Capsid inhibitor with HBV RNA Destabilizer Demonstrate Complementary Efficacy Results
Subcutaneous RNAi Agent Demonstrates Durable HBsAg Reduction Following a Single Dose
"Data presented at EASL 2018 is an endorsement of our combination strategy and the breadth and quality of our therapeutic candidates,” said Dr.
Oral Presentation #3503: “Preclinical Antiviral Drug Combination Studies Utilizing Novel Orally Bioavailable Investigational Agents for Chronic Hepatitis B Infection: AB-506, a Next Generation HBV Capsid Inhibitor, and AB-452, an HBV RNA Destabilizer” by Rene Rijnbrand, VP Head of Biology at
Summary: We evaluated the anti-HBV activities of two novel orally administered agents, an HBV capsid inhibitor AB-506 and an HBV RNA destabilizer AB-452, in combination with approved standard of care (SOC) therapies: nucleos(t)ide analogs (NA), entecavir (ETV), tenofovir disproxil fumarate (TDF), tenofovir alafenamide (TAF), and our lead RNAi agent, ARB-1467. The in vitro dual combinations of AB-506 or AB-452 with approved NAs or ARB-1467 ranged from additive to moderately synergistic at reducing HBV rcDNA and HBsAg levels with no significant effects on cell viability. After a once-daily 7-day oral treatment period in HDI HBV mice, dual combinations of AB-506+AB-452, AB-506+TDF, and AB-452+TDF demonstrated a strong antiviral activity with mean 1.4, 1.9, and 2.2 log reductions in serum HBV DNA vs. the vehicle control, respectively, whereas the triple combination effected larger serum HBV DNA reductions, 2.8 log vs. the vehicle control.
Oral Presentation #2646: “Durable Inhibition of Hepatitis B Virus Replication and Antigenemia Using Subcutaneously Administered siRNA
Summary: AB-729 is a next-generation siRNA therapeutic targeted to hepatocytes using our novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology. This is a promising new subcutaneously administered agent, which acts on multiple HBV viral transcripts, enabling inhibition of viral replication and suppression of all viral antigens. AB-729 showed more durable in vivo preclinical activity than earlier-generation siRNA agents for the treatment of chronic HBV infection. In comparison to lipid nanoparticle (LNP)-mediated intravenous delivery, GalNAc-conjugated subcutaneous delivery of the same reference siRNA required a 10-fold greater dose to achieve similar mean maximum inhibition of serum HBsAg in AAV-HBV mice. However, HBsAg suppression in the LNP treatment group had fully resolved by Week 4 whereas the GalNAc treatment group nadir persisted from Week 2 through to Week 6. One dose of AB-729 was sufficient to achieve mean maximum HBsAg reductions of 1.4, 2.8 and 3.9 log10 at 1, 3 and 9 mg/kg, respectively, in AAV-HBV mice with baseline serum HBsAg 3.6 log10 IU/mL. In vivo AB-729 suppression of HBsAg was also highly durable, with 83%, 89% and 99%, respectively, of the mean maximal effect remaining at Week 10 after a single dose.
EASL 2018 presentations are available by visiting the Investor section of Arbutus' website at www.arbutusbio.com and selecting Events and Presentations.
Forward-Looking Statements and Information
This press release contains forward-looking statements within the meaning of the Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). Forward-looking statements in this press release include statements about possible inclusion of AB-506 and AB-452 in future drug combination regimens; further clinical evaluation of our clinical assets, including
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Manager, Investor Relations
Source: Arbutus Biopharma Corporation