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DT-109 significantly prevents progression of diet-induced non-alcoholic fatty liver disease

December 4, 2020

Rom et al report today that the oral administration of the simple tri-peptide, DT-109 (Patent US8664177B2), prevents both development of non-alcoholic fatty liver disease (NAFLD) and late stage fibrosis in a murine model of diet-induced non-alcoholic steatohepatitis (NASH). The study titled, “Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome” was published in Science Translational Medicine on December 2, 2020.


About DT-109 Development for Human NASH


DT-109 is a 3 amino acid, orally active peptide, that stimulates release of intestinal GLP-1. Dr. Eugene Chen and his team at the University of Michigan identified DT-109 as having dual glucose/lipid-lowering effects and potently lowering steatohepatitis and fibrosis in a long-term pre-clinical NASH model. Applying advanced multi-omics approaches, the team identified underlying mechanisms by which DT-109 protects against NAFLD. These included modulation of the gut microbiome, stimulation of lipid utilization in the liver and the production of one of the most protective antioxidants, glutathione.


Dr. Oren Rom, the study lead author stated “We thought outside the box and focused on understudied aspects linking dysregulated amino acid metabolism to NAFLD. Our studies not only provided metabolic explanations for impaired glycine metabolism in NAFLD, but also identified a novel glycine-based treatment”.


“This promising study shows that certain glycine-based treatments attenuate experimental NAFLD by stimulating hepatic fatty acid oxidation and glutathione synthesis and therefore warrants clinical evaluation beyond initial animal model and in-vitro data. Further studies would be well justified in clinical trials to continue to deliver on the positive outcomes thus far” said Mathew Diggle FRCPath, Ph.D. DLSH&TM MSc - Consultant Microbiologist, Associate Professor and member of the International Working Group for Diabetic Foot Infection.


DT-109 has been licensed from the University of Michigan by Diapin Therapeutics LLC. Dr. Bruce Markhan, CEO of Diapin stated “DT-109 has been designated as a lead NASH compound and is currently being evaluated in preclinical IND enabling studies and developed in chemical manufacturing control. We see this as a breakthrough molecule for the treatment of NASH and other co-morbidities associated with metabolic syndrome. “


About NAFLD and NASH


NAFLD, is a common and serious chronic liver disease, affects 25% of the population worldwide. NAFLD encompasses a spectrum of liver pathologies ranging from hepatic fat accumulation to non-alcoholic steatohepatitis (NASH), characterized by liver cell damage, lobular inflammation, fibrosis and cirrhosis that can lead to liver failure or hepatocellular cancer. NAFLD is common in metabolic disease patients including those with obesity, type 2 diabetes (T2D), metabolic syndrome, dyslipidemia and atherosclerosis. Cardiovascular disease is the leading cause of death in NAFLD patients, particularly those with NASH. Despite the global burden of NAFLD and substantial efforts in drug development, no therapy has yet been approved.


About Diapin Therapeutics, LLC
Diapin Therapeutics LLC is a University of Michigan spinoff company focused on the development of new therapies for treating cardiovascular and metabolic diseases. Diapin is developing two assets. The first, DT-109, a 3 amino acid, orally active peptide is being developed for multiple indications including non-alcoholic steatohepatitis (NASH), type 2 diabetes, hypertension, and atherosclerosis/dyslipidemia. The second asset is DT-678, an orally active novel antiplatelet agent that is significantly more efficacious with less bleeding risk than clopidogrel in preclinical models. Both DT-109 and DT-678 are moving toward the clinical development process. Diapin has established a strategic partnership with Beijing SL Pharmaceuticals Ltd. to advance its programs more rapidly and efficiently. Diapin Therapeutics was founded in 2012 by Dr. Eugene Chen, Frederick Huetwell Professor of Cardiovascular Medicine, Vice-Chair for Basic and Translational Research, Cardiac Surgery, and Director of the Center for Advanced Models for Translational Sciences and Therapeutics at the University of Michigan. www.diapin.com


Forward Looking Statements
Any statements in this press release that are not statements of historical fact, including statements about Diapins future expectations, plans and prospects, including statements about Diapin’s prospects, future operations, and clinical development of its product candidate, expectations for the future competitive environment for DT-109, and other statements containing the words "believes," "anticipates," "estimates," "expects," "intends," "plans," "predicts," "projects," “promising,” "targets," "may," "potential," "will," "would," "could," "should," "continue," “scheduled” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. These forward-looking statements should not be relied upon as representing Diapin’s views as of any date subsequent to the date hereof.


Categories: Omics & Genetics, Healthcare
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