Elebsiran

SAN FRANCISCO--(BUSINESS WIRE)--Vir Biotechnology, Inc. (Nasdaq: VIR) today announced 24-week post-end of treatment data from Part B of the ongoing MARCH Phase 2 clinical study evaluating tobevibart and elebsiran without or with pegylated interferon alpha (PEG-IFNα) in participants with chronic hepatitis B (CHB). The study-defined primary endpoint, proportion of participants with undetectable hepatitis B surface antigen (HBsAg) at 24 weeks post-end of treatment, was achieved by 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL receiving tobevibart and elebsiran without or with PEG-IFNα, respectively. The detailed data were presented today at the European Association for the Study of the Liver (EASL) congress in Amsterdam (The Netherlands). CHB is a long-lasting, inflammatory liver disease caused by the hepatitis B virus (HBV).1 The World Health Organization estimates that 254 million people live with CHB, and an estimated 1.1 million yearly deaths are associated with the disease.2 Complications from CHB may include liver cirrhosis, liver failure and liver cancer.3 Although CHB can be treated, there is currently no cure.1 Participants in the trial received tobevibart and elebsiran without or with PEG-IFNα. Tobevibart was administered at 300 mg every 4 weeks; elebsiran, at 200 mg every 4 weeks; and PEG-IFNα, for patients receiving it, at 180 µg weekly. Participants with HBsAg loss (seroclearance) after 48 weeks of treatment who met eligibility criteria discontinued both NRTI (nucleos(t)ide reverse transcriptase inhibitor) as well as tobevibart and elebsiran without or with PEG-IFNα treatment. The current analysis includes data from participants in the trial who have reached Week 24 post-end of treatment: 51 participants receiving tobevibart and elebsiran without PEG-IFNα and 32 receiving tobevibart and elebsiran with PEG-IFNα. An additional 18 participants receiving tobevibart and elebsiran with PEG-IFNα are currently advancing through the trial. Study-defined primary efficacy endpoint – The study-defined primary efficacy endpoint is proportion of participants with HBsAg seroclearance (defined as undetectable HBsAg) at 24 weeks post-end of treatment. Tobevibart and elebsiran without or with PEG-IFNα resulted in HBsAg loss 24 weeks post-end of treatment in 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL, respectively. These proportions were 8% (4/51) and 16% (5/32) for tobevibart and elebsiran without or with PEG-IFNα, respectively, in all participants. Functional cure – Functional cure is defined as sustained undetectable HBsAg and HBV DNA below the lower limit of quantification (0.05 IU/mL) at 24 weeks post-end of treatment after discontinuing NRTIs. Tobevibart and elebsiran without or with PEG-IFNα resulted in functional cure in 11% (2/18) and 15% (2/13) of participants with HBsAg<1000 IU/mL, respectively. These proportions were 4% (2/51) and 10% (3/30) for the combinations without or with PEG-IFNα, respectively, in all participants. Modified functional cure (allowing viral blips) – An exploratory modified functional cure, allowing transient viremia (viral blips) defined as HBV RNA or HBsAg equal or above the lower limit of quantification for ≤35 days, was also evaluated. Tobevibart and elebsiran without or with PEG-IFNα resulted in 24 weeks post-end of treatment modified functional cure rates of 11% (2/18) and 23% (3/13) in participants with HBsAg<1000 IU/mL, respectively. These proportions were 6% (3/51) and 13% (4/30) for the combinations without or with PEG-IFNα, respectively, in all participants. The safety and tolerability profile of tobevibart and elebsiran is consistent with prior studies. The data show that the combination is well tolerated, with no new safety concerns and generally only mild or moderate treatment emergent adverse events being reported throughout the study. "The MARCH data demonstrate that combinations of tobevibart and elebsiran can achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels,” said Mark Eisner, M.D., MPH, Chief Medical Officer, Vir Biotechnology. “These findings provide important insights into the challenges of achieving functional cure in chronic hepatitis B and will inform future development efforts in the field.” As previously communicated, Phase 3 development of combinations of tobevibart and elebsiran in CHB will not move forward without a global development and commercialization partner, which has not been secured. The Company plans to streamline the final stages of the MARCH Phase 2 program to ensure continued participant benefit and safety, while applying continued financial stewardship. Cash runway guidance into mid-2027 remains unchanged, based on the current operating plan. Vir Biotechnology is fully committed to the continued development of tobevibart and elebsiran in chronic hepatitis delta, based on the transformational potential of the first-of-its-kind investigational combination to achieve complete suppression of the hepatitis delta virus, as shown by compelling positive efficacy and safety data from the Phase 2 SOLSTICE clinical trial. About Tobevibart and Elebsiran Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. The Fc domain has been engineered to increase immune engagement and clearance of HBsAg immune complexes and incorporates Xencor’s Xtend™ technology to extend half-life. