- Favorable safety and tolerability profile-
Superior antiviral activity with ABI-H0731 in combination with
nucleos(t)ide therapies- Selected for inclusion in “Best of ILC”
presentation- Company to host conference call Monday, April 15,
2019 at 8am EDT
Assembly Biosciences, Inc. (NASDAQ: ASMB), a clinical-stage
biotechnology company developing innovative therapeutics targeting
hepatitis B virus (HBV) and diseases associated with the
microbiome, presented interim results from two Phase 2a clinical
trials of ABI-H0731 (731), a novel antiviral in development for the
treatment of chronic HBV infection. The data were presented during
a late-breaker oral session on Saturday, April 13, 2019, at The
International Liver Congress™(ILC), the Annual Meeting of the
European Association for the Study of the Liver (EASL) in Vienna,
Austria. The late-breaker abstract was also selected for inclusion
in the ‘Best of ILC’ presentation as well as for press release
coverage at ILC 2019. A copy of the presentation will be posted to
the Events & Presentations page in the Investors section of the
company's website at assemblybio.com.
“This interim analysis of two Phase 2a studies supports that 731
in combination with nucleos(t)ide therapy (Nucs) demonstrates rapid
and enhanced anti-HBV activity,” said Dr. Jacob Lalezari, of Quest
Clinical Research in San Francisco. “The data we have seen thus far
are directionally correct and decreases in HBeAg and HBsAg have
been observed in some individuals in both studies. The accelerated
decline and significant loss of baseline RNA and DNA viremia
suggest that combination therapy with a core inhibitor + Nuc has
the potential to significantly advance treatments for patients with
HBV.”
“Assembly’s 731 combination interim data demonstrate the
potential of core inhibitors in combinations with Nuc therapy to be
the backbone of HBV cure regimens going forward,” said Derek Small,
President and Chief Executive Officer. “We are encouraged by the
safety, tolerability and initial antiviral activity we’ve seen to
date from the core inhibitor and Nuc combination and look forward
to results throughout the year following longer-term treatment. The
data generated from these studies and the ongoing extension study
will help inform timelines for our future trials and regulatory
proposals regarding registration strategies.”
The oral presentation reviewed interim analyses from two ongoing
double-blind, placebo-controlled Phase 2a studies of 731 in HBV
subjects evaluating the potential benefit of combination with
standard of care (SOC) Nuc therapy. The studies explore the first
two critical steps thought to be necessary for a direct acting
antiviral therapy to achieve higher cure rates, including the
ability to eliminate residual viremia and prevent new viral
replication, and the prevention of new cccDNA generation. Interim
analyses suggest faster and deeper declines in HBV DNA and HBV RNA
are possible with combination therapy.
The ABI-H0731-201 (201) study enrolled 47 HBeAg positive and 26
negative subjects whose viral load was already suppressed on active
Nuc therapy and the ABI-H0731-202 (202) study enrolled 25 treatment
naïve HBeAg positive subjects. The primary efficacy endpoints are
the log10 reduction in HBeAg or HBsAg at week 24 (Study 201) and
the log10 reduction in HBV DNA at weeks 12 and 24 (Study 202).
While 89 subjects have reached the 12 week interim endpoint across
the two studies, few subjects on combination therapy have reached
the 24 week endpoint.
In Study 201, the interim analysis includes 65/73 subjects that
have completed the week 12 assessments and 11 that have completed
week 24. All subjects receiving 731 in combination with a Nuc had
significant reductions in HBV RNA levels compared to the group
receiving Nuc + placebo. Approximately 60% of subjects on
combination therapy with quantifiable RNA at entry demonstrated RNA
decline (below the limit of quantitation (LOQ) 200 copies/mL) by
week 16 compared to 0% on Nuc monotherapy. Additionally, DNA
viremia was persistently detectable at the LOQ in all subjects on
Nuc monotherapy, while several subjects on combination therapy
showed a further reduction in HBV DNA to below the limits of a
highly sensitive PCR assay (2-5 copies). Reduction of residual
viral replication may be a critical milestone for cure and does not
occur on Nuc monotherapy.
Study 201 (Nuc Suppressed HBeAg + Subjects),
Mean Log10 Declines |
Marker |
Week |
Nuc (n) |
731+Nuc (n) |
P values |
RNA |
12 |
0.05 (18) |
2.34 (23) |
<.001 |
24 |
0.15 (4) |
2.20 (6) |
.012 |
Study 201 (Available subjects at week 24), HBV
DNA (+/-) |
DNA, PCR TND* |
24 |
0 (4) |
5 (6) |
N/A |
*Assembly Internal semiquantitative PCR: Limit of quantitation
2-5 IU/mL
In Study 202, 24 treatment-naive subjects have completed week 12
assessments, and 12 have completed week 24. The combination of 731
+ entecavir (ETV) reduced both HBV DNA and HBV RNA significantly
faster and deeper compared to ETV monotherapy as early as week 2.
More subjects with liver inflammation at baseline experienced
improvement on combination therapy.
