Eli Lilly and Company Japan KK, Kobe, Japan and Takeda Chemical Industries, Ltd., Osaka, Japan announced that Eli Lilly and Company, Indianapolis, Indiana and Takeda signed an agreement on December 18, 2003, on joint development and co-marketing for ruboxistaurin mesylate (PKC ß Inhibitor, LY333531) in the Japanese market.

This agent is an investigational compound for oral administration discovered and developed by Eli Lilly and Company that is currently in Phase 3 clinical studies outside of Japan and Phase 2 studies have been initiated in Japan. Under the agreement, Eli Lilly Japan, a subsidiary of Eli Lilly and Company and Takeda will jointly develop and submit an NDA in Japan for the treatment of diabetic peripheral neuropathy and diabetic retinopathy, and subsequently, co-market this product in Japan.

Under the hyperglycemic condition, PKC (Protein kinase C) ß, one of the enzymes PKC known as adjusters of various cellular functions, becomes overactive and is implicated in the underlying process of microvascular damages of angiogenesis and vascular flow disorder, leading to diabetic microvascular complications.

Preclinical data have demonstrated that ruboxistaurin is a specific inhibitor of PKC ß. Ongoing clinical trials, conducted by Eli Lilly and Company, are investigating ruboxistaurin as a treatment for diabetic peripheral neuropathy, diabetic retinopathy (damage to the small blood vessels of the eye), and diabetic nephropathy (damage to the small blood vessels of the kidneys), the three major diabetic microvascular complications.

Eli Lilly Japan and Takeda expect to contribute to the treatment of diabetic microvascular complications once this investigational agent is approved and launched, which could represent a significant benefit to the patients with diabetes.