Novel combination for HBV

Spring Bank and Arbutus Biopharma agree to preclinical collaboration for chronic hepatitis B

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HOPKINTON, Mass.—About 240 million people worldwide are chronically infected with the hepatitis B virus (HBV), leading to progressive liver disease and one million deaths each year. There are relatively few new therapies in development for the treatment of HBV, which is often asymptomatic until significant liver damage has occurred.
Spring Bank Pharmaceuticals Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for the treatment of viral infections, cancer and inflammatory diseases, is partnering with Arbutus Biopharma Corp. to perform collaborative preclinical studies in chronic HBV involving the co-administration of Spring Bank’s SB 9200, an orally available selective immune-modulator, and Arbutus Biopharma’s AB-423, a capsid assembly inhibitor. Both investigational compounds are being developed for the treatment of chronic HBV.
According to Dr. Nezam Afdhal, chief medical officer of Spring Bank, “The preclinical study of the combination of SB 9200 and AB-423 is the first step in evaluating how a capsid assembly inhibitor can be combined with an oral immune-modulator in the treatment of chronic HBV and potentially lead to novel combination therapeutic strategies for patients with chronic HBV.”
SB 9200, Spring Bank’s novel small-molecule, orally-available selective immune-modulator compound, is being developed as both monotherapy and combination therapy as a backbone for the treatment of chronic HBV and other viral diseases. The compound is currently being studied in the ACHIEVE Phase 2 global trial. Part A of the ACHIEVE study is a placebo-controlled, sequential cohort, double-blind trial to evaluate increasing doses of SB 9200 as monotherapy for 12 weeks followed by tenofovir disoproxil fumarate 300mg (Viread from Gilead Sciences Inc.) for a further 12 weeks. Part B of the ACHIEVE study will evaluate SB 9200 in combination with tenofovir and as monotherapy versus tenofovir monotherapy after the optimal doses of SB 9200 are determined in Part A.
Spring Bank Pharmaceuticals is working on the discovery and development of a novel class of therapeutics using its proprietary small-molecule nucleic acid hybrid, or SMNH, chemistry platform. The company is designing SMNH compounds, small segments of nucleic acids that selectively target and modulate the activity of specific proteins involved in various disease states.
SB 9200 has been designed to selectively activate within infected cells the cellular proteins retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2), which have been linked with the body’s immune response to viral infections. Spring Bank believes that SB 9200 may play an important role in antiviral therapy by modulating the body’s immune response through its mechanisms of action to fight viral infections such as HBV. SB 9200 could provide a functional cure of HBV by increasing the clearance of HBsAg, the surface antigen of the hepatitis B virus that indicates active hepatitis B infection.
Arbutus Biopharma is developing a portfolio of drug candidates with multiple mechanisms of action to create a combination therapy to cure hepatitis B virus disease. Its HBV product development pipeline is focused on discovering, acquiring or in-licensing and developing drug candidates that attack multiple targets of the HBV lifecycle, including the aggressive suppression of HBV replication and the formation, inhibition and elimination of cccDNA. Such drug candidates can bolster the host immune response to chronic HBV infection.
HBV core protein, or capsid, is required for viral replication. This core protein may have additional roles in cccDNA function. While current nucleoside analog therapy significantly reduces HBV DNA levels in the serum, HBV replication continues in the liver, thereby enabling HBV infection to persist. Effective therapy for patients requires new agents which will effectively block viral replication.
Arbutus is developing core protein inhibitors (also known as capsid assembly inhibitors) as oral therapeutics for the treatment of chronic HBV infection. By inhibiting assembly of the viral capsid, they impair the ability of hepatitis B virus to replicate, resulting in reduced cccDNA.
To deliver a cure for HBV, Arbutus will apply its strategy for developing a cure for hepatitis C virus and advancing RNAi technology and other therapies into clinical trials. In order to accomplish this, the company will target three key factors driving chronic HBV persistence: uncontrolled HBV replication within the body; suppression of the host immune response by HBsAg or other viral antigens; and a stable reservoir of cccDNA in infected liver cells that continues to express virus and antigen.

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