BRII-179 / Brii Biosci - LARVOL DELTA

Functional cure rate in chronic hepatitis B virus infected participants receiving elebsiran and pegylated interferon alfa: final results from the phase 2 ENSURE study (EASL 2026) - "Compared to PEG-IFN, the addition of elebsiran resulted in higher FC rate. Furthermore, BRII-179 experienced participants achieved higher FC rate, especially in anti-HBs responders, suggesting that BRII- 179 might play an important role in achieving lasting immunological control of the virus."

Clinical • Late-breaking abstract • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Clinical efficacy of BRII-179 therapeutic vaccine provided by a mismatched T cell epitope of prehistoric origin (EASL 2026) - "et al.Elebsiran and PEG-IFNα for chronic hepatitis B infection: a partially randomized, open-label, phase 2 trial. Enhanced HBsAg loss rates following siRNA and PegIFN-alpha treatment are associated with the expansion of epitope-mismatched vaccine-specific CD4 T cells and HBs-specific B cell maturation. These findings underscore the role of HBs-specific B cells in achieving HBsAg loss. The notable immunogenicity of this ancient HBV sequence raises the possibility that viral epitopes lost during evolution may hold the key to eliciting therapeutically effective antiviral immunity."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • IFNA1 • IL2

Therapeutic vaccination for chronic hepatitis B: why most vaccines failed and what may work. (PubMed, Antiviral Res) - "Only a recent trial combining siRNA Elebsiran and PEG-IFN-α reported a remarkable ∼50% HBsAg loss rate in chronic HBV patients who responded to a therapeutic vaccine based on PreS1/S2/S recombinant protein (BRII-179) administered prior to the trial. Here we dissect the immunological basis for this differential clinical outcome, and chart a path toward the next generation of effective therapeutic HBV vaccines."

Journal • Review • Hepatitis B • Infectious Disease • Inflammation • IFNA1

Cross-study analysis of HBsAg rebound following treatments of elebsiran/BRII-179 in combination with peginterferon alfa (APASL 2026) - No abstract available

Combination therapy

Elebsiran and PEG-IFNα for chronic hepatitis B infection: a partially randomized, open-label, phase 2 trial. (PubMed, Nat Med) - P2 | "Functional cure is a goal for the treatment of chronic hepatitis B virus (HBV) infection; however, it is infrequently achieved with currently approved treatments. Furthermore, the increased HBsAg loss rate in BRII-179 anti-HBs responders suggests that BRII-179 may be a valuable tool for immunological profiling to optimize curative outcomes in patients with HBV infection. ClinicalTrials.gov registration: NCT05970289 ."

Journal • P2 data • Hepatitis B • Infectious Disease • Inflammation • IFNA1

A Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and PEG-IFNα in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE) (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Brii Biosciences Limited | N=180 ➔ 250 | Active, not recruiting ➔ Recruiting

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

Brii Bio Presents Late-Breaking Data from Its Ongoing Phase 2 ENSURE Study at EASL Congress 2025, Suggesting BRII-179's Role in Advancing Higher HBsAg Loss (PRNewswire) - P2 | N=75 | ENSURE (NCT05970289) | Sponsor: Brii Biosciences Limited | "18 and 10 participants had peak anti-HBs titer ≥ 10 IU/L (defined as anti-HBs responders) and < 10 IU/L (defined as non-responders) induced by BRII-179 in the previous study, respectively...Among the anti-HBs responders who lost HBsAg, 91% (10/11) had anti-HBs titers ≥ 100 IU/L at EOT; BRII-179 experienced participants achieved HBsAg loss faster than BRII-179 naïve participants, with 83% (10/12) of HBsAg loss occurring by Week 24 (vs 55% [6/11] in BRII-179 naïve participants); Elebsiran + PEG-IFNα was generally safe and tolerated in BRII-179 experienced participants...Incidence of treatment emergent adverse events (TEAEs) was comparable between combination therapy cohorts and PEG-IFNα alone cohort. Most TEAEs were consistent with known side effects of PEG-IFNα....Key data readouts will be shared in the coming months at scientific conferences throughout 2025."

