Brii Biosciences Announces Publication of Phase 2 ENSURE Study Results in Nature Medicine

• Findings provide scientific insights into the contribution of small interfering RNA (siRNA) and therapeutic vaccination towards the HBV functional cure strategy

DURHAM, N.C. and BEIJING, Nov. 7, 2025 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio," or the "Company," stock code: 2137.HK), a biotechnology company developing therapies to improve patient health across diseases with high unmet medical need, today announced the publication of results from its Phase 2 ENSURE study in the peer-reviewed journal Nature Medicine. The study evaluates the efficacy and safety of an siRNA, elebsiran, in combination with pegylated interferon alfa (PEG-IFNα), compared to PEG-IFNα monotherapy. Furthermore, this study evaluates the potential role of an HBV therapeutic vaccine, BRII-179, in identifying immunologically responsive patients and improving hepatitis B surface antigen (HBsAg) loss rates.

The article, titled "Elebsiran and PEG-IFNα for chronic hepatitis B infection: a partially randomized, open-label, phase 2 trial", is now available online [link].

The ENSURE study was conducted in two parts in virally suppressed chronic HBV patients. In Part I (Cohorts 1-3), participants naïve to BRII-179 were randomized to receive 48 weeks of PEG-IFNα alone or in combination with elebsiran (200 mg or 100 mg administered every 4 weeks [Q4W]). In Part II (Cohort 4), participants previously treated with 9 doses of elebsiran and BRII-179 in a completed Phase 2 study (BRII-179-835-001) were categorized as BRII-179 anti-HBs responders or non-responders based on peak hepatitis B surface antibody (anti-HBs) levels (≥10 IU/L or <10 IU/L, respectively), and subsequently received 48 weeks of elebsiran (100 mg Q4W) plus weekly PEG-IFNα in the ENSURE study.

Key results from this publication include:

• Cohorts 1-3: At 24 weeks post-EOT, HBsAg loss was observed in 4 of 19 participants (21.1%) in Cohort 2 (elebsiran 200 mg + PEG-IFNα) and 6 of 18 participants (33.3%) in Cohort 3 (elebsiran 100 mg + PEG-IFNα), compared to 1 of 18 participant (5.6%) in Cohort 1 (PEG-IFNα monotherapy).
• Cohort 4: At 24 weeks post-EOT, HBsAg loss was observed in 9 of 31 participants (29.0%), with a notably higher response among BRII-179 anti-HBs responders (8/19, 42.1%) compared to non-responders (1/12, 8.3%). BRII-179 anti-HBs responders also achieved more rapid HBsAg reductions and HBsAg seroclearance compared to non-responders.
• Elebsiran and PEG-IFNα combination therapy was generally safe and well tolerated across all cohorts.

The randomized, active-controlled design of Cohorts 1-3 was a gold standard in validating the clinical benefit of elebsiran over PEG-IFNα monotherapy, providing an important benchmark for future development of siRNA towards HBV functional cure.

The novel design of Cohort 4 explored a patient response-guided treatment approach for more personalized decision-making, maximizing response rates in those most likely to benefit while avoiding unnecessary and lengthy treatments in others.

Other important observations are 1) participants previously treated with BRII-179 and elebsiran experienced faster decline and loss of HBsAg, suggesting that BRII-179 may prime the immune system for improved responsiveness to subsequent curative therapy; 2) 50% (4/8) of anti-HBs responders who achieved sustained HBsAg loss had baseline HBsAg levels exceeding 1,500 IU/mL when enrolled in the previous BRII-179-835-001 study, suggesting that BRII-179 may elicit anti-HBs responses in patients with high baseline HBsAg levels. With its favorable safety profile, BRII-179 could play a unique role in priming and enriching patients regardless of the baseline HBsAg levels, expanding the population eligible for future curative regimens.

"The ENSURE study was designed to provide much-needed clarity and to answer critical scientific questions about curative treatment for chronic hepatitis B," said Professor Jidong Jia, lead principal investigator of the ENSURE study, "It is encouraging to see that the 24-week follow-up data remain consistent with the EOT results, substantiating the added clinical benefit of elebsiran and pointing to the potential new roles of BRII-179 in priming and enriching CHB patients for achieving higher cure rates. We look forward to validating these findings in confirmatory studies."

About Hepatitis B

Hepatitis B virus (HBV) infection is one of the world's most significant infectious disease threats with more than 254 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 infection each year.^[1] HBV is of exceptional concern in China, where 87 million people are chronically infected.^[2]

About BRII-179

BRII-179 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. In November 2023, the Center for Drug Evaluation (the "CDE") of the National Medical Products Administration (the "NMPA") granted BRII-179 Breakthrough Therapy Designation.

About Elebsiran

Elebsiran is an investigational subcutaneously administered HBV-targeting siRNA designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. It has the potential to have direct antiviral activity against HBV and HDV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus 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 elebsiran for the Greater China territory from Vir Biotechnology, Inc. in 2020. In May 2024, the CDE of the NMPA granted elebsiran Breakthrough Therapy Designation.

About Brii Bio

Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a 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 diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B virus (HBV) infection. 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.

SOURCE Brii Biosciences Limited