Preclinical Study Results Show Potential Effect of GLP-1R/GCGR Dual Agonist Mazdutide (IBI362) in Reducing Serum Uric Acid Levels

Recently, the results of the preclinical study on the reduction of serum uric acid level by mazdutide were published in a Late-breaking abstract (# 77-LB) at the American Diabetes Association's® 83rd Scientific Sessions as one of the 20 Chinese preclinical studies selected for presentation. Professor Hongwei Jiang, the principal investigator from Department of Endocrinology, the First Affiliated Hospital of Henan University of Science and Technology, initiated this study to explore the potential effect of mazdutide on decreasing serum uric acid levels. Hyperuricemia model was established in 12-week-old male rats, and the rats were divided into control group, disease group, treatment groups with subcutaneous injection of mazdutide (low-, medium- and high-dose groups (0.025 mg/kg, 0.05 mg/kg and 0.075 mg/kg), treatment group with subcutaneous injection of semaglutide 0.05 mg/kg and treatment group with intragastric administration of allopurinol 25 mg/kg. Biochemical indicators such as serum uric acid, serum creatinine and blood urea nitrogen as well as oxidative stress and renal pathological indicators were observed after 18 days of administration. The results of the study showed that mazdutide statistically significantly reduced serum uric acid levels compared to semaglutide in the hyperuricemia model. Mazdutide, at all 3 administered doses, demonstrated a reduction of approximately 50% in serum uric acid levels compared to the hyperuricemia group. As a positive control, allopurinol exhibited a similar decrease in serum uric acid levels, while a comparable dose of semaglutide did not alleviate hyperuricemia compared to the disease group. Treatment with mazdutide and allopurinol also significantly reduced serum creatinine and blood urea nitrogen levels compared to the hyperuricemia group, whereas semaglutide treatment did not show such reductions. Besides, oxidative stress and renal pathological indicators were also improved in mazdutide groups, which needs verification in further studies. This study preliminarily demonstrates the regulation of serum uric acid by mazdutide in the animal model, which may be related to glucagon receptor (GCGR) agonism. The mechanism of the reduction of serum uric acid by mazdutide remains to be explored in further research. Abstract link The Principal Investigator of this Study, Professor Hongwei Jiang of the First Affiliated Hospital of Henan University of Science and Technology, stated, “In clinical trials, we found that mazdutide can potentially reduce serum uric acid levels in participants. Therefore, we designed this preclinical study to evaluate the effect of mazdutide on uric acid and related metabolic markers. The results showed that in the rat model of hyperuricemia, mazdutide decreased the level of serum uric acid with improvement of oxidative stress indicators, suggesting that mazdutide may potentially regulate uric acid metabolism. We will continue to explore the specific mechanism of action of mazdutide in reducing uric acid levels, and look forward to verifying the efficacy of mazdutide in improving uric acid metabolism in future clinical trials.” Dr. Lei Qian, Vice President of Innovent, stated, “In phase I and phase II clinical studies, mazdutide has demonstrated excellent weight loss and glucose-lowering efficacy, and simultaneously brings multiple benefits to patients in cardiovascular metabolic indicators such as blood pressure, blood lipids, liver enzymes and serum uric acid. This preclinical study serves as an exploration of the effect and mechanism of mazdutide on the regulation of uric acid, and the results suggest that mazdutide has potentially differentiating efficacy compared with other GLP-1 drugs. We look forward to collaborating with more experts in the field of endocrinology and metabolism to further reveal the role and mechanism of metabolism regulation by mazdutide, and provide comprehensive theoretical support for the clinical development of mazdutide.” About Mazdutide（IBI362） Innovent entered into a licensing agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of 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 (DREAM-1 and DREAM-2) subjects are underway. The Phase 2 clinical study of mazdutide 9 mg in Chinese patients with obesity is in progress. 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 disease, metabolic disorder 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 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 9 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab injection), SULINNO® (adalimumab injection), HALPRYZA® (rituximab injection), Pemazyre® (pemigatinib oral inhibitor), olverembatinib(BCR ABL TKI), Cyramza® (ramucirumab), Retsevmo® (selpercatinib) and FUCASO® (Equecabtagene Autoleucel). An additional 2 assets are under NMPA NDA review, 6 assets are in Phase III or pivotal clinical trials, and 18 more molecules are 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, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center 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. Disclaimer: Innovent does not recommend any off-label usage. 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. Retsevmo® (selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Forward-Looking Statements 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. Contact: Media: [email protected] +86 512-6956 6088 Investors: [email protected] +86 512-6956 6088

The release as fetched from its publisher. innoventbio.com ↗