Brii Biosciences Limited ("Brii Bio"), a biotechnology company focused on developing therapies for diseases with high unmet needs, unveiled new data from two Phase 2 studies at the European Association for the Study of the Liver (EASL) Congress 2024. These studies evaluated BRII-179, either in combination with BRII-835 (elebsiran) or as an adjunct to pegylated interferon-alpha (PEG-IFNα) treatment for chronic hepatitis B virus (HBV) infection.

In an oral presentation, data from a Phase 2 clinical trial demonstrated that BRII-179, a therapeutic vaccine, in combination with BRII-835 (elebsiran) induced significant HBV-specific B and T cell responses. These responses correlated with antiviral effects in a subset of participants with chronic HBV infection. The exploratory translational study found that a Pre-S1-specific T cell response targeting a region adjacent to sodium taurocholate cotransporting polypeptide (NTCP) was linked to high levels of HBsAg reduction in participants treated with BRII-835 and BRII-179. Ex vivo Pre-S1-specific Th1-type cytokines (IL-2) were present in participants with high HBsAg reduction, while Th2-type responses were not associated with such reductions. BRII-179 induced strong anti-HBV neutralizing activity in participants with high levels of HBsAg reduction and HBsAb induction.

"This study shows for the first time direct evidence that immune responses induced by an HBV therapeutic vaccine are associated with HBsAg reduction and viral control in some participants with chronic HBV infection," said Dr. Antonio Bertoletti, Professor at Duke-NUS Medical School. "The antiviral activity appears linked to a boosting of anti-HBs antibodies and Pre-S1-specific T cell responses induced by BRII-179, supporting its potential to break immune tolerance and impact sustained viral control."

Additionally, late-breaker poster presentation data from another Phase 2 clinical trial indicated that BRII-179, when administered alongside PEG-IFNα, improved the overall HBsAg loss rate from end-of-treatment (EOT) to at least 24 weeks post-nucleos(t)ide reverse transcriptase inhibitors (NRTI) discontinuation. The study involved 114 virally-suppressed participants with chronic HBV infection, showing that a higher percentage of participants in the BRII-179 + PEG-IFNα group maintained HBsAg loss compared to the placebo + PEG-IFNα group (19.3% vs. 12.3% in the full analysis set [FAS]).

Sustained improvement in overall HBsAg loss rate from EOT (26.3% vs. 19.3% in FAS) to at least 24 weeks post NRTI discontinuation was observed. Additionally, a higher percentage of participants in the BRII-179 + PEG-IFNα group with HBsAb ≥ 100 IU/L compared to the placebo + PEG-IFNα group (36.4% vs. 14.3% in FAS) at ≥ 24 weeks post NRTI discontinuation. No participant with an HBsAb titer ≥ 100 IU/L at EOT experienced HBsAg rebound through the cut-off date, suggesting robust antibody responses are necessary for sustained off-treatment HBsAg loss.

The combination of BRII-179 and PEG-IFNα was generally safe and well-tolerated, with no new risks identified during the post-EOT follow-up period. These findings support further clinical evaluation of BRII-179 in combination with other modalities, such as siRNA and PEG-IFNα, aiming for a functional cure for chronic HBV infection.

 About BRII-179

BRII-179 is a novel recombinant protein-based HBV immunotherapeutic candidate expressing the Pre-S1, Pre-S2, and S HBV surface antigens, designed to induce enhanced and broad B-cell and T-cell immunity. Licensed from VBI Vaccines, Inc. in December 2018, Brii Bio extended its global rights in July 2023.

About BRII-835 (Elebsiran)

BRII-835 (elebsiran) is an investigational subcutaneous HBV-targeting siRNA with potential immune-stimulating and direct antiviral activity against HBV and HDV. It includes Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, potentially increasing its therapeutic index. Brii Bio holds exclusive development and commercialization rights for BRII-835 in greater China from Vir Biotechnology, Inc. since 2020.

About Hepatitis B

HBV infection remains a major global health threat, with over 254 million people infected worldwide. Chronic HBV infection leads to significant liver disease and causes approximately 820,000 deaths annually. In China, 87 million people are chronically infected, highlighting the urgent need for effective treatments.

About Brii Bio

Brii Biosciences Limited (stock code: 2137.HK) is a biotechnology company addressing significant public health challenges with high unmet medical needs, focusing on infectious and central nervous system diseases. The company, led by a visionary leadership team, operates in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing, and Shanghai.