Scholar Rock Begins Phase 2 EMBRAZE Trial and Reveals New Data on SRK-439 in Obesity

Scholar Rock, a late-stage biopharmaceutical company, has announced the initiation of the Phase 2 EMBRAZE proof-of-concept trial. This trial is designed to evaluate the safety and efficacy of apitegromab, a selective myostatin inhibitor, in preserving lean muscle mass in individuals with obesity who are already undergoing treatment with a GLP-1 receptor agonist (GLP-1 RA). The findings from this trial will be instrumental in the development of SRK-439, another investigational selective myostatin inhibitor optimized for cardiometabolic disorders, including obesity.

Additionally, Scholar Rock has unveiled new preclinical data comparing SRK-439 with an anti-activin receptor II (anti-ActRII) antibody. The study shows SRK-439's superior capacity to preserve lean mass in patients on GLP-1 RAs, suggesting it may be best in class for this purpose. These findings were presented by Mo Qatanani, Ph.D., Chief Scientific Officer at Scholar Rock, during the company’s Investor Event in New York City.

Jay Backstrom, M.D., MPH, President, and CEO of Scholar Rock, expressed optimism about the early initiation of the EMBRAZE trial and the promising data from the SRK-439 program. He emphasized the importance of selectivity in mitigating potential safety concerns and noted that additional preclinical data would be shared at the American Diabetes Association’s 84th Scientific Sessions.

The preclinical study involved a comparison between an anti-ActRII antibody and a murine equivalent of SRK-439 in a diet-induced obesity (DIO) mouse model. Mice were administered semaglutide with either an IgG control antibody or SRK-439 or the anti-ActRII antibody. The primary method for assessing changes in lean mass was quantitative nuclear magnetic resonance (qNMR) after four weeks of treatment.

Results indicated significant differences in lean mass across all doses of SRK-439, supporting its potential as a therapeutic option for preserving lean mass. SRK-439 showed an ability to counteract lean mass loss driven by GLP-1 RA, even at low doses, with superior outcomes compared to the anti-ActRII antibody across various doses.

The EMBRAZE trial is a randomized, double-blind, placebo-controlled Phase 2 study that will evaluate apitegromab in adults with a BMI over 27 (overweight) or over 30 (obese) who are taking GLP-1 RAs. The trial aims to enroll 100 subjects between 18 and 65 years old who are non-diabetic. Participants will receive either apitegromab or placebo intravenously every four weeks over a 24-week treatment period. The primary endpoint is the change in lean mass from baseline at week 24, assessed by dual-energy X-ray absorptiometry. Secondary endpoints include additional weight loss metrics, safety, tolerability, and pharmacokinetics, with exploratory endpoints covering cardiometabolic parameters and physical function assessed at weeks 24 and 32.

Primary data from the EMBRAZE trial are anticipated in mid-2025 and will guide the further development of SRK-439, with an expected Investigational New Drug (IND) filing in 2025.

SRK-439 is a novel, preclinical myostatin inhibitor with high affinity for pro- and latent myostatin, specifically developed for cardiometabolic disorders. Apitegromab, another investigational monoclonal antibody, targets myostatin activation specifically in skeletal muscle. It has shown clinical proof-of-concept in spinal muscular atrophy (SMA) and has received various designations from the FDA and EMA for its potential in treating SMA.

Scholar Rock is dedicated to discovering and developing transformative therapies for diseases with high unmet needs. The company leverages its expertise in the transforming growth factor beta (TGFβ) superfamily to develop treatments targeting protein growth factors. Their pipeline aims to improve care standards for neuromuscular diseases, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted therapeutics can make a significant impact.