Metabolics Pharma Announces ENT-03 Generates Sustained Weight Loss and Liver Pathology Improvements in an Animal Model for Obesity

Metabolics Pharma (“Metabolics”), a privately held, Doylestown-based, clinical-stage biopharmaceutical company pioneering novel treatments for metabolic diseases, today announced that its drug candidate, ENT-03, showed significant benefit in metabolic dysfunction in addition to sustaining weight loss, improvement in blood glucose, and insulin sensitivity in comparison to semaglutide in an animal model for obesity.

“Metabolics Pharma spun off from its parent company, Enterin, in late 2024 so that the company could focus its efforts on and enhance the value of its lead asset, ENT-03, for the treatment of obesity and certain comorbidities,” said Richard Larson, M.D., Ph.D., Chief Executive Officer, Chief Medical Officer and Board Chairman of Metabolics Pharma. “These preclinical data highlight both the promise and potential value of ENT-03 in the treatment of metabolic disease. The research shows that ENT-03 clearly improves insulin sensitivity and sustained weight reduction that persists following cessation of treatment. This research is the foundation for our Phase 1 clinical trials in healthy obese and diabetic obese subjects.”

ENT-03 is a novel, centrally acting aminosterol with Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, which normalizes glucose and causes weight loss by acting on brain circuits that regulate energy and metabolism. In obese, diabetic mice, ENT-03 rapidly lowers blood glucose, reduces food intake and adiposity, eliminates liver fat, and improves liver function.

This study compared ENT-03 to semaglutide, a combination of the two compounds, and vehicle in Diet Induced Obesity (DIO) mice. While the vehicle-treated mice gained weight through the duration of the study, mice treated with ENT-03, Semaglutide, or a combination of the two drugs all lost weight and reduced insulin and glucose levels. ENT-03 showed a greater reduction in weight than Semaglutide over the 10-week treatment period. Additive weigh loss was seen when the drugs were used in combination. After cessation of therapy, weight loss and reduction in glucose and insulin were sustained for an additional two months in the ENT-03 treated mice but not Semaglutide treated mice. In addition, ENT-03 showed substantially greater preservation of lean mass in comparison to other treatment groups.

“GLP-1 agonists have revolutionized the treatment of obesity and type 2 diabetes,” said Richard Larson, MD, PhD. “However, their impressive efficacy comes at the price of tolerability challenges, the loss of lean body mass, and the need to remain on treatment to sustain weight loss. ENT-03 represents a novel drug candidate that could be an alternative treatment to GLP-1 agonists or used in combination with them. We believe that ENT-03 could have a substantial impact on the obesity drug market since it has potential benefits beyond weight loss.”

Metabolics Pharma has completed a Phase 1a, first in human, randomized, double-blind, single ascending dose study of ENT-03. Results of the Phase 1a trial were presented at the American Diabetes Association 85^th Scientific Sessions on June 22, 2025. A Phase 1b clinical trial is planned to initiate in the second half of 2025.

About Metabolics Pharma

Metabolics Pharma develops novel therapies for the treatment of metabolic diseases including obesity and type 2 diabetes. The Company’s lead compound, ENT-03, in development for the treatment of type 2 diabetes and obesity, increases insulin sensitivity by acting at the level of the brain. ENT-03 has completed a Phase 1a clinical trial and will begin a Phase 1b clinical trial in the second half of 2025. For more information, please visit www.metabolicspharma.com.

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