Millennium Pharmaceuticals Inc. signed its fourth corporatecollaboration and the largest yet for the genomics company, with $90million in committed funding.

Millennium will get the license fees and research payments overseven years from Wyeth-Ayerst in a collaboration to discover anddevelop products for treating central nervous system (CNS)disorders. The value of the deal to Millennium, of Cambridge, Mass.,could increase to well over $100 million through the payment ofmilestones and sales royalties.

Another aspect of the deal entails the sharing by Millennium of itsbioinformatics tools and technologies for use across Wyeth-Ayerst'sresearch and development programs. Millennium will be able to usecertain Wyeth-Ayerst chemical libraries in its own small-moleculedevelopment efforts.

Part of the $90 million Wyeth-Ayerst is paying over the seven yearsof the collaboration is for access to Millennium's genomics andgenetics technologies, including its Rapid Analysis of DifferentialExpression (RADE) system for identification of modulated genes andits transcriptional profiling technologies.

Committed funding from Millennium's partners now totals about$265 million, with the value of the deals in excess of $300 million.This deal is the third in which Millennium is equipping its partnerwith bioinformatics tools and the second in which it gained access tothe partner's libraries.

Both providing bioinformatics tools and developing small moleculesrepresent new business opportunities for Millennium, StevenHoltzman, the company's chief business officer told BioWorld TodayWednesday. In fact, he said, access to genomics technologies mayhave been a bigger draw for Wyeth-Ayerst than the CNScollaboration.

Millennium is developing capabilities for its small-molecule programand plans to partner some of those areas.

"The technology sharing arrangement will enable both companies tomore effectively pursue their own independent drug discovery anddevelopment efforts in a broad range of diseases," Holtzman said.

The collaboration with Wyeth-Ayerst, the Radnor, Pa.,pharmaceutical division of American Home Products Corp., initiallywill focus in psychiatric disorders such as schizophrenia, depressionand anxiety. The deal includes provisions to work together on abroader range of CNS diseases.

Wyeth-Ayerst will be responsible for worldwide development andmarketing of small molecules and vaccines in the CNS area.Millennium has worldwide development and marketing responsibilityfor antisense and diagnostic products arising from the collaboration.Wyeth-Ayerst has rights of first refusal for therapeutic proteins andgene therapies unless Millennium first negotiates a deal with a thirdparty.

Holtzman said Millennium already has extensive work ongoing in theCNS area, using genetic and complementary DNA approaches. Thecompany has research collaborations with universities in the areas ofschizophrenia and affective disorders, with at least one linkage in thelatter area, he said. RADE and cDNA technologies have been appliedextensively to CNS-related genes.

Millennium now is researching six disease areas with its fourcorporate partners: obesity and diabetes with Hoffmann-La RocheInc., of Nutley, N.J.; atherosclerosis and certain cancer targets withEli Lilly and Co., of Indianapolis; and inflammatory disorders of therespiratory system with Astra AB, of Sodertlje, Sweden.

"Our strategic alliance with Millennium demonstrates our continuedcommitment to building a state-of-the-art research program at Wyeth-Ayerst Research," said Robert Levy, president of the division."Millennium's premier genomics technology complements other keytechnologies in our discovery area, and our proven capabilities insmall-molecule chemistry, lead optimization and preclinicaldevelopment."

The companies said Wyeth-Ayerst officials reviewed the capabilitiesof more than a dozen genomics companies before deciding to partnerwith Millennium. One consideration was Millennium'scomprehensive technologies that include approaches in humangenetics, mouse genetics, cDNA and computational biology. Alsocited was Millennium's core genomics capabilities in high-throughput sequencing and genotyping, robotics and automation; itsability to elucidate the biological role and function of genes; and thefact the CNS program already is under way.

Millennium's bioinformatics tools will be used by Wyeth-Ayerst toapply genomic information to selection of molecular targets, speeddevelopment of candidates and help identify patient populations. Thetranscriptional profiling technology will help link human diseases togene defects.

Millennium's stock (NASDAQ:MLNM) closed Wednesday at$11.50, up 25 cents. News of the collaboration will be disclosedtoday. n

-- Jim Shrine

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