uniQure Presents Multiple New Preclinical Data on AMT-130 at the CHDI’s 15th Annual Huntington’s Disease Therapeutics Con...
February 27 2020 - 7:00AM
uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, today announced the presentation of multiple new preclinical
data on AMT-130, its investigational AAV gene therapy for the
treatment of Huntington’s disease (HD), at the 15th Annual CHDI
Huntington’s disease Therapeutics Conference in Palm Springs,
California.
“Our data presentations at CHDI illustrate the
increasing potential of AMT-130 to target the highly toxic exon 1
protein fragment, achieve broad vector biodistribution across
several animal species and show meaningful activity using the
presence of extracellular vesicles as a potential biomarker,”
stated Sander van Deventer, M.D., Ph.D., executive vice president,
research & product development of uniQure. “In addition, we
highlight the use of magnetic resonance spectroscopy as a
potentially important imaging biomarker to measure the restoration
of target tissue. Collectively, these findings represent a robust
package of new preclinical data to better inform how researchers
and clinicians pursue a much-needed treatment for this devastating
disease.”
Four scientific abstracts submitted by uniQure
researchers were accepted for presentation at the conference, of
which one is an oral presentation to be featured today. Important
findings across several preclinical studies presented at the
conference include the following:
Translatable Biomarkers in Gene Therapy
for Huntington Disease: Learnings from Pre-clinical
Studies
- In identifying translatable
biomarkers for gene therapy studies in Huntington’s disease,
transgenic Huntington’s disease minipigs 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 two 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 ongoing study that now includes up to two years
of follow-up, demonstrated stable mHTT protein lowering of up to 30
percent in the cerebrospinal fluid (CSF) of minipigs after a single
administration of AMT-130.
Secreted Therapeutics: Monitoring
Durability of microRNA-based Gene Therapies in Huntington’s
disease
- Neurons derived from the induced
pluripotent stem cells (iPSC) of Huntington’s disease patients were
used to study the presence of extracellular therapeutic microRNA
targeting human huntingtin (miHTT) after transduction with AMT-130.
Extracellular vesicles were identified as carriers of RNA species,
including microRNAs, and are therefore potential biomarkers for
diagnosis and pharmacokinetics. Results from this new study
demonstrated that therapeutic miHTT molecules are secreted in a
dose-dependent manner from AMT-130-treated neuronal cells,
providing the potential of a promising translational marker to
monitor long-term expression of AMT-130 gene therapy in the brain.
- To support these results, non-human
primates received a single administration of AMT-130 resulting in
widespread distribution of therapeutic miHTT molecules in both the
striatum and cortex, as well as the presence of therapeutic miHTT
molecules in the CSF up to 6 months after intrastriatal injection
of AMT-130.
Lowering the Pathogenic Exon 1 HTT
Fragment by AAV5-miHTT Gene Therapy
- In a study using the Q175FDN mouse
model, the target engagement of aberrantly spliced exon 1 HTT
transcript (exon 1 HTT) was investigated. These new preclinical
data demonstrated that the mice treated with AMT-130 experienced a
dose-dependent lowering of exon 1 HTT mRNA in both the striatum and
cortex, as well as the full-length HTT mRNA. The lowering was shown
to be well correlated with the detected levels of vector DNA and
mature miHTT molecules in the mice treated with AMT-130.
Exploring the Effects of Intrastriatal
AAV5-miHTT Lowering Therapy on Neuronal Function, MRS Signal and
Mutant Huntingtin Levels in the Q175FDN Mouse Model of Huntington’s
disease
- Magnetic resonance spectroscopy
(MRS) data in the Q175FDN mouse model of Huntington’s disease
demonstrate that levels of N-acetyl aspartate (NAA), a neuronal
integrity marker, were restored in mice treated with the high dose
of AMT-130, supporting the use of imaging biomarkers in gene
therapy studies for Huntington’s disease. Importantly, effects of
mHTT silencing in the Q175FDN model on MRS were complemented by
additional data on striatal gene expression profiles, demonstrating
a trend towards normalization with AMT-130 treatment. These new
data build on earlier MRS and MRI data suggesting improvement in
brain cell function, a reversal in Huntington’s disease
neuropathology and a partial reversal of volume loss in the
hippocampus, a key brain region involved in memory.
The uniQure data presentations featured at CHDI
are available on the investor page of the Company’s website,
www.uniQure.com
About Huntington’s
DiseaseHuntington’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. 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 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,
hemophilia A, Huntington's disease, Fabry disease, spinocerebellar
ataxia Type 3 and other diseases. www.uniQure.com
uniQure Forward-Looking
StatementsThis 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 AMT-130 will
target the highly toxic exon 1 protein fragment, achieve broad
vector biodistribution across several animal species or show
meaningful activity using the presence of extracellular vesicles as
a potential biomarker, and whether magnetic resonance spectroscopy
will be an important imaging biomarker to measure the restoration
of target tissue. Our actual results could differ materially from
those anticipated in these forward-looking statements for many
reasons, including, without limitation, risks associated with our
and our collaborators’ clinical development activities, clinical
results, collaboration arrangements, corporate reorganizations and
strategic shifts, 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 Quarterly Report on Form 10-Q filed on
October 28, 2019. 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: |
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FOR
INVESTORS: |
FOR MEDIA: |
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Maria E.
Cantor |
Eva M.
Mulder |
Tom
Malone |
Direct: 339-970-7536 |
Direct: +31 20 240 6103 |
Direct: 339-970-7558 |
Mobile: 617-680-9452 |
Mobile: +31 6 52 33 15 79 |
Mobile: 339-223-8541 |
m.cantor@uniQure.cm |
e.mulder@uniQure.com |
t.malone@uniQure.com |
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