Interim Report January – June 2018
The definition of fatty liver is when at least 5 % of the liver´s total weight is fat. Fatty liver was for a long time associated with an overconsumption of alcohol but this was changed in the 1980s. Fat incorporation in the liver also in absolute non-drinking patients – in combination with inflammation – gave the disease the name non-alcoholic steatohepatitis (NASH). The overall term used for this type of fattening of the liver is non-alcoholic fatty liver disease (NAFLD).
When the patient has fibrosis and inflammation in the liver it is defined as NASH, a condition which may develop into liver cirrhosis or hepatocellular cancer (HCC). The present data shows that NeuroVive's non-immunosuppressive cyclophilin inhibitor prevents fibrosis development in a well-validated experimental model of NASH.
NAFLD is one of the most common conditions worldwide. It is estimated that 20 % of the global population suffers from NAFLD and about one-third of the population in the US. There is a strong association between NASH and a variety of metabolic syndromes like diabetes and obesity. Approximately 3-5 % of Americans (approx. 15 million people) suffer from NASH and there are currently no registered drugs for the treatment of this condition. 1)
1) Vernon G. et al. Aliment Pharmacol Ther. 2011;34(3):274-85
NV556 is a potent non-immunosuppressive cyclophilin inhibitor within NeuroVive’s new compound class Sangamides. In this cyclophilin inhibitor chemical family, the oral version of the lead compound NV556 has undergone extensive preclinical development. Further experimental activities with NV556 within NASH are ongoing.
In addition, NeuroVive is developing a new class of compounds with a different mode of action that may offer complementary treatment of NASH.
Liver cancer is often diagnosed at a late stage of the disease and mortality rates are high. There are two major types of liver cancer: hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer. Risk factors associated with HCC are hepatitis B virus or hepatitis C virus infections, alcohol-induced cirrhosis or chronic liver damage. Although liver cancer is less common in northern Europe and the US than In Asia, HCC is the sixth most-common type of cancer and the third most-common cause of death worldwide.1)2)
In recent years, the number of HCC cases has risen all over the world. Early diagnosis and novel therapies may considerably improve the outlook for HCC patients, who otherwise have a very poor outlook with current treatment options.3) Based on its expertise in mitochondrial medicine, NeuroVive has studied a unique aspect of the company’s sanglifehrin-based compounds – anticancer effects – and is developing these compounds for the treatment of HCC in the NVP024 project.
HCC is the sixth most-common type of cancer, with about 780,000 new cases diagnosed globally in 2012, and the third most-common cause of death worldwide. In Europe, HCC is the 14th most-common type of cancer, with about 63,500 new cases diagnosed in 2012. While surgery, chemotherapy and radiotherapy are important starting points for the treatment of liver tumors, there is a major medical need for more, and effective, complementary medical treatments to decrease side effects and increase the survival rate for people with liver cancer.4)
NeuroVive’s NVP024 project is focused on the anticancer properties of a sub-set of the novel sanglifehrin-based compounds. Together with its international partners, NeuroVive’s research team has demonstrated that these compounds show powerful anticancer effects in preclinical models of HCC. Additional confirmatory tests are ongoing.
1) Altekruse SF, McGlynn KA, Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27 (9):1485-91, 2009.
2) Forner A, Llovet JM, Bruix J: Hepatocellular carcinoma. Lancet 379 (9822): 1245-55, 2012.
3) Sandhu DS1, Tharayil VS, Lai JP, Roberts LR. Treatment options for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2008 Feb;2(1):81-92. doi:10.1586/17474188.8.131.52.