On December 19, 2016 Threshold Pharmaceuticals, Inc. (NASDAQ:THLD), a clinical-stage biopharmaceutical company developing novel therapies for cancer, reported that it has entered into a collaboration with the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), to study TH-3424, the company’s new drug candidate for the treatment of cancer (Press release, Threshold Pharmaceuticals, DEC 19, 2016, View Source [SID1234517126]). The collaboration will explore the effects of TH-3424 against T-cell acute lymphoblastic leukemia (T-ALL) xenograft cell lines with high AKR1C3 expression. The studies will be conducted through the NCI-funded Pediatric Preclinical Testing Consortium (PPTC). Under this collaboration, Threshold will supply TH-3424, and the NCI will fund the studies that will be conducted at the PPTC leukemia research program led by Professor Richard Lock of Children’s Cancer Institute (Sydney, Australia). Schedule your 30 min Free 1stOncology Demo! TH-3424 is a novel, small-molecule compound invented at Threshold with potentially broad anticancer properties. TH-3424 is activated by the enzyme AKR1C3, which is over-expressed in a number of different cancers, to release a cytotoxic agent directly to the tumor. Preclinical results showed that TH-3424 is effective in a variety of human xenograft models of cancer, as initially presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2016.
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"TH-3424 is designed to be activated by AKR1C3 inside tumor cells and spare healthy tissue," said Barry Selick, Ph.D., CEO of Threshold Pharmaceuticals. "Evaluating this compound in collaboration with the NCI enables us to expand the scope of our investigations to better inform our strategy for potential future clinical studies for this molecule."
About TH-3424
TH-3424 is a small-molecule drug candidate being evaluated for the potential treatment of hepatocellular cancer (HCC), castrate resistant prostate cancer (CRPC), T-cell acute lymphoblastic leukemias (T-ALL), and other cancers expressing high levels of aldo-keto reductase family 1 member C3 (AKR1C3). Tumors overexpressing AKR1C3 can be resistant to radiation therapy and chemotherapy and immunotherapy. TH-3424 is a prodrug that selectively releases a potent DNA cross-linking agent in the presence of AKR1C3. Investigational New Drug (IND)-enabling toxicology studies are being done in collaboration with Ascenta Pharmaceuticals, Ltd.