READDI Moves From Idea to the Global Stage

How do you turn an idea into action?

That simple but profound question drives everything at Eshelman Innovation.

For answers and to celebrate the institute’s 10th anniversary, we’re looking back at the evolution of the Rapidly Emerging Antiviral Drug Development Initiative. READDI began as an idea sparked by a chance encounter, sketched out over beers at a Chapel Hill dive bar and fueled by a global pandemic.

Five years later, after a major push by Eshelman Innovation, READDI has raised nearly $100 million to discover and develop antiviral therapeutics to protect humanity against future viral outbreaks. Among other milestones, READDI is now a core implementation partner in the G7’s 100 Days Mission, the world’s leading pandemic preparedness effort. READDI helped guide the creation of the recently launched 100 Days Mission Therapeutics Roadmap by sharing insights about virology, drug development timelines and budget projections honed during its startup journey.

“READDI has moved from a project within UNC to being a global entity,” says Angela Kashuba, dean of the UNC Eshelman School of Pharmacy, which houses Eshelman Innovation.

The idea

Back in 2018, during a session for prospective graduate students, Nat Moorman, associate professor in the UNC School of Medicine’s microbiology and immunology department, noticed a research poster about measuring the activity of kinases. It was from the lab of his medical school colleague Lee Graves. Kinases, enzymes involved in cell behavior, are a common target for drugs, including kinase inhibitors used to treat cancer, the focus of Graves’ research.

Moorman, a virologist, wondered how kinases in host cells respond to viral infection. He and Graves did a study and found that drugs that inhibited kinases also inhibited virus replication in those same host cells. 

“As I was toying with the idea,” Moorman recalls, “I talked to Mark and Ralph and said, ‘Hey, what if we did this more broadly across different virus families?’”

He’s referring to Carolina virologists Mark Heise, a School of Medicine professor of genetics, and Ralph Baric, William R. Kenan, Jr. Distinguished Professor in the UNC Gillings School of Global Public Health’s epidemiology department and professor in the School of Medicine’s microbiology and immunology department. During informal sessions in Carolina’s Burnett-Womack Building and at the Dead Mule Club, a favorite after hours watering hole, Moorman and colleagues discussed the possibility of creating drugs that work broadly against multiple viruses similar to the way antibiotics broadly fight bacterial infection.

Though this was well before the emergence of SARS-CoV-2, the novel coronavirus that caused the COVID-19 pandemic, the three virologists were fully aware of the looming threat of a pandemic. By 2018, the 21st century had already seen a growing number of deadly viral outbreaks, including SARS and MERS, Chikungunya, Ebola and Zika. The warming world with its globe-hopping humans was like a petri dish of doom.

“We needed to be more forward-thinking in how we develop drugs against viruses,” says Baric, one of the world’s leading coronavirus experts. 

Back in the lab, the trio found that, yes, small-molecule drugs that targeted host-cell kinases would broadly inhibit the replication of multiple viruses. There are 24 virus families known to cause disease in humans. Around one-third of those families are known to have pandemic potential. Antivirals that work broadly against all the viruses in a family could offer treatment against both known viruses and those that do not yet exist.

At the time, Moorman had zero drug development experience. He was a basic scientist who studied how viruses replicate. But a lesson learned from his post-doctoral adviser at Princeton University, a legendary scientist named Thomas Shenk, echoed in his head.

“Tom always instilled the idea in me that if you found something useful, it was your obligation to see if you could do something useful with it,” Moorman says. “By funding your research, the NIH lets you go out and learn new things. But the NIH’s mission is to better the lives of the people of the United States.”

So that was the idea: Develop broad-spectrum antivirals to prepare for the coming pandemics. How, then, to turn the idea into action?

‘Let’s get started’

Moorman, Heise and Baric put together a team and applied for a 2019 Creativity Hub award, a program launched the prior year by the Office of the Vice Chancellor for Research to accelerate research “in the pursuit of moonshot thinking to make tangible impacts.” Calling its broad-spectrum antiviral project the Infectious Disease Drug Discovery Program, or UNCID3@UNC Hub, the team won. The effort relied on the collaboration of three powerhouse Carolina schools: UNC School of Medicine, Eshelman School of Pharmacy and UNC Gillings School of Global Public Health.

