Innovent Biologics announces the publication of the high-dose cohort results of Mazdutide's Phase Ib clinical study in overweight or obese subjects in China, in the Lancet eClinicalMedicine

Innovent Biopharmaceutical Group (HKEx: 01801), a biopharmaceutical company dedicated to the development, production and marketing of innovative drugs for the treatment of major diseases such as tumors, metabolic diseases, autoimmunity, etc.
, announced glucagon-like peptide-1 receptor (GLP-1R)/glucagon receptor, GCGR) dual agonist mazdutide (IBI362) results from a high-dose cohort of a multi-dose phase Ib clinical study in overweight or obese subjects in China were published online in the internationally renowned medical journal eClinicalMedicine (IF: 17.
03) ( PIIS2589-5370(22)00421-7/fulltext）
。 Professor Linong Ji and Professor Leili Gao of Peking University People's Hospital are the co-first authors of the paper, and Professor Linong Ji and Dr.
Qian Lei, Vice President of Innovent Biopharmaceutical Group, are the co-corresponding authors
of the paper.

The study is a randomized, placebo-controlled clinical study (NCT04440345)
to evaluate the safety, tolerability and pharmacokinetic profile of multiple dose escalation doses of Mazdutide in overweight or obese subjects in China.
Low-dose (3 mg, 4.
5 mg, and 6.
0 mg) cohort results were published in eClinicalMedicine in 2021[1].

Results from the high-dose (9 mg and 10 mg) cohorts
are presented this time.
A total of 24 overweight or obese subjects were enrolled in the high-dose cohort, and 12 subjects in each cohort were randomized to receive a mazdutide dose titration of 2.
5-5.
0-7.
5-10.
0 mg or 3.
0-6.
0-9.
0 mg in a 2:1 ratio or placebo, administered subcutaneously once a week for 4 weeks
at each dose level.

The results of the study showed that Mazdutide titrated to 10 mg and 9 mg was well tolerated, and no participants withdrew from the study
due to adverse events.
No serious adverse events or severe adverse events
occurred.
The most commonly reported adverse events during the treatment period were gastrointestinal adverse events, the vast majority of which were mild
.
After 16 weeks of dosing, subjects treated with Mazdutide in the 10 mg cohort lost an average of 7.
62 kg from baseline (9.
5% reduction); After 12 weeks of dosing, subjects treated with Mazdutide in the 9 mg cohort lost an average of 9.
23 kg (11.
7% decrease)
from baseline.
Improvements in BMI and waist circumference, as well as metabolic markers such as blood pressure, lipids, and blood uric acid, in subjects treated with mazdutide were consistent
with trends observed in low-dose cohorts.

At present, there are several clinical studies underway in mazdutide, including 1) the high-dose cohort of phase II clinical studies in obese subjects in China has completed the dosing of the first subject in September 2022, and 2) the phase III clinical study in overweight or obese subjects in China was approved for IND official launch
in October 2022.

Professor Ji Linong of Peking University People's Hospital, the principal investigator of the study, said: "I am very pleased to see the successful publication
of the phase I study results of high-dose mazdutide.
High-dose mazdutide has demonstrated good tolerability and safety in phase I studies, as well as rapid and robust weight-loss efficacy, promising treatment options
comparable to bariatric surgery for severely obese patients.
Combined with the results of phase I and phase II studies of low-dose mazdutide, mazdutide has become one of
the most promising innovative weight loss drugs in the world.
I am very confident that mazdutide will succeed in phase III clinical studies and benefit overweight and obese patients
as soon as possible.
" "

Dr.
Qian Lei, Vice President of Clinical Development at Innovent Biologics, said: "The publication of the Phase I study results of the Mazdutide 9 mg and 10 mg cohorts further demonstrates the efficient translation and collaboration capabilities
of Chinese academia and industry in the early stage of drug development in the field of metabolism 。 The high-dose Phase I results of Mazdutide make it the world's first weight loss monotherapy with a weight loss of more than 11.
5% within 12 weeks of administration, and we are very confident that we can observe more encouraging efficacy in the ongoing 9 mg Phase II study, laying a good foundation
for its potential alternative to metabolic surgery.
" At the same time, the phase III study of mazdutide has been fully launched, and it is expected to provide new treatment options
for overweight and obese patients in China in the near future.
"

[1] Ji 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

About obesity

China is the country with the largest obese population in the world, and it is gradually rising
.
Obesity can lead to a range of complications or related diseases that can affect life expectancy or lead to a reduced
quality of life.
In more severe obese patients, the incidence and mortality of cardiovascular disease, diabetes and certain tumors have increased
significantly.
Obesity is a chronic disease that requires long-term treatment, and there is currently a lack of long-term effective and safe treatment
.
Lifestyle intervention is the first choice and basic treatment for overweight or obese patients, but there are still a considerable number of patients who cannot achieve the desired weight loss goal for various reasons and need to use drugs to assist weight
loss.
Traditional weight loss drugs have limited effect and have safety problems
.

About Mazdutide

Mazdutide is an innovative compound of gastric acid modulator (OXM3) jointly promoted by Innovent Biologics and Eli Lilly, which is a GLP-1R and GCGR double agonist
with best-in-class potential.
As a long-acting synthetic peptide similar to mammalian gastric acid regulators, Mazdutide uses fatty acyl side chains to prolong the duration of action, allowing weekly
administration.
The effect of Mazdutide is thought to be mediated by binding and activation of GLP-1R and GCGR and has a similar mechanism of action to OXM, so it is expected to improve glucose tolerance and reduce body weight
.
In addition to GLP-1R agonists promoting insulin secretion, lowering blood sugar and reducing weight, mazdutide may also have effects
such as increasing energy expenditure and improving liver fat metabolism through the activation of GCGR.
The treatment of metabolic diseases by developing multiple metabolically related targets at the same time is the latest trend in the development of new drugs in the world