Preclinical Studies Show Robust Uptake
and Glycogen Reduction in Multiple Tissues, Including Brain and
Spinal Cord
Amicus Therapeutics (Nasdaq: FOLD) today announced initial
preclinical data from its investigational adeno-associated viral
(AAV) gene therapy program for Pompe disease in mice. These data
will be highlighted in a poster (Poster 82, Abstract 518) entitled
“Development of a Novel Gene Therapy for Pompe Disease: Engineered
Acid Alpha-Glucosidase Transgene for Improved Expression and Muscle
Targeting,” at the American Society of Gene & Cell Therapy
(ASGCT) 22nd Annual Meeting in Washington, D.C. today at 5:00 p.m.
ET.
Pompe disease is an inherited lysosomal storage
disorder caused by deficiency of the enzyme acid alpha-glucosidase
(GAA). Reduced or absent levels of GAA lead to accumulation of
glycogen in cells, which results in the clinical manifestations of
Pompe disease. Amicus, in collaboration with the Gene Therapy
Program of the Perelman School of Medicine at the University of
Pennsylvania (Penn), is developing a novel gene therapy for Pompe
disease that combines the Amicus protein-engineering and
glycobiology expertise with Penn’s adeno associated virus (AAV)
gene transfer technologies.
This initial preclinical study used a single
high dose of AAV in GAA knockout mice with either natural
unmodified hGAA (“natural hGAA”) or an Amicus/Penn engineered hGAA
transgene with a lysosomal-targeting cell receptor binding motif
(“engineered hGAA”). The Amicus/Penn engineered hGAA is designed
for optimal expression, secretion, and targeting which enables
efficient cross-correction in target tissues (via the binding
motif).
Preclinical Poster Highlights for
Amicus/Penn AAV Gene Therapy for Pompe Disease:
- The Amicus/Penn hGAA AAV gene
therapy demonstrated more uniform cellular uptake and lysosomal
targeting compared to natural hGAA AAV gene therapy.
- The engineered hGAA AAV gene
therapy demonstrated robust glycogen reduction in all key tissues
in Pompe disease that were assessed.
- In the central nervous system
(CNS), the engineered hGAA AAV gene therapy showed robust glycogen
reduction in neuronal cells, suggesting this may be an effective
way to address neuronal aspects of Pompe disease. Natural hGAA AAV
gene therapy did not show glycogen reduction in neuronal
cells.
- Initial findings validate the
Amicus/Penn collaboration, as well as the potential of this
platform to design constructs that enhance protein targeting across
multiple lysosomal disorders.
- Additional preclinical studies to
evaluate this engineered hGAA with various doses and routes of AAV
administration are underway.
- The Pompe AAV gene therapy program
builds upon the protein engineering and manufacturing expertise
used to successfully develop AT-GAA, the Company’s late-stage
enzyme replacement therapy (ERT)-chaperone treatment paradigm.
Hung Do, PhD, Chief Science Officer of Amicus
Therapeutics, stated, “These very important preclinical results
validate our capabilities to develop engineered GAA proteins that
can efficiently cross-correct target cells and tissues via a gene
replacement therapy for Pompe disease. This approach may be
applicable to other lysosomal disorders as we continue to combine
our Amicus protein engineering expertise, together with Penn’s
vector engineering expertise, to develop novel gene therapies.”
John F. Crowley, Chairman and Chief Executive
Officer of Amicus Therapeutics, added, “Developing a potential cure
for Pompe has been a personal and professional goal for many years.
These data are profound and it is extremely rewarding to see these
preclinical results that show our Amicus engineered GAA is
optimized for uptake into target tissues and gets to the right
cellular compartments, especially in the central nervous system.
These data also provide preliminary and compelling evidence that
the Amicus technology to design constructs that enhance protein
targeting may be a significant platform for multiple lysosomal
disorders. As these data exceed our expectations, our preclinical
studies are progressing well ahead of schedule and we now expect to
select a clinical candidate in 2019 to move forward into
IND-enabling studies. Our mission has always been to develop
potential best in class medicines and that is precisely what we are
doing with both our novel, late-stage treatment paradigm AT-GAA as
well as this preclinical gene therapy program.”
Amicus is currently developing AAV gene
therapies in collaboration with the Gene Therapy Program of the
Perelman School of Medicine at the University of Pennsylvania
(Penn) for Pompe disease, Fabry disease, CDKL5 deficiency disorder
(CDD) and one additional undisclosed rare metabolic disease. The
agreement between Amicus and Penn is a Research, Collaboration and
License Agreement, providing funding to Penn to advance the
preclinical research programs in the Wilson Lab and to license
certain technologies invented under the funded Research
Collaboration.
