8-K: Arbutus Biopharma Announces Positive Phase 2a Data for Imdusiran in Chronic Hepatitis B Treatment

Arbutus Biopharma's imdusiran, combined with interferon, shows promising results in reducing hepatitis B surface antigen levels and achieving sustained loss in some patients.

Summary

• Arbutus Biopharma announced new data from its Phase 2a clinical trial IM-PROVE I, evaluating imdusiran, an RNAi therapeutic, in combination with pegylated interferon alfa-2 (IFN) and ongoing nucleos(t)ide analogue (NA) therapy for chronic hepatitis B (cHBV).
• The trial showed that some patients achieved undetectable levels of hepatitis B surface antigen (HBsAg) at the end of treatment, with some maintaining this loss 24 weeks after completing imdusiran and IFN treatment.
• Specifically, 33.3% of patients receiving 48 weeks of imdusiran and 24 weeks of IFN achieved undetectable HBsAg at the end of treatment, and this was sustained in 100% of these patients 24 weeks after treatment.
• Six patients who stopped all therapy maintained undetectable levels of HBsAg and HBV DNA, with two of these patients reaching 12 weeks off all therapy.
• All six patients with sustained HBsAg loss also seroconverted and had high levels of anti-HBsAg antibodies, suggesting immune control.
• The combination of imdusiran and IFN was generally safe and well-tolerated, with no serious adverse events related to the treatment and no adverse events leading to discontinuation.
• The company is also conducting other Phase 2a trials evaluating imdusiran with other immunomodulators.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results with a potential for a functional cure for HBV, which is a significant unmet medical need. The safety profile is also encouraging. However, the trial is still ongoing and long-term data is needed.

Positives

• The combination of imdusiran and interferon showed a significant reduction in HBsAg levels, a key marker for HBV infection.
• A subset of patients achieved sustained undetectable HBsAg levels, even after stopping treatment, indicating a potential functional cure.
• The treatment was generally safe and well-tolerated, with no serious adverse events related to the therapy.
• The results suggest that imdusiran, when combined with an immunomodulator, has the potential to provide a functional cure for patients with chronic HBV.
• The company has a strong financial position with a cash runway through Q2 2026.

Negatives

• The trial involved small groups of patients, which may limit the generalizability of the results.
• The study is still ongoing, and long-term data is needed to confirm the durability of the treatment response.
• The treatment requires a combination of drugs, which may increase the complexity of treatment and potential side effects.

Risks

• The clinical trial results are preliminary and may not be replicated in larger studies.
• The development of a functional cure for HBV is complex and may face challenges.
• Regulatory approvals for the treatment are not guaranteed.
• The company faces competition from other companies developing HBV treatments.
• The company is involved in patent litigation which could impact future revenue.

Future Outlook

The company plans to continue following the progress of patients in the IM-PROVE I trial and those in other Phase 2a trials evaluating imdusiran with other immunomodulators. They also anticipate preliminary data from the AB-101 trial in the second half of 2024.

Management Comments

• Professor Man-Fung Yuen commented that the data is impressive with robust HBsAg response rates that are sustained after end-of-treatment.
• Dr. Karen Sims stated that the data further supports their belief that lowering surface antigen with imdusiran and incorporating an immunomodulator has the potential to provide a functional cure for patients with cHBV.

Industry Context

The announcement is significant in the context of the ongoing efforts to find a functional cure for chronic hepatitis B, a disease affecting over 250 million people worldwide. The results suggest that Arbutus's approach of combining an RNAi therapeutic with an immunomodulator could be a promising strategy.

Comparison to Industry Standards

• The results are notable as they show a higher rate of sustained HBsAg loss compared to standard treatments like pegylated interferon alone, which typically achieve functional cure rates of less than 5%.
• Other RNAi candidates in development have been evaluated in combination with IFN, but imdusiran achieved these results with less frequent administration, at a lower dose, and when combined with a shorter 24-week course of IFN.
• Companies like Gilead Sciences and Vir Biotechnology are also developing HBV therapies, but Arbutus's approach of combining RNAi with immunomodulation is a differentiated strategy.
• The use of the Abbott HBsAg Next Qualitative assay, an ultrasensitive assay, to confirm HBsAg loss is a rigorous approach that provides confidence in the results.

Legal Proceedings

• The company is involved in patent litigation with Moderna and Pfizer/BioNTech regarding COVID-19 vaccine sales.

Stakeholder Impact

• Shareholders may react positively to the promising clinical trial results.
• Patients with chronic hepatitis B may benefit from the development of a potential functional cure.
• The company's employees may be motivated by the positive progress in clinical development.
• The company's partners may be encouraged by the positive results and potential for commercialization.

Next Steps

• The company will continue to follow the patients in the IM-PROVE I trial.
• The company will continue to evaluate imdusiran in other Phase 2a trials with different immunomodulators.
• The company expects preliminary data from the AB-101 trial in the second half of 2024.

Key Dates

Keywords

Hepatitis B, HBV, Imdusiran, RNAi, Interferon, HBsAg, Functional Cure, Clinical Trial, AB-729, Antiviral, Immunomodulator