Assembly Biosciences, Inc. (Nasdaq: ASMB), a clinical-stage
biotechnology company developing innovative therapeutics targeting
hepatitis B virus (HBV) and diseases associated with the
microbiome, provided an update on the ongoing open-label Phase 2
extension study (Study 211) of vebicorvir (VBR, or ABI-H0731) in
patients with chronic HBV infection. A first of its kind, Study 211
is exploring whether sustained virologic response (SVR) could be
achieved after discontinuing therapy in virologically-suppressed
patients who had received at least 12-18 months of combination
treatment with core inhibitor VBR and a nucleos(t)ide analogue
reverse transcriptase inhibitor (NrtI). Study patients who met the
treatment stopping criteria discontinued therapy and have been
assessed monthly for safety and relapse. The study has not achieved
meaningful SVR rates as 39 of 41 patients have now relapsed.
Among the patients who have discontinued treatment, 22 of the 23
with HBeAg negative HBV have relapsed (SVR = 4% at last visit),
defined as off-treatment quantifiable HBV DNA by the COBAS TaqMan
(2.0) assay (lower limit of quantification = 20 IU/mL). Sixteen of
these patients relapsed at post-treatment Week 4, three at
post-treatment Week 12, and three patients at post-treatment
Week 16. Among the HBeAg positive patients, 17 of 18
relapsed at post-treatment Week 4 (SVR = 6% at last visit).
Assembly Bio continues to collect and analyze study data and
intends to submit more detailed findings to a future medical
meeting.
Study 211 Interim Off-Treatment
Virologic Results
Number of patients |
Discontinued treatment with VBR+NrtI |
Relapsed at post-treatment Week 4 |
Relapsed at post-treatment Week 8 |
Relapsed at post-treatment Week 12 |
Relapsed at post-treatment Week 16 |
Have not relapsed* |
HBeAg negative |
23 |
16 |
0 |
3 |
3 |
1 |
HBeAg positive |
18 |
17 |
0 |
0 |
0 |
1 |
*These 2 patients have completed the post-treatment Week 8
visit
John McHutchison, AO, MD, Chief Executive Officer and President
of Assembly Biosciences, stated, “With the addition of our
first-generation core inhibitor, vebicorvir, to NrtI, we were able
to drive viral suppression deeper in patients with chronic HBV
infection to levels below the limits of our highly sensitive assays
for six months or more. Patients like these normally face a
lifetime of therapy, so we took the pioneering step to test whether
their virologic response could be sustained off treatment. As we
had previously indicated, we believe an SVR24 rate of at least 15%
would have marked a meaningful first advance in HBV finite therapy,
but preliminary results have shown that we will fall short of that
mark. While we are just beginning to analyze the data and this is
not the outcome we were hoping for, we firmly believe it was the
right experiment to conduct, and the learnings will inform the
field and our ongoing development programs.”
Dr. McHutchison continued, “We remain committed to driving the
field of HBV therapeutics forward, and have made additional
progress toward initiating a Phase 3 registrational program of
vebicorvir with BeiGene focused on chronic suppressive therapy in
China, home to one-third of the world’s individuals living with
chronic HBV infection. This Phase 3 program will include a
population representing the 10-30% of HBV patients who only achieve
partial viral suppression after a year or more on NrtI therapy, a
group that has limited treatment options today. In parallel, we
continue to advance our second and third core inhibitor candidates,
which are substantially more potent than vebicorvir against the
generation of cccDNA and have shown a more favorable resistance
profile. Enrollment and dosing are underway in the Phase 2 trial of
ABI-H2158 in patients with chronic HBV infection and the Phase 1
study of ABI-H3733 in healthy volunteers. Additionally, in the
first half of 2021 we plan to begin triple combination Phase 2
trials combining VBR’s core inhibitor mechanism with NrtI and an
RNAi therapeutic from Arbutus and, separately, with
interferon.”
Assembly Bio’s Phase 2 trials, Study 201 and 202, demonstrated
that the addition of VBR to NrtI therapy achieved a more rapid and
deeper level of viral suppression than seen with NrtI alone and
with a similar safety and tolerability profile. Based on these
data, Assembly Bio has reached agreement with the Chinese
regulatory body, National Medical Products Administration, Center
for Drug Evaluation, and continues discussions with the U.S. Food
and Drug Administration, on a Phase 3 registrational program for
VBR plus NrtI as a chronic suppressive therapy (CST) for certain
patient populations with chronic HBV infection. The Company expects
to initiate Phase 3 CST trials in the first half of 2021 in
collaboration with BeiGene for the partnered China territory as
part of the global registration program.
Assembly Bio also continues to advance ABI-H2158 (2158) and
ABI-H3733 (3733), which have demonstrated in preclinical studies
10-fold and 40- to 50-fold higher potency, respectively, than VBR
in inhibiting the formation of new cccDNA. A multi-center,
randomized, placebo-controlled Phase 2 trial is evaluating 2158
with entecavir versus placebo with entecavir in treatment naïve
HBeAg positive patients with chronic HBV infection. Additionally, a
Phase 1 trial of 3733 is evaluating safety, tolerability, and
pharmacokinetics following single ascending dose and multiple
ascending dose administrations in healthy subjects.
