Vir Biotechnology, Inc. announced new data from its robust hepatitis B virus (HBV) portfolio aimed at achieving a functional cure. These data, plus health outcomes research, are being presented at the American Association for the Study of Liver Diseases The Liver Meeting® in two oral presentations, both of which were selected for inclusion in the “Best of the Liver Meeting” summary, a poster and a late-breaking poster presentation. The “Best of the Liver Meeting” designation underscores the strength of Vir's broad hepatitis portfolio, which is addressing both HBV and hepatitis D virus (HDV).

In one oral presentation, new preliminary data from an ongoing Phase 2 trial demonstrated that 30.8% of participants receiving 48 weeks of VIR-2218, an investigational small interfering ribonucleic acid (siRNA), initiated concurrently with pegylated interferon alpha (PEG-IFN-a), achieved HBsAg seroclearance with anti-HBs seroconversion. Additionally, 48 weeks of VIR-2218 plus PEG-IFN-a provided greater reductions in hepatitis B surface antigen (HBsAg) (mean decrease of -2.9 log10 IU/mL) compared to VIR-2218 alone or with shorter regimens of the combination. No new safety signals were identified.

In a separate oral presentation, new results from Part A of the Phase 2 MARCH (Monoclonal Antibody siRNA Combination against Hepatitis B) trial, including all three cohorts, demonstrated a mean HBsAg reduction of >2.5 log10 IU/mL. These data showed that VIR-2218 and VIR-3434, an investigational HBsAg-targeting monoclonal antibody engineered to potentially act as a therapeutic vaccine, are additive in reducing HBsAg. The combination of VIR-2218 and VIR-3434 through up to 20 weeks of treatment in Part A was generally well tolerated.

Combining the learnings from the VIR-2218 plus PEG-IFN-a trial with these encouraging new results have led to additional cohorts evaluating the triple combination of VIR-2218, VIR-3434 and PEG-IFN-a being added to Part B of the MARCH trial. Initial data from Part B are expected in the second half of 2023. Additionally, Phase 1 data presented as a poster demonstrated that a single 75 mg or 300 mg dose of VIR-3434 resulted in rapid reductions in HBsAg and HBV DNA in the majority of viremic participants with chronic HBV infection in the absence of nucleot(s)ide reverse transcriptase inhibitor (NRTI) therapy.

Finally, a real-world analysis of 20 years of medical records in the U.S., to be highlighted in a late-breaking poster presentation, revealed that the majority of people with chronic HBV infection remained untreated throughout the study period. Chronic hepatitis B virus (HBV) infection remains an urgent global public health challenge associated with significant morbidity and mortality. Approximately 300 million people around the world are living with HBV, and approximately 900,000 of them die from associated complications each year.

These patients are significantly underserved by existing therapies with low functional cure rates, lifelong daily therapy and poor tolerability. Vir is working to achieve a functional cure for the millions of people with HBV around the world through its broad and differentiated portfolio. Chronic hepatitis D virus (HDV) infection occurs as a simultaneous co-infection or super-infection with hepatitis B virus (HBV).

An estimated 12 million patients globally are infected with HDV, representing approximately 5% of those infected with HBV. HDV-HBV co-infection is considered the most severe form of chronic viral hepatitis due to more rapid progression toward hepatocellular carcinoma and liver-related death. VIR-2218 is an investigational subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and have 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. VIR-2218 is the first asset in the Company's collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical trials. VIR-3434 is an investigational subcutaneously administered antibody designed to block entry of HBV and HDV viruses into hepatocytes and to reduce the level of virions and subviral particles in the blood.

VIR-3434, which incorporates Xencor's Xtend™ and other Fc technologies, has been engineered to potentially function as a T cell vaccine against HBV and HDV in infected patients, as well as to have an extended half-life.