Several models of liver injury have been tested showing the potent anti-inflammatory activity of VLX103 and providing strong support for the development of VLX103 in the treatment of NASH and ASH. Combined with its hepatoselectivity property, VLX103 has the ideal product profile for treating liver diseases associated with a liver inflammation component (e.g., NAFLD, NASH, ASH).
VLX103 in Preclinical NASH Model
In a mouse model of NASH, animals were fed a high-fat diet for several weeks and then treated with VLX103 for 3 weeks. VLX103 significatively reduced liver inflammation and elevation of ALT was reduced by up to 47%.
The abstract detailing these results was presented at the American Association for the Study of Liver Disease (AASLD) in 2016. Abstract #1611 at the Liver Meeting®, in Boston, in November 2016 is available below.
VLX103 in Preclinical ASH Model
VLX103 is efficacious in the gold standard alcoholic liver disease mouse model (the NIAAA model). The model consists in a 10-day feeding of an alcohol-containing liquid diet, followed by a single high-dose feeding of alcohol to approximate binge drinking, causing marked liver enzyme elevations. Oral administration of VLX103 reduced the elevation of ALT by up to 50%.
The abstract detailing these early results was presented at the American Association for the Study of Liver Disease (AASLD) in 2015. Abstract #1333 at the Liver Meeting®, in San Francisco, in November 2015 is available below.
VLX103 in Preclinical Fulminant Liver Injury Model
A mouse preclinical model of fulminant, inflammation-driven, liver injury has been used to test the hepatoprotective properties of the drug. In this model, pentamidine markedly decreased liver injury and mortality. ALT concentrations in treated mice were reduced by more than 95% when compared to untreated mice. Such dramatic hepatoprotective effect is highlighted by the absence of liver injury in histological assessments of treated mice and achieved through a complete inhibition of the TNF-dependent mitochondrial cell death pathway.
In this model, untreated mice typically suffer lethal liver failure within 6-8 hours. Mice treated with pentamidine showed significant improvement in survival.
The abstract detailing these early results has received a presidential distinction from the selection committee of the American Association for the Study of Liver Disease (AASLD) in 2014. Abstract #1072 at the Liver Meeting®, in Boston, in November 2014 is available below.
Poster presented by Oncozyme Pharma (now Verlyx Pharma): A Novel Oral Form of Pentamidine (VLX103) Blocks TNF-Mediated Mouse Liver Injury from GalN/LPS