Innovent Announces Robust Weight Loss Efficacy, Multiple Metabolic Benefits and Favorable Safety Profile of Higher Dose 9 mg Mazdutide (IBI362) after 48-week Treatment in Phase 2 Study for Obesity

• Mazdutide demonstrates its differentiated advantages as a novel dual agonist of GLP-1 and GCG receptor with superior weight loss efficacy, significant improvement in a series of cardiometabolic indicators (waist circumference, blood pressure, liver enzyme, triglyceride, low-density lipoprotein cholesterol, and serum uric acid etc.), and mean reduction of liver fat content by 73.3%.
• Following 48 weeks of treatment, mazdutide 9 mg achieved 18.6% placebo-adjusted mean body weight loss from baseline; significantly more subjects achieved ≥15% and ≥20% weight loss than 24 weeks.
• Favorable safety and tolerability with a simple two-step titration regimen; no SAE and no treatment discontinuation led by AE was observed through 48 weeks of treatment.
• The Phase 3 study of mazdutide 9 mg for obesity is expected to commence by the end of 2023.

ROCKVILLE, Md. and SUZHOU, China, Oct. 30, 2023 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, today announced the 48-week treatment results of the Phase 2 clinical study (ClinicalTrials.gov, NCT04904913) of higher dose (9 mg) mazdutide (Innovent R&D Code: IBI362) in Chinese subjects with obesity, demonstrating significant weight loss efficacy, favorable safety, and multiple metabolic benefits. The results suggested that mazdutide 9 mg may provide an alternative option to metabolic surgery for long-term weight management of Chinese subjects with moderate-to-severe obesity. Innovent plans to initiate a Phase 3 clinical study of mazdutide 9 mg in Chinese patients with obesity by the end of 2023.

The Phase 2 study is a randomized, double-blind, placebo-controlled study intended to evaluate the efficacy and safety of higher dose 9mg mazdutide in Chinese subjects with obesity [mean baseline body mass index (BMI) of 34.3 kg/m²]*. A total of 80 subjects were enrolled and randomized in a 3:1 ratio to mazdutide 9 mg or to placebo. The primary endpoint of the study is the percent change in body weight from baseline versus placebo after 24 weeks of treatment. The study also extended to 48 weeks in subjects that agreed to continue receiving additional 24 weeks of double-blind extension treatment.

*Metabolic surgery is recommended for Chinese population with a BMI of 32.5 kg/m² or above.

Robust weight loss efficacy

• In May 2023, Innovent announced that this clinical study met its 24-week primary endpoint. After 24 weeks of treatment, the placebo-adjusted mean percent change in body weight from baseline was -15.4% (-14.7 kg). Meanwhile, 31.7% and 21.7% of the subjects in the mazdutide 9 mg group achieved 15% or more and 20% or more weight loss from baseline, respectively.
• After reaching the 24-week primary endpoint, 59 subjects (43/60 in the mazdutide group and 16/20 in the placebo group; mean baseline BMI of 34.7 kg/m², mean baseline weight of 98.4 kg) agreed to continue into the 24-week double-blind extension period of the study drug.
• After 48 weeks of treatment, the placebo-adjusted mean percent change in body weight from baseline was -18.6% (-17.8 kg). 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.
• Corresponding to changes in body weight, the mean waist circumference and blood pressure of subjects in the mazdutide group also decreased.

Favorable safety profile

• No subject in the mazdutide group discontinued treatment due to adverse events through 48 weeks of treatment. No serious adverse events occurred through 48 weeks of treatment.
• Gastrointestinal adverse reactions (nausea, vomiting and diarrhea) were the most common adverse events, most of mild or moderate severity. The incidence of gastrointestinal adverse reactions reduced during the extended treatment period to 48 weeks and most were mild.
• The increase in heart rate in the mazdutide group was similar to that in the placebo group after 24 weeks of treatment, with no further increase in heart rate being observed during the extended treatment period to 48 weeks. No signal of increased cardiovascular risk was observed throughout the treatment period of 48 weeks.
• The profile of adverse events through 48 weeks of treatment was consistent with that observed in previous studies of mazdutide and other GLP-1-based drugs, with no new safety signals observed.

Multiple metabolic benefits

• In subjects with baseline liver fat content (as measured by MRI-PDFF) greater than 5%^#, the liver fat content was reduced by 73.3% after 24-week treatment of mazdutide. In the overall population, mazdutide induced 45.5% reductions in ALT levels relative to placebo after 24-week treatment. The above benefits were maintained during extended treatment period to 48 weeks.
  
  ^#The guideline of NAFLD form American Association for the Study of Liver Diseases (AASLD) recommended a liver fat content of 5% measured by MRI-PDFF as a diagnostic threshold hepatic steatosis.

• After 24-weeks of treatment, mazdutide 9 mg significantly reduced triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and serum uric acid (sUA) levels, and the reductions were maintained during the extended treatment period to 48 weeks. In addition, high-density lipoprotein cholesterol (HDL-C) levels were stable throughout the treatment period of 48 weeks.

More details of the study will be disclosed at medical conferences or in full manuscript in academic journals in the future.

