Arbutus Biopharma Corporation (Nasdaq: ABUS), an industry-leading
Hepatitis B Virus (HBV) therapeutic solutions company, today
announced preliminary results from a Phase 1a/1b clinical trial in
healthy subjects and two cohorts of chronic hepatitis B (CHB)
subjects who received AB-506 monotherapy. A detailed analysis of
these Phase 1a/1b preliminary results will be submitted for
presentation at a future scientific meeting later this year.
William H. Collier, President and Chief
Executive Officer of Arbutus, stated, “Preliminary results from
this first Phase 1a/1b clinical trial demonstrate that AB-506 is a
potent oral capsid inhibitor. These results also support our
confidence in its potential to contribute to the inhibition of HBV
replication as part of a combination regimen.”
Summary of preliminary results with
AB-506
- No serious adverse events (SAEs) or
clinically significant safety findings were observed in healthy
subjects (N=33). Importantly, ALT levels and other liver function
tests remained normal throughout the 10 days of dosing in healthy
subjects.
- Mean HBV DNA and HBV RNA decreases
at Day 28 (end of treatment) ranged from -2.0 log (160mg dose) to
-2.8 log (400mg dose) and -2.4 log (for both doses), respectively,
comparable with other capsid inhibitors currently in
development.
- No SAEs were observed in CHB
subjects (N= 24).
- Four CHB subjects (two in each of
the cohorts) experienced Grade 4 alanine aminotransferase (ALT)
flares which returned to baseline levels upon AB-506
discontinuation or completion of the 28-day treatment period.
Aspartate aminotransferase (AST) values were also elevated to a
lesser degree, however, none of the subjects met the criteria for
drug induced liver injury (DILI) as bilirubin values and liver
synthetic function remained normal. All four ALT flares occurred
after the subjects experienced a >2 log decline in HBV DNA from
baseline. - We believe at least one of the ALT flare cases was
immune-mediated and beneficial, as one subject in the 400 mg cohort
who experienced a Grade 4 ALT flare also had notable declines in
HBsAg and HBeAg of -1.4 log and -2.0 log, respectively, by Day 100
following AB-506 discontinuation. This subject was
immediately put on nucleoside analog therapy after AB-506
discontinuation per investigator’s decision. In addition,
serum-based cytokine analysis of this subject showed an abrupt
increase in IFN-gamma at the time of the flare, suggesting an
immune-mediated response. For the other 3 subjects we continue to
investigate the nature of the flares.- Of these four subjects, two
(one in each cohort) were asymptomatic, the other two (one in each
cohort) had various mild to moderate AEs at the time of their
flares, one with mild heaviness in head, flatulence, discomfort and
moderate fatigue, one with mild rash (knees, ankles, fingers and
buttock).
- Two subjects in the 160 mg cohort
experienced Grade 2 ALT flares. Both were asymptomatic and returned
to baseline levels upon completing the 28-day treatment
period.
“While ALT flares have occurred with other
capsid inhibitors, thus far none have appeared to be associated
with meaningful declines in HBsAg,” said Dr. Gaston Picchio, Chief
Development Officer of Arbutus Biopharma. “We believe this
could represent the first case of an immune-mediated capsid
inhibitor-induced ALT flare associated with significant and
sustained reductions in both HBsAg and HBeAg.”
Dr. Picchio added, “To date, all capsid
inhibitor studies done in healthy subjects have been limited to a
maximum of 14 days of dosing. In the second half of 2019 we intend
to initiate a healthy subjects study testing 28 days of dosing. An
absence of flares in this study, if observed, should help us better
understand the nature of the ALT flares observed in the CHB
cohorts.”
Next Steps
A detailed analysis of these Phase 1a/1b
preliminary results, including a complete characterization of the
ALT flare cases and preliminary results from the new 28 day study
in healthy subjects, will be submitted for presentation at a
scientific meeting later this year.
About the AB-506 Phase 1a/1b Clinical
Trial
AB-506-001 is a double-blind, randomized,
placebo controlled, single and multiple dose clinical trial
evaluating the safety, tolerability and pharmacokinetics of AB-506,
an oral class II capsid inhibitor, in healthy subjects and HBV-DNA
positive subjects with chronic HBV infection. The healthy subject
portion of the clinical trial and two cohorts of CHB subjects have
been completed. The healthy subject portion consisted of a single
ascending dose (SAD) part in which subjects were randomized 6:2
(active: placebo), n=21, to receive AB-506 doses ranging from
30-1000 mg, including investigation of food effect, and a multiple
dose (MD) part in which subjects (randomized 10:2, n=12) received
400 mg of AB-506 once daily for 10 days. The third part of the
study is enrolling HBV DNA+, HBeAg-positive or -negative CHB
subjects (randomized 10:2; n=12 per cohort) at different doses of
AB-506, with or without a nucleoside analog, once daily for 28
days. Dosing of additional cohorts is
planned.
About AB-506
AB-506 is an oral HBV capsid inhibitor. HBV core
protein assembles into a capsid structure, which is required for
viral replication. The current standard-of-care therapy for HBV,
primarily nucleoside analogues that work by stopping the viral
polymerase, significantly reduce virus replication, but not
completely. Capsid inhibitors inhibit replication by preventing the
assembly of functional viral capsids and also by inhibiting the
uncoating step of the viral life cycle thus reducing the formation
of new covalently closed circular DNA (cccDNA), the viral reservoir
which resides in the cell nucleus.
Conference Call Today
Arbutus will hold a conference call and webcast
today, Monday, July 15, 2019 at 4:45 PM Eastern Time, to discuss
the preliminary Phase 1a/1b clinical trial results for
AB-506. You can access a live webcast of the call through the
Investors section of Arbutus' website at www.arbutusbio.com.
Alternatively, you can dial (866) 393-1607 or (914) 495-8556 and
reference conference ID 8499742.
An archived webcast will be available on the
Arbutus website after the event. Alternatively, you may access a
replay of the conference call by calling (855) 859-2056 or (404)
537-3406, and reference conference ID 8499742.
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 infection. Arbutus is developing
multiple drug candidates, each of which have the potential to
improve upon the standard of care and contribute to a curative
combination regimen. 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 the safety and efficacy of AB-506; the timing and
expectations regarding Arbutus’ ongoing clinical trials; the
potential for AB-506 to contribute to the inhibition of HBV
replication as part of a combination regime; and the potential for
our drug candidates to improve upon the standard of care and
contribute to a curative combination regime.
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 preclinical and clinical trials, and the usefulness
of the data; the availability and timing of data from clinical
trials; and the adequacy of any clinical models. 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; the possibility
that interim data of the Phase 1a/1b clinical trial are not
indicative of final data from all patients in the clinical trial
and final data may not be positive with regard to the safety or
efficacy of AB-506; 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, Quarterly Reports on Form 10-Q and periodic and
continuous disclosure filings, which are available
at 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
InvestorsWilliam H. Collier President and CEO
Phone: 604-419-3200 Email: ir@arbutusbio.com
MediaPam Murphy Investor Relations Consultant
Phone: 604-419-3200 Email: ir@arbutusbio.com
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