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 was designed to assess the safety of TH-302 and establish a maximum tolerated dose as a monotherapy in patients with various solid tumors. In August and September 2008, we initiated additional clinical trials of TH-302. The clinical trial design of those studies include separate treatment arms that will each examine TH-302 in combination with one of the following chemotherapeutic agents: gemcitabine, docetaxel, pemetrexed, or doxorubicin. Underlying TH-302 is a discovery team focused on developing additional drug candidates that, like TH-302, are either selectively activated by or otherwise target solid tumors.

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, has been evaluated in a Phase 1 clinical trial. 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.