Peregrine Pharmaceuticals Inc has received approval from the U.S. Food and Drug Administration (FDA) to start its Cotara Phase III registration clinical study in recurrent glioblastoma multiforme (GBM). The approved clinical protocol is designed to rigorously evaluate the safety and efficacy of Cotara in a multi-center clinical trial. This single trial will be sufficient for the FDA to evaluate the efficacy and the safety of Cotara for product registration.

"We are pleased to reach this important milestone in the development of the Cotara program. Cotara now has a clear regulatory path for product approval," said Edward J. Legere, Peregrine's president and CEO. "This approved protocol provides a roadmap to product licensure for brain cancer that should make the Cotara program even more attractive to potential licensees or partners. The Company is actively seeking a strategic partner in order to further advance its Cotara program that includes the treatment of brain cancer as well as colorectal carcinoma and other solid tumor types."

Cotara is the company's first Tumor Necrosis Therapy (TNT) based product. TNT based drugs directly target and bind to the dead and dying regions of virtually all solid tumors. Rapidly growing tumors contain a significant proportion of degenerating or dead cells in addition to numerous proliferating viable cancer cells. These dead or dying cells result from incomplete formation of tumor blood vessels and impaired immune cell response. The accumulation of dying cells results in the formation of a dead, or necrotic, core present in virtually all solid tumors beyond a very small size. TNT based drugs enter and bind to targets only available for binding in the necrotic areas of cancer. Hence, TNT-based therapeutic agents have the potential to deliver therapeutic agents preferentially targeted to virtually all solid tumors.

TNT antibodies bind to universal intracellular antigens, DNA histone complexes, exposed in the necrotic core of malignant solid tumors. While TNT is capable of binding with nuclear histones found in all cells, preclinical studies indicate that TNT antibodies do not penetrate normal cells with an intact cell membrane, making TNT highly specific to necrotic tumor tissue.

Given TNT's high specificity for necrotic tumor cells, TNT antibodies make excellent delivery molecules for a wide variety of anti-cancer killing agents. To date, the TNT technology platform has been used to deliver various killing agents such as radioactive isotopes, cytokines, chemokines and liposomes to solid tumors. Peregrine believes that many other anti-cancer compounds could potentially benefit from targeted delivery using TNT antibodies.

Glioblastoma Multiforme is a grade four brain cancer that is very aggressive and almost universally fatal. Recurrent (patients who have relapsed from their primary treatments) GBM has always been a difficult clinical problem. Recurrence typically occurs in approximately 80% of patients within 6-12 months after resection (primary surgery). Re-treatment for GBM patients often is with a palliative intent. Re-treatment options include radiation therapy, surgical resection or chemotherapy. Since the approval of temozolomide for refractory anaplastic astrocytoma in 1999, use of temozolomide has increased for the treatment of refractory GBM as well. However, data from randomized and non-randomized temozolomide clinical studies show only modest clinical efficacy in this patient population with a median time to progression of 11-17 weeks and a median survival time of 21-28 weeks. New therapies for recurrent GBMs are desperately needed.