When Jeffrey Glenn, MD, PhD (Associate Professor of Medicine [Gastroenterology and Hepatology] and Microbiology and Immunology) submitted his proposal to the NIH for a U19 Cooperative Agreement, he was well on his way to creating the team that today is reaping the benefits of receiving that grant. With $28 million of NIH funding over 5 years to support the new Stanford Center for Excellence in Translational Research (CETR), he and his team hope to make progress from the bench toward the bedside with new antiviral therapies.

“The focus of this NIH program is a wide spectrum of priority pathogens: those of greatest concern from a biodefense perspective or an emerging infections perspective,” said Glenn. “We want to change the paradigm for creating antiviral drugs. Instead of continuing to develop one drug for one bug, we are seeking to identify characteristics of the host that viruses depend on for their lifecycle so that we can deprive the virus of access to that host function. Often a variety of viruses have evolved to take advantage of the same host function, so one drug could target multiple bugs.”

Structure of the Grant

How is the Stanford team structured to reach its goal? Glenn continued: “We have five individual projects aligned around the central theme; these projects collaborate with each other while maintaining an independent focus. Each project is led by a pair of co-investigators so there are two labs devoted to each project. Part of the reason why we were selected for the U19 was the caliber of our team members.”

“We also created two new cores—a Pharmacology Core and a Translational Incubator Core—which have a collection of outstanding faculty and consultants contributing their advice and scientific insights. And we have an external advisory committee with world-renowned virologists and people in industry who can provide their expertise about how to develop real-world drugs, which is something that people in academia oftentimes aren’t familiar with. And we also have dedicated regulatory support from a former FDA regulator.”

Support for the Science

As the labs begin to do their work, they will have unique support along the entire pathway toward clinical studies. Glenn explains: “There is support for all stages of the drug development process starting with in vitro and in vivo activities, which are part of the characterization of molecules to identify potential clinical candidates. When we find a candidate lead molecule off initial hits, we often have to do some structural activity relationships and some medicinal chemistry to optimize the molecules. So within our Pharmacology Core we have dedicated medicinal chemistry. There is also money to pay for some of the investigational new drug (IND)-enabling toxicology studies.

“Some of the pathogens that we’re focusing on are viruses that infect the human liver. We have some support for humanized mice (special mice that have human liver inside their bodies), and that allows us then to study human hepatitis viruses in a more natural environment where they can actually infect the liver cells. Then we can treat them with candidate antiviral agents, and we can in most cases do simultaneous pharmacokinetic and pharmacodynamic assessments."

“We also have a Translational Incubator core to give advice on all the translational aspects of these projects and support pilot studies to bring in new technologies and investigators whose research can enhance the Center’s goals.”

Learning About the Drug Development Process

Glenn recognized some time ago that he would have to learn something about the processes involved in taking a molecule from the lab to the clinic. He puts it this way: “If you want to get a new drug into the clinic, it has to be cool science plus it has to meet all of these other requirements along the way.“ So he set about learning about the “other requirements.”

“I’ve been increasingly involved in various aspects of drug development,” he says. “As a physician-scientist that’s what the dream is – to move things from the lab into the clinic -- and I have been engaging in those activities on a variety of levels: consulting and helping big pharma and small pharma. I founded a couple of my own companies to help move these antiviral strategies further along. I’m also a member of the FDA Antiviral Advisory Committee. So I have come to recognize the importance of thinking about the critical regulatory aspects and safety issues with what we’re doing too.”

“There is an amazing talent pool dispersed throughout Stanford, with people able to share expertise and experience that is relevant to many of the key aspects of drug development. This grant will help us bring some of these individuals together to uniquely focus and synergize their efforts—and importantly provide critical leveraging and enabling resources.”

Potential Impact at Stanford

“When I initially saw the announcement for this grant I realized it was one of the first opportunities to get sufficient resources to really begin to move the translational needle in a meaningful way. Importantly, I think it could help more than just us; I think it could help the broader community here at Stanford as some of our discoveries and capabilities are also able to help other scientists with their activities.”