Widely Applicable to Most Solid Tumors

2-Deoxyglucose (2DG), our product candidate for the treatment of solid tumors, is in a Phase 1 trial. 2DG is an orally administered small molecule that employs Metabolic Targeting to treat solid tumors by directly inhibiting glycolysis. Because tumor cells in general, and those in hypoxic zones in particular, are dependent on glycolysis for survival, tumor cells are particularly sensitive to the effect of 2DG. This compound is a synthetic glucose analog that distributes selectively to tumor tissue because of metabolic changes related to increased glucose consumption. Because tumor cells exhibit increased levels of glucose transport proteins, these cells actively transport 2DG into the cells. Once inside the cell, 2DG interferes with cellular mechanisms for generating energy by competing with glucose for key enzymes in glycolysis. The in vivo efficacy of 2DG has been studied in mouse and rat models of sarcomas, adenocarcinomas, leukemias, melanomas and bladder, colon and breast tumors. In particular, treatment with 2DG, alone and in combination with other chemotherapy, resulted in increased lifespan or a reduction in tumor growth in many of these models.

Phase 1 Trial

We were developing 2DG based on its specificity for targeting tumor cells and extensive human safety data, as well as demonstrated animal efficacy that we and our collaborators at the University of Miami published in Cancer Research in January 2004.

We launched a Phase 1 clinical trial of 2DG in January 2004. This trial was a dose-escalation study to determine the safety, pharmacokinetics and maximum tolerated dose of daily oral doses of 2DG given alone or in combination with Taxotere. Thirty-four patients with advanced solid malignancies who had relapsed after chemotherapy were enrolled in the trial. The objectives of the trial were to determine the MTD of 2DG and to evaluate the PK of 2DG alone and in combination with docetaxel. The combination of 2DG and docetaxel appeared to be safe with no evidence of PK interactions. Some evidence of anti-tumor activity was observed including a partial response in one patient with breast cancer and disease stabilization in multiple patients with head and neck tumors. However, at this time, the Company is not planning on conducting any further development of 2DG.

Prior Clinical Trials

2DG has been administered in clinical trials to approximately 700 people, principally to evaluate the hormonal and metabolic effects of glucose deprivation. Collectively, these studies have shown that single intravenous doses of 2DG as high as 200 mg/kg do not cause any serious adverse events.