Assembly Biosciences, Inc. (Nasdaq: ASMB), a clinical-stage
biotechnology company developing innovative, investigational
therapeutics targeting hepatitis B virus (HBV) and other viral
diseases, today announced promising interim efficacy, safety and
pharmacokinetic (PK) results from two ongoing clinical studies of
its investigational next-generation HBV core inhibitors, a Phase 1b
clinical study of ABI-H3733 (3733) and a Phase 1a clinical study of
ABI-4334 (4334).
“We are excited to see that these interim results from ongoing
Phase 1 studies of our next-generation core inhibitors 3733 and
4334 are exceeding our expectations for key elements of the
clinical profile we’re looking for to impact chronic HBV
infection,” said John McHutchison, AO, MD, chief executive officer
of Assembly Bio.
Assembly Bio specifically designed 3733 and 4334 to optimize
potency against both new virus production (first mechanism) and
formation of covalently closed circular DNA (cccDNA), the viral
reservoir (second mechanism). Both compounds have demonstrated
significantly increased potency preclinically against both
mechanisms compared to first-generation core inhibitors. This
increased potency, particularly against cccDNA formation, is
critical to Assembly Bio’s HBV strategy to bring finite therapies
and cures for those living with chronic HBV (cHBV) infection.
“In this first look at antiviral activity for 3733 in the Phase
1b study, we are seeing steep declines in HBV DNA at the low
starting dose of 50 mg,” continued Dr. McHutchison. “The antiviral
activity from this cohort against the first mechanism surpasses
both what we demonstrated preclinically for 3733 as well as what we
saw clinically in similar time frames with our first-generation
core inhibitors at much higher doses. We are also highly encouraged
by the initial pharmacokinetic data from our first-in-human
clinical study of our most potent core inhibitor, 4334, which show
the potential to reach high levels of activity against both
mechanisms clinically at a low dose.”
Jason Okazaki, president and chief operating officer and
CEO-elect of Assembly Bio, concluded, “With 100 mg cohorts of both
3733 (28-day dosing) and 4334 (single dose) underway, we are eager
to see and share data in early 2023 that we anticipate will drive
the optimal dose selection to maximize activity against both
mechanisms of action. While early, we believe the interim results
in both studies are an encouraging indication that the preclinical
potency documented for our next-generation core inhibitors against
the second mechanism of cccDNA formation will translate into the
clinic with longer-term dosing.”
Complete results of these clinical trials, when available,
together with ongoing nonclinical and chronic toxicity studies,
will inform future clinical development planning for Assembly Bio’s
next-generation core inhibitor programs.
Phase 1b Study for 3733 – Study
ABI-H3733-102
The ongoing Phase 1b clinical trial is a randomized,
multi-center, double-blind and placebo-controlled study evaluating
the safety, PK and antiviral activity of 3733, including changes in
HBV DNA and other viral parameters associated with 3733 treatment
in adults with cHBV infection who are treatment naïve or off
treatment. Patients were randomized 8:2 between the new tablet
formulation of 3733 and placebo for a period of 28 days. The
patient population for the data included here consists primarily of
e-antigen negative patients. The study remains externally blinded,
so individual patient data are not provided.
The dose selected for the first cohort was 50 mg. Given the
potent antiviral activity observed at 50 mg, a 25 mg dose was
selected for the second cohort to further explore the dose response
curve of 3733. A dose of 100 mg has been selected for the third
cohort, for which dosing is ongoing with initial data anticipated
in the first quarter of 2023.
50 mg Cohort Efficacy (Viral Nucleic Acids):
As of the data cutoff date of December 18, 2022, dosing in the
3733 Phase 1b trial has been completed for all 10 patients in the
first cohort of 50 mg. Nine of 10 patients enrolled were HBeAg
negative, so efficacy data are provided for these patients. Interim
efficacy results from this cohort at the data cutoff date include
HBV DNA, HBV RNA and antigen measurements for all patients for the
full 28-day dosing period.
In the 50 mg cohort, six of eight patients receiving 3733
achieved HBV DNA less than the lower limit of quantification
(<LLOQ) within 21 days, with a mean decline in HBV DNA over the
treatment period of approximately 3.1 logs. Data on HBV RNA
declines were limited due to low baseline levels in predominantly
e-antigen negative patients.
