National Editor

Having kicked off last year with a $30 million financing, genomics-era survivor Perlegen Sciences Inc. is coming on strong again in 2004 - signing three deals in as many days: two with existing partner Pfizer Inc. and one with new collaborator AstraZeneca plc.

"We signed the deals just before the holidays, so we came out with them at the first available opportunity," said Philip Sussman, vice president of business development and chief financial officer for Mountain View, Calif.-based Perlegen.

The research pact with London-based AstraZeneca is to identify DNA variants that raise heart attack risk. Privately held Perlegen will use its genotyping technologies and data to identify genes associated with heart attack, genotyping single nucleotide polymorphisms (SNPs) in more than 1,000 samples to identify disease-associated markers for AstraZeneca.

"It's a very specific disease indication" with a new partner, distinguishing it from the Pfizer deals, Sussman noted. An agreement entered with New York-based Pfizer in late 2002 is to investigate genetic contributions to cardiovascular disease.

In one new deal with Pfizer, Perlegen will study drug response in patients with major depression disorder, again genotyping SNPs in clinical samples to identify markers associated with drug response. The two firms will share in therapeutic and diagnostic rights resulting from the deal, "which is very significant for us," Sussman said, with Pfizer providing research funds, plus undisclosed milestone payments.

"The focus is on drugs," he said. "We're taking DNA from people, but they're people who've been treated with a drug, so we're correlating their response to the drug with their genetic makeup."

The other SNP-genotyping deal with Pfizer also shares rights and is focused on research into markers associated with metabolic syndrome, which involves a set of symptoms that dramatically increase the risks of developing cardiovascular disease and Type II diabetes, two major worldwide killers.

Metabolic syndrome, which increases in the population with age, typically involves such factors as extra weight, elevated blood pressure, high triglyceride levels, increased blood glucose and low levels of high-density lipoprotein.

"We're looking at, in a sense, multiple diseases," Sussman said. On a scale never feasible before, the companies plan to conduct detailed genome-wide searches in thousands of patient samples.

"These were patient samples Perlegen collected," Sussman told BioWorld Today. The metabolic-syndrome deal - the first of the three to be disclosed, which was made public Jan. 7 - represents "the first time we're publicly disclosing we've been doing that," he added.

Perlegen's other activities have been known for some time. In its SNP discovery effort, the company performed full-genome scans on the DNA of 50 unique individuals - "the next step beyond" genomics, Sussman said.

Other genomics firms were sequencing, "and we did what's called re-sequencing to get the data to do genotyping," he said. "We took 50 different human genomes and looked at every base in them to identify where they differed. In a year and a half, we re-sequenced 50 genomes. We were able to do that because we had a draft of the human genome, at that point about 85 percent of the bases were known."

Perlegen uses high-density arrays of DNA probes on glass wafers. Each wafer holds about 60 million DNA probes that can be used to recognize longer sample DNA sequences. The method finds which probes the sample DNA hybridizes more strongly to in order to determine if a known sequence of DNA is present in the sample. The company is able to "interrogate" 1.7 million SNPs, using 500 cases and 500 controls in each instance.

Perlegen also has partnering arrangements with London-based GlaxoSmithKline plc; Bristol-Myers Squibb Co., of New York; Eli Lilly and Co., of Indianapolis; and Unilever plc, of London.