May 19, 2000

Start of Clinical Trial at the EORTC using an Antibody as an Anti-Cancer Agent

Toagosei in cooperation with Protein Design Labs, Inc. (PDL; Fremont, California, USA ) has been developing an antibody-based drug using an anti-VEGF humanized monoclonal antibody as an anti-cancer agent. They entered into a phase I clinical trial in January 2000 under the auspices of EORTC ( European Organization for Research and Treatment of Cancer ).

The candidate anti-cancer drug, being of the humanized type, features a very strong neutralizing reactivity against VEGF protein secreted from the cells of solid tumors, and is a so called angiogenesis inhibitor, which inhibits growth of solid tumors by prohibiting evolution of blood veins around the tumor. The humanized antibodies generally have much lower toxicity compared with normal chemical agents, since their chemical structures are very close to those of the human immunoglobulin. It is thus expected that both marked clinical efficacy and reduction of side effects will be simultaneously expressed, especially when the above antibody is administered in combination with common cancer drugs ( chemical anti-tumor agents ). In tests conducted at the Toagosei laboratory, when the antibody drug was administered in combination with a chemical anti-tumor agent to mice in which a species of human tumors had been transplanted, the tumors were observed to dramatically shrink, and the dissection results showed that in more than 80% of the treated mice, the tumors were completely vanished.

Toagosei granted a non-exclusive license of its intellectual property rights of the anti-VEGF antibodies to PDL. Both companies will share the costs and expenses for the clinical development and will also share the results. The marketing rights in North America and the first option to the marketing rights in Europe and other territories outside of Japan are granted to PDL, and the profits of commercial sales of the product will be allocated between Toagosei and PDL. Toagosei holds solely the rights for the territory of Japan.

Notes:

1. PDL ( Protein Design Labs, Inc. )

   NASDAQ-listed American biotechnology company with a proprietary and strong antibody-humanization technology with experiences in clinical development of various antibody-drugs. In the past, Toagosei has invested 200,000,000 yen in PDL stock.

2. EORTC ( European Organization for Research and Treatment of Cancer )

   Primary European organization dedicated to the progress in medical treatment of cancer through research of new drugs, clinical development, etc. It has about 350 clinical facilities in 31 different countries as participants, and manages clinical treatment annually of about 7000 cancer patients.

3. Angiogenesis-Inhibiting Agent

   The growth of solid tumor necessitates generation of new blood veins.
   The angiogenesis inhibitor suppresses their generation, by priventing the supply of oxygen and other materials needed for the growth of tumor cells.