Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

Inclusion Criteria:

1. Informed consent is obtained from a competent custodial parent or guardian with legal
capacity to execute a local IRB/IEC approved consent. Informed assent will be sought
from capable subjects, in accordance with the directive of the IRB/IEC and with local
requirements.

2. Males aged 17 years and younger, at the time of parental/guardian consent and, where
appropriate, subject assent.

3. Active cerebral ALD as defined by:

1. Elevated very long chain fatty acids (VLCFA) values, and

2. Active central nervous system (CNS) disease established by central radiographic
review of brain MRI demonstrating

i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and

ii. Gadolinium enhancement on MRI of demyelinating lesions.

4. Neurologic Function Score (NFS) ≤1.

Exclusion Criteria:

1. Prior receipt of an allogeneic transplant or gene therapy.

2. Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note:
subjects must discontinue use of these medications at time of consent.

3. Receipt of an investigational study drug or procedure within 3 months before Screening
that might confound study outcomes. Use of investigational study drugs is prohibited
throughout the course of the study.

4. Any conditions that make it impossible to perform MRI studies (including allergies to
anesthetics or contrast agents).

5. Hematological compromise as evidenced by:

1. Peripheral blood ANC count <1500 cells/mm3,

2. Platelet count <100,000 cells/mm3, or

3. Hemoglobin <10 g/dL.

4. Uncorrected bleeding disorder.

6. Hepatic compromise as evidenced by:

1. Aspartate transaminase (AST) value >2.5 × ULN

2. Alanine transaminase (ALT) value >2.5 × ULN

3. Total bilirubin value >3.0 mg/dL, except if there is a diagnosis of Gilbert's
Syndrome and the subject is otherwise stable

7. Baseline estimated glomerular filtration rate <70 mL/min/1.73 m2

8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%

9. Immediate family member with a known or suspected Familial Cancer Syndrome

10. Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or
prion associated infection.

11. Positive for HIV, hepatitis B or C virus, or human T lymphotrophic virus 1 (HTLV-1)

12. Any clinically significant cardiovascular or pulmonary disease, or other disease or
condition that would be contraindicated for any of the other study procedures.

13. Absence of adequate contraception for fertile subjects.

14. Any contraindications to the use of G-CSF or plerixafor during the mobilization of
hematopoietic stem cells, and any contraindications to the use of busulfan or
fludarabine, including known hypersensitivity to the active substances or to any of
the excipients in their formulations.