August 5, 2002

Kissei Pharmaceutical Co., Ltd.
Takeda Chemical Industries, Ltd.

Kissei Pharmaceutical Co., Ltd., Nagano, Japan, ("Kissei", President and CEO: Mutsuo Kanzawa) and Takeda Chemical Industries, Ltd., Osaka, Japan ("Takeda", President: Kunio Takeda) jointly announced that both parties entered into a co-marketing agreement on August 5, 2002 for "mitiglinide" (development code: KAD-1229) in Japan.   Kissei originally invented and has developed this novel short-acting insulin secretagogue to suppress postprandial hyperglycemia, and is currently preparing for NDA filing in Japan.

Under the agreement, Kissei will co-market the product with Takada under the same product name in Japan after obtaining the NDA approval.

For the recent years, the number of diabetic patients in Japan has been constantly on the increase, and accordingly, a therapy, that can prevent diabetic complications and its progress according to the individual patient condition, is expected to become available.   Mitiglinide suppresses and controls well postprandial hyperglycemia which recently began to be taken as an independent risk factor of diabetic complications such as cardiovascular diseases.   This agent is less likely to cause hypoglycemia than existing products such as sulfonylureas and leads to less burden to the pancreatic βcells, therefore, it is expected to improve the quality of diabetic treatment.

[Comments from both companies]
Kissei Pharmaceutical Co., Ltd. : Yukiyoshi Ajisawa, Ph.D., Managing Director, Division Director, Corporate Planning & Management"Kissei aims to become an "R&D-oriented pharmaceutical company which contributes to the health of people in the world through developing and offering original pharmaceutical agents". By co-marketing this original agent developed, mitiglinide, with Takeda, Kissei expects that the drug will be reached to many diabetic patients, and thus contribute to the improvement in medical treatment of this field.   In addition to mitiglinide, Kissei is promoting development of other antidiabetic drugs such as selective SGLT2 inhibitor, and we hope that Kissei can continuously contribute to the health of people in the world through development and supply of our original pharmaceutical products."

Takeda Chemical Industries, Ltd. : Makoto Yamaoka, Member of the Board, General Manager, Pharmaceutical Marketing Division The area of life-style related diseases, where patients are rapidly increasing, is one of the main fields wherein we focus on complying with our management mission; "Striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products".
In the diabetic field, a sub-category of the life-style related diseases, this co-marketing alliance with Kissei will add the novel short-acting insulin secretagogue agent to our current product line consisting of "BasenR" and "ActosR". We are confident that, under the cooperation with Kissei, we will be able to contribute more to the treatment of diabetes according to the individual patient condition, and to the QOL of more number of diabetic patients. That will really match our anagement mission.

< Reference >
1) Mitiglinide
Mitiglinide was invented and has been developed by Kissei Pharmaceutical Co., Ltd. as a rapid-onset, short-acting insulin secretagogue, which is effective from low doses. It is a unique blood glucose lowering agent that controls blood glucose effectively by suppressing postprandial glucose spike because of the rapid insulin release after dosing compared with currently available insulin secretagogues. The postprandial glucose spike is recently drawing much attention as an independent risk factor of diabetic complications such as cardiovascular diseases. Also, due to the short-acting characteristic of this agent, it is less likely to cause hypoglycemia, and it is expected to cause less fatigue of the insulin-releasing pancreatic β-cell function.
In the double-blind, comparative Phase III clinical study which was recently completed, mitiglinide significantly improved indices of blood glucose control: HbA1c, postprandial glucose and fasting plasma glucose levels. At the same time, it was confirmed that the incidence of adverse effects such as hypoglycemia, the major safety concern connected with the clinical use of blood glucose lowering agents, remained as low as placebo.

2) NDA filing of Mitiglinide
Kissei is currently preparing for filing an NDA for this agent with the Japanese regulatory authority (Ministry of Health, Labor and Welfare) by the end of this year.

3) Overseas Development of Mitiglinide
Kissei licensed mitiglinide to Servier in France to develop in Europe and Asian countries including China, and they are conducting comparative Phase III clinical trials mainly in Europe. In U.S., Kissei's subsidiary, Kissei Pharma U.S.A. is conducting phase II clinical trials.

4) SGLT2 Selective Inhibitor
This agent inhibits the activity of SGLT2, the transportor  related to reabsorption of sugar, selectively present in the kidney, thus suppresses the reabsorption of sugar in the proximal tubules, makes excessive sugar excreted in the urine and leads to normalization of blood sugar level.

For further information, please contact:

Kissei Pharmaceutical Co., Ltd.
Public Relations, General Administration Phone: +81-263-25-9523

Takeda Chemical Industries, Ltd.

	Corporate Communications Dept.		(Osaka) +81-6-6204-2038
			(Tokyo) +81-3-3278-2039