• Added clarification to Secondary Outcome and Statistical Analysis that the Vineland Adaptive Behavior Scale II will be used • Clarified sample types for lab work to include: o Screening, Pre-infusion, Days 7, 14, 30, 90, 180, Months 12, 18, 24 visits: Aspartate aminotransferase (AST), alanine transaminase (ALT), serum/plasma gamma-glutamyl transpeptidase (serum/plasma GGT), Serum/plasma total bilirubin o Day 1: Serum/plasma total bilirubin o Days 45, 60, 75, 120, 150, 2-weeks post steroid taper visits: AST, ALT, serum/plasma GGT • Clarified for Screening, Day 30, 180, Month 12 visit regarding abdominal magnetic resonance imaging (MRI) to measure liver and spleen volumes • Clarified Section 6.3.1 Day of Gene Transfer (Day 0) instructions • Section 6.4.1.1, added clarification regarding tapering instructions • Added assessment at Day 30 for amylase levels • Section 7.4.1, deleted ‘recession’ • Section 7.4.3: Updated with new data available • Updated References

• Separated signature pages for Sponsor and Principal Investigator • Added tables to describe document history • Clarified clinical phase of study • Clarified study population and updated inclusion/exclusion criteria • Updated primary, secondary and exploratory outcomes • Reorganized the introduction sections according to a new template • Removed age criteria • Added inclusion criterion: Cognitive Development Quotient (DQ) lower than 60 • Added exclusion criteria: • Participants with concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or precludes the child from participating in the protocol assessments and follow up • Participants with a positive response for the ELISPOT for T-cell responses to AAV9 • Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone) • Previous treatment by Haematopoietic Stem Cell transplantation • Previous participation in a gene/cell therapy or enzyme replacement therapy (ERT) clinical trial • Deleted exclusion criteria: • Prior treatment with n-sulfoglucosamine sulfohydrolase (SGSH) ERT • Updated Primary and Secondary Outcome Measures and added Exploratory Measures • Remove the Dose Limiting Toxicity section • Included a section with Dosing New Participants, to clarify that patients will be treated with a 14-day interval • Modify the Stopping Rules, to indicate that study will be halted if 2 or more SAEs (not Grade III AEs) are reported. • Deleted neurocognitive assessment using Leiter scale • Inclusion of a neurocognitive validity form • Inclusion of the Vineland, Bayley, Mullen and Kaufman (depending on developmental age) scale neurocognitive assessment for all participants participating. • Added Pediatric Quality of Life Inventory (PedsQL™), Parenting Stress Index, 4th Edition (PSI-4) and Children’s Sleep Habits Questionnaire (CSHQ) clinical questionnaire

(continued) • Added Sanfilippo Behavior Rating Scale (SBRS) Scales assessment, Parent Global Impression Score, Clinical Global Impression Improvement Scale and Parent Symptom Score Questionnaire • Included diffusion tensor imaging (DTI) analysis on the brain MRI images. • Changed the patient weight for dosing to the one obtained in Screening visit 2. • Included four audiometry clinical assessments (Screening, Month 6, 12 and 24). • Provided more detailed information about the vital sign collection after treatment • Changed some study visit windows to allow more flexibility. • Included new clinical biomarkers such as plasma and CSF cytokines, GM2/GM3. • Added CSF biobanking • Included new gene therapy biomarkers such as neutralizing antibodies against the adeno-associated Virus 9 (AAV9) capsid. • Included a participant questionnaire to collect information on the quality of the service provided by vendors interacting with participants. • Reorganized the safety sections according to a new template • Limited the SAEs to those who are following the regulatory definition by International Conference on Harmonization (ICH) and not all grade 3, 4 or 5. • Replaced terminology of ‘subject’ with ‘participant’ • Added 60-minute electroencephalogram (EEG) at Months, 6, 2, 18, and 24

• Added inclusion criterion: ‘Age range of 2 years up to 18 years (excluded)’. • Updated the version of CTCAE to be referenced for AEs, to v4.03. • Revised the following secondary outcome to exploratory outcome: • Change from baseline in the Sanfilippo Behavior Rating Scale [Time Frame: Month 6, 12, 18, 24] • Removed brain MRI assessment and brain DTI analysis at Days 30 and 180. • Clarification of the scale to be used for the two arms in the study above and below 18 months of chronological age. • Removed medical history assessment at Visits 2 and 3. • Added urine pregnancy test (if applicable) at Day 0, Months 12 and 24. • Added troponin in the panel of labs, to be assessed at Visit 1, Days -1 and 1, and at Visits 4 to 12. • ELISpot assessment: removed from Day 7 and added at Days 45, 75, 120, and at 2-weeks post-steroid, if needed based on previous results. • Corrected several inconsistencies between the schedule of evaluations table and Section 5, study procedures. • Revised the electroencephalogram (EEG) assessment from 60-minute EEG to 45-minute EEG. • Clarified that audiometry evaluations will start with tympanometry and otoacoustic emissions (OAE). In case relevant alterations are detected, an auditory brainstem response (ABR) along all frequencies will be assessed. • Added the acceptable method of contraception for the study and instructions on reporting of pregnancy during the study. • Specified the prohibited medications for the study and instructions on capturing concomitant medication/therapy. • Specified that the blood sample schedule and collection allows for a maximum blood volume of 35 ml per study visit, with flexibility to the sites to reduce volume as per site policy if needed and that additional ad-hoc analysis on blood samples collected at any particular visit may be performed at the discretion of the principal investigator (PI).

(continued) • Specified the order of certain scales to be administered and the provision for use of an external qualified and trained rater, if the family signed the consent annex. • Added that prophylactic enteral prednisone or prednisolone will not be provided by the Sponsor; the standard of care at the site/country should be used for prophylaxis. • Revised the wording on long-term monitoring to include the long-term follow-up study designed to enroll participants who complete the current study. • Provided rationale on the choice of primary and secondary outcomes. • Clarified the definitions and reporting of AEs, SAEs and serious adverse reactions (SAR). • Clarified the stopping/discontinuation rules for the study (Section 7.2). • Added that the date of birth and age of the participant at screening will be collected to ensure that the appropriate age-based assessments are performed throughout the study. Demographic data including age, gender, race and date of birth will be collect at Visit 1. • Clarified the Data Safety Monitoring Board (DSMB) roles and requirements, including an update to the minimum number of members required, from 3 to 4 members. • Several editorial changes for clarity and correction of errors throughout the protocol. • Clarified the EEG roles and requirements, including an update to the minimum number of members required, from 3 to 4 members. • Several editorial changes for clarity and correction of errors throughout the protocol.