uniQure Highlights Pipeline Expansion and Advancements in Technology at Research & Development Day
20 November 2018 - 4:15AM
uniQure Highlights Pipeline Expansion and Advancements in
Technology at Research & Development Day
uniQure N.V. (NASDAQ: QURE), a leading gene therapy company
advancing transformative therapies for patients with severe medical
needs, today announced the expansion of its research pipeline with
novel AAV gene therapy approaches to treating Hemophilia A, Fabry
disease and Spinocerebellar Ataxia Type 3 at the Company’s Research
& Development Day held this morning in New York City.
“We are very proud of the progress the Company
has made to deliver extensive preclinical data for these new gene
therapy programs that expand our pipeline and further validate
uniQure’s potential best-in-class vector delivery platform,” stated
Sander van Deventer, M.D., Ph.D., chief scientific officer at
uniQure. “The addition of these gene therapy candidates for
indications in the liver and CNS brings us yet another step closer
towards uniQure's goal of delivering transformational medicine to
patients suffering from genetic diseases. We look forward to
advancing these programs closer to the clinic in 2019.”
New Gene Therapy Programs
- Introduced new product candidate AMT-180, a novel hemophilia A
gene therapy that has the potential to treat all hemophilia A
patients including those with past and current inhibitors.
- Approximately 30 percent of patients with severe hemophilia A
will develop an inhibitor that neutralizes the infused Factor VIII
(FVIII) activity. This patient population has in the past been
excluded from gene therapy approaches in clinical development.
- AMT-180 is a one-time, intravenously-administered, AAV5-based
gene therapy incorporating a proprietary modified Factor IX gene,
Super9™, that has been demonstrated in preclinical studies to
circumvent inhibitors to FVIII.
- A proof-of-concept study demonstrated that administration of
Super9 resulted in clinically relevant FVIII mimetic activity in
hemophilia A mice and was not associated with hypercoagulability in
wild-type mice.
- Another study in non-human primates demonstrated that a single
dose of AMT-180 resulted in expression levels that translate into
FVIII mimetic activity expected to be clinically relevant in
hemophilia A patients with or without inhibitors. In addition,
Super9 induced clinically relevant thrombin activation in
FVIII-depleted human plasma with or without inhibitors.
- These data show that AMT-180 may lead to durable expression in
hemophilia A patients and may provide long-term prevention of
bleeds.
- Introduced new product candidate AMT-190, a differentiated gene
therapy for the treatment of Fabry disease.
- Fabry disease is an inherited lysosomal storage disorder caused
by a defect in a gene that encodes for a protein called
α-galactosidase A (GLA). The GLA protein is an essential enzyme
required to breakdown globotriaosylsphingosine (Gb3) and
lyso-globotriaosylsphingosine (lyso-Gb3). In patients living with
Fabry disease, Gb3 and lyso-Gb3 accumulate in various cells
throughout the body causing progressive clinical signs and symptoms
of the disease. Current treatment options, which consist of
bi-weekly intravenous enzyme replacement therapy, have no
therapeutic benefit in patients with advanced renal or cardiac
disease. Studies have also shown that a majority of male patients
develop antibodies that inhibit the GLA protein and interfere with
therapeutic efficacy.
- AMT-190 is a one-time, intravenously-administered, AAV5-based
gene therapy designed to circumvent GLA antibodies that can inhibit
efficacy in Fabry patients. AMT-190 incorporates a modified version
of α-N-acetylgalactosaminidase (NAGA), a protein that is
structurally similar to the GLA protein but is not recognized by
GLA-neutralizing antibodies. As such, AMT-190 has the potential to
be a more effective, longer-term treatment of Fabry disease.
- In cultured cells and in a study in wild-type
mice, AMT-190 resulted in clinically relevant GLA
activity.
- In a preclinical proof-of-concept study, Fabry mice were
injected with a single dose of AMT-190, resulting in modified NAGA
expression with subsequent GLA-activity in plasma. At 2 and 4
weeks post-dosing, this GLA activity already translated to up to 50
percent reduction in lyso-Gb3 levels.
