8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 1, 2019

AUDENTES THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

Delaware

(State or other jurisdiction of incorporation)

001-37833	46-1606174
(Commission File Number)	(IRS Employer Identification No.)
600 California Street, 17th Floor San Francisco, California	94108
(Address of principal executive offices)	(Zip Code)

(415) 818-1001 

(Registrant’s telephone number, including area code)

Not Applicable

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐	Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐		Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐	Pre-commencement communication pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐	Pre-commencement communication pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

Item 8.01 Other Events.

On May 1, 2019, Audentes Therapeutics, Inc. (the “Company”) issued a press release attached hereto as Exhibit 99.1 announcing new data from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of X-linked Myotubular Myopathy.  In addition, the Company plans to present the information in the presentation attached hereto as Exhibit 99.2 on May 1, 2019 at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy in Washington D.C. during the plenary session, “Presidential Symposium & Presentation of the Top Abstracts,” scheduled to begin at 2:15 pm ET.

Item 9.01 Financial Statements and Exhibits.

Exhibit Number	Description
99.1	Press release titled “Audentes Therapeutics Presents New Positive Data from ASPIRO, the Phase 1/2 Clinical Trial of AT132 for X-linked Myotubular Myopathy, at 22nd Annual Meeting of the American Society of Gene and Cell Therapy”.
99.2	ASGCT Meeting Presentation.

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

AUDENTES THERAPEUTICS, INC.
By:	/s/ Thomas Soloway
	Thomas Soloway
	Chief Financial Officer

Date: May 1, 2019

EX-99.1

Exhibit 99.1

Audentes Therapeutics Presents New Positive Data from ASPIRO, the Phase 1/2 Clinical Trial of AT132 for X-linked Myotubular Myopathy, at 22nd Annual Meeting of the American Society of Gene and Cell Therapy

- New data include 48 weeks of follow-up for six treated patients in dose Cohort 1 and 24 weeks for three treated patients in dose Cohort 2

- Significant and sustained improvements in neuromuscular function in both dose cohorts, with corresponding achievement of clinically meaningful motor milestones

- Significant improvements in respiratory function with four patients achieving ventilator independence by the 48-week timepoint

- Robust tissue transduction, protein expression, and histological improvements in 24 and 48-week muscle biopsies in all patients

- AT132 has been generally well-tolerated and has shown a manageable safety profile across both dose cohorts with no clinically meaningful safety differences between doses to date

- Presentation scheduled to begin at 2:15 pm ET.  Slides used during today’s presentation will be available on the Investor + Media section of the Audentes website for approximately 30 days.

SAN FRANCISCO, May 1, 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 announced new positive data from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of X-linked Myotubular Myopathy (XLMTM).  The data are being presented today at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy by Perry B. Shieh, M.D., Ph.D., Associate Professor of Neurology, University of California Los Angeles and Principal Investigator for ASPIRO during the plenary session, “Presidential Symposium & Presentation of the Top Abstracts,” scheduled to begin at 2:15 pm ET.

"The encouraging clinical profile established by AT132 in the ASPIRO Phase 1/2 study is further supported by the new data shared today,” stated Dr. Shieh.  “Results across both dose cohorts show clinically meaningful improvements in neuromuscular and respiratory function, durable improvements in muscle pathology, and progressive attainment of motor developmental milestones.”

“We are excited to share today’s results and are working hard toward our goal of making AT132 available to patients living with XLMTM globally as rapidly as possible,” stated Matthew R. Patterson, Chairman and Chief Executive Officer of Audentes.  “We look forward to important next steps for the program, including selection of the optimal dose and further discussions with regulators in the U.S. and Europe regarding possible pathways to license applications.”

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, to present this most recent data update and gain further alignment on the license application submission pathways for AT132 in the United States and Europe.

