Lirentelimab (AK002) is a humanized anti-sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) antibody that induces apoptosis of IL-5-activated eosinophils and inhibits IL-5-mediated mast cell activation, and is used in the study of refractory inert systemic mastocytosis and allergic conjunctivitis.

SIGLEC8:464 pM (affinity)

The antigen-binding fragment of Lirentelimab binds with an affinity of 464 pM to the extracellular structural domain of recombinant SIGLEC8. Lirentelimab exhibits a high affinity for in vitro-expressed SIGLEC8 as well as SIGLEC8 expressed on eosinophils and via the Fc region on NK cells. At a concentration of 1 µg/mL, Lirentelimab selectively binds to eosinophils in human peripheral blood as well as eosinophils and mast cells in human lung tissue. In addition, Lirentelimab induced apoptosis in IL-5-activated eosinophils when acted at concentrations ranging from 0.0001 to 100 μg/mL for 30 minutes. In peripheral blood leukocyte samples from healthy donors, Lirentelimab had a half-maximal effect concentration of 1.9 ng/mL on eosinophils and elicited an antibody-dependent cytotoxic response.Lirentelimab also reduced the number of eosinophils in isolated human tissues. [1]

Lirentelimab significantly inhibited IgE-mediated mast cell activation after a single intravenous injection at a dose of 100 μg in a mouse model of systemic allergic reaction. [1]