SOURCE: Threshold Pharmaceuticals

Threshold Pharmaceuticals

November 03, 2015 08:10 ET

Threshold Pharmaceuticals Announces Preclinical Data on Combination of Evofosfamide With Immune Checkpoint Inhibitors to Be Presented at the SITC 2015 Meeting

Evofosfamide Helps to Restore Immune Function in the Tumor Microenvironment and Sensitize Treatment Resistant Prostate Cancer Models to Anti-CTLA-4/Anti-PD-1 Therapy

SOUTH SAN FRANCISCO, CA--(Marketwired - Nov 3, 2015) - Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced that preclinical data on the combination of evofosfamide with immune checkpoint inhibitors will be presented in a scientific poster at the Society for Immunotherapy of Cancer (SITC) annual meeting in Maryland, November 4-8, 2015. Evofosfamide is Threshold's investigational hypoxia-activated prodrug, which is currently the subject of two fully-enrolled Phase 3 clinical trials for which Threshold expects to announce top-line data around the end of 2015.

"This is an exciting time for the field of cancer immunotherapy, and continued progress will depend on a better understanding of the tumor microenvironment and finding novel combination therapies that are more effective than immunotherapy alone," said Michael A. Curran, Ph.D., Assistant Professor at the University of Texas M.D. Anderson Cancer Center and senior author on the scientific poster. 

"Our research shows that hypoxia in the tumor microenvironment forms a barrier to T cell infiltration and fosters immunotherapy resistance in prostate cancer and other solid tumors," Curran said. "We found that evofosfamide-driven disruption of hypoxic zones sensitizes highly resistant prostate cancer models to treatment with immune checkpoint inhibitors anti-CTLA-4 and anti-PD-1."

Research conducted in Curran's laboratory shows that hypoxic zones in prostate tumors resist infiltration by T cells, which are capable of attacking and killing tumor cells. In contrast, normoxic areas of the same tumor experience robust infiltration by T cells.

In mouse models of prostate cancer, Curran and colleagues show that combination therapy with evofosfamide and anti-CTLA-4/anti-PD-1 treatment opens up the hypoxic zones to T cell infiltration.

Furthermore, evofosfamide helps sensitize otherwise immunotherapy-resistant prostate tumors to anti-CTLA-4/anti-PD-1 therapy in models of prostate cancer as evidenced by the smallest tumor burdens on average being observed with combination therapy.

"This combination of hypoxia disruption and T cell checkpoint blockade has potential to render some of the most therapeutically resistant cancers sensitive to immunotherapy," Curran said.

"Combining with immunotherapy is an exciting possibility that fits well with our development strategy to maximize the potential therapeutic applications of evofosfamide," said Tillman Pearce, M.D., Chief Medical Officer at Threshold. "The data from Dr. Curran's research suggests that combining evofosfamide with immune checkpoint inhibitors warrants further investigation."

The poster titled "Tumor hypoxia drives immune suppression and immunotherapy resistance" by Midan Ai et al. will be presented on Saturday, November 7, 2015, from 12:45 PM - 2:00 PM. The abstract is now available at http://www.sitcancer.org/2015 or by clicking here

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug that is thought to be activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Evofosfamide is currently in two Phase 3 trials, both of which are fully recruited: one in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma (STS) (the TH-CR-406 trial), and the other in combination with gemcitabine versus gemcitabine and placebo in patients with locally advanced unresectable or metastatic pancreatic cancer (the MAESTRO trial). Top-line data for both trials are expected around the end of 2015. Both Phase 3 trials are being conducted under Special Protocol Assessment (SPA) agreements with the FDA. The FDA and the European Commission have granted evofosfamide Orphan Drug designation for the treatment of STS and pancreatic cancer. The FDA has also granted Fast Track designation for evofosfamide for both STS and pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 trial designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical trials of other solid tumors and hematological malignancies.

Threshold has a global license and co-development agreement for evofosfamide 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 anticipated development activities and clinical development outlook related to company- and Merck KGaA, Darmstadt, Germany-sponsored clinical trials for evofosfamide, including the expected efficient execution and expected timing of and availability of the top-line results from the ongoing evofosfamide Phase 3 clinical trials the potential therapeutic uses and benefits of evofosfamide, including evofosfamide's potential to be a component of new combination approaches with immune checkpoint inhibitors. 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 evofosfamide 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 preclinical studies in animal models of disease may not accurately predict the results of human clinical trials of evofosfamide; the risk that the final data from ongoing trials may be materially different from the preliminary data that Threshold has reported; 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 evofosfamide which could significantly delay the development of evofosfamide; 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 evofosfamide, including the commencement of additional clinical trials; and Threshold's need for and the availability of resources to develop evofosfamide 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 July 30, 2015 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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