WALTHAM, Mass.--(BUSINESS WIRE)--Adagio Therapeutics, Inc., today pre-published in vitro and in vivo data demonstrating its lead antibody candidate, ADG2, shows similar or higher potency against SARS-CoV-2 compared to monoclonal antibodies (mAbs) in clinical development, while also uniquely offering broad neutralization against a range of sarbecoviruses that pose a threat to humans. Adagio expects its half-life engineered version of ADG2, called ADG20, to enter clinical studies in early 2021. The manuscript summarizing the Adagio findings has been accepted for review by the journal Science and was made available on the bioRxiv.org pre-print server.
“These studies demonstrate our lead antibody shows comparable or higher neutralization potency against SARS-CoV-2 than most leading antibodies currently in development for COVID-19, and yet maintains its ability to potently neutralize SARS-CoV and additional pre-emergent SARS-like coronaviruses currently circulating in bats,” said Laura Walker, Ph.D., chief scientific officer of Adagio. “All of the antibodies currently in clinical development trade-off breadth for potency. They either show broad activity against other sarbecoviruses but lack neutralization potency, or they show high neutralization potency against SARS-CoV-2 but lack activity against other coronaviruses. These data suggest that ADG20 holds the promise of being a broadly protective agent against SARS-CoV-2 as well as future SARS-like coronaviruses that are likely to emerge.”
Data highlights:
Potency and breadth of coverage
- ADG2 (the precursor to ADG20) provided complete protection against severe SARS-CoV-2 and SARS-CoV disease in mouse models.
- When compared to other monoclonal antibodies (mAbs) in development, ADG2 showed similar or higher potency against SARS-CoV-2 in two authentic neutralization assays.
- ADG2 also showed broad and potent neutralizing activity against SARS-CoV and two SARS-related coronaviruses currently known to be circulating in bat populations (WIV-1 and SHC014).
- The epitope targeted by ADG2 is highly conserved across clade 1 sarbecoviruses, and ADG2 binds with high affinity to a large panel of clade I sarbecovirus receptor binding domains (RBDs).
Viral escape variants
- ADG2 binds with high affinity to the 30 most frequently observed SARS-CoV-2 RBD variants reported in the GISAID database, including variants resistant to other monoclonal antibodies in development.
- Notably, no mutations have been reported at key ADG20 contact residues in full length viral genomic sequences (>152,000) of SARS-CoV-2 included in the GISAID database as of October 19, 2020, suggesting a low risk of pre-existing resistance to ADG20 in the clinic.
Other enhanced attributes
- In vitro engineering of ADG2 avoided many of the common pitfalls associated with monoclonal antibody enhancements. Specifically, ADG2 demonstrated favorable biophysical properties in a series of in vitro assays that have been shown to be predictive of downstream behaviors such as serum half-life, ease of manufacturing, ability to formulate to high concentrations, and long-term stability.
- Although not included in the pre-publication, Adagio also engineered ADG2 to extend serum half-life and enhance mucosal localization.
“As we look to the future, it is clear we will need potent treatment and prevention for not only COVID-19 but also for future coronaviruses, which we can now say with near certainty will continue to emerge,” said Tillman Gerngross, Ph.D., chief executive officer of Adagio. “Based on these data, we believe ADG20 has the potential to offer unsurpassed treatment and prevention for COVID-19 while serving as a potent and broadly protective countermeasure to protect against resistant strains of SARS-CoV-2 as well as future sarbecovirus threats. Importantly, we took our time to develop ADG20 without sacrificing duration of effect, manufacturability, and affordability. We look forward to advancing ADG20 into the clinic in 2021 to learn how it may provide protection from the greatest pandemic of our lifetime.”
About Adagio Therapeutics
Adagio is developing best-in-class antibodies that can broadly neutralize SARS-CoV-2, SARS-CoV and additional pre-emergent coronaviruses. We believe our antibodies will match or exceed the potency and coverage of conventional SARS-CoV-2 antibody programs and can be used in both treatment and durable prevention. Our candidates are engineered using industry-leading antibody discovery capabilities and are designed to maximize potency and duration of effect. Our portfolio includes multiple, non-competing antibodies with distinct binding targets, enabling a strategy that can avoid viral escape. Our lead program, ADG20, is expected to enter the clinic in early 2021. ADG20 was designed to provide patients and clinicians with an unsurpassed combination of potency, breadth, durable protection (via half-life extension), manufacturability, tolerability, and affordability. For more information: www.adagiotx.com
