BMS-986089 is a high affinity anti-myostatin adnectin that increases muscle volume in three preclinical species

Myostatin is a negative regulator of skeletal muscle. Genetic ablation or pharmacologic inhibition of myostatin results in increased skeletal muscle size in several species including human. Reducing myostatin is a potential therapeutic approach for skeletal muscle diseases such as Duchenne's muscular dystrophy (DMD). BMS-986089 is an anti-myostatin adnectin (engineered scaffold based on the 10th fibronectin type III domain) that exhibits high affinity for myostatin (Kd = 0.17–0.45 nM) and inhibits myostatin and GDF-11 second messenger signaling in cells (IC50s = 0.06–1 nM and 0.09–0.7 nM, respectively). In male SCID mice (to avoid immunogenic responses), four weekly sub-cutaneous (SC) doses (0.1–100 mpk) of BMS-986089 produced dose- and time-dependent increases in lower limb muscle volume (MRI) of up to approximately 30%. In male rats, a single SC administration of BMS-98089 (0.3−25 mpk) produced time- and dose-dependent increases in lower limb muscle volume that reached a maximum of up to 16%, 15 days post-dose. In male cynomolgus monkeys, four weekly SC doses (0.3–25 mpk) of BMS-986089 produced dose- and time-dependent increases in lower limb muscle volume of up to approximately 5%. In each study serum free myostatin was suppressed in a dose and time dependent manner. These data support further development of BMS-986089 in diseases such as DMD.