uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, presented new preclinical data on its gene therapy
candidates AMT-150 for Spinocerebellar Ataxia type 3, AMT-190 for
Fabry disease, and AMT-180 for the treatment of Hemophilia A. The
data are featured in presentations at the American Society of Gene
and Cell Therapy (ASGCT) Annual Meeting. uniQure is
delivering a total of 22 data presentations at the meeting, which
is taking place virtually from May 12 to May 15.
“Our collective presence at ASGCT showcases the
breadth of uniQure’s gene therapy expertise and leadership,
including our research capabilities and excellence in developing
and manufacturing novel gene therapies,” stated Matt Kapusta, chief
executive officer at uniQure. “We are happy to share new
preclinical data on our gene therapy candidates, as well as our
innovations in technology and manufacturing.”
The uniQure presentations in Spinocerebellar
Ataxia type 3 (SCA3) show a continuation of strong proof-of-concept
data in mice and other preclinical models, as well as encouraging
new data in non-human primates (NHPs). Additionally, new data
related to AAV biology show that a single administration of
AAV5-hFIX in newborn mice led to stable hFIX expression up to 18
months after dosing.
AMT-150 for Spinocerebellar Ataxia type
3 (SCA3)
SCA3, also known as Machado-Joseph disease, is
caused by a CAG-repeat expansion in the ATXN3 gene that results in
an abnormal form of the protein ataxin-3. People with SCA3
experience brain degeneration that results in movement disorders,
rigidity, muscular atrophy and paralysis. There is currently no
treatment available that slows the progressive course of this
lethal disease. AMT-150 is a one-time,
intracisternally-administered, AAV gene therapy incorporating the
Company’s proprietary miQURE™ silencing technology that is designed
to halt ataxia in early manifest SCA3 patients. AMT-150 is
currently in pre-investigational new drug enabling
studies.
In an in vivo preclinical study featured in an
oral presentation, six non-human primates (NHP) received a one-time
injection of AMT-150 via the cisterna magna to assess expression
and distribution. Samples taken after 8 weeks showed widespread
transduction of the brain and spinal cord, with the highest genome
copies found in the posterior fossa and cortical regions.
ATXN3-microRNA was expressed in all brain regions and was
correlated with the number of vector genome copies. Using in-situ
hybridization, researchers confirmed the presence throughout the
brain of high quantities of mature miATXN3 microRNA molecules.
In other preclinical studies featured in
separate poster presentations, researchers evaluated AMT-150 in
SCA3 mouse models, as well as human induced pluripotent stem cell
(iPSC)-derived neurons and astrocytes, to investigate potential
off-target effects of AAV5-miATXN3. The iPSC-derived cell cultures,
which were derived from two SCA3 patients, represent the most
disease-relevant cell type for therapeutic targeting of AMT-150. A
clear dose-dependent expression of miATXN3 was observed in the
iPSC-derived neurons and astrocytes transduced with AMT-150. Mature
miATXN3 molecules were also associated with extracellular vesicles
that strongly correlated with the dose and miATXN3 expression,
suggesting the potential therapeutic spread of the engineered
miATXN3. Additionally, AMT-150 clearly demonstrated ATXN3 knockdown
in human neurons and various SCA3 mouse models with subsequent
neuropathology improvement.
AMT-190 for Fabry Disease
Fabry disease is an X-linked genetic disorder
resulting from a deficiency of α-galactosidase A (α-gal or GLA).
The current standard of care for Fabry disease is bi-weekly
infusions of enzyme replacement therapy, a treatment that has
limited effectiveness in many patients due to poor
cross-correction, which hampers clearance of substrates in the
target organs, in particular the kidney and the heart. In addition,
a significant number of patients develop antibodies to the enzyme,
α-gal or GLA. AMT-190 provides expression of a proprietary,
exclusively licensed modified NAGA (ModNAGA), which shows a high
structural resemblance to α-gal and has GLA activity. ModNAGA may
have several advantages over current therapies, including higher
stability in plasma, circumvention of GLA-inhibitors and better
uptake in target organs.
