Audentes Therapeutics has announced plans to commence patient dosing in the fourth quarter of 2019 with AT702 produced by Nationwide Children’s Hospital. AT702 is designed to induce exon 2 skipping to treat Duchenne caused by duplications of exon 2 (Dup2) and mutations in exons 1-5 of the dystrophin gene.

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Audentes Therapeutics Reports Second Quarter 2019 Financial Results and Provides Corporate Update

– Commenced enrollment of 8 patients into an ASPIRO pivotal expansion cohort to confirm the safety and efficacy profile of AT132 for the treatment of X-linked myotubular myopathy (XLMTM) at dose of 3×10 14 vg/kg

– Biologics License Application (BLA) submission for AT132 planned in mid-2020; Marketing Authorization Application (MAA) planned for second half of 2020

– Completed IND-enabling dose ranging and toxicology studies of AT845 for Pompe disease; on track to submit IND in Q3 2019

– Plan to commence Duchenne muscular dystrophy (DMD) patient dosing with AT702 manufactured by Nationwide Children’s Hospital (NCH) in Q4 2019; plan to submit IND for Audentes AT702 construct in Q1 2020

– Vector screening studies underway for AT466 for myotonic dystrophy type 1 (DM1); plan to submit IND in 2020

– Strong balance sheet with June 30, 2019 cash, cash equivalents and marketable securities of $378.6 million

SAN FRANCISCO, Aug. 6, 2019 /PRNewswire/ — Audentes Therapeutics, Inc. (Nasdaq: BOLD), a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases, today reported its financial results for the second quarter ended June 30, 2019 and provided an update on the company’s recent achievements and anticipated upcoming milestones.

“It is a very busy time at Audentes, and we are excited by the significant progress we have made across our portfolio,” stated Matthew R. Patterson, Chairman and Chief Executive Officer.  “Following collaborative interactions with FDA and EMA, we have initiated enrollment of eight additional XLMTM patients into an ASPIRO pivotal expansion cohort, which is designed to confirm the safety and efficacy profile of AT132 at a dose of 3×10¹⁴vg/kg.  We are optimistic that these data will support the submission of a BLA for AT132 in mid-2020.”

Mr. Patterson continued, “We remain on track for a third quarter IND submission of AT845 for the treatment of Pompe disease.  And importantly, we’ve made substantial progress advancing our DMD program.  We expect patient dosing with NCH’s AT702 construct to commence as planned in the fourth quarter of 2019 and to submit an IND in the first quarter of 2020 for the Audentes AT702 construct, which is designed to serve as the platform for our rapid expansion into additional DMD genotypes next year. Together with our work in myotonic dystrophy, we believe this rich development pipeline positions us well for continued growth and industry leadership in the field of AAV-based genetic medicines for neuromuscular disease.”

Recent Achievements & Upcoming Key Events

AT132 for XLMTM:

• Positive data update from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of XLMTM, presented at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in May 2019.
• 3×10¹⁴ vg/kg selected as optimal dose.
• Following collaborative interactions with the FDA and EMA, initiated enrollment of eight additional XLMTM patients into the ASPIRO pivotal expansion cohort, designed to confirm the safety and efficacy profile of AT132 at a dose of 3×10¹⁴ vg/kg.
• Enrollment in the pivotal expansion cohort is expected to be complete in the fall of 2019.
• BLA submission for AT132 planned in mid-2020; MAA submission planned for the second half of 2020.
• Next clinical data presentation planned at the 24th International Annual Congress of the World Muscle Society (WMS) in Copenhagen, Denmark, October 1-5, 2019.

Additional information on the ASPIRO Pivotal Expansion Cohort:

• The pivotal expansion cohort is enrolling eight patients, consisting of four age-matched pairs (+/- 6 months), with one patient from each pair randomized to receive a single dose of AT132 (3×10¹⁴ vg/kg) or serve as a delayed treatment control.  Delayed treatment control patients will be administered AT132 following the collection of 24-week data from the full pivotal cohort.
• Patients will be followed for safety and efficacy for five years, with the primary analysis occurring 24 weeks post treatment.
• Key inclusion criteria: less than 5 years of age or have been enrolled in INCEPTUS, on invasive ventilator support for 20-24 hours per day, unable to sit without assistance for at least 30 seconds.
• The primary efficacy endpoint is defined as change from baseline in hours of ventilatory support over time through week 24.  As of the April 2019 ASPIRO data analysis, all nine patients treated achieved sustained and meaningful reductions in ventilatory support, with four patients successfully completely weaned off of mechanical ventilation.

AT845 for Pompe Disease:

• Completed IND-enabling dose ranging and toxicology studies.
• On track to submit IND in the third quarter of 2019.

AT702/AT751/AT753 for DMD:

• Plan to commence patient dosing in the fourth quarter of 2019 with AT702 produced by NCH. AT702 is designed to induce exon 2 skipping to treat DMD caused by duplications of exon 2 (Dup2) and mutations in exons 1-5 of the dystrophin gene.
• Dose ranging and toxicology studies underway to support a first quarter 2020 IND submission for the Audentes AT702 construct and transition the balance of the AT702 DMD program into a Phase 1/2 clinical study utilizing this product candidate.
• The construct backbone of the Audentes AT702 product is designed to serve as a vectorized exon skipping platform for rapid expansion into additional DMD genotypes.
• Preclinical work is underway to advance AT751 and AT753 to treat DMD patients with genotypes amenable to exons 51 and 53 skipping.
• In combination, AT702, AT751 and AT753 have the potential to address more than 25% of DMD patients; plan to leverage our vectorized exon skipping platform to develop additional product candidates with the potential to address up to 80% of DMD patients over time.

AT466 for DM1:

• Preclinical vector screening studies underway.
• Plan to submit IND in 2020.

Manufacturing:

• Advanced chemistry, manufacturing, and controls (CMC) BLA and MAA-readiness efforts for AT132.
• State-of-the-art, internal, large-scale cGMP manufacturing facility provides sufficient capacity for AT132 global commercialization as well as the near-term clinical development of all pipeline programs.
• Completed construction and commissioning of state-of-the-art, internal plasmid manufacturing facility to support production of nonclinical and cGMP-grade plasmids for all of our development programs, including the potential commercialization of AT132.

Corporate:

• Appointed Edward R. Conner, M.D. as Senior Vice President and Chief Medical Officer. Ed is responsible for leading the company’s global clinical development strategy and oversees clinical development, clinical operations, regulatory affairs, medical affairs and patient advocacy.
• Promoted Fulvio Mavilio, Ph.D. to Senior Vice President of Translational Science. Fulvio is responsible for advancing the company’s pipeline from discovery through to IND-enabling preclinical development and oversees discovery biology, pharmacology/toxicology, bioinformatics and bioanalytics.

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