DURHAM, N.C. and BEIJING, June 8, 2024 — Brii Biosciences Limited (“Brii Bio,” “we,” or the “Company”, stock code: 2137.HK), a biotechnology company developing therapies to improve patient health and choice across diseases with high unmet needs, presented new data from two Phase 2 studies evaluating BRII-179 either as a combination therapy with BRII-835 (elebsiran) or as an add-on therapy to pegylated interferon-alpha (PEG-IFNα) treatment for chronic hepatitis B virus (HBV) infection at the EASL™ (European Association for the Study of the Liver) Congress 2024.
Data presented in an oral presentation from a Phase 2 clinical trial demonstrated BRII-179, a therapeutic vaccine, in combination with BRII-835 (elebsiran) induced substantial HBV-specific B and T cell responses that correlate with antiviral effect in a subset of participants with chronic HBV infection. The exploratory translational study evaluating the correlation of treatment-induced immune response with antiviral effects demonstrated:
- Pre-S1-specific T cell response targeting a region adjacent to sodium taurocholate cotransporting polypeptide (NTCP) was identified to be associated with high levels of HBsAg reduction in some participants receiving BRII-835 (elebsiran) and BRII-179.
- Ex vivo Pre-S1-specific Th1-type cytokines (IL-2) were detected in participants with high HBsAg reduction, while Th2-type responses were not associated with HBsAg reduction.
- BRII-179 induced robust 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 is associated with HBsAg reduction and viral control in some participants with chronic HBV infection,” said Antonio Bertoletti, MD, Professor, Emerging Infectious Diseases Program at Duke-NUS Medical School. “The antiviral activity appears to be linked with a boosting of anti-HBs antibodies and Pre-S1-specific T cell responses induced by BRII-179, supporting that BRII-179 can break immune tolerance and have an impact on sustained control of the viral infection.”
Additionally, late-breaker poster presentation data from a Phase 2 clinical trial demonstrated that BRII-179, administrated on top of PEG-IFNα, improved overall HBsAg loss rate from end-of-treatment (EOT) to at least 24 weeks post nucleos(t)ide reverse transcriptase inhibitors (NRTI) discontinuation compared to the PEG-IFNα group. Follow-up data from this randomized, double-blind, placebo-controlled clinical trial in 114 virally-suppressed participants with chronic HBV infection showed:
- Among the participants who met NRTI discontinuation criteria and entered NRTI discontinuation monitoring period (NDMP), a higher percentage of participants in the BRII-179 + PEG-IFNα group maintained HBsAg loss (19.3% vs 12.3% in full analysis set [FAS]) compared to the placebo + PEG-IFNα group. The improvement in overall HBsAg loss rate was sustained from EOT (26.3% vs 19.3% in FAS) to at least 24-week post NRTI discontinuation (cut-off date) or 36-week post EOT in the BRII-179 + PEG-IFNα group. No participant who discontinued NRTI required NRTI retreatment.
- A higher percentage of participants in the BRII-179 + PEG-IFNα group maintaining HBsAg loss had HBsAb ≥ 100 IU/L compared to the placebo + PEG-IFNα group (36.4% vs 14.3% in FAS) at ≥ 24-week post NRTI discontinuation.
No participant with HBsAb titer ≥ 100 IU/L at EOT experienced HBsAg changed from < 0.05 IU/mL (LLOQ) to ≥ 0.05 IU/mL (i.e. HBsAg rebound) through the cut-off date, suggesting that robust antibody responses against HBV are necessary for sustained off-treatment HBsAg loss. - Treatment with BRII-179 and PEG-IFNα combination was generally safe and tolerated. No new risk was identified in the post EOT follow-up period and NDMP.
The favorable benefit-risk profile and scientific insights from these studies support further clinical evaluation of BRII-179 in combination with other modalities such as siRNA and PEG-IFNα as key components for the treatment of chronic HBV infection, with the goal of achieving functional cure.
