Addressing tumor hypoxia , which has been associated with resistance to chemotherapy and radiotherapy, is the mainstay of biotechnology company Threshold Pharmaceuticals Inc.'s (THLD) research offerings.
Before we take a look at this Redwood City, California-based company, here's a brief summary of what tumor hypoxia means...
Tumor hypoxia, which is core issue in tumor physiology and cancer treatment, is a situation where tumor cells have been deprived of oxygen. This deficiency of oxygen in tumor cells is a reason for treatment failures with radiation and chemotherapy because conventional anti-cancer therapies typically target actively dividing cells. Due to lack of oxygen, the hypoxic tumor cells do not divide rapidly thus rendering the conventional treatments ineffective.
Threshold Pharma's lead product candidate is TH-302, an anticancer agent that targets levels of hypoxia that are common in tumors but are rare in normal tissues. TH-302 is less likely to produce systemic toxicity caused by most cytotoxic chemotherapies, as it selectively targets the hypoxic regions of solid tumors.
The ongoing clinical trials with TH-302 are as follows :
* A phase I trial, known as 410, evaluating TH-302 in combination with Pfizer Inc. 's (PFE) Sutent in patients with advanced renal cell carcinoma and gastrointestinal stromal tumors. The study was initiated in June of this year and is currently recruiting participants.
* A phase III clinical trial of TH-302 in combination with chemotherapy drug Doxorubicin in patients with advanced soft tissue sarcoma, designed under a Special Protocol Assessment. The trial dubbed 406 was initiated late last month and enrollment is expected to be completed by the end of 2013.
* A phase II crossover clinical trial of TH-302 in combination with chemotherapy drug Gemcitabine in patients with first line pancreatic cancer. This trial named 404 was initiated last June and enrollment was completed in June of this year.
* A phase 1/2 trial dose escalation study of TH-302 in combination with Doxorubicin in patients with soft tissue sarcoma. The ongoing clinical trial known as 403 was initiated in August 2008, but is not recruiting participants.
* A phase I dose-escalation study known as 401, evaluating TH-302 in patients with advanced solid tumors. The study, which was initiated in June 2007, is ongoing but not recruiting participants.
* A phase 1 /2 dose escalation trial of TH-302, in combination with Gemcitabine or Docetaxel or Pemetrexed methotrexate, in the treatment of pancreatic cancer, castrate-resistant prostate cancer, and non-small cell lung cancer, respectively. This study known as 402 has completed enrollment.
* A phase I dose escalation trial named 407 that is evaluating TH-302 in patients with advanced leukemias. The study was initiated last June and is currently recruiting participants.
Upcoming Milestones
Threshold Pharma expects to report updated top line results from the phase I clinical trial of TH-302 in advanced leukemias this year. The objectives of the phase 1 trial are to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety, tolerability, clinical activity and pharmacokinetics of TH-302 in patients with advanced leukemia.
Advanced leukemia is an acute or chronic cancer involving the blood-forming tissues in the bone marrow. The four most common types of leukemia are acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia and chronic lymphocytic leukemia.
Last December, the company reported promising results from the 407 trial, which demonstrated activity in multiple subjects with relapsed/refractory acute myelogenous leukemia and acute lymphoblastic leukemia as evidenced by stabilization or reduction of bone marrow blast counts.
Another event to watch out for this year is the release of pancreatic cancer trial data.
The company expects to report top line efficacy analysis results from the phase II trial of TH-302 in combination with Gemcitabine in patients with first line pancreatic cancer at the end of 2011.
The phase II study was designed to enroll 165 patients, but it exceeded recruitment expectations and enrolled at least 200 patients. Patients were randomized equally into one of three cohorts namely, TH-302 at a dose of 240 mg/m2 plus gemcitabine, TH-302 at a dose of 340 mg/m2 plus gemcitabine, or gemcitabine alone. The primary endpoint of the trial is progression-free survival. The secondary endpoints are overall response rate, overall survival, event-free survival, CA 19-9 response rate (Serum cancer antigen 19-9 levels) as well as various safety parameters.
Pancreatic cancer is the fourth leading cause of cancer death. It is estimated that this year, 38,000 Americans will be diagnosed with pancreatic cancer and about 34,000 will die from it.
A quick look at the balance sheet...
Since inception in 2001 through June 30, 2011, the company had incurred net losses of $242.7 million. Being a development stage company, Threshold Pharma has not generated any revenue from the sale of its product candidates.
In the second quarter of 2011, net loss widened to $7.9 million or $0.16 per share from $0.3 million or $0.01 per share in the year-ago quarter. The company had cash of $31.5 million at June-end 2011, which is believed to be sufficient to fund currently planned activities, in the absence of additional cash, into the second half of 2012.
Threshold went public on February 4, 2005 offering its shares at $7 each. A 1 for 6 reverse stock split was implemented on August 20, 2008.
THLD has a 52-week price range of $1.07 to $3.34. The stock closed Tuesday's trading more than 3% higher at $1.65, with volume at 104,400.
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June 05, 2026 16:18 ET A busy week for economic news flow saw a slew of reports being released that reflected the trends in the U.S. labor market. In Europe, economic growth and inflation data gained attention as the European Central Bank and Bank of England head for policy session later in the month. In Asia, the monetary policy session of the Indian central bank was in focus as the country, a major oil importer, reels under the pressures of a weaker rupee and rising inflation.