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10-K
AUDENTES THERAPEUTICS, INC. filed this Form 10-K on 03/13/2017
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Table of Contents

The second canine study was designed to compare the effects of three different doses of AT132 delivered by systemic administration versus untreated XLMTM and normal dogs. The three doses, a low dose (3 x 1013 vg/kg), a mid-dose (2 x 1014 vg/kg) and a high dose (5 x 1014 vg/kg), were administered to XLMTM dogs at ten weeks of age and the dogs were evaluated for 45 weeks. Three dogs were treated at each dose. In this study, the low dose was deemed to be the minimally effective dose, meaning that it produced somewhat extended survival and some improvement in functional parameters, including muscle strength, but not optimal restoration of function. Dosing at both the mid and high doses resulted in dramatically superior efficacy outcomes as compared to untreated XLMTM dogs, including improvements in muscle strength, normalization of gait, neurological and respiratory function and 100% survival. In the mid and high dose cohorts, the study reported homogeneous biodistribution of the vector in skeletal muscle throughout the body, and robust expression levels of myotubularin. Specifically, the mid dose resulted in a range of 10% to 40% of normal myotubularin levels, and the high dose resulted in approximately 100% of normal myotubularin levels as measured in a wide range of skeletal muscle.

Clinical Development of AT132

The clinical development plan for AT132 consists of three studies to evaluate AT132 in children with XLMTM and to characterize the disease. We submitted an IND for AT132 in the first quarter of 2017 and have initiated RECENSUS, a retrospective medical chart review study, and INCEPTUS, a clinical assessment and Phase 1/2 run-in study. We plan to report initial data from the RECENSUS and INCEPTUS studies in mid-2017. We are also planning to initiate ASPIRO, the Phase 1/2 study of AT132, in 2017, and to report preliminary data from ASPIRO in the fourth quarter of 2017.

 

RECENSUS - Retrospective Medical Chart Review Study (Ongoing): The RECENSUS study is an international, retrospective medical chart review of approximately 120 living and deceased XLMTM patients. The purpose of this study is to further characterize the clinical manifestations and natural history of XLMTM. In addition, this study may serve as a historical control for the planned Phase 1/2 ASPIRO trial. However, given that RECENSUS is a retrospective medical chart review of historical patient records, many of the assessments and patient management plans will be different than those used in INCEPTUS and ASPIRO.  Accordingly, we may be unable to make rigorous comparisons between the results obtained in RECENSUS and those obtained in the INCEPTUS and ASPIRO trials.

 

INCEPTUS - Clinical Assessment and Phase 1/2 Run-In Study (Ongoing): INCEPTUS is an international, clinical assessment study of approximately 12 to 16 patients, less than four years of age, with XLMTM. The primary objective of this study is to characterize the disease course and natural history of children with XLMTM, with a specific focus on respiratory and neuromuscular measurements. In addition, the study will assess the burden of disease on XLMTM subjects and caregivers.  The study is also expected to identify patients for potential enrollment in ASPRIRO, the Phase 1/2 study of XLMTM, and to serve as a within patient control for ASPIRO.

 

ASPIRO - Phase 1/2 Study (Planned): The Phase 1/2 study of AT132 is a multicenter, multinational, open-label, ascending dose, delayed-treatment concurrent control study to evaluate the safety and preliminary efficacy of AT132 in approximately 12 XLMTM patients less than five years of age. The study is expected to include nine AT132 treated subjects and three delayed-treatment concurrent control subjects. Primary endpoints include safety (adverse events and certain laboratory measures, including immunological parameters) and efficacy (assessments of neuromuscular and respiratory function). Secondary endpoints include the burden of disease and health related quality-of-life, and muscle tissue histology and biomarkers. The primary efficacy analysis is expected to be conducted at 12 months, with interim evaluations expected to be conducted at earlier time points. After the primary 12-month assessment, subjects are expected to be followed for another four years to assess long term safety, durability of effect and developmental progression.

 

Regulatory Interactions

We have held pre-IND meetings with the FDA regarding our IND submission, and with EU regulatory authorities regarding our planned CTA submissions.  In addition, both the FDA and European Medicines Agency, or EMA, have granted orphan drug designation for AT132.

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