The myostatin/activin type II receptor (ActRII) pathway has been identified to 
be critical in regulating skeletal muscle size. Several other ligands, including 
GDF11 and the activins, signal through this pathway, suggesting that the ActRII 
receptors are major regulatory nodes in the regulation of muscle mass. We have 
developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent 
binding of ligands to the receptors and thus inhibit downstream signaling. 
BYM338 enhances differentiation of primary human skeletal myoblasts and 
counteracts the inhibition of differentiation induced by myostatin or activin A. 
BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of 
Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. 
BYM338 dramatically increases skeletal muscle mass in mice, beyond sole 
inhibition of myostatin, detected by comparing the antibody with a myostatin 
inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy 
in myostatin mutant mice, further confirming a beneficial effect on muscle 
growth beyond myostatin inhibition alone through blockade of ActRII ligands. 
BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via 
prevention of muscle and tetanic force losses. These data highlight the 
compelling therapeutic potential of BYM338 for the treatment of skeletal muscle 
atrophy and weakness in multiple settings.