Apitegromab

Myostatin, also known as growth/differentiation factor 8 (GDF8), is a member of the transforming growth factor β superfamily and negatively regulates skeletal muscle growth. It is expressed as an inactive precursor that requires two sequential proteolytic events for activation: a furin-like proprotein convertase cleaves an RXXR motif between the prodomain and the growth factor to yield a latent, noncovalent complex, and subsequent cleavage within the prodomain by a BMP1/tolloid family metalloprotease activates that latent complex. Apitegromab-mstn binds to promyostatin and latent myostatin and inhibits the activation of myostatin, blocking downstream myostatin signaling. By targeting the proforms rather than the mature growth factor, the antibody acts on the activation process itself. The pharmacodynamic consequence of this blockade is an accumulation of circulating latent myostatin.