- These studies demonstrate proof-of-concept of AMT-190 as a gene
therapy candidate for Fabry disease. A one-time
administration of AMT-190 could potentially lead to long-term
expression of GLA in the liver, kidneys and heart, with no loss of
expression due to inhibitors.
-
- Introduced new gene therapy candidate AMT-150, a novel
treatment for Spinocerebellar Ataxia Type 3, a central nervous
system disorder.
- Spinocerebellar Ataxia Type 3 (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, intrathecally-administered, AAV gene
therapy incorporating the Company’s proprietary miQURE™ silencing
technology that is designed to halt ataxia in early manifest SCA3
patients.
- In an in-vitro study with human Induced Pluripotent Stem (IPS)
derived neurons, AMT-150 has been shown to lower the human ataxin-3
protein by 65 percent, without any off-target effects. The Company
also performed a proof-of-concept in-life study in SCA3 mice
demonstrating that AMT-150 was able to lower toxic ataxin-3 protein
by 65 percent in the brain stem after a single administration.
Further studies in non-human primates demonstrate the ability to
distribute and express a reporter gene at a clinically relevant
level in the most degenerated brain regions in SCA3.
- These preclinical studies show that a single administration of
AMT-150 results in sustained expression and efficient processing
with on-target engagement. They also show that AMT-150 appears to
be safe due to the lack of off-target activity. The Company is
currently performing studies in large animals to demonstrate
further safety and efficacy.
Advances in Technology and Manufacturing
- Presented the Company’s miQURE™ technology – a proprietary,
next-generation gene silencing platform.
- miQURE is uniQure’s novel technology platform designed to
degrade disease-causing genes, without off-target toxicity, and
induce silencing of the entire target organ through secondary
exosome-mediated delivery. Gene therapy candidates designed with
miQURE incorporate proprietary, therapeutic miRNA constructs that
can be delivered using AAVs to potentially provide long-lasting
activity.
- Preclinical studies of miQURE-based gene therapies have
demonstrated several important advantages, including enhanced
tissue-specificity, improved nuclear and cytoplasmic gene lowering
and no off-target effects associated with impact to the cellular
miRNA or mRNA transcriptome. miQURE technology has been
incorporated in AMT-130, an investigational gene therapy for
Huntington’s disease, and is expected to be applied to AMT-150 for
SCA3.
- Announced Advances in Manufacturing and Research
Technology.
- uniQure presented data on a highly potent, next-generation
promoter for liver-directed gene therapies. Two preclinical studies
demonstrate that the optimized liver promoter can generate up to 40
times more protein expression compared to the reference promoter.
The optimized promoter will be incorporated in the Company’s gene
therapy candidate AMT-180 for the treatment of hemophilia A.
- The Company highlighted the advantages of uniQure’s
patent-protected Dual Baculovirus manufacturing technology,
including reduced variability, higher vector purity and easier
scalability.
A replay of the webcast from the Company’s
Research and Development Day will be available on the Investor
section of the corporate website at www.uniQure.com along with a
copy of the presentation.
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
liver/metabolic, central nervous system 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, the achievement of any
of our planned near term or other milestones, the development of
our gene therapy product candidates including each of the product
candidates at the pre-clinical stage of development, the ability to
achieve therapeutic effects in human patients in any of our product
candidates, the ability to produce a product candidate that is safe
and effective, the ability to obtain regulatory approval for any of
our product candidates, 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 our and our collaboration activities, product
development activities, 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 Annual Report on Form 10-K filed on March 14, 2018 and
Quarterly Report on Form 10-Q filed on November 6, 2018. 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.
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uniQure
Contacts: |
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FOR
INVESTORS: |
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FOR
MEDIA: |
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Maria E.
Cantor |
Eva M.
Mulder |
Tom
Malone |
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Direct: 339-970-7536 |
Direct: +31 20 240 6103 |
Direct: 339-970-7558 |
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Mobile: 617-680-9452 |
Mobile: +31 6 52 33 15 79 |
Mobile: 339-223-8541 |
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m.cantor@uniQure.com |
e.mulder@uniQure.com |
t.malone@uniQure.com |
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