Brii Bio Announces New Data from Partners Underscoring Potential for HBV Functional Cure at EASL™ Congress 2023

Late-breaking data from BRII-835 + PEG-IFN-a study demonstrate anti-HBs titers at the end of treatment were associated with sustained HBsAg loss 24 weeks after the end of treatment 

New data show more robust and persistent anti-HBs titers following vaccination with VBI's 3-antigen prevention vaccine PreHevbrio®

Data support the continued development of BRII-835, BRII-877 and BRII-179 to achieve best-in-class functional cure in broad HBV patient populations

DURHAM, N.C. and BEIJING, June 25, 2023 /PRNewswire/ -- 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, today announced that its strategic partners, Vir Biotechnology, Inc. ("Vir," NASDAQ: VIR) and VBI Vaccines, Inc. ("VBI," NASDAQ: VBIV), presented results from multiple clinical studies for the treatment and prevention of chronic hepatitis B viral (HBV) infection at the European Association for the Study of the Liver (EASL) Congress 2023 that further support the clinical evaluation of Brii Bio's assets as a potential best-in-class functional cure for chronic HBV infection.

"In concert with our partners, we look forward to leveraging these exciting insights gained from the trials to progress our scientific approach," said David Margolis, MD, Infectious Disease Therapeutic Area Head of Brii Bio. "By design, we have intentionally crafted our HBV portfolio with the ability to explore multiple novel combination treatments to improve the probability of achieving a high rate of functional cure for broad HBV patient populations, and we remain committed to driving scientific innovation on behalf of patients."

In a late-breaker oral presentation, Vir announced 24-week follow-up data from a Phase 2 trial that demonstrated when VIR-2218 (BRII-835) was given for 24 or 48 weeks on top of a course of up to 48 weeks of pegylated interferon alpha (PEG-IFN-⍺), 26% (8/31) of virally suppressed participants with chronic HBV achieved HBsAg loss at end of treatment. 

• 16% (5/31) of participants demonstrated sustained HBsAg loss 24 weeks after end of treatment; Two of the five participants had baseline HBsAg levels greater than 1,000 IU/mL. No new safety findings were observed during the follow-up.
• Four participants with anti-HBs titers greater than 500 mIU/mL at the end of treatment achieved a sustained HBsAg loss at 24 weeks after the end of treatment suggesting the potential use of anti-HBs titers as an on-treatment biomarker of off-treatment sustained response.

In another oral presentation, Vir announced 48-week post-treatment data from Part A of the Phase 2 MARCH trial. VIR-2218 (BRII-835) and VIR-3434 (BRII-877) as combination treatment for chronic HBV infection resulted in 2.7-3.1 log₁₀ IU/mL decrease in HBsAg levels following five or 12 weeks of combination treatment with 90% of participants achieving HBsAg less than 10 IU/mL at the end of this short treatment.

• The majority of participants met the criteria for discontinuing nucleotide reverse transcriptase inhibitor (NRTI) therapy because they achieved all of the following: HBsAg less than 100 IU/mL and at or greater than 1 log₁₀ IU/mL reduction from baseline HBsAg level; HBV DNA below the lower limit of quantification (LLOQ); HBeAg-negative and ALT at or less than twice the upper limit of normal. 67% (4/6) of those participants remained off NRTI therapy as of the last available follow up.
• Combination treatment with VIR-2218 (BRII-835) and VIR-3434 (BRII-877) was generally well tolerated and associated primarily with mild adverse events. All treatment-related adverse events were Grade 1, with no study discontinuations.

In a poster presentation, Vir highlighted the single dose pharmacokinetics of VIR-3434 (BRII-877) from a Phase 1 clinical trial in patients with chronic HBV infection, with data supporting continued evaluation of VIR-3434 (BRII-877).

• The highest and most durable free VIR-3434 (BRII-877) exposure was observed with the 300 mg dose, regardless of baseline HBsAg level. Other doses evaluated include 6 mg, 18 mg and 75 mg.
• VIR-3434 (BRII-877) has a shorter terminal half-life and was cleared faster in participants with higher baseline HBsAg.

In addition, VBI presented follow-up data in a subset of participants from the pivotal Phase 3 study, PROTECT, up to 3.5 years after completion of immunization with PreHevbrio®, a prophylactic 3-antigen HBV vaccine, to determine magnitude and duration of immune response. PreHevbrio consists of the same recombinant HBV surface antigens, Pre-S1, Pre-S2 and S, in virus-like particles, used in BRII-179 (VBI-2601).

• At all measured timepoints, participants immunized with PreHevbrio had significantly higher (P<0.0001) mean HBsAg antibody titers as compared to those who were immunized with Engerix-B®.
• The data highlight that PreHevbrio induced T-cell responses against Pre-S1 and Pre-S2 proteins that correlated with high anti-HBs titers.
• At 3.5 years follow up, the mean ant-HBs titers in participants vaccinated with PreHevbrio were 5.1x higher than those vaccinated with Engerix-B (1287.2 vs. 253.7 mIU/mL) suggesting that T-cell responses of PreHevbrio may contribute to long lasting and strong humoral immune responses and greater durability compared with Engerix-B.

As part of Brii Bio's unique approach to develop a functional cure for HBV, the Company and its partners are progressing multiple studies, including BRII-835 (VIR-2218) and BRII-179 (VBI-2601) combination, BRII-179 and PEG-IFN-⍺ combination, BRII-835 (VIR-2218), BRII-877 (VIR-3434) with or without PEG-IFN-⍺, and BRII-835 (VIR-2218)  and/or BRII-877 (VIR-3434) in combination with other agents. To date, approximately 390, 240, and 180 subjects have been treated with BRII-835 (VIR-2218), BRII-877 (VIR-3434), and BRII-179 (VBI-2601), respectively.  

About BRII-835 (VIR-2218)

BRII-835 (VIR-2218) is a GalNAc-conjugated small interfering ribonucleic acid (siRNA) targeting all HBV viral RNAs that has shown to block viral transcription, reduce viral protein and alleviate immune suppression.

About BRII-877 (VIR-3434)

BRII-877 (VIR-3434) is an investigational subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. BRII-877 (VIR-3434), which incorporates Xencor's Xtend™ and other Fc technologies, has been engineered to potentially function as a T-cell vaccine against HBV in infected patients, as well as to have an extended half-life.

About BRII-179 (VBI-2601)

BRII-179 (VBI-2601) is a novel recombinant, protein-based HBV immunotherapeutic candidate that expresses the Pre-S1, Pre-S2, and S HBV surface antigens, and is designed to induce enhanced B-cell and T-cell immunity.

About Hepatitis B

Hepatitis B viral infection (HBV) is one of the world's most significant infectious disease threats with more than 290 million people infected globally.^[1] Chronic HBV infection is the leading cause of liver disease and an estimated 820,000 people die of complications from chronic HBV each year.^[1] HBV is of exceptional concern in China, where 87 million people are infected.^[2]

About Brii Bio

Brii Biosciences is a biotechnology company developing therapies to address some of the world's most common diseases where patients experience high unmet medical needs, limited choice and significant social stigmas. With a focus on infectious and central nervous system diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs to develop a novel functional cure for hepatitis B viral infection (HBV) and a first-of-its-kind treatment for postpartum depression (PPD). The Company is led by a visionary and experienced leadership team and has operations in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing and Shanghai. For more information, visit https://www.briibio.com/.