Nearly 20 GLP-1-Based Multi-Target Therapeutics from Chinese Pharma Giants Including Hengrui, Innovent, and Huadong Medicine Enter Clinical Development

▎Edited by the WuXi AppTec content team

Recently, Eli Lilly and Company's tirzepatide injection in ChinaApproved for Marketing, attracting widespread attention in the industry. As aGIP/GLP-1 Receptor Dual Agonist，Tirzepatide in Type 2 Diabetes, Weight Loss, andMetabolic Dysfunction-Associated Steatohepatitis (MASH, formerly known as NASH), obstructive sleep apnea and other indications have already shown promising clinical application potential.

In recent years, GLP-1 receptor agonists have continued to achieve breakthroughs. At the same time, the exploration of GLP-1 dual-target and triple-target new drugs has gradually attracted widespread attention. These new drugs have shown encouraging application potential in multiple therapeutic areas. According to publicly available information,Recently20A GLP-1 dual or triple agonist new drug developed by a Chinese company has also entered the clinical development stage.In this article, we will introduce these new drugs based on publicly available information, examine their highlights, and explore which patients they are expected to benefit.

Clinical-stage GLP-1 class multi-target new drugs partially developed by Chinese companies

GIPR/GLP-1R Dual-Target New Drug

Glucose-Dependent Insulinotropic Polypeptide (GIP)It is an incretin that can supplement the action of GLP-1 receptor agonists. Studies have shown that GIP can reduce food intake and increase energy expenditure, thereby reducing body weight. When combined with GLP-1 receptor agonists, it may have a greater impact on glucose levels and body weight.

According to the China Drug Clinical Trial Registration and Information Disclosure Platform and publicly available data, at least nine GIPR/GLP-1R dual-target new drugs independently developed or co-developed through acquired rights by Chinese companies have entered the clinical research stage.These products, which are respectively from Hengrui Pharma, Zhongsheng Pharmaceutical, CQP, and Hansoh Pharma, among others, have indications under development that coverType 2 Diabetes, Overweight or Obesity, MASH。

Among them, the product with relatively faster progress is HRS9531 Injection developed by Hengrui Pharma. This is aPeptide GIPR and GLP-1R dual agonist,Has entered the Phase 3 clinical research stage in China for the treatment of overweight or obesity. Hengrui Pharma has also developed this product.OralTablet dosage form,Recently approved for clinical use in China. Notably, on May 16 this year, Hengrui Pharma reached an agreement worth over $6 billion with U.S.-based Hercules Pharmaceuticals.CooperationThe latter will obtain exclusive rights to develop, manufacture, and commercialize the GLP-1 portfolio globally, excluding Greater China, which includes HRS9531 injection and oral products.

GCGR/GLP-1R Dual Agonist

Glucagon (GCG) can increase energy expenditure and promote the conversion of white fat, which stores energy in the body, into brown fat that consumes energy. It synergizes with GLP-1 to promote more effective weight loss than GLP-1 receptor agonist monotherapy.

Public information shows that at least four GCGR/GLP-1R dual-target new drugs developed by Chinese companies have entered the clinical research stage, with proposed indications coveringOverweight/Obesity, Type 2 Diabetes, Liver Fibrosis, NASH, etc.Among the products with relatively rapid progress, Mastytide, jointly developed by Innovent Bio and Eli Lilly, has already been submitted in China for the weight loss indication.Marketing Application。In May this year, Innovent Bio announced that the product had been tested on Chinese subjects with type 2 diabetes.Phase 3 ClinicalThe study also met the primary endpoint, with the potential to file for a new indication marketing application by mid-year.

PegBioPB-718, a GCGR/GLP-1R dual agonist under development, has completed Phase 1 clinical research. This product is mainly developed for the treatment of obesity and MASH. In February this year, PegBio submitted documents to the Hong Kong Stock Exchange.IPOApplication. According to the prospectus, PegBio expects to complete the Phase 1b/2a clinical study of PB-718 in China in the second quarter of 2024.

In addition,Shenzhen Tuwei Anchuang Technology Development Co., Ltd.The polypeptide GLP-1R/GCGR dual agonist TB001 is currently being targetedChronic Hepatitis B with Liver FibrosisConduct Phase 2 clinical research;Tianjin Institute of Pharmaceutical ResearchTY751 Injection, a self-developed peptide-based GLP-1R/GCGR dual agonist, has also been approved for clinical trials in China this February and is intended to be developed for type 2 diabetes.

FGF21/GLP-1R Dual Agonist

Fibroblast Growth Factor 21 (FGF21) is an endogenous metabolic hormone that regulates energy expenditure as well as glucose and lipid metabolism. Public data shows,FGF21 is mainly expressed in the liver and is an important target for MASH treatment, playing a key role in glucose and lipid metabolism regulation.FGF21/GLP-1R Dual AgonistExpected to produce synergistic effects of blood sugar reduction and weight loss.

Currently,HEC CJ PHARM's Self-Developed Fc Fusion ProteinFGF21/GLP1R Dual AgonistHEC88473 is currently in Phase 2 clinical trials for type 2 diabetes. The product is also being developed for indications including non-alcoholic steatohepatitis (NASH), obesity, and others.CHIATAI TIANQINGAP026 (TQA2226), currently under development, is also a novel FGF21/GLP-1R bifunctional protein drug, and is undergoing Phase 1 clinical trials in China.

Image Source: 123RF

GLP-1 Triple-Agonist New Drug

In addition to the aforementioned GLP-1 dual-target new drugs, several Chinese companies are also developing GLP-1 class triple-target innovative drugs. Among them, Minwei BiotechnologyGCGR/GIPR/GLP1R Triple AgonistMWN101 Injection is currently in Phase 2 clinical trials for type 2 diabetes, obesity, or overweight. The injection is independently developed by Federal Pharmaceutical.Long-acting GLP-1/GIP/GCG Triple Receptor AgonistUBT251 Injection is currently in Phase 1b clinical trials. In terms of mechanism of action, the triple targets GCGR/GIPR/GLP1R exhibit synergistic effects. For instance, GIP can complement the action of GLP-1 receptor agonists and promote GCG secretion to raise blood glucose levels under hypoglycemic conditions, significantly reducing the risk of hypoglycemia.

In addition, Doer Biologics, a subsidiary of Huadong Medicine, is currently developingLong-acting FGF21/GCGR/GLP1R Tri-agonistDR10624, and is currently conducting a Phase 1 clinical study for weight management in overweight or obese populations. According to a previous press release by Doer Biologics, DR10624 is an Fc fusion protein drug that exerts a synergistic effect by simultaneously modulating three receptor-mediated signaling pathways, thereby achieving the effects of lowering blood sugar, reducing weight, and decreasing lipid levels.

We hope that the subsequent clinical trials of these drugs under research will proceed smoothly, achieve further breakthroughs as soon as possible, and bring better treatment options to patients.

Related Reading:

• Overview of Phase 3 Clinical Trials for China's GLP-1 "Weight Loss" New Drugs

[2] Official websites of various companies and publicly available information