About X-linked Myotubular Myopathy

XLMTM is a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure, and early death. Mortality rates are estimated to be 50 percent in the first 18 months of life, and for those patients who survive past infancy, there is an estimated 25% mortality by the age of 10. XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation, and function of skeletal muscle cells. The disease affects approximately 1 in 40,000 to 50,0000 newborn males.

XLMTM places a substantial burden of care on patients, families and the healthcare system, including high rates of healthcare utilization, hospitalizationand surgical intervention. More than 80 percent of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support. In most patients, normal developmental motor milestones are delayed or never achieved. Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.

About AT132 for the treatment of X-linked Myotubular Myopathy

Audentes is developing AT132, an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of XLMTM. AT132 may provide patients with significantly improved outcomes based on the ability of AAV8 to target skeletal muscle and increase myotubularin expression in targeted tissues following a single intravenous administration. The preclinical development of AT132 was conducted in collaboration with Genethon (www.genethon.fr).

AT132 has been granted Regenerative Medicine and Advanced Therapy (RMAT), Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the U.S. Food and Drug Administration (FDA), and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency (EMA).

About Audentes Therapeutics, Inc.

Audentes Therapeutics (Nasdaq: BOLD) is a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases.  We are leveraging our AAV gene therapy technology platform and proprietary manufacturing expertise to develop programs across three modalities: gene replacement, vectorized exon skipping, and vectorized RNA knockdown.  Our product candidates are showing promising therapeutic profiles in clinical and preclinical studies across a range of neuromuscular diseases. Audentes is a focused, experienced and passionate team driven by the goal of improving the lives of patients.

For more information regarding Audentes, please visit www.audentestx.com.

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 potential benefits and availability of AT132 for patients and the expected timing for optimal dose selection and final agreement on regulatory submission pathways for AT132.  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 commercialize 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
415.818.1033

achang@audentestx.com

Media Contact:

Sarah Spencer

415.957.2020

sspencer@audentestx.com

Katie Hogan
415.951.3398

khogan@audentestx.com

EX-99.2

ASPIRO Phase 1/2 Gene Therapy Trial in X-Linked Myotubular Myopathy (XLMTM): Update on Preliminary Safety and Efficacy Findings Perry Shieh, MD PhD Associate Professor of Neurology, University of California Los Angeles Exhibit 99.2

Disclosures Principal Investigator in the INCEPTUS and ASPIRO XLMTM clinical trials Advisory boards Audentes, Sarepta, Roche, Avexis, Biogen Speakers’ bureau Biogen, Alexion, CSL Behring, Grifols

MTM1 gene produces myotubularin protein1 Myotubularin dephosphorylates critical second messenger proteins 1 2 3 Myotubularin required for correct Muscle growth and differentiation2,3 Cellular organization and structure2–4 Cellular function2,4,5 SR SR, sarcoplasmic reticulum Raess MA, et al. Adv Biol Regul 2017;63:49–58 Buj-Bello A, et al. PNAS 2002;99:15060–5 Di Paolo G, et al. Nature 2006;443:651–7 Hnia K, et al. J Clin Invest 2011;121:70–85 Amoasii L, et al. J Cell Sci 2013;126(Pt 8):1806–19 Lawlor MW, et al. J Neuropathol Exp Neurol 2016;75:102–10 X-Linked Myotubular Myopathy (XLMTM) Monogenic disease caused by mutations in the MTM1 gene1 scale bar = 40 µm Muscle biopsy from 2-month old boy with XLMTM shows:6 Abnormal fiber size variation Central nucleation (inset) Muscle fiber atrophy MTM1 gene

Annoussamy M, et al. Neurology 2019;92:e1852–67 Beggs AH, et al. Muscle Nerve 2018;57:550–60 Vandersmissen I, et al. Neuromuscul Disord 2018;28:766–7 Amburgey K, et al. Neurology 2017;89:1355–64 XLMTM – Natural History Incidence ≈1 in 40–50K newborn males1–4 Estimated 50% mortality by 18 months2 10-year survival of ≈75% thereafter3 Motor milestones are substantially delayed or not achieved1,4 Most cannot sit without support >10s4 ≈70–85% of patients are nonambulant1,4 >80% require breathing support and feeding tubes1,2 High rates of healthcare utilization, hospitalization, and surgical intervention1,2 Half of XLMTM patients do not survive past 18 months

