SOURCE: Threshold Pharmaceuticals

Threshold Pharmaceuticals

November 03, 2014 06:59 ET

Threshold Pharmaceuticals' Partner Merck KGaA, Darmstadt, Germany, Completes Target Enrollment in the TH-302 Phase 3 MAESTRO Study in Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma

SOUTH SAN FRANCISCO, CA--(Marketwired - Nov 3, 2014) - Threshold Pharmaceuticals, Inc. (NASDAQ: THLD), today announced that Threshold's partner Merck KGaA, Darmstadt, Germany, through its biopharmaceutical division, has completed target enrollment of 660 patients in the global Phase 3 MAESTRO (MetastAtic or unrESectable pancreaTic adenocarcinoma) study assessing the efficacy and safety of TH-302 in combination with gemcitabine in patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma. Threshold has a global license and co-development agreement with Merck KGaA, Darmstadt, Germany for TH-302, which includes an option for Threshold to co-commercialize in the U.S.

"The MAESTRO trial of TH-302 for patients with advanced pancreatic cancer is the second of two pivotal Phase 3 trials of TH-302 to complete enrollment, the first being our trial for previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "We are pleased to have completed enrollment in both trials. We anticipate conducting the primary analysis of overall survival for our Phase 3 trial in patients with advanced soft tissue sarcoma in the first quarter of 2016 and having top-line data for MAESTRO in 2016."

MAESTRO is a randomized, placebo-controlled, international, multi-center, double-blind Phase 3 trial of TH-302 plus gemcitabine compared with placebo plus gemcitabine. The primary efficacy endpoint is overall survival; the secondary endpoints include efficacy measured by progression-free survival (PFS), overall response rate and disease control rate, as well as assessments of safety and tolerability, pharmacokinetics and biomarkers. The study is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). The study design was also discussed with the European Medicines Agency (EMA) during a scientific advice procedure.

About Pancreatic Cancer
It is estimated that 337,872 cases of pancreatic cancer are diagnosed worldwide every year, accounting for 2.4% of all cancers.1 Almost 67% of cases are diagnosed in people aged 65 and over; it is uncommon in people under the age of 45.2 Pancreatic cancer has a low survival rate regardless of stage of disease, with 93% of patients dying from their disease within 5 years.2 It is estimated that there are 330,372 deaths from pancreatic cancer worldwide each year.1

About TH-302
TH-302, an investigational hypoxia-activated prodrug, is designed to be activated under severe 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 locally advanced unresectable or metastatic soft tissue sarcoma (STS), and the other in combination with gemcitabine versus gemcitabine and placebo in patients with advanced pancreatic cancer (the MAESTRO trial). Both Phase 3 trials are being conducted under Special Protocol Assessment (SPA) agreements with the FDA. The FDA and the European Commission have granted TH-302 Orphan Drug Designation for the treatment of STS and pancreatic cancer. TH-302 is also being investigated in earlier-stage clinical trials of other solid tumors and hematological malignancies.

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).

References

1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on October 31, 2014.
2. National Cancer Institute Surveillance Epidemiology and End Results (SEER). Available at http://seer.cancer.gov/statfacts/html/pancreas.html. Last accessed: October 31, 2014.

Forward-Looking Statements

Except for statements of historical fact, the statements in this press release are forward-looking statements, including all statements regarding the anticipated timing for top-line data for the MAESTRO trial, the anticipated timing of the primary analysis of overall survival for Threshold's Phase 3 clinical trial of TH-302 in patients with advanced STS, or the 406 trial, and the potential therapeutic uses and benefits of TH-302 to treat patients with advanced STS, advanced pancreatic cancer and 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 of Threshold and Merck KGaA, Darmstadt, Germany, to complete TH-302 clinical trials, including the MAESTRO trial and the 406 trial; the time and expense required to conduct such clinical trials and analyze data; the risk that because the timing of the top-line results of the MAESTRO trial and the timing of the primary efficacy analysis for the 406 trial is driven by the number of events in each trial, which neither Threshold nor Merck KGaA, Darmstadt, Germany, controls, Threshold cannot predict with certainty when these events will occur; issues arising in the regulatory or manufacturing process and the results of such clinical trials (including product safety issues and interpretation of efficacy results by regulatory authorities); the risk that later trials, including either the MAESTRO trial or the 406 trial, may not confirm the results of earlier trials; the risk that the design of, or data collected from, the MAESTRO trial and the 406 trial may be inadequate to demonstrate safety and efficacy, or otherwise may be insufficient to support regulatory submissions and/or approvals, and that despite the potential benefits of SPA agreements with the FDA, significant uncertainty remains regarding the regulatory approval process for TH-302 and that TH-302 may not receive any marketing approvals for the advanced STS or advanced pancreatic cancer indication, or in any other indications, in a timely manner or at all; Threshold's and Merck KGaA's (Darmstadt, Germany) 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 Exhibit 99.1 to Threshold's Current Report on Form 8-K, which has been filed with the Securities and Exchange Commission on October 9, 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.

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