Atea Pharmaceuticals Announces Presentation of Bemnifosbuvir Preclinical Data at the 38th International Conference on Antiviral Research (ICAR) 2025

Rhea-AI Summary

Atea Pharmaceuticals (AVIR) presented preclinical data for bemnifosbuvir (BEM) at the 38th International Conference on Antiviral Research 2025. The research demonstrated that BEM's metabolism to its active triphosphate is cell-line dependent, highlighting the importance of cell model selection in evaluating antiviral efficacy.

Following successful Phase 2 results in December 2024 and FDA End-of-Phase 2 meeting in January 2025, Atea is launching a global Phase 3 program for HCV treatment in April 2025. The program consists of two open-label trials, each enrolling approximately 800 treatment-naïve patients:

• Non-cirrhotic patients: 8 weeks of BEM/ruzasvir vs 12 weeks of sofosbuvir/velpatasvir
• Compensated cirrhotic patients: 12 weeks of both regimens

The primary endpoint is sustained virologic response 12 weeks post-treatment, measured as HCV RNA below quantitation limit at 24 weeks from treatment start.

Positive

• Phase 3 trials launching in April 2025 following successful Phase 2 results
• Potential for shorter 8-week treatment duration vs standard 12-week regimen for non-cirrhotic patients (90% of US HCV cases)
• Global program expansion with trials in US/Canada and international locations

Negative

• Cell-line dependent metabolism may complicate efficacy evaluation
• Longer 12-week treatment still required for cirrhotic patients

Insights

Biotech Analyst

Atea Pharmaceuticals' announcement represents a significant advancement in their hepatitis C virus (HCV) clinical program. Following a successful End-of-Phase 2 meeting with the FDA in January and positive Phase 2 results announced in December 2024, the company is now preparing to initiate its global Phase 3 program with patient enrollment starting next month.

The planned Phase 3 program consists of two substantial open-label trials, each enrolling approximately 800 treatment-naïve HCV patients, creating a robust dataset for potential approval. The trial design is comprehensive, including patients with and without compensated cirrhosis, and features treatment durations of 8 weeks for non-cirrhotic patients and 12 weeks for those with cirrhosis.

What's particularly noteworthy is the comparison against the current standard-of-care regimen of sofosbuvir and velpatasvir. This head-to-head design demonstrates Atea's confidence in their bemnifosbuvir/ruzasvir combination and positions it as a potential new standard if successful. The company's statement about developing a "potential best-in-class HCV regimen" signals their competitive ambitions in this space.

The HCV market remains significant despite advances in treatment, with over 90% of U.S. HCV patients being non-cirrhotic according to the company's statistics. This represents a substantial commercial opportunity if Atea's regimen demonstrates advantages over existing options, particularly if it can deliver equivalent efficacy with shorter treatment duration for the majority of patients.

While the preclinical data presentation itself is less material to investors, the insights regarding cell-line dependency for bemnifosbuvir metabolism highlight the company's scientific expertise and understanding of their compound's pharmacology.

Clinical Development Specialist

The progression to Phase 3 trials for bemnifosbuvir/ruzasvir represents a critical development milestone in Atea's clinical program. The company has successfully completed the regulatory gateway of an End-of-Phase 2 meeting with FDA, which traditionally serves as a significant de-risking event in the drug development process.

The trial design details reveal sophisticated strategic planning: The company is pursuing an ambitious enrollment target of approximately 1,600 patients across two trials, with a design that directly challenges the current standard of care. Most importantly, they're testing a reduced treatment duration of 8 weeks versus the standard 12 weeks for non-cirrhotic patients (representing 90% of U.S. HCV cases), which could offer meaningful patient benefits if successful.

From a clinical perspective, the primary endpoint selection demonstrates regulatory savvy. By measuring sustained virologic response (SVR12) with timing normalized to 24 weeks from treatment initiation across all arms, they've created a balanced comparison that should satisfy regulatory requirements while accounting for different treatment durations.

The preclinical findings on cell-line dependency have important methodological implications. They suggest Atea possesses sophisticated understanding of nucleotide prodrug pharmacology and appropriate model selection - critical expertise for developing this therapeutic class. This technical understanding may provide advantages in developing and optimizing their antiviral pipeline beyond just the lead HCV program.

