SAN FRANCISCO, Feb. 6, 2018 /PRNewswire/ -- Audentes
Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology company
focused on developing and commercializing gene therapy products for
patients living with serious, life-threatening rare diseases, today
announced it has selected an optimized clinical development
candidate for its Pompe disease program. Data supporting the
selection were presented today during a general session at the
14th Annual WORLDSymposium 2018 in Poster #123, titled:
"A Novel Hybrid Promoter Directing AAV-mediated Expression of Acid
Alpha-Glucosidase to Liver, Muscle, and CNS Yields Optimized
Outcomes in a Mouse Model of Pompe Disease."
Pompe disease is caused by mutations in the gene that encodes
the enzyme acid alpha-glucosidase, or GAA, which is responsible for
degrading lysosomal glycogen. Dysfunction or absence of functional
GAA results in toxic accumulation of glycogen in cells which leads
to severe muscular weakness and respiratory failure. Tissues and
cells most affected by the disease are predominantly skeletal
muscle, cardiac muscle and the nervous system.
Dr. Suyash Prasad, Senior Vice
President and Chief Medical Officer of Audentes, stated "The only
approved treatment for Pompe disease is bi-weekly enzyme
replacement therapy, or ERT. Clinical outcomes are variable with
ERT, and the utility of this approach in Pompe is hampered by the
immune responses to ERT and the inability of ERT to sufficiently
penetrate key tissues relevant to the disease." Dr. Prasad
continued, "We are excited by the potential of systemic AAV gene
therapy with this novel vector to directly address the limitations
of current therapy with the aim of improving outcomes for patients,
and we look forward to advancing AT982 into clinical development
later this year."
The poster presented today describes the results of an AAV gene
therapy construct selection study conducted in a well-characterized
mouse model of Pompe disease. The study evaluated both AAV8
and AAV9 capsid serotypes, paired with novel promoter elements
designed to target GAA expression in a range of tissues, including
skeletal and cardiac muscle, the nervous system and the
liver. The study included a range of doses and utilized a
broad battery of biochemical and immunological assays. Of the
six vectors evaluated, an AAV8 vector with a novel hybrid promoter
was selected as the clinical development candidate, AT982.
This vector was confirmed to provide GAA expression and activity in
target tissues, improved muscle pathology and a favorable
immunogenicity profile.
"We are very excited to present the data highlighting the
immunological and glycogen reduction benefits provided by our novel
hybrid promoter vector in the Pompe disease mouse model," stated
John Gray, PhD, Senior Vice
President and Chief Scientific Officer. "This innovative
design reflects our commitment to gene therapy vector engineering
and immunology, and strengthens our hope for the translation of
AT982 into a transformative therapy for the Pompe patient
community."
Audentes plans to file an IND for AT982 in the second quarter of
2018 and plans to initiate a Phase 1/2 clinical study in the fourth
quarter of 2018.
About AT982 for Pompe disease
AT982 is the Audentes
product candidate being developed to treat Pompe disease, a
serious, progressive genetic disease characterized by severe muscle
weakness, respiratory failure leading to ventilator dependence and,
in infants, increased cardiac mass and heart failure. In untreated
infants, the disease is often fatal due to cardio-respiratory
failure within the first year of life, and in adults the disease is
progressive and life-limiting with significant ventilator and
wheelchair use. Pompe disease is caused by mutations in the gene
encoding the lysosomal enzyme alpha-glucosidase, or GAA, which
results in a deficiency of GAA protein and leads to the
accumulation of glycogen. The incidence of Pompe disease is
approximately one in 40,000 births. AT982 consists of an AAV8
vector that delivers a GAA gene expression cassette containing a
novel hybrid promoter designed to increase GAA activity in targeted
tissues, including skeletal and cardiac muscle, the nervous system
and the liver. Audentes holds exclusive global rights to both
AAV8 and AAV9 in Pompe disease from REGENXBIO.
About Audentes Therapeutics, Inc.
Audentes
Therapeutics (Nasdaq: BOLD) is a biotechnology company focused
on developing and commercializing gene therapy products for
patients living with serious, life-threatening rare diseases.
We are currently conducting a Phase 1/2 clinical study of our lead
product candidate AT132 for the treatment of X-Linked Myotubular
Myopathy (XLMTM) and have three additional product candidates in
development, including AT342 for the treatment of Crigler-Najjar
Syndrome, AT982 for the treatment of Pompe disease, and AT307 for
the treatment of the CASQ2 subtype of Catecholaminergic Polymorphic
Ventricular Tachycardia (CASQ2-CPVT). We are a focused,
experienced and passionate team committed to forging strong, global
relationships with the patient, research and medical
communities.
For more information regarding Audentes, please
visit www.audentestx.com.
Forward Looking Statements
This press release contains
forward-looking statements within the meaning of the "safe harbor"
provisions of the Private Securities Litigation Reform Act of 1995,
including, but not limited to: the timing of an IND filing and
initiation of a Phase 1/2 clinical study of AT982. All
statements other than statements of historical fact are statements
that could be deemed forward-looking statements. Although the
company believes that the expectations reflected in such
forward-looking statements are reasonable, the company cannot
guarantee future events, results, actions, levels of activity,
performance or achievements, and the timing and results of
biotechnology development and potential regulatory approval is
inherently uncertain. Forward-looking statements are subject
to risks and uncertainties that may cause the company's actual
activities or results to differ significantly from those expressed
in any forward-looking statement, including risks and uncertainties
related to the company's ability to advance its product candidates,
obtain regulatory approval of and ultimately commercial its product
candidates, the timing and results of preclinical and clinical
trials, the company's ability to fund development activities and
achieve development goals, the company's ability to protect
intellectual property and other risks and uncertainties
described under the heading "Risk Factors" in documents the company
files from time to time with the Securities and Exchange
Commission. These forward-looking statements speak only as of
the date of this press release, and the company undertakes no
obligation to revise or update any forward-looking statements to
reflect events or circumstances after the date hereof.
Audentes Contacts:
Investor Contact:
Andrew Chang
415.818.1033
ir@audentestx.com
Media Contact:
Paul Laland
415.519.6610
media@audentestx.com
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SOURCE Audentes Therapeutics, Inc.