Innovent Showcases Mazdutide and IBI3030 Data at ADA Conference
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New data presented at the American Diabetes Association (ADA) annual Meeting highlights the potential of Innovent’s investigational therapies, mazdutide (IBI362) and IBI3030, in addressing metabolic diseases. Mazdutide,a dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist,demonstrated promising results in reducing liver fat,improving fibrosis,and lowering serum uric acid in preclinical studies.IBI3030, a PCSK9 inhibitor, showed efficacy in reducing LDL-c and lp(a) levels, improving glucose tolerance, reducing body weight, and preserving insulin sensitivity.
The ADA meeting featured investigator-initiated studies (IITs) focusing on mazdutide’s effects. These studies explored the drug’s mechanism of action in reducing liver fat, improving fibrosis, and lowering serum uric acid.
Mazdutide’s Impact on Liver Fat and Fibrosis
One study (Abstract Number: 777-P) compared mazdutide to semaglutide, a GLP-1 receptor agonist, in improving liver fat accumulation in mice. The research, led by Tianpei Hong from Peking University Third Hospital, found that mazdutide treatment predominantly activated oxidative phosphorylation and fatty acid degradation pathways compared to semaglutide. Lipid metabolism-related genes were also upregulated in the mazdutide group. the study identified activating transcription factor 3 (Atf3) as a potential functional transcription factor regulating lipid degradation in the liver.
Another study (Abstract Number: 1616-P), led by Ling Li from Zhongda Hospital, School of Medicine, Southeast University, investigated mazdutide’s effects on MASH (metabolic dysfunction-associated steatohepatitis) and hepatic fibrosis in mice. The results showed that mazdutide decreased body weight, liver weight, and hepatic triglyceride levels.It also mitigated hepatic fat accumulation, inflammation, and hepatic fibrosis compared to single GLP1R or GCGR agonists. The study suggests that mazdutide regulates lipid metabolism and the gut microbiota, potentially offering a novel therapeutic approach for MASH.
“Mazdutide exhibited a better efficacy in weight loss and liver fat accumulation alleviation compared with the GLP-1R agonist semaglutide.”
Mazdutide’s Effect on Hyperuricemia
A third study (Abstract Number: 775-P), led by Hongwei Jiang from The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, examined mazdutide’s impact on hyperuricemia in rats. The study found that mazdutide considerably lowers serum uric acid levels by enhancing fatty acid oxidation and regulating cellular energy metabolism in hepatocytes. This process suppresses the expression of genes associated with glucose and purine metabolism in the liver, reducing the generation and utilization of purine precursors. The study also noted that mazdutide increased the expression of GCGR in hepatocytes, while semaglutide slightly inhibited it. Mazdutide promoted fatty acid oxidation and improved overall energy metabolism, offering more significant benefits in lowering uric acid levels compared to semaglutide.
IBI3030: A Novel Therapeutic Strategy
in addition to mazdutide, Innovent is developing IBI3030 (PCSK9-GGG), a novel modality with a unique mechanism of action. Preclinical studies have demonstrated that IBI3030 significantly reduces LDL-c (p<0.01 vs. baseline) and Lp(a), improves oral glucose tolerance (OGTT), reduces body weight, and preserves insulin sensitivity in multiple models (mice, rats, and non-human primates). It also exhibits excellent safety in non-human primates, with a maximum tolerated dose reaching 50 mg/kg.
Frequently Asked Questions
what is the mechanism of action of mazdutide?
Mazdutide is a dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist. It promotes insulin secretion, lowers blood glucose, reduces body weight, increases energy expenditure, and improves hepatic fat metabolism.
What are the potential benefits of IBI3030?
IBI3030 is a PCSK9 inhibitor that has shown efficacy in reducing LDL-c and Lp(a) levels, improving glucose tolerance, reducing body weight, and preserving insulin sensitivity in preclinical studies.
What is MASH and how does mazdutide help?
MASH (metabolic dysfunction-associated steatohepatitis) is a liver disease characterized by inflammation and liver cell damage caused by a buildup of fat in the liver. Mazdutide has shown promise in mitigating hepatic fat accumulation, inflammation, and hepatic fibrosis in preclinical studies.
By Amelia Hernandez | CITY,STATE — Date
SOURCE: Innovent Data Analysis
