Scholar Rock, a late-stage biopharmaceutical company, has released promising preclinical data for SRK-439, an investigational anti-myostatin antibody. The data suggest SRK-439 can increase lean mass and decrease fat mass gain when combined with metformin. These findings were presented at the ObesityWeek conference in San Antonio, Texas.
The preclinical study utilized a diet-induced obesity mouse model. Mice received a high-fat diet, followed by either metformin or a control. Subsequently, they received either SRK-439 or a control antibody. This process was repeated in both young and mature mice to assess age-related effects. Quantitative nuclear magnetic resonance (qNMR) measured lean mass changes throughout the study.
Results showed a substantial increase in lean mass in the group receiving both SRK-439 and metformin compared to the metformin-only group. This positive effect was observed across both age groups. Furthermore, in younger mice, the combination of SRK-439 and metformin resulted in a greater reduction in fat mass gain compared to either treatment alone. These results highlight SRK-439’s potential to improve body composition and support healthier weight management, particularly for individuals with obesity and type 2 diabetes.
Scholar Rock’s anti-myostatin portfolio includes both SRK-439 and apitegromab. Apitegromab is currently being evaluated in the Phase 2 EMBRAZE trial for adults with a BMI over 27 (overweight) or over 30 (obese) who are also taking a GLP-1 receptor agonist (tirzepatide or semaglutide). The trial aims to enroll 100 non-diabetic participants aged 18-65. Subjects will receive either apitegromab or a placebo alongside a GLP-1 receptor agonist for 24 weeks. The primary endpoint is the change in lean mass, measured by dual-energy X-ray absorptiometry. Secondary endpoints include additional weight loss metrics, safety, tolerability, and pharmacokinetic outcomes. Exploratory endpoints involve cardiometabolic parameters, body composition, and physical function assessments at weeks 24 and 32.
SRK-439 is a preclinical, investigational myostatin inhibitor. It exhibits high affinity for pro- and latent myostatin with selectivity for myostatin, meaning it does not bind to GDF11 or Activin-A. It is being developed for cardiometabolic disorders, including obesity. Preclinical data suggest SRK-439 may preserve lean mass during weight loss, contributing to healthier weight management. However, its efficacy and safety in humans have not yet been established, and it has not received FDA approval.
Apitegromab, another Scholar Rock therapy, is a monoclonal antibody that inhibits myostatin activation by binding to its pro- and latent forms in skeletal muscle. It is the first muscle-targeted therapy to demonstrate clinical proof-of-concept in spinal muscular atrophy (SMA). Myostatin’s absence is linked to increased muscle mass and strength. Scholar Rock believes apitegromab’s selective targeting of myostatin may improve motor function in SMA patients. It has received Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA, and Priority Medicines (PRIME) and Orphan Medicinal Product designations from the EMA. However, it has not yet been approved for any use.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
