Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II

The objectives of the study are to provide long term expression of IDS and improve the
current clinical outcome of enzyme replacement therapy (ERT) in subjects with MPS II, a
recessive lysosomal storage disorder that results from mutations in the gene encoding IDS.
SB-913 is a therapeutic for ZFN-mediated genome editing which will be delivered by
adeno-associated virus (AAV)-derived vectors. SB-913 is intended to function by placement of
the corrective copy of IDS transgene into the genome of the subject's own hepatocytes, under
the control of the highly expressed endogenous albumin locus, and is expected to provide
permanent, liver-specific expression of Iduronate 2-Sulfatase for the lifetime of an MPS II
patient.

Inclusion Criteria:

- Male or female ≥ 5 years of age

- Clinical diagnosis of MPS II (based on evidence of hepatosplenomegaly, dysostosis
multiplex by X-ray, valvular heart disease, or obstructive airway disease) IDS
deficiency confirmed by gene sequencing.

Exclusion Criteria:

- Known to be unresponsive to ERT

- Neutralizing antibodies to AAV 2/6

- Serious intercurrent illness or clinically significant organic disease (unless
secondary to MPS II)

- Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or
hepatitis C or HIV 1/2

- Lack of tolerance to idursulfase treatment with significant IARs or occurrence of
anaphylaxis

- Markers of hepatic dysfunction

- Creatinine ≥ 1.5 mg/dL

- Contraindication to the use of corticosteroids for immunosuppression

- Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use
(topical treatment allowed)

- Participation in prior investigational drug or medical device study within the
previous 3 months

- Prior treatment with a gene therapy product

- Elevated or abnormal circulating α-fetoprotein (AFP)

- Weight < 20 kg at Screening Visit