Significant Weight Loss and Multiple Metabolic Benefits: Phase 1b Study Results of IBI362 in Chinese Participants with Overweight or Obesity Published in EClinicalMedicine by the Lancet

SAN FRANCISCO and SUZHOU,China,Aug. 18,2021 --Innovent Biologics,Inc. ("Innovent") (HKEX: 01801),a world-class biopharmaceutical company that develops,manufactures and commercializes high quality medicines for the treatment of cancer,metabolic,autoimmune and other major diseases,today announced that phase 1b study results of IBI362,a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist,in Chinese participants with overweight or obesity have been published in EClinicalMedicine by the Lancet. This is the first time that a phase 1 clinical study results of an innovative drug in the field of metabolism developed in China were published in the Lancet journals. Professor Linong Ji from Peking University People's Hospital and Professor Hongwei Jiang from Henan University of Science and Technology the First Affiliated Hospital are joint first authors of the article,and Professor Linong Ji is also the corresponding author.

Led by Professor Linong Ji,this is the first clinical study to assess the safety and efficacy of a weekly dose GLP-1R and GCGR dual agonist in Chinese adults. Apart from achieving significant weight loss,IBI362 confers multiple metabolic benefits on blood pressure,lipids,hepatic enzymes and serum uric acid.

Professor Linong Ji stated,"It is exciting to see the results of the first study of IBI362 in Chinese adults with overweight or obesity published in EClinicalMedicine. It is a monumental moment because this is the first time that a phase 1 clinical study results of an innovative drug in the field of metabolism in China got published in the Lancet journals. It reflects the cutting-edge science and novelty of the study design,as well as the expertise of researchers in the field of endocrine and metabolism in China on translational medicine and early clinical development,representing a milestone in the field of metabolic innovative drugs development in China. In this phase 1 clinical study,IBI362 showed a favorable safety profile and robust efficacy,including weight loss and multiple metabolic benefits,underlying the advantages and potential of IBI362 as a new generation GLP-1 based drug. We believe that through the efforts of investigators and close cooperation with the sponsor,IBI362 will demonstrate promising efficacy as a multi-target innovative drug in the subsequent phase 2 clinical study in participants with overweight or obesity."

Dr. Lei Qian,Executive Director of Medical Sciences and Strategies of Special Diseases of Innovent,stated,"The publication of the phase 1b study results of IBI362 in overweight or obese people in EClinicalMedicine achieved a breakthrough in publishing phase 1 studies of innovative drugs in high-impact medical journals in the field of obesity in China,reflecting the scientific excellence of our investigators and the solid clinical R & D ability of Innovent. IBI362 demonstrated weight loss of best-in-class potential,as well as comprehensive metabolic benefits including blood pressure,blood lipids,and liver enzymes. In addition,our further analysis found that IBI362 significantly reduced serum uric acid levels in obese subjects. To the best of our knowledge this is the first clinical evidence that a GLP-1R agonist induced a significant reduction in serum uric acid level in early clinical studies. We are very confident that through solid clinical research and scientific development,we will provide better treatment options for obese patients as early as possible."

About the Study

Background

IBI362(LY3305677) is a novel weekly-dose glucagon-like peptide-1 and glucagon receptor dual agonist being developed for the treatment of obesity and type 2 diabetes. The aim of this randomised,placebo-controlled,multiple ascending dose phase 1b study was to evaluate the safety,tolerability,pharmacokinetics and efficacy of IBI362 in Chinese adults with overweight or obesity.

Methods

This study enrolled adults with overweight (body mass index[BMI]≥24 kg/m2) accompanied by hyperphagia and/or at least one comorbidity or obesity (BMI≥28 kg/m2) from six study centers in China. Eligible participants were randomised 2:1 to receive once-weekly subcutaneous injection of IBI362 or placebo in each of the three ascending dose cohorts for 12 weeks with additional 8 weeks of safety follow-up. The dose-escalation regimens were: 3.0 mg cohort (1 mg weeks 1-4; 2.0 mg weeks 5-8; 3.0 mg weeks 9-12); 4.5 mg cohort (1.5 mg weeks 1-4; 3.0 mg weeks 5-8; 4.5 mg weeks 9-12); 6.0 mg cohort (2.0 mg weeks 1-4; 4.0 mg weeks 5-8; 6.0 mg weeks 9-12). The participants,investigators and study site personnel involved in treating and assessing participants within each cohort were masked to treatment allocation. The primary endpoint was safety and tolerability of IBI362. The secondary endpoints included pharmacokinetics and pharmacodynamics,as well as body weight,waist circumference,BMI,blood pressure and lipid levels changes from baseline. This study is registered with ClinicalTrials.gov,number NCT04440345.

