Threshold Pharmaceuticals, Inc. (NASDAQ:THLD) announced that the company has initiated a Phase 2 clinical trial of tarloxotinib bromide, or “tarloxotinib” (TH-4000), for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) or skin (SCCS). Tarloxotinib is Threshold’s proprietary, hypoxia-activated, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor licensed from the University of Auckland, New Zealand.

“New and effective treatment options are urgently needed for patients with squamous cell carcinomas,” said Danny Rischin, M.D., Co-Director, Division of Cancer Medicine at Peter MacCallum Cancer Centre and Principal Investigator of the Phase 2 trial. “Tarloxotinib represents a novel treatment approach that may allow effective inhibition of EGFR signaling in the tumor microenvironment with relative sparing of normal tissues.”

Elevated expression of wild-type EGFR and its stimulatory ligands occurs in the majority of squamous cell carcinomas. Aberrant EGFR signaling can lead to uncontrolled tumor cell growth. One mechanism likely to be involved is hypoxia, or low-oxygen conditions, which is a prevalent feature of solid tumors including squamous cell carcinomas. In preclinical studies hypoxia has been shown to increase EGFR signaling by upregulation, stabilization, and hyperphosphorylation of EGFR, through multiple mechanisms.1-6 Gene expression-based profiling of clinical samples supports the observations of a strong causal link between elevation in the tumor EGFR pathway and hypoxia signatures.7

“We are pleased that tarloxotinib is actively being investigated in two monotherapy Phase 2 proof-of-concept trials, the other being in patients with non-small cell lung cancer,” said Tillman Pearce, M.D., Chief Medical Officer of Threshold. “These clinical settings, in which EGFR is already a validated therapeutic target, represent opportune development paths for tarloxotinib, which is designed to exploit the reported overlap between elevated EGFR signaling and tumor hypoxia. By selectively targeting the hypoxic tumor microenvironment, tarloxotinib has the potential to increase the therapeutic index and overcome limitations of current EGFR inhibitor therapy, which may lead to improved outcomes for patients with these EGFR-dependent cancers.” (Original Source)

Shares of Threshold Pharmaceuticals closed yesterday at $4.11. THLD has a 1-year high of $5.41 and a 1-year low of $2.58. The stock’s 50-day moving average is $4.22 and its 200-day moving average is $4.13.

On the ratings front, Threshold Pharmaceuticals has been the subject of a number of recent research reports. In a report issued on August 10, Piper Jaffray analyst Charles Duncan maintained a Buy rating on THLD. Separately, on July 30, Cantor Fitzgerald’s Daniel Brims maintained a Buy rating on the stock and has a price target of $14.

According to, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Charles Duncan and Daniel Brims have a total average return of 6.1% and -3.2% respectively. Duncan has a success rate of 47.5% and is ranked #961 out of 3734 analysts, while Brims has a success rate of 34.0% and is ranked #3087.

Threshold Pharmaceuticals Inc is a biotechnology company. It is engaged in discovery and development of drugs targeting the microenvironment of solid tumors as novel treatments for patients living with cancer.