ITR, inverted terminal repeat; Des, human desmin promoter polyA, polyadenylation signal; SA, splice acceptor; SD, splice donor 1. Mack DL, et al. Mol Ther 2017;25:839–54 AT132: rAAV8-Des-hMTM1 First systemic gene therapy utilizing the muscle-specific desmin promoter AAV8 effectively transduces skeletal muscle1 MTM1 gene encodes myotubularin, an enzyme required for normal development and function of skeletal muscle

CHOP INTEND, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders BL, baseline; mo, months; Wk, week ASPIRO, NCT03199469; INCEPTUS, NCT02704273 ASPIRO Phase 1/2 Clinical Study of AT132 An open-label, ascending-dose, safety and preliminary efficacy study AT132 administration Inclusion criteria Subject is male <5 years old, or enrolled in INCEPTUS Genetically confirmed XLMTM Requires ventilator support Key efficacy assessments Respiratory Ventilator use Maximal inspiratory pressure (MIP) Neuromuscular Developmental milestones CHOP INTEND Muscle biopsy Histology Vector copy number Protein expression Weeks 9–16 taper Wk 12 Wk 11 Wk 10 Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6 Wk 8 Wk 9 Wk 7 Assessments Neuromuscular Respiratory Developmental milestones Muscle biopsy INCEPTUS Subjects Wk 13 Wk 14 Weeks 1–8 Prednisolone 1mg/kg/day BL Wk 15 6 mo 12 mo Wk 16 9 mo

ASPIRO Patient Enrollment and Follow-up Eleven patients enrolled in the INCEPTUS observational run-in study have transitioned into ASPIRO Interim data as of April 8, 2019 Duration in the study (years) Age at dosinga (years) Cohort 1 Cohort 2 Patient ID 0.8 4.1 2.5 4 0.8 0.7 0.7 1.3 6.8 2.3 2.4 Follow-up period aFor control patients, age recorded at baseline visit Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg Age (years)

Safety and Tolerability

Since the initiation of the study (Sep 2017): there are 47 AEs (including SAEs) considered related/possibly related. There are 35 non-serious AEs related/possibly related Interim data as of April 8, 2019 Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg; AE, adverse event; CK, creatine kinase AT132 Well Tolerated with Manageable Safety Profile No clinically meaningful differences observed between doses Cohort Patient # Possibly/probably treatment-related serious AEs Comments Cohort 1 1 None 2 None 3 Previously reported, Week 7: Troponin I increased, CK increased, and possible myocarditis Previously reported, Week 21: Atrial tachycardia Troponemia/possible myocarditis resolved with treatment Patient was noted to have experienced an episode of tachycardia prior to enrollment in ASPIRO 5 None 6 None 7 None 4 (Control) None Cohort 2 8 None 9 Week 11: Cholestasis Cholestasis treated with ursodeoxycholic acid and oral steroids (patient had history of cholestasis and hyperbilirubinemia). Resolved 10 Week 1: Vomiting, nausea, fever and thrombocytopenia Week 4: Troponin I and ST segment elevation indicative of mild myocarditis Platelet count of 74,000/microliter, recovered in < 1 week Mild myocarditis, troponin I and ST segment elevation resolved with treatment. Normal ejection fraction and no wall motion abnormalities 11 (Control) None

Muscle Biopsy

Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg Interim data as April 8, 2019 Robust Transduction, Transcription and Protein Expression AT132 produced dose-dependent increases in the gastrocnemius muscle at Week 24 Patient 1 Patient 2 Patient 3 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Cohort 1 Cohort 2 Median (vc/dg) 2.46 13.8 Cohort 1 Cohort 2 Median (ratio) 21.72 69.5 Cohort 1 Cohort 2 Median (% normal) 83.2 202.3 vc/diploid genome MTM1 mRNA ratio (Transgene:Reference gene) Myotubularin expression (% normal) Vector copy number mRNA Protein expression

