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C. David Weaver, Ph.D., (right), shows a plate used to screen compounds for drug-like activity to P. Jeffrey Conn, Ph.D., director of drug discovery in the Vanderbilt Institute of Chemical Biology. Weaver oversees Vanderbilt's new high-throughput screening facility, which opened this month on the eighth floor of MRBI. photo by Anne Rayner

Agreement enhances drug discovery efforts

BY: BILL SNYDER

3/25/2005 - Vanderbilt University Medical Center has signed a “master research agreement” with Amgen, the world's largest biotechnology company, to aid the discovery and development of new drugs.

Under the agreement, Amgen will provide funding this year for two projects at VUMC investigating a potential new class of drugs. Other projects can be added in the future.

The agreement represents an as-yet-unrealized hope that, by combining the knowledge base of the university with the financial and drug-discovery firepower of industry, the two entities can accomplish more than either of them can individually.

“What we're trying to do at Vanderbilt is really out of the box,” explained P. Jeffrey Conn, Ph.D., professor of Pharmacology and director of drug discovery for the Vanderbilt Institute of Chemical Biology.

“We're actually trying to engage in the early phase (of drug discovery) with infrastructure developed here at Vanderbilt and hopefully work with partners like Amgen to take drug discovery programs on through later phases.”

The National Institutes of Health, which pays for the bulk of basic biomedical research in the United States, traditionally has not funded early-stage drug discovery, in part because it is so expensive, Conn said. “By partnering with Amgen, we can take these projects a lot further than we ever could with NIH,” he said.

The agreement also is part of the Medical Center's strategy to diversify support of its research enterprise, said Jeffrey R. Balser, M.D., Ph.D., associate vice chancellor for Research.

While VUMC ranked first in the nation with a 22.4 percent increase in the compound annual growth rate of NIH grant awards between 1999 and 2003, federal funding of research is slowing down.

“It is essential to diversify support and to choose strategic partners who share our vision for bringing new and better drugs to our patients,” Balser said.

Unlike government research grants, there is no guarantee that funding for the first two projects will continue beyond the first year. Even if the research is “going great,” Conn said, the company could decide after a year not to pursue it. If that happens, however, it's still a “win” for Vanderbilt because the research will be much further along than it would have been otherwise, he said.

Conn, former head of the neuroscience department at Merck Research Laboratories, is the lead Vanderbilt scientist in both of the first two projects included in the Amgen agreement.

Drug companies traditionally have been reluctant to invest the tens of millions of dollars required to determine whether an interesting approach actually has a chance of becoming a clinical candidate. To bridge that gap, the Vanderbilt group proposes to screen a vast amount of compounds for their ability to activate the targets of interest.

If Vanderbilt is successful and Amgen decides to develop these compounds, Conn said he hopes his team will continue to be involved in the research.

“As they're running a full chemistry effort, we're providing the biology hands-on support, and if they get to the clinical development phase, we've got an outstanding Neurology department that could support the early proof-of-concept studies,” he said.

The Amgen agreement follows the establishment in 2002 of the Vanderbilt Institute of Chemical Biology with support from the university's Academic Venture Capital Fund.

“Our goal with that institute is to take those very early-stage discoveries around how drugs may work, and go another step toward handing that information off to biotechnology and pharmaceutical companies and other organizations that can hopefully translate that into new drugs for patients,” Balser said.

In the past two years the institute, directed by Lawrence J. Marnett, Ph.D., Mary Geddes Stahlman Professor of Cancer Research, has received more than $20 million in funded or pending research grants, he added.

About the time the institute was getting off the ground, Conn decided to leave Merck to direct a new program in Translational Neuropharmacology within Vanderbilt's Pharmacology Department.

Conn said he came to Vanderbilt because he saw an unusual willingness to invest in early-stage drug discovery. “What we're building at Vanderbilt is the ability for scientists to actually take the next step,” he said.

Two years ago, Conn began discussing a possible collaboration with H. Christian Fibiger, Ph.D., vice president of neuroscience research at Amgen who recently had moved from Eli Lilly & Co.

Amgen and the Vanderbilt Institute of Chemical Biology are currently exploring ways to identify additional projects of interest, and to potentially broaden the range of collaborative research projects that could be supported by the master research agreement.

The agreement represents “a whole new approach” to pursuing science that otherwise might have stopped with the publication of a basic research paper. “If it works,” Conn said, “my hope is that (this relationship) will grow.”

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