in Tear Fluid From Patients With Allergic Conjunctivitis

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

July 2022 Preclinical

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

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

July 2022 Preclinical

MRGPRX2 Mediates Mast Cell Activation and Neurogenic Inflammation in Lesional Biopsies From Patients With Atopic Dermatitis

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

July 2022 Preclinical

An Agonistic Monoclonal Antibody Against Siglec-6 Selectively Inhibits and Reduces Human Tissue Mast Cells

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

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