-- One-time Administration of
AMT-130 Demonstrates for the First Time Efficacy in Large Animal
Model
-- Strong Dose-Dependent Reduction
of Mutant Huntingtin Protein and Widespread Vector Distribution in
Brain
-- IND-enabling Toxicology Study to
Commence in 2H 2017 --
LEXINGTON, Mass. and AMSTERDAM,
the Netherlands, April 26, 2017 (GLOBE NEWSWIRE) -- uniQure
N.V. (NASDAQ:QURE), a leading gene therapy company advancing
transformative therapies for patients with severe medical needs,
today presented new preclinical data on AMT-130, a gene therapy
candidate for the treatment of Huntington's disease (HD),
at the 12th Annual CHDI HD Therapeutics Conference in Malta.
Data from the study demonstrate
widespread and effective AAV5 vector distribution and extensive
silencing of the human mutant huntingtin gene (HTT) in minipigs,
among the largest HD animal models available for testing. AMT-130
consists of an AAV5 vector carrying a DNA cassette encoding
artificial micro-RNA (miHTT) that silences the huntingtin gene. The
proof-of-concept study was performed by uniQure in collaboration
with Prof. Jan Motlik, Director of the Institute of Animal
Physiology and Genetics in the Czech Republic and Ralf Reilmann,
Founding Director of the George Huntington Institute in
Germany.
"Using AAV vectors to deliver
micro-RNAs directly to the brain represents a highly innovative
approach to treating Huntington's disease," stated Prof. Motlik.
"This study demonstrated that a single administration of AAV5-miHTT
resulted in significant reductions in HTT mRNA in all regions of
the brain transduced by AMT-130, as well as in the cortex.
Consistent with the reduction in HTT mRNA, we also observed a clear
dose-dependent reduction in mutant huntingtin protein levels in the
brain, with similar trends in the cerebral spinal fluid. Taking
into account the similarities of CHDI's proprietary transgenic pig
model to the human brain, these results provide additional data to
support moving forward with clinical trials of uniQure's promising
gene therapy for Huntington's disease."
Preclinical Data Findings
Researchers in the study
investigated the feasibility, efficacy and safety of AMT-130 in
diseased animals with a larger brain size using a transgenic HD
minipig model developed by Prof. Motlik and supported by the CHDI
Foundation. AMT-130 was administered bilaterally into the striatum
and thalamus of the minipigs using convection-enhanced, real-time
MRI-guided delivery.
Three months after treatment,
widespread, dose-dependent distribution of the vector was observed
throughout the minipig brain that corresponded strongly with the
miHTT expression. Expression of mutant HTT mRNA was significantly
reduced in all regions of the brain transduced by AMT-130 by 50% to
80%, as well in the cortex by up to 40%, compared with control.
Researchers also observed a dose-dependent reduction in mutant
huntingtin protein levels of more than 50% in the brain, as well as
similar trends in cerebral spinal fluid. Both the surgical
procedure and AAV5-miHTT treatment were well tolerated with no
adverse events.
"This study is an important step
in our Huntington's disease gene therapy program, demonstrating for
the first time in a large animal model that AAV5 can be used safely
and effectively to deliver micro-RNAs to silence mutant
huntingtin," stated Pavlina Konstantinova, Ph.D., director of new
therapeutic target discovery at uniQure. "We are very
encouraged by the significant reductions in mutant huntingtin
protein, and believe that knock-down of this magnitude has the
potential to significantly alter the course of the disease. The
positive data from this study, together with data from our previous
studies in rodent models showing strong reductions in huntingtin
and prevention of neuronal dysfunction, provide strong proof of
concept for AMT-130 as a potential groundbreaking treatment for
patients suffering from Huntington's disease. We look forward to
commencing the toxicology study in non-human primates later this
year, which we expect to support an Investigational New Drug (IND)
application for AMT-130 in 2018."
About
Huntington's Disease
Huntington's disease is a rare, inherited neurodegenerative
disorder that leads to loss of muscle coordination, behavioral
abnormalities and cognitive decline, resulting in complete physical
and mental deterioration over a 12- to 15-year period of time. The
disease is caused by an autosomal dominant mutation, a
cytosine-adenine-guanine (CAG) expansion, in the first exon of the
huntingtin gene leading to a non-functional, aggregation prone
mutated protein. Despite the clear etiology, there are no therapies
available to treat the disease, delay onset or slow progression of
a patient's decline.
About
uniQure
uniQure is delivering on the promise of gene therapy - single
treatments with potentially curative results. We are leveraging our
modular and validated technology platform to rapidly advance a
pipeline of proprietary and partnered gene therapies to treat
patients with hemophilia, Huntington's disease and cardiovascular
diseases. www.uniQure.com
uniQure
Forward-Looking Statements
This press release contains forward-looking
statements. All statements other than statements of historical fact
are forward-looking statements, which are often indicated by terms
such as "anticipate," "believe," "could," "estimate," "expect,"
"goal," "intend," "look forward to," "may," "plan," "potential,"
"predict," "project," "should," "will," "would" and similar
expressions. Forward-looking statements are based on management's
beliefs and assumptions and on information available to management
only as of the date of this press release. These forward-looking
statements include, but are not limited to, statements regarding
the winding down of our Glybera program, the development of our
other gene therapy product candidates, the success of our
collaborations and the risk of cessation, delay or lack of success
of any of our ongoing or planned clinical studies and/or
development of our product candidates. Our actual results could
differ materially from those anticipated in these forward-looking
statements for many reasons, including, without limitation, risks
associated with corporate reorganizations and strategic shifts,
collaboration arrangements, our and our collaborators' clinical
development activities, regulatory oversight, product
commercialization and intellectual property claims, as well as the
risks, uncertainties and other factors described under the heading
"Risk Factors" in uniQure's 2016 Annual Report on Form 10-K filed
on March 15, 2017. Given these risks, uncertainties and other
factors, you should not place undue reliance on these
forward-looking statements, and we assume no obligation to update
these forward-looking statements, even if new information becomes
available in the future.
uniQure Contacts:
Maria E. Cantor
Direct: 339-970-7536
Mobile: 617-680-9452
m.cantor@uniQure.com
Tom Malone
Direct: 339-970-7558
Mobile: 339-223-8541
t.malone@uniQure.com
Eva M. Mulder
Direct: +31 20 240 6103
Mobile: +31 6 52 33 15 79
e.mulder@uniQure.com
This
announcement is distributed by Nasdaq Corporate Solutions on behalf
of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely
responsible for the content, accuracy and originality of the
information contained therein.
Source: uniQure N.V. via Globenewswire
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