Last week, Adagio Therapeutics raised $80 million in a series B financing to speed its COVID-19 antibody into development. This week, it provided some details about how its approach differs from the many other antibodies in development—and showed some hints of efficacy in mice.
A pre-engineered version of Adagio’s lead drug candidate, ADG20, protected against SARS-CoV and SARS-CoV-2—the virus that causes COVID-19—in mouse models, the company reported on the journal preprint site bioRxiv. In lab tests, the drug also neutralized WIV-1 and SHC014, two related coronaviruses known to be circulating in bats.
“All of the antibodies currently in clinical development trade-off breadth for potency. They either show broad activity against other [viruses] but lack neutralization potency, or they show high neutralization potency against SARS-CoV-2 but lack activity against other coronaviruses,” said Laura Walker, Ph.D., chief scientific officer of Adagio, in a statement.
Adagio’s goal was to find an approach that offered both potency and breadth of protection. So it put together a library of antibodies that bind to a portion of the spike protein on SARS-CoV-2 and other viruses.
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For the current study, Adagio’s team engineered three SARS-CoV-2 antibodies derived from memory B cells of one patient who survived SARS-CoV in 2003. They used a technology called yeast-surface display to improve the ability of the antibodies to bind to the spike protein, they explained in the paper.
In addition to testing the lead compound in mouse models, Adagio used neutralization assays to show that the ADG20 precursor had similar or better potency than other antibody treatments being tested in COVID-19, the company said.
The Adagio researchers also reported that the antibody binds to 30 SARS-CoV-2 variants that are known to confer resistance to similar drugs in development.
Adagio has joined a crowded field of biopharma companies working on antibody treatments for COVID-19. Competitors include Amgen, GlaxoSmithKline and AstraZeneca, not to mention Eli Lilly, which scored an emergency use authorization from the FDA Nov. 10 for its antibody drug bamlanivimab.
Regeneron is awaiting an answer from the FDA on an emergency use request for its antibody cocktail. A safety concern prompted an independent monitoring board to recommend against using the drug in the sickest patients, but the company is optimistic the drug will find use in other patient populations. It has promised to have 80,000 doses ready by the end of November and 200,000 by early January.
Then there are Pfizer and Moderna’s mRNA vaccines, which are expected to go to the FDA for emergency use consideration shortly. That may dampen the demand for antibody treatments in the short term, but there will still be a need for them in the future, Adagio’s scientists argued.
In the new study, they wrote, “the recurrent zoonotic spillover of CoVs into the human population, along with the broad diversity of SARS-like CoVs circulating in animal reservoirs, suggests that novel pathogenic CoVs are likely to emerge in the future and underscores the need for broadly active countermeasures.”