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Scientists discover the beneficial effects of a novel FGF21 analog B1344 on nonalcoholic steatohepatitis in nonhuman primates

2020-05-15
11431
Kunming, China, May 15, 2020

Today KBI announce that The effects of B1344, a novel fibroblast growth factor 21 analog, on nonalcoholic steatohepatitis in nonhuman primates published in the prestigious journal DIABETES, Dr. Shaohui Ji, scientist form Kunming Biomed International as the co-first author.
 
Nonalcoholic steatohepatitis (NASH) is associated with increased incidence of cirrhosis, hepatocellular carcinoma and cardiovascular disease. There are currently no approved medications for treating nonalcoholic fatty liver disease (NAFLD) and NASH. Fibroblast growth factor 21 (FGF21) is an important metabolic regulator, and has shown beneficial effects on the improvement of NAFLD and NASH. However, due to the short half-life in vivo, the development of wild-type FGF21 as a drug is challenging. B1344 is developed as a site-specific PEGylated human FGF21 analog. The reengineering of FGF21 leads to significantly improved biopharmaceutical properties, extended half-life and pharmacokinetics, and reduced immunogenicity.


In collaboration with Professor MA Xiaohui at Tasly Pharmaceutical Co. Ltd and scientists at Kunming Biomed International (KBI), a team of scientists led by Professor LI Yu from Shanghai Institute of Nutrition and Health, CAS demonstrate that in L6 myoblasts with the overexpression of βKlotho/FGFR1c, B1344 was sufficient to activate βKlotho/FGFR1c signaling and appears to show stronger potency in terms of the activation of downstream signaling than that of wild-type FGF21. Moreover, using high-fat diet-fed cynomolgus monkeys and methionine- and choline-deficient diet-induced mice of NASH models, scientists demonstrated the salutary effects of B1344 on the protection against the progression of nonalcoholic steatohepatitis. In the cynomolgus monkeys with NAFLD, administration of B1344 for 11 weeks caused a remarkable reduction of hepatic fat content, inflammation and fibrosis as evidenced by magnetic resonance imaging and histological analysis of the liver biopsy. Meanwhile, the metabolic benefits of B1344 on lowering body weight, blood glucose, glucose tolerance and improving plasma lipid profile were observed in the monkey, whereas no obvious changes of the bone mineral density were observed. Consistently with the monkey data, the anti-NASH effects were also observed in choline-deficient diet-induced rodent model.


This study provides preclinical validation for an innovative therapeutics to NAFLD, and support further clinical testing of B1344 for treating nonalcoholic steatohepatitis and other metabolic diseases in humans.


This work was published online in Diabetes on April 30, 2020, DOI:10.2337/db20-0209 as a research article entitled “The effects of B1344, a novel fibroblast growth factor 21 analog, on nonalcoholic steatohepatitis in nonhuman primates”.


“This reflects the fact that KBI emphasizes science and promotes value-driven CRO services to our partners from both industry and academia”, commented from Bob Zhang, CEO of KBI. “In addition to NASH model in NHPs, KBI’s other human disease-like animal models including obesity, diabetes, diabetic complications such as heart failure, kidney diseases and retinal eye diseases have also provided tremendous values to our worldwide collaborators in facilitating their R&D programs. KBI commits to the continuous investment and development of pharmacology models and technology platforms based on our deep scientific understanding of NHP models and collective expertise from our strategic partners and consultants”, further commented from Dr. Zhang.


Related website: https://diabetes.diabetesjournals.org/content/early/2020/04/30/db20-0209.long

 

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