Arbutus Biopharma Corporation (Nasdaq: ABUS), a Hepatitis B Virus
(HBV) therapeutic solutions company, today announced positive
preliminary results from a Phase 1a/1b clinical trial (AB-729-001)
in healthy subjects and two cohorts of chronic hepatitis B subjects
on nucleos(t)ide antiviral therapy, all of whom received a single
subcutaneous injection of AB-729. AB-729-001 is an ongoing Phase
1a/1b clinical trial designed to determine the most effective dose
and dosing interval for use in future Phase 2 combination clinical
trials.
William Collier, President and Chief Executive
Officer of Arbutus, stated, “These encouraging preliminary results
demonstrate that AB-729 is a potent RNAi agent capable of reducing
HBsAg plasma levels and support its further development as a
treatment for people living with chronic hepatitis B. Our
plan is to move forward into the multiple dose portion of the
clinical trial with the 60 mg dose and, in parallel, to explore
additional single dose cohorts beginning with the 90 mg dose. We
intend to initiate these cohorts as soon as possible; however, at
this point, it is not possible to predict if the COVID-19 pandemic
will negatively impact our plans and timelines. Provided we can
execute our clinical trials as planned, we continue to expect these
data sets in the second half of the year.”
Mean HBsAg changes from
baseline:
|
60 mg Cohort (N=6) |
180 mg Cohort (N=4) |
Day 29 mean log10 IU/mL (SE) |
-0.24# (0.13) |
-0.81* (0.38) |
Week 12 mean log10 IU/mL (SE) |
NA |
-0.98 (0.22) |
#In the 60 mg cohort, the maximum Day 29 decline
was -0.62 log10. *In the 180 mg cohort, excluding one subject
with a HBsAg decline of -1.94 log10, the mean (SE) reduction for
the remaining 3 subjects was -0.44 log10 (0.07) at Day 29 and -0.77
log10 (0.06) at Week 12.
Dr. Gaston Picchio, Chief Development Officer of
Arbutus, stated, “AB-729 dosed at either 60 mg or 180 mg in chronic
hepatitis B subjects was generally safe and well tolerated and
resulted in meaningful reductions in HBsAg levels. Additionally,
after a single 180 mg dose, HBsAg levels continued to decline well
beyond Week 12, suggesting that AB-729 has the potential to be
dosed less frequently than every four weeks.”
Dr. Picchio added, “The subject receiving the
180 mg dose who experienced the highest HBsAg decline also
experienced a Grade 3 ALT/AST flare. While the flare may have been
related to an acute gastroenteritis and self-medication, we believe
evaluating at least one additional single dose cohort starting at
90 mg is appropriate and should allow us to determine if a mid-dose
would provide the greatest benefit in terms of safety, efficacy and
dosing interval.”
Preliminary safety summary in healthy
subjects
- In the 60 mg, 180 mg and 360 mg
cohorts, no serious adverse events (SAEs) were observed; most
adverse events (AEs) were mild (13/15) and considered unrelated
(12/15) to AB-729.
- Two subjects in the 360 mg cohort
had asymptomatic, reversible Grade 3 ALT elevations assessed as
related to AB-729. Neither subject had meaningful changes in any
other laboratory parameter excepting Grade 1 or 2 AST
elevation.
- There were no other clinically
relevant abnormalities in laboratory tests, ECGs, or vital
signs.
Preliminary safety and efficacy summary
in chronic HBV subjects
- HBsAg declines were observed in all
4 subjects (3 HBeAg negative, 1 HBeAg positive) in the 180 mg
cohort, with a mean HBsAg (SE) log10 reduction of -0.81 (0.38) at
Week 4 and -0.98 (0.22) at Week 12.
- In the 180 mg cohort, maximum HBsAg
decline of -1.94 log10 occurred at Week 4 in one subject (HBeAg
negative). HBsAg declines continued beyond Week 12 for 2/3 subjects
in the 180 mg cohort with available data, exceeding -1.00 log10 in
both subjects. A 4th subject in the 180 mg cohort had continuous
HBsAg decline up to 12 weeks post-dose, with a maximum decline of
-0.73 log10 at Week 12 (the last available time point).
- Mean log10 (SE) HBsAg decline in
the 6 subjects in the 60 mg cohort (all HBeAg negative) was -0.24
(0.13) at Day 29. The maximum HBsAg decline in this cohort was
-0.62 log10 at Day 29. Subjects in the 60 mg cohort will continue
to be followed for twelve weeks. At this time only the four week
data are available for the 60 mg cohort.
