By Karen Young

Bayer AG and Millennium Pharmaceuticals Inc. expanded their $465 million 1998 collaboration to include three additional indications.

However, Millennium discontinued efforts related to the collaboration in osteoporosis and liver fibrosis.

Also, the companies to date have identified more than 140 drug targets, many of which have moved into assay development and high-throughput screening. Six projects are into lead optimization with structurally attractive compounds, including four projects that have shown disease efficacy in animals. Millennium said that the first of these compounds is scheduled to enter clinical testing soon, but would not disclose the indication or precisely when the testing would begin.

¿Really, the financial structure of the deal has not changed,¿ said Anna Protopapas, vice president of business development for Millennium, of Cambridge, Mass. ¿We restructured some of the therapeutic areas.¿

The alliance has focused on the use of gene analysis to find new active substances in the areas of cardiovascular disease, cancer, pain, hematology and viral infections. The new drug targets are relevant to thrombosis, urinary incontinence and benign prostatic hypertrophy.

A big part of the program is focused on cardiovascular indications and arteriosclerosis, Protopapas said, noting that some of the targets that Millennium discovered in the areas of osteoporosis and liver fibrosis have been returned to Millennium.

¿The overall structure of the relationship has not changed,¿ Protopapas said. ¿We deliver 225 new targets, and at the end of the day, Bayer takes those into drug discovery. So, we¿re not jointly developing and commercializing products.¿

Protopapas said that, clearly, over the last three years the alliance has created a critical mass in the discovery process, noting that the companies have the breadth of the pipeline to see things moving forward.

In a Robertson Stephens report by analyst Mike King, he noted that ¿the expansion of the alliance is based on continued success of the drug discovery program, proven by the companies¿ ability to move from gene discovery to clinical candidate status in less than 18 months, a remarkable increase in productivity.¿

The original deal was the largest drug development collaboration in biotechnology history at the time it was announced. The agreement called for Bayer, of Leverkusen, Germany, to pay Millennium up to $368.4 million in guaranteed funding and performance fees for drug targets identified by Millennium and a license fee for the use of Millennium¿s genomics technologies. The remaining $96.6 million was to be paid as an equity investment. With that investment and the license fee, Millennium was to get a total of $130 million up front.