September 30, 2016
By Alex Keown, BioSpace.com Breaking News Staff
SOUTH SAN FRANCISCO – Shares of Threshold Pharmaceuticals plunged more than 58 percent in pre-market trading after the company announced it was terminating about one-fourth of its workforce following the failure of its Phase II cancer treatment.
This marks the second time in less than a year when Threshold was forced to terminate a large number of employees. In December 2015, the company slashed two-thirds of its employees following the failure of late-stage trials evaluating another cancer product.
On Thursday Barry Selick, chief executive officer of Threshold, announced the overall results from tarloxotinib did not meet activity thresholds required to move the drug study forward despite “the promising results seen in preclinical translational studies.” Trials evaluating Tarloxotinib in patients for the treatment of non-small cell lung cancer as well as for patients with recurrent or metastatic squamous cell carcinomas of the head and neck or skin have been discontinued. Tarloxotinib bromide, also called TH-4000, is designed to selectively release a covalent (irreversible) EGFR tyrosine kinase inhibitor under severe hypoxia.
With the failure of the trials, the company said members of the biostatistics and data management group will be departing the company. One notable figure leaving the company following the trials’ failure is Stewart Kroll, Threshold’s chief operating officer. The job cuts are expected to cost the company a one-time charge of about $900,000 in the fourth quarter. The job cuts are expected to be completed by Oct. 7, the company said.
Despite the cuts and trial failures, Threshold said Kristen Quigley, executive director of clinical operations at Threshold, will “retain leadership of all clinical trial operational responsibilities.”
Following Thursday’s release of interim data from its two Phase II proof-of-concept clinical trials of tarloxotinib, Threshold said it was shuttering the program and shifting focus to two other programs—the more clinically-advanced evofosfamide program as well as an earlier-stage anticancer candidate, TH-3424. Selick said the company will build on previous efforts to demonstrate the potential therapeutic value of adding evofosfamide to immune checkpoint inhibition. Threshold said it plans to initiate a Phase I clinical trial with four disease specific expansions of evofosfamide in combination with immune checkpoint antibodies in collaboration with researchers and clinicians at The University of Texas MD Anderson Cancer Center.
Additionally, Selick said the company will continue to pursue discussions with Japanese regulatory authorities regarding potential registration pathways for evofosfamide and to advance TH-3424 through IND-enabling toxicology studies with the goal of reaching the clinic in 2017.
“We plan to provide additional operational guidance in the fourth quarter of 2016,” Selick said in a statement.
In January Threshold acquired all rights to evofosfamide from Merck KgaA following the failure of two Phase III trials in patients with non-squamous non-small cell lung cancer. The German company had a global licensing co-development agreement with Threshold for the drug, but opted to return the therapy to Threshold. Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, according to company information.
Threshold’s TH-3424 is the company’s new, small-molecule drug candidate. It is being evaluated for the potential treatment of hepatocellular (liver) 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), the company said.
Shares of Threshold closed at $1.18 on Thursday, but fell to 37 cents per share in pre-market trading. Shares of Threshold stock have not recovered from an 85 percent fall in December 2015 after evofosfamide failed the two late-stage trials.
