OXiGENE To Commence First Ever Oncology Clinical Trial Combining A Vascular Disrupting Compound, Combretastatin A4P, With An Anti-Angiogenic Agent, Avastin

WALTHAM, Mass., Dec. 5 /PRNewswire-FirstCall/ -- OXiGENE, Inc. , a leading developer of biopharmaceutical compounds designed to treat cancer and certain ophthalmologic diseases, today announced that it will initiate a new clinical trial with its lead vascular disrupting compound, Combretastatin A4 Phosphate (CA4P). The Company will commence a Phase Ib clinical study to evaluate CA4P in combination therapy with Avastin(R) (Bevacizumab), a drug that is owned and marketed by Genentech . The Phase Ib clinical trial follows previously announced preclinical data presented at a recent conference of the American Association for Cancer Research (AACR/NCI/EORTC) which showed that the combination of CA4P with the anti-angiogenic drug, Avastin, produced significant anti-tumor activity and could offer a powerful and highly targeted treatment strategy for fighting solid tumors. This will be the first human clinical trial to pair a vascular disrupting compound and an anti-angiogenic agent in the treatment of cancer, specifically in people who have failed previous treatment and who are in advanced stages of disease.

This trial is an important strategic complement to the breadth of studies evaluating CA4P in combination therapy in oncology, and it confirms OXiGENE’s lead clinical position as the first developer of VDAs to pair a small molecule with chemotherapy, radiotherapy, and now, anti-angiogenic therapy.

“Preclinical models continue to support the theory that the combination of compounds targeted toward tumor vasculature could have a profound anti-tumor effect in humans,” stated David Chaplin, Ph.D., Chief Scientific Officer and Head of Research and Development at OXiGENE. “In addition, we believe the complementary action of a VDA with anti-angiogenic approaches may have utility not only in cancer, but in other diseases where abnormal new vessel growth underlies the disease pathology.”

In recent preclinical studies that examined the efficacy of combining Avastin with CA4P in a human renal cell carcinoma model (Caki-1), CA4P was shown to enhance the effect of Avastin. The data showed that treatment with Avastin or CA4P alone resulted in tumor growth delays of 8 days and 6 days, respectively. The data also showed that CA4P was effective at causing extensive vasculature damage and tumor cell death in the central regions of solid tumors. However, when CA4P was administered in combination with Avastin, statistically significant, enhanced anti-tumor effects were observed: The combination of CA4P plus Avastin led to a tumor growth delay of 13 days -- an increase of approximately 61 per cent in the effectiveness of Avastin.

The enhanced anti-tumor effect achieved from combining these compounds in this preclinical model may correlate to the complementary approaches of each compound. OXiGENE’s CA4P is a novel, small molecule vascular disrupting agent that causes massive and rapid tumor death by disrupting the function of abnormal blood vessels that support tumor growth and survival. CA4P causes extensive destruction of central regions of tumors -- areas that are believed to contain cells that are resistant to most conventional therapies, such as chemotherapy and radiation. Avastin, by contrast, is a recombinant humanized antibody to Vascular Endothelial Growth Factor (VEGF). Avastin is designed to bind to and inhibit VEGF, a protein that plays a critical role in tumor angiogenesis (the formation of new blood vessels to the tumor). OXiGENE believes that combining these compounds could ultimately offer a new and viable cancer treatment strategy that destroys a tumor by targeting not only new blood vessel growth, but also by razing the already established tumor blood vessel network.

The FDA, in February 2004, approved Avastin for use in combination with intravenous 5-Fluorouracil-based chemotherapy as a treatment for patients with first-line -- or previously untreated -- metastatic cancer of the colon or rectum. Genentech is pursuing a broad late-stage clinical development program with Avastin, evaluating its potential use in multiple tumor types. Phase III clinical trials in adjuvant colorectal cancer, renal cell carcinoma, prostate cancer, and metastatic and locally advanced pancreatic cancer are being conducted. Genentech reports that a Phase III trial in first-line ovarian cancer is planned. (1)

OXiGENE’s Phase Ib combination trial with Avastin will be a traditional open-label, multi-center trial designed to determine the safety and tolerability of ascending doses of CA4P administered intravenously in combination with Bevacizumab. Dosing levels of CA4P will be escalated until a maximum tolerated dose is achieved. Anti-tumor effects and tumor response will be evaluated using the international standard for oncology clinical trials, known as Response Evaluation Criteria In Solid Tumors (RECIST). Pharmacodynamic effects to assess blood flow shutdown to the tumor will be assessed with Magnetic Resonance Imaging (MRI).

