Innovent Announces Phase Ib Results of Higher-dose Mazdutide (IBI362) in Chinese Participants with Overweight or Obesity Published in eClinicalMedicine

ROCKVILLE, Md. and SUZHOU, China, Oct. 16, 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, metabolic, autoimmune and other major diseases, announced that results of higher-dose cohorts in a phase 1b study of mazdutide (IBI362), a glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, in Chinese participants with overweight or obesity have been published online in eClinicalMedicine (https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00421-7/fulltext). Professor Linong Ji and Professor Leili Gao from Peking University People's Hospital are joint first authors of the article. Professor Linong Ji and Dr. Lei Qian are the corresponding authors.

This randomized, placebo-controlled multiple-ascending-dose study evaluated the safety, tolerability and pharmacokinetics/pharmacodynamics characteristics of mazdutide in Chinese participants with overweight or obesity (NCT04440345). The results of lower-dose (3 mg, 4.5 mg and 6.0 mg) cohorts have been published in eClinicalMedicine in August 2021¹. In higher-dose cohorts, 12 participants in each cohort were randomized 2:1 to receive subcutaneous 2.5-5.0-7.5-10.0 mg (10 mg cohort) or 3.0-6.0-9.0 mg (9 mg cohort) mazdutide or placebo once weekly, with each dose level administered for 4 weeks.

In higher-dose cohorts, mazdutide up-titrated to 10 mg and 9 mg were both well tolerated. No participant discontinued the study due to adverse events. No serious adverse event or severe adverse event was reported. The most-commonly-reported treatment-emergent adverse events were gastrointestinal adverse events, mostly mild in severity. At week 16, the mean reduction (percent reduction) from baseline in body weight was 7.62 kg (9.5%) for participants receiving mazdutide in the 10 mg cohort. At week 12, the mean reduction (percent reduction) from baseline in body weight was 9.23 kg (11.7%) for participants receiving mazdutide in the 9 mg cohort. Improvements in BMI, waist circumference, blood pressure, lipid and serum uric acid were similar with those observed in the low-dose cohorts.

Multiple clinical studies of mazdutide are ongoing, including 1) the higher-dose cohort of a Phase II study of mazdutide in Chinese adults with obesity, with first participant dosing completed in September 2022 and 2) a Phase III clinical study in Chinese adults with overweight or obesity initiated, which received IND approval in October 2022.

Professor Linong Ji the principal investigator of this study, from Peking University People's Hospital, stated: "We are delighted that the results of higher-dose mazdutide in phase 1b study has now been published. Higher-dose mazdutide showed favorable tolerability and safety profiles, as well as rapid and robust body weight loss efficacy, and has the potential to provide patients with severe obesity with treatment options comparable to the efficacy of bariatric surgery. Combined with the results of phase I and phase II studies of lower-dose mazdutide, mazdutide has the potential to become one of the most powerful innovative anti-obesity drugs worldwide. I am very hopeful that mazdutide will achieve a great success in the phase III clinical studies and demonstrate benefit to patients as soon as possible."

Dr. Lei Qian, Vice President of Clinical Development at Innovent, said: "The publication of the Phase I results of mazdutide 9 mg and 10 mg cohorts further reflects the efficiency and translational collaboration between Chinese biopharmaceuticals and academia in early-stage clinical development of innovative metabolic drugs. The results of the higher-dose mazdutide make it the first single-agent anti-obesity drug worldwide to achieve a 12-week body weight loss by more than 11.5%. We are expecting more encouraging results in the ongoing phase II clinical study of mazdutide 9 mg, which will lay a solid foundation for its potential as an alternative therapy of bariatric surgery. Mazdutide phase III studies are in progress and we hope that it may provide brand-new treatment options for Chinese patients who are overweight or obesein the near future."

¹Ji L, Jiang H, An P, et al. (2021) IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. EClinicalMedicine 39: 101088. 10.1016/j.eclinm.2021.101088

China has the largest obese population in the world, with a gradual increasing trend. Obesity can lead to a range of complications or related diseases that impact life expectancy and lead to a decrease in quality of life. In more severely obese patients, the incidence and mortality of cardiovascular disease, diabetes, and certain cancer increase significantly. 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 the most basic treatment for patients with overweight or obesity. However, a considerable number of patients cannot achieve the desired weight loss goal due to various reasons and may use medications. Traditional anti-obesity drugs are associated with limited weight-loss effects and safety concerns.

Innovent entered into a licensing agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as Mazdutide, IBI362 or LY3305677), a dual GLP-1 and glucagon receptor 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 is estimated to improve glucose tolerance and induce 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.

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 34 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 8 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), olverembatinib (BCR ABL TKI), CYRAMZA® (ramucirumab) and selpercatinib, 2 assets under NMPA NDA review, 4 assets in Phase 3 or pivotal clinical trials, and an additional 20 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, 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. 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, Lilly). CYRAMZA® was discovered and developed by Lilly and licensed to Innovent for commercialization in Mainland China.

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.

SOURCE Innovent Biologics