Findings

Between June 15th,2020 and January 15th,2021,12 participants were enrolled and randomised in each cohort. Throughout the study,no participant discontinued the treatment due to safety reason and no serious adverse event was reported. Gastrointestinal adverse events and decreased appetite were the most common adverse events and mostly mild in severity. Three participants receiving IBI362 reported mild and asymptomatic cardiac disorders revealed by electrocardiogram. Estimated percentage changes in mean body weight from baseline to week 12 were −4.81% (95%CI −6.61 to −3.02),−6.40% (−8.23 to −4.58) and −6.05% (−7.91 to −4.18) for participants receiving IBI362 in the 3.0 mg,4.5 mg and 6.0 mg cohort,respectively,compared with 0.60% (−0.86 to 2.07) for those receiving placebo. Waist circumference,blood pressure,cholesterol and triglycerides also improved with IBI362.

Figure 1: Percent changes from baseline in body weight (CFB = change from baseline; LS = least squares; CI = confidence interval)[1]

Conclusions

IBI362 was well tolerated and showed a robust body weight-lowering effect and improved metabolic profiles in Chinese adults with overweight or obesity.

Link to the publication in EclinicalMedicine:

https://doi.org/10.1016/j.eclinm.2021.101088

About Obesity

China has the largest obese population in the world,with obesity rate likely to increase. Obesity can lead to a range of complications or related diseases that impact life expectancy or lead to a decrease in quality of life. In more severely obese patients,the incidence and mortality of cardiovascular disease,diabetes,and certain tumors 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 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 due to various reasons and may require pharmacological intervention. Traditional anti-obesity drugs have limited weight-loss effects and are associated with safety issues.

About IBI362

Innovent entered into a licensing agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3,a dual GCGR and GLP-1R agonist,in China (IBI362). In parallel,Lilly is developing OXM3 outside China. IBI362 is a synthetic long-acting mammalian oxyntomodulin analog (OXM3) and is a GLP-1R and GCGR dual agonist with best-in-class potential. IBI362 utilizes a fatty acyl side chain to prolong the duration of action,allowing once-weekly dosing. As an OXM analog,the effects of IBI362 are thought to be mediated through the binding and activation of GLP-1R and GCGR. In addition to the effects of GLP-1R agonists on promoting insulin secretion,lowering blood glucose and reducing body weight,IBI362 may also increase energy expenditure and improve hepatic fat metabolism through the activation of GCGR. 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 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 25 valuable assets in the fields of cancer,autoimmune disease and other major therapeutic areas,with 5 products – TYVYT® (sintilimab injection),BYVASDA® (bevacizumab biosimilar injection),SULINNO® (adalimumab biosimilar injection),HALPRYZA® (rituximab biosimilar injection) and Pemazyre® (pemigatinib oral inhibitor) – officially approved for marketing,1 asset's NDA under NMPA review,sintilimab's Biologics License Application (BLA) acceptance in the U.S.,5 assets in Phase 3 or pivotal clinical trials,and an additional 14 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.

Note:

Sintilimab is not an approved product in the United States.

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

TYVYT® (sintilimab injection,Innovent)

BYVASDA® (bevacizumab 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.

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[1]Reprinted from EClinicalMedicine,https://doi.org/10.1016/j.eclinm.2021.101088,Linong Ji,Hongwei Jiang,Pei An,Huan Deng，Meng Liu,Li Li,Liqi Feng,Baili Song,Han Han-Zhang,Qingyang Ma,Lei Qian,IBI362 (LY3305677),a weekly-dose GLP-1 and glucagon receptor dual agonist,in Chinese adults with overweight or obesity: A randomised,multiple ascending dose phase 1b study