uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, today announced that three manuscripts on preclinical data
from its gene therapy candidate AMT-130 in Huntington’s disease
have been accepted for publication, in the journals Science
Translational Medicine, Brain Science, and Brain Communications.
The publications show the safety and efficacy of AMT-130 in the
deep brain structures of a large animal model and outline a
promising novel efficacy biomarker for AMT-130.
“Taken together, these publications demonstrate
widespread biodistribution and strong, durable efficiency of
AMT-130 in disease-relevant regions in a large brain,” stated
Ricardo Dolmetsch, Ph.D., president of research and development at
uniQure. “The data provide further support for the potential
therapeutic value of AMT-130, and we remain enthusiastic about our
Phase I/II clinical trial of AMT-130 in patients with Huntington’s
disease.”
Widespread and Sustained Target Engagement in
Huntington Disease Minipigs
The paper published this week in Science
Translational Medicine examines the translatability and long-term
durability of AMT-130 in transgenic Huntington’s disease minipigs,
which were used to assess the biodistribution and target engagement
in a larger brain. The minipig model is the largest diseased animal
model available, generally weighing up to 300
pounds.
AMT-130 was administered by MRI-guided
convention-enhanced delivery (CED) at a single dose, bilaterally in
the caudate and putamen. Vector DNA distribution and transgene
expression in minipig brains demonstrated extensive brain coverage
comparable at the interim sacrifice timepoints of 6- and 12-months
post administration, leading to significant lowering of mutant
huntingtin (mHTT) protein in the brain.
At 12 months, the most pronounced mHTT protein
lowering was observed in the putamen (85%), caudate (80%) and
amygdala (78%), followed by thalamus (56%) and cerebral cortex
(44%).
The publication, “Widespread and Sustained
Target Engagement in Huntington Disease Minipigs upon Intrastriatal
MicroRNA-based Gene Therapy,” is available online in the journal
Science Translational Medicine (DOI:
10.1126/scitranslmed.abb8920).
Well-tolerated in non-human primates and
rats
In addition, a GLP toxicity study of AMT-130 in
non-human primates and rats was published in January 2021 in the
journal Brain Science. The study demonstrated an excellent safety
profile and biodistribution after MRI-guided CED of AMT-130 in the
treated animals. One-time bilateral administration in the caudate
and putamen resulted in widespread vector DNA and miHTT transgene
distribution in the brain, particularly in areas associated with HD
pathology. Intrastriatal administration of AAV5-miHTT was well
tolerated, with no clinically relevant changes in either
species.
The publication, “Intrastriatal Administration
of AAV5-miHTT in Non-Human Primates and Rats Is Well Tolerated and
Results in miHTT Transgene Expression in Key Areas of Huntington
Disease Pathology,” is available online in the journal Brain
Science (DOI: 10.3390/brainsci11020129).
Monitoring Durability of MicroRNA-based
Therapies
A third manuscript was published last week in
the journal Brain Communications, examining the potential use of
measuring therapeutic HTT microRNA (miHTT) in extracellular
vesicles in CSF as sources to monitor the expression and durability
of gene therapies in the brain. After AAV treatment in non-human
primates, the secretion of mature engineered microRNA molecules was
confirmed, with extracellular microRNA levels correlating with
viral dose and cellular microRNA expression in neurons. In
investigating the detection of engineered microRNAs over time in
the CSF of non-human primates after a single intrastriatal
injection of AAV5-miHTT, quantifiable engineered microRNA levels
enriched in extracellular vesicles were detected in the CSF up to
two years after brain infusion.
The results confirm the long-term expression (up
to two years) of AAV5-delivered microRNAs in non-human primates and
provide further support for the potential use of extracellular
vesicle-associated microRNAs as novel biomarkers in ongoing
clinical trials of gene therapies for neurodegenerative diseases,
including AMT-130.
The publication, “Secreted therapeutics:
Monitoring durability of microRNA-based gene therapies in the
central nervous system,” is available online in the journal Brain
Communications (DOI: 10.1093/braincomms/fcab054).
About AMT-130
AMT-130 comprises a recombinant AAV5 vector
carrying a DNA cassette encoding a microRNA that lowers Huntingtin
protein in Huntington’s disease patients. AMT-130 is uniQure’s
first clinical program incorporating its proprietary miQURE™
platform. miQURE is designed to degrade disease-causing genes
without off-target toxicity and induce silencing of the entire
target organ through secondary exosome-mediated delivery.
About Huntington’s Disease
Huntington’s disease is a rare, inherited
neurodegenerative disorder that leads to motor symptoms including
chorea, and behavioral abnormalities and cognitive decline
resulting in progressive physical and mental deterioration. The
disease is an autosomal dominant condition with a disease-causing
CAG repeat expansion in the first exon of the huntingtin gene that
leads to the production and aggregation of abnormal protein in the
brain. Despite the clear etiology of Huntington’s disease, there
are no currently approved therapies to delay the onset or to slow
the disease’s progression.
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 gene therapies to treat
patients with hemophilia B, Huntington's disease, Fabry disease,
spinocerebellar ataxia Type 3 and other
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 whether we will advance
our Phase I/II gene therapy clinical trial of AMT-130 in
Huntington’s disease. uniQure’s actual results could differ
materially from those anticipated in these forward-looking
statements for many reasons, including, without limitation, risks
associated with the impact of the ongoing COVID-19 pandemic on our
Company and the wider economy and health care system, our
Commercialization and License Agreement with CSL Behring, the
regulatory approval of that transaction, our clinical development
activities, clinical results, collaboration arrangements,
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
periodic securities filings, including its Annual Report on Form
10-K filed March 1, 2021. Given these risks, uncertainties and
other factors, you should not place undue reliance on these
forward-looking statements, and uniQure assumes no obligation to
update these forward-looking statements, even if new information
becomes available in the future.
uniQure Contacts:
FOR
INVESTORS: |
|
FOR
MEDIA: |
|
|
|
Maria E. Cantor |
Chiara Russo |
Tom Malone |
Direct: 339-970-7536 |
Direct: 617-306-9137 |
Direct: 339-970-7558 |
Mobile: 617-680-9452 |
Mobile: 617-306-9137 |
Mobile:339-223-8541 |
m.cantor@uniQure.com |
c.russo@uniQure.com |
t.malone@uniQure.com |
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