Patient 1 Patient 2 Patient 3 Patient 5 Patient 6 Patient 7 MTM1 mRNA ratio (Transgene:Reference gene) Interim data as April 8, 2019 Molecular Findings Consistent Across Muscle Groups Cohort 1 showed robust increases in transduction, transcription, and protein expression in the vastus lateralis muscle at Week 48 Vector copy number Protein expression Cohort 1 Cohort 2 Median (vc/dg) 2 Pending Cohort 1 Cohort 2 Median (ratio) 24.2 Pending Cohort 1 Cohort 2 Median (% normal) 85.2 Pending Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg Myotubularin expression (% normal) mRNA vc/diploid genome

H&E NADH Healthy 5-year-old Baseline Week 24 Week 48 Improvement in Histopathological Hallmarks of XLMTM Cohort 1 Representative Histology Baseline – Classic XLMTM pathology including fiber smallness, internally placed nuclei, and central aggregates of organelles on NADH stain Week 24 – Organelle mislocalization improves markedly, but abnormalities of fiber size and internal nucleation remain Week 48 – Fiber size abnormalities are markedly improved in most samples between 24 and 48 week timepoints, but internal nucleation persisted in many samples Overall pattern is consistent across Cohort 1 biopsies Interim data as April 8, 2019 Cohort 1: 1x1014vg/kg H&E, hematoxylin and eosin; NADH, nicotinamide adenine dinucleotide Cohort 1 shows progressive improvement from 24 to 48 weeks

Healthy 2-year-old Baseline Week 24 Histopathological Findings in Cohort 2 Suggest More Rapid Rate of Pathological Recovery Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg H&E, hematoxylin and eosin; NADH, nicotinamide adenine dinucleotide Cohort 2 Representative Histology Cohort 2 biopsy at Week 24 shows the same recovery as observed in patients from Cohort 1 at 48 weeks  Baseline – Classic XLMTM pathology including fiber smallness, internally placed nuclei, and central aggregates of organelles on NADH stain Week 24 – Fiber size and organelle mislocalization improvements are similar to or better than Cohort 1 biopsies Interim data as April 8, 2019 H&E NADH

Neuromuscular Function CHOP INTEND and Developmental Milestones

64 Control patients Patient ID Baseline score Latest score Change from baseline (%) Cohort 1 1 29 56 (Wk48) +93 2 45 64 (Wk48) +42 3 34 39 (Wk48) +15 4 49 47 (Wk48) -4 5 36 63 (Wk48) +75 6 39 53 (Wk48) +36 7 43 64 (Wk48) +49 Cohort 2 8 36 61 (Wk24) +69 9 39 55 (Wk24) +41 10 29 46 (Wk24) +59 11 42 37 (Wk12) -12 Significant Improvements in Neuromuscular Function All treated patients showed rapid and clinically meaningful increases in CHOP INTEND scores CHOP INTEND, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg Interim data as of April 8, 2019 Maximum score = 64 points (typically reached by healthy infants approximately 3-6 months of age) Patient in halo traction device

CHOP INTEND, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders BL, baseline; LS, Least Squares Bars indicate standard error Interim data as of April 8, 2019 LS Mean Increase in CHOP INTEND Score Treated patients showed sustained clinical improvements in motor function Treated Control Weeks after ASPIRO baseline Change from baseline in CHOP INTEND score (LS mean) BL

