Threshold Pharmaceuticals Initiates Phase 2 Study of TH-302 in Patients With Advanced Melanoma

Threshold Pharmaceuticals, Inc.

today announced the initiation of a Phase 2 clinical trial to evaluate the efficacy and safety of TH-302, its investigational hypoxia-targeted drug, in patients with melanoma. The study will also investigate a range of biomarkers including serum, tumor biopsy, and PET imaging hypoxia biomarkers that may predict treatment outcomes and be associated with tumor response to TH-302 therapy. Threshold's partner for the development of TH-302, Merck KGaA, Darmstadt, Germany, will fund 70% of development costs associated with this study. Tumor hypoxia, or regions of low-oxygen, is a hallmark of many solid tumors and is associated with poor prognosis. Cells in the hypoxic regions exhibit an increased potential for invasiveness, metastasis, and treatment resistance. Furthermore, hypoxia may also suppress the immune response to cancer. "Hypoxia is believed to be an important therapeutic target for patients with metastatic melanoma," said Principal Investigator Anthony Joshua, a medical oncologist at the Princess Margaret Cancer Centre and also Assistant Professor at University of Toronto. "Targeting hypoxic melanoma cells may help in slowing tumor progression and treatment resistance and has the potential to be an adjunct to current therapies. We are excited to initiate this study." In a previous Phase 1 trial, responses were observed in patients with advanced melanoma treated with TH-302. Out of 34 patients, seven patients (21%) achieved a partial response including patients with BRAF mutant and wild-type tumors, and 12 patients (35%) achieved stable disease yielding a clinical benefit rate of 56%. Median progression-free survival was 3.5 months. "We are excited to collaborate with world class researchers in the field of tumor hypoxia at the University of Toronto," said Tillman Pearce, M.D., Chief Medical Officer of Threshold. "This Phase 2 study holds strategic importance for the overall TH-302 development program in potentially broadening therapeutic applications for TH-302 as well as facilitating potentially important biomarker research." About the Phase 2 Study The Phase 2 trial is a single-arm, multi-center study investigating the clinical efficacy and safety of TH-302 administered at 480 mg/m2 weekly on a 28-day cycle (three weeks on, one week off) in up to 40 patients with advanced melanoma. The primary endpoint is three-month progression-free survival. Secondary endpoints include response rate, duration of response, overall survival, safety and evaluation of potential imaging, serum, and tissue biomarkers that may be associated with tumor response and predict for efficacy and safety of TH-302 therapy. About Melanoma The American Cancer Society estimates there will be 76,690 new cases of melanoma and 9,480 deaths in the U.S. in 2013. The five-year survival rate for metastatic melanoma ranges from 5% to 10% with a median survival of less than eight months with treatment. The introduction of immunotherapies in recent years as well as BRAF and MEK inhibitors has had a significant impact of the treatment of patients with advanced melanoma, yet new therapies are still needed. About TH-302 TH-302 is an investigational hypoxia-targeted drug that is designed to be activated under tumor hypoxic conditions, a hallmark of many cancers. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood supply as a result of aberrant vasculature. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. TH-302 is currently under evaluation in two Phase 3 trials: one in combination with doxorubicin versus doxorubicin alone in patients with soft tissue sarcoma (STS), and the other in combination with gemcitabine versus gemcitabine and placebo in patients with advanced pancreatic cancer (MAESTRO). Both Phase 3 trials are being conducted under Special Protocol Agreements with the U.S. Food and Drug Administration (FDA). The FDA and the European Commission have granted TH-302 Orphan Drug Designation for the treatment of STS. TH-302 is also being investigated in hematological malignancies and in combination with other therapies in a variety of solid tumors. Threshold has a global license and co-development agreement for TH-302 with Merck KGaA, Darmstadt, Germany, which includes an option for Threshold to co-commercialize in the U.S. About Threshold Pharmaceuticals Threshold Pharmaceuticals, Inc. is a biotechnology company focused on the discovery and development of drugs targeting tumor hypoxia, the low oxygen condition found in the microenvironments of most solid tumors as well as the bone marrows of some patients with hematologic malignancies. This approach offers broad potential to treat a variety of cancers. By selectively targeting tumor cells, we are building a pipeline of drugs that hold promise to be more effective and less toxic to healthy tissues than conventional anticancer drugs. For additional information, please visit our website (www.thresholdpharm.com). Forward-Looking Statements Except for statements of historical fact, the statements in this press release are forward-looking statements, including statements regarding the timing and potential results of the Phase 2 trial of TH-302 in patients with advanced melanoma, and potential therapeutic uses and benefits of TH-302 to treat patients with soft tissue sarcoma, pancreatic cancer or other cancers. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to, the ability to enroll or complete anticipated clinical trials, the time and expense required to conduct such clinical trials and analyze data, whether later trials confirm the results of earlier trials, whether the Phase 3 trial data is sufficient to support regulatory approval to market TH-302, and issues arising in the regulatory or manufacturing process and the results of such clinical trials (including product safety issues and efficacy results). Further information regarding these and other risks is included under the heading "Risk Factors" in Threshold's Quarterly Report on Form 10-Q, which has been filed with the Securities and Exchange Commission on August 1, 2013 and is available from the SEC's website (www.sec.gov) and on our website (www.thresholdpharm.com) under the heading "Investors." We undertake no duty to update any forward-looking statement made in this news release.