Arbutus and Barinthus Bio Report IM-PROVE II Data: Nivolumab Boosts HBsAg Loss in Chronic Hepatitis B

Arbutus Biopharma Corporation, a clinical-stage biopharmaceutical company focused on developing therapies for chronic hepatitis B virus (cHBV) infection, and Barinthus Biotherapeutics, also a clinical-stage biopharmaceutical company specializing in immunotherapeutics, have announced promising preliminary data from their Phase 2a IM-PROVE II clinical trial. This trial, presented at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2024, focuses on patients with chronic hepatitis B.

The study's new insights come from Group C, which included participants treated with repeat doses of Arbutus' RNAi therapeutic imdusiran, followed by Barinthus' T-cell stimulating immunotherapeutic, VTP-300, with or without low-dose nivolumab, an anti-PD-1 monoclonal antibody. Data show that participants in Group C receiving nivolumab had higher rates of HBsAg loss compared to those in Groups A and B, who were treated with imdusiran and VTP-300 or placebo. Previous results from Groups A and B were shared at the European Association for the Study of the Liver (EASL) Congress in June 2024.

Group C consisted of 22 participants, all non-cirrhotic and virally suppressed, with HBsAg levels between 100 and 5,000 IU/mL at the start of the trial and on stable nucleos(t)ide analogue (NUC) therapy for at least a year. Among these, 13 were eligible for low-dose nivolumab.

Preliminary results from Group C up to Week 48 indicated that:
- Imdusiran treatment led to a mean decline in HBsAg levels similar to those observed in Groups A and B.
- Participants in Group C receiving both imdusiran and VTP-300 with nivolumab had significantly greater mean declines in HBsAg levels at Week 48 compared to those in Groups A and B, and Group C without nivolumab.
- 23% of participants (3 out of 13) receiving the combination of imdusiran, VTP-300, and low-dose nivolumab achieved HBsAg loss by Week 48.
- Increases in immune biomarkers linked to immune checkpoint proteins, inflammation, and T-cell activation were noted in participants who experienced HBsAg loss at any time through Week 48.
- The treatment regimen was generally well tolerated, with no immune-related adverse events reported.

Dr. Leon Hooftman, Chief Medical Officer of Barinthus Bio, commented on the findings, noting the significant impact of combining VTP-300 with low-dose nivolumab in achieving HBsAg loss. Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma, emphasized the importance of reducing surface antigen to promote HBV-specific immune responses, highlighting that imdusiran’s reduction of HBsAg was a key component before the introduction of immunomodulatory agents VTP-300 and low-dose nivolumab.

The IM-PROVE II Phase 2a clinical trial initially included 40 participants in Groups A and B, all of whom were non-cirrhotic and virally suppressed on stable NUC therapy. These participants received imdusiran (60mg every 8 weeks) for 24 weeks alongside NUC therapy, followed by either VTP-300 (Group A) or placebo (Group B) at specified intervals.

The trial was later amended to incorporate Group C, which enrolled 22 additional participants. Thirteen of these participants received imdusiran (60mg every 8 weeks) for 24 weeks with ongoing NUC therapy, followed by VTP-300 at Weeks 26 and 30, plus up to two low doses of nivolumab (0.3 mg/kg) at Week 30. The remaining nine participants followed the same regimen without nivolumab.

After completing the treatment period at Week 48, participants who met specific criteria had the option to discontinue NUC therapy and be monitored for an additional 48 weeks. Those not meeting the criteria continued NUC therapy for an extra 24 weeks of follow-up.

**About Imdusiran (AB-729)**
Imdusiran is an RNA interference (RNAi) therapeutic designed to reduce all HBV viral proteins and antigens, including the hepatitis B surface antigen. It targets hepatocytes using Arbutus' GalNAc delivery technology, which allows for subcutaneous administration. Clinical data have shown that imdusiran is generally safe and well-tolerated, providing significant reductions in hepatitis B surface antigen and hepatitis B DNA. It is currently undergoing multiple Phase 2a clinical trials.

**About VTP-300**
VTP-300, developed by Barinthus Bio, is an immunotherapeutic candidate composed of an initial dose using the ChAdOx vector and subsequent doses using the MVA vector, both encoding multiple HBsAg, including surface, polymerase, and core antigens. VTP-300 is the first immunotherapy shown to induce sustained reductions in HBsAg. Barinthus Bio is investigating VTP-300 in combination with other agents to control chronic HBV infection and counteract immune suppression and T cell exhaustion in the liver.

**About Arbutus Biopharma Corporation**
Arbutus Biopharma Corporation is dedicated to developing novel therapeutics for chronic hepatitis B virus (cHBV) infection. Their approach involves suppressing HBV DNA, reducing surface antigen, and boosting HBV-specific immune responses. Arbutus' pipeline includes an RNAi therapeutic, imdusiran (AB-729), and an oral PD-L1 inhibitor, AB-101, both showing promise in clinical trials.

**About Barinthus Biotherapeutics**
Barinthus Biotherapeutics focuses on developing immunotherapeutics for chronic infectious diseases and autoimmunity. Their pipeline includes VTP-300 for chronic HBV infection and VTP-1000 for celiac disease. They are also conducting a Phase 1 trial for VTP-850, targeting recurrent prostate cancer.

Overall, the preliminary data from the IM-PROVE II trial suggests that the combination of imdusiran, VTP-300, and low-dose nivolumab holds promise for achieving significant reductions in HBsAg levels and improving immune responses in patients with chronic hepatitis B virus infection.