Multiple Research Results from Innovent's General Biomedicine Pipeline to be Showcased at the ADA 85th Scientific Sessions

SAN FRANCISCO and SUZHOU, China, June 22, 2025 /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, autoimmune, cardiovascular and metabolic, ophthalmology and other major disease areas, announced that multiple exploratory mechanism-of-action (MoA) analyses of mazdutide (investigator-initiated trials) as well as a preclinical study of IBI3030 (PCSK9-GGG antibody-peptide-conjugate) will be showcased at the American Diabetes Association's (ADA) 85th Scientific Sessions. Details are listed below：

Title: A novel antibody-peptide conjugate targeting PCSK9, GLP-1R, GCGR, GIPR improves cardiovascular risk markers in preclinical study
Abstract Number：1886-LB
Presentation Form: Poster
Presentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M.

CDT
Location: Poster Hall (Hall F1)
Author: Dr. Decheng Ren, Innovent Biologics

IBI3030 is a novel anti-PCSK9 antibody conjugated with peptides targeting GLP-1R, GCGR, and GIPR. Through multi-target synergistic effects, it significantly improves cardiovascular metabolic risk indicators. Mechanistically, the anti-PCSK9 antibody component inhibits LDL receptor degradation, thereby lowering reduce plasma LDL-c levels. Simultaneously, the triple-target agonist peptide activates GLP-1R/GCGR/GIPR receptors, enhancing hepatic fatty acid oxidation capacity, with demonstrates superior efficacy compared to the control.

Preclinical studies demonstrate that in multiple models (mice, rats, and non-human primates), IBI3030 significantly reduces LDL-c (p<0.01 vs. baseline) and Lp(a), improves oral glucose tolerance (OGTT) (effective even in GLP-1R knockout mice), reduces body weight, and preserves insulin sensitivity. Additionally, it exhibits excellent safety in non-human primates, with a maximum tolerated dose reaching 50 mg/kg.

Furthermore, mazdutide, the fastest-developing dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist globally, has ignited significant research interest in the scientific community due to its comprehensive metabolic benefits. This year's ADA Annual Meeting featured multiple MoA studies on mazdutide's effects in reducing liver fat, improving fibrosis, and lowering serum uric acid. The following are investigator-initiated studies:

Topic: The Dual Glucagon and Glucagon-Like Peptide 1 Receptor Agonist Mazdutide Outbalanced Glucagon-Like Peptide 1 Receptor Agonist Semaglutide Monotherapy in Improving Mice Liver Fat Accumulation
Abstract Number: 777-P
Presentation Form: Poster
Presentation Time: Sunday, June 22, 2025.

12:30 P.M. - 1:30 P.M. CDT
Location: Poster Hall (Hall F1)
Author: Tianpei Hong, Peking University Third Hospital

Liver RNA-sequencing and KEGG enrichment analysis showed that compared with Semaglutide treatment, Mazdutide treatment predominantly activated oxidative phosphorylation and fatty acid degradation pathways. Meanwhile, lipid metabolism-related genes were upregulated in Mazdutide group compared to Semaglutide group. We further screened differentially expressed transcription factors (TF) through the TRRUST database and found that activating transcription factor 3 (Atf3) upregulated in the Mazdutide treatment group might be the functional TF regulating lipid degradation in the liver.

The dual GCGR/GLP-1R agonist mazdutide exhibited a better efficacy in weight loss and liver fat accumulation alleviation compared with the GLP-1R agonist semaglutide monotherapy potentially due to its promotion of fatty acid oxidation via transcription factor ATF3.

Topic: Mazdutide，a GCG/GLP-1R dual-agonist, alleviates MASH and hepatic fibrosis
Abstract Number: 1616-P
Presentation Form：Poster
Presentation Time: Sunday, June 22, 2025. 12:30 P.M. - 1:30 P.M. CDT
Location: Poster Hall (Hall F1)
Author: Ling Li, Zhongda Hospital, School of Medicine, Southeast University,

With the mice presented NASH and fibrosis phenotypes, Mazdutide decreased body weight, liver weight and hepatic triglyceride levels. Notably, Mazdutide also mitigated hepatic fat accumulation, inflammation, and hepatic fibrosis, compared with a single GLP1R or GCGR agonist.

