Melanocortin 4 Receptor Agonists As Oral Weight Loss Drugs

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Obesity is a major public health crisis in the United States; over 40% of American adults qualify as obese. Obesity significantly increases the risk of developing chronic diseases like heart disease, type 2 diabetes, and some cancers. GLP-1 agonists, have revolutionized obesity treatment, with the ability to reduce body weight up to 20.9% over 72 weeks (Aronne et al. 2024).

 However, there are a number of issues with GLP-1s.  For example, the efficacy of GLP-1’s plateau over time, patients experience large rebounds in weight after coming off the GLP-1’s, and there are tolerability issues for GLP-1’s, including nausea and vomiting.  These issues highlight the need for new modality weight loss drugs. 
 

At Endevica Bio, we have developed melanocortin-4 receptor (MC4R) agonists that match the weight loss efficacy of GLP-1’s in rats and that do not result in large rebounds in weight after removal of drug (See data below). In orally dosed NHPs, our MC4R agonists demonstrate drug-like PKs with AUC ≥ 2000 ng*h/mL and T1/2 > 6 h.  As a result, we expect these compounds to be orally efficacious in NHPs and humans.  

Internal Data

At Endevica Bio, we have developed melanocortin-4 receptor (MC4R) agonists that match the weight loss efficacy of GLP-1's in rats. . ."

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