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

Arbutus Biopharma's combination therapy of imdusiran and VTP-300 shows significant reduction in HBsAg levels in chronic hepatitis B patients, with a high percentage achieving NA therapy discontinuation criteria.

Summary

• Arbutus Biopharma announced positive preliminary end-of-treatment data from its Phase 2a clinical trial (IM-PROVE II) for chronic hepatitis B (cHBV) patients.
• The trial evaluated the combination of imdusiran, an RNAi therapeutic, and VTP-300, an immunotherapeutic, in patients on standard nucleos(t)ide analogue (NA) therapy.
• The results showed that the combination was generally safe and well-tolerated, leading to a significant reduction in HBsAg levels.
• Specifically, 94% of patients in the treatment arm achieved HBsAg levels of <100 IU/mL at the end of treatment (Week 48), compared to 84% in the placebo arm.
• At 24 weeks post-treatment (Week 72), 80% of patients in the treatment arm had HBsAg levels <100 IU/mL, compared to 16% in the placebo arm.
• A significant difference (p<0.05) in HBsAg levels was observed between the treatment and placebo arms at 24 weeks post-EOT.
• 84% of patients in the treatment arm met the criteria to discontinue NA therapy after Week 48, compared to 53% in the placebo arm.
• One patient in the treatment arm achieved undetectable HBsAg, and another had a >1.5 log10 decline during the NA-therapy discontinuation follow-up period.
• The trial also includes an additional cohort evaluating the potential of nivolumab to enhance responses, with preliminary data expected in the second half of 2024.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results, with statistically significant improvements in key metrics and a good safety profile. The company also has a strong cash position and a clear strategy for future development. The sentiment is very positive from an investment perspective.

Positives

• The combination therapy demonstrated a statistically significant reduction in HBsAg levels, a key marker for HBV infection.
• A high percentage of patients in the treatment arm were able to discontinue NA therapy, potentially reducing the burden of long-term treatment.
• The treatment was generally safe and well-tolerated, with no serious adverse events reported.
• The study showed a clear separation in HBsAg levels between the treatment and placebo arms at Week 72.
• Imdusiran has shown consistent reductions in HBsAg, making it a promising component of combination therapies.
• The addition of nivolumab to the trial could further enhance treatment responses.

Negatives

• The study only included a small number of patients in the treatment and placebo arms at the 24-week post-EOT analysis (n=5 and n=6 respectively).
• Some patients experienced mild injection site reactions and transient ALT increases.

Risks

• The trial is still ongoing, and further data is needed to confirm the long-term efficacy and safety of the treatment.
• The success of the treatment may depend on the specific characteristics of the patients and the stage of their disease.
• Regulatory approvals are required before the treatment can be made available to patients.
• The company faces competition from other companies developing treatments for HBV.
• The company's financial position may be impacted by the costs of clinical trials and regulatory approvals.

Future Outlook

Arbutus anticipates preliminary data from the additional cohort of the IM-PROVE II trial evaluating nivolumab in the second half of 2024, and is also expecting preliminary data from the multiple-ascending dose healthy subject cohorts of the AB-101-001 trial in the second half of 2024.

Management Comments

• Dr. Kosh Agarwal stated that the data shows that adding imdusiran and VTP-300 to ongoing NA therapy in cHBV patients meaningfully reduces HBsAg after the end of the treatment period.
• Dr. Agarwal was impressed with the number of patients that qualified to stop NA therapy in the VTP-300 group and the clear separation in HBsAg levels between the treatment arm and placebo at Week 72.
• Dr. Karen Sims commented that imdusiran consistently provides notable reductions in HBsAg prior to combining with other therapies, which may improve the response rates of these immunomodulatory approaches.
• Dr. Sims also stated that they continue to believe that lowering surface antigen is key to promoting HBV-specific immune reawakening.

Industry Context

This announcement is significant in the context of the ongoing efforts to find a functional cure for chronic hepatitis B. The combination of an RNAi therapeutic and an immunotherapeutic represents a novel approach to addressing the complex nature of the disease. The results are promising and could potentially lead to a new treatment paradigm for cHBV patients.

Comparison to Industry Standards

• Current standard of care for cHBV involves lifelong daily NA therapy, which aims to reduce HBV DNA and the risk of cirrhosis and liver cancer, but has a low functional cure rate of less than 5%.
• Pegylated interferon (Peg-IFN) is another treatment option, but it is poorly tolerated and has a low functional cure rate of less than 5%.
• The results from the IM-PROVE II trial show a significantly higher rate of HBsAg reduction and NA therapy discontinuation compared to the current standard of care.
• Other companies are also developing novel therapies for HBV, including RNAi therapeutics, immunotherapies, and combination therapies. Arbutus' approach of combining imdusiran with VTP-300 and potentially nivolumab is competitive with these other approaches.
• The trial results are comparable to or better than some other combination therapies in development, particularly in terms of the percentage of patients achieving HBsAg levels below 100 IU/mL and the rate of NA therapy discontinuation.

Legal Proceedings

• Arbutus is involved in patent litigation against Moderna and Pfizer/BioNTech regarding their COVID-19 vaccines.
• A Markman Hearing occurred in the Moderna case on February 8, 2024, and the court ruled in favor of Arbutus on the majority of the claims on April 3, 2024.
• The trial date for the Moderna case is set for April 21, 2025.
• The lawsuit against Pfizer is ongoing, and a date for the claim construction hearing has not been set.

Stakeholder Impact

• Shareholders: The positive clinical trial results and strong cash position are likely to have a positive impact on shareholder value.
• Patients: The potential for a more effective and finite treatment for cHBV is a significant benefit for patients.
• Employees: The company's progress in clinical development and patent litigation is likely to have a positive impact on employee morale and job security.
• Partners: The company's strategic partnerships, such as the one with Qilu Pharmaceutical, are likely to be strengthened by the positive clinical trial results.

Next Steps

• The company will continue to follow patients in the IM-PROVE II trial to assess the long-term efficacy and safety of the treatment.
• The company will analyze the data from the additional cohort of the IM-PROVE II trial evaluating nivolumab.
• The company will continue to enroll patients in the IM-PROVE III trial.
• The company will continue to advance the development of AB-101, its oral PD-L1 inhibitor.
• The company will continue to pursue its patent litigation against Moderna and Pfizer/BioNTech.

Key Dates

Keywords

Hepatitis B, cHBV, Imdusiran, VTP-300, RNAi, Immunotherapy, HBsAg, Clinical Trial, Phase 2a, Nivolumab, Nucleos(t)ide Analogue, Functional Cure