DRUG HUNTERS The Road to Discovery

ITis a rare honor to meet someone whose life you have saved.

Emory drug hunters Dennis C. Liotta, Raymond F. Schinazi, and Woo-Baeg Choi, however, know the feeling. The drugs they developed for HIV—Epivir and Emtriva—have saved countless lives.

At conferences, in restaurants, those who are still here because of the work of these scientists, or love someone who is, often step forward to express their thanks. It doesn’t get old. How could it?

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Though rightly celebrated for the magnitude of their discoveries, Schinazi and Liotta, who remain at Emory, rub elbows with a host of colleagues whose work is also groundbreaking. During the past two decades, Emory scientists and clinicians have developed medications to treat influenza, cancer, hepatitis, hemophilia, measles, heart disease, dry eye, hot flashes, and other disorders.

In that time, a brass bell outside the Emory Office of Technology Transfer (OTT) has gotten a workout. Whenever the office signs a deal to license an Emory researcher’s invention to a company wanting to develop it as a new product or drug, Todd Sherer—associate vice president for research and OTT’s executive director—rings the bell outside his office, and everyone within earshot applauds.

In 2013, Sherer sounded the bell for an obscure drug called EIDD-2801, which Emory scientist George Painter developed as a countermeasure against Venezuelan equine encephalitis. Painter later found that it worked against respiratory viruses such as influenza and, eventually, a disease no one had heard of until two years ago: COVID-19.

EIDD-2801 evolved into molnupiravir, the first oral antiviral pill approved in the world to treat symptoms of the novel coronavirus that has killed more than five million people worldwide. The medication received Emergency Use Authorization from the US Food and Drug Administration on December 23, 2021, and its manufacturer, Merck, rushed to make the red capsules available to highrisk patients.

25 FDA-APPROVED DRUGS AND COUNTING

But none of that was foreseeable when Painter synthesized the precursor of the drug and Sherer clanged his bell. “It was but a glimmer in the eyes of us all,” Sherer says. “This is standard fare for universities, where discovery occurs years before success becomes obvious.”

Molnupiravir is the twenty-fifth FDA-approved drug born at Emory. Thirteen others are in clinical testing, and six more are in preclinical trials.

Given the flurry of work by Emory researchers in response to the pandemic, molnupiravir isn’t even the first approved COVID-19 drug credited to Emory. That distinction goes to baricitinib, an arthritis medication marketed by Eli Lilly, which Emory researchers discovered could be used to treat the complications of severe COVID-19.

Emory has become a drug-development nexus because of a rare confluence of institutions and expertise. The presence of the Emory Healthcare system, Centers for Disease Control and Prevention, Yerkes National Primate Research Center, and research partners such as Georgia Tech, Georgia State University, University of Georgia, and Morehouse School of Medicine have created a hothouse of drug innovation and attracted a growing number of renowned scientists to the university.

“We have a very broad-based faculty with interest in immunology, vaccinology, and drug discovery and development,” says Schinazi, a medical chemist who has helped generate some of Emory’s biggest drug breakthroughs.

The university counts more than 2,500 scientific researchers who received almost $900 million in funding from the US government, private foundations, and other sources in the past fiscal year. They carry out their discov-

It Takes Guts

When David S. Stephens, vice president for research in the Woodruff Health Sciences Center, was considering his career options in the early 1980s, he interviewed at Emory. His colleagues at Vanderbilt University advised him not to go there.

“Emory at the time was not known as a place of innovation or discovery,” he remembers. “We were known for clinical medicine, education, teaching. But we were not known for translational research. I think we’ve changed that paradigm.”

One of the early landmarks in that transformation, he believes, was the 1979 gift of $105 million from Coca-Cola magnate Robert W. Woodruff and his brother George W. Woodruff. That commitment continues. A 2018 pledge of $400 million from the Woodruff Foundation is helping to create a new home for drug sentence to a manageable chronic disease,” he says.

Liotta partnered with Emory researchers Schinazi and Choi, and they patented an HIV drug in early 1990, just seven days ahead of their competition. It took a decade of laboratory refinement, testing, and patent prosecution and litigation before the compound could reach the market. “[The university] ended up spending over $20 million in legal fees,” Liotta says. “It took guts.”

The resulting medication, Epivir, became the first Emory-developed drug to win FDA approval in 2001. Emtriva, a second drug created by the same team, followed two years later. More than 90 percent of HIV patients in the United States have taken or are taking the drugs, as they became part of a once-a-day pill regimen that prevents the withering disease. Epivir is also widely used for the treatment of HBV, an infection affecting telbivudine, a drug highly effective and specific for HBV infections.

The collaboration that the three scientists demonstrated is a staple of the Emory program. When the overriding goal is the health of patients, every source of insight and expertise is welcome.

Jonathan Lewin, Emory’s executive vice president for health affairs and CEO of Emory Healthcare, believes the culture of collaboration across schools and disciplines is one of the university’s strengths. “The fact that

vice president for research; executive director, Office of Technology Transfer

our scientists work together—people across medicinal chemistry, the School of Medicine, and our other schools—has enabled us to tackle some of the most challenging diseases around,” he notes.

The success of the HIV medications helped secure the future of drug development at Emory. In one of the largest intellectual property deals ever struck by a university, Emory in 2005 sold rights to future Emtriva royalties for $525 million. It reinvested most of the proceeds into research, in accordance with federal law, while Liotta gave millions from his lab’s share of earnings from the sale to create EIDD and DRIVE. The two entities work hand-in-glove—EIDD concentrating on science, DRIVE focusing on antivirals that address critical treatment gaps—and were instrumental in the discovery of molnupiravir.

Painter, DRIVE’s CEO, started working on what would become molnupiravir in 2013 after the Defense Threat Reduction Agency put out a call to develop countermeasures against equine encephalitis, a tropical infection that it feared could be used as a bioterrorism weapon. He learned that the drug could suppress a wide variety of viruses, especially coronaviruses, by stunting their ability to reproduce.

The promise of an oral medication against COVID-19 drew global attention. Painter found the glare distracting. “I have spent my career as a drug developer, nose down, getting things done,” he says.

When he heard the trial results from Merck confirming that molnupiravir could help treat COVID-19 patients at high risk for severe disease, he admits that his scientific detachment melted. He started weeping.

And then he got back to work. “Our continuing mission is to search for other antiviral agents that are usable by the general public to address other tough diseases,” Painter says. “So we are on it. That’s our job.”