New translational data\u00a0demonstrate that BRII-179-induced immune responses are associated with high HBsAg reduction in a subset of participants with chronic HBV infection <\/p>\n
BRII-179 as add-on therapy induces functional antibody responses and contributes to improved sustained HBsAg loss in PEG-IFNa-treated participants with chronic HBV infection<\/p>\n
DURHAM, N.C.\u00a0and\u00a0BEIJING, June 7, 2024<\/span> \/PRNewswire\/ — Brii Biosciences Limited<\/a>\u00a0(“Brii Bio<\/span>,” “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, presented new data from two Phase 2 studies evaluating BRII-179 either as a combination therapy with BRII-835 (elebsiran) or as an add-on therapy to pegylated interferon-alpha (PEG-IFN\u03b1) treatment for chronic hepatitis B virus (HBV) infection at the EASL\u2122 (European Association for the Study of the Liver) Congress 2024. \u00a0<\/p>\n Data presented in an oral presentation<\/a> from a Phase 2 clinical trial demonstrated BRII-179, a therapeutic vaccine, in combination with BRII-835 (elebsiran)\u00a0induced substantial HBV-specific B and T cell responses that correlate with antiviral effect in a subset of participants with chronic HBV infection.\u00a0The\u00a0exploratory translational study evaluating\u00a0the correlation of treatment-induced immune response with antiviral effects demonstrated:<\/p>\n Pre-S1-specific\u00a0T cell response targeting a region adjacent to sodium taurocholate cotransporting polypeptide (NTCP)\u00a0was identified to be associated with high levels of HBsAg reduction in some participants receiving BRII-835\u00a0(elebsiran)\u00a0and BRII-179. Ex\u00a0vivo\u00a0Pre-S1-specific\u00a0Th1-type cytokines (IL-2) were detected in participants with high HBsAg reduction, while Th2-type responses were not associated with HBsAg reduction.\u00a0 BRII-179 induced robust\u00a0anti-HBV neutralizing activity in participants with high levels of HBsAg reduction and HBsAb induction. <\/p>\n “This study shows for the first time direct evidence that immune responses induced by an HBV therapeutic vaccine is associated with HBsAg reduction and viral control in some participants with chronic HBV infection,” said Antonio Bertoletti<\/span>, MD, Professor, Emerging Infectious Diseases Program at Duke-NUS Medical School. “The antiviral activity appears to be linked with a boosting of anti-HBs antibodies and Pre-S1-specific T cell responses induced by BRII-179, supporting that BRII-179 can break immune tolerance and have an impact on sustained control of the viral infection.”<\/p>\n Additionally, late-breaker poster<\/a> presentation data from a Phase 2 clinical trial demonstrated that BRII-179, administrated on top of PEG-IFN\u03b1, improved overall HBsAg loss rate from end-of-treatment (EOT) to at least 24 weeks post nucleos(t)ide\u00a0reverse\u00a0transcriptase\u00a0inhibitors (NRTI) discontinuation compared to the PEG-IFN\u03b1 group. Follow-up data from this randomized, double-blind, placebo-controlled clinical trial in 114 virally-suppressed participants with chronic HBV infection showed:<\/p>\n Among the participants who met\u00a0NRTI discontinuation criteria and entered NRTI discontinuation monitoring period (NDMP), a higher percentage of participants in the BRII-179 + PEG-IFN\u03b1 group maintained HBsAg loss (19.3% vs 12.3% in full analysis set [FAS]) compared to the placebo + PEG-IFN\u03b1 group. The improvement in overall HBsAg loss rate was sustained from EOT (26.3% vs 19.3% in FAS) to at least 24-week post NRTI discontinuation (cut-off date) or 36-week post EOT in the BRII-179 + PEG-IFN\u03b1 group. No participant who discontinued NRTI required NRTI retreatment. A higher percentage of participants in the BRII-179 +\u00a0PEG-IFN\u03b1 group maintaining HBsAg loss had HBsAb \u2265 100 IU\/L compared to the placebo + PEG-IFN\u03b1 group (36.4% vs 14.3% in FAS) at \u2265 24-week post NRTI discontinuation. No participant with\u00a0HBsAb titer \u2265 100 IU\/L at EOT experienced HBsAg changed from < 0.05 IU\/mL (LLOQ) to \u2265 0.05 IU\/mL (i.e. HBsAg rebound) through the cut-off date, suggesting that robust antibody responses against HBV are necessary for sustained off-treatment HBsAg loss. Treatment with BRII-179 and PEG-IFN\u03b1\u00a0combination was generally safe and tolerated. No new risk was identified in the post EOT follow-up period and NDMP. <\/p>\n The favorable benefit-risk profile and scientific insights from these studies support further clinical evaluation of BRII-179 in combination with other modalities such as siRNA and PEG-IFN\u03b1 as key components for the treatment of chronic HBV infection,\u00a0with the goal of achieving functional cure.