While Phase 3 success remains to be determined, the comprehensive trial design, strategic endpoint selection, and previous Phase 2 success suggest Atea has positioned this program with careful attention to both regulatory and competitive considerations.

BOSTON, March 19, 2025 (GLOBE NEWSWIRE) -- Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (Atea or Company), a clinical-stage biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today announced the poster presentation of bemnifosbuvir preclinical data at the 38th International Conference on Antiviral Research (ICAR) 2025 taking place March 17-21, 2025 in Las Vegas, Nevada.

“The results presented at ICAR highlight Atea’s deep scientific expertise in antiviral drug development by demonstrating metabolism of nucleotide prodrugs, such as bemnifosbuvir, is highly cell-line dependent and cell model selection needs to be taken into account when evaluating in vitro antiviral efficacy,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and founder of Atea. “Bemnifosbuvir is being developed in a fixed dose combination regimen with ruzasvir for the treatment of hepatitis C virus (HCV). We look forward to starting patient enrollment in the Phase 3 program evaluating this potential best-in-class HCV regimen in April.”

Details for the poster presentation are as follows:

Poster Number: 500

Date and Time: Tuesday, March 18, 2025, 5:30 - 7:30 PM PDT and Thursday, March 20, 2025, 8:00 - 10:00 AM PDT

Title: Metabolism of Bemnifosbuvir to its Active Triphosphate Metabolite AT-9010 is Cell-Line Dependent

Bemnifosbuvir (BEM), an oral prodrug of a 6-modified guanosine nucleotide analog, is a potent HCV NS5B inhibitor being developed in a fixed dose combination regimen with ruzasvir, a highly potent NS5A inhibitor for the treatment of chronic HCV infection. The activation of BEM is mediated by cellular enzymes including CatA/CES1, HINT1, ADALP1, GUK1, and NDPK to yield the intracellular active triphosphate metabolite AT-9010. In this preclinical study, the metabolism of BEM to its active triphosphate was demonstrated to be cell-line dependent, indicating that cell model selection is critical when evaluating in vitro efficacy of antiviral prodrugs such as BEM.

Global Phase 3 Program for Hepatitis C Virus (HCV)

Based upon a successful engagement with the US Food and Drug Administration (FDA) at the End-of-Phase 2 meeting in January 2025, Atea is initiating a global Phase 3 program and expects patient enrollment to start in April 2025.

In December 2024, Atea announced that its Phase 2 study evaluating the regimen of BEM and ruzasvir for the treatment of HCV, met its primary endpoints. Atea plans to conduct two open label Phase 3 trials, one in the US and Canada and one outside of North America. Each Phase 3 trial is expected to enroll approximately 800 treatment-naïve patients, including those with and without compensated cirrhosis. For patients without cirrhosis, 8 weeks of the regimen of BEM and ruzasvir will be compared to 12 weeks of the regimen of sofosbuvir (SOF) and velpatasvir. For patients with compensated cirrhosis, 12 weeks of the regimen of BEM and ruzasvir will be compared to 12 weeks of the regimen of sofosbuvir and velpatasvir. In the US, it is estimated that more than 90% of people with HCV are non-cirrhotic.

The primary endpoint for both trials encompasses sustained virologic response 12 weeks post-treatment (SVR12) in each arm and is HCV RNA < lower limit of quantitation (LLOQ) 24 weeks from the start of treatment. Measurement at 24 weeks from the start of treatment is selected to ensure the primary endpoint occurs at the same relative timepoint from start of treatment in all patients.

About Bemnifosbuvir and Ruzasvir for Hepatitis C Virus (HCV)

BEM has been shown in in vitro studies to be approximately 10-fold more active than SOF against a panel of laboratory strains and clinical isolates of HCV GT 1–5. In vitro studies have also demonstrated BEM remained fully active against SOF resistance-associated substitutions (S282T), with up to 58-fold more potency than SOF. The PK profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV. BEM has been shown to have a low risk for drug-drug interactions. BEM has been administered to over 2,300 subjects and has been well-tolerated at doses up to 550 mg for durations up to 12 weeks in healthy subjects and patients.

