pevifoscorvir sodium (ALG-000184) / Aligos Therap - LARVOL DELTA

ALG-001075, the parent of pevifoscorvir sodium, exhibits potent in vitro antiviral properties compared to other HBV capsid assembly modulators in clinical development (EASL 2026) - No abstract available

Preclinical • Hepatitis B

Pevifoscorvir sodium demonstrated profound antiviral activity in untreated HBeAg+ subjects, regardless of baseline ALT level (EASL 2026) - No abstract available

Clinical • Hepatitis B • Hepatology • Infectious Disease

Sustained reduction of HBV antigen levels at ≥6 months follow-up in HBeAg-positive participants with chronic hepatitis B infection after 96 weeks of 300 mg pevifoscorvir sodium monotherapy (EASL 2026) - No abstract available

Monotherapy • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Population pharmacokinetics of pevifoscorvir sodium (ALG-000184) in healthy participants and participants with chronic hepatitis B in support of phase 2 dose selection (EASL 2026) - No abstract available

Clinical • P2 data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

ALG-000184-202: Phase 2 Study Evaluating the Efficacy and Safety of ALG-000184 Compared with Tenofovir Disoproxil Fumarate in Untreated HBeAg-Positive and HBeAg-nNegative Adult Subjects with Chronic Hepatitis B (B-SUPREME) (clinicaltrialsregister.eu) - P1/2 | N=50 | Recruiting | Sponsor: Aligos Therapeutics Inc.

New P1/2 trial • Hepatitis B • Infectious Disease • Inflammation

Single Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Aligos Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Infectious Disease • Inflammation • Renal Disease

Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Aligos Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Infectious Disease

Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Aligos Therapeutics

New P1 trial • Hepatology • Infectious Disease

Single Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Aligos Therapeutics

New P1 trial • Hepatitis B • Infectious Disease • Inflammation • Renal Disease

ALG-000184 (pevifoscorvir sodium) monotherapy in participants with chronic HBV infection: a phase 1, multicentre, randomised, dose escalation trial. (PubMed, Lancet Gastroenterol Hepatol) - P1 | "ALG-000184 was safe and well tolerated, demonstrated predictable pharmacokinetic properties, and reduced HBV DNA and HBV RNA at all doses regardless of HBeAg status. These results support the evaluation of 300 mg ALG-000184 over longer periods in larger studies to determine its potential role in chronic suppressive therapy, with or without a nucleos(t)ide analogue, or as part of a finite curative regimen."

Journal • Monotherapy • P1 data • Hepatitis B • Infectious Disease • Inflammation • Pain • Respiratory Diseases

A Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects (clinicaltrials.gov) - P1 | N=165 | Completed | Sponsor: Aligos Therapeutics | Active, not recruiting ➔ Completed

First-in-human • Trial completion • Hepatitis B • Infectious Disease • Inflammation

A Phase 1 study of the safety, tolerability, and pharmacokinetics of ALG-000184 (pevifoscorvir sodium), a novel Class E capsid assembly modulator, in healthy participants. (PubMed, Antivir Ther) - P1 | "Urinary excretion of ALG-001075 was low following single or multiple ALG-000184 doses.ConclusionsALG-000184 demonstrated good tolerability, safety and pharmacokinetic properties in healthy participants. The pharmacokinetic profile suggests that a daily dose of 100 mg or higher will provide efficacious exposures in patients with chronic HBV infection.Clinical trial numberNCT04536337 (https://clinicaltrials.gov/study/NCT04536337)."

Clinical • Journal • P1 data • PK/PD data • Hepatitis B • Infectious Disease

CAPSID ASSEMBLY MODULATOR ALG-001075 BINDS AND DIRECTLY TARGETS HBEAG (AASLD 2025) - "ALG-001075 demonstrated direct binding to HBeAg and pronounced in vitro reductions in secreted HBeAg levels, in line with clinical observations for its prodrug ALG-000184, suggesting direct inhibition of HBeAg as a third mechanism of action for ALG-001075. Although the direct HBeAg effect requires higher compound concentrations than the primary and secondary effects of CAMs, the high pharmacokinetic exposure achieved with prodrug ALG-000184 and relative HBeAg-targeting potency of parent ALG-001075 likely enable the clinical observation of this effect."

Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

SUSTAINED REDUCTION OF HBV ANTIGEN LEVELS DURING THE 8-WEEK FOLLOW-UP PERIOD IN TREATMENT NAÏVE (TN) OR CURRENTLY-NOT-TREATED (CNT) HBEAG-POSITIVE SUBJECTS WITH CHRONIC HEPATITIS B VIRUS INFECTION AFTER 96-WEEK 300 MG ALG-000184, WITH OR WITHOUT ENTECAVIR (ETV) (AASLD 2025) - P1 | "100 or 300 mg ALG-000184 ± ETV for ≤ 24 weeks or ≤ 96 weeks resulted in dose- and duration-dependent multi-log reductions in HBV antigens in TN/CNT HBeAg+ subjects. Additionally, sustained reductions in HBV antigens were observed during the 8-week post-ALG-000184 follow-up period after longer treatment with higher dose of 300 mg ALG-000184. This may indicate cccDNA depletion, associated with the CAM-E secondary mechanism of action."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