Therefore, Mazdutide alleviates hepatic fibrosis in MASH mice and regulates lipid metabolism as well as the gut microbiota, which may contribute to providing a novel therapeutic method and therapeutic target for MASH

Topic: Mazdutide, a Dual GLP-1R/GCGR Agonist, Alleviates Hyperuricemia by Modulating Hepatic Energy and Lipid Metabolism and Inhibiting Purine Pathways
Abstract Number: 775-P
Presentation Form: Poster
Presentation Time: Sunday, June 22, 2025. 12:30 P.M.- 1:30 P.M. CDT
Location: Poster Hall (Hall F1)
Author: Hongwei Jiang, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology

Mazdutide significantly lowers serum uric acid levels in hyperuricemic rats, primarily by enhancing fatty acid oxidation and regulating cellular energy metabolism within hepatocytes. This process suppresses the expression of genes associated with glucose and purine metabolism in the liver, leading to a reduction in the generation and utilization of purine precursors. SnRNA-Seq analysis indicates that mazdutide increases the expression of GCGR in hepatocytes, whereas semaglutide slightly inhibits it.

In hyperuricemic rats, the expression of key genes involved in fatty acid oxidation, such as Cpt1a, Fabp1, Apoa1, Acox1, and Acaa1a is significantly reduced. However following Mazdutide treatment, the expression of these genes markedly increases, promoting fatty acid oxidation and improving overall energy metabolism. In contrast, genes associated with fatty acid synthesis, such as Acaca and Fasn, show a significant reduction in expression. Furthermore, after Mazdutide intervention, the expression of genes related to glucose metabolism and purine metabolism, including Pklr, G6pc1, Glul, Gckr, Gk, Nt5e, and Ppat, also experience significant decreases. This shift may reflect a change in cellular metabolism towards more efficient fatty acid oxidation, resulting in reduced the generation and utilization of purine precursors. Compared to Semaglutide, Mazdutide offers more substantial benefits in lowering uric acid levels.

Dr.

Lei Qian from Innovent Biologics, stated, "We are delighted to see mazdutide's mechanism exploration studies featured extensively at the ADA conference. The growing body of scientific evidence will further validate mazdutide's differentiated profile as a next-generation GCG/GLP-1 dual receptor agonist, particularly in liver fat and serum urine reduction. Moreover, in the field of cardiovascular and metabolic diseases, Innovent is dedicated to developing next-generation innovative therapies. This includes IBI3030 (PCSK9-GGG), a novel modality with a unique MoA that embodies an innovative 'one-drug, multiple-effects' therapeutic strategy. IBI3030 has the potential to deliver comprehensive therapeutic benefits and meaningfully improve outcomes for more patients worldwide."

*Poster 2-4 are results from investigator-initiated trials (IITs)

About Mazdutide (IBI362)

Innovent entered into an exclusive license 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, mazdutide may offer additional benefits beyond those of GLP-1 receptor agonists—such as promoting insulin secretion, lowering blood glucose and reducing body weight—by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies. It has also shown benefits in reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, as well as improving insulin sensitivity.

Currently, Mazdutide has two NDAs accepted for review by NMPA, including for:

• Long-term weight management in adults with obesity or overweight.
• Glycemic control in adults with type 2 diabetes (T2D).

Mazdutide is currently being evaluated in seven Phase 3 clinical studies, including:

• GLORY-1: A Phase 3 trial in Chinese participants with overweight or obesity.
• GLORY-2: A Phase 3 trial in Chinese participants with moderate-to-severe obesity.
• GLORY-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with overweight/obesity and metabolic dysfunction-associated fatty liver disease (MAFLD).
• GLORY-OSA: A Phase 3 trial in Chinese participants with obstructive sleep apnea (OSA) and obesity.
• DREAMS-1: A Phase 3 trial in treatment-naïve Chinese participants with T2D.
• DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese T2D participants with inadequate glycemic control on oral antidiabetic drugs.
• DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with T2D and obesity.

Among these, GLORY-1, DREAMS-1, and DREAMS-2 have already met their primary endpoints and the other four studies are currently ongoing.

In addition, several new clinical studies of mazdutide are initiated or planned, including:

• A Phase 3 trial in adolescents with obesity.
• New studies in metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF).

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases.

Innovent has launched [15/16] products in the market. It has [3/2] new drug applications under regulatory review, 4 assets in Phase 3 or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).

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