National Editor

Appointing a new president and CEO, FivePrime Therapeutics Inc. raised $12 million in its second round of financing to push functional screening of what the start-up company calls the Pharmanome, and to advance protein therapeutics.

FivePrime was founded "on the basis of creating solutions to the bottlenecks in drug discovery that have arisen with the wealth of information coming out of the genome," said new leader Gail Maderis. Scientists refer to the phosphate end of DNA as the "five prime" end.

"Everyone's bought into the vision and the concept" of handling the avalanche of genomics data, she noted. "The trick is having the right tools to make this happen."

Until July, Maderis was vice president of Cambridge, Mass.-based Genzyme Corp., and president of the Genzyme Molecular Oncology unit.

Former FivePrime CEO Lewis "Rusty" Williams, who started the company in 2001, is staying on as executive chairman and leader of research efforts. Lewis co-founded Cor Therapeutics Inc., of South San Francisco, bought by Cambridge, Mass.-based Millennium Pharmaceuticals Inc. two years ago. (See BioWorld Today, Dec. 7, 2001.)

Williams also was the head of research and development at Chiron Corp., of Emeryville, Calif., before starting FivePrime, which "really geared up about mid-year 2002," Maderis said. The South San Francisco-based firm is seeking to exploit "the entire set of pharmaceutically relevant genes and proteins," which it calls the Pharmanome.

Specifically, FivePrime is using data gathered from full-length complementary DNA's of "whole sets" of proteins in functional assays that are done in vivo and in vitro. The intended upshot is more leads with better specificity and selectivity, plus economies of scale.

"What we're aiming to do is turn drug discovery on its head, so that instead of saying, I have a gene, what is it good for?' and putting it through umpteen functional assays, trying to figure out its utility, we're starting with medically focused screens," Maderis said. "We hope within the next year to have multiple therapeutic leads."

FivePrime boasts "massively parallel, full-length cDNA-generating, high-throughput protein production" to be deployed with its functional assay and testing engines.

"We can make hundreds of proteins at a time," she told BioWorld Today. "Our initial screens are set up in Type II diabetes and lymphocyte reconstitution, looking at factors that would be involved in the proliferation and reconstitution in, for example, post-bone marrow transplant [patients]." There also are programs in immune-mediated diseases, cancer and osteoarthritis.

"The platform is applicable to all kinds of drug discovery," Maderis noted, but the company is focusing for now on secreted proteins "because the protein is the drug. It's a very fertile field to pursue and a fruitful area for partnering, we believe."

The partnering effort is "just getting ready to start," she said. "The first year was [spent] building up the collection of cDNAs and getting the high-throughput production running at full speed."

She acknowledged the "painful re-direction" of genomics that has taken place in recent years and said FivePrime has avoided hazards met by other firms because it has "established a set of full-length clones through collaborations without any infrastructure development. The clone collection, the cDNA, is all through collaboration."

Its libraries are made in Japan, through a collaboration with Tokyo-based Dnaform, a spin-off from Japan's Institute of Physical and Chemical Research.

"All of the [FivePrime] employees are devoted to the biology, the screens and the downstream efforts," Maderis said. "If you walk through our labs, it's molecular biology, tissue culture, the standard kinds of work. We do have some proprietary in vivo models."

She spent "11 wonderful years at Genzyme," Maderis said, leaving when the company decided to eliminate its tracking stocks and reabsorb the molecular oncology unit she was in charge of - a move that has become the subject of litigation by Genzyme's biosurgery unit. (See BioWorld Today, June 5, 2003, and Aug. 19, 2003.)

FivePrime "approached me, and the opportunity to transform protein discovery was very compelling," Maderis said. "It's really an exceptional company."

The financing was co-led by existing investors Kleiner Perkins Caufield and Byers, of Menlo Park, Calif.; Versant Ventures, also of Menlo Park; and TPG Ventures, of San Francisco. New investors participating in the round were Advanced Technology Ventures, of Palo Alto, Calif.; Singapore Economic Development Board; and The Wellcome Trust, of London.

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