New in vitro data presented at CROI show that Atea Pharmaceuticals’ oral nucleotide analogue AT-587 demonstrates markedly superior potency against hepatitis E virus compared with existing off-label options, supporting plans to advance the candidate into phase 1 clinical development in 2026.
Atea Pharmaceuticals has reported encouraging preclinical findings for its investigational antiviral AT-587, highlighting the compound’s potential as a first-in-class treatment for hepatitis E virus (HEV).
The results, presented at the ongoing Conference on Retroviruses and Opportunistic Infections (CROI) being held in Denver, Colorado, demonstrated that AT-587 and a second proprietary nucleotide analogue, AT-2490, were highly potent inhibitors of HEV replication in vitro, with no observed toxicity in human liver cells.
HEV is a positive-sense, single-stranded RNA virus that primarily infects hepatocytes and represents a growing global health concern. Although genotypes 1 and 2 are most prevalent in low-income regions of Asia and Africa, genotypes 3 and 4 are endemic in industrialized regions such as the United States and Europe. In immunocompromised individuals—including transplant recipients and patients with hematologic malignancies or preexisting liver disease—chronic HEV infection can progress rapidly, leading to cirrhosis within 3 to 5 years. Despite this risk, there are currently no approved antiviral therapies for HEV, and existing off-label treatments are limited by suboptimal efficacy and tolerability.
In laboratory studies, AT-587 and AT-2490 showed striking antiviral activity, demonstrating 30- to 150-fold greater potency against HEV compared with sofosbuvir and ribavirin, 2 agents sometimes used off label. Beyond HEV, both compounds exhibited activity against a broad range of RNA viruses, including all flaviviruses tested as well as rubella and chikungunya. Importantly, antiviral activity was confirmed in the tissue of interest—human liver cells—where high levels of the active intracellular metabolite were detected. Neither compound demonstrated cytotoxicity, supporting a favorable in vitro safety profile.
AT-587 and AT-2490 were 30 to 150 times more potent against HEV in vitro than sofosbuvir and ribavirin, with no observed toxicity in human liver cells.
Both compounds demonstrated activity beyond HEV, including against flaviviruses, rubella, and chikungunya.
With no approved HEV therapies and high risk of rapid disease progression in immunocompromised patients, AT-587 could fill a critical treatment gap as it advances toward phase 1 development.
“These results underscore the potential of AT-587 as a first-in-class direct-acting antiviral for HEV,” Atea CEO Jean-Pierre Sommadossi, PhD, said in a statement. “We are excited to share these preclinical results at CROI showing the potent activity and promising in vitro safety profiles of AT-2490 and AT-587, our HEV product candidate.”
Based on the strength of these findings, Atea selected AT-587 as the lead candidate for its HEV program earlier this year and anticipates initiating a phase 1 clinical trial in mid-2026. According to Sommadossi, the unmet need is substantial. “With no antivirals currently marketed for HEV, AT-587 has the potential to address a significant unmet need for patients with chronic HEV infection who are immunocompromised or at high risk for rapid progression to cirrhosis,” he said. “We look forward to advancing AT-587 to a phase 1 program midyear.”
If these promising preclinical results translate into clinical benefit, AT-587 could represent a meaningful advance for a vulnerable patient population with few therapeutic options.
