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 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.
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 |
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 |
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 |
European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting |
| July 2022 | Preclinical |
European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting |
| July 2022 | Preclinical |
European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting |
| July 2022 | Preclinical |
European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting |