REDWOOD CITY, Calif., July 22, 2008 (PRIME NEWSWIRE) -- Threshold Pharmaceuticals, Inc. (Nasdaq:THLD) today announced a presentation on its clinical stage hypoxia-activated prodrug, TH-302, at the American Association for Cancer Research (AACR) Centennial Conference on Translational Cancer Medicine: Cancer Clinical Trials and Personalized Medicine, being held July 20-23, 2008, at the Hyatt Regency Hotel in Monterey, CA. Translational research with the incorporation of laboratory scientific breakthroughs into the medical treatment of cancer is a priority of the AACR which views this conference, and others like it, as a forum for current advances in translational cancer medicine and progress against cancer.
Select interim results were presented from an ongoing Phase 1 clinical trial evaluating the safety and preliminary efficacy of TH-302 in patients with advanced solid tumors. The clinical trial was designed with an initial accelerated titration design followed by a standard dose escalation schema. The trial has completed the accelerated titration design component and has enrolled the eighth dosing cohort. The weekly dose has been escalated from the initial dose of 7.5 mg/m2 to 670 mg/m2. None of the 20 patients enrolled to date has experienced any dose limiting toxicities (DLTs). Importantly, one patient with refractory small cell lung cancer metastatic to the liver had a partial response at their initial response assessment with a greater than 45% reduction in target lesion diameters. The patient, who has received two cycles of TH-302 at 480 mg/m2, is being followed by RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Additionally, this patient experienced a marked improvement in liver function tests. Other anti-tumor activity observed include one patient with non-small cell lung cancer with tumor shrinkage lasting over 6 months.
"While these results are preliminary, they are encouraging to us, our clinical investigators and, importantly, to patients," said John Curd, M.D., Threshold's president and chief medical officer. "We remain focused on completing this clinical trial as well as starting Phase 1/2 trials with TH-302 in combination with several widely-used chemotherapeutic agents."
The Company also reported on in vivo translational studies designed to select effective combinations of TH-302 and standard chemotherapies in order to complement the activity and tolerance of chemotherapy. In preclinical models, TH-302 demonstrated single agent activity; however, combination therapy was associated with higher complete response rates, longer survival and greater tumor growth inhibition in multiple preclinical models utilizing various tumor types and tumor implantation methods.
In a poster entitled Targeting Tumor Hypoxia with TH-302 and Complementary Chemotherapy, combinations of TH-302 with docetaxel, paclitaxel, or gemcitabine were associated with complete responses and increased survival in orthotopic models of pancreatic cancer (MIA PaCa-2) and prostate cancer (PC-3) and in models of established bone (PC-3) and lung metastases (H460). Combinations of TH-302 and 5FU, carboplatin, cisplatin, or pemetrexed were also evaluated in human tumor xenografts. Combination therapy tumor growth inhibition was superior compared with TH-302 or chemotherapy alone.
The results from the preclinical studies outlined yesterday at the AACR conference facilitated the planning of the next clinical trial of TH-302, a multiple-arm, Phase 1/2 clinical trial of TH-302 in combination with docetaxel, in combination with gemcitabine, and in combination with pemetrexed. The Company plans to commence this trial in the third quarter of 2008.
A copy of the poster 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 Tumor Hypoxia, the low oxygen condition found in microenvironments of most solid tumors. 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
Except for statements of historical fact, the statements in this press release are forward-looking statements, including statements regarding Threshold's product candidates, clinical trial results and plans, and potential therapeutic uses and benefits of our product candidates. 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, Threshold's ability to commence its anticipated clinical trials, the time and expense required to conduct such clinical trials and analyze data, the possibility that results from these trials will not be confirmed in subsequent trials, potential adverse side effects, 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 was filed with the Securities Exchange Commission on May 8, 2008 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.