Gene Transfer Study of AAV9-CLN3 for Treatment NCL Type 3

Open-label, dose escalation clinical trial including two study cohorts of NCL type 3 (CLN3
disease) subjects. Cohort 1 will evaluate a one-time low-dose via intrathecal injection of
AAV-CLN3 and Cohort 2 evaluating a one-time high-dose intrathecal injection of AAV-CLN3
vector construct containing human CLN3 transgene. This study will be monitored by a Data
Safety Monitoring Committee (DSMB). Cohort 2 subjects (high-dose) will proceed with treatment
after evaluation by the DSMB of AAV9-CLN3 in Cohort 1 (low-dose) subjects. Both subject
cohorts will participate in the ongoing study for a period of at least three years. Periodic
assessments including clinical, laboratory, cognitive and medical imaging assessment will be
performed. Participating subjects will be asked to participate in a separate long term
follow-up study for a total duration of approximately 5 years from the time of completion of
the active phase of the current study.

Inclusion Criteria:

- CLN3 diagnosis, confirmed by the presence of a mutation in the CLN3 gene as determined
by gene sequencing from a laboratory certified by the Clinical Laboratory Improvement
Act/Amendment (CLIA) or an equivalent organization.

- Age ≥3 years through 10 years of age

- UBDRS physical impairment score of ≤7

- Mobility: Independently walking for a distance of at least 50 feet

Exclusion Criteria:

- Presence of another neurologic, metabolic or immunologic disease

- Presence of another neurological illness resulting in cognitive decline

- Recent generalized motor status epilepticus

- Prior corneal or intraocular surgery

- Active viral infection or severe bacterial infection

- Hepatic laboratory values (ALT) outside of the protocol required range

- Pre-existing Anti-AAV9 antibody titers above the protocol-required limit

- Clinically significant abnormal laboratory values as defined in the protocol

- Prior stem cell or bone marrow or organ transplantation

- Recent Chemotherapy, radiotherapy or other immunosuppression therapy

- Current use of cannabinoids and any by-products

- Contraindications for intrathecal injection procedure

- Contraindications for MRI scans

- Recent participation in a clinical trial of an investigational treatment