By Randall Osborne

SAN FRANCISCO — In a four-year deal billed as the next step in "the post-genomics revolution," Oxford GlycoSciences plc and Incyte Pharmaceuticals Inc. have launched a joint program in proteomics, which is the large-scale, high-throughput analysis of protein expression.

Michael Kranda, CEO of Oxford GlycoSciences, said the science of proteomics "truly achieves the aim of combinatorial biology" and will "unleash the real promise of genomics-based drug discovery."

Kranda shared details of the company's technology in his presentation at the 16th Annual Hambrecht & Quist Healthcare Conference here.

"The essence of proteomics is the discovery and characterization of proteins, receptors and enzymes in the disease pathway to complete the picture and find the new targets, the new diagnostics, the new treatment strategies that the genomics revolution promises," Kranda said.

Under the terms of the deal, Oxford GlycoSciences, of Oxford, U.K., will develop and commercialize proteomics databases with Palo Alto, Calif.-based Incyte, which brings its expertise in genomics and bioinformatics to the collaboration.

Incyte will make a $5 million equity investment in Oxford GlycoSciences and provide access to the LifeSeq database of gene sequences and the PathoSeq microbial database. The two will share profits and will jointly own any intellectual property developed.

"Proteins have always been the link between genes and diseases," Kranda said. "Successful drugs target proteins, and to look at DNA and RNA alone is not enough."

The presence of DNA or RNA does not necessarily mean a protein is being expressed, nor does it reveal how much, or how it has been modified, Kranda said. "People have always wanted to do this, but the technologies weren't available," he told BioWorld Today.

Randy Scott, president and chief scientific officer of Incyte, called proteomics "a killer application" of the existing database technology.

"What do our customers want to do next? They want to know which genes, which proteins are turned on and off in which settings. Instead of running to the lab with the latest, greatest target, we're systematically taking biology apart," Scott said.

"[Incyte] started out on the proteomics side," he added. With the advent of automated DNA sequencing, Incyte shifted into genomics, because sequencing proteins was too slow. "We've come full circle," Scott said.

Raj Parekh, research director at Oxford GlycoSciences, said the company's technology, by tracking the flow of information in a biological system, complements rather than competes with genomics. "We don't believe proteomics is in any way a replacement for genomics," Parekh said. "Far from it."

Kirk Raab, former president and CEO of South San Francisco-based Genentech Inc., is chairman of Oxford GlycoSciences. He said the more progressive researchers are "almost relieved" at having proteomics as a way to advance genomics.

One of the more important aspects of protein expression analysis is often overlooked, Raab said. By keeping track of proteins and determining which patients have a propensity to develop a particular disease, scientists can speed up the drug development process.

"You can make sure the right people get the drug," Raab said.

As an example, Kranda said Oxford GlycoSciences has an orally available small molecule compound in Phase I testing for liver cancer.

"We now believe we have the specific set of proteins which correlate with disease onset," Kranda said. This is important because diagnosis of liver cancer usually is done by radiological scanning. "By that time, you have a tumor in your liver, and the chance of efficacy of available therapies is very low," Kranda said.

Finding a particular pattern of protein expression, on the other hand, indicates a high probability that the patient is converting from hepatitis or sclerosis of the liver to cancer. Clearance for Phase II trials is expected this year.

"We will use the molecular marker for patient selection," Kranda said, thus making the trial more efficient. The compound also will be studied for metastatic colon cancer that localizes in the liver, he said.

As more proteins are analyzed, new clinical molecular markers will become available, Kranda said. "These surely exist for many human diseases, but have not yet been found due to the lack of a systematic, high-throughput, sensitive protein-expression platform," he said. "This is changing as proteomics matures, and we intend to drive that."

Oxford GlycoSciences was founded in 1988 by Oxford University. The privately held company with 100 employees has products in clinical trials for cancer and glycolipid storage disease. Its pipeline includes more candidates in oncology, as well as inflammation and infectious disease.

Kranda said glycobiology — the area of its internal drug discovery program — deals with a promising subset of proteins that can be identified with proteomics. "There are hundreds, if not thousands, of potential targets in this area," he said.

The company will use glycobiology, glycochemistry, and Incyte's LifeSeq and other databases to pursue its programs, Kranda said.

As of the end of 1997, Oxford GlycoSciences had $18 million in cash, and aims to go public this year on the London Stock Exchange.

Incyte Inks Another Database Deal

Incyte, in a separate deal, has entered into a genomic database partnership with Novartis AG, of Basel, Switzerland. The multiyear agreement provides Novartis with access to Incyte's LifeSeq database, with potential royalties on future sales of any products developed using the technology. Financial terms were not disclosed.

Incyte reported a net income for 1997 of $10.4 million, with a profit of $4.4 million in the fourth quarter. Revenues for the year jumped 111 percent, to $88.4 million, and for the last quarter rose by 87 percent to $26.6 million, mostly from new database agreements and expansion of deals already in place.

At the end of 1997, Incyte had $114.7 million in cash. The company's stock (NASDAQ:INCY) closed Wednesday at $40.125, up $2.125. *

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