Scholar Rock Shares New Preclinical Data on SRK-439 Showing Lean Mass Preservation and Reduced Fat Rebound Post GLP-1 Agonist Withdrawal

Scholar Rock, a late-stage biopharmaceutical company focused on innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious conditions, has made significant progress in its research efforts. The company recently announced the initiation of the Phase 2 EMBRAZE trial, which aims to evaluate the safety and efficacy of apitegromab, an investigational, highly selective myostatin inhibitor, in preserving lean muscle mass among individuals living with obesity who are also on GLP-1 receptor agonist (GLP-1 RA) therapy. The trial will also investigate the effects of apitegromab on the durability of weight loss after the discontinuation of GLP-1 RA therapy. The outcomes of this trial are expected to provide valuable insights for the development of SRK-439, another selective myostatin inhibitor optimized for treating cardiometabolic disorders, including obesity.

In parallel with the EMBRAZE trial, the company presented new preclinical data supporting SRK-439's potential to enhance lean mass and improve body composition after GLP-1 RA treatment is halted. These findings were presented by Dr. Melissa Fulham at the American Diabetes Association’s 84th Scientific Sessions in Orlando, Florida. The preclinical study highlighted the benefits of SRK-439 in a diet-induced obesity mouse model, showing that the mice treated with SRK-439 maintained more favorable body composition compared to controls. Specifically, SRK-439 administration led to better preservation of lean mass during GLP-1 RA treatment and a significant increase in lean mass after treatment cessation. Moreover, the treatment attenuated fat mass rebound post-GLP-1 RA withdrawal compared to the control group.

Dr. Jay Backstrom, President and CEO of Scholar Rock, expressed satisfaction with the early dosing of participants in the EMBRAZE trial and the promising preclinical data of SRK-439. He emphasized the potential of SRK-439 to contribute to healthier weight management and significant advancements in weight loss management.

The preclinical study employed a diet-induced obesity mouse model, where mice were fed a high-fat diet and administered semaglutide with either a control antibody or SRK-439. Treatment spanned eight weeks, with semaglutide withdrawn after four weeks. Body composition changes were analyzed using quantitative nuclear magnetic resonance (qNMR). The results indicated that SRK-439 administration during and after semaglutide treatment helped maintain higher lean mass and lower fat mass compared to controls, suggesting a beneficial effect on body composition.

The Phase 2 EMBRAZE trial is a randomized, double-blind, placebo-controlled study targeting adults aged 18-65 with a body mass index (BMI) of over 27 (overweight) or over 30 (obese) who are on GLP-1 RA therapy. The trial aims to enroll 100 participants and will last 24 weeks, with subjects receiving either apitegromab or a placebo via intravenous infusion every four weeks. The primary endpoint is the change in lean mass from baseline at Week 24, measured by dual-energy X-ray absorptiometry, with secondary endpoints including weight loss measures, safety, tolerability, and pharmacokinetic outcomes.

SRK-439 is a novel investigational myostatin inhibitor designed to bind pro- and latent myostatin with high affinity, selective for myostatin, and intended to address cardiometabolic disorders such as obesity. While the efficacy and safety of SRK-439 are yet to be established, preclinical data suggest its potential in promoting healthier weight management by preserving lean mass during weight loss.

Apitegromab, another investigational myostatin inhibitor developed by Scholar Rock, is a fully human monoclonal antibody targeting the pro- and latent forms of myostatin in skeletal muscle. It is the first muscle-targeted treatment to show clinical proof-of-concept in SMA, with potential implications for improving motor functions in patients. While the FDA and EMA have granted various designations to apitegromab for SMA treatment, its efficacy and safety are still under review.

Scholar Rock continues to leverage its expertise in the biology of the TGFβ superfamily to develop transformative therapies for serious diseases, striving to enhance the standard of care in neuromuscular diseases, cardiometabolic disorders, and more.