Impressed by the concept’s potential for life-saving impact, Eshelman Innovation leadership put up half the Creativity Hub award funding.

Eight months later, in early 2020, the virologists’ worst nightmare became reality. A novel coronavirus emerged in China, and the world watched as Chinese construction crews threw up 1,000-bed hospitals in a matter of weeks to house the sick, whose bodies had insufficient immunities to fight the new bug. The need for a moonshot was now.

“I was sitting with Ralph and Mark in a conference room realizing that we were about to have a full-blown pandemic, frustrated that we weren’t going to have the medicines we needed,” Moorman says. “When we reached out, Eshelman Innovation didn’t hesitate. They said, ‘Yes. Let’s get started.’”

“If any institution could do this, it was UNC,” says Eshelman Innovation CEO John Bamforth, who doubled down on the institute’s commitment to advancing the antiviral project. “Carolina had the expertise in virology and medicinal chemistry and other sciences. And the institute brought the translational know-how. Eshelman Innovation was a resource to bring this to life.”

To build a company, they would need capital, so Eshelman Innovation engaged the University’s development team, with efforts led by Eshelman Innovation Lead Development Officer Kelly Collins.

Around this time, the team came up with a new name — the Rapidly Emerging Antiviral Drug Development Initiative. The acronym “READDI” was perfect: When a pandemic hits, the world needs to be ready, not reactive.

With pro bono marketing help, the Eshelman Innovation team developed early branding. They built a website and created PowerPoint presentations for potential funders. They tapped their professional networks for help. Former UNC Board of Trustees member and venture capitalist Alston Gardner, for example, gave feedback that greatly improved the READDI pitch deck.

They started making calls, hoping to convince philanthropic organizations, government agencies, investors and pharmaceutical companies to put up seed money to move the idea into action.

No one imagined just how many calls they would make.

Building a moonshot

That overarching question — how to turn the READDI idea into action? — led to countless sub-questions. One of the most important: how much would it cost?

Early in the process, the team settled on small-molecule antivirals — pills, like aspirin — rather than, say, monoclonal antibodies or other biologics. Pills are relatively easy to manufacture and transport, shelf-stable and require no refrigeration. In short, they are more accessible to populations around the world, a top READDI priority.

And they expanded their approach from drugs that target host-cell kinases to include direct-acting antivirals, which target highly conserved functions of the viruses themselves.

Tapping pharmacy school expertise, the team charted average industry costs for each step in the small-molecule drug discovery and development pipeline, taking into consideration things like anticipated attrition rates.

Another big question: What should READDI look like? Was the most advantageous structure a University institute or center? A spin-out company? For-profit or nonprofit?

The University was a big supporter during these early days. Moorman remembers Provost Bob Blouin saying about READDI, “Not only should we do this, but we have to do this.” Chancellor Kevin Guskiewicz provided critical funding to hire a consulting firm to help decide the best structure for an initiative like READDI.

“Along the way we reached every decision after rigorous strategic debate sessions,” says Roy Zwahlen, Eshelman Innovation’s chief strategy officer. “We have our own red-teaming process, where we constantly challenge each other: Do we have the right strategy? Why do we know what we know? What’s changed from day to day?”

The deeper they got, the clearer it became that the scope of READDI extended beyond the walls of UNC-Chapel Hill.

“We needed people who knew how to make assays and do screens,” Moorman says. “Based on the scope of what we wanted to do, we needed versatile medicinal chemists and a lot more virologists. Here’s a simple example. We knew filoviruses had to be on the list. Those pathogens require a Level 4 biosafety lab. We don’t have a BSL-4 at Carolina.”

READDI needed to be a global public-private effort. What Moorman originally envisioned as a spin-out company truly was a moonshot.

600 pitch meetings

With a global pandemic raging, the READDI founders and their Eshelman Innovation partners didn’t have the luxury of first mapping out strategy and structure and then raising money. Those things happened simultaneously. Early research suggested READDI needed $500 million to develop five Phase-2-ready broad-spectrum drugs — one for each of the virus families of highest risk. It was a daunting goal that left lots of potential funders shaking their heads.

After every “no” the team debriefed and used what they learned to improve the pitch. One early lesson was that most people were unfamiliar with the role of antivirals, how they treat existing viral disease, whereas vaccines build immunity against future disease. Both are necessary in a pandemic. The world was focused on vaccines to prevent sickness, but the world needed antivirals immediately for the millions who were already overcrowding hospitals.

