Threshold Pharma completes sale of TH-3424 to OBI Pharma for $3M，Jun. 22, 2017 Threshold Pharmaceuticals (NASDAQ:THLD) finalizes the sale certain rights to cancer candidate TH-3424, a small molecule prodrug, to Taiwan's OBI Pharma for total consideration of $3M.
Eighteen months after being poleaxed by the failure of its lead drug, Threshold Pharma's recovery efforts—including a planned merger—are looking brighter thanks to a licensing deal with Taiwan biotech OBI Pharma. OBI is buying rights to TH-3424—billed by Threshold as a first-in-class drug targeting cancers that overexpress the enzyme aldo-keto reductase 1c3 (AKR1C3)—for an undisclosed, one-off payment. The Taiwan firm gets rights to the drug in all world markets, but excluding several Asian countries including China, Japan and India. The drug, which will be renamed OBI-3424, is a prodrug that releases a tumor cell-killing alkylating agent in the presence of AKR1C3, seen in a number of hard-to-treat cancers, including liver and prostate cancer as well as T-cell acute lymphoblastic leukemia. OBI says it plans to file for approval to start trials in the U.S. early next year. In December 2015, Threshold was hit by the failure of its lead cancer drug evofosfamide (TH-302)—formerly partnered with Merck KGaA—in two phase 3 trials, and the following year a second candidate called tarloxotinib flunked a phase 2 proof-of-concept study in skin cancer and was dropped. Threshold still hasn't wholly given up on the drug, as it maintains it saw an improvement in overall survival among a subset of Asian patients in Merck's MAESTRO study. Discussions with the Japanese authorities about the possibility of a marketing application based on the data came to naught, however, and the company has been informed it has to carry out another trial. For now, its focus on evofosfamide is on a clinical trial looking at the drug in combination with Bristol-Myers Squibb's checkpoint inhibitor Yervoy—which is being carried out in collaboration with MD Anderson Cancer Centre—and on investigator-led trials of the drug alongside angiogenesis inhibitor drugs. In a recent SEC filing, Threshold said it had resources on hand for another 12 months or so of operations and was looking at partnering TH-3424 and possibly another early-stage candidate—PET imaging agent HX4—to help fund future development of evofosfamide. The embattled biotech called in strategic advisers in the wake of the phase 3 failure to work out which way to turn, and in March agreed a merger with Molecular Templates, pooling their respective cancer pipelines with a $20 million venture cash injection pledge from Longitude Capital. That deal hasn't yet gone through, but if it comes to fruition will see the two companies operate under the Molecular Templates banner, adding the latter's lead candidate MT-3724, an anti-CD20 drug in a phase 1 trial that has shown activity in heavily pre-treated non-Hodgkin lymphoma (NHL) patients, to their joint pipeline. With the OBI licensing deal in hand, Threshold's appeal to its would-be merger partner looks likely to have gone up.
Threshold Pharmaceuticals and National Cancer Institute to Collaborate on Drug Candidate TH-3424 December 19, 2016 08:02 ET | Source: Threshold Pharmaceuticals, Inc.-- Preclinical studies will explore the effects of TH-3424 against T-cell acute lymphoblastic leukemia cancer cell lines with high AKR1C3 expression --SOUTH SAN FRANCISCO, Calif., Dec. 19, 2016 (GLOBE NEWSWIRE) -- Threshold Pharmaceuticals, Inc. (NASDAQ:THLD), a clinical-stage biopharmaceutical company developing novel therapies for cancer, today announced 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. 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). 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 Annual Meeting in April 2016."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.
OBI-3424(TH-3424) 為一化療前驅型新藥，它會選擇性地在AKR1C3酵素作用下，釋出強效DNA烷基化劑；這種選擇性的啟動機制﹐OBI-3424與傳統烷基化藥物，如cyclophosphamide 與ifosfamide有很大區別。根據雙方合約，Threshold將會移轉OBI-3424所有權。及臨床前和製造相關數據予浩鼎；浩鼎將支付Threshold一次性款項，未來則不需要另行支付Threshold任何款項或權利金。這項轉讓除了亞洲區部份國家（不包括大陸、香港、澳門、台灣、日、韓、新加坡、馬來西亞、泰國、土耳其及印度）外，浩鼎將取得OBI-3424的全球智慧財產及其商務、開發與生產權利。根據文獻，AKR1C3在多種抗藥性及難治癌症的腫瘤細胞中均有過度表現，舉例來說﹐大多數肝細胞癌病人即有AKR1C3高度表現。
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