Threshold Pharmaceuticals

About Threshold Pharmaceuticals

Threshold Pharmaceuticals, Inc. was a clinical-stage biopharmaceutical company founded in 2001 with a focus on developing treatments for cancer. The company's primary strategy revolved around targeting tumor hypoxia, a condition of low oxygen found in the microenvironments of most solid tumors, which is believed to contribute to resistance against conventional cancer therapies. The company was headquartered in South San Francisco, California.

The company's lead product candidate was evofosfamide (formerly TH-302), a hypoxia-activated prodrug designed to be activated specifically in the low-oxygen environments of tumors. This selective activation was intended to make it more effective against cancer cells while being less toxic to healthy tissues. Evofosfamide was investigated in numerous clinical trials for various cancers, including soft tissue sarcoma, pancreatic cancer, and multiple myeloma. The company had a global license and co-development agreement for evofosfamide with Merck KGaA. Another notable candidate in their pipeline was tarloxotinib bromide, an EGFR tyrosine kinase inhibitor.

Despite some promising early-stage results and receiving FDA Fast Track designation for evofosfamide for certain indications, the drug ultimately failed to meet its primary endpoints in two pivotal Phase 3 trials in late 2015. This significant setback led to Merck KGaA returning all rights to the drug and resulted in substantial workforce reductions at Threshold in December 2015 and again in September 2016. Faced with these challenges, the company began exploring strategic alternatives. In March 2017, Threshold Pharmaceuticals entered into a definitive agreement for a reverse merger with Molecular Templates, Inc., a privately held biopharmaceutical company. The merger was completed in August 2017, with the combined entity operating under the name Molecular Templates, Inc. and trading under the ticker symbol MTEM. Threshold's CEO at the time, Barry Selick, became the chairman of the board of the newly combined company.