Motor Milestones: Head Control Treated patients show progressive attainment of milestones regardless of age Months after birth Age 1 Age 2 Age 3 Age 4 Age 5 Age 6 Age 7 1 2 3 4 5 6 7 8 9 10 11 12 Head control   1 11 2 9   5 10 4   6   7   8 Interim data as of April 8, 2019 Patient 3 not evaluable because of halo traction device Control Patients (4 and 11): Untreated; Cohort 1: Treated patients received AT132 1´1014 vg/kg; Cohort 2: Treated patients received AT132 3´1014 vg/kg Upper end of normal window of achievement # # # Patient ID (Control, Cohort 1, Cohort 2) Able to perform Unable to perform Data not available For all patients, colored bars start at the age of the patient at treatment start and end at the latest assessment visit per patient

Motor Milestones: Rolling From Back to Stomach Treated patients show progressive attainment of milestones regardless of age Months after birth Age 1 Age 2 Age 3 Age 4 Age 5 Age 6 Age 7 1 2 3 4 5 6 7 8 9 10 11 12 Rolling from back to stomach   1 11 2 9 5 10 4 6 7 8 Interim data as of April 8, 2019 Patient 3 not evaluable because of halo traction device Control Patients (4 and 11): Untreated; Cohort 1: Treated patients received AT132 1´1014 vg/kg; Cohort 2: Treated patients received AT132 3´1014 vg/kg Upper end of normal window of achievement # # # Patient ID (Control, Cohort 1, Cohort 2) Able to perform Unable to perform Data not available For all patients, colored bars start at the age of the patient at treatment start and end at the latest assessment visit per patient

Motor Milestones: Sitting 30 sec Without Support Treated patients show progressive attainment of milestones regardless of age Months after birth Age 1 Age 2 Age 3 Age 4 Age 5 Age 6 Age 7 1 2 3 4 5 6 7 8 9 10 11 12 Sitting 30 sec without support 1 11 2 9 5 10 4 6 7 8 Interim data as of April 8, 2019 Patient 3 not evaluable because of halo traction device Control Patients (4 and 11): Untreated; Cohort 1: Treated patients received AT132 1´1014 vg/kg; Cohort 2: Treated patients received AT132 3´1014 vg/kg Upper end of normal window of achievement # # # Patient ID (Control, Cohort 1, Cohort 2) Able to perform Unable to perform Data not available For all patients, colored bars start at the age of the patient at treatment start and end at the latest assessment visit per patient

Motor Milestones: Makes Stepping Movements Treated patients show progressive attainment of milestones regardless of age Months after birth Age 1 Age 2 Age 3 Age 4 Age 5 Age 6 Age 7 1 2 3 4 5 6 7 8 9 10 11 12 Makes stepping movements 1 11 2 9 5 10 4 6 7 8 Interim data as of April 8, 2019 Patient 3 not evaluable because of halo traction device Control Patients (4 and 11): Untreated; Cohort 1: Treated patients received AT132 1´1014 vg/kg; Cohort 2: Treated patients received AT132 3´1014 vg/kg Upper end of normal window of achievement # # # Patient ID (Control, Cohort 1, Cohort 2) Able to perform Unable to perform Data not available For all patients, colored bars start at the age of the patient at treatment start and end at the latest assessment visit per patient

Respiratory Function Maximal Inspiratory Pressure (MIP) and Ventilator Dependence

MIP 80 cmH2O: Estimated lower limit of normal in healthy children <5 years of age MIP (cmH2O) Weeks after ASPIRO baseline BL Uncuffed tracheostomy, gas leak: Patients 7 and 8 Significant Improvements in Respiratory Function Interim data as of April 8, 2019 MIP, maximum inspiratory pressure BL, baseline; MIP, maximal inspiratory pressure; Wk, week Increased respiratory muscle strength as assessed by MIP following AT132 Patient ID Baseline MIP Most recent MIP Change from baseline Cohort 1 1* 33 89 (Wk24) +170% 2 44 112 (Wk48) +155% 3 26 50 (Wk48) +92% 4 58 49 (Wk48) -16% 5 14 69 (Wk48) +393% 6 35 108 (Wk24) +209% 7 29 64 (Wk48) +121% Cohort 2 8 31 45 (Wk24) +45% 9 11 40 (Wk24) +264% 10 28 16 (Wk24) -43% 11 34 29 (Wk12) -15% Control patients *Unable to collect at Week 48 due to forceful opposition by the patient Maximum Inspiratory Pressure (cmH2O)

