AHB-137 Demonstrates High Cure Rates, Sustained Viral Suppression in Chronic Hepatitis B

Chronic hepatitis B (CHB) affects an estimated 254 million people worldwide and remains a leading driver of cirrhosis, hepatocellular carcinoma, and liver-related mortality. Despite the availability of nucleos(t)ide analogues (NAs) that suppress HBV DNA, a functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg) off all treatment, remains elusive for the vast majority of patients. AHB-137, an unconjugated antisense oligonucleotide developed by Ausper Biopharma, has emerged as a candidate capable of simultaneously targeting viral replication and driving profound reductions in hepatitis B surface antigen (HBsAg). Two posters at the European Association for the Study of Liver (EASL) Congress 2026 shed further light on its potential: one reporting end of study (EOS) results from a phase 2 trial in treatment-naive CHB participants and a second presenting preclinical data supporting a sequential combination strategy with an HBV vaccine.^1,2

Clinical Findings: Phase 2 Results in Treatment-Naive Patients

The ongoing phase 2 study (NCT06829329) evaluates AHB-137 monotherapy in treatment-naive CHB participants, a population distinct from the NA-suppressed patients in whom the agent has previously been assessed.¹ Part A, from which the EOS data are reported, was a randomized, double-blind, placebo-controlled design. Eligible participants had baseline HBsAg levels of 100 to 10,000 IU/mL and HBV DNA of 20 to 2000 IU/mL. Participants were randomized 4:1 to receive weekly subcutaneous AHB-137 (300 mg) or placebo for 16 weeks as monotherapy, without concomitant NA therapy, followed by a 24-week off-treatment follow-up period.

The primary end point was complete response (CR), defined as HBsAg below 0.05 IU/mL and HBV DNA below 10 IU/mL, at the end of treatment (EOT). FC, defined as sustained CR 24 weeks after discontinuation of all therapy, was evaluated at EOS. Efficacy was assessed in the per-protocol set and safety in the safety set.

Viral Suppression and HBsAg Reduction

The PPS comprised 31 participants: 25 in the AHB-137 arm and 6 receiving placebo. Results demonstrated rapid and potent antiviral activity. All 25 participants (100%) in the AHB-137 arm achieved HBV DNA below 10 IU/mL by week EOT, a finding that underscores the agent's capacity for complete viral suppression even in the absence of concomitant NA therapy.

Among the 19 participants with baseline HBsAg at or below 3000 IU/mL, 84% (16 of 19) achieved HBsAg loss by EOT. All 6 participants with baseline HBsAg above 3000 IU/mL demonstrated reductions of at least 4.5 log10 IU/mL, with 3 of those 6 achieving outright HBsAg loss. In total, 68% of participants (17 of 25) achieved CR at EOT.

Functional Cure and Off-Treatment Durability

At EOS, 24 weeks after all treatment was discontinued, 32% of participants (8 of 25) had achieved functional cure, maintaining both HBsAg loss and HBV DNA suppression. Outcomes were particularly favorable for participants with lower baseline HBsAg: among those with baseline HBsAg at or below 1000 IU/mL, 70% (7 of 10) achieved FC by EOS.

Among participants with baseline HBsAg above 1000 IU/mL, 33% (5 of 15) achieved what the investigators termed "partial cure" at EOS, characterized by sustained HBV DNA suppression and HBsAg below 10 IU/mL, suggesting durable antiviral benefit even in those who did not meet the full FC definition.

Additionally, the safety profile of AHB-137 in this treatment-naive cohort was generally consistent with observations in prior studies conducted in NA-suppressed patients. The majority of treatment-related adverse events were grade 1 or 2, with reversible elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) representing the most commonly observed events; the investigators noted these appeared to be associated with the rapid decline in HBsAg rather than direct drug toxicity.

One treatment-related serious adverse event (SAE) was reported: an ALT elevation accompanied by concurrent increases in bilirubin and HBV DNA. No clinical symptoms were present, and the event resolved completely without sequelae. No additional SAEs were attributed to study treatment.

Overall, the authors concluded that AHB-137 monotherapy demonstrated potent inhibition of HBV DNA replication and profound HBsAg reduction in treatment-naïve CHB participants, yielding a high functional cure rate alongside durable off-treatment viral suppression.

Preclinical Findings: Sequential Combination With HBV Vaccine

The second poster reported preclinical findings from the AAV-HBV mouse model, examining whether sequential administration of AHB-137 followed by an approved recombinant HBV vaccine could sustain HBsAg loss and induce protective immunity. The scientific rationale is grounded in a widely held view in the field: Durable viral control requires not only potent antigen suppression to break immune tolerance but also the activation of effective antiviral immune responses.²

C57BL/6 mice infected with rAAV8-1.3HBV received subcutaneous AHB-137 at 60 mg/kg for 6 doses over approximately 3 weeks (days 1, 4, 8, 11, 15, and 22), followed by an intramuscular HBV vaccine at either 1.5 μg or 5.0 μg per animal for 5 doses administered between days 29 and 90. Serial serum samples were evaluated for HBsAg, hepatitis B e-antigen (HBeAg), HBV DNA, and HBsAb. Terminal samples were assessed for HBsAb neutralizing activity using HBV-infected NTCP-HepG2 cells. Liver tissue was analyzed by immunohistochemistry for HBsAg and HBcAg expression, and HBsAg-specific B cell responses in the liver and spleen were evaluated.

Key Findings

AHB-137 monotherapy produced rapid and substantial reductions in serum HBsAg, HBeAg, and HBV DNA, driving all markers below the lower limit of quantification. However, consistent with observations in prior preclinical and clinical settings, HBsAg began to rebound following the completion of AHB-137 dosing, detectable from approximately day 50 onward.

The sequential addition of the HBV vaccine fundamentally altered this trajectory. Animals that received the vaccine following AHB-137 maintained sustained HBsAg loss through study termination at day 106. During this period of sustained antigen loss, high-titer HBsAb with confirmed neutralizing activity was rapidly induced, and HBsAg-specific B cells were detected in both the liver and spleen, indicating the activation of functional humoral immunity.

By contrast, animals receiving the HBV vaccine alone developed detectable serum HBsAb, but the antibody lacked neutralizing activity, and HBsAg levels showed minimal change. This comparison highlights the critical role of prior antigen reduction by AHB-137 in creating a permissive immunological environment for meaningful vaccine response.

The sequential regimen also reduced HBsAg, HBeAg, HBV DNA, and HBV ribonucleic acid levels in the liver. Whether immune cytotoxicity was activated by the combination strategy remains under active investigation. All animals tolerated the regimen well, with no treatment-related abnormalities in clinical observations or clinical pathology.

The investigators concluded that sequential combination of AHB-137 with HBV vaccine in the AAV-HBV mouse model effectively sustained HBsAg loss by activating HBsAg-specific B cells capable of producing high-titer neutralizing antibodies. They proposed that this preclinical finding provides a mechanistic rationale for clinical combination therapy, potentially offering a strategy to achieve higher rates of functional cure in patients with CHB than either agent alone.

References

1. Qiu Y, Gao H, Zhang D, et al. AHB-137 monotherapy elicits high functional cure rates and sustained DNA suppression in treatment-naïve chronic hepatitis B participants: results from an ongoing phase II study. Presented at: EASL Congress; May 27-30, 2026; Barcelona, Spain.
2. Lu T, Lei J, Hou R, et al. Sequential combination of antisense oligonucleotide AHB-137 followed by HBV vaccine leads to HBsAg loss and seroconversion in the AAV-HBV mice. Presented at: EASL Congress; May 27-30, 2026; Barcelona, Spain.