Clinical trial results of Threshold's TH-302 hypoxia-activated prodrug presented at 16th CTOS annual meeting

Threshold Pharmaceuticals, Inc. (Nasdaq:THLD) today announced clinical trial results related to Threshold's clinical stage hypoxia-activated prodrug, TH-302. The results were presented at the 16^th Annual Connective Tissue Oncology Society (CTOS) Meeting taking place in Paris, France from November 11 to 13, 2010.

Today's presentation focused on a clinical trial, the 403 trial, which is investigating TH-302 in combination with doxorubicin in patients with soft tissue sarcoma who have not received prior doxorubicin. Fifty-four patients have had at least one evaluable post-treatment tumor assessment. The results are summarized in the table below including, for comparison, results from the 403 trial presented at another medical meeting, ASCO, earlier this year. Responses are measured by RECIST (Response Evaluation Criteria In Solid Tumors). In addition to the reported response rates, median progression free survival remains 6.4 months (95% confidence interval: 5.6 to 6.9 months). Fifteen of the 54 patients continue to receive TH-302 after receiving TH-302 for 3 to 12 three-week cycles. Based on these data, the Company is designing a controlled clinical trial with a primary efficacy endpoint of overall survival.

"We are very pleased to have achieved a response rate of 33% in a meaningful number of patients which compares favorably with historic, albeit controlled data. The durability of response is also quite promising," said John Curd, M.D., Threshold's chief medical officer. "If confirmed in a controlled trial, the potential benefit to sarcoma patients of TH-302 plus doxorubicin would be great—significantly better than the current standard of doxorubicin alone for these patients who are in serious need of better treatment options."

TH-302 continues to be well tolerated. After observing significant, but not dose limiting toxicity at a TH-302 dose of 240 mg/m², prophylactic growth factor support was initiated. As reported in June this year, two dose limiting toxicities, were observed in 2 of 4 patients treated at a TH-302 dose of 340 mg/m². The maximum tolerated dose (MTD) of 300 mg/m² was established earlier this year as well. Nausea and fatigue were the most commonly reported adverse events and were each reported in 37 (65%) of the 57 patients assessed for safety. Skin rash and hyperpigmentation, both reversible, were reported in 30% and 25% of patients respectively. Stomatitis, an inflammation of the mucous lining in the mouth and throat, and also reversible, was reported in 37% of patients. In regards to hematologic toxicity, at the MTD the frequency of grade 3/4 neutropenia was 24%. Five events (9%) of febrile neutropenia have been reported. In summary, the safety of adding TH-302 to full dose doxorubicin has been established.