Bristol-Myers Squibb has taken a 9 percent equity investmentin Ixsys Inc. and agreed to fund a $10 million, three-yearresearch and development program between the twocompanies.

This agreement, announced Wednesday, reinforces the ongoingrelationship between the companies, which have beencollaborating on methods to develop monoclonal antibodiesdirected at solid tumors since 1991. The two companiesformalized their research agreement (although they didn'tdisclose terms) in October 1992.

Under the terms of the latest agreement, Bristol-Myers Squibb(BMS) of Princeton, N.J., has already made an initial payment toIxsys of $6 million. Ixsys of San Diego will receive milestonepayments and royalties on each product developed, and BMSwill receive exclusive marketing rights to all solid-tumorrelated antibodies resulting from the collaboration.

As well, BMS will receive licenses to certain Ixsys technologies,including limited access to Ixsys' peptide libraries. "We sawthese libraries as a potential source of new drug candidates,"said William Scott, senior vice president of exploratory anddrug discovery research at BMS's Pharmaceutical ResearchInstitute.

Those libraries stem from a technology developed by scientistsfrom both companies and reported in two papers appearing inthe Journal of Immunology in December 1992. The technology,codon-based mutagenesis, allows researchers to rapidly adjustcodons -- whether they are in the business end of a monoclonalantibody or in a peptide drug candidate -- to fit their targetreceptor or antigen more closely.

The researchers have already used the technology to tailor-make monoclonals with affinities 15 times higher than thoseproduced by the human body's immune system.

"We will continue to collaborate on R&D for at least threeyears," explained Michael Hanifin, Ixsys' vice president ofbusiness development. The companies have a number ofexisting projects, he added, and "we anticipate there will beother projects added to that related to monoclonals againstsolid tumors."

Specifically, the partners are developing L-6, a monoclonalantibody designed to target lung cancer cells. Other cancersbeing targeted at this stage include those of the breast, colonand prostate. BMS developed the starting antibodies, whichwere either entirely murine in nature or chimeras, to whichIxsys has applied its codon-based mutagenesis to optimizecharacteristics such as specificity and affinity, Hanifinexplained.

Ixsys also intends to apply another of its technologies, in vitroimmunization, to develop antibody candidates. Ixsys licensedthe in vitro immunization method from the University ofCalifornia in July 1992. It involves creating human monoclonalsby immunizing human spleen cells with antigen. Bristol-Myerswill be providing the antigens; in fact, those experiments havealready started, Hanifin told BioWorld.

Bristol-Myers Squibb (NYSE:BMY) also has a current productalliance with Immunex Corp. (NASDAQ:IMNXD) on the Seattlecompany's recombinant cytokine therapeutic PIXY321, and anR&D and equity alliance with Procept Inc. of Cambridge, Mass.,to develop therapeutics for autoimmune disease and organtransplantation rejection.

The agreement with Ixsys "offers us a relationship with acompany whose technologies may optimize the potential ofmonoclonal antibodies ... which continue to be an importantstrategic focus for our company," said Peggy Ballman, directorof public affairs at BMS's pharmaceutical group.

"Bristol-Myers wants to establish its leadership not only as apharmaceutical company, but also as a biotechnologycompany," she added.

-- Jennifer Van Brunt Senior Editor

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