bispecific antibody targeting DKK1 and sclerostin

A bispecific antibody targeting DKK1 and sclerostin is a dual-acting therapeutic platform designed to promote bone formation and inhibit bone resorption for the treatment of metabolic bone disorders, such as osteoporosis and osteogenesis imperfecta (OI). Sclerostin and Dickkopf-1 (DKK1) are two key extracellular antagonists of the canonical Wnt/beta-catenin signaling pathway in osteoblasts. While monotherapies targeting sclerostin (such as romosozumab) successfully stimulate bone accretion, they often trigger a compensatory upregulation of DKK1, which dampens the long-term anabolic response. By simultaneously neutralizing both sclerostin and DKK1, these bispecific antibodies prevent this feedback inhibition, leading to synergistic and sustained increases in bone mineral density, bone mass, and skeletal strength. Clinical-stage candidates within this class include Angitia Biopharmaceuticals' AGA2115 (under development for osteogenesis imperfecta) and AGA2118 (for osteoporosis), as well as Amgen's preclinical candidate AMG 147.

Other names

anti-DKK1/sclerostin bispecific antibodybispecific anti-sclerostin/anti-DKK1 antibodyDKK1/sclerostin bispecific antibodysclerostin/DKK1 bispecific antibody