“We believe that the results from this trial could have a profound impact on the development of therapeutic approaches to treat cancer by targeting the abnormal vasculature associated with solid tumors,” said Frederick Driscoll, President and Chief Executive Officer at OXiGENE. “With Genentech’s approval for Bevacizumab for the treatment of colorectal cancer, as well as the myriad of trials investigating its use for solid tumor types such as renal cell carcinoma, pancreatic cancer and others, we are hopeful that this combination will have a potentially dramatic impact on cancer treatment therapies.”

About Combretastatin A4P (CA4P)

CA4P leads a novel class of small molecule drug candidates called vascular disrupting agents (VDAs). CA4P works via two potentially synergistic processes that selectively target pericyte-depleted neovessels, which lack ensheathment from smooth muscle support cells. CA4P is a potent and reversible tubulin depolymerizing agent that causes newly formed endothelial cells that line blood vessels to change shape, round up and detach from the vessel wall. Recent preclinical research has also shown that CA4P disrupts the molecular engagement of VE-cadherin, a junction protein important for endothelial cell survival and function, and inhibits the associated B-catenin/AKT signaling pathway, leading to rapid vascular collapse and necrosis. These complementary mechanisms block the flow of blood to a tumor and deprive it of oxygen and nutrients essential to its survival. Similarly, in eye diseases that are characterized by abnormal blood vessel growth, CA4P has been shown in preclinical studies to suppress development and induce regression of these unnecessary blood vessels.

The commencement of this Phase Ib clinical trial brings to seven the total number of actively enrolling clinical studies evaluating CA4P in oncology. These clinical trials involve the use of CA4P in both single-agent and combination therapies including a Phase II trial evaluating CA4P in combination with carboplatin/paclitaxel for the treatment of platinum- resistant ovarian cancer, as well as a Phase Ib/II trial studying CA4P in combination with radiotherapy. The lead investigators of this trial recently reported synergistic effects with CA4P and radiotherapy, as well as evidence of sustained blood flow shutdown to tumors, and side effects in patients that are mild and self-limiting. CA4P is also being studied in a Phase II clinical trial in myopic macular degeneration.

About OXiGENE, Inc.

OXiGENE is an emerging pharmaceutical company developing novel small- molecule therapeutics to treat cancer and eye diseases. The Company’s major focus is the clinical advancement of drug candidates that selectively disrupt abnormal blood vessels associated with solid tumor progression and visual impairment. OXiGENE is dedicated to leveraging its intellectual property position and therapeutic development expertise to bring life saving and enhancing medicines to patients.

Footnotes: (1) http://www.genentech.com Safe Harbor Statement

This news release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Any or all of the forward-looking statements in this press release may turn out to be wrong, including statements regarding the therapeutic efficacy and future success of CA4P either in single agent therapy or in combined therapy with Avastin or other compounds or therapies in treating cancer; the potential of CA4P to inhibit tumor growth either as a single agent or in combination therapy; and, the capabilities of CA4P to cause significant anti-tumor effects as a single- agent and in combination with other therapies. Forward-looking statements can be affected by inaccurate assumptions OXiGENE might make or by known or unknown risks and uncertainties. Additional information concerning factors that could cause actual results to materially differ from those in the forward-looking statements is contained in OXiGENE’s reports to the Securities and Exchange Commission, including OXiGENE’s Form 10-Q, 8-K and 10-K reports. However, OXiGENE undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise. Please refer to our Annual Report on Form 10-K for the fiscal year ended December 31, 2004 for a description of these risks.

All trademarks and/or registered trademarks in this release are the property of their respective holders.

OXiGENE, Inc.

CONTACT: Susan Hager, Director, Corporate Communications of OXiGENE, Inc.,+1-781-547-5900, shager@oxigene.com; or Media: Jenny Moede of WaggenerEdstrom Bioscience, +1-503-443-7507, jmoede@wagged.com

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