On Jun. 30, 2021, Atea Pharmaceuticals announced positive interim results from the global Phase 2 study evaluating AT-527 in hospitalized patients with mild-to-moderate COVID-19. Roche and Atea are jointly developing AT-527, an oral direct-acting antiviral (DAA) agent derived from Ateaﾒs purine nucleotide prodrug platform.

The interim analysis of the Phase 2 study included data from 70 hospitalized, high-risk patients with COVID-19 of which data from 62 patients were evaluable for virology analysis. Interim virology results
indicated that AT-527 rapidly reduced viral load levels. At Day 2, patients receiving AT-527 experienced a 0.7 log₁₀ (80%) greater mean reduction from baseline viral load as compared to placebo. A sustained difference in viral load reduction was maintained through Day 8.

AT-527’s SARS-CoV-2 potent antiviral activity was also observed in patients with higher baseline viral loads above the median of 5.26 log₁₀ as compared to placebo. When evaluating a strict RT-qPCR threshold of 500 copies/mL with no detectable ribonucleic acid (RNA) virus (target not detected, TND), the AT-527 arm achieved SARS-CoV-2 clearance as early as Day 2 (in 6% of patients), Day 8 (in 7% of patients) Day 10 (in 33% of patients), and Day 12 (in 31% of patients) compared to 0% of patients in the placebo arm at the same timepoints. By Day 14 (last viral sampling study day) approximately 47%
of patients in the AT-527 arm and 22% in the placebo arm had no detectable RNA virus (TND). Nasopharyngeal swabs were measured in a reverse transcription polymerase chain reaction test (RT-qPCR) for the quantitative detection of nucleic acid from SARS-CoV-2.

Consistent with previous studies, AT-527 was generally safe and well tolerated. In this hospitalized study, there were no drug-related serious adverse events. Non-serious adverse events were equally distributed across treatment arms. Most were mild-to-moderate in severity and assessed as not related to the study drug. No safety concerns or newly determined risks were identified.

Data from recently completed preclinical studies demonstrated that AT-527 inhibits SARS-CoV-2 through unique dual mechanisms targeting both RNA dependent RNA polymerase (RdRP) and the nidovirus RdRp-associated nucleotidyltransferase (NiRAN) of viral non-structural protein (nsp12) polymerase, which is essential for viral RNA replication and transcription. In addition, analysis of samples treated with AT-511 (the free base of AT-527) by next generation sequencing (NGS) confirmed that AT-527 is not a mutagen and does not introduce mutations in the viral genome. These data will be submitted for peer-reviewed publication.