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Scientists Identify New Therapeutic Target for Fatty Liver Disease

Scientists Identify New Therapeutic Target for Fatty Liver Disease
  • Preclinical study highlights a novel therapy for the treatment of fatty liver disease, which affects up to 25% of the global population
  • Inhibiting interleukin 11 (IL11) signalling addresses multiple aspects of non-alcoholic steatohepatitis (NASH), including hepatic inflammation and fibrosis
  • Enleofen will be advancing first-in-class IL11 antibody therapeutics into a Phase 1 clinical trial

SINGAPORE, May 22, 2019 /PRNewswire/ -- Enleofen Bio ("Enleofen") today announced the publication of promising data from a preclinical study of a novel therapy targeting a severe form of fatty liver disease. The data was published in Gastroenterology, the leading scientific journal for liver and gut diseases.

The therapy under preclinical investigation is an inhibiting interleukin 11 (IL11) antibody treatment that addresses multiple aspects of non-alcoholic steatohepatitis (NASH), including hepatic inflammation and fibrosis. The study was led by Enleofen's co-founders, Professor Stuart Cook and Assistant Professor Sebastian Schäfer, and conducted with an international team of scientists at Duke-NUS Medical School ("Duke-NUS") and National Heart Centre Singapore ("NHCS").

"The data from this preclinical study suggests that Enleofen's IL11 signal inhibition strategy could be effective in treating this common but currently incurable type of liver disease even at an advanced stage," said Dr. Stuart Cook.

The researchers discovered that IL11 was elevated in the livers of NASH patients. Further studies showed conclusively that liver cells start to produce IL11 as soon as the liver is loaded with fat. IL11 then triggers hepatocyte damage and promotes inflammation and fibrosis. Antibodies neutralising IL11 signalling were administered to several preclinical models of NASH and effectively blocked this vicious disease cycle, which resulted in strong therapeutic effects. Turning off scarring of the liver is very difficult to achieve and is one of the highlights of the novel therapy.

The study also showed that as the liver recovered, the overall metabolic profile also improved as indicated by lowered blood cholesterol and glucose during treatment. This highlights the central importance of the liver for metabolic disease and suggests Enleofen's therapies may provide a holistic approach for treating multiple aspects of ill health in diabetic and obese individuals with liver disease.

"IL11 has been overlooked as a therapeutic target, but we found that it is the central player of this liver disease," added Dr. Sebastian Schäfer. "We look forward to validating this strategy in a Phase 1 clinical trial."

Fatty liver disease affects one in four people around the world and is most common in obese and diabetic people. It can progress to NASH, which is characterised by liver inflammation, fibrosis and an increased risk of liver failure. NASH causes fatigue, abdominal pain, itchy skin, nausea, and can ultimately lead to liver cirrhosis or cancer. There are currently no approved treatments for NASH.


Widjaja et al. (2019) Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Non-Alcoholic Steatohepatitis. Gastroenterology. DOI: 10.1053/j.gastro.2019.05.002


Enleofen Bio was founded in 2017 as a spin-out from National Heart Centre Singapore (NHCS), SingHealth and Duke-NUS Medical School with Series A funding. Enleofen develops first-in-class antibody therapeutics for the treatment of fibro-inflammatory human diseases. The initial discovery science and drug target validation was carried out at NHCS and Duke-NUS, funded by Professor Stuart Cook's STAR award from the National Medical Research Council (NMRC).

Several patent applications and a number of advanced antibody and inhibitor drug candidates arising from the scientific work have been licensed to the company, giving it a significant head start in drug development. Key patents have been granted in Europe, the US and further countries. Enleofen aims to have its lead antibody in clinical trials by the end of 2020 with the goal of developing a drug that can be used to treat multiple fibro-inflammatory diseases for which there are currently no treatment options.

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