Clinical Programs - Product Opportunity 1

MitoQ® Development

MitoQ® is mitoquinone formulated as a stable powder suitable for oral formulations. Antipodean has synthesized kilogram batches of MitoQ® to GMP standard and formulated a stable tablet. MitoQ is rapidly distributed to all organs in the body and penetrates the blood-brain barrier. MitoQ pharmacokinetics supports a once-daily dosing schedule in man.

MitoQ® is being evaluated as an oral treatment for liver inflammation that leads to fibrosis and is associated with metabolic dysfunction.

Phase I Pharmacokinetic And Safety Study

Our target in Phase I was to produce MitoQ® plasma levels in the ng/ml range and this was achieved. From animal studies we can correlate such levels with effective tissue and mitochondrial concentrations of MitoQ®. The results of this study confirmed the doses for the Phase II studies.

Target Indication: Non-Alcoholic Fatty Liver Disease (NAFLD)

NAFLD is a combination of fatty liver and inflammation of the liver. Approximately 3-5% of the US and European populations have the disease. Diet and genetic predisposition have made NAFLD one of the most common liver diseases in the developed world.

MitoQ for NAFLD

MitoQ presents an exciting pharmaceutical opportunity to be the first targeted treatment for NAFLD. A positive outcome of the phase 2b study would release its huge commercial potential and is ourkey success factor. in NAFLD.

Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-Alcoholic Fatty Liver Disease (NAFLD) impacts a significant portion of the US population, with some recent published estimates indicating an incidence of up to 30%. The disease is highly correlated to obesity, impacting 25-70% of the morbidly obese. Accumulation of fat in the liver results in inflammation, which can be detected by the use of liver enzyme tests, principally ALT. As the disease progresses, the inflammation leads to scarring and fibrosis of the liver, resulting in Non-alcoholic Steatohepatitis (NASH) – approximately 3% of the US population, or 9 million people, have NASH. Of these NASH patients, approximately 30% will progress to cirrhosis, 5% will develop liver cancer, and 2.5% will require a liver transplant.

Market Opportunity in NAFLD Exceeds $1 Billion

There are currently no pharmaceutical products to treat NAFLD. Lifestyle changes such as losing weight and doing exercise are recommended but usually fail. As a result there is increasing research aimed at discovering a pharmaceutical intervention. Unfortunately side effects will prevent future development of caspase inhibitors and glitazone derivatives. Physicians currently may use high dose antioxidant vitamin treatment, metformin or even drugs used to treat biliary cirrhosis in an effort to prevent the progression of liver inflammation to cirrhosis.

The Company estimates that in the next 3 years awareness of NAFLD will have grown and that 50% of the 9 million people with NASH (based on today’s numbers, with no growth factored in) will be diagnosed. Of this total, it is assumed that 70% will seek and comply with treatment. A first in class product would have sales potential in excess of US$1 billion.

The liver disease indication for MitoQ or a successor pipeline product eventually could be extended to viral hepatitis, alcoholic liver disease and cardiometabolic syndrome. In all these diseases the mechanism of cell death is similar to NAFLD.

Successful Phase 2a study

Antipodean successfully completed and published the results of a phase 2a, 30-patient proof of concept study in patients with elevated plasma ALT caused by HCV viral infection. The study confirmed animal data showing MitoQ’s ability to effectively treat liver inflammation. The phase 2a clinical study showed that MitoQ reduced blood levels of ALT compared with baseline, with statistically significant reductions of 26% for 40 mg (p=0.002) and 28% for 80 mg (p=0.005) observed after treatment for 28 days. The decrease in ALT continued after cessation of MitoQ therapy for at least 7 days. Once therapy was discontinued, ALT levels trended back up to the level of placebo-treated patients by the end of the follow-up period. There did not appear to be any significant additional benefit in the 80 mg group compared with the 40 mg group.

The phase 2a clinical study also showed that MitoQ had a positive impact on a secondary clinical endpoint, reduction of elevated plasma AST, another liver enzyme. The impact on AST, similar to that on ALT, confirmed a genuine liver cell protective effect of MitoQ.

Phase 2B study – MitoQ in NAFLD

Study Title:

A Double-blind Randomised Placebo-controlled Multicentre Study of 40 mg MitoQ and Placebo for the Treatment of Participants with Raised Liver Enzymes due to Non-Alcoholic Fatty Liver Disease (NAFLD)

Chief Investigator Prof. Chris Day

Pro Vice Chancellor and Professor of Liver Medicine, Faculty of Medical Sciences, Newcastle University Medical School, Framington Place, Newcastle Upon Tyne, NE2 4 HH, UK.