READDI – or not? – for the next pandemic

Many of us don’t worry much about Covid-19 these days, despite a recent uptick in infections. But researchers at UNC-Chapel Hill are already preparing for the next viral pandemic.¹

“It’s a question of when – not if,” Dr. Nat Moorman, co-founder of the Rapidly Emerging Antiviral Drug Development Initiative (READDI), told a symposium of researchers and public-health professionals last week.

Scientists can’t predict the exact virus that will next erupt across the globe. But they can identify about half a dozen virus families that pose severe risks.

READDI AIMS to develop “broad-spectrum” antiviral drugs as treatments for those viral families – READDI CEO Jimmy Rosen likened it to targeting the suits in a deck of cards, rather than the individual cards.

“We have to be ready with drugs for every suit in the deck,” he said. “Because we don’t know what the next virus is going to be.”

Pharmaceutical makers often won’t invest in developing a drug unless it has an existing market, Rosen said.

But if we wait for a “market” to develop in the midst of a pandemic, millions could die awaiting drug development.

As a result, READDI will rely on government, industry and philanthropic institutions to drive much of its research, Rosen said.

Moorman, virologist Dr. Ralph Baric at the Gillings School of Global Public Health and Dr. Mark Heise, professor of genetics and virology at the UNC School of Medicine, first conceived of READDI in January 2020, when the Covid pandemic was just gathering momentum.

UNC-Chapel Hill Chancellor Kevin Guskiewicz noted that the NC General Assembly provided $18 million for the effort two years ago. And with the help of then-Sen. Richard Burr, it received $65 million from the National Institutes of Health last spring.

DR. NANCY MESSONNIER, Dean of the UNC Gillings School of Global Public Health, oversaw distribution of COVID-19 vaccines for the Centers for Disease Control and Prevention during the pandemic.

Messonnier traced the history of outbreaks since the anthrax scares of 2001 through the Ebola, Zika and Covid viruses. In every case, the country was ill-prepared, with a lack of diagnostics, drugs to treat the condition and vaccines to prevent it, she said.

And those drugs don’t appear by magic.

“It’s not a miracle,” she said. “It’s science.”

Dr. Matthew Hepburn spent 23 years in the U.S. Army as an infectious disease specialist. He later served as the COVID Vaccine Lead for Operation Warp Speed.

With UNC’s world-class virology and chemistry departments, “Without a doubt, you’re on the cutting edge of scientific discovery here,” Hepburn told the symposium.

It’s unusual to see a university take on a “mash-up” of everything from discovery of a molecule to drug development, financing and manufacturing, he said, but with North Carolina’s medical systems and drug-manufacturing presence, it is uniquely positioned.

Hepburn posed a troubling question, though: If READDI develops five drugs with the potential to stop a pandemic, and each takes $1 billion to bring to market, but READDI has a budget of $1 billion, which drug should it pursue?

The threats call for a portfolio of treatments.

“You’ve got to have something to face each family of viruses,” he said.

FORMER SENATOR BURR, a READDI board member who was involved with drug development and pandemic preparedness as a member of Congress, said that after the 2001 anthrax scare, “We looked at it and found out we had no architecture to handle something like that.”

There was no national stockpile of drugs to respond, Burr said. But later legislation created the framework that allowed drug makers to produce a Covid vaccine in 12 months.

Burr noted that there was only one person wearing a mask in the audience at the Carolina Inn. “Nobody’s too worried right now,” he said. Yet he said he received calls from three people last Wednesday morning alone telling him they had tested positive for Covid.

Burr warned that with Social Security, Medicare and the Department of Defense considered off-limits in current budget negotiations on Capitol Hill, Congress could well cut research funding. And work to develop vaccine boosters often can’t keep up with mutations in the virus.

“Everything sort of leads to this approach,” he said of READDI.

Charlotte Baker, deputy head of the G7 countries’ International Pandemic Preparedness Secretariat in London, agreed that “pandemic fatigue” is the prevailing sentiment at the moment. But investments now could help develop multiple tools to respond when they’re needed.

“It’s not about the sprint of response from the moment that we’re all panicking,” she said. “It’s about the marathon of preparedness before Day Zero.”

“The middle of a pandemic is not the time to be discussing how you will work together,” she said.

MOORMAN outlined five virus families the initiative is targeting.

“We don’t know what the next virus is … but we do know that viruses are related,” he said.

The Flavivirus family – which includes Zika, West Nile and Dengue – is an insect-borne virus with no known treatments, Moorman said. Yet Dengue alone infects 350 million people a year.

“No vaccines. No therapeutics,” he said.

Access to and affordability of drugs are important, especially in developing countries.

Moorman described a compound called NZ-804 that was developed at Texas A&M and has a similar target as Paxlovid, blocking the ability of the Covid virus to replicate in the lungs.

Why pursue a drug similar to one that already exists? Sixty million Americans can’t take Paxlovid due to potential interactions with other drugs – and NZ-804 is less expensive to make, he said.

“We make decisions along the way where access … actually drives the science,” he said.

Moorman estimated it would take $1.2-1.5 billion in direct costs to develop two drugs for each of the priority virus families and take them through Phase I safety trials so that they are ready for Phase II trials.

“It is just a matter of time before the next pandemic arrives…. We need to get ready now so we don’t go through the same thing,” he said.

“We’re getting this done – now. We’re not waiting.”

¹ https://readdi.org/stories/symposium-underscores-readdis-role-in-marathon-of-preparedness/.