Courage MC4R agonist drug candidates demonstrate potential to transform GLP1 obesity therapy
Newton, MA — July 16, 2024 — Courage, a pre-clinical stage biotech company, announced groundbreaking results, funded in part by an NIDDK funded STTR research grant on obesity. The article “Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice” was published in the Journal of Clinical Investigation by senior author and Courage co-founder Dr. Roger Cone. It reports on synergy between GLP1RA and MC4R agonist drugs, demonstrating that low doses of MC4R agonists can significantly improve the dose-responsiveness of GLP1RA drugs to reduce food intake and drive weight loss through a novel mechanism that can improve GLP1RA weight loss efficacy without increasing side effects.
“This synergy between the MC4R circuit and GLP1RA agents could revolutionize the obesity treatment landscape similar to how GLP1/GIP combinations such as tirzepatide have recently shown dramatic improvements in weight loss.” said Dan Housman CEO.
Courage completed a successful four-year drug discovery campaign resulting in a market leading portfolio of optimized MC4R peptide agonist drug candidates designed to address the combination opportunity. Clinical candidates have demonstrated significantly higher potency and selectivity in animal models than setmelanotide, the only MC4R agonist currently approved for obesity treatment. The selectivity eliminates MC1R activity which drives a pigmentation side effect that has limited pharma development of MC4R agonists in dietary obesity. Combining Courage products with GLP1RA drugs such as Ozempic and Mounjaro in new ways is expected to improve the safety of GLP1RA drugs by lowering nausea, increasing physical activity, and reducing gastrointestinal discomfort.
“Based on their deep expertise in the field of melanocortin biology, Courage scientists have developed a range of peptide drugs that activate the MC4R. The potency and specificity of these drugs represent a significant advance on the only currently licensed activator of this receptor, setmelanotide. Their current paper in the Journal of Clinical Investigation Dahir et al adds to the evidence that combining low doses of a melanocortin 4 agonist with anti-obesity drugs acting through the GLP1Receptor can lead to greater weight loss in mice than when these drugs are used alone. Combining a specific and potent MC4R agonist with a drug acting on GLP1R opens up the exciting possibility of novel “dual action” anti-obesity agents with improved efficacy, safety and tolerability said Stephen O’Rahilly, Professor of Clinical Biochemistry and Medicine at the University of Cambridge and chair of Courage’s Scientific Advisory Board.
The company is initiating pre-clinical studies to bring product candidates into the clinic. Additionally, Courage is seeking partnerships with GLP1RA drug companies.
Go to the article: “Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice,” Journal of Clinical Investigation. Link: https://doi.org/10.1172/JCI178250
Additional information is available at the University of Michigan web site.
This award was granted by the National Institutes of Health under Award Number R42DK127817. The content of this press release is solely the responsibility of the author and does not necessarily represent the official views of the NIH.
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Courage Therapeutics
Courage Therapeutics is a pre-clinical stage biopharmaceutical company focused on treating obesity and eating disorders. The company is led by an experienced team of scientists and pharmaceutical industry experts focusing on developing scientific discoveries regarding the brain’s response to energy signals from the body. The company has a licensing agreement with the University of Michigan to develop treatments based on a portfolio of intellectual property jointly invented by Courage. Led by Dr. Tomi Sawyer the Courage medicinal chemistry team has pending patents on multiple compounds with highly selective and potent MC4R and MC3R activity.
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