About Us

Developing Targeted Therapies for Cancer

Targeting Tumor Hypoxia: A Novel and Powerful Therapeutic Approach

Threshold is a clinical stage biopharmaceutical company focused on the discovery and development of cancer therapeutics based on a novel and powerful approach of targeting tumor hypoxia. Hypoxia, or severe oxygen deprivation, is characteristic of virtually all solid tumors as well as the bone marrows of patients with some hematologic malignancies. Normal healthy tissues are not usually hypoxic because they are well oxygenated by virtue of having a regular and highly structured network of blood vessels that provide for adequate blood flow and delivery of oxygen and nutrients. In contrast, the vasculature supporting solid tumor masses is typically highly aberrant, resulting in inadequate blood flow and the consequent development of hypoxic regions. Not only are the cells that reside in hypoxic regions of tumors resistant to conventional cancer therapy, it has also more recently been shown that hypoxia plays a central role in tumor progression, metastasis, and ultimately treatment failure. Research also suggests that hypoxia within the bone marrow is associated with certain blood cancers, such as leukemia and multiple myeloma. By designing molecules to be activated under conditions of severe tumor hypoxia, we are building a pipeline of “hypoxia-activated prodrugs”, or “HAPs”, that selectively target tumor cells. We believe that HAPs hold promise to be more effective in killing tumor tissue and less toxic to healthy tissue than conventional anti-cancer drugs.

HAPs: Broad Clinical Applicability to Multiple Tumor Types

Threshold’s scientific platform based on HAP technology has potential for broad clinical applicability, offering therapies to treat most solid tumors and blood cancers. TH-302, a HAP discovered by scientists at Threshold, is currently the subject of multiple clinical studies. The most advanced study is a pivotal Phase 3 clinical trial evaluating TH-302 in combination with doxorubicin in patients with soft tissue sarcoma, which was initiated in September 2011. A second Phase 3 study, which opened in December 2012, is designed to evaluate TH-302 in combination with gemcitabine in patients with advanced pancreatic cancer. In addition, multiple early-stage clinical trials are evaluating the safety and efficacy of TH-302 in a variety of solid and hematologic tumors either as monotherapy or in combination with other established anti-cancer therapies.

[18F]HX4: Hypoxia PET Imaging

In March 2013, Threshold announced the acquisition of [18F]HX4 [flortanidazole (18F)] from Siemens Healthcare. [18F]HX4 is an investigational radiolabeled Positron Emission Tomography (PET) tracer for hypoxia. [18F]HX4 could potentially be used as a companion diagnostic to hypoxia-targeted therapeutics based on Threshold’s drug discovery platform. Our initial intent is to develop [18F]HX4 to determine a patient’s tumor hypoxia profile, which may identify patients who will best respond to Threshold’s hypoxia-targeted therapeutics.

Cancer: Addressing a Significant Unmet Medical Need

Cancer is the second leading cause of death in the United States and presents a significant unmet medical need. The American Cancer Society estimates more than 577,000 people will have died from cancer in the United States in 2012. Many cancers, such as pancreatic, lung and liver cancer, have few effective treatments and very low survival rates. Conventional anti-cancer therapies are not highly effective at killing hypoxic tumor cells, and their lack of selectivity often leads to serious off-target toxicity. In addition, more recently introduced antiangiogenic therapies are designed to interrupt tumor vasculature and, in doing so, may also increase levels of tumor hypoxia. Threshold’s HAP technology offers the potential to expand therapeutic options available for cancer patients and their physicians by fostering a new generation of hypoxia-targeted drugs designed to selectively kill tumor cells and spare normal healthy tissue. Research demonstrates Threshold’s hypoxia-targeted drug TH-302 has anti-tumor activity when used alone and increases tumor-killing activity when used in combination with a wide variety of both traditional as well as more recently developed anti-cancer therapies.