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta. Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) discovered by Alnylam Pharmaceuticals, Inc. It is designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta. About Vir Biotechnology, Inc. Vir Biotechnology, Inc., is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. Its clinical-stage portfolio includes programs for chronic hepatitis delta and multiple dual-masked T-cell engagers across validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website. References: 1 CDC Hepatitis B Basics | Hepatitis B | CDC, accessed April 2025. 2 World Health Organization. Global Hepatitis Report 2024: Action for Access in Low- and Middle-income Countries. World Health Organization; 2024. 3 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B - NIDDK (nih.gov), accessed April 2025. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “should,” “could,” “may,” “might,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements regarding: the therapeutic potential of the combination of tobevibart and elebsiran to treat chronic hepatitis B and chronic hepatitis delta; Vir Biotechnology’s commitment to the continued development of the combination of tobevibart and elebsiran in chronic hepatitis delta and the transformational potential of the combination to achieve complete hepatitis delta viral suppression in a majority of patients; Vir Biotechnology’s anticipated cash runway; Vir Biotechnology’s strategy and plans; and any assumptions underlying any of the foregoing. Many factors may cause differences between current expectations and actual results, including, without limitation: unexpected safety or efficacy data or results observed during clinical studies or in data readouts, including the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; challenges in accessing manufacturing capacity; clinical site activation rates or clinical enrollment rates that are lower than expected; the timing and outcome of Vir Biotechnology’s planned interactions with regulatory authorities, as well as general difficulties in obtaining any necessary regulatory approvals; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors, as well as changes in expected or existing competition; geopolitical changes or other external factors; and unexpected litigation or other disputes. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. The actual results may vary from the anticipated results, and the variations may be material. You are cautioned not to place undue reliance on any scientific data presented or these forward-looking statements, which are based on Vir Biotechnology’s available information, expectations and assumptions as of the date of this press release. Other factors that may cause Vir Biotechnology’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir Biotechnology’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir Biotechnology assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

End of treatment (EOT) data from Cohort 4 of the ENSURE study suggest that patients responding to prior BRII-179 treatment achieved faster and higher rate of surface antigen clearance with curative treatments compared to BRII-179 naïve participants, strengthening the case for a novel enrichment strategy, utilizing BRII-179 to identify and prime patients for improved functional cure outcomes 24 Week follow-up results from Cohorts 1-3 of the ENSURE study demonstrated sustained off-treatment benefits of elebsiran + PEG-IFNα combination therapy vs PEG-IFNα alone DURHAM, N.C. and BEIJING, May 7, 2025 /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 medical need, today announced data from its ongoing Phase 2 ENSURE study as late-breaking posters at the European Association for the Study of the Liver (EASL) Congress 2025 in Amsterdam, the Netherlands. ENSURE (NCT05970289) is a multicenter, open-label Phase 2 study. Cohorts 1-3 were designed to evaluate the contribution of elebsiran, an investigational small interfering ribonucleic acid (siRNA), to the combination treatment with pegylated interferon alpha (PEG-IFNα) in participants with chronic HBV infection with baseline hepatitis B surface antigen (HBsAg) of 100-3,000 IU/mL. Cohort 4 enrolled participants who completed 9 doses of BRII-179, a recombinant protein-based therapeutic vaccine, in combination with elebsiran in a previous APAC study BRII-179-835-001 (NCT04749368) to receive elebsiran