8-K: Barinthus Bio Announces Promising Hepatitis B Trial Results, Including Functional Cures

Barinthus Biotherapeutics reports positive data from its Phase 2 trials for chronic hepatitis B, showing increased rates of HBsAg loss and functional cures with its VTP-300 immunotherapy.

Summary

• Barinthus Bio announced updated data from the IM-PROVE II and HBV003 trials at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2024.
• The IM-PROVE II trial showed that adding low-dose nivolumab to imdusiran and VTP-300 resulted in a 23% HBsAg loss rate by Week 48, compared to other groups.
• The HBV003 trial reported eight participants with complete HBsAg loss and two participants meeting the criteria for functional cure.
• Two of the eight participants with HBsAg loss also developed anti-hepatitis B antibodies (HBsAb), including one of the participants who achieved functional cure.
• 66% of participants who discontinued nucleos(t)ide analogue (NUC) therapy remained off treatment, with two achieving functional cure and two seroconverting to HBsAb positivity.
• The data suggests that the combination of VTP-300 and low-dose nivolumab may lead to stronger responses in patients with chronic hepatitis B.
• Both trials showed that the treatment regimens were generally well-tolerated with no significant safety concerns.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results, indicating a potential breakthrough in the treatment of chronic hepatitis B. The achievement of functional cures and HBsAb seroconversion is highly encouraging. However, the forward-looking statements and risks associated with clinical trials and funding temper the overall sentiment slightly.

Positives

• The addition of nivolumab to imdusiran and VTP-300 in the IM-PROVE II trial significantly increased HBsAg loss rates.
• The HBV003 trial demonstrated that VTP-300 can induce sustained reductions in HBsAg, leading to functional cures.
• The development of HBsAb positivity in some participants suggests a potential for long-term control of the infection.
• The ability of some participants to discontinue NUC therapy and remain off treatment is a significant positive outcome.
• Both trials showed that the treatment regimens were generally well-tolerated with no treatment-related serious adverse events.

Risks

• The forward-looking statements are subject to risks and uncertainties related to clinical trial success, regulatory approvals, and funding.
• The company's cash runway is estimated to last into Q2 2026, but this is subject to change.
• Global economic uncertainty, including disruptions in the banking industry, could impact the company's operations.
• Conflicts in Ukraine, Israel, and Gaza could also pose risks to the company's operations.

Future Outlook

The company anticipates further readouts from the HBV003 and IM-PROVE II trials in H1 2025, and is also progressing its VTP-1000 celiac disease program with single ascending dose data expected in H1 2025.

Management Comments

• Dr. Leon Hooftman, Chief Medical Officer of Barinthus Bio, stated that the combination of VTP-300 and low-dose nivolumab is promising and consistent with data from the HBV003 trial.
• Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma, commented that imdusiran provided meaningful reductions in HBsAg prior to treatment with immunomodulatory agents.
• Dr. Chun-Jen Liu, investigator on HBV003, noted that the data indicates a durable loss of HBsAg, including two participants who met the criteria for functional cure.
• Dr. Nadege Pelletier, Chief Scientific Officer of Barinthus Bio, highlighted the ability of VTP-300 to stimulate the immune response and induce sustained reductions in HBsAg.

Industry Context

These results are significant in the context of the ongoing efforts to find a functional cure for chronic hepatitis B, a disease with limited treatment options and high unmet need. The combination of immunotherapies and RNAi therapeutics represents a promising approach to addressing this challenge.

Comparison to Industry Standards

• Current standard of care for chronic hepatitis B, nucleos(t)ide analogs (NUCs), have low cure rates and require chronic treatment, with less than 10% of patients achieving a functional cure.
• Pegylated interferon, another treatment option, has significant side effects.
• The results from Barinthus Bio's trials, particularly the functional cure rates and HBsAb seroconversion, are notably higher than those typically seen with existing therapies.
• Companies like Gilead Sciences and Vir Biotechnology are also developing therapies for chronic hepatitis B, but Barinthus Bio's approach of combining an antigen-specific immunotherapy with a checkpoint inhibitor is unique.
• The use of RNAi therapeutics like imdusiran, developed by Arbutus, is also a novel approach to reducing HBsAg levels, which is a key step in achieving a functional cure.

Stakeholder Impact

• Shareholders are likely to react positively to the promising clinical trial results.
• Patients with chronic hepatitis B may have increased hope for a functional cure.
• Employees of Barinthus Bio and Arbutus Biopharma may be motivated by the positive results.
• The results could lead to increased interest from potential partners and investors.

Next Steps

• The company will continue follow-up with participants in the HBV003 trial to assess if they will meet functional cure criteria.
• Further data readouts from the HBV003 and IM-PROVE II trials are expected in H1 2025.
• The company will continue to advance its VTP-1000 celiac disease program, with single ascending dose data expected in H1 2025.

Key Dates

Keywords

Hepatitis B, VTP-300, Nivolumab, Imdusiran, Functional Cure, HBsAg Loss, Immunotherapy, Clinical Trial, HBV003, IM-PROVE II