Cadus Pharmaceutical Co. has been refining its yeast-basedscreening technologies for the past year and a half. Now, ina $35 million collaboration with Bristol-Myers Squibb Co.,Cadus will begin identifying lead compounds.The companies, both based in New York, said Thursdaythey will work together in developing compounds screenedby Cadus' G protein-coupled receptor technology. Thereceptors regulate the physiologic behavior of the cells byblocking or transmitting signals from outside the cell,through G proteins (found in the inner surface of the cellmembrane), to the cell's interior.Cadus uses genetically altered yeast strains that containhuman G protein-coupled receptors and function as if theywere in human cells. The strains then can be used to seehow they react to compounds, thus identifying drugcandidates."We're the only company in our field [of G proteins],"Jeremy Levin, president and CEO of Cadus, told BioWorld."Cadus is going to be a leader in target-based drugscreening."Cadus is assured of at least $34.5 million in thecollaboration. Bristol-Myers will provide $4 million inannual research funding for three years with an option fortwo more years; make an equity investment of $12.5million for about 15 percent of Cadus; commit to a furtherequity investment up to $5 million upon achievement ofcertain milestones or at Cadus' next private financing; andcommit up to $5 million upon Cadus' initial publicoffering. Cadus also will receive specific milestone androyalty payments.The collaboration is the largest Bristol-Myers has had witha biotechnology company, William Dunnett, Bristol-Myers' manager, public affairs, told BioWorld."We'll be able to screen thousands of drugs in a very shorttime," Dunnett said. "The other benefit of this technology isthat it allows more specific screening of compounds. Werecognize it as a very promising early stage technology thatwill enhance and complement our own internal drug-screening efforts."Leon Rosenberg, president of Bristol-MyersPharmaceutical Research Institute, said, "Most mammaliancell-based screening only determines if a compound showsbinding activity necessary in a therapeutic candidate. Thescreening technology developed by Cadus also determinesa biological effect, which makes the screening moremeaningful."Cadus was spun off in March 1992 from ImClone SystemsInc., which owns 27 percent of Cadus. It was founded bymolecular biologists from Princeton University and theUniversity of North Carolina, Chapel Hill. Other initialinvestors were Icahn Holding Corp. and The Global HealthSciences Fund (Invesco). The new company licensedexclusive worldwide rights to the drug-discoverytechnologies based on signal-transducing G proteinreceptors from Duke University of Durham, N.C., in March1993.Cadus has developed the receptor-based technology andincorporated two other areas into its program _ peptidecombinatorial technology and orphan receptor technology,which allows insertion of orphan receptors (receptors ofunknown function inserted into human cells) into a yeastcell. Levin said the technology stretches over three majormarket areas: inflammation, cardiovascular and neurology."It's designed to discover multiple leads for differenttargets in the human cell," he said."Many of the G coupled receptors are orphan receptors,"Levin said. "Now we only understand the function of about200 of these receptors, if that, and there are potentially acouple thousand."Levin said he could not disclose specific molecular targetscovered in the collaboration. But he said the agreementallows Cadus to work on other programs. n

-- Jim Shrine

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