Scholar Rock 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. 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 Following four weeks of treatment, semaglutide was withdrawn from both treatment groups and mice remained on either the IgG control antibody weekly or on SRK-439.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).