Atea Pharmaceuticals, Inc. announced new data from the lead-in cohort (n=60) of the Company?s ongoing Phase 2 combination study of bemnifosbuvir, an oral nucleotide NS5B polymerase inhibitor, and ruzasvir, an oral NS5A inhibitor, for the treatment of hepatitis C virus (HCV). With an 8-week treatment duration, the Phase 2 data from the lead-in cohort of non-cirrhotic patients showed a 97% sustained virologic response rate at 12 weeks post-treatment (SVR12), which is the primary efficacy endpoint of the study. The Company will also present preclinical data further demonstrating a high barrier to resistance and pharmacokinetics for bemnifosbuvir and a low risk of drug-drug interactions for ruzasvir.

These data are being presented at the European Association for the Study of the Liver (EASL) Congress taking place June 5-8, 2024, in Milan, Italy. Results from the lead-in cohort of the Phase 2 study also showed a 100% SVR12 rate in participants infected with genotype 3 (n=13), a historically difficult-to-treat genotype of HCV. The combination regimen was well tolerated, with no drug-related severe adverse events (SAEs) or treatment discontinuations.

Based on these positive data from the lead-in cohort, the Phase 2 study continues, with the aim of enrolling up to an additional 220 subjects, including those with compensated cirrhosis. More than 2 million people in the U.S. are living with chronic HCV, and approximately 100,000 new chronic cases are diagnosed each year. HCV diagnoses continually outpace annual treatment rates, as less than a third of those diagnosed with HCV receive timely treatment.

Data Presented at EASL Include: Poster Title: Lead-in Cohort Results From a Phase 2 Study of a Novel 8-Week Combination Regimen of Bemnifosbuvir and Ruzasvir in Patients with Chronic Hepatitis C Virus Infection (THU-382). Conclusion: Data from the lead-in cohort of 60 patients in the Phase 2 clinical trial of bemnifosbuvir and ruzasvir in HCV-infected subjects showed a high SVR12 rate of 97% in the lead-in cohort with a short 8-week duration of treatment. The primary endpoints of the study are safety and SVR12.

Viral kinetics were similar in genotype 1 and genotype 3 infected subjects, including a 100% SVR12 rate in historically difficult-to-treat genotype 3 infected subjects. The combination was generally safe and well tolerated. There were no drug-related serious adverse events or treatment discontinuations, and adverse events were mostly mild.

Poster Title: Bemnifosbuvir is a Potent HCV NS5B Inhibitor with a Favorable Antiviral Profile and High Resistance Barrier (SAT-402). Conclusion: Viral resistance is an important consideration for direct-acting antiviral (DAA) use as it may impact the efficacy of treatments for HCV infection. Results demonstrated that bemnifosbuvir is at least ten-fold more potent than sofosbuvir, a medication to treat HCV infections, across all genotypes tested and is not resistant to resistance-associated substitutions (RASs) that have been found to alter the activity of sofosbuvir.

While the C223H mutation was found to be the primary bemnifosbuvir RAS in genotype 1b, multiple additional substitutions at other NS5B regions were required to confer meaningful resistance, suggesting that bemnifosbuvir provides a high barrier to resistance. Based upon the data demonstrated to date, it is expected that the bemnifosbuvir and ruzasvir combination should have a more compelling antiviral profile against major HCV NS5A RAVs than the current standard of care. Poster Title: Absorption, Distribution, Metabolism, and Excretion of [14C]-Bemnifosbuvir in Rats (SAT-411).

Conclusion: This preclinical study in rats was conducted to better understand the tissue distribution, metabolites, and excretion routes following bemnifosbuvir treatment. Following a single oral dose in rats, bemnifosbuvir has favorable overall absorption, distribution, metabolism, and excretion (ADME) properties, including good bioavailability (>60%) and wide distribution to tissues with low penetration into the brain. Bemnifosbuvir was highly and rapidly metabolized to the metabolite AT-273, consistent with the proposed metabolic and activation pathway.

Poster Title: Low Risk of Drug-Drug Interactions for Ruzasvir Based Upon In Vitro Metabolism and Transporter Interaction Studies (SAT-412). Conclusion: Many patients infected with HCV are also taking multiple co-medications, which may impact treatment decisions. This preclinical study aimed to further understand the risk of drug-drug interactions (DDIs) for ruzasvir by analyzing its metabolism in human liver microsomes and cells.

Based on these in vitro data and static DDI risk assessment models, ruzasvir has a low potential to be a perpetrator of DDIs via inhibition or induction of CYP450. Similarly, it has a low potential to inhibit OATP1B1 and OATP1B3 transporters. The relevance of bile salt export pump (BSEP) inhibition to DDIs is limited.