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Threshold Pharmaceuticals, Inc. (THLD) Initiates 440-Patient, Randomized, Double-Blind, Placebo-Controlled Trial Of TH-302 In Combination With Pemetrexed In Advanced Non-Squamous Non-Small Cell Lung Cancer



7/1/2014 11:12:38 AM

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SOUTH SAN FRANCISCO, CA--(Marketwired - July 01, 2014) - Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced initiation of a 440-patient, randomized, double-blind, placebo-controlled trial of its investigational hypoxia-activated prodrug, TH-302, in combination with pemetrexed in advanced non-squamous non-small cell lung cancer (NSCLC). The international Phase 2 trial is designed to compare the combination of TH-302 and pemetrexed versus the combination of pemetrexed and placebo as second-line therapy in this patient population. A TH-302 dose of 400 mg/m2 will be utilized in combination with full-dose pemetrexed. Overall survival is the primary endpoint; secondary endpoints include safety and assessment of anti-tumor activity as determined by progression-free survival and objective response rate.

"The initiation of this trial is yet another example of our commitment, and that of our partner Merck KGaA based in Darmstadt, Germany, to develop TH-302 for the potential treatment of a broad range of cancers," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "Independent studies have demonstrated the presence of hypoxia in tumors from patients with NSCLC.(1) Early clinical research conducted by Threshold also supports further evaluation of TH-302 in combination with pemetrexed as a potential second-line treatment for patients with non-squamous NSCLC, many of whom still face a poor prognosis because of limited treatment options."

"While over the past decade the ability to detect and treat specific mutations in NSCLC has proven beneficial to some patients with recurrent disease who harbor those mutations, there is still a significant need for the development of new safe and effective medicines that improve survival outcomes," said Jonathan Goldman, MD, Director of Clinical Trials in Thoracic Oncology, UCLA Hematology & Oncology, and principal investigator of the ongoing trial. "TH-302 is a hypoxia-activated prodrug that has shown encouraging anti-tumor activity across a wide range of cancers in investigational trials, and we are excited about evaluating TH-302 in combination with pemetrexed as potential second-line treatment for patients with non-squamous NSCLC."

In a completed Phase 1/2 study that evaluated TH-302 in combination with full-dose pemetrexed in 18 patients with relapsed/refractory non-squamous NSCLC, median progression-free survival was 7.0 months and median overall survival was 14.9 months. Of 15 patients evaluable for response, 6 (40%) achieved a partial response including 4 confirmed responses, 6 (40%) achieved stable disease, and 3 (20%) had progressive disease. The most common adverse events following combination therapy of TH-302 and pemetrexed were fatigue, anemia, stomatitis and nausea.

About NSCLC
Lung cancer is the leading cause of cancer death worldwide claiming the lives of some 1.4 million people each year.(2) There are approximately 1.6 million new cases of lung cancer diagnosed each year.(2) About 85% of lung cancers are non-small cell lung cancer (NSCLC), and 15% are small-cell lung cancers (SCLC).(3) There are several types of NSCLC, each characterized by different types of cancer cells that grow and spread in unique ways. The two main subdivisions are "squamous" or "non-squamous", with non-squamous comprising 70-75%.(3) The American Society for Clinical Oncology (ASCO) guidelines recommend that first-line treatment for NSCLC should include a platinum-containing regimen in combination with a second therapeutic agent.(4) In the second-line setting, chemotherapy is continued until disease progression or unacceptable toxicity.(4) Historically, non-squamous NSCLC patients receiving second-line chemotherapy show median progression-free survival of approximately 3 to 4 months and median overall survival of approximately 8 to 10 months.

About TH-302
TH-302 is an investigational hypoxia-activated prodrug 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, 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 Designations for the treatment of soft tissue sarcoma and pancreatic cancer. TH-302 is also being investigated in earlier-stage clinical trials of other solid tumors and hematological malignancies, in combination with chemotherapy and antiangiogenic therapy, and for certain cancers, is being investigated as a monotherapy.

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 microenvironments of most solid tumors as well as the bone marrows of some 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 potential therapeutic uses and benefits of TH-302, statements regarding the TH-302 clinical development program, including the expected enrollment and conduct of ongoing clinical trials including the above-described Phase 2 clinical trial, and statements regarding continued collaborative activities under Threshold's collaboration with Merck KGaA, Darmstadt, Germany. 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 of Threshold and Merck KGaA, Darmstadt, Germany, to enroll or complete TH-302 clinical trials; the time and expense required to conduct such clinical trials and analyze data; issues arising in the regulatory or manufacturing process and the results of such clinical trials (including product safety issues and efficacy results); the risk that later trials may not confirm the results of earlier trials; Threshold's and Merck KGaA's dependence on single source suppliers, including the risk that these single source suppliers may be unable to meet clinical supply demands for TH-302 which could significantly delay the development of TH-302; risks related to Threshold's dependence on its collaborative relationship with Merck KGaA, Darmstadt, Germany, including its dependence on decisions by Merck KGaA, Darmstadt, Germany, regarding the amount and timing of resource expenditures for the development of TH-302; and Threshold's need for and the availability of resources to develop TH-302 and to support Threshold's operations. 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 May 1, 2014 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.

References

1. Zegers, CML et al. Hypoxia imaging with [18F]HX4 PET in NSCLC patients: Defining optimal imaging parameters. Radiotherapy and Oncology 2013;109:58-64.

2. American Cancer Society. Global Cancer Facts & Figures (2nd edition). http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-027766.pdf. Accessed June 30, 2014.

3. American Cancer Society. Lung Cancer (Non-Small Cell). http://www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf.pdf. Accessed June 30, 2014.

4. Azzoli, CG et al. American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. J Clin Oncol 2009;27:6251-6266.


Contact
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
Phone: 650-474-8206
E-mail: lhansen@thresholdpharm.com



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