- In chronic hepatitis B subjects
administered 180 mg (N=4) or 60 mg (N=6) of AB-729 there were no
SAEs. In the 180 mg cohort, 8 AEs were observed and included
asymptomatic, transient Grade 1 ALT/AST in 1 subject, Grade 1 ALT
only in 1 subject, and 1 subject with Grade 1 ALT /AST at baseline
who experienced unrelated gastroenteritis and self-medicated
associated with transient Grade 3 ALT/AST elevations. In the 60 mg
cohort, 2 AEs were observed, and all subjects had normal ALT/AST
levels.
Summary of clinical trial
design
Study AB-729-001 is an ongoing first-in-human
clinical trial of AB-729 consisting of three parts:
- In Part 1, 3 cohorts of healthy subjects were randomized 4:2 to
receive single doses (60mg, 180mg or 360mg) of AB-729 or
placebo.
- In Part 2, non-cirrhotic, HBeAg positive or negative, chronic
hepatitis B subjects (N=6) currently taking nucleos(t)ide antiviral
therapy with HBV DNA below the limit of quantitation received
single doses (60mg or 180mg) of AB-729. All subjects continued
their nucleos(t)ide antiviral therapy throughout the trial. Part 2
is designed to include dosing of AB-729 in HBV DNA positive chronic
hepatitis B subjects.
- In Part 3, chronic hepatitis B subjects, HBV DNA negative first
and HBV DNA positive later, will receive multiple doses of AB-729
for up to six months.
COVID-19
In December 2019 an outbreak of a novel strain
of coronavirus (COVID-19) was identified in Wuhan, China. This
virus continues to spread globally, has been declared a pandemic by
the World Health Organization and has spread to nearly every
country in the world. The impact of this pandemic has been, and
will likely continue to be, extensive in many aspects of society.
The pandemic has resulted in and will likely continue to result in
significant disruptions to businesses. A number of countries and
other jurisdictions around the world have implemented extreme
measures to try and slow the spread of the virus. These
measures include the closing of businesses and requiring people to
stay in their homes, the latter of which raises uncertainty
regarding the ability to travel to hospitals in order to
participate in clinical trials. Additional measures that have had,
and will likely continue to have, a major impact on clinical
development, at least in the near-term, include shortages and
delays in the supply chain, and prohibitions in certain countries
on enrolling subjects in new clinical trials (e.g. in
Australia). It is not possible to predict if the COVID-19
pandemic will negatively impact our plans and timelines.
About AB-729
AB-729 is a RNA interference (RNAi) therapeutic
targeted to hepatocytes using Arbutus’ novel covalently conjugated
N-acetylgalactosamine (GalNAc) delivery technology that enables
subcutaneous delivery. AB-729 inhibits viral replication and
reduces all HBV antigens, including hepatitis B surface antigen in
preclinical models. Reducing hepatitis B surface antigen is thought
to be a key prerequisite to enable reawakening of a patient’s
immune system to respond to the virus.
Conference Call and Webcast
Today
Arbutus will hold a conference call and live
webcast today, March 26, 2020 at 4:30 PM Eastern Time, to discuss
the preliminary Phase 1a/1b clinical trial results for AB-729. You
can access the live webcast, which will include presentation
slides, through the Investors section of Arbutus' website at
www.arbutusbio.com or directly at Live Webcast.
Alternatively, please dial (866) 393 - 1607 or (914) 495 -
8556 and reference conference ID 2169859.
An archived webcast will be available on the
Arbutus website after the event.
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 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 our expectations regarding the timing and clinical
development of our product candidates, including the evaluation of
multiple dose and additional single-dose cohorts in our Phase 1a/1b
clinical trial for AB-729 during 2020; and the potential for our
drug candidates to improve upon the standard of care and contribute
to a curative combination regimen for chronic HBV.
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 studies and clinical trials, and the
usefulness of the data; the timeliness of regulatory approvals; 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, including uncertainties and
contingencies related to the ongoing COVID-19 pandemic.
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 pre-clinical studies and
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; changes in Arbutus’ strategy regarding its product
candidates and clinical development activities; Arbutus may not
receive the necessary regulatory approvals for the clinical
development of Arbutus’ products; economic and market conditions
may worsen; market shifts may require a change in strategic focus;
and the ongoing COVID-19 pandemic could significantly disrupt our
clinical development programs.
A more complete discussion of the risks and
uncertainties facing Arbutus appears in Arbutus’ Annual Report on
Form 10-K, Arbutus’ Quarterly Reports on Form 10-Q and Arbutus’
continuous and periodic 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
Investors and MediaWilliam H. Collier President
and CEO Phone: 604-419-3200 Email: ir@arbutusbio.com Pam Murphy
Investor Relations Consultant Phone: 604-419-3200 Email:
ir@arbutusbio.com
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