Bristol-Myers Squibb Co. signed an agreement with aSan Diego start-up company to tryout its unique methodof combining chunks of microorganism DNA withbacterial hosts, such as Escherichia coli, to generate newdrug leads.

ChromaXome Corp., founded in 1993, uses what it callscombinatorial biology to unleash large quantities ofpotentially therapeutic biochemicals and enzymes frommarine and terrestrial microbes that are difficult orimpossible to culture. Although the marine bacteria can'tbe grown, ChromaXome has developed a method oftaking multiple gene sequences from the microbes andexpressing them in E. coli or another bacterial host, suchas Streptomyces.

Robert Leach, ChromaXome's chairman and CEO, saidhis company's technology also provides a way to activateuntapped metabolic pathways in microbes already known.

"Usually only 10 percent of the pathways inmicroorganisms are expressed," Leach said. "Ninetypercent aren't and we have a method of accessing thosesilent pathways."

In addition, ChromaXome's approach will allowresearchers to mix genes from different microorganismsand combine them with E. coli to see the new kinds ofbiochemicals that are expressed.

Under terms of the agreement, New York-based Bristol-Myers will use ChromaXome's technology to generatecompounds from the pharmaceutical company's library ofmicrobes.

Prabhavathi Fernandes, Bristol-Myers' vice president ofbiomolecular screening, said ChromaXome is the onlycompany she knows of using combinatorial biology.

She said ChromaXome demonstrated it can expresscomplicated pathways using multiple genes in E. coli.

"Whether they can express drugs is another matter," shesaid. Fernandes noted that normally one gene is used in abacterial host to generate a single protein, such as insulin.

"[ChromaXome] has come up with a clever way ofexpressing many genes in a sequential way in E. coli,"she observed.

"Ten years ago there was skepticism about combinatorialchemistry," she said, adding that the concept is similar toChromaXome's DNA biology.

"We don't know if combinatorial biology will work,"Fernandes said. "If it does, it will be big."

Leach said ChromaXome generates huge quantities ofcompounds quickly by taking large amounts of DNA andcombining it with the bacterial host to generate as muchgenetic expression as possible.

The research collaboration with Bristol-Myers is the firstmajor partnership for ChromaXome. No financial termswere disclosed, but Leach said the deal is significant forhis fledgling company. He said ChromaXome likely willboost its 10-person staff to 20.

Leach said ChromaXome has generated potential anti-infectant and anti-cancer compounds with itscombinatorial DNA technology and biological screeningcapabilities, but has no drug candidates in preclinicaltrials.

"We view ourselves as a service company," he said,adding that ChromaXome does not intend to developdrug candidates.

Leach said ChromaXome filed patents earlier this year tocover its combinatorial biology. n

-- Charles Craig

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