Professor Linong Ji, the leading principal investigator of the study, Peking University People's Hospital, stated, "As a chronic disease with complex causes, obesity is an important risk factor of metabolic diseases, cardiovascular and cerebrovascular diseases and tumors. Obesity requires long-term treatment and management as well as the attention of the entire society. The 48-week results of mazdutide 9 mg in Chinese subjects with obesity revealed robust weight loss efficacy of GLP-1R and GCGR dual agonists, which is at the forefront of the weight loss efficacy of GLP-1 drugs. We also observed cardiometabolic benefits after mazdutide 9 mg treatment, including reductions in uric acid levels and liver fat content. Mazdutide has demonstrated strong and long-term efficacy, as well as good tolerability and safety, suggesting the advantages of mazdutide as a novel dual agonist of GLP-1 and GCG receptors. Mazdutide 9 mg is anticipated to provide an effective and safe weight loss treatment for Chinese subjects with moderate-to-severe obesity and may offer a potential alternative to surgery. I am looking forward to the Phase 3 clinical study of mazdutide 9 mg in Chinese subjects with obesity, and its translation into clinical applications in the future. "

Dr. Lei Qian, Vice President of Clinical Development at Innovent stated, "Mazdutide 9 mg induced a placebo-adjusted 18.6% weight loss after 48 weeks of treatment. The weight loss effect is even comparable to that of metabolic surgery, and is also the highest placebo-adjusted weight loss among the current GLP-1 drugs in Chinese subjects after 48 weeks of treatment. Mazdutide 9 mg also provided additional benefits, such as reduced waist circumference, blood pressure, blood lipids, liver fat content, ALT and serum uric acid in subjects with obesity. The robust efficacy, favorable long-term safety and metabolic benefits, combined with two-step titration treatment regimen, further suggests mazdutide 9 mg as a highly competitive therapy for treating obesity. We expect to initiate the Phase 3 study of mazdutide 9 mg by the end of 2023. We hope that mazdutide 9 mg will show excellent weight loss efficacy and multiple metabolic benefits as well as good safety in the Phase 3 study, and provide an alternative medical treatment for moderate or severe obesity soon."

About Obesity
China has the largest overweight and obese population in the world, with the obesity rate likely to increase. Obesity can lead to a range of complications or related diseases that impact life expectancy and deteriorate the quality of life. In more severely obese patients, the incidence and mortality of cardiovascular disease, diabetes, and certain tumors increase significantly. Deaths caused by overweight and obesity accounted for 11.1% of deaths related to chronic non-communicable diseases in 2019, showed a significant increase from 5.7% in 1990¹. Obesity is a chronic disease that requires long-term management, and there is a lack of long-term effective and safe treatments. Lifestyle intervention is the first choice and basic treatment for patients with overweight or obesity. However, a considerable percentage of patients fail to achieve the desired weight loss goal upon lifestyle intervention and may require pharmacological intervention. Traditional pharmacological therapies have been of limited efficacy and safety issues, highlighting the unmet need for more effective and safe therapies.

About Mazdutide
Innovent entered into a licensing 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, in addition to the effects of GLP-1 receptor agonists on promoting insulin secretion, lowering blood glucose and reducing body weight, mazdutide may also increase energy expenditure and improve hepatic fat metabolism through the activation of glucagon receptor. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies, as well as reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes and liver fat content, as well as improving insulin sensitivity, bringing multiple metabolic benefits. Currently, three key Phase 3 studies of mazdutide 4 mg and 6 mg in Chinese patients with overweight or obesity (GLORY-1) and type 2 diabetic (DREAMS-1 and DREAMS-2) subjects are underway. The Phase 2 clinical study of mazdutide 9 mg in Chinese patients with obesity is in progress. The Phase 3 clinical study of mazdutide 9 mg in Chinese subjects with obesity will be initiated at the end of 2023.

About Innovent
Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to discover and develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to discovering and developing, manufacturing and commercializing high-quality innovative medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, and ophthalmology diseases to enhance the quality of the patients' lives. Innovent has 10 products in the market, including TYVYT® (Sintilimab Injection), BYVASDA® (Bevacizumab Injection), SULINNO® (Adalimumab Injection), HALPRYZA® (Rituximab Injection), Pemazyre® (Pemigatinib Oral Inhibitor), olverembatinib, Cyramza® (Ramucirumab Injection), Retsevmo® (Selpercatinib Capsules), FUCASO® (Equecabtagene Autoleucel Injection) and SINTBILO® (Tafolecimab Injection). Additionally, 7 assets are in Phase III or pivotal clinical trials, and 17 more molecules are in early clinical stage.

Innovent has also entered into 30 strategic collaborations with Eli Lilly, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. We strive to work with many collaborators to help advance the biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/

Disclaimer:

Innovent does not recommend any off-label usage.

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. The Company 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 the Company 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 the Company'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, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company 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 materialise or turn out to be incorrect.

¹ Institute for Health Metrics and Evaluation. Global Health Data Exchange. GBD results tool. http://ghdx.healthdata.org/gbd-resultstool (accessed Jan 10, 2021).