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

ZYBRESTAT exerts its anti-tumor effects through the well-validated therapeutic mechanism of tumor blood supply deprivation. By selectively affecting and disabling tumor vasculature, ZYBRESTAT 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 2007 OXiGENE initiated a large-scale study with ZYBRESTAT for the treatment of anaplastic thyroid cancer, a highly lethal and aggressive malignancy for which there is currently no treatment.

In this and other clinical studies to date, ZYBRESTAT has shown promising results:

• In five Phase I studies ZYBRESTAT consistently demonstrated significant ability to cause reduction in tumor blood-flow.
• In an open-label Phase II study of ZYBRESTAT (monotherapy) in patients with advanced, relapsed anaplastic thyroid cancer, both median survival time and one-year survival rate exceeded the published survival statistics reported in clinical literature for similar patient cohorts.
• In addition to anaplastic thyroid cancer, ZYBRESTAT has also shown clinical activity (complete response, partial response and stable disease) in other tumor types, including ovarian cancer.

ZYBRESTAT 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 studies ZYBRESTAT demonstrated synergistic or additive effects when incorporated in various combination regimens with all of these modes of treatment.

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

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