Scholar Rock Presents New Preclinical Data Demonstrating Potential Benefit of SRK-439 for Healthy Weight Loss Management

Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, today announced new preclinical data showing the potential of SRK-439 to preserve lean mass and improve metabolic health as part of healthy weight loss. These data showed that SRK-439 maintained lean mass and improved fat mass loss when used in combination with a GLP-1 receptor agonist (GLP-1 RA; in separate experiments with semaglutide and liraglutide) in diet-induced obesity (DIO) mice. SRK-439 treatment also led to incremental lowering of fasting glucose beyond the levels seen with semaglutide alone. Detailed results were presented by Melissa Fulham, PhD, of Scholar Rock, at the Keystone Symposia’s Obesity: Causes and Consequences meeting in Vancouver, BC, Canada on February 5.

“These preclinical data showing that SRK-439 preserves lean mass and improves fat mass loss provide compelling scientific rationale to study SRK-439 in combination with GLP-1 RA therapies for healthy weight loss management,” said Jay Backstrom, M.D., MPH, President and CEO of Scholar Rock. “We believe that preserving lean muscle mass through our highly selective approach to myostatin inhibition in combination with GLP-1 RA therapy has the potential to transform the management of weight loss. We look forward to initiating our proof-of-concept study with apitegromab in combination with GLP-1 RA therapy in obesity as we also continue to advance SRK-439 to clinic.”

In January, Scholar Rock announced that the U.S. Food and Drug Administration cleared the company’s Investigational New Drug (IND) application for its Phase 2 proof-of-concept trial of apitegromab to treat obesity in patients taking a GLP-1 RA. Trial initiation is on track for mid-2024, and data from the apitegromab Phase 2 trial are expected in mid-2025. In parallel, Scholar Rock is developing SRK-439, a novel investigational selective myostatin inhibitor, optimized for the treatment of obesity.

Selectivity and affinity: SRK-439 works by selectively binding to the pro- and latent forms of myostatin, as confirmed through in vitro ELISA testing that shows SRK-439 does not bind to closely related TGFβ family members GDF11 and Activin A, both of which, if inhibited, have potentially detrimental effects outside of the muscle. The studies confirmed that SRK-439 binds to latent myostatin with 0.579 nM affinity. This selectivity and affinity, along with favorable developability characteristics and durable pharmacokinetics suggests that SRK-439 could be suitable for dosing in a subcutaneous formulation and in a low dose volume in a population of adults with obesity.