TH-302, which was discovered at Threshold, is a novel drug candidate that is activated under the metabolic condition typical of cancer cells — hypoxia. In July 2007, we initiated a Phase 1 clinical trial of TH-302, a hypoxia-activated prodrug (HAP) for the potential treatment of solid tumors. This clinical trial is designed to assess the safety of TH-302 and establish a maximum tolerated dose as a monotherapy in patients with various solid tumors. In 2008, we plan to commence a Phase 1/2 clinical trial of TH-302 in combination with additional chemotherapeutic regimens. The HAP research platform is focused on producing additional preclinical candidates that are activated under tumor hypoxia.We plan to nominate at least one additional HAP preclinical candidate in 2008.

Glufosfamide has completed several clinical trials in patients with various solid tumors including pancreatic, ovarian and small cell lung cancer, and soft tissue sarcoma. The soft tissue sarcoma trial was completed and provided evidence of clinical activity. In a phase 2 clinical trial of glufosfamide in combination with gemcitabine for the treatment of advanced pancreatic cancer, the data indicated that glufosfamide plus gemcitabine may benefit patients with chemotherapy naive pancreatic cancer. Enrollment in the ovarian cancer trial was stopped due to a lack of efficacy and enrollment challenges. The small cell lung cancer trial was stopped after a planned interim analysis due to lack of adequate response.

2-Deoxyglucose, or 2DG, for the treatment of solid tumors, is being evaluated in a Phase 1 clinical trial.