All three subjects dosed in the study have rolled over to the Long-Term Follow-up Study IVPRP-LT01 (NCT04628871)

The purpose of the study is to evaluate the safety, tolerability of ascending doses of SB-318. SB-318 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the α-L-iduronidase (IDUA) gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDUA enzyme.

The objectives of the study are to provide long term expression of IDUA and improve the current clinical outcome of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) therapy in subjects with attenuated MPS I, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDUA. SB-318 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-318 is intended to function by placement of the corrective copy of the IDUA 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 iduronidase for the lifetime of an MPS I patient.

Inclusion Criteria:

• Male or female ≥ 5 years of age
• Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)

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 I)
• Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or hepatitis C or HIV 1/2
• Lack of tolerance to laronidase 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

The original protocol anticipated 9-12 subjects in 3 cohorts at ascending doses. However, enrollment ended after 3 subjects were enrolled in 2 cohorts. (No subjects were enrolled in cohort 3). After interim data analysis, the sponsor decided to stop enrollment in this study at 3 subjects enrolled, all adults, in 2 cohorts. (No subjects were enrolled in cohort 3) The sponsor continues to monitor the subjects in a 10-year,follow-up study ST-IVPRP-LT01 (NCT04628871).

Adverse event data was collected from the subject's date of screening until their end of study visit at 36 months.

No subjects were enrolled in Cohort 3

Continuous data will be summarized using the following descriptive statistics: the number of subjects (n), mean, standard deviation (SD), median, minimum and maximum, where appropriate. Categorial percentage (%) of subjects for each category, where appropriate.