Audentes Therapeutics Announces Selection of Optimized Clinical Development Candidate for Pompe Disease Program

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SAN FRANCISCO, Feb. 6, 2018 – 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

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
[email protected]

Media Contact:
Paul Laland
[email protected]

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SOURCE Audentes Therapeutics, Inc.

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