Batten CLN6 Gene Therapy

The proposed clinical trial is the first human, open-label, single dose study of
self-complementary AAV9 carrying the CLN6 gene under the control of a hybrid CMV
enhancer/chicken-β-actin promoter (scAAV9.CB.CLN6) delivered one-time through an intrathecal
catheter inserted by a lumbar puncture into the interspinous into the subarachnoid space of
the lumbar thecal sac. All twelve patients will receive a dose equivalent to (1.5 x10^13 vg).
This will be administered premixed with 2.5 mL of the contrast Omnipaque™ at a concentration
of 180 mgI/mL of the contrast via a 10 mL syringe and a Spinal Needle. If no clinically
significant improvement without toxicity is observed, the possibility of adding an additional
escalation cohort at a higher dose will be discussed with the FDA, DSMB and relevant
oversight regulatory agencies.

Inclusion Criteria:

- Diagnosis of CLN6 disease determined by genotype available at Screening

- Quantitative clinical assessment of the Hamburg motor-language aggregate score at
Screening on CLN2 disease motor-language scale, as defined in the Ratings Assessment
Guideline.

- Age ≥1 year

- Written informed consent from parent or legal guardian and assent from subject, if
appropriate.

- Ability to comply with protocol required assessments (laboratory sample collection,
EEG, ECG, MRI, etc.

Exclusion Criteria:

- Another inherited neurologic disease, e.g., other forms of CLN or seizures unrelated
to CLN2 disease (patients with febrile seizures may be eligible)

- Another neurological illness that may have caused cognitive decline (e.g., trauma,
meningitis, hemorrhage) before screening

- Active viral infection

- Has received stem cell or bone marrow transplantation for CLN6 disease

- Contraindications for spinal tap procedure (e.g., spina bifida, meningitis,
impairment, or clotting abnormalities)

- Contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in
the eye, aneurysm clip in the brain)

- Episode of generalized motor status epilepticus within 4 weeks before the First Dose
visit

- Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks
before the First Dose visit (enrollment may be postponed)

- Has received any investigational medication within 30 days before the first infusion
of study drug

- Patients with Anti-AAV9 antibody titers ≥ 1:50 as determined by ELISA binding
immunoassay.

- Has a medical condition or extenuating circumstance that, in the opinion of the
investigator, might compromise the subject's ability to comply with the protocol
required testing or procedures or compromise the subject's wellbeing, safety, or
clinical interpretability

- Pregnancy any time during the study; a female subject judged by the investigator to be
of childbearing potential will be tested for pregnancy

- Abnormal laboratory values considered clinically significant (GGT > 3XULN, Bilirubin ≥
3.0 mg/dL , Creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 15,000 per cmm)