DIFFERENTIATION OF HBV CAPSID ASSEMBLY MODULATORS BASED ON STABILIZATION OF CORE PROTEIN OLIGOMERIZATION AND RESIDENCE TIME (AASLD 2025) - "ALG-000184 is a prodrug of ALG-001075, a novel capsid assembly modulator leading to the formation of empty capsids (CAM-E)... We developed a novel jump dilution assay to assess the biochemical potency/residence time of CAM compounds. Our results demonstrate that the stability of Cp oligomerization and target residence time are important parameters for the characterization of next-generation CAMs."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

CAPSID ASSEMBLY MODULATOR ALG-001075 PREVENTS CCCDNA FORMATION AND HBV DNA INTEGRATION IN VITRO (AASLD 2025) - "ALG-000184 is a prodrug of ALG-001075, a novel capsid assembly modulator leading to the formation of empty capsids (CAM-E)...This was not the case for nucleos(t)ide analogs entecavir and tenofovir... ALG-001075 demonstrated potent prevention of HBV cccDNA formation and HBV DNA integration, further confirming its best-in-class properties and superiority over commonly used nucleos(t)ide analogs."

Preclinical • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

ORAL ONCE-DAILY 300 MG ALG-000184, A NOVEL CAPSID ASSEMBLY MODULATOR, DEMONSTRATED PROFOUND AND SUSTAINED SUPPRESSION OF HBV DNA TO < 10 IU/ML IN ALL TREATMENT NA&IUML; VE (TN) OR CURRENTLY-NOT-TREATED (CNT) SUBJECTS WITH CHRONIC HBV INFECTIO (AASLD 2025) - P1 | "Treatment with 300 mg ALG-000184 monotherapy for 96 weeks led to maintained, profound suppression of HBV DNA in TN/CNT chronic HBV infection subjects with no viral breakthrough. These findings support the continued development of ALG-000184 as a potentially improved monotherapy regimen for chronic suppression. A head-to-head comparison of ALG-000184 vs Tenofovir monotherapy has been initiated in the Phase 2 B-SUPREME study."

Clinical • Hepatitis B • Infectious Disease

A Study Evaluating the Efficacy and Safety of ALG-000184 Compared With Tenofovir Disoproxil Fumarate in Untreated HBeAg-Positive and HBeAg- Negative Adult Subjects With Chronic Hepatitis B (B-SUPREME) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Aligos Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Infectious Disease • Inflammation

A Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects (clinicaltrials.gov) - P1 | N=165 | Active, not recruiting | Sponsor: Aligos Therapeutics | Recruiting ➔ Active, not recruiting | N=336 ➔ 165 | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Nov 2023 ➔ Jun 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hepatitis B • Infectious Disease • Inflammation

A Study Evaluating the Efficacy and Safety of ALG-000184 Compared With Tenofovir Disoproxil Fumarate in Untreated HBeAg-Positive and HBeAg- Negative Adult Subjects With Chronic Hepatitis B (B-SUPREME) (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Aligos Therapeutics

New P2 trial • Hepatitis B • Infectious Disease • Inflammation

Viral kinetics and sequence analysis of a phase I monotherapy study in subjects with chronic hepatitis B reveals a high barrier of resistance to the capsid assembly modulator ALG-000184 (EASL 2025) - No abstract available

Clinical • Monotherapy • P1 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Monotherapy with the novel capsid assembly modulator ALG-000184 for up to 96 weeks results in profound and sustained HBV DNA suppression in untreated subjects with chronic HBV infection (EASL 2025) - No abstract available

Clinical • Monotherapy • Hepatitis B • Infectious Disease

Viral kinetics and sequence analysis of a phase I monotherapy study in subjects with chronic hepatitis B reveals a high barrier of resistance to the capsid assembly modulator ALG-000184 (EASL 2025) - "No viral breakthrough or non-response, as measured by HBV DNA levels was observed in the 21 CHB participants undergoing ALG-000184 monotherapy for up to 96 weeks. Consistently, none of the major ALG-000184 resistance mutations identified in vitro (T33N, T33P and V124G) were detected in any of the baseline or on-treatment samples, indicating a high barrier to resistance. The lack of viral breakthrough and emerging resistance, combined with the significant reduction in HBV DNA, positions ALG-000184 as a promising candidate for further clinical development as a potential backbone of therapy for chronic viral suppression."

Clinical • Monotherapy • P1 data • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Monotherapy with the novel capsid assembly modulator ALG-000184 for up to 96 weeks results in profound and sustained HBV DNA suppression in untreated subjects with chronic HBV infection (EASL 2025) - P1 | "ALG-000184, in combination with ETV for up to 96 weeks, was well tolerated and led to profound suppression of HBV DNA in untreated HBeAg+ subjects with high baseline HBV DNA levels. These results indicate the potential of ALG-000184 in different combination therapies for chronic HBV infection. Full data for 96 weeks of treatment and 8 weeks of follow-up will be shared at the EASL conference."

Clinical • Monotherapy • Hepatitis B • Hepatology • Infectious Disease • Inflammation

The safety and antiviral effect of oral daily 300 mg ALG-000184 in combination with Entecavir for up to 96 Weeks in untreated HBeAg-positive subjects with chronic hepatitis B virus infection (EASL 2025) - P1 | "ALG-000184, in combination with ETV for up to 96 weeks, was well tolerated and led to profound suppression of HBV DNA in untreated HBeAg+ subjects with high baseline HBV DNA levels. These results indicate the potential of ALG-000184 in different combination therapies for chronic HBV infection. Full data for 96 weeks of treatment and 8 weeks of follow-up will be shared at the EASL conference."

Clinical • Combination therapy • Hematological Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Neutropenia