25 mg Cohort Efficacy (Viral Nucleic Acids):
The second cohort, evaluating a dose of 25 mg, is fully
enrolled. Nine of 10 patients enrolled were HBeAg negative, so
efficacy data are provided for these patients. In the five patients
that have so far completed 28 days of treatment, the mean reduction
in HBV DNA was approximately 1.9 logs. Data on HBV RNA levels were
not available as of the data cutoff date.
50 and 25 mg Cohorts (Safety, PK and Viral Antigens):
Safety data reported here reflect data received for both cohorts
through the data cutoff date. In these initial cohorts, all
treatment-emergent adverse events (AEs) and laboratory
abnormalities reported were Grade 1 or Grade 2. Further, no AEs led
to treatment discontinuation, and no clinically significant ECG
abnormalities or patterns of AEs or lab abnormalities were
noted.
The observed PK for the new tablet formulation of 3733 was
consistent with predictions from preclinical studies, providing
exposure equivalent to the liquid formulation evaluated in the
Phase 1a study for 3733. Clinical PK exposures exhibited
dose-proportional increases from 25 mg to 50 mg, as measured by
maximum concentration (Cmax) and area-under-curve (AUC).
As expected given the 28-day dosing period, limited changes in
viral antigens were observed in both the 50 mg and 25 mg
cohorts.
Phase 1a Study for 4334 – Study
ABI-4334-101
The Phase 1a clinical trial is a randomized, blinded and
placebo-controlled study evaluating the safety, tolerability and PK
of 4334 following single ascending dose and multiple ascending dose
administration in healthy subjects. The objectives of the study
include assessment of the proportion of subjects with AEs,
premature treatment discontinuation due to AEs and abnormal
laboratory results.
Dosing has completed for all eight subjects in the initial 30 mg
single dose cohort. In this cohort, 4334 had a mean half-life of 24
hours, supporting once-a-day (QD) dosing. Based on the PK data from
this initial cohort and preclinical studies, daily minimum plasma
trough concentrations (Cmin) are projected to achieve double-digit
multiples of the protein-adjusted EC50 for both antiviral activity
and against cccDNA formation at a low dose of 4334.
In this initial cohort, treatment-emergent AEs and laboratory
abnormalities were mild to moderate and all were considered not
related to study treatment. There were no clinically significant
ECG abnormalities or patterns of AEs or laboratory abnormalities
noted.
A dose of 100 mg has been selected for the second single-dose
cohort. Dosing for the second cohort is complete and initial data
from this cohort are anticipated in the first quarter of 2023.
About Assembly BiosciencesAssembly Bio is
a clinical-stage biotechnology company pioneering the development
of novel therapeutics for serious viral diseases. Assembly Bio is
advancing a leading portfolio of more potent, next-generation core
inhibitor drug candidates that aim to break the complex viral
replication cycle of hepatitis B virus (HBV) to achieve finite and
potentially curative therapies for the 296 million people living
with HBV worldwide. The company’s research pipeline includes
differentiated antiviral approaches against HBV/hepatitis delta
virus and herpesviruses. 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 successfully execute its
previously announced reprioritization and restructuring activities,
including the CEO transition; potential adverse legal,
reputational, operational and financial effects on Assembly Bio
resulting from the reprioritization and restructuring activities;
Assembly Bio’s ability to initiate and complete clinical studies
involving its therapeutic product candidates, including studies
contemplated by Assembly Bio’s collaboration agreements, 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; results of nonclinical
studies may not be representative of disease behavior in a clinical
setting and may not be predictive of the outcomes of clinical
studies; continued development and commercialization of ABI-H3733,
if successful, in the China territory will be dependent on, and
subject to, Assembly Bio’s collaboration agreement governing this
activity in the China territory; Assembly Bio’s ability to maintain
financial resources necessary to continue its clinical studies and
fund business operations; any impact that the COVID-19 pandemic may
have on Assembly Bio’s business and operations, including
initiation, enrollment and continuation of its clinical studies 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.
ContactsInvestor and
Corporate:Shannon RyanSVP, Investor Relations, Corporate
Affairs and Alliance Management(415)
738-2992sryan@assemblybio.com
Media:Sam Brown Inc. Hannah
Hurdle (805) 338-4752 ASMBMedia@sambrown.com
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