Adagio Therapeutics today published in vitro and in vivo data in Science on its lead antibody candidate, ADG2, which demonstrated similar or higher potency against SARS-CoV-2 compared to other monoclonal antibodies (mAbs) in clinical development and strong binding to all known SARS-CoV-2 variants. Uniquely, ADG2 also showed broad and potent neutralization against a range of sarbecoviruses that pose a threat to humans and protective efficacy in murine models of SARS and COVID-19. The data show that ADG2 effectively binds to and has the potential to protect against common circulating SARS-CoV-2 variants as well as future SARS-related viruses with pandemic potential. Adagio’s half-life engineered version of ADG2, called ADG20, could offer protection against COVID-19 for up to a year. Adagio expects ADG20 to enter Phase 1 clinical studies in early 2021.
“These studies demonstrate our lead antibody shows comparable or higher neutralization potency against SARS-CoV-2 than leading antibodies currently in development for COVID-19 and binds effectively to all of the most commonly circulating SARS-CoV-2 variants, indicating that it should not be affected by known resistance mutations. Unlike most antibodies currently in clinical development or approved for emergency use, ADG20 binds to a highly conserved epitope, so we believe it will also be effective against future emerging SARS-CoV-2 strains and related pre-emergent sarbecoviruses,” said Laura Walker, Ph.D., chief scientific officer of Adagio.
Potency and breadth of coverage
- ADG2 (the precursor to ADG20) provided complete protection against severe SARS-CoV-2 and SARS-CoV disease in murine models of COVID-19 and SARS, respectively.
- When compared to other mAbs in development or approved for emergency use, ADG2 showed similar or higher potency against SARS-CoV-2 in two authentic neutralization assays.
- ADG20 demonstrated strong binding to all commonly circulating SARS-CoV-2 variants.
- 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 resistance variants
- ADG2 binds with high affinity to more than 30 of the most frequently observed SARS-CoV-2 RBD variants reported in the GISAID database, including the known variants resistant to other monoclonal antibodies in development or approved for emergency use.
- 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 December 9, 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.
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