Bamforth, Moorman and Collins maintained a tireless cadence of pitch meetings, all of them via Zoom because of stay-at-home directives. The pitch count surpassed 100, then 200, then 300 with no one stepping up to offer funding. “It became clear at some point that we had talked to all the obvious big-ticket funders,” Moorman says. “We realized this was going to be a slog — the hard yards, not a quick touchdown.”

Antivirals for pandemic preparedness have generally been neglected because they’re perceived to be less lucrative than, say, cancer or cardiovascular drugs. Eshelman Innovation, known for charging toward the toughest health care challenges, never wavered, Moorman says.

“Eshelman Innovation had a clear picture of what the products needed to look like. They knew the people we would need to bring into our project, and they had a framework for how to stage our efforts and keep them focused.”

Nevertheless, the rejection was discouraging, he remembers. “On any given day, I or John or Kelly might want to quit, but the team was there to keep us going. Everybody had their bad days, but the others would help that individual get back on track.”

The pandemic raged on.

Bamforth estimates that it took 18 months and 500 calls before the team landed its first outside funding — a $1.5 million grant from the NC Collaboratory, established in 2016 by the North Carolina General Assembly to fund life-changing research in the state. That vote of confidence was a lifesaver.

“The Collaboratory was built to be nimble and efficient and allow for a quick response to real-world issues,” says Executive Director Jeff Warren, who later kicked in more Collaboratory funding for READDI from the N.C. General Assembly.

The fundraising calls continued, surpassing 600.

Six months after READDI received the Collaboratory funds, RTI International awarded a team led by READDI a $5 million Forethought Challenge grant.

“All of a sudden, there was traction. There was movement. There were actual funds to support the work,” Moorman says. “I remember seeing Gov. Roy Cooper on TV announcing that his budget included funding for READDI. That was a huge moment.”

Indeed, in early 2022, the North Carolina General Assembly awarded READDI $18 million.

Moorman said all that funding allowed READDI to begin putting its operational structure in place to show how it would proceed efficiently and effectively. “That was another place Eshelman Innovation was incredibly helpful,” he says. “We started bringing in people to help move projects forward and keep track of everything.”

The READDI team leveraged that momentum and the knowledge gained up to that point to land its biggest award to date: $65 million from the National Institutes of Health to create the READDI Antiviral Drug Discovery Center, or READDI-AC, one of nine national AViDD centers. It’s led by Baric and Tim Willson, Ph.D., professor in the Eshelman School of Pharmacy and chief scientist for the Structural Genomics Consortium (SGC), an open science public-private partnership that accelerates drug discovery. The SGC was a founding partner of READDI, along with UNC-Chapel Hill and the Eshelman Institute.

“The devastating effects of the SARS-CoV-2 pandemic illustrate the critical need for new antiviral treatments for both existing and future viral disease threats,” READDI Co-founder Heise said after news of the NIH grant broke.

The funding was welcome validation, but the challenge was far from over. There was — and still is — plenty of drug discovery and development work to be done before READDI reaches its end goal, which is two Phase-2-ready broad-spectrum antivirals for every virus family with pandemic potential.

But the financial support accelerated progress. Along the way, Eshelman Innovation helped build a board of directors stacked with global thought leaders, including former U.S. Sen. Richard Burr, an early champion of the Pandemic All Hazards Preparedness Act, and executives from Johnson & Johnson, the Bill and Melinda Gates Foundation and the Drugs for Neglected Diseases Initiative. After serving as interim READDI CEO, Bamforth oversaw a national search for a permanent CEO, Jimmy Rosen, who brought experience from the worlds of health care venture capital, philanthropy, finance and startup leadership.

“Being an entrepreneur is a lonely endeavor. When you have a team behind you that supports you, encourages you and collaborates with you to do your best thinking, it’s really motivating,” says Rosen. “Eshelman Innovation did a lot of that early work to start READDI and set a good foundation.”

Moorman agrees. “Eshelman Innovation was part of the team from the beginning. Our mission then, and our mission now is to make sure we have these drugs ready for use in humans before the next pandemic strikes, creating a better life for the people of the state and the world.”