CureGene Doses First Participant in Phase I Trial of Oral Liver-Targeting THR-β Agonist CG-0416
核心洞察
CureGene has dosed the first subject in a Phase I trial of CG-0416, a novel oral liver-targeting THR-β (搜索) agonist, in Australia.
CG-0416 is a prodrug designed for MASH and obesity (搜索), offering liver-targeted delivery, up to 92% oral bioavailability, and a non-CYP metabolism pathway that minimizes drug-drug interactions.
Preclinical data show weight-loss efficacy comparable to GLP-1 receptor agonists such as semaglutide while preserving muscle mass, with synergistic effects when combined with GLP-1 RAs.
CureGene has dosed the first participant in its Phase I clinical trial of CG-0416, a novel oral liver-targeting THR-β (搜索) agonist developed in-house, in Australia. The company announced the milestone on Aug. 21, 2026, noting that subject enrollment is progressing smoothly. The first-in-human (FIH) study marks a step forward in CureGene's strategic expansion into cardiovascular and metabolism disease.
CG-0416 is designed based on CureGene's proprietary prodrug platform, incorporating precise design and structural optimization to achieve several key differentiators. The candidate employs liver-targeting delivery, achieving high intrahepatic release of the active moiety to produce low systemic exposures and minimize off-target effects in tissues other than the liver. It also demonstrates a non-CYP metabolism pathway, in which hydrolysis-mediated activation avoids CYP450 oxidative metabolism, thereby minimizing drug–drug interactions (DDI) and individual variability. The compound offers high oral bioavailability of up to 92%, with a favorable safety and tolerability profile that supports long-term daily use.
Preclinical data demonstrated that CG-0416 potently activates lipid metabolism in the liver, markedly reduces liver fat accumulation, and consequently ameliorates inflammation and fibrosis. As a monotherapy, CG-0416 has shown weight-loss efficacy comparable to that of mainstream GLP-1 receptor agonists (RA), such as semaglutide, while showing minimum muscle loss. When combined with GLP-1 RA agents, CG-0416 exhibits a strong synergistic effect for additional weight reduction with high-quality muscle preservation. These characteristics position CG-0416 as a promising oral therapy for chronic metabolic diseases, including obesity (搜索) and metabolic dysfunction-associated steatohepatitis (MASH) (搜索).
CG-0416 is described as a novel liver-targeted THR-β (搜索) prodrug in development for MASH and obesity (搜索)-related complications. Its tissue-selective activation mechanism simultaneously addresses hepatic lipid accumulation, inflammation, and fibrosis, while demonstrating superior metabolic control to resmetirom and VK-2809 in preclinical studies. As a potential oral adjunct to GLP-1 therapies, CG-0416 combines rapid fat reduction with muscle preservation, positioning it as a next-generation metabolic modulator.
The FIH Phase I trial in Australia is a randomized, double-blind, placebo-controlled study in healthy participants, designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CG-0416 following single and multiple ascending doses. Leveraging Australia's well-established Phase I clinical infrastructure, the trial will generate critical data to support subsequent global development and indication expansion of CG-0416.
"The first subject dosed in our Phase I trial marks another solid step forward in CureGene's strategic expansion into cardiovascular and metabolism disease," said Dr. Gongxin He, Founder and Chief Executive Officer of CureGene. "Through continuous innovation using the prodrug technology, we are dedicated to bring safer, clinically valuable, and more convenient therapies to the patients worldwide."
CureGene Pharmaceutical (搜索), founded in 2018, possesses proprietary core platform technologies and independent high-efficiency innovation capabilities. The company primarily focuses on therapeutic areas including cardiovascular and cerebrovascular diseases and antiviral therapies, striving to become a China-rooted, globally oriented innovative pharmaceutical enterprise. Leveraging its proprietary platforms, CureGene has built a pipeline of innovative assets with broad market value and global independent intellectual property rights, with multiple candidates actively progressing through clinical development.