During the first half of 2021, Assembly Bio also intends to
initiate a Phase 2 trial to evaluate the triple combination of VBR,
Arbutus Biopharma’s RNAi therapeutic AB-729 and NrtI in patients
with chronic HBV infection. Combining multi-drug regimens with
non-overlapping mechanisms has the potential to generate higher
response rates in certain HBV patient populations and potentially
shorten their duration of treatment. The Company also anticipates
initiating a triple combination study in the first half of 2021 to
evaluate the addition of interferon to VBR and NrtI.
Assembly Bio’s Webcast
and Conference
CallAssembly Bio will host a webcast and
conference call today at 2:00 p.m. PT / 5:00 p.m. ET. The live
audio webcast may be accessed through the “Events &
Presentations” page in the “Investors” section of Assembly Bio’s
website at https://investor.assemblybio.com/events-presentations.
Alternatively, participants may dial (866) 438-0453 (domestic) or
(409) 220-9366 (international) and refer to conference ID 5739584.
Call participants are encouraged to connect at 1:45 p.m. PT / 4:45
p.m. ET to ensure a timely connection to the call or to utilize the
webcast link for listen-only access.
The archived webcast will be available on Assembly Bio’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 Biosciences’ HBV Core Inhibitor
PortfolioAssembly Bio’s HBV portfolio includes three
clinical-stage small molecule candidates, all of which are HBV core
inhibitors that target multiple steps of the HBV replication cycle.
In Phase 2 clinical trials, first-generation core inhibitor
vebicorvir (VBR, or ABI-H0731) administered with nucleos(t)ide
analogue reverse transcriptase inhibitor (NrtI) therapy has been
well-tolerated, has shown statistically superior antiviral activity
in HBV DNA suppression compared to NrtI therapy alone, and has
demonstrated significant declines in HBV pgRNA that may indicate
decreased cccDNA levels.
Assembly Bio’s HBV portfolio also includes two, more potent core
inhibitor candidates, ABI-H2158 (2158) and ABI-H3733 (3733), which
have demonstrated in preclinical studies 10-fold and 40- to 50-fold
higher potency, respectively, than VBR in inhibiting the formation
of new cccDNA. 2158 is in Phase 2 development, and 3733 is in Phase
1 development.
Vebicorvir and 2158 both have been granted Fast Track
designation by the U.S. Food and Drug Administration for
the treatment of chronic HBV infection.
About HBVChronic hepatitis B virus (HBV)
infection is a debilitating disease of the liver that afflicts over
250 million people worldwide with up to 90 million people
in China, as estimated by the World Health Organization.
HBV is a global epidemic that affects more people than hepatitis C
virus (HCV) and HIV infection combined—with a higher morbidity and
mortality rate. HBV is a leading cause of chronic liver disease and
need for liver transplantation, and up to one million people
worldwide die every year from HBV-related causes.
The current standard of care for patients with chronic HBV
infection is life-long suppressive treatment with medications that
reduce, but do not eliminate viral replication, resulting in very
low cure rates. There is a significant unmet need for new therapies
to treat HBV.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 microbial
biotherapeutic candidates with Assembly Bio’s fully integrated
platform, including a robust process for strain identification and
selection, GMP manufacturing expertise and targeted delivery to the
lower gastrointestinal tract with the GEMICEL® technology. For more
information, visit assemblybio.com.
Forward-Looking StatementsThe information in
this press release contains forward-looking statements that are
subject to certain risks and uncertainties that could cause actual
results to materially differ. These risks and uncertainties
include: Assembly Bio’s ability to initiate and complete
clinical trials involving its HBV therapeutic product candidates in
the currently anticipated timeframes; safety and efficacy data from
clinical studies may not warrant further development of Assembly
Bio’s product candidates; clinical and nonclinical data presented
at conferences may not differentiate Assembly Bio’s product
candidates from other companies’ candidates; Assembly Bio may not
observe sustained virologic response in patients who stop
therapy in Study 211; Assembly Bio’s ability to maintain financial
resources necessary to continue its clinical trials and fund
business operations; any impact that the spread of the coronavirus
and resulting COVID-19 pandemic may have on Assembly Bio’s business
and operations, including initiation and continuation of its
clinical trials or timing of discussions with regulatory
authorities; and other risks identified from time to time in
Assembly Bio’s reports filed with the U.S. Securities and
Exchange Commission (the SEC). You are urged to consider
statements that include the words may, will, would, could, should,
might, believes, hopes, estimates, projects, potential, expects,
plans, anticipates, intends, continues, forecast, designed, goal or
the negative of those words or other comparable words to be
uncertain and forward-looking. Assembly Bio 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. More information about Assembly Bio’s risks and
uncertainties are more fully detailed under the heading “Risk
Factors” in Assembly Bio’s filings with the SEC, including its
most recent Annual Report on Form 10-K, Quarterly Reports on Form
10-Q and Current Reports on Form 8-K. Except as required by law,
Assembly Bio assumes no obligation to update publicly any
forward-looking statements, whether as a result of new information,
future events or otherwise.
ContactsAssembly Biosciences, Inc.Lauren
GlaserSenior Vice President, Investor Relations and Corporate
Affairs(415) 521-3828lglaser@assemblybio.com
Media ContactSam Brown Inc. Audra Friis (917) 519-9577
ASMBMedia@sambrown.com
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