AB-25E9 mAb
Alethia’s most promising target in this indication, Siglec-15, is a cell-surface protein whose expression is stimulated very early in osteoclast differentiation in response to RANK ligand. Attenuation of Siglec-15 by RNA interference causes a swift inhibition of differentiation, a significant reduction in the expression of bone degradative enzymes, and an abrogation of bone resorption in vitro. The cell-surface localization of Siglec-15 and its role in osteoclast activity implied that this protein could be an excellent candidate for a therapeutic mAb. As a proof of concept, differentiating human osteoclasts were treated with a high affinity mAb specific for Siglec-15 resulting in efficient inhibition of differentiation .
Blocking Siglec-15 with an antibody inhibits osteoclast differentiation
Currently, AB-25E9 mAb against Siglec-15 is being evaluated in-vivo in mouse models of severe bone loss. AB-25E9 mAb will represent a rare osteoclast-targeted immunotherapeutic in the field of cancer-induced bone loss.
