A Trial of a Single ProHema-CB Product Transplant in Pediatric Patients With Inherited Metabolic Disorders

This study is an open-label trial of the safety of a single cord blood transplant using
ProHema-CB following busulfan/cyclophosphamide/ATG conditioning for pediatric patients with
inherited metabolic disorders.

A maximum of 12 eligible male and female subjects (1 to 18 years old, inclusive) will be
enrolled and treated in the trial at approximately 1 to 3 centers within the U.S.

All subjects will be admitted to the hospital, per institutional practice and will receive a
conditioning regimen, after which they will receive a HLA-matched or partially matched
ProHema -CB unit on Day 0.

They will receive study follow up assessments weekly following Day 0 through Day 100 and
study visit Days 180, 270, 365 and 730.

Inclusion Criteria:

1. Patients must have a confirmed diagnosis of an inherited metabolic disorder (IMD) and
be amenable to treatment by hematopoietic cell transplantation:

- Mucopolysaccharidoses: Hurler Syndrome (MPS IH), MPS I-HS (Hurler-Scheie
Syndrome), Hunter Syndrome (MPS II), Sanfilippo Syndrome (MPS III), or MPS VI
(Maroteaux-Lamy syndrome) with early neurologic involvement and/or sensitization
to enzyme replacement therapy (ERT); or

- Leukodystrophies: Krabbe disease (Globoid Leukodystrophy), Metachromatic
Leukodystrophy (MLD), Adrenoleukodystrophy (ALD and AMN); or

- Other IMD with lysosomal storage disorder including glycoproteinoses
(Alpha-Mannosidosis, Mucolipidosis II or I-Cell disease), sphingo- and other
lipidoses (Sandhoff disease, Tay Sachs disease, Pelizaeus Merzbacher (PMD),
Niemann-Pick disease, GM1 gangliosidosis, Wolman's disease.

2. Male and female subjects aged 1 to 18 years, inclusive.

3. Lack of 4 6/6 HLA matched non-carrier related UCB or 8/8 HLA A, B, C, DRß1 matched
non-carrier related or 8/8 unrelated bone marrow donor; or donor not available within
appropriate timeframe, as determined by the transplant physician.

4. Availability of suitable primary and secondary umbilical cord blood (UCB) units.

5. Adequate performance status, defined as:

- Subjects ≥ 16 years: Karnofsky score ≥ 70%.

- Subjects < 16 years: Lansky score ≥ 70%.

6. Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening
fraction > 26%.

7. Pulmonary:

- Subjects > 10 years: DLCO (diffusion capacity) > 50% of predicted (corrected for
hemoglobin)

- FEV1, FVC > 50% of predicted; Note: If unable to perform pulmonary tests, then O2
saturation > 92% on room air.

8. Renal: Serum creatinine within normal range for age, or if serum creatinine outside
normal range for age, then renal function (creatinine clearance or GFR) >
70mL/min/1.73m2.

9. Hepatic: Bilirubin ≤ 2.5 mg/dL (except in the case of Gilbert's syndrome, ongoing
hemolytic anemia, or due to the primary IMD); and ALT, AST and Alkaline Phosphatase ≤
x 3 ULN (all elevations beyond the ULN must be secondary to the primary IMD and not a
comorbid condition).

10. Signed IRB approved Informed Consent Form (ICF).

Exclusion Criteria:

1. Evidence of HIV infection or HIV positive serology.

2. Current uncontrolled bacterial, viral or fungal infection (progression of clinical
symptoms despite therapy).

3. Requirement for continuous respiratory supportive therapy (e.g. ventilator). Patients
on intermittent respiratory support should be discussed with the Sponsor.

4. Active problems related to chronic aspiration.

5. Uncontrolled seizures.

6. Any active malignancy or myelodysplastic syndrome or any history of malignancy.

7. Inability to give informed consent/assent or to comply with the requirements for care
after allogeneic stem cell transplantation.

8. Female subjects that are breastfeeding or with a positive pregnancy (HCG) test at
Screening.

9. Use of an investigational drug within 30 days prior to screening for the primary IMD.