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 target SARS-CoV-2 RNA polymerase (nsp12), a highly conserved gene responsible for both viral RNA replication and transcription.

2021 Status: ROCHE ENDS COLLABORATION—Atea acknowledged November 16 that Roche will terminate its collaboration with Atea to co-develop AT-527. As a result, rights and licenses granted by Atea to Roche under the strategic collaboration will be returned to Atea, which will have full rights to continue clinical development and future commercialization of AT-527 worldwide.

“We believe strongly in the potential of AT-527 with its unique dual mechanism of action, antiviral activity against the major variants of concern and its market potential given the need for additional therapeutic options for COVID-19,” stated Jean-Pierre Sommadossi, PhD, Atea’s CEO and founder. “We have the financial resources and the talent to independently drive forward the Phase 3 MORNINGSKY clinical trial program, and we continue to expect data from this trial during the second half of 2022.

The collaboration with Roche will be terminated on February 10, 2022. Atea’s announcement of the termination noted that the company reported cash and cash equivalents of $839.7 million as of September 30, with a cash runway through 2023.

$50M Milestone Achieved—Atea said June 16 it expected to receive $50 million from Roche for achieving an undisclosed development milestone for AT-527.

Dosing Begins in Phase III Trial—Atea said April 29 that the first patient had been dosed in the Phase III MORNINGSKY trial, being conducted with Roche. The global multicenter trial is designed to assess AT-527 in mild or moderate COVID-19 patients in an outpatient setting. The trial, which is anticipated to enroll approximately 1,400 non-hospitalized adults and adolescents with mild to moderate COVID-19, is currently enrolling patients at clinical trial sites outside the U.S.

MORNINGSKY’s endpoint—assessing the efficacy of AT-527 compared with placebo—will measure the time to alleviation or improvement of COVID-19 symptoms. Other efficacy endpoints will include number of patients requiring medically attended visits or hospitalization for COVID-19. Additionally, among other secondary and exploratory endpoints, the study will also identify and/or evaluate biomarkers that are predictive of an antiviral response to AT-527.

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.

On February 8, 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.

On February 4, Atea said the first patient was dosed in a Phase II virology trial designed to evaluate the antiviral activity, safety, and pharmacokinetics of AT-527 in mild or moderate COVID-19 adult outpatients. The up-to-220 patient trial, being conducted with Roche, will enroll patients in the U.K., Ireland, and other countries. The trial’s primary endpoint is change from baseline in amount of SARS-CoV-2 virus RNA as measured by RT-PCR at specified timepoints.

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