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RO7445482 + RO7191863 + nucleos(t)ide

Development stage: Unknown
Lead developer: Roche
Modality: Small Molecules, Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, MicroRNA (miRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics
Administration: Subcutaneous, Oral

Overview

This is a combination regimen under clinical investigation for the treatment of **chronic hepatitis B**. It consists of: - **RO7445482**: a small interfering RNA (siRNA) molecule targeting hepatitis B viral transcripts, leading to suppression of hepatitis B surface antigen (HBsAg) and viral replication, - **RO7191863**: a locked nucleic acid (LNA) oligonucleotide designed to target and inhibit the expression of **programmed death-ligand 1 (PD-L1)** in the liver, aiming to modulate immune response and restore HBV-specific immune control, - **Nucleos(t)ide**: referring to nucleos(t)ide analogues (such as tenofovir or entecavir), the current standard antiviral backbone for HBV, which inhibits HBV reverse transcriptase and blocks viral replication. This combination is being studied to achieve greater rates of HBsAg clearance and functional cure in chronic hepatitis B patients by simultaneously interrupting viral replication (siRNA, nucleos(t)ide), boosting antigen clearance, and restoring T-cell responsiveness (anti-PD-L1 LNA)[1][2][3].

Other names: RG6346 (for RO7445482)

Targets

HBV RNA (Hepatitis B virus RNA)HBV Pol (Hepatitis B virus polymerase)CD274 (Programmed cell death protein 1 ligand 1)

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