In vivo studies in wild-type (WT) NHPs were
conducted to assess expression of ModNAGA upon AAV-injection. These
studies demonstrated that a single administration of AMT-190
resulted in modNAGA expression in the liver and significant
increases of GLA activity levels in the NHP plasma.
Earlier in vivo studies in GLA knock-out
(GLA-KO) and WT mice demonstrated that AMT-190 resulted in up to
ten-fold higher GLA activity in plasma, compared to the relevant
control group, and successful lowering of Gb3 and LysoGb3 in plasma
and target organs of GLA-KO mice. The data presented also show that
a single administration of AMT-190 in GLA-KO mice continued to
elevate GLA-activity levels in the liver and plasma and reduce
GLA-substrates in plasma and target organs up to 30-weeks
post-injection.
AMT-180 for Hemophilia A
Hemophilia A is an X-linked bleeding disorder
resulting from a deficiency in coagulation Factor VIII that serves
as a cofactor for Factor IX in the activation of the coagulation
cascade. About 30 percent of the hemophilia A patient population
develops inhibitors to Factor VIII over the course of the disease.
AMT-180 comprises a recombinant AAV5 vector incorporating a
proprietary modified Factor IX gene.
Data from multiple in vivo studies in rodents
and NHPs demonstrated that a single administration of AMT-180 was
well-tolerated and without increased coagulation activation
markers. The preclinical studies were used to predict suitable
clinical doses by assessing Factor VIII-independent clotting
activity and correlating this to FIX-FIAV protein levels. The
studies demonstrated that the dose calculation model in NHPs
predicted dose-dependent increases in FVIII-independent activity.
A Single Administration of AAV5-hFIX in
Newborn, Juvenile and Adult Mice Leads to Stable hFIX Expression up
to 18 Months after Dosing
In addition to updates on our preclinical
programs, an oral presentation provides important new data on AAV
biology, showing that AAV5/FIX expression was maintained long-term,
up to 18 months after dosing, in mice that were treated very early
in life. The total number of genomic transgene copies was
remarkably constant during the lives of the mice. FIX expression
was maintained during the 18 months after dosing, despite the cells
in the liver having turned over several times. The original volume
of liver that was transduced is smaller in younger mice, but the
mice livers did not lose the initial transduction/expression during
cell division over time.
“The question of whether re-treatment will be
needed is an important issue in gene therapy,” stated Sander van
Deventer. “These data show that there was almost no loss of the
transduced cells following administration of AAV5-hFIX during the
life span of the mouse. This suggests that the AAV episomes were
transferred to daughter cells during cell division – a very
important finding in terms of AAV biology and an encouraging sign
for the longevity of gene therapy in humans.”
An overview of the data presented at ASGCT can
be found on the Investor section of uniQure’s corporate
website.
About uniQureuniQure 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 other severe genetic 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 AMT-150 will be
effective as a one-time, intrathecally-administered, AAV gene
therapy or will halt ataxia in early manifest SCA3 patients,
whether ModNAGA may have one or more advantages over current
therapies, including higher stability in plasma, circumvention of
GLA-inhibitors and better uptake in target organs, whether the
AMT-180 doses predicted by our preclinical studies will be
effective in clinical studies in hemophilia A patients, and whether
gene therapies will demonstrate longevity for humans in liver or
other treatments. Our 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 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 our Quarterly
Report on Form 10-Q filed on April 29, 2020. 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:
FOR INVESTORS:
Maria E. Cantor
Direct:
339-970-7536
Mobile: 617-680-9452
m.cantor@uniQure.com
FOR MEDIA:
Tom
Malone
Direct: 339-970-7558Mobile:339-223-8541t.malone@uniQure.com
uniQure NV (NASDAQ:QURE)
Historical Stock Chart
From Jun 2024 to Jul 2024
uniQure NV (NASDAQ:QURE)
Historical Stock Chart
From Jul 2023 to Jul 2024