BRII-179 / Brii Biosci - LARVOL DELTA

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

Study to Investigate the Safety and Efficacy of BRII-835 and BRII-179 Combination Therapy Treating Chronic HBV Infection (clinicaltrials.gov) - P2 | N=91 | Completed | Sponsor: Brii Biosciences Limited | Active, not recruiting ➔ Completed | N=135 ➔ 91

Combination therapy • Enrollment change • Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation

VBI Vaccines and Brii Biosciences Expand Hepatitis B Partnership To Address Both Prevention and Treatment in License and Collaboration Agreements for up to $437 Million Plus Royalties (Businesswire) - "VBI Vaccines...announced the expansion of its hepatitis B (HBV) partnership with Brii Biosciences....Through two license and collaboration agreements, Brii Bio expanded its exclusive license to VBI-2601 (BRII-179), VBI’s HBV immunotherapeutic candidate, to global rights and acquired an exclusive license for PreHevbri, VBI’s 3-antigen hepatitis B vaccine, in the Asia Pacific region (APAC)....As part of the collaborations, Brii Bio will pay VBI an upfront payment of $15 million, including an equity investment of approximately $3 million, contingent on achievement of near-term milestones. VBI is also eligible to receive up to an additional $422 million in potential regulatory and commercial milestone payments, and potential double-digit royalties in the licensed territories, which is worldwide for VBI-2601 and APAC, excluding Japan, for PreHevbri."

Financing • Licensing / partnership • Hepatitis B • Infectious Disease

Study to Investigate the Safety and Efficacy of BRII-835 and BRII-179 Combination Therapy Treating Chronic HBV Infection (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: Brii Biosciences Limited | Trial primary completion date: Mar 2023 ➔ Jul 2023

Combination therapy • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Preliminary Safety and Efficacy of the Combination Therapy of BRII-835 and BRII-179 Treating Chronic HBV Infection (APASL 2023) - "The siRNA therapeutic, BRII-835, either alone or in combination with therapeutic vaccine BRII-179 was generally well tolerated with similar HBsAg reductions from baseline across all dose regimens. The significant suppression of HBsAg observed in a small subset of participants receiving combination treatment is associated with robust HBV specific antibody and T cell responses. Further analyses will be performed when all participants complete follow-up."

Clinical • Combination therapy • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

Brii Biosciences Provides Corporate Update and Reports Full Year 2021 Financial Results (PRNewswire) - "BRII-179 (VBI-2601) and BRII-835 (VIR-2218) (therapeutic vaccine and siRNA) Combination...Phase 2 BRII-179 (VBI-2601)/BRII-835 (VIR-2218) MRCT combination study is fully enrolled with interim topline clinical data expected by the end of 2022. If positive results are achieved for the combination study, we plan to submit an Investigational New Drug Application (IND) application to China Center for Drug Evaluation (CDE) to initiate a pivotal study in 2023....BRII-179 (VBI-2601) and PEG-IFN-α Combination...Patient enrollment for part 1 (Phase 2a of approximately 120 patients) of the study is expected to complete in the second half of 2022, with interim topline results expected in the first half of 2023."

Enrollment status • New trial • P2 data • P2a data • Hepatitis B • Infectious Disease

VBI Vaccines Reports Fourth Quarter and Full Year Financial Results for 2021, Provides Corporate Update and Outlook for 2022 (Businesswire) - "VBI-2601 (BRII-179): HBV Immunotherapeutic Candidate...H2 2022: Initial data from Phase 2 combination study expected...H1 2023: Initial data from the Phase 2a/2b 'add-on' study expected...Research and Development (R&D): R&D expenses for the full year 2021 were $19.6 million compared to $14.9 million for the same period in 2020. The increase in R&D spend was mainly a result of the increase in costs related to the continued development of our eVLP vaccine candidates and increased regulatory costs related to our 3-antigen HBV vaccine."

Commercial • P2 data • P2a data • P2b data • Hepatitis B • Infectious Disease