ME-143

Our family of NADH oxidase inhibitors have demonstrated single-agent activity as well as synergy with both cytotoxic and targeted therapeutics in vitro and in vivo. NADH oxidase is a regulator of the plasma membrane quinone-quinol cation pump that is selectively expressed in rapidly proliferating tumor cells. The biochemical target of inhibition is the sphingosine kinase-Akt signaling pathway, which induces caspase-mediated apoptotic cell death.


 

first generation: Phenoxodiol

Phenoxodiol has been administered to more than 400 patients in clinical trials via oral or intravenous routes and appears to be well tolerated with low toxicity. In a Phase II clinical trial of intravenous Phenoxodiol in combination with platinum-based chemotherapy in women with recurrent ovarian cancer, a clinical response was observed in 19% of patients (three out of 16). These results were published in the May 2011 issue of the International Journal of Gynecological Cancer.

By contrast, in a randomized, placebo-controlled Phase III clinical trial of oral Phenoxodiol in combination with platinum-based chemotherapy in women with advanced ovarian cancer resistant or refractory to platinum-based drugs, a clinical response was observed in less than 1% of patients (one out of 142). Furthermore, pharmacokinetic studies suggest that significantly higher levels of active drug are measured when next-generation compounds of Phenoxodiol are administered intravenously versus orally.

next generation: ME-143

Pre-clinical studies show that ME-143, a next-generation analogue of Phenoxodiol, demonstrates superior anti-tumor activity against a broad range of tumor cell lines when used alone or in combination with platinum-based chemotherapy when compared to Phenoxodiol.

Our Investigational New Drug (IND) application for ME143 was approved by the U.S. Food and Drug Administration (FDA) in August 2011. We initiated a Phase I clinical trial of intravenous ME-143 in patients with refractory solid tumors in September 2011. Results from a Phase I clinical trial of ME-143 were presented at the American Society of Clinical Oncology Annual Meeting in June 2012. ME-143 was generally well tolerated in the study at all dose levels on a weekly dosing schedule and the maximum tolerated dose was defined as 20 mg/kg.

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