“Amicus has differentiated itself by focusing on
proteins and protein engineering, with a specific track record in
the lysosomal disorders, which I believe are critically important
to developing AAV gene therapies that can safely and effectively
address these diseases,” said James M. Wilson, MD PhD, Professor of
Medicine and Pediatrics at the Perelman School of Medicine at Penn.
“These initial preclinical results are a significant step in
highlighting our collaboration to rapidly advance gene therapies
into the clinic for patients with urgent unmet needs in a disease
like Pompe. These results demonstrate that the Amicus gene
therapy that we have jointly developed has the potential to address
both the neuromuscular as well as the motor neuron aspects of Pompe
disease.”
Conference Call and Webcast on April 30,
2019 at 8:30 a.m. ETAmicus Therapeutics will host a
conference call and audio webcast today, April 30, 2019 at 8:30
a.m. ET to discuss the preclinical data presented at ASGCT.
Interested participants and investors may access the conference
call by dialing 877-303-5859 (U.S./Canada) or 678-224-7784
(international), conference ID: 1866796.
A live audio webcast and accompanying slide deck
can also be accessed via the Investors section of the Amicus
Therapeutics corporate website at http://ir.amicusrx.com/, and will
be archived for 30 days. Web participants are encouraged to
register on the website 15 minutes prior to the start of the call.
A replay of the call will be available for seven days beginning at
11:30 a.m. ET on April 30, 2019. Access numbers for this replay are
855-859-2056 (U.S./Canada) and 404-537-3406 (international);
conference ID: 1866796.
About Pompe DiseasePompe
disease is an inherited lysosomal storage disorder caused by
deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or
absent levels of GAA leads to accumulation of glycogen in cells,
which results in the clinical manifestations of Pompe disease. The
disease can be debilitating, and is characterized by severe muscle
weakness that worsens over time. Pompe disease ranges from a
rapidly fatal infantile form with significant impacts to heart
function to a more slowly progressive, late-onset form primarily
affecting skeletal muscle. It is estimated that Pompe disease
affects approximately 5,000 to 10,000 people worldwide.
About Amicus Therapeutics
Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated
biotechnology company focused on discovering, developing and
delivering novel high-quality medicines for people living with rare
metabolic diseases. With extraordinary patient focus, Amicus
Therapeutics is committed to advancing and expanding a robust
pipeline of cutting-edge, first- or best-in-class medicines for
rare metabolic diseases. For more information please visit the
company’s website at www.amicusrx.com, and follow us on Twitter and
LinkedIn.
Forward-Looking StatementsThis
press release contains "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements relating to initial preclinical data from its
investigational adeno-associated viral (AAV) gene therapy program
for Pompe disease in mice and the potential implications of these
data for the future advancement and development of a gene therapy
for Pompe disease and other lysosomal disorders and development of
potential platform technologies. Words such as, but not limited to,
“look forward to,” “believe,” “expect,” “anticipate,” “estimate,”
“intend,” "confidence," "encouraged," “potential,” “plan,”
“targets,” “likely,” “may,” “will,” “would,” “should” and “could,”
and similar expressions or words identify forward-looking
statements. The forward looking statements included in this press
release are based on management's current expectations and belief's
which are subject to a number of risks, uncertainties and
factors, including that the preliminary data based on a small
patient sample and reported before completion of the study
will not be predictive of future results, that results
of additional preliminary data or data from the completed
study or any future study will not yield results that are
consistent with the preliminary data presented, that the Company
will be not able to demonstrate the safety and efficacy of
AT-GAA, that later study results will not support
further development, or even if such later results are
favorable, that the Company will not be able to successfully
complete the development of, obtain regulatory approval for, or
successfully commercialize AT-GAA. In addition, all
forward looking statements are subject to the other risks and
uncertainties detailed in our Annual Report on Form 10-K for the
year ended December 31, 2018. As a consequence, actual
results may differ materially from those set forth in this press
release. You are cautioned not to place undue reliance on
these forward looking statements, which speak only of the date
hereof. All forward looking statements are qualified in their
entirety by this cautionary statement and we undertake no
obligation to revise this press release to reflect events or
circumstances after the date hereof.
CONTACTS:
Investors/Media:Amicus TherapeuticsSara
Pellegrino, IRCVice President, Investor Relations & Corporate
Communicationsspellegrino@amicusrx.com(609) 662-5044
Media:Amicus TherapeuticsMarco
Winkler Director, Corporate Communications
mwinkler@amicusrx.com(609) 662-2798
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