<\/p>\n About BRII-179 <\/p>\n 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. Brii Bio<\/span> licensed BRII-179 from VBI Vaccines, Inc. (“VBI”) in December 2018<\/span> and has extended the exclusive license to global rights since July 2023<\/span>.<\/p>\n About BRII-835 (Elebsiran)<\/p>\n BRII-835 (elebsiran) 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 and HDV. 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<\/span> licensed exclusive rights to develop and commercialize BRII-835 (elebsiran) for the greater China<\/span> territory from Vir Biotechnology, Inc. (“Vir”) in 2020.<\/p>\n About Hepatitis B\u00a0<\/p>\n 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<\/span>, where 87 million people are chronically infected.[2]<\/p>\n About Brii Bio<\/span><\/p>\n Brii Biosciences Limited (“Brii Bio<\/span>“, 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 and central nervous system diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B virus (HBV)\u00a0infection. 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<\/span>, Beijing<\/span> and Shanghai<\/span>. For more information, visit www.briibio.com<\/a>.<\/p>\n [1] World Health Organization. (April\u00a02024). Global hepatitis report 2024: action for access in low- and middle-income countries.\u00a0World Health Organization. Retrieved from https:\/\/www.who.int\/publications\/i\/item\/9789240091672<\/a><\/span><\/p>\n [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<\/a>.<\/span><\/p>\n<\/div>\n \u00a0<\/p>","protected":false},"excerpt":{"rendered":" <\/p>\n New translational data\u00a0demonstrate that BRII-179-induced immune responses are associated with high HBsAg reduction in a subset of participants with chronic HBV infection <\/p>\n BRII-179 as add-on therapy induces functional antibody responses and contributes to improved sustained HBsAg loss in PEG-IFNa-treated participants with chronic HBV infection<\/p>\n DURHAM, N.C.\u00a0and\u00a0BEIJING, June 7, 2024<\/span> \/PRNewswire\/ — Brii Biosciences Limited<\/a>\u00a0(“Brii Bio<\/span>,” “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, presented new data from two Phase 2 studies evaluating BRII-179 either as a combination therapy with BRII-835 (elebsiran) or as an add-on therapy to pegylated interferon-alpha (PEG-IFN\u03b1) treatment for chronic hepatitis B virus (HBV) infection at the EASL\u2122 (European Association for the Study of the Liver) Congress 2024. \u00a0<\/p>\n Data presented in an oral presentation<\/a> from a Phase 2 clinical trial demonstrated BRII-179, a therapeutic vaccine, in combination with BRII-835 (elebsiran)\u00a0induced substantial HBV-specific B and T cell responses that correlate with antiviral effect in a subset of participants with chronic HBV infection.\u00a0The\u00a0exploratory translational study evaluating\u00a0the correlation of treatment-induced immune response with antiviral effects demonstrated:<\/p>\n Pre-S1-specific\u00a0T cell response targeting a region adjacent to sodium taurocholate cotransporting polypeptide (NTCP)\u00a0was identified to be associated with high levels of HBsAg reduction in some participants receiving BRII-835\u00a0(elebsiran)\u00a0and BRII-179. Ex\u00a0vivo\u00a0Pre-S1-specific\u00a0Th1-type cytokines (IL-2) were detected in participants with high HBsAg reduction, while Th2-type responses were not associated with HBsAg reduction.