- New Pharmacokinetic and Safety Results from Phase 1a Study of
HBV Core Inhibitor EDP-514, Highlighting Good Safety and
Tolerability, and Pharmacokinetics Suitable for Once Daily
Dosing
- Phase 2a ARGON-1 Study for FXR Agonist EDP-305 Targeting NASH,
Showing Significant Alanine Transaminase and Liver Fat Content
Reduction
- Preclinical Findings for Follow-on FXR Agonist EDP-297
Targeting NASH, Demonstrating Potent Anti-Fibrotic,
Anti-Inflammatory and Hepatoprotective Effects
Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a clinical-stage
biotechnology company dedicated to creating small molecule drugs
for viral infections and liver diseases, announced that data from
Enanta’s wholly-owned development programs for non-alcoholic
steatohepatitis (NASH) and hepatitis B virus (HBV) will be
presented at the European Association for the Study of the Liver
(EASL) Digital International Liver Congress™ 2020.
Data presented include results from the Phase 1a clinical trial
of EDP-514, Enanta’s core inhibitor for HBV. Additionally, Enanta’s
NASH program will be discussed in an oral presentation detailing
the Phase 2a ARGON-1 study of EDP-305, Enanta’s lead Farnesoid X
receptor (FXR) agonist, and two posters highlighting preclinical
data on EDP-297, Enanta’s follow-on FXR agonist.
“We are pleased to share scientific data across multiple
candidates in our pipeline, supporting our chemistry-driven
approach to developing innovative treatments for viral infections
and liver diseases,” stated Jay R. Luly, Ph.D., President and Chief
Executive Officer of Enanta Pharmaceuticals. “The positive results
from our first-in-human Phase 1a study of EDP-514, demonstrating a
strong safety, tolerability and pharmacokinetic profile, gave us
the confidence to advance our HBV program into two ongoing Phase 1b
clinical studies in HBV patients. Additionally, the data presented
for our NASH candidates further demonstrate the potential of both
FXR agonists. EDP-305 shows statistically significant improvements
in liver biochemistry and hepatic steatosis, and our follow-on NASH
candidate EDP-297 demonstrates a potent anti-fibrotic effect.”
August 28, 2020, 12:15 PM - 12:30 PM
CEST
ASO78: “EDP-305, a Non-Bile Acid Farnesoid X Receptor (FXR)
Agonist, Showed Statistically Significant Improvements in Liver
Biochemistry and Hepatic Steatosis in the Phase 2a ARGON-1
Study,” Vlad Ratziu, M.D., Ph.D., France
This oral presentation highlights the final results at week 12
of the randomized, double-blind, placebo-controlled Phase 2a
ARGON-1 trial. The study’s primary endpoint was achieved with a
statistically significant alanine transaminase (ALT) reduction of
28 U/L in the EDP-305 2.5mg arm versus 15 U/L in the placebo arm at
week 12 (p=0.049). There was a statistically significant reduction
in liver fat content with EDP-305 at the 2.5mg dose as measured by
MRI-PDFF (p<0.001). EDP-305 also exhibited strong target
engagement as shown by reductions in C4 and increases in FGF-19 and
alkaline phosphatase (ALP). A robust gamma-glutamyl transferase
(GGT) reduction was also observed. Overall, EDP-305 was generally
safe, with the majority of treatment-emergent adverse events
(TEAEs) being mild to moderate. In this study, mild to moderate
pruritis was more frequent with the 2.5mg dose and there was a
higher frequency of treatment discontinuation compared to the 1mg
dose or placebo. Treatment with EDP-305 was associated with a
modest effect on lipids as demonstrated by a minimal absolute
change of 6 mg/dL, 5 mg/dL, and -4 mg/dL, with the 2.5mg dose, 1mg
dose and placebo, respectively. These data warrant further
development of EDP-305 in a NASH proven liver-biopsy patient
population.
August 28, 2020, 09:30 AM - 19:30 PM
CEST
FRI109: “EDP-297, a Novel and Potent FXR Agonist, Exhibits
Robust Anti-Fibrotic Effects with Significant Liver Function
Improvement in a Rat Model of Non-Alcoholic Steatohepatitis,”
Mozhdeh Sojoodi, Ph.D., United States
Data in this poster demonstrate that treatment with EDP-297
significantly reduced fibrosis progression and improved liver
function measured by key biomarkers in a rat model that closely
resembles the human disease progression of NASH. Rats were
randomized to receive either vehicle control (0.5%
methylcellulose), 0.1 mg/kg EDP-297, or 0.3 mg/kg EDP-297 by
once-daily oral gavage at the first signs of fibrosis (5 weeks, n=8
per group). EDP-297 demonstrated a highly statistically significant
improvement in liver function as measured by a 78.9% reduction
(p<0.001) in ALT, a 73.5% reduction (p<0.001) in aspartate
aminotransferase (AST) and a 75.7% reduction (p<0.001) in total
bilirubin. These results suggest that EDP-297 may have a potent
anti-fibrotic effect in NASH patients, including those with
late-stage F3/4 fibrosis.
