In a collaboration described as its fifth majorbiotechnology alliance, Bristol-Myers Squibb Mondayagreed to pay Ixsys Inc. up to $40 million to identifytumor-associated antigens that can be used as targets fordevelopment of anti-cancer drugs.

Of the $40 million, Bristol-Myers, of New York,guaranteed $18 million that will be paid over the nextthree years in the form of an equity investment andresearch funding. The balance of the deal is tied toachievement of drug development milestones.

Bristol-Myers' agreement with privately held Ixsys, ofSan Diego, extends a partnership that began in 1991 todevelop cancer fighting monoclonal antibodies.

Two years ago, in a $10 million collaboration, thepharmaceutical firm purchased a 9 percent stake in Ixsys.The companies Monday declined to disclose Bristol-Myers' additional ownership interest.

Monty Mars, Ixsys' director of business development,said the 1993 alliance focused on use of his company'smolecular design technology, called codon-basedmutagenesis, to optimize the antigen binding affinity andspecificity of Bristol-Myers' antibodies. Ixsys also usedthe codon-based mutagenesis to humanize the drugmaker's mouse antibodies.

Peggy Ballman, Bristol-Myers spokeswoman, said as aresult of that first collaboration, Bristol-Myers hasprogressed to Phase II trials with a monoclonal antibody(BR96) and doxorubicin conjugate aimed at treatingbreast and pancreatic cancers. Other antibodies from thealliance are in preclinical development.

In the new agreement, Mars said Ixsys will attempt toidentify and characterize previously undiscoveredantigens on the surface of cancer tumor cells. Thecompany then will apply its molecular design techniquesto generate drugs targeting the antigens. In addition todeveloping monoclonal antibodies, the companies saidthey will explore use of other therapeutic compounds.

The Bristol-Myers agreement is Ixsys' largestpharmaceutical company partnership. For Bristol-Myers,Ballman said, the alliance is the fifth major biotechnologyagreement in the past 18 months. The total potentialinvestment of the five collaborations is $160 million, sheadded.

In July 1994, Bristol-Myers entered a $35 millionpartnership with Cadus Pharmaceutical Co., ofTarrytown, N.Y., to develop drugs targeting G protein-coupled receptors, which regulate cellular behavior byblocking or transmitting external signals.

The pharmaceutical company in February 1995 boostedits genomics research in a deal with SEQ Ltd., ofPrinceton, N.J., focused on use of the latter's genesequencing technology. Terms of the agreement were notdisclosed.

In two other collaborations this year, Bristol-Myers madeits first move into gene therapy in a $20 million deal withSomatix Therapy Corp., of Alameda, Calif., andexpanded its research on Alzheimer's disease in a $50million agreement with San Diego-based Sibia Inc. n

-- Charles Craig

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