ARCUS Therapeutics, LLC: New Study Shows Vascular Targeting Can Starve Tumors in Mice; Validates Pioneering Work of Dr. Philip Thorpe.

Business Editors/Health & Medical Writers

WATERTOWN, Mass., STOCKHOLM, Sweden, & TUSTIN, Calif.--(BUSINESS WIRE)--Feb. 22, 2001--ARCUS Therapeutics, LLC, a joint venture between Peregrine Pharmaceuticals (Nasdaq: PPHM) and OXiGENE, Inc. (Nasdaq: OXGN; SSE: OXGN), announced today that a publication in the journal Cancer Research validates ARCUS's Vascular Targeting Agent (VTA) technology for treating cancer. VTAs are anti-cancer agents that act by cutting off the supply of oxygen and nutrients to tumor cells. The group that performed the new studies is based at the Institute of Pharmaceutical Sciences in Zurich, Switzerland and is headed by Dr. Dario Neri.

Dr. Neri's group treated three types of solid tumors in mice by directing a blood clotting protein, truncated tissue factor (tTF), to a molecular marker (the ED-B domain of fibronectin) naturally expressed on the tumor vasculature. Once localized to the tumor blood vessels, the tissue factor protein activated a chain reaction leading to the formation of blood clots that blocked the blood vessels, thereby starving the tumor. At the highest doses (35 ug of the protein), Dr. Neri observed complete tumor eradication without apparent side effects in 30% of the mice treated. This is therapeutically relevant for three reasons:

-- The marker Dr. Neri used is found in tumor vessels in both mice and humans

-- It is expressed in a majority of aggressive solid tumors

-- It does not appear in normal vessels and tissues.

Dr. Neri's study built upon and further validated the vascular targeting strategy pioneered by Dr. Philip Thorpe, the inventor of the VTA technology and a consultant for ARCUS in the development of its VTA technology. Dr. Thorpe first demonstrated the proof-of-concept for vascular targeting using coagulation proteins in a study published in Science in 1997. In this study, Dr. Thorpe used a monoclonal antibody to direct tTF towards a marker engineered to be artificially expressed in the tumor vasculature. Complete tumor regression was observed in 38% of the mice.

"Our work indicated that cancer therapies could be created by targeting tissue factor towards a naturally-expressed marker in tumor blood vessels," said Dr. Thorpe. "It is very exciting that Dr. Neri has identified such a marker and has constructed a drug that selectively clots tumor vessels."

"Dr. Neri's study demonstrates the enormous potential of vascular targeting and the use of tTF as a therapeutic tool for the treatment of a wide variety of cancers," said Edward Legere, Director and Interim President and CEO of Peregrine Pharmaceuticals. "With broad patent coverage of the VTA technology, ARCUS will lead the efforts to further develop and commercialize this next-generation cancer therapy."

"This independent peer reviewed study is a significant step forward in the validation of Dr. Thorpe's work and reaffirms the potential value of the VTA technology of ARCUS," said Bjorn Nordenvall, M.D., Ph.D., Chairman and CEO of OXiGENE, Inc.

ARCUS Therapeutics, LLC is a joint venture established in May 2000 between Peregrine Pharmaceuticals (Nasdaq: PPHM) and OXiGENE, Inc. (Nasdaq: OXGN; SSE: OXGN) for the development of Vascular Targeting Agents (VTAs) to treat a wide variety of cancers. Combining Peregrine's VTA technology and OXiGENE's next-generation tubulin binding compounds, in conjunction with broad patent coverage, ARCUS is positioned to be a premier vascular targeting company.

Peregrine Pharmaceuticals Inc. is a biopharmaceutical company focused on the development, commercialization and licensing of unique technologies for the treatment of cancer, primarily based on its "collateral targeting technologies." These technologies therapeutically target cell structures and cell types, rather than surface cancer cells, as a means to attack solid tumors, without causing damage to surrounding healthy tissue. The Company has three collateral targeting technologies: Cotara(TM), Vasopermeation Enhancement Agents (VEA), and Vascular Targeting Agents, (VTA). The Company also has a direct tumor-targeting agent called Oncolym(R) for the treatment of advanced non-Hodgkin's B-cell Lymphoma. Oncolym has been licensed to Schering AG, Germany, which is now responsible for all existing and future Oncolym clinical trial programs as well as marketing.

OXiGENE, Inc. is an international biopharmaceutical company and a world leader in vascular targeting, developing a diverse portfolio of innovative products to combat cancer and other major diseases. The Company's mission is to develop new therapeutics that will enhance the effectiveness of traditional cancer treatments and to introduce therapies that attack cancer in new ways. The Company's flagship technology CA4P, licensed to Bristol-Myers Squibb (BMS), works through its effect on endothelial cells that line the interior tumor blood vessels. In November 2000, BMS received approval from the FDA on its Investigational New Drug application to begin the next phase of its clinical development. The Company also has an NF-KB inhibiting anti-cancer drug, Declopramide, which began Phase II efficacy studies in December 2000. OXiGENE has its international corporate headquarters in Boston, MA.

Safe Harbor Statement: Certain statements made in this press release are forward-looking and are made pursuant to the safe harbor provisions of the Securities Litigation Reform Act of 1995. These statements, which are often preceded by words such as "will," "may," "can," "could," "should," and "are expected to," as well as verbs reflecting the future tense, involve risks and uncertainties that may cause OXiGENE's, Peregrine's or ARCUS's actual results or outcomes to be materially different from those anticipated and discussed in this press release as a result of risks included in OXiGENE's and Peregrine's respective most recent Annual Reports on Form 10-K and in their separate other filings with the Securities and Exchange Commission during the past 12 months.