Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B

The objective of the study is to provide long term expression of Factor IX in subjects with
severe hemophilia B. SB-FIX is a therapeutic for ZFN-mediated genome editing which will be
delivered by adeno-associated virus (AAV)-derived vectors. SB-FIX is intended to function by
placement of a corrective copy of the Factor IX 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 Factor IX for the lifetime of a
hemophilia B subject.

Inclusion Criteria:

- Male >18 years of age

- Severe hemophilia B (native circulating FIX activity <1%, with or without cross
reactive material)

Exclusion Criteria:

- Presence of neutralizing antibodies

- History of hypersensitivity response or an allergic reaction to FIX or FIX products

- Currently receiving long acting FIX replacement therapy

- FIX mutations known to be associated with FIX inhibitors

- Polymorphisms in the ZFN target region

- Presence of any liver mass on MRI, or elevated alpha-fetoprotein (AFP)

- Any contraindication to the use of corticosteroids for immunosuppression

- Currently receiving antiviral therapy for hepatitis B or C or with history or active
hepatitis B or hepatitis C or HIV-1 or HIV1/2 antibody positive.

- Chronic anemia, leukopenia, or thrombocytopenia

- Past medical history of active tuberculosis or significant fungal disease

- Symptomatic cardiovascular disease as a co-morbid condition

- Markers of hepatic inflammation or overt or occult cirrhosis

- History of chronic renal disease or creatinine ≥ 1.5 mg/dL

- Systemic (iv or oral) immunomodulatory agent or steroid use (topical treatment is
allowed)

- History of chronic infection or other chronic disorder considered an unacceptable risk

- History of malignancy except for treated basal cell or squamous cell carcinoma

- History of alcohol or substance abuse

- Previously received gene therapy product

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

- History of therapeutic non-adherence

- Any other reason that, in the opinion of the Investigator or Medical Monitor, would
render the subject unsuitable for participation in the study