Study 202 (Tx Naïve HBeAg + Subjects), Mean
Log10 Declines |
Marker |
Week |
ETV (n) |
731+ETV (n) |
P values |
DNA |
12 |
3.29 (12) |
4.54 (12) |
<.011 |
24 |
3.99 (6) |
5.94 (6) |
<.005 |
RNA |
12 |
0.44 (12) |
2.27 (12) |
<.005 |
24 |
0.61 (5) |
2.54 (6) |
<.005 |
Blinded, pooled results across both studies indicate favorable
safety and tolerability for 731 when combined with SOC Nuc therapy.
Adverse events (AEs) were mild, infrequent, and evaluated as
generally unrelated to treatment. There were no treatment related
discontinuations, no serious adverse events and no clinical AEs
greater than Grade 2 observed. Lab abnormalities were mostly Grade
1, transient, and not thought to be related to drug. To date,
across all clinical studies,731 has been dosed in over 150 subjects
and has exhibited a favorable safety profile.
Both studies are ongoing, with subjects receiving treatment
through 24 weeks, and Assembly expects to report final data later
in 2019. At the conclusion of 24 weeks of treatment, all
subjects from both studies will have the opportunity to roll over
to an open label combination (‘731 + Nuc) extended treatment study
for up to an additional year. The data generated over the course of
these studies will help to inform timelines and Assembly’s
registration strategies for its core inhibitors.
About the Phase 2a StudiesABI-H0731-201 is a
Phase 2a “viral antigen” proof-of-concept study that enrolled HBeAg
positive and negative subjects whose viral load was already
suppressed on active Nuc therapy. The enrolled subjects continue
their Nuc therapy and were randomized 3:2 to either placebo or
ABI-H0731 for six months. This study is designed to evaluate the
effectiveness of ABI-H0731 in inhibiting the generation of new
covalently closed circular DNA (cccDNA). Inhibition of new cccDNA
generation is anticipated to occur once HBV DNA and RNA are
eliminated and decay of existing cccDNA should manifest as a
decline in viral antigens HBsAg and HBeAg.
ABI-H0731-202 is a Phase 2a “viral load” study that enrolled
treatment-naïve HBeAg positive subjects and is designed to evaluate
the de novo combination of ABI-H0731 and ETV to ETV monotherapy
alone. This study is designed to assess the antiviral efficacy and
potential benefit of combination therapy by comparing the relative
rates of HBV viral load declines at 12 and 24 weeks.
ABI-H0731-211 is an open label extension study that will allow
subjects in studies 201 and 202 to continue therapy on 731 + SOC
Nuc for up to an additional year.
Conference Call and WebcastAssembly will host a
conference call and live audio webcast on Monday, April 15, 2019 at
8:00am EDT. The live audio webcast can be accessed through the
Events & Presentations page in the Investors section of the
company's website at assemblybio.com. Alternatively, participants
can dial (866) 438-0453 (domestic) or (409) 220-9366
(international) and refer to conference ID 8497467.
The archived webcast will be available on Assembly’s website
beginning approximately two hours after the event and will be
archived and available for replay for at least 30 days after the
event.
About Assembly BiosciencesAssembly
Biosciences, Inc. is a clinical-stage biotechnology company
developing innovative therapeutics targeting hepatitis B virus
(HBV) and diseases associated with the microbiome. The HBV program
is focused on advancing a new class of potent, oral core inhibitors
that have the potential to increase cure rates for chronically
infected patients. The microbiome program is developing novel
oral live synthetic biotherapeutic candidates with Assembly’s fully
integrated platform, including a robust process for strain
identification and selection, GMP banking and production, and
targeted delivery to the lower gastrointestinal tract with the
GEMICEL® technology. For more information,
visit assemblybio.com.
Forward-Looking Statements The information in
this press release contains forward-looking statements regarding
future events, including statements about the clinical and
therapeutic potential of core inhibitors, including ABI-H0731, the
timing of reporting data and the results of nonclinical and
clinical studies being predictive of results in future clinical
studies. Certain forward-looking statements may be identified by
reference to a future period or by use of forward-looking
terminology such as “anticipated,” “expects”, “may” “suggest”,
“will” and “potential.” Assembly intends such forward-looking
statements to be covered by the safe harbor provisions contained in
Section 27A of the Securities Act of 1933, as amended, and Section
21E of the Securities Exchange Act of 1934, as amended. Actual
results or developments may differ materially from those projected
or implied in these forward-looking statements. More information
about the risks and uncertainties faced by Assembly are more fully
detailed under the heading “Risk Factors” in Assembly's Annual
Report on Form 10-K for the year ended December 31, 2018 filed
with the Securities and Exchange Commission. Except as
required by law, Assembly assumes no obligation to update publicly
any forward-looking statements, whether as a result of new
information, future events or otherwise.
Contacts Assembly Biosciences, Inc. Investors:
Lauren Glaser (415) 521-3828 lglaser@assemblybio.com
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