\u00a0 BRII-179 induced robust\u00a0anti-HBV neutralizing activity in participants with high levels of HBsAg reduction and HBsAb induction. <\/p>\n “This study shows for the first time direct evidence that immune responses induced by an HBV therapeutic vaccine is associated with HBsAg reduction and viral control in some participants with chronic HBV infection,” said Antonio Bertoletti<\/span>, MD, Professor, Emerging Infectious Diseases Program at Duke-NUS Medical School. “The antiviral activity appears to be linked with a boosting of anti-HBs antibodies and Pre-S1-specific T cell responses induced by BRII-179, supporting that BRII-179 can break immune tolerance and have an impact on sustained control of the viral infection.”<\/p>\n Additionally, late-breaker poster<\/a> presentation data from a Phase 2 clinical trial demonstrated that BRII-179, administrated on top of PEG-IFN\u03b1, improved overall HBsAg loss rate from end-of-treatment (EOT) to at least 24 weeks post nucleos(t)ide\u00a0reverse\u00a0transcriptase\u00a0inhibitors (NRTI) discontinuation compared to the PEG-IFN\u03b1 group. Follow-up data from this randomized, double-blind, placebo-controlled clinical trial in 114 virally-suppressed participants with chronic HBV infection showed:<\/p>\n Among the participants who met\u00a0NRTI discontinuation criteria and entered NRTI discontinuation monitoring period (NDMP), a higher percentage of participants in the BRII-179 + PEG-IFN\u03b1 group maintained HBsAg loss (19.3% vs 12.3% in full analysis set [FAS]) compared to the placebo + PEG-IFN\u03b1 group. The improvement in overall HBsAg loss rate was sustained from EOT (26.3% vs 19.3% in FAS) to at least 24-week post NRTI discontinuation (cut-off date) or 36-week post EOT in the BRII-179 + PEG-IFN\u03b1 group. No participant who discontinued NRTI required NRTI retreatment. A higher percentage of participants in the BRII-179 +\u00a0PEG-IFN\u03b1 group maintaining HBsAg loss had HBsAb \u2265 100 IU\/L compared to the placebo + PEG-IFN\u03b1 group (36.4% vs 14.3% in FAS) at \u2265 24-week post NRTI discontinuation. No participant with\u00a0HBsAb titer \u2265 100 IU\/L at EOT experienced HBsAg changed from < 0.05 IU\/mL (LLOQ) to \u2265 0.05 IU\/mL (i.e. HBsAg rebound) through the cut-off date, suggesting that robust antibody responses against HBV are necessary for sustained off-treatment HBsAg loss. Treatment with BRII-179 and PEG-IFN\u03b1\u00a0combination was generally safe and tolerated. No new risk was identified in the post EOT follow-up period and NDMP. <\/p>\n The favorable benefit-risk profile and scientific insights from these studies support further clinical evaluation of BRII-179 in combination with other modalities such as siRNA and PEG-IFN\u03b1 as key components for the treatment of chronic HBV infection,\u00a0with the goal of achieving functional cure.<\/p>\n About BRII-179 <\/p>\n 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. Brii Bio<\/span> licensed BRII-179 from VBI Vaccines, Inc. (“VBI”) in December 2018<\/span> and has extended the exclusive license to global rights since July 2023<\/span>.<\/p>\n About BRII-835 (Elebsiran)<\/p>\n BRII-835 (elebsiran) 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 and HDV. 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<\/span> licensed exclusive rights to develop and commercialize BRII-835 (elebsiran) for the greater China<\/span> territory from Vir Biotechnology, Inc. (“Vir”) in 2020.<\/p>\n About Hepatitis B\u00a0<\/p>\n 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<\/span>, where 87 million people are chronically infected.[2]<\/p>\n About Brii Bio<\/span><\/p>\n Brii Biosciences Limited (“Brii Bio<\/span>“, 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 and central nervous system diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B virus (HBV)\u00a0infection. 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<\/span>, Beijing<\/span> and Shanghai<\/span>. For more information, visit www.briibio.com<\/a>.<\/p>\n [1] World Health Organization. (April\u00a02024). Global hepatitis report 2024: action for access in low- and middle-income countries.\u00a0World Health Organization. Retrieved from https:\/\/www.who.int\/publications\/i\/item\/9789240091672<\/a><\/span><\/p>\n