The Omicron variant has driven home the reality that COVID-19 may be with us for a long time. But if one of New England’s leading biotech thinkers is right, there could soon be a new way to fight it.
The day after Thanksgiving, as reports of the variant were circulating, Tillman Gerngross’s team at Adagio Therapeutics ran a test that suggested the company’s experimental antibody treatment, which is still in clinical trials, would work against Omicron.
There’s a much bigger idea at stake: The therapy is designed to work against all variants of the coronavirus, and also could help prevent disease. Whether it will or not remains to be seen — it is very early. But with questions swirling around how effective vaccines and treatments will be against Omicron and future strains, it’s a key moment for Adagio, which has positioned its antibody drug as a supplement to existing options.
Investors have liked its approach. The market value of the 18-month-old public company, based in Waltham, doubled after Thanksgiving to about $5 billion, before settling around $4.3 billion on Tuesday.
Adagio is one of several players in the growing field of monoclonal antibody treatments, which have been gaining traction since the rise of the Delta variant last summer. The Biden administration has purchased millions of doses from Regeneron and Eli Lilly, as well as an antibody treatment from GlaxoSmithKline and Vir Biotechnology, which on Tuesday reported promising results against Omicron mutations in lab tests.
Monoclonal antibodies are based on proteins developed in a laboratory, and they mimic the immune system’s ability to fight off viruses. They are given usually by intravenous infusion in a hospital, and work by binding to the virus and blocking it from entering cells.
Gerngross, a prominent scientist-turned-entrepreneur, didn’t originally plan to join the fray of companies working on COVID-19 therapeutics. But during the first wave in the spring of 2020, he was intrigued by an idea from his colleague Laura Walker, an expert in antibody science.
Given the time and money it takes to develop drugs, she said, it would make sense to create a monoclonal antibody treatment that would work against COVID-19, any potential variant, and even other SARS-like viruses that might emerge in the future.
Several drug and vaccine makers have targeted the spike protein, a part of the coronavirus that the pathogen uses to invade cells. Omicron’s spike protein has more than 30 mutations, and scientists are concerned that they might diminish the ability of antibodies to bind to and neutralize the virus. But Walker analyzed antibodies that worked against the virus that causes COVID-19, the virus that caused the SARS outbreak in 2003, and other known bat viruses to find a patch on the spike protein that didn’t appear to change over time. In theory, an antibody that binds to that spot could neutralize multiple coronaviruses and be less vulnerable to mutations.
“[Laura] said that’s important, because that’s going to make this molecule work when ‘SARS-CoV-3′ [the next coronavirus] comes around, and also make it more useful against variants, which at the time no one was talking about,” Gerngross said.
That conversation, which took place at their separate antibody company Adimab in Lebanon, N.H., led them in July 2020 to spin out Adagio, which raised hundreds of millions of dollars from investors and went public in August 2021, valued at $1.8 billion.
It’s a dizzying pace for a startup whose name was inspired by a musical term for going slow. But Gerngross, a bioengineering professor at Dartmouth College who is CEO of both Adimab and Adagio, has always done things a little differently.
“Everyone else was going allegro,” Gerngross said, moving quickly to get experimental vaccines and treatments into the clinic. But he decided to move at a more deliberate pace (adagio), so Walker could find the perfect molecule.
“To actually generate this molecule, we were coming to work while everyone else was hunkering down at home,” Walker said.
In June 2020, Walker settled on a particular monoclonal antibody, called ADG20. Adimab tried to shop it around to a pharmaceutical partner. But negotiating a deal could take months.
So Gerngross cofounded Adagio with Walker and René Russo, the chief executive of Xilio Therapeutics in Waltham.
Russo had led another Gerngross-founded antibody startup, Arsanis, until 2018, when its drug candidate failed. She wasn’t surprised when Gerngross called her and said, “I need you to take a look at something.” She joined Adagio after one board meeting.
“I canvassed everyone I knew who were no-nonsense, hard-core, infectious disease development people,” said Russo, chair of Adagio’s board of directors. “I begged them to come to this company that didn’t exist.”
Gerngross was tasked with raising money. He corralled 20 venture capitalists on a Zoom call on June 11. It was a highly unusual way to ask for support, but these were people who had poured hundreds of millions of dollars into his previous companies. A day after the call, Adagio raised $50 million.
“I think he prefers the most efficient, candid, straightforward way to get to a solution,” said Terry McGuire of Boston venture capital firm Polaris Partners, who was on the call. McGuire sits on the boards of Adimab and Adagio and has invested in every Gerngross startup since he cofounded GlycoFi, which Merck bought for $400 million in 2006.
Adagio would raise another $400 million from investors before completing a $356 million IPO. The company has 85 employees across 25 states and considers Waltham its headquarters. (Gerngross is based in New Hampshire.)
The company’s antibody is now in clinical trials as both a prophylactic — a drug that aims to prevent disease — and a treatment. It’s different from a vaccine, which prepares your immune system to make antibodies if you are exposed to the virus; here the drug is the antibody.
Adagio’s can be delivered via an intramuscular shot in the thigh in an outpatient setting. Lab data suggests it might be effective at preventing disease for up to one year, the company says. It expects to have clinical results, which would support an emergency use authorization filing, in the second quarter of 2022.
Meanwhile, COVID-19 vaccines from Moderna, Pfizer, and Johnson & Johnson, antibody treatments from Regeneron, Eli Lilly, and GSK/Vir, and antiviral pills from Pfizer and Merck are either authorized in the United States or nearing clearance.
But it’s becoming clear that each option has limitations. COVID vaccines and boosters don’t work well for some 8 to 10 million immunocompromised people, not to mention the vaccine-hesitant or countries that can’t afford to buy them, Gerngross said. And he thinks a vaccine booster strategy that reacts to variants is “really dumb,” so Adagio is studying its antibody as a supplement to vaccination.
“By the time they have Omicron ready, we’re going to be at whatever the next letter in the Greek alphabet is,” he said. “This game of whack-a-mole and chasing your own tail . . . we are not going to vaccinate ourselves out of this problem.”
Oral pills, which treat COVID infection, would be more convenient and less expensive than antibodies, but they would not offer long-lasting protection.
Dr. Helen Boucher, an infectious disease specialist at Tufts Medical Center and interim dean of Tufts University School of Medicine, said Adagio’s strategy to broadly target coronaviruses seems promising, especially with the emergence of Omicron. If its preventative treatment could last for a year, she said, that would be “extremely helpful.” (Monoclonal antibodies typically dissipate in a few weeks or months.)
Adagio has spent $400 million to have 4 million doses ready for a potential FDA authorization next year. A “Warp Speed 2.0,″ or advance purchase commitments, would help increase supply, Gerngross said.
Biotech investor Robert Nelsen, cofounder and managing director of Arch Venture Partners and a board member of San Francisco-based Vir, a competitor to Adagio, said there is an undersupply of antibodies.
“I’m a huge fan of Tillman and I think they likely have a good antibody,” he said. “What Adagio is doing is great, what Regeneron is doing is great, what Vir is doing is great. Vaccines are the best, but for breakthrough [cases] or people that are unvaccinated, they should get antibodies.”
Peter Dedon, who heads the Singapore-MIT Alliance for Research and Technology, agreed that more antibodies are needed. But he is skeptical of Adagio’s claims about Omicron. “Adagio comes out and makes a rosy prediction with no data,” he said. “Everyone else is hedging their bets.”
But to Gerngross, that’s the point — we need a hedge against the existing approaches. He thinks antiviral pills, such as the one from Pfizer, will be useful against Omicron, but he expects some vaccines and antibodies to take a hit.
Gerngross has long warned that a COVID-19 variant could wipe out existing therapeutics that were not designed to work as well after the virus mutates. And beyond that, he’s certain there will be another COVID-like pandemic in the future.
When that day comes, he said, “I would rather hold my cards than anyone else’s cards.”