Ruzasvir has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and clinical studies. Ruzasvir has been administered to over 2,100 subjects at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. The PK profile of ruzasvir supports once-daily dosing.

About Hepatitis C Virus (HCV)

HCV is a blood-borne, positive-sense, single-stranded (ss) RNA virus that primarily infects liver cells. HCV is a leading cause of chronic liver disease and liver transplants, spreading via blood transfusion, hemodialysis and needle sticks, with 242,000 deaths occurring each year. Despite the availability of direct-acting antivirals, HCV continues to be a significant global healthcare issue. An estimated 50 million people worldwide are chronically infected with HCV and there are approximately one million new infections each year. In the US, between 2.4 and 4 million people are estimated to have HCV with annual new infections outpacing treatment rates. HCV infections in the US predominate in patients in the age group between 20-49 years old, and it is estimated that less than 10% of HCV-infected patients in the US have cirrhosis. Chronic HCV infection is the leading cause of liver cancer in the US, Europe and Japan.

About Atea Pharmaceuticals

Atea is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral antiviral therapies to address the unmet medical needs of patients with serious viral infections. Leveraging Atea’s deep understanding of antiviral drug development, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea has built a proprietary nucleos(t)ide prodrug platform to develop novel product candidates to treat single stranded ribonucleic acid, or ssRNA, viruses, which are a prevalent cause of serious viral diseases. Atea plans to continue to build its pipeline of antiviral product candidates by augmenting its nucleos(t)ide platform with other classes of antivirals that may be used in combination with its nucleos(t)ide product candidates. Our lead program and current focus is on the development of the regimen of bemnifosbuvir, a nucleotide analog polymerase inhibitor, and ruzasvir, an NS5A inhibitor, to treat HCV. For more information, please visit www.ateapharma.com.

Forward-Looking Statements

This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to statements regarding the development of the regimen of bemnifosbuvir and ruzasvir for the treatment of HCV, including the anticipated initiation of patient enrollment in the Phase 3 program, and the potential best in class profile of the regimen . When used herein, words including “expected,” “should,” “anticipated,” “believe.” “will,” “plans”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Atea’s current expectations and various assumptions. Atea believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Atea may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, the timeline for the completion of the strategic alternatives review process is unknown and there can be no assurance that the process will result in any particular outcome; dependence on the success of Atea’s most advanced product candidates, in particular the combination of bemnifosbuvir and ruzasvir for the treatment of hepatitis C; as well as the other important factors discussed under the caption “Risk Factors” in Atea’s Annual Report on Form 10-K for the year ended December 31, 2024 as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC’s website at www.sec.gov. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While Atea may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing Atea’s views as of any date subsequent to the date of this press release.

Contacts

Jonae Barnes
SVP, Investor Relations and Corporate Communications
617-818-2985
Barnes.jonae@ateapharma.com

Joyce Allaire
LifeSci Advisors
Jallaire@lifesciadvisors.com

FAQ

When will Atea Pharmaceuticals (AVIR) begin Phase 3 trials for bemnifosbuvir HCV treatment?

Atea will begin patient enrollment for the Phase 3 trials in April 2025, following successful Phase 2 results and FDA End-of-Phase 2 meeting.

How many patients will be enrolled in AVIR's Phase 3 HCV trials?

Each of the two Phase 3 trials will enroll approximately 800 treatment-naïve patients, totaling around 1,600 patients.

What is the treatment duration for bemnifosbuvir in AVIR's Phase 3 HCV trials?

8 weeks for non-cirrhotic patients and 12 weeks for patients with compensated cirrhosis.

How does AVIR's bemnifosbuvir treatment duration compare to the current standard of care?

Bemnifosbuvir/ruzasvir offers 8 weeks treatment for non-cirrhotic patients compared to 12 weeks with sofosbuvir/velpatasvir, potentially reducing treatment time by 33%.

What is the primary endpoint for AVIR's Phase 3 HCV trials?

The primary endpoint is sustained virologic response (SVR12) measured as HCV RNA below quantitation limit at 24 weeks from treatment start.