Background

The globally high prevalence of obesity is associated with the development of chronic liver diseases characterised by the build up of extra fat in liver cells. Chronic liver diseases range from steatosis to NASH featuring inflammation, hepatocyte death and various degrees of fibrosis. NASH is the most severe form of non-alcoholic fatty liver disease and may lead to liver cancer and end-stage liver disease. In addition, 75% of a growing diabetes community suffer from NASH.

Currently, there is no recommended treatment that is classed as safe and effective worldwide for the disease NASH (60% of patients non-responsive). Current Clinical Guidelines state the current pharmacotherapies for NASH/NAFLD are not recommended due to:

Insufficient evidence to recommend
Evidence to avoid use for some clinical indications
No single FDA-approved pharmacotherapy for NASH
Significant interest in novel agents that may meaningfully alter the natural history of the disease

The last line of defence treatment is a liver transplant and pending need will outweigh demand unless a safe and effective treatment emerges soon. Enhancements in clinical biomarkers are providing a pathway to enabling new therapeutics.

Technology Overview

Researchers at Trinity have developed a novel panel of analogues which have been synthesised and evaluated in vitro. The lead candidate, compound N, has been demonstrated to improve NASH resolution:

Liver cell cyto-protective mechanisms
Modulation of the Unfolded Protein /ER stress response
Impacting Lipid metabolic factors
Anti-inflammatory mechanisms

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Benefits

Compound N has been demonstrated to improve NASH resolution:

Reduced Liver weight & Improvements in lipid metabolism
Reduced levels of AST/ALT liver damage markers
Improved NAS score –encompassing cell damage, inflammation and fibrosis
In all animal models markers of liver damage were decreased to a greater extent than the current commercial therapeutic used for liver disease-UDCA

Opportunity

Available for partnering or for further collaborative work if required.

Novel Therapeutic for the Treatment of NASH

Patents

IP Status

Seeking