Cardiometabolic Disorders

SRK-439 for obesity

Results from the EMBRAZE trial will inform the development of SRK-439, a novel investigational, preclinical muscle-targeted therapy designed to support healthier weight management and lean muscle preservation during and after treatment with obesity therapies such as those that target GLP-1 and GIP. Muscle plays a key role in cardiometabolic disorders and healthy weight management. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean muscle mass during weight loss. Preclinical data also demonstrates greater potency of SRK-439 compared to an anti-ACTRII antibody, which could translate to a lower target dose of SRK-439 that is administered subcutaneously and potentially best-in-class profile.

While recently approved therapies for obesity are experiencing rapid uptake, up to 40% of the total body weight loss caused by therapies that target GLP-1 and GIP may be attributed to loss of lean mass.^{3, 4} Therapies that can maintain muscle mass, while enhancing body fat loss, could potentially offset the muscle loss often associated with obesity treatment and help improve cardiometabolic health. Strong clinical and preclinical evidence in SMA indicates that our approach has the potential to maintain muscle mass, while minimizing adverse effects.

SRK-439 is an investigational myostatin inhibitor that binds to pro- and latent myostatin with high affinity and is selective for myostatin. Myostatin is a protein growth factor expressed primarily in skeletal muscle, which functions to restrict muscle mass and growth. When myostatin is activated, it works with other growth factors and hormones to inhibit muscle growth. Our approach selectively targets the latent, or inactive, forms of myostatin to block its activation and subsequent signaling in the muscle.