REDWOOD CITY, Calif., April 20, 2009 (GLOBE NEWSWIRE) -- Threshold Pharmaceuticals, Inc. (Nasdaq:THLD), today announced multiple preclinical presentations on its clinical stage hypoxia-activated prodrug, TH-302, at the American Association for Cancer Research (AACR) Annual Meeting, being held April 18 to 22, 2009, at the Colorado Convention Center in Denver, CO.
"While these results are preclinical, they are very encouraging to us," said Charles Hart, Ph.D., Threshold's vice president of biology. "Especially encouraging is the superior efficacy and less toxicity observed with TH-302 compared to ifosfamide in human lung cancer models."
Poster 4517 (TH-302, a novel hypoxia-activated prodrug, shows superior efficacy and less toxicity than ifosfamide in metastatic and ectopic human lung carcinoma models) indicates that TH-302 has superior activity and less toxicity than ifosfamide in two preclinical models. Efficacy endpoints included tumor growth inhibition and survival and toxicity endpoints included body weight loss and myelosuppression. The therapeutic index of TH-302 was greater than ifosfamide. These results are consistent with the initial data presented at the EORTC conference in October last year where interim Phase 1 clinical trial results in patients with solid tumors demonstrated very little myelosuppression as well as some anti-tumor activity.
Poster 1819 (Preclinical dose sequence and regimen optimization of the hypoxia-activated prodrug TH-302) evaluated the dosing schedule of TH-302 when used in combination with conventional chemotherapies in two cancer xenograft models of prostate and non-small cell lung cancer. In summary, TH-302 given two to four hours before chemotherapy resulted in the highest anti-tumor efficacy, and lower doses of TH-302 with more frequent dosing resulted in a better safety profile than less frequent, higher doses. Coincident administration of TH-302 and chemotherapy showed the highest toxicity when compared to the other schedules. These results have helped to guide the Company's clinical trial design for the drug candidate.
Poster 230 (TH-302 pharmacological activity in 3D multicellular tumor spheroid models) studied the in vitro pharmacology of TH-302 in three-dimensional multicellular tumor spheroid models which have been used extensively to study aspects of the tumor microenvironment. H460 non-small cell lung cancer spheroids were employed to profile TH-302 in comparison to other chemotherapeutics. TH-302 exhibited favorable penetration, prodrug activation, cytotoxicity and bystander effect. The bystander effect in tumor therapy is the extended zone of tumor cell killing resulting from the activation of a cytotoxic agent in only some of the tumor cells and the resulting diffusion of the toxin to adjacent cells.
A copy of the posters presented at AACR may be obtained by calling the Company.
About Threshold Pharmaceuticals
Threshold is a biotechnology company focused on the discovery and development of drugs targeting the tumor microenvironment. This approach offers broad potential to treat most solid tumors. 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
To the extent that statements in this press release about the use of TH-302 in preclinical models are viewed as predictions of the ability of TH-302 to treat cancer patients, such statements are forward looking statements and 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, Threshold's ability to commence its anticipated 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). Further information regarding these and other risks is included under the heading "Risk Factors" in Threshold's Annual Report on Form 10-K, which was filed with the Securities Exchange Commission on March 13, 2009 and is available from the SEC's website (www.sec.gov) and on our website (www.thresholdpharm.com) under the heading "Investors." We do not intend to update any forward-looking statement made in this news release.