Moving from Theory to Therapy
Moving from Theory to Therapy | drug discovery, Jeffrey Conn, Vanderbilt, schizophrenia, pharmacology, Janssen Pharmaceutica

Jeff Conn in the lab - Photo by Anne Rayner

Vanderbilt Helps Close the Gap in Drug Discovery

"The Valley of Death"... that's how researchers refer to the gap between basic science and commercial clinical application where many a promising research project has gone to wither away.

Five years ago, P. Jeffrey Conn, PhD, left pharmaceutical giant Merck to launch a new program at Vanderbilt focused on helping researchers navigate the vast expense... and expanse... between discovery in a lab and a prescription pad in a physician's office.

As director of the Vanderbilt Program in Drug Discovery, Conn is using previous academic and commercial experience to bridge the gap between the two sides of the drug discovery equation. He noted that in academia, researchers are encouraged to look for novel approaches but lack the infrastructure to discover drug leads or see if a drug will be truly viable as a therapeutic agent. Conversely, the commercial setting has impressive labs and a team of researchers to discover and test new drugs but not the luxury of tinkering with interesting science that might suggest novel treatment approaches.

The university invested heavily in drug discovery infrastructure including high throughput screening, state-of-the-art chemistry and molecular biology labs, pharmacology testing and a new animal model neurobehavioral lab (see related story). To build his program, Conn has relied heavily on recruiting prominent drug discovery scientists from the commercial sector.

"Most of us come at a fiscal loss," he noted. "I saw that as a potential big problem when I came here, but it has ironically helped us get an even stronger base because it selects for highly innovative people who are passionate about this mission."

Conn said the leadership team is almost exclusively from the pharmaceutical industry. Craig Lindsley, PhD, who worked with Conn at Merck, is a renowned chemist. David Weaver, PhD, brought to Nashville his knowledge of high-throughput screening from his years at Bristol-Myers Squibb; and Carrie Jones, PhD, an in vivo pharmacology expert, came to Vanderbilt via Eli Lilly. "All of these people are world class, and they were recruited from companies that were known as the best in their fields," Conn said.

"However, we are also a unique training ground for drug discovery scientists. The fifth member of the leadership team, Colleen Niswender, PhD, is the first of what we expect will be a number of outstanding drug discovery scientists who emerge from our own program," continued Conn.

The team is currently working on an exciting project that could potentially change the way schizophrenia is treated and also revolutionize the current model for drug discovery. Like his colleagues, Conn is nationally recognized for his work on brain disorders including schizophrenia, Parkinson's and Alzheimer's. A recent partnership with Janssen Pharmaceutica N.V. will provide a needed infusion of cash to continue research and ultimately bring Conn's research to the marketplace.

Several years ago, Conn began focusing on a new option for the targeted treatment of schizophrenia by identifying compounds to act on a neurotransmitter receptor target.

"It was a very speculative idea … not one that had enough basis to warrant focus by a pharmaceutical company," he recalled.

Before Vanderbilt's program, a typical academic institution wouldn't have the resources necessary to flesh out his ideas. "Vanderbilt really deserves a lot of institutional credit," noted Conn. "I think Vanderbilt showed tremendous foresight in investing early and being at the forefront of the game."

He continued, "To start the studies, we needed to screen large libraries of compounds. We've discovered molecules that have all the properties you'd want to that would have the effects on this receptor that we thought would be beneficial. We've generated enough data to show this really is an approach that could go the distance … it truly is a viable approach to treat schizophrenia."

Even though Conn and his colleagues have discovered the important compounds, they are still far from the finish line. Through the licensing and research agreement, Janssen has committed $10 million up front with additional payments if certain milestones are met and through royalties on product sales. Janssen's deal also includes the ability to license rights to additional novel compounds over the course of the next three years.

Currently, Conn and his colleagues are fine-tuning the molecules so they will meet FDA requirements for testing in humans. He added the major investment for Janssen would come as Vanderbilt's portion draws to a close when the pharmaceutical company begins clinical trials.

"It is critical that those of us in institutions funded by the NIH, such as Vanderbilt, take seriously the public trust that has been placed in us and the need to translate advances in basic research into new treatment strategies. We must be much more proactive in ensuring that this national investment ultimately helps to improve patients' lives," Conn concluded.