MediciNova Announces Positive Results in NASH Mouse Model With MN-001 and Prepares to Initiate Phase 2 Trial in the U.S.

MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market

and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), today announced positive results from a study that examined the potential clinical efficacy of MN-001 for the treatment of NASH (nonalcoholic steatohepatitis). MN-001 administered orally once daily (10, 30, and 100 mg/kg) for 3 weeks, was evaluated in the STAM™ (NASH-HCC) mouse model of nonalcoholic steatohepatitis, as measured by liver biochemistry and histopathology, NAFLD activity score (NAS), and percent of fibrosis and gene expression. MN-001, in a dose-dependent manner, significantly reduced fibrosis area compared with vehicle (p <0.01) as demonstrated by a reduction in liver hydroxyproline content, supporting MN-001's anti-fibrotic properties. MN-001 significantly improved NAS (p <0.01), and this was most likely attributed to the reduction in lobular inflammation and hepatocyte ballooning, the latter being most notable. Hepatocyte ballooning is thought to be derived from oxidative stress-induced hepatocellular damage and is associated with disease progression of NASH. MN-001, in this animal model, improved NASH pathology by inhibiting hepatocyte damage (p <0.01) and ballooning (p <0.01). Congruently, MN-001 was shown to down-regulate certain gene expression levels in the liver. At low and mid doses, MN-001 significantly down-regulated MCP-1 (p <0.01) and CCR2 mRNA (p < 0.01) expression levels compared to vehicle. Similarly, MN-001 significantly down-regulated Collagen type 1 (p <0.01) and TIMP-1 mRNA (p <0.001) expression levels at low and mid doses. These gene expression data imply that MN-001 prevents the formation of fibrosis in the NASH model. Collectively, these results provide compelling evidence that MN-001 warrants further evaluation for the treatment of NASH in humans. Accordingly, MediciNova is preparing to initiate a Phase 2 trial for the treatment of NASH in the U.S. About MN-001 MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity in preclinical models. It is postulated that inhibition of the 5-LO pathway exerts anti-inflammatory actions, which has implications in various inflammatory diseases such as arthritis, osteoarthritis, allergy, and asthma (Martinez-Clemente et al 2011). Recently, 5-LO has been postulated as a pathogenic factor in liver injury (Titos et al 2010). MN-001 is thought to exert an inhibitory effect on 5-LO and the 5-LO/LT pathway, which is considered to be a novel target for fatty liver disease. Previously, MediciNova evaluated MN-001 for its potential clinical efficacy in asthma and completed a Phase 2 study in asthma with positive results. This compound has been exposed to more than 600 subjects. MN-001 was considered generally safe and well-tolerated. About NASH (nonalcoholic steatohepatitis) According to the National Digestive Diseases Information Clearinghouse (NDDIC), NASH prevalence in the U.S. is 2-5%. An additional 10-20% of Americans have fat in their liver, but no inflammation or liver damage, a condition called "fatty liver." The underlying cause of NASH is unclear, but it most often occurs in persons who are middle-aged and overweight or obese. Many patients with NASH have elevated serum lipids, diabetes or pre-diabetes. Progression of NASH can lead to liver cirrhosis. Liver transplantation is the only treatment for advanced cirrhosis with liver failure. At this time, there is no treatment for NASH. About MediciNova MediciNova, Inc. is a publicly-traded biopharmaceutical company founded upon acquiring and developing novel, small-molecule therapeutics for the treatment of diseases with unmet medical needs with a commercial focus on the U.S. market. MediciNova's current strategy is to focus on MN-166 (ibudilast) for neurological disorders, MN-221 for the treatment of acute exacerbations of asthma, and MN-001 for NASH. MN-166 is being developed in multiple indications, largely through investigator-sponsored trials and outside funding. MediciNova is engaged in strategic partnering and consortium funding discussions to support further development of its programs. For more information on MediciNova, Inc., please visit www.medicinova.com.