Significant Glycemic Control and Weight Loss: Innovent Announces Phase 2 Study of Mazdutide (IBI362) in Chinese Patients with Type 2 Diabetes Met Primary Endpoint

SAN FRANCISCO and SUZHOU, China, July 18, 2022 /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, autoimmune, metabolic, ophthalmology and other major diseases, announces that the primary endpoint was met in a multi-center, randomized, double-blind, placebo and dulaglutide-controlled phase 2 study of mazdutide (R&D code: IBI362), a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese patients with type 2 diabetes.

This study (ClinicalTrials.gov, NCT04965506) was designed to evaluate the efficacy and safety of mazdutide in Chinese patients with type 2 diabetes inadequately controlled by lifestyle intervention with or without stable metformin for at least 3 months. A total of 252 patients were randomized to receive 3.0 mg, 4.5 mg, 6.0 mg of mazdutide, placebo or dulaglutide 1.5 mg subcutaneously once-weekly for 20 weeks, including a 4 or 8 week' titration period. The primary endpoint was the change from baseline in HbA1c after 20-week treatment compared with placebo. The mean duration of diabetes ranged from 4.0 to 5.7 years and the mean baseline HbA1c ranged from 7.94% to 8.16% across different dose groups.

All doses of mazdutide significantly reduced HbA1c levels, compared with placebo (p < 0.0001 for all comparisons versus placebo). The least squares mean change from baseline to week 20 in HbA1c levels were −1.41% (95%CI：−1.70, −1.13; 3.0 mg), −1.67% (−1.95, −1.39; 4.5 mg), and −1.54% (−1.83, −1.25; 6.0 mg) in the mazdutide groups; −1.35% (−1.63, −1.07) in the dulaglutide 1.5 mg group and 0.03% (−0.25, 0.31) in the placebo group. The proportion of patients with HbA1c less than 7.0% at week 20 were 62.8% (3.0 mg), 74.4% (4.5 mg) and 78.3% (6.0 mg) for mazdutide, 69.8% for dulaglutide 1.5 mg and 20.0% for placebo.

Mazdutide reduced body weight in a dose-dependent manner. The least squares mean percent change from baseline to week 20 in body weight were −7.14% (95% CI: −8.49, −5.79) for mazdutide 6.0 mg (p < 0.0001 versus dulaglutide and placebo), −2.69% (−4.02, −1.37) for dulaglutide 1.5 mg and −1.38% (−2.70, −0.06) for placebo. The proportion of patients achieving HbA1c less than 7.0% and body weight reduction of 5% or more from baseline to week 20 was 52.2% for mazdutide 6.0 mg, 14.0% for dulaglutide 1.5 mg and 0% for placebo.

Meanwhile, mazdutide reduced fasting blood glucose, postprandial blood glucose, blood pressure, low-density lipoprotein cholesterol and triglycerides, and improved insulin sensitivity, providing comprehensive benefits to patients.

Mazdutide was safe and well-tolerated. No patient withdrew prematurely from the study due to an adverse event. No severe hypoglycemia events occurred during the study. The overall safety profile was similar to those observed in early phase development of mazdutide and with other GLP-1-based agonists and co-agonists. The most frequently reported treatment-emergent adverse events included decreased appetite, nausea, vomiting, and diarrhea, mostly mild or moderate in severity and transient.

The data are under further analysis and the results will be presented in peer-reviewed journals.

Professor Wenying Yang, the principal investigator of the study, China Japan Friendship Hospital, stated, "The overall targeted attainment rate of blood glucose in Chinese patients with type 2 diabetes is still low. Patients are often associated with a variety of cardiovascular risk factors, such as obesity, hyperlipidemia, coronary heart disease, fatty liver, gout and other conditions, which not only increase the disease burden, but also add to the difficulty and complexity of treatment. There is an urgent clinical need for efficacious innovative drugs that are also safe, with low hypoglycemic risk, convenient, and can provide cardiovascular benefits. I am pleased to see the exciting phase 2 study results of mazdutide, a novel GLP-1R/GCGR dual agonist, in Chinese patients with type 2 diabetes. Mazdutide demonstrated robust efficacy on both glycemic control and body weight loss, the latter of which is potentially superior to dulaglutide. I look forward to the upcoming phase 3 study and the potential benefits to patients."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "Mazdutide is the first weekly-dosed GLP-1R/GCGR dual agonist with both significant glucose-lowering and body weight loss efficacy. The phase 2 study of mazdutide in Chinese patients with type 2 diabetes met the primary endpoint. The glucose-lowering, weight loss, and multiple metabolic benefits were fully proved, with a good safety profile. This result lays a solid foundation for the upcoming phase 3 study. It is worth noting that we compared the efficacy of mazdutide with dulaglutide (1.5 mg) in this phase 2 study, and obtained encouraging results, reinforcing our strong confidence in mazdutide's potential. After adequate communication with regulatory authorities, we will actively enroll phase 3 study and look forward to potentially providing new options to Chinese physicians and diabetic patients soon."

About Diabetes

The prevalence of diabetes among adults in China is 11.6%, of which type 2 diabetes accounts for about 90% of the total number of diabetic patients, and the number of patients is still increasing. Poor glycemic control will lead to irreversible microvascular and macrovascular complications such as decreased visual acuity, blindness, renal insufficiency, peripheral neuropathy, myocardial infarction, stroke, amputation, etc. As a latent disease with serious complications and high incidence, diabetes mellitus has seriously threatened human health. Currently, there are many treatment options for diabetes, and in addition to effective glycemic control, the development of new hypoglycemic drugs may also provide additional benefits for diabetic patients in terms of weight loss, cardiovascular risk reduction, and renal protection.

About Mazdutide (IBI362)

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. In parallel, Lilly is developing OXM3 outside China. Mazdutide is a long-acting synthetic peptide related to mammalian oxyntomodulin (OXM), which uses a fatty acid side chain to prolong the duration of action and allow once-weekly administration. Mazdutide is thought to exert its biological effects by activating GLP-1 receptor and glucagon receptor in human beings, which improves glucose tolerance and induces weight loss, mimicking the effects of endogenous oxyntomodulin.

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. The treatment of metabolic diseases by activating multiple metabolism-related targets simultaneously is currently the worldwide trend in drug development.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 32 valuable assets in the fields of cancer, autoimmune, metabolic, ophthalmology and other major therapeutic areas, with 7 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor) and olverembatinib (BCR-ABL TKI) and Cyramza® (ramucirumab), 2 asset under NMPA NDA review, 4 assets in Phase 3 or pivotal clinical trials, and an additional 19 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's 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/.

Note:

TYVYT® (sintilimab injection) is not an approved product in the United States.

BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab biosimilar injection, Innovent)

HALPRYZA® (rituximab biosimilar injection, Innovent)

SULINNO® (adalimumab biosimilar injection, Innovent)

Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer:

1. This indication is still under clinical study, which hasn't been approved in China.

2. Innovent does not recommend any off-label usage.

Forward-looking statement

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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.

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