News Release

Yamanouchi Pharmaceutical Co., Ltd.

Yamanouchi Pharmaceutical Licenses Vasopressin Receptor Antagonist Now Under Development to U.S.-Based Warner-Lambert Company

May 7, 1998

In April 1998, Yamanouchi Pharmaceutical Co., Ltd. (Masayoshi Onoda, president and CEO), signed a licensing agreement with Warner-Lambert Company. (Melvin R.Goodes, Chairman and CEO), of the United States, covering YM087, a Yamanouchi-developed vasopressin receptor blocker that is undergoing clinical development as a treatment for patients with edema, hyponatremia (low sodium), and congestive heart failure. Under the agreement, Warner-Lambert acquires marketing rights to YM087 in North America, South America, Europe, and Africa. However, Yamanouchi retains co-promotion rights in these regions. Clinical development of the drug will be conducted jointly by the two companies.

YM087, a non-peptide, low-molecular-weight compound, is expected to become the first drug in the world that can antagonize both V1 and V2 vasopressin receptors. This new approach should, with a single drug, help improve cardiac dysfunction, cardiac hypertrophy, and pulmonary congestion and at the same time alleviate edema and maintain blood sodium levels. Both oral and injectable formulations are being developed. YM087 has entered Phase II of clinical development in Japan and Europe, well ahead of potential competing drugs in the same field. In the United States, an IND was submitted on April 3.

Yamanouchi has licensed and is now clinically developing atorvastatin, Warner-Lambert's HMG-CoA reductase inhibitor, a treatment for hyperlipidemia, for the Japanese market. Under a quid-pro-quo agreement, Warner-Lambert secured the right to select a Yamanouchi drug in development for cross-licensing. The introduction of YM087 will represent the fulfillment of this agreement. Regarding the clinical development of atorvastatin in Japan, Phase III trials are almost complete, and application for approval will be submitted soon. The drug has been marketed by Warner-Lambert and Pfizer Inc. in the United States under the brand name Lipitor since 1997, and has achieved approximately $1.4 billion in sales since its introduction.

Note: Vasopressin
A hormone secreted by the pituitary gland. There are two types of receptors that are sensitive to this hormone: V1 in the vascular smooth muscles and V2 in the kidney. The first causes the smooth muscles of the veins to contract, while the second promotes the reabsorption of water from the renal tubule, thus having an antidiuretic effect.

Warner-Lambert Company
Established: November 1955
Head office: Morris Plains, New Jersey
Annual sales: US$8.2billion
Chairman and CEO: Melvin R. Goodes
Main business: Discovery, development, manufacture and marketing of pharmaceutical, consumer health care and confectionery products


Yamanouchi Pharmaceutical Co., Ltd.
Established: April 1923
Head office: Nihonbashi-Honcho 2-3-11, Chuo-ku, Tokyo
Sales: ¥ 454.7 billion (consolidated results for the year ended March 31, 1997)
President and CEO: Masayoshi Onoda
Main business: Production, marketing, and import/export of ethical drugs, quasi drugs, food products, and medical machinery and equipment