Preclinical results of TH-302 presented at AACR Translational Cancer Medicine Meeting

Threshold Pharmaceuticals, Inc. (Nasdaq:THLD), today announced two preclinical presentations on its clinical stage hypoxia-activated prodrug, TH-302, at the American Association for Cancer Research (AACR) Translational Cancer Medicine Meeting, being held July 11 to 14, 2010, in San Francisco, CA. The preclinical presentations describe new findings regarding the efficacy of TH-302 when combined with multi-kinase inhibitors that inhibit VEGF signaling, as well as the efficacy of TH-302 in combination with gemcitabine in models of pancreatic cancer.

"These results extend our understanding of the breadth of TH-302's anticancer activity," said Charles Hart, Ph.D., Threshold's vice president of biology. "In addition, the observations noted in the preclinical study of TH-302 in combination with antiangiogenic agents provide a strong translational rationale for combining TH-302 with these agents to potentially increase treatment benefit to patients."

Poster A42, C.P.Hart et al., (Antiangiogenic-induced increase in tumor hypoxia in RCC and NSCLC human tumor xenografts and its selective targeting by the hypoxia-activated prodrug TH-302: a model for clinical exploration?) studied the hypothesis that TH-302 would exhibit enhanced efficacy in the context of an antiangiogenic-mediated increase in tumor hypoxia and potentiate the antitumor efficacy of the antiangiogenic. All combination therapy treatment groups (TH-302 plus sunitinib or sorafenib) exhibited superior efficacy compared to the corresponding monotherapy groups.

Poster A22, J.D.Sun et al., (Hypoxia-dependent antitumor activity of TH-302, a hypoxia-activated prodrug, in preclinical pancreatic xenograft models) supports the hypothesis that TH-302 and gemcitabine work in a complementary manner by targeting two distinct tumor compartments, thus adding support for hypoxic compartment selectivity of the mechanism of action of TH-302.

Sunitinib and sorafenib are multikinase antiangiogenic agents that are known to increase the degree and severity of hypoxia in tumors. TH-302 is a prodrug that is selectively activated by deep hypoxia. The experiments reported here demonstrate for the first time that TH-302 can enhance the activity and efficacy of both agents in translational preclinical cancer models and provide a strong rationale for evaluating combinations of TH-302 with anti-angiogenic agents in patients living with cancer.