-Eccogene, a clinical-stage biopharmaceutical company developing next-generation oral small molecule therapeutics for chronic cardiometabolic and inflammatory conditions, today announced that the first patient has been enrolled in MIST, the company’s Phase 2a clinical trial evaluating ECC4703 as an adjunct to semaglutide in adults with obesity.

The MIST trial is designed to assess the potential additive or synergistic effects of ECC4703 in combination with a GLP-1 receptor agonist. In this study, participants receive injectable semaglutide once weekly, with ECC4703 or placebo administered orally once daily. The trial will evaluate the contribution of ECC4703 to weight loss and other pharmacodynamic measures over 12 weeks of treatment.

“We are pleased to advance ECC4703 into this Phase 2a study in obesity,” said Jingye Zhou, Chief Executive Officer of Eccogene. “While GLP-1–based therapies have established a new standard of care, important questions remain regarding tolerability, body composition, and overall quality of weight loss. Our preclinical data suggest ECC4703 may contribute to deeper weight reduction driven primarily by fat mass loss over lean mass loss, and, to our knowledge, we are one of the first in the industry to test this hypothesis in a robustly designed clinical trial.”

MIST (Metabolic Intervention with Semaglutide and THR-β) is a multicenter, randomized, double-blind, placebo-controlled Phase 2a trial expected to enroll approximately 160 adults with obesity. The primary endpoints include changes in body weight and liver fat content as assessed by MRI-PDFF. Secondary and exploratory endpoints include additional metabolic parameters, safety, and tolerability.

“Obesity is not a single-pathway disease, and for many patients, monotherapy simply doesn’t address the full metabolic burden,” said Julio Rosenstock, MD, Lead Investigator and Eccogene’s Senior Scientific Advisor. “By combining semaglutide with ECC4703, a selective thyroid hormone receptor-beta agonist designed to act in the liver, we’re exploring whether a dual-mechanism approach can meaningfully enhance metabolic control—particularly by further reducing liver fat—beyond what GLP-1 therapy alone can achieve.”