MIP, maximal inspiratory pressure; ctrl, control; BL, baseline; Wk, week LS, Least Squares means estimated with Repeated Measures ANOVA Model Bars indicate standard error Interim data as April 8, 2019 Sustained Clinically Meaningful Improvement in Respiratory Strength in Treated Patients Weeks after ASPIRO baseline Treated Control Weeks after ASPIRO baseline MIP (cmH2O) LS mean increase from baseline BL

Significant and Rapid Reductions in Ventilator Use in All Treated Patients Interim data as of April 8, 2019 Cohort 1: 1x1014vg/kg; Cohort 2: 3x1014vg/kg BiPAP, bilevel positive airway pressure; BL, baseline; Inv, invasive; Wk, week Ventilator independence achieved by 4 patients to date Interim data as of April 8, 2019 Patient ID Status at baseline (h/day) Most recent status Change from baseline Cohort 1 1 BiPAP (12h) 0 (Wk48) -100% 2 Inv (17h) 6 (Wk 48) -65% 3 Inv (24h) 0 (Wk48) -100% 4 BiPAP (12h) 12 (Wk48) 0% 5 Inv (22.7h) 2 (Wk48) -88% 6 Inv (24h) 0 (Wk48) -100% 7 Inv (23.5h) 0 (Wk48) -100% Cohort 2 8 Inv (22.5h) 8 (Wk28) -64% 9 Inv (24h) 18 (Wk24) -25% 10 Inv (24h) 13.5 (Wk24) -56% 11 Inv (23.8h) 24 (Wk20) +0.84% Control patients Ventilator status Ventilator dependence over 24 hours Weeks after ASPIRO baseline BL

NMD, neuromuscular disease; BL, baseline; LS, Least Squares means estimated with Repeated Measures ANOVA Model Bars indicate standard error Interim data as April 8, 2019 Treated Patients Have Achieved Reductions in Ventilator Dependence Not Previously Observed in Chronically Ventilated Patients with NMD Ventilator dependence over 24 hours Weeks after ASPIRO baseline Treated Patient 4 (Control) Patient 11 (Control) BL

Patient Video Please: No photographic or video recordings of patient videos

Interim data as of April 8, 2019 ASPIRO Key Findings to Date AT132 has been generally well tolerated and has shown manageable safety profile across both dose cohorts Muscle biopsies show robust dose-dependent transduction, transcription, protein expression and histological improvements through Week 48 Rapid CHOP INTEND improvements maintained in both dose cohorts, with corresponding developmental milestone achievement Patients are attaining clinically significant milestones such as sitting, crawling, standing with support and stepping movements Continued unprecedented reductions in ventilator dependence, with four patients now ventilator independent

Acknowledgements XLMTM Preclinical Studies and ASPIRO Clinical Trial Anna Buj Bello Genethon Martin K. (Casey) Childers David Mack University of Washington, USA Alan H. Beggs Children’s Hospital Boston, USA Michael W. Lawlor Children’s Hospital and Medical College of Wisconsin, USA My team at the UCLA Medical Center Fellow principal investigators and their teams Carsten G Bönnemann James Dowling Nancy Kuntz Wolfgang Müller-Felber Francesco Muntoni Laurent Servais Barbara Smith and Barry Byrne The children, families and the entire XLMTM patient community for their cooperation and participation in these studies Patient advocacy organizations The Joshua Frase Foundation MTM-CNM Family Connection The Myotubular Trust Where There’s a Will There’s A Cure Foundation for Myotubular Myopathy ZNM – Zusammen Stark! Study expert trainers Biopsy Review Committee Audentes team members Audentes Board of Scientific and Clinical Advisors