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Threshold Pharmaceuticals, Inc.
Drug Names(s): TH-302, TH-4000
TH-302 is a nitroimidazole-linked Hypoxia-Activated Prodrug (HAP) of a brominated derivative of an isophosphoramide mustard previously used in cancer drugs such as ifosfamide, cyclophosphamide, and glufosfamide. TH-302 consists of two distinct parts, a toxic portion and an attached trigger molecule. To prevent general toxicity, the trigger molecule keeps the toxin inactive until the prodrug is in the hypoxic (low-oxygen) region of the tumor, where it is then activated by low oxygen concentration. Once activated, the toxin kills cells in its vicinity. This may be particularly helpful, as cancer cells in these hypoxic regions are believed to accumulate the genetic mutations that ultimately lead to resistance to the original chemotherapy, relapse, and metastasis. Thus, therapeutics that target hypoxic regions of tumors could provide significant additional anti-tumor activity and clinical benefit over current chemotherapeutic and radiation treatments.
The chemical name for TH-302 is (1-methyl-2-nitro-1H-imidazole-5-yl)methyl N,N’-bis(2-bromoethyl)diamidophosphate.
Deal Structure: TH-302 was originally developed by Threshold.
Merck KGaA and Threshold
In February 2012, Threshold announced that a global agreement was signed with Merck KGaA to co-develop and commercialize TH-302. Under the terms of the agreement, Merck will receive co-development rights, exclusive global commercialization rights and will provide Threshold an option to co-commercialize the therapeutic in the United States. In exchange, Threshold will receive an upfront payment of $25 million and could receive up to $35 million in additional development milestones during 2012. Threshold is also eligible to receive a $20 million milestone payment based on positive results from its randomized Phase II trial in pancreatic cancer. Total potential milestone payments are $525 million, comprised of $280 million in regulatory and development milestones and $245 million in sales-based milestones.
In the United States, Threshold will have primary responsibility for development of TH-302 in...See full deal structure in Biomedtracker
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