Fosbretabulin (combretastatin-A4 phosphate/CA4P) is OXiGENE's lead tumor vascular disrupting agent (VDA) product candidate, and poised to become a first-in-class VDA product. Fosbretabulin is currently being evaluated in multiple clinical trials as a treatment for solid tumors.

Fosbretabulin exerts its anti-tumor effects through the well-validated therapeutic mechanism of tumor blood supply deprivation. By selectively affecting and disabling tumor vasculature, fosbretabulin reduces the blood supply necessary for tumor growth and survival. The resulting oxygen starvation and build-up of tumor metabolic by-products causes the cancer cells within the central core of the tumor to die.

In clinical studies to date, fosbretabulin has shown promising results:

• In five Phase I studies fosbretabulin consistently demonstrated significant ability to cause reduction in tumor blood-flow.
• In an open-label Phase II study of fosbretabulin (monotherapy) in patients with advanced, relapsed anaplastic thyroid cancer (ATC), both median survival time and one-year survival rate exceeded the published survival statistics reported in the clinical literature for similar patient cohorts.
• In one phase 1 study with CA4P monotherapy, 1 subject with ATC had a complete response which was durable and lasting over 10 years.

In addition to anaplastic thyroid cancer, fosbretabulin has also shown clinical activity (partial response and stable disease) in other tumor types, including ovarian cancer. For further information on our clinical trials, please visit the OXiGENE website at: www.oxigene.com.

Fosbretabulin has also demonstrated broad potential therapeutic value when combined with mainstay oncology modes of treatment including chemotherapy, radiation therapy and the more recent "molecularly-targeted therapies," such as the tumor angiogenesis inhibitors used to treat a wide range of solid tumor types.

In preclinical and human studies fosbretabulin demonstrated synergistic or additive effects when incorporated in various combination regimens with these modes of treatment.

Fosbretabulin is the first tumor VDA to be tested in combination with a tumor-angiogenesis-inhibiting drug (bevacizumab / AVASTIN®) in humans.