Adagio Therapeutics, Inc., (Nasdaq: ADGI), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of antibody-based solutions for infectious diseases with pandemic potential, today summarized recent findings reported in three separate publications that show ADG20, its lead monoclonal antibody (mAb), has neutralization activity against the Omicron (B.1.1.529) variant of SARS-CoV-2, and outlined initiatives to address current and future SARS-CoV-2 variants of concern. Adagio is evaluating ADG20 in its global Phase 2/3 clinical trials for both the prevention and treatment of COVID-19. Adagio is engaging with the U.S. Food and Drug Administration (FDA) regarding potential protocol updates to its global Phase 2/3 clinical trials, including an increased dose of ADG20 for the potential prevention and treatment of COVID-19 resulting from the Omicron variant.
ADG20 Neutralizing Activity Against Omicron
Recently published in vitro studies examined the neutralization potencies of large panels of mAbs against the Omicron variant in both authentic and pseudovirus assays. Findings across all three studies show that among mAbs in late-stage clinical development or with Emergency Use Authorization (EUA), ADG20 is one of only a few mAbs that demonstrated neutralizing activity against Omicron. Across two distinct authentic neutralization assays against Omicron, the data show that ADG20 had an IC₅₀, a measurement of neutralization potency, of approximately 0.4 to 1.1 µg/mL, which is comparable with the two other active mAbs, sotrovimab and AZD7742.
“What is critical to assessing potential clinical effectiveness of SARS-CoV-2 mAbs is the neutralization potency by the mAb against a specific variant. While findings may show that ADG20 has reduced potency against Omicron when compared to its high potency against all other variants of concern, including Delta, the data support that ADG20 is among the few mAbs to demonstrate neutralizing activity against the Omicron variant and warrants its continued development,” said Laura Walker, Ph.D., chief scientific officer and co-founder of Adagio.
These data add to previously reported in vitro data from a variety of preclinical studies that showed that ADG20 retains activity against other variants of concern including Alpha, Beta, Delta and Gamma, and that ADG20 retains neutralizing activity against a diverse panel of circulating SARS-CoV-2 variants, including the Lambda, Mu and Delta plus variants.
Clinical Trial Update to Address Omicron
Adagio is continuing evaluation of ADG20 in its EVADE and STAMP clinical trials. Adagio is engaging with the FDA on dosing strategy, including an increased dose of ADG20 and other protocol updates in light of the spread of the Omicron variant. Adagio is pausing the enrollment of new patients in the 300 mg dose arm in both clinical trials as the company updates its protocols. Follow-up and monitoring of patients previously administered ADG20 are continuing per the original protocols.
Additional Efforts to Address Omicron and Future Variants
In addition to its clinical trial updates, Adagio is pursuing multiple strategies to address both Omicron and potential future variants that may emerge. Leveraging its exclusive partnership with Adimab LLC, a global leader in antibody engineering, Adagio is exploring the potential to engineer ADG20 to further improve binding to the Omicron variant to enhance its neutralization potency against Omicron while retaining its broad neutralization against other SARS-CoV-2 variants of concern. In parallel, Adagio is assessing several hundred mAbs from its proprietary library of previously isolated SARS-CoV-2 antibodies for their neutralization potency against Omicron. Such an additional neutralizing mAb could be developed as a stand-alone product or as part of a combination approach. These efforts are underway, and the company anticipates preliminary findings from its research in the first quarter of 2022.
“SARS-CoV-2 is a quickly evolving virus, and at Adagio, we are committed to adapting just as quickly. It is abundantly clear that no single product will fully address the evolving nature of the COVID-19 pandemic, and that multiple preventative and therapeutic solutions are needed. Based on both in-house data and third-party findings, we are confident that ADG20 can be an important tool in the fight against this virus,” added Tillman Gerngross, Ph.D., co-founder and chief executive officer of Adagio.
ADG20, an investigational monoclonal antibody targeting the spike protein of SARS-CoV-2 and related coronaviruses, is being evaluated in global clinical trials for the prevention and treatment of COVID-19, the disease caused by SARS-CoV-2. ADG20 was designed to possess high potency and broad neutralization activity against SARS-CoV-2 and additional clade 1 sarbecoviruses by targeting a highly conserved epitope in the receptor binding domain. ADG20 was further engineered to provide an extended half-life for durable protection. In vitro data from a variety of preclinical studies have shown that ADG20 retains neutralizing activity against all known SARS-CoV-2 variants of concern. In a Phase 1 trial, ADG20 was well-tolerated with no safety signals identified through a minimum of three months follow-up across all cohorts. ADG20 has not been approved for use in any country, and safety and efficacy have not yet been established.