Adagio Therapeutics has dosed the first subject with its anti-SARS-CoV-2 antibody. Administration of the candidate, which Adagio expects to be effective against coronavirus variants, continues the rapid rise of the biotech helmed by Tillman Gerngross, Ph.D.
The fast development of vaccines that provide high initial levels of protection against the pandemic coronavirus has raised doubts about how significant a role anti-SARS-CoV-2 antibodies will play in the response to the crisis. Those doubts were intensified by the emergence of variants which, based on early studies, appear to have some level of resistance to antibody neutralizing.
Yet Adagio, a 2020 Fierce 15 winner, sees a significant ongoing role for antibodies in the fight against SARS-CoV-2 and related coronaviruses. Adagio took a step toward the realization of that vision Monday when it disclosed the dosing of the first subject in a phase 1 clinical trial of its monoclonal antibody candidate ADG20.
The U.S. phase 1 will assess the safety, tolerability and pharmacokinetics of ADG20 in healthy adults. Once it has “adequate” safety data, Adagio plans to move into global pivotal trials to assess whether ADG20 can treat and prevent COVID-19.
In a statement, Adagio Chief Medical Officer Lynn Connolly, M.D., Ph.D., said her team will assess “ADG20 across multiple clinical settings on a global basis from pre- and post-exposure prophylaxis to treatment.” Adagio intends to include sites in countries that have high levels of resistant variants, such as the B.1.351 virus first identified in South Africa.
Adagio has preclinical evidence that its lead candidate is effective against emerging variants. In mice, Adagio found ADG20 neutralizes SARS-CoV-2 as effectively as similar molecules and is potent against other clade 1 sarbecoviruses, including the virus that caused the 2003 SARS outbreak.
The preclinical efficacy of ADG20 against multiple coronaviruses is a result of Adagio’s decision to target a highly conserved epitope overlapping the receptor-binding site. Adagio discovered ADG20 by isolating antibodies from a 2003 SARS survivor that cross-neutralize multiple SARS-related viruses. By engineering the antibodies, Adagio hit upon a candidate that appears to be both potent and broadly effective.
If the clinical trials confirm that early-stage finding, Adagio could position ADG20 in the response to SARS-CoV-2 variants that can cause COVID-19 in vaccinated individuals and as a weapon in the likely ongoing fight against SARS-related viruses. Having seen two SARS-related viruses spread in humans in less than 20 years, post-pandemic governments may be in the market for products that can manage and stamp out the next potential crisis.
Demonstrating ADG20 is effective against an evolving coronavirus is only part of the challenge facing Adagio. The biotech will also need to deliver a product that fits in with the workflows and budgets of healthcare systems. With that in mind, Adagio will test an intramuscular formulation of ADG20 as well as an intravenous version in phase 1 and has tried to make the molecule as easy to manufacture at scale as possible. Adagio has raised $130 million to fund the work since launching in July.
Connolly, who called intramuscular administration a potential “critical differentiator,” said her team is “currently focused on outpatient populations, including an emphasis on addressing unmet needs in vulnerable groups such as the immune compromised and children.”