Threshold Pharmaceuticals Selectively Targets Tumor Cells in Cancer Therapeutics

By Herina Ayot

Cancer, the second leading cause of death in the United States after cardiovascular disease, is a persisting problem that many talk about but few have yet to find effective treatments. The American Cancer Society estimates that 569,490 people died from cancer in the United States in 2010. Many cancers, such as pancreatic, lung and liver cancer, have few effective treatments and very low survival rates.

Threshold Pharmaceuticals (NASDAQ:THLD) takes advantage of the differences in metabolic activity between cancerous and normal, healthy biological tissue. Tumors are infused with considerably aberrant blood vessels that have a decreased ability to transport nutrients, leading to low oxygen levels (hypoxia) and modified sugar consumption within the tumor.

To this end, the company has developed a prodrug that is only activated in the presence of low oxygen content, therefore targeting cancerous masses. Tumor hypoxia, or low oxygen concentration represents a compelling target for anti-cancer intervention. Conventional anti-cancer therapies typically target actively dividing cells, but there are many irregularities and abnormalities in tumor vasculature, including a wide variation in the distance between the blood vessels that carry oxygen and other vital nutrients to tissues. In normal tissues, the distance between blood vessels is carefully regulated by several processes. However, in tumors, the growth of malignant cells is unregulated and some cells or regions literally outgrow their blood supply, leading to severe deficiencies in the perfusion of oxygen and nutrients.

Threshold Pharmaceuticals has designed TH-302 to be selectively activated within these hypoxic cells, killing them as well as those in close proximity via a bystander effect. Preclinical as well as early clinical data suggest that TH-302 exerts significant anti-tumor activity both alone as well as in combination with other therapies that target the rapidly proliferating cells found in solid tumors. TH-302 targets levels of hypoxia that are common in tumors but are rare in normal tissues – this is how selective targeting of the tumor occurs.

Additionally, the company has developed two modified sugar therapeutics that selectively target tumors due to their increased sugar utilization. The company’s drugs serve a highly unmet medical need in oncology, as traditional chemotherapy damages both healthy and malignant tissue leading to severe side effects. Furthermore, the decreased side effects obtained with the company’s therapies enable the use of higher drug concentrations, as well as the use of the company’s product as an adjunct to currently used drug regimens. The company’s hypoxia prodrug and modified sugar drugs are currently in Phase 1 and Phase 2 clinical trials, respectively.

As of March 31, Threshold had $38.4 million in cash, cash equivalents and marketable securities. The company currently expects 2011 operating cash requirements to be in the range of $27.0 million to $29.0 million. The company also expects existing cash, cash equivalents and marketable securities to be sufficient to fund the company’s projected operating requirements into the third quarter of 2012.

Threshold Pharmaceuticals, a presenting company at OneMedForum NY 2011, currently anticipates reporting top line results from the Phase 1 clinical trial in advanced leukemias in the second half of 2011, reporting top line efficacy analysis results from the randomized Phase 2 trial in pancreatic cancer at the end of 2011, and initiating a pivotal Phase 3 clinical trial of TH-302 plus doxorubicin compared to doxorubicin alone in patients with metastatic or locally advanced unresectable soft tissue sarcoma in the middle of 2011.