Candidate: AT-527

Category: ANTIVIRAL

Type: Highly selective, oral direct acting antiviral (DAA) derived from Atea’s purine nucleotide prodrug platform. AT-527 is designed to inhibit viral RNA dependent RNA polymerase enzyme.

2021 Status: Atea said February 19 that Chugai Pharmaceutical, a Member of the Roche Group, has in-licensed from Roche the rights to Atea’s AT-527 for the treatment of COVID-19 in Japan, for an undisclosed price. Roche and Atea are jointly developing AT-527 for COVID-19 under a strategic collaboration giving Roche the right to commercialize AT-527 outside the U.S.; Atea retains U.S. rights, with the option to request support from Genentech, a Member of the Roche Group.

Atea said February 8 that researchers have published preclinical data in Antimicrobial Agents and Chemotherapy showing highly potent in vitro antiviral activity of AT-527 against SARS-CoV-2. AT-527 was activated in cultured normal human nasal and bronchial epithelial cells. Since the respiratory tract is the initial site of the SARS-CoV-2 infection, Atea reasons, activation of AT-527 with its substantial half-life suggested sustained inhibition of viral replication of SARS-CoV-2 in these tissues.

The results also showed that AT-511, the freebase of AT-527, exhibited highly potent activity in inhibiting the replication of SARS-CoV-2, through extensive activation in key human primary cells, nasal and bronchial epithelial cells. The half-life seen in those primary human cells of the upper and lower respiratory tract was approximately 40 hours—allowing accumulation of the active triphosphate metabolite of the drug candidate in key tissues, thus resulting in the potent inhibition of SARS-CoV-2 viral replication by AT-527.

A simulation using human PK data combined with non-human primate tissue levels showed that within two hours of dosing, AT-9010—a triphosphate active metabolite of AT-527—achieved concentrations that according to Atea should inhibit SARS-CoV-2 replication, and should be maintained throughout therapy.

2020 Status: Atea and Roche said October 22 that they entered into a strategic collaboration to develop, manufacture, and distribute AT-527 for COVID-19. AT-527 is under study in a Phase II trial in hospitalized patients with moderate COVID-19, with a Phase III trial expected to start in the first quarter of 2021, will explore the potential use in patients outside of the hospital setting. AT-527 may be developed for post-exposure prophylactic settings, and could also be the first oral treatment option for COVID-19 patients that are not hospitalized, the companies added.

Atea said May 20 that the FDA cleared its IND for AT-527 for the treatment of adults hospitalized with moderate COVID-19 disease, with one or more risk factors for poor outcomes. A Phase II clinical trial (NCT04396106) was recruiting patients as of July 31. The trial is designed to evaluate the safety and efficacy of AT-527 in this patient population.

Atea also said it completed a $215 million Series D financing whose proceeds are intended to support clinical development of the company’s COVID-19 candidate AT-527, in addition to advancing its broader pipeline of treatments for viral diseases. The financing was led by Bain Capital Life Sciences and also included new investors RA Capital Management, Perceptive Advisors, Rock Springs Capital, Adage Capital Management, funds and accounts managed by T. Rowe Price Associates, Redmile Group, and Omega Funds. Existing Atea investors, including Morningside Ventures, Cormorant Asset Management, Ally Bridge Group, and Sectoral Asset Management, as well as other investors also participated in this financing.

According to Atea, AT-527 has shown in vitro and in vivo antiviral activity against several enveloped single-stranded RNA viruses, including human flaviviruses and coronaviruses—while antiviral activity and safety of AT-527 has been shown in Phase II clinical studies of hepatitis C patients.


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA