Translating a disease gene discovery into effective therapeutictreatments requires deciphering its function and a Cambridge, Mass.,start-up company, Exelixis Pharmaceuticals Inc., believes it has twokey technologies to help unlock those complicated secrets.

Formed in 1995, privately held Exelixis just completed its first majorfinancing round, generating $12.3 million from a group of investorsled by Atlas Venture, of Boston, Oxford Bioscience Partners, of LosAngeles, and PaineWebber Inc., of New York.

"We've raised a total of about $16 million, including $4 million lastyear," said Remi Barbier, Exelixis' chief operating officer. Barbierwas former vice president of corporate development at Xoma Corp.,of Berkeley, Calif.

Jean-Francois Formela, of Atlas Venture, is acting CEO and AlanWalton, of Oxford Bioscience, is chairman.

Barbier said Exelixis is "not a product shop" nor is it a "genesequencing shop."

What the company does, he said, "is come up with the optimaltargets, from genes, for drugs."

To accomplish that feat, Exelixis attempts to plot the pathway ofgenetic activity unleashed by a disease gene.

"You can think of us in terms of triple A [Automobile Association ofAmerica]," Barbier said. "If you want to travel from Boston to SanFrancisco, we can provide a detailed road map to get you there."

Exelixis studies fruit fly (Drosophila melanogaster) and mousemodels to track genetic pathways involving human genes related todisease. The company uses flies and mice because their genomes arevery similar to humans. And in the case of Drosophila, fruit flygenerations are measured in weeks, instead of years, providing a fast-forward look at human gene development.

With Exelixis' fly model system, called PathFinder Screens, thecompany can take a known human disease gene, insert it in the flygenome, and track the biochemical pathway unleashed by proteinsexpressed by the gene. Because the fly reproduces so quickly, themodel also is used to determine the effects of altering genes.

In the mouse model system, called ExCell Trap, Exelixis targetssecretory genes, whose proteins are released from cells.

Secretory proteins include molecules such as enzymes, hormones andantibodies that perform their functions outside cells and are a majorfocus of biotechnology drug development.

In the ExCell Trap mouse model, secretory genes of the mousegenome are disrupted at random to track the proteins they express.

Exelixis, Barbier said, is "focused on functional genomics. We are asecond generation genomics company. We are able to identify thecomplete pathway. We can say this is what it looks like and thismolecule is the optimal target (for a therapeutic treatment). Manytimes it is not the gene. The target is somewhere downstream."

Exelixis' business strategy is aimed at three types of potentialcollaborations, he said. One would involve pharmaceuticalcompanies and big biotechnology firms who have collections ofgenes and want to find out how they work.

A second type would involve start-up biotechnology firms withlimited resources. In return for future compensation, Exelixis wouldattempt to boost the value of their discovered genes by defining theirfunctions.

A third type of collaboration, Barbier added, would focus on drugdiscovery based on genes found by Exelixis.

Barbier said the company came out of its first major round offinancing with more money than expected because initial talks withpotential corporate partners were encouraging. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.