ruzasvir (MK-8408) / Merck (MSD), Atea Pharma - LARVOL DELTA

Multiscale Modeling of an 8-Week Combination Regimen of Bemnifosbuvir and Ruzasvir in Patients with Chronic Hepatitis C Virus Infection. (PubMed, Clin Pharmacol Ther) - P2 | "The estimated efficacy of therapy was similar across genotypes 1 to 4. Thus, our modeling supports the conclusions that BEM/RZR is pan-genotypic, has high antiviral effectiveness and leads to rapid viral clearance in both cirrhotic and non-cirrhotic patients."

Journal • Fibrosis • Hepatitis C • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

AT-01B-010: Study of Bemnifosbuvir/Ruzasvir as a Fixed-dose Combination in Subjects With Normal or Severely Impaired Renal or Hepatic Function (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion • Hepatology • Renal Disease

Proton-pump inhibitor Omeprazole did not affect the plasma pharmacokinetics of Bemnifosbuvir and Ruzasvir fixed-dose combination in healthy participants (EASL 2026) - "BEM/RZR FDC was safe and well-tolerated when administered alone or concomitantly with OMEP. While OMEP 20 mg, a common dose for GERD did not affect the plasma exposure to BEM/AT-273/RZR, a higher 40 mg dose of OMEP with BEM/RZR dosed 2h later to allow for maximal acid-suppressive effect did not meaningfully reduce plasma exposure to BEM/AT-273/RZR either. Results support concomitant use of OMEP 20 mg or 40 mg with BEM/RZR in HCV-infected individuals without restriction."

Clinical • PK/PD data • Gastroesophageal Reflux Disease • Hepatitis C • Infectious Disease

Bemnifosbuvir and ruzasvir administered as a fixed-dose-combination have low potential to inhibit P-gp, BCRP or OATP1B1/3 mediated transport (EASL 2026) - "A Ph 1 study in healthy participants was conducted to assess the clinical implications of these results using digoxin (DIG) and rosuvastatin (ROSU) as P-gp and BCRP/OATP1B1/1B3 index substrates, respectively... A single dose of BEM 550 mg/RZR 180 mg administered as 2xFDC tablets only slightly increased the plasma exposure of the P-gp and BCRP/OATP1B1/3 index drugs DIG and ROSU. With GMR<2, BEM/RZR therefore have low potential to exhibit clinically meaningful inhibition of these transporters. No dose adjustment will be needed for drugs that are sensitive substrates of P-gp or BCRP/OAT1B1/3 when co- administered with BEM/RZR; staggered dosing may lessen any DDI risk."

Breast Cancer • Solid Tumor

AT-01B-010: Study of Bemnifosbuvir/Ruzasvir as a Fixed-dose Combination in Subjects With Normal or Severely Impaired Renal or Hepatic Function (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Trial completion date: Nov 2025 ➔ May 2026 | Trial primary completion date: Nov 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Hepatology • Renal Disease

Drug-drug Interaction Study of Bemnifosbuvir/Ruzasvir (BEM/RZR) and Ethinyl Estradiol/Levonorgestrel (EE/LNG) (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P1 trial

C-BEYOND: Efficacy and Safety of BEM/RZR vs. SOF/VEL in Subjects With Chronic HCV (clinicaltrials.gov) - P3 | N=880 | Active, not recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis C • Infectious Disease • Inflammation

MULTISCALE MODELING OF RESULTS: FROM A PHASE 2 STUDY OF AN 8-WEEK COMBINATION REGIMEN OF BEMNIFOSBUVIR AND RUZASVIR IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION (AASLD 2025) - P2 | "BEM/RZR for 8 weeks was highly effective in blocking both viral replication and viral assembly/secretion in HCV-infected patients independent of genotype and fibrosis score. The time to cure estimates support 8 wk treatment for non-cirrhotic patients and longer treatment duration (e.g., up to 12 wks) for those with compensated cirrhosis."

Clinical • P2 data • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

BEMNIFOSBUVIR AND RUZASVIR PROVIDED AS A FIXED-DOSE-COMBINATION DEMONSTRATES HIGH RELATIVE BIOAVAILABILITY TO THEIR INDIVIDUAL FORMULATIONS AND CAN BE DOSED WITH NO REGARD TO FOOD (AASLD 2025) - P1 | "The BEM/RZR FDC was safe and well-tolerated when dosed without or with food or with famotidine. BEM/RZR FDC demonstrated a high rBA to the BEM and RZR individual reference formulations. A HFHC meal or simultaneously co-administered famotidine had no meaningful effect on plasma exposure of the FDC."

Clinical

AT-01B-010: Study of Bemnifosbuvir/Ruzasvir as a Fixed-dose Combination in Subjects With Normal or Severely Impaired Renal or Hepatic Function (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Trial completion date: Aug 2025 ➔ Nov 2025 | Trial primary completion date: Aug 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Hepatology • Renal Disease

NO IMPACT OF RASS ON THE HIGH EFFICACY OF BEM AND RZR IN COMBINATION: RESISTANCE ANALYSIS FROM A PH 2 STUDY IN HCV-INFECTED PATIENTS (AASLD 2025) - P2 | "Background: Bemnifosbuvir (BEM) and ruzasvir (RZR) are potent pan-genotypic inhibitors of HCV NS5B and NS5A, respectively... The combination of BEM/RZR in this phase 2 study showed strong antiviral activity against all tested HCV genotypes (GT 1-4). VK and PK data indicated most VFs were due to poor adherence and resulted from NS5A resistance to RZR. BEM/RZR is currently in phase 3 development."

Clinical • Hepatitis C • Liver Cirrhosis

Drug-drug Interaction Study of Omeprazole and Bemnifosbuvir/Ruzasvir (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Not yet recruiting ➔ Completed

Trial completion

Drug-drug Interaction Study of Bemnifosbuvir/Ruzasvir (BEM/RZR) and Digoxin and Rosuvastatin (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion

C-Forward: Efficacy and Safety of BEM/RZR vs SOF/VEL in Subjects With Chronic HCV (clinicaltrials.gov) - P3 | N=880 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P3 trial • Hepatitis C • Infectious Disease • Inflammation

Drug-drug Interaction Study of Omeprazole and Bemnifosbuvir/Ruzasvir (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P1 trial

AT-01B-010: Study of Bemnifosbuvir/Ruzasvir as a Fixed-dose Combination in Subjects With Normal or Severely Impaired Renal or Hepatic Function (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2025 ➔ Aug 2025

Enrollment open • Trial completion date • Trial primary completion date • Hepatology • Renal Disease

Drug-drug Interaction Study of Bemnifosbuvir/Ruzasvir (BEM/RZR) and Digoxin and Rosuvastatin (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

No DDI between Bemnifosbuvir/Ruzasvir and Bictegravir/Emtricitabine/Tenofovir Alafenamide (EASL 2025) - "BEM/RZR and B/FTC/TAF, alone and co-administered, were well tolerated in healthy subjects with no clinically relevant PK DDI. These results support the enrollment of HCV/HIV-co- infected subjects receiving B/FTC/TAF in BEM/RZR clinical trials."

Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetics of bemnifosbuvir in participants with hepatic impairment (EASL 2025) - P1 | "Background and Aims: Bemnifosbuvir (BEM, AT-527) is an oral double prodrug of a guanosine nucleotide analog with potent activity against coronaviruses and flaviviruses including hepatitis C virus (HCV). BEM in combination with ruzasvir (HCV NS5A inhibitor), is under clinical development for the treatment of chronic HCV infection... BEM 550 mg was safe and well-tolerated in participants with impaired or normal hepatic function. Plasma exposures to the parent BEM, but not the metabolite AT-273, surrogate for the active triphosphate, increased as hepatic function worsened. These results provide PK support for dosing BEM 550 mg in HCV-infected participants with compensated or decompensated cirrhosis."

PK/PD data • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease

Efficacy and safety of Bemnifosbuvir and Ruzasvir after 8 weeks of treatment in patients with chronic hepatitis C virus (HCV) infection (EASL 2025) - P2 | "In this population with NS5A RAS high prevalence at baseline, high efficacy was observed, regardless of treatment adherence. These data support that non-cirrhotic patients can effectively be treated for 8 weeks with BEM+RZR, while cirrhotic patients will require 12 weeks of dosing to maximize efficacy. The regimen was well tolerated with no drug-related SAEs or treatment discontinuations due to AEs."

Clinical • Fibrosis • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis

Efficacy and safety of Bemnifosbuvir and Ruzasvir after 8 weeks of treatment in patients with chronic hepatitis C virus (HCV) infection (EASL 2025) - No abstract available

Clinical • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Pharmacokinetics of bemnifosbuvir in participants with renal impairment (EASL 2025) - P1 | "BEM in combination with ruzasvir (HCV NS5A inhibitor), is under clinical development for the treatment of HCV... BEM 550 mg was safe and well-tolerated in participants with impaired or normal renal function. Plasma exposure to BEM was not affected by RI but increased with worsening renal function especially for the inactive nucleoside metabolite AT-273. The high renal clearance of AT-273 which exceeded GFR indicated the involvement of active transport in its renal elimination."

PK/PD data • Chronic Kidney Disease • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Nephrology • Novel Coronavirus Disease • Renal Disease

Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "No serious adverse events or premature drug discontinuations were reported. Overall, the study results support further evaluation of bemnifosbuvir and ruzasvir combination therapy for treating chronic HCV."

Journal • P1 data • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Drug-drug Interaction Study of Bemnifosbuvir/Ruzasvir (BEM/RZR) and Digoxin and Rosuvastatin (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P1 trial

Study of Bemnifosbuvir/Ruzasvir as a Fixed-dose Combination in Subjects With Normal or Severely Impaired Renal or Hepatic Function (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P1 trial • Hepatology • Renal Disease