Late-breaking abstract • P2 data • Hepatitis B

Chronic hepatitis B virus infected participants responding to prior BRII-179 treatment achieved faster and higher rate of hepatitis B virus surface antigen seroclearance on elebsiran plus peginterferon-alfa: end of treatment data from ENSURE study (EASL 2025) - P2 | "After receiving elebsiran plus PEG-IFN alfa treatment, a substantially higher rate of HBsAg seroclearance was achieved in participants who had BRII-179 induced anti-HBs response (respon- ders) than in those who did not (non-responders). These responders also achieved faster HBsAg seroclearance compared to those without prior BRII-179 treatment, most of whom achieved HBsAg seroclear- ance after 24 weeks of elebsiran + PEG-IFN alfa (Jia, 2024; Yuen, 2022). These data suggest that BRII-179 induced immune responses may identify patients who are more responsive to curative treat- ments."

Late-breaking abstract • Hepatitis B • Hepatology • Idiopathic Arthritis • Infectious Disease • Inflammation • IFNA1

Responders to Prior BRII-179 Treatment Achieved Faster and Higher Rate of HBsAg Seroclearance Following Treatment of Elebsiran and PEG-IFNα in Participants with Chronic Hepatitis B Virus Infection: Preliminary Data from ENSURE Study (APASL 2025) - P2 | "Preliminary data showed that a substantially higher rate of HBsAg seroclearance was achieved following elebsiran and PEG-IFNα treatment in participants who previously had BRII-179 induced anti-HBs response than those who did not. Responders to prior BRII-179 appeared to achieve a faster HBsAg seroclearance compared to BRII-179 naïve participants receiving elebsiran+PEG-IFNα as previously reported (Jia, 2024). Longer treatment up to 48 weeks is ongoing."

Hepatitis B • Hepatology • Idiopathic Arthritis • Infectious Disease • Inflammation • IFNA1

Combination treatment with siRNA (elebsiran) and therapeutic vaccine (BRIM79) induced anti-HBs associated with Pre-S1/S2-specific T cell responses and HBsAg reduction in a subset of chronic hepatitis B participants (APASL 2025) - "BRII-179, in combination with elebsiran, induced substantial HBV-specific B and T responses in a subset of CHB participants. Anti-HBs induction is correlated with vaccine-induced Pre-S1/S2-specific T cell responses. Furthermore, the neutralizing activity in representative sera was inversely associated with HBsAg levels, suggesting immune response induced by BRII-179 may play a role in reducing HBsAg and controlling HBV."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1 • IL2

A Novel Point-of-Care Assay for Profiling HBV-Specific T Cell Dynamics in Clinical Samples (APASL 2025) - " Six CHB patients received an HBV-targeted siRNA (elebsiran), either alone (n=1) or in combination with a VLP-based therapeutic vaccine (BRII-179) containing Pre-S1, Pre-S2, and S antigens (n=5). The WB-HBV-CRA, requiring only a small blood volume, effectively quantifies and profiles the functional dynamics of HBV-specific T cell responses in clinical samples of CHB patients. Table and Figure:Figure 1.Whole-Blood HBV Cytokine Release Assay"

Clinical • Hepatitis B • Hepatitis C • Hepatology • Inflammation • GZMB • IFNG • IL4 • IL5 • TNFA

Brii Biosciences Provides Corporate Update and Reports Full-Year 2024 Financial Results (PRNewswire) - "Upcoming pivotal data sets from the Company's ongoing ENRICH (BRII-179 in priming HBV-specific immunity and enriching patients with competent immunity) and ENSURE (elebsiran in combination with PEG-IFNα versus PEG-IFNα alone) studies are expected throughout 2025-2026..."

P2 data • Hepatitis B

The impact of HBsAg reduction via siRNA treatment on natural and vaccine (BRII-179)-induced HBV-specific humoral and cellular immune responses. (PubMed, Gastroenterology) - "SiRNA-induced HBsAg reduction may contribute to the persistence and efficacy of the humoral arm of HBV-specific adaptive immunity in CHB participants receiving therapeutic vaccine BRII-179."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • IFNA1 • IL2

A Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and PEG-IFNα in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE) (clinicaltrials.gov) - P2 | N=180 | Active, not recruiting | Sponsor: Brii Biosciences Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study to Investigate the Efficacy and Safety of Regimens Containing BRII-179, BRII-835, and PEG-IFNα Treating Chronic Hepatitis B Virus (HBV) Infection (ENRICH) (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Brii Biosciences Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Brii Bio Announces Signing of Asset Purchase Agreements Acquiring BRII-179 IP Rights and Completed Patient Enrollment for ENRICH Study (PRNewswire) - "Brii Biosciences Limited...announced today that it has entered into an agreement with VBI Vaccines, Inc. and certain of its subsidiaries ('VBI') and its creditor K2 VBI Equity Trust, LLC and K2 HealthVentures LLC, acquiring the intellectual property (IP) and other assets relating to BRII-179. Under the agreement, among other matters, the Company will fully acquire the BRII-179 patents, BRII-179 know-how, and relevant BRII-179 materials, eliminating all future milestones and royalty obligations payable to VBI. The total consideration to be paid by Brii is US$18 million. Upon the closing of this transaction, Brii and VBI will also terminate their agreements announced on February 14, 2024, which were not consummated due to the discontinuation of operations of VBI....A large, prospective and confirmatory Phase 2b study evaluating sequential treatment of BRII-179 followed by elebsiran and PEG-IFNα combination (the ENRICH study) is now fully enrolled."

Commercial • Enrollment closed • Hepatitis B

Study to Investigate the Efficacy and Safety of Regimens Containing BRII-179, BRII-835, and PEG-IFNα Treating Chronic Hepatitis B Virus (HBV) Infection (ENRICH) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Brii Biosciences Limited | Not yet recruiting ➔ Recruiting

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

A Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and PEG-IFNα in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE) (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Brii Biosciences Limited | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and PEG-IFNα in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE) (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: Brii Biosciences Limited

Combination therapy • New P2 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study to Investigate the Efficacy and Safety of Regimens Containing BRII-179, BRII-835, and PEG-IFNα Treating Chronic Hepatitis B Virus (HBV) Infection (ENRICH) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Brii Biosciences Limited

New P2 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Therapeutic vaccine (BRII-179) induced immune response associated with HBsAg reduction in a subset of chronic hepatitis B participants (EASL-ILC 2024) - "Therapeutic vaccine BRII-179, in combination with siRNA BRII-835, induced substantial HBV-specific B and T responses in certain CHB participants. The unique immune response pattern observed in these participants receiving combination therapy, and their correlation with the reduction of HBsAg levels among these evaluable participants, suggests that T cells induced by BRII-179 may play a role in reducing HBsAg and controlling HBV. Assessing the neutralizing efficacy of anti-HBs in selected serum against different HBV genotype viruses is currently ongoing."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

BRII-179 induced functional immune response, demonstrating potential to improve chronic hepatitis B functional cure (EASL-ILC 2024) - "The investigational BRII-179 and PEG combination treatment was generally safe and tolerated. The BRII-179 add-on induced functional immune responses, which improved HBsAg loss and NRTI discontinuation, demonstrating potential to improve CHB functional cure."

Late-breaking abstract • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Functional Hbsab Responses induced by Brii-179 Are Strongly Associated with Improved Hbsag Loss (APASL 2024) - "BRII-179 add-on was generally safe and tolerated. It induced functional immune responses and may improve CHB functional cure. 102"

Hepatitis B • Infectious Disease • IFNA1

PHASE 2 INTERIM RESULTS: BRII179 (VBI-2601), A PROTEIN-BASED HBV THERAPEUTIC VACCINE, INDUCED ROBUST HBSAB RESPONSES THAT ARE STRONGLY ASSOCIATED WITH INCREASED HBsAg LOSS IN SUBJECTS RECEIVING PEG-IFNα TREATMENT (AASLD 2023) - "BRII-179/PEG-IFNα combination was generally safe and tolerated. The addition of BRII-179 induced robust immune responses that may improve the rate and duration of HBsAg loss in CHB patients who receive PEG-IFNα treatment, thereby significantly increasing the CHB functional cure rate."

Clinical • Late-breaking abstract • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

BRII-179 INDUCED DISTINCT ANTIHBS ANTIBODY RESPONSES IN CHRONIC HEPATITIS B PARTICIPANTS WITH DIVERSE UNDERLYING IMPAIRMENT OF HUMORAL IMMUNITY (AASLD 2023) - "In CHB participants on NA therapy, BRII-179 (therapeutic vaccine), alone or in combination with BRII-835 (siRNA), induced substantial anti-HBs antibody responses in some CHB participants, suggesting that the anti-HBV humoral immunity of certain participants is impaired to mount effective antibody responses. Several studies including the recently presented VIR-2218 (BRII-835)/PEG-IFN-α combination study demonstrated that strong anti-HBs antibody responses were associated with sustained HBsAg seroclearance. Immune profiling by BRII-179 has the potential to select participants with optimal intrinsic humoral immunity and increases likelihood of achieving functional cure."

Late-breaking abstract • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1