Second Head-to-head Phase 3 Study of Mazdutide versus Semaglutide Completes First Participant Dosing in Adults in China with Overweight or Obesity Accompanied Fatty Liver Disease (GLORY-3)

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SAN FRANCISCO and SUZHOU, China, May 15, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, announces that the first participant has been successfully dosed in GLORY-3, a Phase 3 clinical study of mazdutide (Innovent R&D Code: IBI362), a dual glucagon (GCG) and glucagon-like peptide 1 receptor (GLP-1) receptor agonist. The study targets adults in China with overweight or obesity accompanied metabolic dysfunction-associated fatty liver disease (MAFLD).

GLORY-3 is a multicenter, randomized, open-label Phase 3 clinical study (NCT06884293) comparing the efficacy and safety of mazdutide versus semaglutide in Chinese adults with overweight or obesity accompanied MAFLD. This study plans to enroll approximately 470 participants with overweight or obesity (BMI ≥ 27 kg/m²) accompanied MAFLD, who will be randomized 1:1 to receive mazdutide 9 mg or semaglutide 2.4 mg. The primary endpoints are the percentage change in liver fat content (LFC) as measured by magnetic resonance proton density fat fraction (MRI-PDFF) and the percentage change in body weight from baseline to week 48.

A Phase 2 study conducted in Chinese adults with obesity (BMI ≥ 30 kg/m², NCT04904913) showed that after 48 weeks of treatment, mazdutide 9 mg achieved an 18.6% (17.8kg) placebo-adjusted mean percent reduction in body weight. Meanwhile, 51.2% and 34.9% of the subjects in the mazdutide 9 mg group achieved 15% or more and 20% or more weight loss from baseline, respectively. Among participants with baseline LFC≥ 5% (measured by MRI-PDFF), the percent change in LFC from baseline to week 24 was reduced by 73.3% in the mazdutide 9 mg group. This decrease was sustained during the 48-week extended treatment period, suggesting that mazdutide can effectively reduce body weight and liver fat in participants with overweight or obesity.

Professor Lixin Guo, the Principal Investigator of the Study, Peking University People's Hospital, stated, "MAFLD is now the most common chronic liver disease in the world and has surpassed viral hepatitis as the leading chronic liver disease in China. Obesity is a key risk factor, with MAFLD affecting up to 81.8% people with obesity in China^[1]. The latest Chinese guidelines recommended GLP-1 agents such as semaglutide for treating obesity and MAFLD ('Guideline for chronic weight management and clinical practice of anti-obesity medications'). As a dual GCG/GLP-1 receptor agonist, mazdutide 9 mg has shown strong weight loss effects and notable improvements in liver fat and enzyme levels, thanks to its additional GCG activity. GLORY-3 is the first clinical trial comparing a dual GCG/GLP-1 receptor agonist with a GLP-1R-only drug in Chinese adults with obesity. It will compare the efficacy and safety of mazdutide 9 mg versus semaglutide 2.4 mg in participants with overweight or obesity accompanied MAFLD. Together with our investigator team, I am committed to conducting this study to the highest standards and to delivering a better treatment option for the Chinese population with overweight or obesity accompanied MAFLD."

Dr. Lei Qian, Senior Vice President of Clinical Development at Innovent, stated, "Mazdutide, as a dual GCG/GLP-1 receptor agonist, enhances lipolysis and fatty acid oxidation by stimulating the GCG receptor, offering a series of comprehensive metabolic benefits compared to GLP-1 single receptor agonist drugs. In our Phase 2 study conducted in Chinese adults with obesity, participants with baseline LFC ≥ 5% had a 73.3% reduction in liver fat content after 24 weeks of treatment with mazdutide 9 mg, which preliminarily demonstrated the efficacy of mazdutide in reducing liver fat content. I am very confident that mazdutide will continue to show strong clinical efficacy in the GLORY-3 study, including in weight loss and liver metabolism, and provide a better treatment option for Chinese patients with overweight or obesity accompanied MAFLD."

About Obesity

China has the world's largest population of people with overweight or obesity^[2], with the obesity rate likely to rise. Obesity contributes to multiple comorbidities, reducing life expectancy and quality of life. In 2019, overweight and obesity accounted for 11.1% of deaths related from chronic non-communicable diseases in China, a significant increase from 5.7% in 1990^[3].

As obesity is a chronic disease, it requires long-term management, and China faces a lack of long-term effective and safe treatments. Despite lifestyle interventions being the first-line treatment, many patients fail to achieve their desired weight loss goals, underscoring the need for more effective and safer pharmacological interventions.

About MAFLD

MAFLD is the most common chronic liver disease worldwide, with a global prevalence estimated around 32.4% and increasing. Obesity is one of the risk factors for MAFLD, and the prevalence of MAFLD in those with obesity worldwide has reached 75.3%. In China, MAFLD has overtaken viral hepatitis as the leading chronic liver condition, affecting 81.8% of obese individuals^[1]. China also has the world's highest incidence of MAFLD in both normal and obese populations. Treatment goals include reducing body weight and waist circumference, improving insulin resistance, preventing and treating metabolic-related syndromes, and reversing fibrosis. For patients with MAFLD and overweight or obesity, combining lifestyle and pharmacological interventions is considered the most effective strategy to improve health outcomes and quality of life.

About Mazdutide (IBI362)

Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, mazdutide may offer additional benefits beyond those of GLP-1 receptor agonists—such as promoting insulin secretion, lowering blood glucose and reducing body weight—by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies. It has also shown benefits in reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, as well as improving insulin sensitivity.

Mazdutide currently has two NDAs accepted for review by NMPA, including:

• For chronic weight management in adults with overweight of obesity;
• For glycemia control in adults with type 2 diabetes.

Mazdutide is currently being evaluated in six Phase 3 clinical studies, including:

• GLORY-1: A Phase 3 trial in Chinese participants with overweight or obesity.
• GLORY-2: A Phase 3 trial in Chinese participants with moderate-to-severe obesity.
• GLORY-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with overweight/obesity and metabolic dysfunction-associated fatty liver disease (MAFLD).
• DREAMS-1: A Phase 3 trial in treatment-naïve Chinese patients with T2D.
• DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese T2D patients with inadequate glycemic control on oral antidiabetic drugs.
• DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese patients with T2D and obesity.

Among these, GLORY-1, DREAMS-1 and DREAMS-2 studies have all met their endpoints.

In addition, several new clinical studies of mazdutide are planned, including:

• A Phase 3 trial in adolescents with obesity.
• A Phase 3 trial in Chinese participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity.
• New studies in metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF).

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: (1)Innovent does not recommend the use of any unapproved drug (s)/indication (s).

（2）Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company.

Forward-looking statement

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

References

[1] Chen K, Shen Z, Gu W, Lyu Z, Qi X, Mu Y, Ning Y; Meinian Investigator Group. Prevalence of obesity and associated complications in China: A cross-sectional, real-world study in 15.8 million adults. Diabetes Obes Metab. 2023 Nov;25(11):3390-3399.

[2] Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol 2021; 9: 373–92.

[3] Institute for Health Metrics and Evaluation. Global Health Data Exchange. GBD results tool. http://ghdx.healthdata.org/gbd-resultstool (accessed Jan 10, 2021).

SOURCE Innovent Biologics