August 29, 2020, 09:30 AM - 19:30 PM
CEST
SAT042: “A Novel FXR Agonist EDP-297 Exerts Anti-Inflammatory
and Hepatoprotective Effects in Human Liver 3D Microtissues and
Rodent NASH and Liver Injury Models,” Mary Chau, Ph.D., United
States
Data in this poster highlight the pharmacologic activity of
EDP-297 as evaluated in multiple in vitro assays and further
characterized in a human liver 3D microtissue system and in rodent
models of NASH and liver injury. In 3D NASH microtissues, EDP-297
modulated multiple pathways associated with the pathogenesis of
NASH. Specifically, decreased expression of genes encoding multiple
lipogenic and inflammatory proteins was observed. EDP-297 treated
rats with bile duct ligation showed significantly reduced
expression of inflammatory and fibrotic genes and normalized
circulating markers of liver injury, including ALT (76% reduction,
p<0.001), AST (83% reduction, p<0.001) and GGT (76%
reduction, p<0.001). Histological analysis confirmed the
hepatoprotective effects of EDP-297 with reduced immune cell
infiltration and necrosis. EDP-297 was shown to be hepatoprotective
in a diet-induced obese NASH model in mice.
August 29, 2020, 09:30 AM - 19:30 PM
CEST
SAT440: “EDP-514, a Novel Pangenotypic Class II Hepatitis B
Virus Core Inhibitor: Final Results of a Phase 1 Study in Healthy
Adult Subjects,” Kajal Larson, Ph.D., United States
Data in this poster present the safety and pharmacokinetic
results of single ascending doses and multiple ascending doses of
EDP-514 in a first-in-human, Phase 1 study. EDP-514 was rapidly
absorbed and its exposure increased with escalating single and
multiple dosing of 600 mg and 400 mg, respectively. EDP-514 was
generally safe and well-tolerated over a broad range of single and
multiple doses for up to 14 days, with all TEAEs being of mild
severity. There were no severe or serious TEAEs and no
discontinuations due to adverse events. Further, there were no
significant individual lab data findings or pattern of lab
abnormalities. EDP-514 exhibited pharmacokinetics suitable for once
daily oral dosing. Following multiple dosing with EDP-514 when
administered with and without a standard meal, the geometric mean
plasma concentration at 24 hours (C24) was several fold higher than
the in vitro serum protein adjusted EC50 (paEC50) of 71 ng/mL under
fasted conditions (5.8- to 9.3-fold) and fed conditions (standard
meal, 22.1-fold), suggesting that EDP-514 can be administered
without regard to meals.
EDP-514 is currently being studied in two ongoing Phase 1b
clinical studies, in viremic HBV patients, and in HBV patients
treated with a nucleos(t)ide reverse transcriptase inhibitor
(NUC-suppressed patients). Enanta anticipates reporting preliminary
safety and virologic data from the viremic study in the first half
of 2021, and preliminary data in NUC-suppressed patients in the
second quarter of 2021.
The full scientific program for The Digital International Liver
Congress 2020, as well as the abstracts, can be found at
https://ilc-congress.eu/programme-digital-ilc-2020/.
About Enanta
Enanta is using its robust, chemistry-driven approach and drug
discovery capabilities to become a leader in the discovery and
development of small molecule drugs for the treatment of viral
infections and liver diseases. Enanta’s research and development
efforts have produced clinical candidates for the following disease
targets: respiratory syncytial virus (RSV), non-alcoholic
steatohepatitis (NASH) and hepatitis B virus (HBV). Enanta is also
conducting research in human metapneumovirus (hMPV) and SARS-CoV-2
(COVID-19).
Enanta’s research and development activities are funded by
royalties from hepatitis C virus (HCV) products developed under its
collaboration with AbbVie. Glecaprevir, a protease inhibitor
discovered by Enanta, is sold by AbbVie in numerous countries as
part of its leading treatment for chronic HCV infection under the
tradenames MAVYRET® (U.S.) and MAVIRET® (ex-U.S.)
(glecaprevir/pibrentasvir). Please visit www.enanta.com for more
information.
Forward Looking Statements Disclaimer
This press release contains forward-looking statements,
including statements with respect to the prospects for further
developments with respect to EDP-305 and EDP-297 for NASH and
EDP-514 for HBV. Statements that are not historical facts are based
on management’s current expectations, estimates, forecasts and
projections about Enanta’s business and the industry in which it
operates and management’s beliefs and assumptions. The statements
contained in this release are not guarantees of future performance
and involve certain risks, uncertainties and assumptions, which are
difficult to predict. Therefore, actual outcomes and results may
differ materially from what is expressed in such forward-looking
statements. Important factors and risks that may affect actual
results include: the development risks of early stage discovery
efforts in the disease areas in Enanta’s research and development
pipeline, such as NASH and HBV; the impact of development,
regulatory and marketing efforts of others with respect to
competitive treatments for NASH and HBV; Enanta’s limited clinical
development experience; Enanta’s need to attract and retain senior
management and key scientific personnel; Enanta’s need to obtain
and maintain patent protection for its product candidates and avoid
potential infringement of the intellectual property rights of
others; and other risk factors described or referred to in “Risk
Factors” in Enanta’s most recent Form 10-Q for the quarter ended
June 30, 2020 and other periodic reports filed more recently with
the Securities and Exchange Commission. Enanta cautions investors
not to place undue reliance on the forward-looking statements
contained in this release. These statements speak only as of the
date of this release, and Enanta undertakes no obligation to update
or revise these statements, except as may be required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20200828005048/en/
Investor Jennifer Viera 617-744-3848
jviera@enanta.com
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