Audentes (BOLD) Reports Positive Interim Data from First Dose Cohort of ASPIRO, a Phase 1/2 Clinical Trial of AT132 in Patients With XLMTM

January 4, 2018 7:06 AM

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 positive interim data from the first dose cohort of ASPIRO, a Phase 1/2 clinical trial of AT132 in patients with X-Linked Myotubular Myopathy (XLMTM). ASPIRO is a multicenter, multinational, open-label, ascending dose study to evaluate the safety and preliminary efficacy of AT132 in approximately 12 XLMTM patients less than five years of age.

"The early AT132 efficacy data observed in our first dose cohort of patients have exceeded our expectations," stated Dr. Suyash Prasad, Senior Vice President and Chief Medical Officer of Audentes. "At the 12-week timepoint, Patient 1 has improved from a severely compromised baseline to achieve a CHOP-INTEND score and maximal inspiratory pressure that are approaching the ranges normally seen in healthy children. Importantly, Patient 1 has also attained several age-appropriate developmental milestones within this time period, including head-control, rolling over and sitting unassisted. While still early in the trial, we view these initial efficacy data as a promising indicator of the potential for AT132 to bring meaningful benefit to patients and families living with this devastating disease."

ASPIRO Interim Data Summary The interim data includes safety and efficacy assessments for the first dose cohort of ASPIRO, comprised of three AT132-treated patients dosed at 1x1014 vector genomes (vg) per kilogram (kg), and one delayed-treatment control patient. As of December 21, 2017, individual patient follow-up ranged from 4 to 12 weeks.

Safety SummaryThere have been a total of six adverse events (AEs) reported in ASPIRO, two of which were determined to be serious adverse events (SAEs). Both SAEs occurred in Patient 3, the first of which was a hospitalization one week post-administration due to pneumonia and was deemed not treatment-related. Patient 3 was also hospitalized at week 7 post-administration due to a gastrointestinal infection and elevated troponin levels, the latter of which was deemed probably treatment-related and is responding to treatment with intravenous steroid administration and supportive care.

Of the four non-serious AEs, two have been determined to be probably or possibly treatment-related. Patient 1 experienced a mild, clinically asymptomatic exacerbation of a preexisting elevated bilirubin level, which was deemed possibly treatment-related and resolved with treatment. Patient 2 experienced a clinically asymptomatic elevation in liver enzyme levels toward the end of the protocol-specified prednisolone weaning period, which was deemed to be probably treatment-related and was controlled by extending the duration of steroid coverage.

Efficacy Summary The key assessment of neuromuscular function in this first data set from Cohort 1 is the CHOP-INTEND scale, in which a maximal score of 64 reflects the level of neuromuscular function that a healthy baby is expected to approach by 3-6 months of age. Additional analyses to be reported based on longer term follow-up include the MFM-20 and Bayley-III™ scales of infant and toddler development (fine and gross motor function). Motor developmental milestones are captured within each of the neuromuscular assessments.

The key assessment of respiratory function in this first data set from Cohort 1 is a measurement of maximal inspiratory pressure (MIP), for which values ≥ 80 cmH20 are considered normal in healthy children less than 5 years of age. Additional analyses to be reported based on longer term follow-up include measurement of maximal expiratory pressure (MEP), time per day on invasive ventilatory support (tracheostomy) or non-invasive respiratory support (BiPAP), and for those patients who are on 24-hour continuous ventilatory support, an assessment of ability to maintain adequate respiratory function while off a ventilator, termed "respiratory sprinting."

Patient Interim Data Summaries:

Physicians and caregivers have reported progressive qualitative improvements in disease severity in all treated patients. Ventilator settings (pressure, rate and volume of mechanical ventilation) have been reduced in Patients 1 and 2. All treated patients have demonstrated improvements in airway clearance control, including swallowing and coughing, which is critical to preventing aspiration. By way of example, at baseline Patient 1 required suctioning of the oro-pharyngeal cavity several times per hour, and by week 12 he required no suctioning. In addition, investigators report anecdotally that all treated patients have increased limb and trunk strength, which is an early indicator of gross motor function improvement, and that the velocity and accuracy of their movements have increased. Caregivers also report that patients have increased vocalization, improving their ability to communicate.

"Physician and caregiver reports of patient progress are an important complement to the formal neuromuscular and respiratory data being collected," stated Dr. Prasad. "These qualitative assessments of the child's overall disease state and degree of change between visits provide further insight into the impact of AT132 on the XLMTM disease course."

Audentes is currently reviewing the interim efficacy and safety data with the independent Data Monitoring Committee of ASPIRO prior to initiating enrollment and dosing of the next cohort. Audentes plans to provide the next update on interim data from ASPIRO in the second quarter of 2018.

"This is a promising start to ASPIRO," stated Matthew R. Patterson, President and Chief Executive Officer of Audentes. "While the data are preliminary, we are very encouraged and will continue to advance this important work as rapidly as possible, keeping in mind our goal of bringing a potentially transformative treatment to patients living with this devastating disease."

Conference CallAt 8:00 a.m. Eastern Time today, Audentes management will host a conference call and a simultaneous webcast to discuss the interim data from the first dose cohort of ASPIRO. To access a live webcast of the conference call, please visit the Investor and Media page of the Audentes website at Alternatively, please call 1-833-659-8620 (U.S.) or 1-409-767-9247 (international) and dial the conference ID 4957669 to access the call. A replay of the webcast will be available on the Audentes website for approximately 30 days.


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