——A First-in-Class Hydrolysis-Activated Liver-Targeted THR-β Prodrug Demonstrating A Dual Advantage of Fat Reduction and Muscle Preservation

SHANGHAI, May 17, 2025 /PRNewswire/ -- At the European Association for the Study of the Liver (EASL) Annual Congress, CureGene Pharmaceuticals ("CureGene") announced late-breaking preclinical results for its investigational liver-targeted thyroid hormone receptor beta (THR-β) prodrug, CG-0416. Presented in a Late-Breaking Poster session, the data highlight triple therapeutic potential of CG-0416 in metabolic dysfunction-associated steatohepatitis (MASH) and weight management: including 58% reduction in hepatic lipid accumulation; 66% improvement in weight loss efficacy; and 50% lower muscle loss rate compared to standard therapies. These findings position CG-0416 as a novel dual-mechanism candidate for concurrent MASH and obesity management.

Addressing Current Therapeutic Limitations

While GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) face challenges in sustained weight control and muscle preservation, CG-0416 employs precision targeting of complementary metabolic pathways to overcome these limitations.

Key Innovations
1. Enhanced Safety Profile
CG-0416's liver-specific activation achieves intrahepatic active metabolite concentrations 20-fold higher than in peripheral tissues, minimizing systemic THR-β activation and improving long-term safety.
2. Muscle Preservation Breakthrough
In 26-week diet-induced obesity (DIO) murine models, CG-0416 combined with low-dose semaglutide demonstrated:
66% greater fat mass reduction (vs. semaglutide monotherapy)
Muscle-to-fat loss ratio of 0.18 kg/kg (vs. 0.35-0.63 kg/kg in existing therapies)
Advantages of Translational research for CG-0416
1. Dual-Pathway Synergy
CG-0416 enhances GLP-1-mediated hepatic lipid oxidation while activating the IGF-1/Akt/FOXO3a axis to suppress muscle catabolism.
2. Oral Administration Potential
With 92% oral bioavailability – doubling that of approved THR-β therapies – CG-0416 may enable the first oral combination regimen with GLP-1 agonists.
CG-0416's EASL debut garnered significant attention for its rigorous preclinical validation and innovative design. The compound's ability to reprogram metabolic pathways while maintaining safety underscores its potential to redefine standards in metabolic disease treatment.

About CG-0416‌
CG-0416 is a novel liver-targeted THR-β prodrug in development for MASH & obesity-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.

About CureGene 
CureGene was founded in 2018. Based in China, we strive to become a globally focused innovative biopharmaceutical company. We have established innovative platforms based on our core expertise and capability. Currently we are focused on cardio-cerebrovascular and antiviral disease areas. We have developed a number of pipelines of drugs with huge market potential and fully owned global IP rights and are actively moving these projects forward. Guided by our shared mission statement, we have assembled a group of talented and highly accomplished scientists with global pharmaceutical experience from China and overseas. With a comprehensive strategic vision, CureGene has successfully and highly efficiently moved from research stage startup into a clinical stage company, with all pipelines capable of First-in-Class or Best-in-Class potential.

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