and PEG-IFNα combination treatment. These participants were grouped based on their anti-HBs response induced by prior BRII-179 treatment: those with peak anti-HBs titers ≥ 10 IU/L are defined as anti-HBs responders, and those with peak anti-HBs titers < 10 IU/L as non-responders. The design of Cohort 4 as part of this study was based on the insight that BRII-179 could differentiate between immune responders and non-responders, offering the potential to predict future response to therapy. Interim data from Cohort 4 showed that anti-HBs responders achieved a substantially higher rate of HBsAg seroclearance than non-responders. At EOT (Week 48), 61% (11/18) of anti-HBs responders achieved HBsAg seroclearance, compared to 10% (1/10) of non-responders. Among the 11 anti-HBs responders who achieved HBsAg loss, 91% (10/11) had anti-HBs titers ≥ 100 IU/L at EOT. Of note, BRII-179 experienced participants in Cohort 4 achieved HBsAg loss faster than BRII-179 naïve participants in Cohort 2 and 3. 83% (10/12) of HBsAg loss in BRII-179 experienced participants occurred by Week 24, compared to 55% (6/11) in BRII-179 naïve participants. These findings suggest rapid HBsAg seroclearance in subjects with higher anti-HBs titers may translate into durable HBsAg loss and the potential to evaluate shorter treatment durations of PEG-IFNα. Additional data from Cohorts 1-3 of the ENSURE study showed the combination therapy of elebsiran either 100 mg or 200 mg and PEG-IFNα resulted in higher HBsAg loss rate at 24 weeks post EOT compared to PEG-IFNα alone, supporting the additive benefit of siRNA. "The data from Cohort 4 of the ENSURE study are encouraging. We saw in target populations that patients who were immune-responsive through pre-treatment with BRII-179 demonstrated a significant advantage in achieving a higher HBsAg seroclearance rate," said David Margolis, MD, Chief Medical Officer of Brii Bio. "With BRII-179, we may identify patients with less impaired intrinsic immunity and further prime their immune response. This approach may provide more durable HBsAg loss and potentially shorter treatment duration of PEG-IFNα. We are moving full speed ahead with our clinical efforts to deliver a meaningful option to the chronic hepatitis B patients long left waiting." Abstract Number: LB25123/ LBP-018 Title: 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 pegylated interferon-alfa: end of treatment data from ENSURE study Presenter: Grace Lai-Hung Wong, MBChB (CUHK), MD (CUHK), FRCP (Lond, Edin), FHKCP, FHKAM (Medicine), Professor of Gastroenterology and Hepatology at CUHK Medical Data Analytics Centre (MDAC) and Department of Medicine and Therapeutics in Hong Kong SAR, China A total of 28 participants with baseline HBsAg > 100 and ≤ 3000 IU/mL were analyzed. 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. Median [range] HBsAg at the time of initiating elebsiran + PEG-IFNα was numerically higher in anti-HBs responders (539.4 [106.7-2165.0] IU/mL) than in non-responders (219.3 [106.7-671.5] IU/mL). At EOT (Week 48), 61% (11/18) of anti-HBs responders achieved HBsAg seroclearance, compared to 10% (1/10) of non-responders. 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. Abstract Number: LB25115/ LBP-016 Title: Efficacy and safety of elebsiran and pegylated interferon alfa combination therapy versus pegylated interferon alfa in participants with chronic hepatitis B virus infection: follow-up results from the ongoing phase 2, randomized, open-label ENSURE study Presenter: David Margolis, MD, MPH, Chief Medical Officer of Brii Biosciences At Week 72 (24 weeks post EOT), higher HBsAg loss rate was observed in participants on combination therapy of either elebsiran 200mg or 100 mg and PEG-IFNα compared to PEG-IFNα alone (21.1% [4/19] or 33.3% [6/18] vs 5.6% [1/18]). All the 11 participants with HBsAg loss had baseline HBsAg < 1500 IU/mL. 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. As part of Brii Bio's unique approach to developing a functional cure for HBV, the Company and its partners are actively progressing multiple combination studies with our differentiated portfolio, including BRII-179 being evaluated in multiple combination studies with elebsiran led by Brii Bio; elebsiran being evaluated in combination with PEG-IFNα in studies led by Brii Bio; and tobevibart, an investigational broadly neutralizing monoclonal antibody targeting HBV, being evaluated in multiple Phase 2 and 3 tobevibart and elebsiran combination studies led by Vir Biotechnology. Key data readouts will be shared in the coming months at scientific conferences throughout 2025. 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 (previously known as BRII-835, VIR-2218) 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. 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 . SOURCE Brii Biosciences Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED