Audentes Therapeutics, Inc. announced new positive data from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of X-linked Myotubular Myopathy (XLMTM). Data Summary: The newly reported data include safety and efficacy assessments for 11 patients enrolled in ASPIRO as of the April 8, 2019 data cut-off date, including 48 weeks of follow-up for seven patients enrolled in Cohort 1 (1x1014 vector genomes per kilogram (vg/kg); six treated and one untreated control) and 24 weeks of follow-up for four patients in Cohort 2 (3x1014 vg/kg; three treated and one untreated control). Key assessments include neuromuscular function as measured by both improvements in the CHOP INTEND score and the achievement of motor milestones; respiratory function as measured by improvements in maximal inspiratory pressure (MIP) and reduction in ventilator dependence; and vector copy number, mRNA, protein expression and histological improvement as assessed via muscle biopsy. Efficacy: Rapid CHOP INTEND improvements have been achieved and maintained in both dose cohorts, and the majority of patients have demonstrated progressive attainment of motor developmental milestones, such as head control, sitting unassisted, crawling, standing with support and initiating stepping movements. Patients receiving AT132 have achieved reductions in ventilator dependence not previously observed in chronically ventilated patients with neuromuscular disorders. Reduction of ventilator dependence is an endpoint considered to be correlated with survival. Four patients were successfully weaned off of ventilation by the 48-week timepoint, with all other treated patients demonstrating sustained and clinically meaningful reductions in ventilator use. Muscle biopsy data show robust dose-dependent transduction, transcription and protein expression. All biopsies show marked improvement in histopathological markers of disease, with a trend toward continued improvement in the Cohort 1 patient samples from 24 to 48-week timepoints, and evidence of more rapid pathological improvement by week 24 in the Cohort 2 biopsy samples. Safety: AT132 has been generally well-tolerated and has shown a manageable safety profile across both dose groups. There have been no possibly or probably treatment-related serious adverse events (SAEs) reported in Cohort 1 since the scientific update in May 2018. There have been eight possibly or probably treatment-related SAEs reported in Cohort 2. All SAEs have been successfully managed and patients have shown no evidence of clinical compromise. Results to date indicate no clinically meaningful differences in the safety and tolerability profile of AT132 between the 1x1014 vg/kg and 3x1014 vg/kg dose cohorts. Next steps in the AT132 development program include selection of the optimal dose in the ASPIRO study, planned to occur in the second quarter of 2019, and further interactions with the FDA and EMA, planned to occur in the third quarter of 2019.