• Device definition was added and device malfunction reporting requirements were more clearly defined. • The Ratings Assessment Guidelines were replaced with the document specific to the BMN 190 program. • Added that the 6-month Safety Follow-Up Visit is to be waived for subjects who receive study drug in another BioMarin-sponsored study or registry within the 6-month period to reduce subject burden. AE and SAE reporting instructions were updated for subjects who receive study drug in another BioMarin-sponsored study or registry. • Clarity was added around the timing of device removal for the sake of patient safety, in order to ensure that the device is removed in a timely manner following the end of study drug administration. • The visit window for the MRI was increased to ±4 weeks to aid with the feasibility of the assessment. • CSF anti-drug immunogenicity testing was removed from the Safety Follow-Up visit because the ICV device and associated infusion system are to be removed from the patient by the time of the visit. • Per Regulatory Agency feedback, modified the inclusion criterion for contraception use to specify that if sexually active and not practicing true abstinence, defined as no sexual activity, males and females of reproductive age were to use a highly effective method of contraception while participating in the study. • The Device Safety Follow-Up Visit was added.

Clarified:Vital signs(SBP,DBP,Heart rate(HR),Respiration rate & temperature)measured within 30(+/-5)min before infusion start/restart, every 30(+/-5)min during infusion, 0.5hrs(+/-5 min), 1hr(+/-5 min) & 4hrs(+/-15 min)after infusion end, every 4hrs(+/-15 min)for next 16hrs To collect accurate BP measurements,BP measured in upper arm using appropriate sized BP cuff. If BP abnormal, manual BP was obtained by trained healthcare professional Subjects with present/past bradycardia, conduction disorders/structural heart disease, ECG(12 lead(HR,Rhythm,Intervals,Axis,Conduction defects & anatomic abnormalities)performed within 30 min before start of infusion(+/-5 min), at 2hrs(+/-15 min)during infusion, within 15(+/-5)min after infusion end, & 12hrs(+/-3hrs)after infusion end for each study drug infusion Clarified standard ECG performed at first infusion & every 24wks within 15(+/-5)min after infusion end Added cardiovascular & ECG AEs as AEs of special interest required reporting to BioMarin Pharmacovigilance, irrespective of severity, seriousness/causality within 24hrs of study site awareness Revised wording requiring fasting for minimum of 2hrs before each BMN190 infusion to state fasting could be considered until subject's reaction to study drug was determined. There were no efficacy/safety considerations required fasting Clarified:If needle dislodged during infusion, it could not be reinserted, as sterility would have been compromised Clarified:Medical device was defined as infusion pump & all contact parts(reservoir & catheter, needles, infusion line with filter, extension sets, & syringes) intended to be used for BMN190 Clarified:language for pregnancy reporting & monitoring Clarified requirement for IV access line during study drug infusion to allow omitting placement in event there had not been significant infusion-related AEs during prior 3 infusions Clarified:In event ICV device was replaced, next infusion to occur atleast 14days, no more than 28days

• For at least one infusion of BMN 190 (and preferably the next infusion), continuous ECG monitoring (3- or 5-lead) was performed for all subjects. The ECG was to begin 15 (± 5) minutes prior to infusion start, continue through infusion of BMN 190, and end after infusion of flushing solution. If a 12-lead ECG was required during this time, continuous monitoring was to be interrupted in order to obtain the 12-lead ECG. • Revised 12-lead ECG assessment was to occur 30 (± 5) minutes after infusion end for all subjects to provide adequate time for the infusion of flushing solution and completion of telemetry prior to the 12-lead ECG assessment. • Added requirement that all removed or replaced implantable ICV devices must be returned to BioMarin in order to evaluate the material integrity of the reservoir, and any other devices (as defined in the protocol) were also to be returned.

• Updates were made to the immunogenicity assessment section to include serum NAb sample collection. This change was made in response to a Regulatory Agency request to evaluate the presence of neutralizing antibodies to BMN 190 in serum. No changes were made to the frequency or schedule of assessments. • Added clarification that for subjects who do not participate in an extension study or registry after the last dose of study drug, the 4-week device safety follow-up visit and 6-month safety follow-up visit was to capture information regarding ongoing events at the time of the last dose or new events related to study drug. • Re-classified EEG from the list of safety assessment to efficacy assessments as this test provides information regarding changes in electrical activity in the brain while on study drug, but does not provide safety information used to determine whether dose modification or interruption is warranted. • Added that central laboratories (or a central reviewer) were used to evaluate EEG scans in order to standardize review and data presentation, and limit site-associated variability. • Added CLN2 disease rating scale assessment to the 4-week device safety follow-up visit and 6-month safety follow-up visit in order to ascertain whether there were any functional changes associated with any reported AEs. • Added ophthalmology/VA assessment every 12 weeks and OCT every 24 weeks in order to provide additional data to supplement the vision domain of the CLN2 rating scale. • Removed EQ-5D-5L Questionnaire in order to decrease study burden and the determination that the other Quality of Life questionnaires administered may be more relevant to this patient population.