Capsid inhibitor with HBV RNA Destabilizer
Demonstrate Complementary Efficacy ResultsSubcutaneous RNAi Agent
Demonstrates Durable HBsAg Reduction Following a Single Dose
Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading
Hepatitis B Virus (HBV) therapeutic solutions company, today made
two presentations supporting our drug combination approach at the
53rd Annual International Liver Congress of the European
Association for the Study of the Liver (EASL) in Paris, France.
"Data presented at EASL 2018 is an endorsement
of our combination strategy and the breadth and quality of our
therapeutic candidates,” said Dr. Mark J. Murray, Arbutus'
President and CEO. “Our next-generation capsid inhibitor AB-506 and
novel HBV RNA destabilizer AB-452 were studied in combination with
our LNP RNAi (siRNA) candidate ARB-1467 and approved HBV therapies.
In these studies, AB-506 and AB-452 exhibited distinct but
complementary antiviral activities, supportive of inclusion in
clinical combination regimens. Separately, compared to earlier RNAi
therapies for HBV, more durable antiviral activity was achieved in
vivo with AB-729, our GalNAc-enabled, subcutaneously delivered,
RNAi candidate. In totality, these data support further clinical
evaluation of our promising new agents and development of a
proprietary drug combination for treatment of chronic HBV.”
Presentations Include:
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 Arbutus Biopharma
- When combined, our capsid inhibitor AB-506 and HBV RNA
destabilizer AB-452 show distinct but
mechanistically compatible antiviral activities that suggest
feasibility of inclusion in a clinical combination
regimen.
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. All AB-506 and AB-452 treated groups demonstrated
reductions in liver HBV DNA, with negligible reduction observed
with TDF alone. Serum HBsAg reduction was detected in AB-452
treated groups, and when combined with AB-506 and/or TDF there was
no adverse effect on the ability of AB-452 to reduce HBsAg. These
preclinical investigations suggest that these agents when combined
have distinct but mechanistically compatible antiviral activities
and may feasibly be used in future combination therapeutic
regimens.
Oral Presentation #2646:
“Durable Inhibition of Hepatitis B Virus Replication and
Antigenemia Using Subcutaneously Administered siRNA Agent AB-729 in
Preclinical Models” by Amy Lee, Senior Director, Research
at Arbutus Biopharma
- GalNAc siRNA offers the potential for subcutaneous
delivery of siRNA therapies and showed more durable in vivo
preclinical activity compared to earlier-generation siRNA agents
for HBV.
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.
Presentations
EASL 2018 presentations are available by
visiting the Investor section of Arbutus' website at
www.arbutusbio.com and selecting Events and Presentations.
About Arbutus
Arbutus Biopharma Corporation is a publicly
traded (Nasdaq:ABUS) biopharmaceutical company dedicated to
discovering, developing, and commercializing a cure for patients
suffering from chronic Hepatitis B (HBV) infection. Arbutus is
developing multiple drug candidates, each of which have the
potential to improve upon the standard of care (SOC) and contribute
to a curative combination regimen to improve patient outcomes and
deliver a potential cure for HBV. For more information, visit
www.arbutusbio.com.
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 AB-506, AB-452 and AB-729, and eventual testing
of a proprietary combination; the potential for subcutaneous
delivery of siRNA therapies; and discovering, developing, and
commercializing a cure for patients suffering from chronic HBV
infection.
With respect to the forward-looking statements
contained in this press release, Arbutus has made numerous
assumptions regarding, among other things: the effectiveness and
timeliness of clinical trials, and the usefulness of the data; the
continued demand for Arbutus’ assets; and the stability of economic
and market conditions. While Arbutus considers these assumptions to
be reasonable, these assumptions are inherently subject to
significant business, economic, competitive, market and social
uncertainties and contingencies.
Additionally, there are known and unknown risk
factors which could cause Arbutus' actual results, performance or
achievements to be materially different from any future results,
performance or achievements expressed or implied by the
forward-looking statements contained herein. Known risk factors
include, among others: anticipated clinical trials may be more
costly or take longer to complete than anticipated, and may never
be initiated or completed, or may not generate results that warrant
future development of the tested drug candidate; Arbutus may not
receive the necessary regulatory approvals for the clinical
development of Arbutus' products; economic and market conditions
may worsen; and market shifts may require a change in strategic
focus.
A more complete discussion of the risks and
uncertainties facing Arbutus appears in Arbutus' Annual Report on
Form 10-K and Arbutus' continuous disclosure filings, which are
available at http://www.sedar.com and at www.sec.gov. All
forward-looking statements herein are qualified in their entirety
by this cautionary statement, and Arbutus disclaims any obligation
to revise or update any such forward-looking statements or to
publicly announce the result of any revisions to any of the
forward-looking statements contained herein to reflect future
results, events or developments, except as required by law.
Contact Information
InvestorsTiffany TolmieManager, Investor
RelationsPhone: 604-419-3200Email: ttolmie@arbutusbio.com
MediaDavid SchullRusso PartnersPhone:
858-717-2310Email: david.schull@russopartnersllc.com
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