Myriad Genetics Inc. said Monday it entered into a collaborationworth up to $60 million with Ciba Pharmaceuticals to discover genesthat will lead to the development of drugs for cardiovascular diseases.

Myriad, a privately held company in Salt Lake City, received $32million in equity funding and research payments in the five-year deal.Myriad also can earn $28 million in milestones, as well as royaltieson product sales.

Ciba Pharmaceuticals, of Summit, N.J., is a division of Ciba-GeigyCorp. USA, which is a wholly owned subsidiary of Ciba-Geigy Ltd.,of Basel, Switzerland. Ciba already has cardiovascular products onthe market and ongoing work in the area, but wanted to expand itsfranchise with a gene-discovery approach.

"It will be a new area for us," Mary-Frances Faraji, CibaPharmaceuticals' manager of communications, told BioWorld. "Weview molecular genetics as a tool we need. We hope to get at thegenetic causes of disease, to find the genes or their mutations.

"We've been not only a pioneer but a leader in cardiovasculartherapies," Faraji said. "This [deal] is to underscore that we're in thisarea for the long term."

Ciba will get exclusive worldwide rights to all therapeutic productsresulting from the collaboration, and Myriad will get worldwidediagnostics rights. An equal number of members from each companywill make up a committee to direct the research.

Myriad, along with government and university collaborators,discovered the BRCA1 breast cancer gene. And researchers fromMyriad and the University of Utah discovered the tumor-suppresserfunction of the MTS1 (multiple tumor suppresser 1) gene thatappears to be involved in the formation of many cancer types.

Peter Meldrum, Myriad's president and CEO, said his company hasbeen working for years in the cardiovascular area. "The resources anddiscovery strategy are the same as for the cancer program, in whichwe've been very successful to date," he told BioWorld.

Myriad has been funding work at the Cardiovascular GeneticResearch Center at the University of Utah, which involves geneticanalyses of families. At the same time, Meldrum said, Myriad hasbeen doing linkage studies in the area of cardiovascular disease.

Neither company would disclose particular target areas, thebreakdown in equity vs. research investment for the initial $32million, nor the events that would trigger milestones. Officials said,however, that milestones can be attained in the preclinical stage.Murdock said Ciba's stake will be less than 10 percent; Eli Lilly andCo., of Indianapolis, which is Myriad's collaborator for BRCA1, alsohas a stake of less than 10 percent.

"We can't talk specifically about the exact stage of the[cardiovascular] research, but we see the area as important,"Meldrum said. "We've made good progress in identifying targets andhave early linkage work going after certain specific genes."

Meldrum said the strategy is to start by studying large families thathave a preponderance of cardiovascular disease. Linkage technologywill be used to locate a disease-causing gene on a particularchromosome. Additional technologies will be used to map andnarrow the region. Then candidates will be screened to find the rightgene. At that point the complete sequence will be obtained andpatents filed.

The discovered gene should lead to commercial opportunities intherapeutics, which Ciba would pursue, and in genetic testing, whereMyriad would develop an assay to identify those who carry mutationsthat would make them susceptible to cardiovascular disease.

Ciba can take the information from the discovered gene and proteinsit encodes, and look at a variety of therapeutic applications, includinggene therapy, development of a small molecule that would mimic thefunction of the protein, and protein replacement therapy. n

-- Jim Shrine

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