Scholar Rock Announces New SRK-439 Preclinical Data Showing Significant Lean Mass Preservation and Attenuation of Fat Mass Rebound Following GLP-1 Receptor Agonist Withdrawal

- SRK-439, a myostatin inhibitor, is part of Scholar Rock’s industry-leading anti-myostatin portfolio

- Obesity program continues to progress, with first participants dosed in Phase 2 EMBRAZE trial of apitegromab in obesity

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- 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 that the first participants were dosed in the Phase 2 EMBRAZE proof-of-concept trial, designed to assess the safety and efficacy of apitegromab, an investigational, highly selective myostatin inhibitor, to preserve lean muscle mass in individuals living with obesity and on background therapy of a GLP-1 receptor agonist (GLP-1 RA). The trial will also evaluate the effects of apitegromab on the durability of weight loss upon withdrawal of GLP-1 RA therapy. The results from this trial will inform the development of SRK-439, a novel investigational selective myostatin inhibitor optimized for the treatment of cardiometabolic disorders, including obesity.

The Company also presented new preclinical data that support the potential of SRK-439 to increase lean mass and contribute to a favorable body composition following withdrawal from GLP-1 RA treatment. These data were presented by Melissa Fulham, PhD, of Scholar Rock, at the American Diabetes Association’s 84th Scientific Sessions on June 23rd in Orlando, Florida.

“We are happy to share the exciting news that we’ve dosed the first participants in our EMBRAZE clinical trial ahead of schedule and to have new preclinical data with SRK-439, our highly selective anti-myostatin, featured at the American Diabetes Association Scientific Sessions,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer at Scholar Rock. “SRK-439 preclinical data to date have demonstrated preservation of lean mass with GLP-1 RA-induced weight loss, attenuation of fat mass regain following GLP-1 RA withdrawal, and greater potency compared to an anti-ACTRII antibody. Together, these data continue to support a best-in-class potential for healthy weight loss management and could be transformative for the management of weight loss. We are looking forward to providing additional updates on our cardiometabolic program as we advance SRK-439, as well as the EMBRAZE trial.”

Preclinical experimental design

For the preclinical research study, the Company tested a murine equivalent of SRK-439 in a diet-induced obesity (DIO) mouse model. Mice were given either a high-fat diet plus semaglutide (0.04 mg/kg, daily) and an IgG control antibody (weekly, 10 mg/kg), or a high-fat diet plus semaglutide (0.04 mg/kg, daily) in combination with weekly injections of SRK-439 (10 mg/kg). Following four weeks of treatment, semaglutide was withdrawn from both treatment groups and mice remained on either the IgG control antibody weekly or on SRK-439. Treatment continued for another four weeks, for a total of eight weeks in the study. Quantitative nuclear magnetic resonance (qNMR) was used to analyze change in lean mass at two weeks and again at four weeks of semaglutide treatment, and every two weeks after that until the end of the subsequent four-week withdrawal period.

Changes in body composition after semaglutide withdrawal

The group that received SRK-439 maintained more favorable body composition than the group receiving IgG antibody. Key findings supporting the potential for SRK-439 in advancing healthier weight management include:

• Administration with SRK-439 attenuated the loss of lean mass during semaglutide treatment and significantly increased lean mass after semaglutide discontinuation as compared to IgG control;
• SRK-439 administration also attenuated the fat mass rebound after semaglutide discontinuation as compared to that in IgG control + semaglutide mice; and
• Body composition, i.e. proportion of lean mass or fat mass to total body weight, was more favorable in mice receiving SRK-439 as compared to IgG control: Mice administered SRK-439 had higher relative lean mass (65.8%) and lower relative fat mass (18.0%) at the end of the withdrawal period compared to IgG control (57.1% lean mass and 28.7% fat mass).

Shown below are results for body composition at baseline (6 days before semaglutide treatment), the end of semaglutide treatment (at 4 weeks), and at the end of the semaglutide withdrawal period (at 8 weeks):