CG-0416, a highly liver-targeted THR-β agonist, demonstrates high-quality weight loss by reducing fat mass while preserving muscle, both as a monotherapy and in combination with GLP-1 RAs.
ATLANTA, Nov. 12, 2025 /PRNewswire/ — CureGene Pharmaceuticals (“CureGene”) today announced the first disclosure of groundbreaking preclinical data for CG-0416, a novel oral non-GLP-1 weight-loss agent, in the Late-Breaking poster session (Poster-350) at Obesity Week 2025. CG-0416 is a highly liver-targeting thyroid hormone receptor beta (THR-β) agonist. Its highlighted profile—oral administration, potent fat reduction, and muscle preservation, and without GLP-1 target associated side effects—positions it as a potential new paradigm that could advance global obesity treatment beyond current GLP-1-based therapies.
While GLP-1 receptor agonists like semaglutide have demonstrated significant efficacy, they are associated with core challenges including muscle loss, gastrointestinal (GI) side effects, and the inconvenience of injectable administration. CG-0416 has been designed to address these limitations through a distinct mechanism. It precisely activates the THR-β receptor in the liver, directly boosting hepatic metabolism to promote fat burning and energy expenditure, without acting on the central appetite control system. This peripheral mechanism fundamentally avoids the potential psychiatric affects and GI adverse events associated with potent appetite suppression and effectively protects muscle tissue.
High-Quality Weight Loss: CG-0416 Monotherapy Achieves “Fat Loss, Not Muscle Loss”
Data presented revealed that in diet-induced obese (DIO) mouse models, CG-0416 monotherapy demonstrated superior “high-quality weight loss.” While achieving weight reduction comparable to semaglutide (Figure 1), approximately 95% of the weight loss with CG-0416 came from fat mass reduction, with minimal muscle loss. In contrast, about one-third of semaglutide-induced weight loss was attributed to lean mass reduction. By not strongly suppressing appetite, CG-0416 is expected to significantly reduce nausea, vomiting, and other GI adverse events, potentially leading to better patient adherence (Figure 2). Furthermore, CG-0416 significantly reduced blood and liver lipid levels and improved glucose tolerance, offering comprehensive metabolic benefits.
Synergistic Effects: CG-0416 in Combination with GLP-1 RAs Breaks Limits in Weight Loss and Remodel the Metabolizing Profile
The studies further explored combination therapies of CG-0416 with various GLP-1 RAs, including semaglutide and oral orforglipron, revealing powerful “1+1>2” synergistic effects.
- Combination with semaglutide: The combination increased weight loss from 24% (semaglutide monotherapy) to 40%, with some obese mice returning to a healthy weight range. It also significantly mitigated the muscle loss associated with GLP-1 RA monotherapy, increasing body muscle percentage. (Figure 3)
- Combination with orforglipron: Similar synergistic effects were observed, confirming the robustness of this approach. (Figure 4)
This innovative dual-pathway strategy—combining “central appetite regulation (GLP-1 RA) + peripheral liver metabolism activation (CG-0416)”—offers a novel solution for patients requiring profound weight loss and metabolic restoration.
Figure 1. Efficacy of CG-0416; Figure 2. Appetite Suppression; Figure 3. Efficacy of CG-0416 + Semaglutide; Figure 4. Efficacy of CG-0416+ Orforglipron
Broad Application Potential Meets Diverse Needs
As a once-daily oral agent, CG-0416 greatly enhances convenience and patient compliance. Its unique advantages cover the needs from different patient populations:
- CG-0416 Monotherapy: Ideal for individuals seeking healthy status (fat loss and muscle preservation) and for patients intolerant to GLP-1-based therapies.
- CG-0416 + GLP-1 RA Combination: Provides a more potent, higher-quality (with reduced muscle loss), and sustainable treatment option for patients with obesity and metabolic syndrome.
The data presented firmly establish the strong potential of CG-0416 as a “next-generation benchmark weight-loss therapy” and further validate the efficiency of CureGene’s “Jade” prodrug technology platform. CG-0416 represents not merely a supplement to existing treatments, but a critical step toward a future of high-quality, sustainable, and personalized weight management.
About Obesity Week 2025
Obesity Week 2025 is the world’s premier international event focused on obesity research and treatment. Co-convened by the American Society for Metabolic and Bariatric Surgery (ASMBS) and The Obesity Society (TOS), the conference takes place in November in the United States. It brings together experts from multiple disciplines including surgery, endocrinology, nutrition, and behavioral science to present the latest advancements in obesity research, prevention, and treatment, including pharmacology, surgery, and lifestyle intervention. As a key industry bellwether, Obesity Week 2025 is a critical platform for announcing major research findings and fostering cross-disciplinary collaboration, dedicated to advancing the science of obesity and improving patient care worldwide.
About CureGene
Founded in 2018 and headquartered in China, CureGene is a clinical-stage biotech company advancing novel therapies for global unmet medical needs. Leveraging proprietary technology platforms, the company has built a diversified pipeline of first-in-class candidates with full global intellectual property rights. Current focus areas include cardio-cerebrovascular disorders, antiviral therapies, and metabolic dysregulation. Its interdisciplinary team integrates world-class scientists and industry veterans from leading multinational pharmaceutical companies, driving rapid translation from discovery, clinical development and commercialization. All pipeline assets are strategically positioned to address multibillion-dollar therapeutic markets, with lead programs demonstrating potential for best-in-class efficacy across preclinical and clinical studies.
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