PeptiDream Announces Preclinical Results Demonstrating Efficacy of Oral Myostatin Inhibitors in Preventing Loss of Lean Mass Associated with Semaglutide Treatment
KAWASAKI, Japan, December 12, 2024--(BUSINESS WIRE)--PeptiDream Inc., a public Kanagawa, Japan-based biopharmaceutical company (President: Patrick C. Reid, hereinafter "PeptiDream")(Tokyo: 4587) today announced the highly promising results from the preclinical testing of the company’s oral myostatin inhibitors, administered in combination with semaglutide (a GLP-1 receptor agonist; a class of molecules known for the ability to aid in weight loss by modulating appetite and promoting satiety) in a mice model of obesity.
PeptiDream has discovered a series of potent macrocyclic and bridged-macrocyclic peptide inhibitors of Myostatin. Myostatin (also known as growth differentiation factor 8, or GDF8), along with GDF11 and Activin, are members of the transforming growth factor-beta (TGFbeta) superfamily, and function in a complex process that regulates muscle growth and function. Numerous preclinical and clinical studies have suggested that myostatin inhibitors can increase lean muscle mass, improve physical strength, reduce visceral fat, and improve metabolic dysfunction, such as insulin-mediated glucose disposal, providing growing evidence that myostatin may be an important therapeutic target for the treatment of a variety of muscular dystrophies, such as Spinal muscular atrophy "SMA", Facioscapulohumeral muscular dystrophy "FSHD", Duchene muscular dystrophy "DMD" and other muscle wasting diseases, as well as more recently the potential treatment for obesity, metabolic syndrome, and type 2 diabetes mellitus.
In preclinical DMD mice models, PeptiDream previously reported weekly administration of its peptide myostatin inhibitors, via subcutaneous or oral administration, resulted in both strong suppression of myostatin signaling and high exposure in muscle, yielding significant improvements in four-limb grip strength in treated animals. These extremely promising findings strongly supported their continued development for potential use in DMD, and given the results, PeptiDream initiated additional studies to investigate the use of its oral myostatin peptide inhibitors in obesity, where there is growing evidence that myostatin inhibitors can preserve lean body mass in individuals living with obesity and taking a GLP-1 receptor agonist (such as semaglutide).
To this end, peptides from this series were tested in a diet-induced obesity ("DIO") model where mice were given either a high-fat (60%) diet plus semaglutide (0.12 mg/kg, daily injection), or a high-fat diet (60%) plus semaglutide (0.12 mg/kg, daily injection) in combination with PeptiDream’s peptides orally administered (0.5, 1.5, 4.5 mg/kg; daily dose or 3, 10, 30 mg/kg; weekly dose). Body weight of the animals was measured every 2 days and Echo MRI was utilized to analyzes changes in both Fat Mass and Lean Body Mass at 14 and 28 days of treatment.
Key Findings:
Significant weight loss: Mice receiving the combination of oral peptide myostatin inhibitor with semaglutide showed a significant reduction in body weight compared to controls, with weight loss maintained over the study period.
Lean mass preservation: Unlike many traditional weight-loss therapies that lead to a loss of both fat and lean muscle mass, both daily and weekly administration of PeptiDream’s oral peptide myostatin inhibitor successfully preserved lean body mass when administered in combination with semaglutide, highlighting its potential for improving body composition.
Enhanced therapeutic potential: The results suggest that the synergistic effects of myostatin inhibition and semaglutide could be an effective strategy for patients with obesity, offering a novel approach to weight management that avoids muscle loss, a common drawback of many current obesity treatments.
"We are very excited to share these preclinical results. Our myostatin inhibitors showed significant lean body mass preservation, with both daily and weekly oral administration, effectively counter-acting the lean mass loss associated with semaglutide-induced weight loss. These findings provide compelling evidence of the first-in-class potential of our oral peptide myostatin inhibitors to be used in combination with other weight loss agents to transform the management of healthy weight loss, as well as providing more convenient and patient-friendly oral treatment options to patients." said Patrick C. Reid PhD, President & CEO of PeptiDream.
PeptiDream presented a portion of these preclinical results at its R&D Day event on December 12, 2024 (R&D Day presentation materials are available on the PeptiDream website). PeptiDream is continuing preclinical development activities while exploring clinical development options for this exciting program, including discussions with potential partners interested in licensing/partnering the program.
About PeptiDream Inc.
PeptiDream Inc. (Tokyo Stock Exchange Prime Market 4587) is leading the translation of macrocyclic peptides into a whole new class of innovative medicines to address unmet medical needs and improve the quality of life of patients worldwide. In its radiopharmaceutical business, through its wholly-owned subsidiary PDRadiopharma, PeptiDream markets and sells a number of approved radiopharmaceuticals and radiodiagnostics in Japan, as well as leveraging its proprietary Peptide Discovery Platform System (PDPS) technology to discover and develop a deep pipeline of innovative targeted radiotherapeutics and radiodiagnostics, spanning both wholly-owned internal programs and globally partnered programs. In its non-radiopharmaceutical business, PeptiDream is similarly leveraging PDPS to discover and develop a broad and diverse pipeline of investigational peptide therapeutics, peptide drug conjugates (PDC) and multi-functional peptide conjugates (MPC) across an extensive global network of discovery and development partners. PeptiDream is headquartered in Kawasaki, Japan. For more information about our company, science and pipeline, please visit www.peptidream.com/en/.
