Adagio Therapeutics, Inc. reported that the primary endpoints were met with statistical significance for all three indications in the company's ongoing global Phase 2/3 clinical trials evaluating its investigational drug adintrevimab (ADG20) as a pre-and-post-exposure prophylaxis (EVADE) and treatment (STAMP) for COVID-19. EVADE and STAMP were primarily conducted during a time when pre-Omicron SARS-CoV-2 variants were dominant. Following the emergence of the Omicron variant, in a pre-specified exploratory analysis in a subset of the pre-exposure cohort, a clinically meaningful reduction in cases of symptomatic COVID-19 was observed with adintrevimab compared to placebo. Across both trials, a single intramuscular (IM) administration of adintrevimab at the 300mg dose had a similar safety profile to that of placebo. Based on these data, Adagio plans to engage with the U.S. Food and Drug Administration (FDA) and to submit an Emergency Use Authorization (EUA) application in the second quarter of 2022 for adintrevimab for both the prevention and treatment of COVID-19. In addition, Adagio provided an update on its ongoing Phase 1 study evaluating adintrevimab at higher doses and on research activities related to adintrevimab re-engineering and the identification of new antibodies to potentially address COVID-19 and other viruses. EVADE is a global, multi-center, double-blind, placebo-controlled Phase 2/3 clinical trial evaluating adintrevimab at the 300mg IM dose in two independent cohorts for the prevention of COVID-19. The study includes a pre-exposure prophylaxis (PrEP) cohort and a post-exposure prophylaxis (PEP) cohort. The study population is comprised of adults and adolescents at risk of SARS-CoV-2 infection due to reported recent exposure or whose circumstances placed them at increased risk of acquiring SARS-CoV-2 infection and developing symptomatic COVID-19. In the primary efficacy analysis of the PrEP cohort, adintrevimab was associated with a lower incidence of symptomatic COVID-19 compared with placebo through month three or the emergence of Omicron, whichever was earlier (12/730, 1.6% vs. 40/703, 5.7%, respectively). The standardized risk difference was -4.0% (95% CI –6.0, -2.1; p <0.0001), demonstrating a 71% relative risk reduction in favor of adintrevimab through three months. There were five (0.7%) COVID-19 related hospitalizations in the placebo group compared to none in the adintrevimab group. In a pre-specified exploratory analysis of the PrEP cohort, which included 402 participants (196 and 206 in the adintrevimab and placebo groups, respectively) following the emergence of Omicron (BA.1), a clinically meaningful reduction in cases of symptomatic COVID-19 was observed with adintrevimab, as compared to placebo. Adintrevimab was associated with a relative risk reduction of 59% and 47% with a median follow-up duration of 56 and 77 days, respectively (nominal p <0.05).

In the primary efficacy analysis in the PEP cohort, adintrevimab met statistical significance and was associated with a lower incidence of symptomatic COVID-19 through day 28 compared with placebo (3/173, 1.7% vs. 12/175, 6.9%, respectively). The standardized risk difference was -4.9% (95% CI: -8.8, -1.0; p=0.0135), demonstrating a 75% relative risk reduction in favor of adintrevimab through 28 days. There were two (1.1%) COVID-19 related hospitalizations in the placebo group compared to none in the adintrevimab group. In the EVADE cohorts across 1,239 adintrevimab-treated participants with a median range of follow up of 140 days for the PrEP cohort and 126 days for the PEP cohort as of the March 2, 2022, data cut off, the safety profile was similar to that of placebo. The incidence of adverse events (AEs), including serious adverse events (SAEs), was similar between adintrevimab and placebo groups. No study drug related SAEs, including deaths, were reported. The most frequently reported AEs were injection-site reactions, the majority of which were mild or moderate in severity and occurred with similar frequency in both groups. STAMP is a global, multi-center, double-blind, placebo-controlled Phase 2/3 clinical trial evaluating adintrevimab at the 300mg IM dose in patients with mild to moderate COVID-19 who are at high risk for disease progression. Adintrevimab was associated with a statistically significant lower incidence of COVID-19 related hospitalization or all cause death through day 29 compared with placebo (8/169, 4.7% vs. 23/167, 13.8%), with a standardized risk difference of -8.6% (95% CI: -14.65, -2.57; p=0.0052), demonstrating a 66% relative risk reduction in favor of adintrevimab. There was one death (0.6%) in the adintrevimab group, compared with six deaths (3.6%) in the placebo group through day 29. In patients treated within three days of symptom onset (adintrevimab n=91, placebo n=85), adintrevimab reduced the risk of COVID-19 hospitalization or death from any cause by 77% compared to placebo. STAMP enrolled 63 participants (29 in the adintrevimab group and 34 in the placebo group) with COVID-19 infection with the Omicron SARS-CoV-2 variant. There were two events of COVID-19 related hospitalization and no deaths through day 29 among the patients with the Omicron variant, and both events of hospitalization occurred in the placebo group. In STAMP, across 192 adintrevimab-treated participants with a median follow up of 73 days in the adintrevimab group as of the February 2, 2022, data cut off, the incidence of AEs, including SAEs, was lower in the adintrevimab group. No study drug related SAEs, including deaths, were reported. The most frequently reported AEs were injection-site reactions, all of which were mild or moderate in severity and occurred with similar frequency in both groups.