Brii Bio Presents New Data Highlighting Progress Towards Achieving HBV Functional Cure at AASLD's The Liver Meeting® 2023

Direct evidence that BRII-179-induced functional antibody responses can contribute to increased and sustained HBsAg loss rate

New insight in utilizing BRII-179 to enriching patients with intrinsic humoral immune responses for higher HBsAg loss or HBV functional cure rates

New data support progression to late-stage clinical development with data expected to inform curative treatment approaches in chronic Hepatitis B

DURHAM, N.C. and BEIJING, Nov. 14, 2023 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio" or the "Company", stock code: 2137.HK), a biotechnology company developing therapies to improve patient health and choice across diseases with high unmet need, today shared three posters at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting^® in Boston, MA, two of which were accepted as late-breakers providing new data from two Phase 2 assets, BRII-179 (VBI-2601) and BRII-835 (VIR-2218), within the chronic hepatitis B (CHB) clinical program.

"We are pleased to share these data at The Liver Meeting that demonstrate the versatility of our HBV portfolio and critical insight in our search for a cure for HBV," said David Margolis, MD, Chief Medical Officer of Brii Bio. "The important connection between HBsAg loss and antibody response provides a clear direction in further improving the functional cure rate and identifying patients who will most likely respond to curative treatments. Our goal is to develop the right treatment regimen for the right patient in the broadest possible populations, while sparing patients from the expensive or less tolerated treatment option that may not benefit them."

In a late-breaking poster presentation, Brii Bio announced additional interim data that were unblinded at the cohort level from a randomized, placebo-controlled and double-blinded Phase 2 study of BRII-179, in combination with pegylated interferon-alpha (PEG-IFNα) in patients with CHB infection. Findings from this presentation include:

• BRII-179 add-on therapy to existing PEG-IFNα treatment was generally safe and tolerated, with adverse events similar to those associated with PEG-IFNα treatment and BRII-179 as previously reported.
• At Week 36 (12 weeks after end-of-treatment [EOT]), BRII-179 + PEG-IFNα combination group achieved higher HBsAg loss rate compared to Placebo + PEG-IFNα group (Full Analysis Set (FAS): 24.6% vs.14.0%, Per Protocol Set (PPS): 31.8% vs.14.9%). The difference in HBsAg loss rate was observed at Week 24 (EOT) and maintained through Week 36. The clinical study also found that the combination group had significantly higher HBsAg seroconversion rates than Placebo + PEG-IFNα group (FAS: 15.8% vs. 1.8%, p=0.016; PPS: 19.6% vs. 2.0%, p=0.0058) at Week 24 (EOT).
• The addition of BRII-179 induced robust and functional HBsAg antibody responses, participants in BRII-179 + PEG-IFNα combination group achieved significantly higher hepatitis B surface antibody (HBsAb) response rate than those in Placebo + PEG-IFNα group both at Week 24 (FAS: 38.6% vs. 14.0%, p=0.0052; PPS: 39.1% vs. 13.7%, p=0.0054) and Week 36 (FAS: 33.3% vs. 12.3%, p=0.0131; PPS: 34.1% vs. 10.6%, p=0.0105). The HBsAb titer was significantly associated with HBsAg loss at Week 24 and 36. 4 out 5 patients who rebounded had no detectable antibody responses.
• The data from this proof-of-concept study demonstrated that the addition of BRII-179 induced functional immune responses that could improve the rate and duration of HBsAg loss in CHB patients who receive PEG-IFNα treatment, thereby increasing the CHB functional cure rate.

In a second late-breaking poster presentation, Brii Bio presented translational research data from BRII-179-001 and BRII-179-835-001 studies, indicating the distinct HBsAg antibody responses induced by BRII-179 observed only in a subset of CHB subjects, suggesting that intrinsic immune responses against HBV in some patients may be more profoundly impaired. Additionally, researchers found:

• BRII-179 in combination with BRII-835 (VIR-2218) was generally well tolerated when administered up to 9 monthly doses, with no treatment related adverse events > Grade 2.
• In CHB participants on nuceos(t)ide reverse transcriptase inhibitors (NrtI) therapy, BRII-179, alone or in combination with BRII-835, induced substantial HBV specific T cell responses, while significant HBsAg antibody responses were elicited in some but not all chronic HBV participants even after 9 doses of vaccination in combination with BRII-835, an HBV-targeting siRNA lowering immunosuppressive viral antigens such as HBsAg.
• Immunological analysis suggests that BRII-179 may offer a unique opportunity to enrich CHB patients who are able to elicit the necessary HBsAg antibody response in achieving higher functional cure rate in some patients while sparing others from unnecessary treatments.

In a poster presentation, Brii Bio highlighted the multiple dose pharmacokinetics (PK) of BRII-835 (VIR-2218) in patients with chronic HBV infection from Phase 1b/2 and Phase 2 clinical trials, and the impact of regional or ethnic background may have on the PK of the drug. Highlights include:

• The PK characteristics of BRII-835 in patients with chronic HBV infection are generally similar to those in healthy volunteers. At doses of 50 and 100 mg, dose dependent increases in systemic exposures were observed. There was no apparent accumulation in plasma after a second dose given four weeks later.
• Similar PK profiles between patients enrolled in the Asia-Pacific region and mainland China demonstrate that Chinese ethnic background from mainland China has no apparent impact, which could serve as a bridge to support mainland China's participation in future global trials for further evaluation of BRII-835.

As part of Brii Bio's unique approach to develop a functional cure for HBV, the Company and its partners are progressing multiple ongoing phase 2 studies, including BRII-835 and BRII-179 combination, BRII-179 and PEG-IFN⍺ combination, BRII-835, BRII-877 (VIR-3434) with or without PEG-IFN⍺. In addition, Vir Biotechnology, Inc. ("Vir") is also investigating VIR-2218 and/or VIR-3434 for the treatment of HBV/HDV co-infection.

About Hepatitis B
Hepatitis B viral infection 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-179
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 and broad B-cell and T-cell immunity. BRII-179 is currently being investigated in two Phase 2 clinical trials in combination with BRII-835 or PEG-IFNα as part of a potential functional cure regimen for the treatment of chronic HBV infection.

Brii Bio licensed BRII-179 from VBI Vaccines, Inc. ("VBI") in December 2018, providing Brii Bio with commercial rights to BRII-179 in the licensed territories of mainland China, Hong Kong, Macau, and Taiwan. The exclusive license for BRII-179 has been extended to worldwide markets since July 2023.

About BRII-835
BRII-835 (VIR-2218) is an investigational subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and has direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. Brii Bio licensed exclusive rights to develop and commercialize BRII-835 for the greater China territory from Vir Biotechnology, Inc. ("Vir") in 2020.

About BRII-877
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. Brii Bio licensed exclusive rights to develop and commercialize BRII-877 for the greater China territory from Vir Biotechnology, Inc. ("Vir") in 2022.

About Brii Bio
Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a commercial stage biotechnology company developing therapies to address major public health challenges 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 against hepatitis B viral infection (HBV), postpartum depression (PPD), and major depressive disorder (MDD). 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 www.briibio.com.

1 World Health Organization. (June 2022). Hepatitis B. World Health Organization. Retrieved from https://www.who.int/news-room/fact-sheets/detail/hepatitis-b
2 World Health Organization. Hepatitis. World Health Organization. Retrieved from https://www.who.int/china/health-topics/hepatitis#:~:text=There%20are%2087%20million%20people,living%20with%20chronic%20hepatitis%20C.