Chronic hepatitis B (HBV) affects an estimated 250 million people globally and remains functionally incurable because of covalently closed circular DNA (cccDNA) — a persistent viral reservoir in hepatocytes that current nucleoside/nucleotide analogs suppress but cannot eliminate. The 2026 functional-cure race has become a multi-modality contest, well represented at EASL 2026 in Barcelona.
The approaches in play: capsid assembly modulators plus antisense oligonucleotide sequencing (Aligos Therapeutics' pevifoscorvir sodium plus ALG-170675 ASO, where 40% of HBeAg-positive patients reached HBsAg levels low enough to qualify for ASO therapy at week 48); gene editing targeting cccDNA directly (Precision BioSciences' PBGENE-HBV, which showed first evidence of cccDNA elimination in patient liver biopsies in the ELIMINATE-B study); epigenetic silencing (TUNE Therapeutics' TUNE-401); and protein-based therapeutic vaccines designed to restore immune control (Brii Bio's BRII-179, Phase 2 ENSURE). HBV is also the obligate partner of hepatitis delta virus (HDV), so HBV entry inhibitors like bulevirtide and ABI-6250 block both viruses.
Stories here cover the HBV functional-cure pipeline across modalities and the HBV/HDV mechanistic overlap. See #hdv, #aligos-therapeutics, and #functional-cure for adjacent threads.
EASL 2026's final day delivered a cluster of hepatitis B functional-cure late-breakers spanning gene, epigenetic, and immune approaches. TUNE Therapeutics presented TUNE-401 (May 30, 13:30 CEST), a first-in-class epigenetic silencer of HBV demonstrating deep and durable antiviral activity. Precision BioSciences presented PBGENE-HBV gene-editing data from the ELIMINATE-B study showing first evidence of elimination and inactivation of cccDNA — the persistent viral reservoir that makes HBV functionally incurable — in liver biopsies from treated chronic HBV patients. Brii Bio presented end-of-study data from the Phase 2 ENSURE study supporting BRII-179, a protein-based therapeutic HBV vaccine designed to restore immune control. The functional-cure wave advances alongside the entry-inhibitor approaches covered earlier in the week — Gilead's just-approved bulevirtide peptide (Hepcludex) and Assembly Biosciences' oral ABI-6250 — illustrating that HBV/HDV is becoming a multi-modality battleground across peptides, gene editing, epigenetic silencing, and therapeutic vaccines.
EASL 2026 closed in Barcelona on May 30 after a week that reshaped two liver-disease narratives. On MASH: the GLP-1/glucagon peptide cohort (survodutide NEJM 47-62% MASH improvement, pemvidutide Best of EASL with cardiometabolic and fibrosis data, MetaVia DA-1726 9.1% weight loss) competed against THR-β agonism (Madrigal Rezdiffra, Aligos ALG-055009 46% liver fat), RNAi (Arrowhead ARO-INHBE), and FGF21 analogs (the Akero and 89bio programs that drew $5.2B and $3.5B acquisitions). On HBV/HDV: the entry-inhibitor peptides (Gilead's newly approved bulevirtide, Assembly's oral ABI-6250) shared the stage with gene editing (Precision PBGENE-HBV cccDNA elimination), epigenetic silencing (TUNE-401), capsid modulation plus ASO sequencing (Aligos), and therapeutic vaccines (Brii BRII-179). The combined week confirmed that liver disease is now a multi-mechanism therapeutic arena where peptides anchor the metabolic and entry-inhibitor lanes while gene and immune modalities pursue functional cure. ADA 2026 (June 5-8 New Orleans) is the next major readout window for the metabolic-peptide side.
Aligos Therapeutics presented additional EASL 2026 data on its chronic hepatitis B (HBV) combination strategy. An analog of ALG-170675, a potential best-in-class antisense oligonucleotide (ASO), demonstrated additive-to-synergistic effects when combined with ALG-001075 (the active parent moiety of pevifoscorvir sodium, a capsid assembly modulator). Separately, 40% of HBeAg-positive chronic HBV patients treated with pevifoscorvir sodium for 48 weeks reached HBsAg reductions low enough to potentially qualify for ASO treatment — supporting a sequencing strategy toward functional HBV cure where the capsid modulator lowers viral antigen load before the ASO finishes the job. The data complements the ALG-055009 THR-β MASH results (46.2% liver-fat reduction) Aligos presented earlier in the week. The combination-and-sequencing approach mirrors the broader trend in liver disease toward layered mechanisms rather than single-agent therapy, and positions Aligos across the HBV, HDV, and MASH liver-disease franchises.
Aligos Therapeutics presented positive data across ten presentations at EASL 2026 Barcelona. The headline MASH data: ALG-055009, a THR-β (thyroid hormone receptor beta) agonist small molecule, met its primary endpoint in the Phase 2a HERALD study with robust liver-fat reduction at week 12 — doses of 0.5 mg to 0.9 mg achieving statistically significant reductions with placebo-adjusted median relative reductions up to 46.2% as measured by MRI-PDFF. On the viral hepatology side, Aligos presented Phase 1 data on pevifoscorvir sodium suggesting a reduced cccDNA reservoir in chronic HBV patients, with an investigator-led study showing ≥24-week follow-up in HBeAg+ participants after 96 weeks of monotherapy. The combined slate spans the Aligos chronic HBV, HDV, MASH, and liver cancer pipeline. The ALG-055009 THR-β mechanism puts Aligos in direct competition with Madrigal's Rezdiffra (resmetirom), the only FDA-approved MASH therapy, on the same receptor target.
Bulevirtide's mechanism reveals why an entry inhibitor succeeded where small-molecule antivirals didn't. HDV is an obligate parasite of HBV — the delta virus uses the HBV envelope to assemble its virions and the HBV-derived large surface protein to enter hepatocytes via the sodium taurocholate cotransporting polypeptide (NTCP) receptor on hepatocyte cell membranes. Existing HBV antiviral nucleoside/nucleotide analogs (entecavir, tenofovir) suppress HBV replication but don't clear circulating HBsAg or interrupt the HDV entry cycle. Bulevirtide's 47-amino acid sequence — derived from the HBV pre-S1 domain — binds NTCP competitively and blocks both HDV and HBV entry. Real-world EU experience since 2020 shows roughly 50-60% of HDV patients achieve undetectable HDV RNA after 96 weeks of treatment, with a favorable safety profile dominated by injection-site reactions. The US approval expands access for an estimated 75,000-100,000 US patients with chronic HDV, most of whom were previously treated empirically with off-label interferon alfa with poor tolerability.