Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency

This is a Phase 1/2, open-label, single arm, multicenter, safety and dose finding study of
DTX301 in adults with late-onset OTC deficiency. The primary objective of the study is to
establish a dose of DTX301 that has a clinically meaningful increase in the rate of
ureagenesis. Eligible subjects will receive a single IV infusion of DTX301. Dose escalation
will be conducted according to a model that uses the collected data to predict the safety
profile of the dose in order to determine the optimal biological dose (OBD). The decision to
proceed to the next dose cohort will be made after the data monitoring committee (DMC) has
evaluated the safety data for all subjects in a dosing cohort.

Subjects will be followed for 52 weeks after dosing. After completion of this study, subjects
will be asked to enroll in a 4-year extension study to evaluate the long term (a total of 5
years) safety and efficacy of DTX301.

This study was previously posted by Dimension Therapeutics, which has been acquired by
Ultragenyx.

Inclusion Criteria:

1. Males and females ≥18 years of age with documented diagnosis of late onset (defined as
first manifestation of signs and symptoms at ≥1 month of age) OTC deficiency,
confirmed via enzymatic, biochemical, or molecular testing

2. Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L.

3. Subject's OTC deficiency is stable as evidenced by either a) no clinical symptoms of
hyperammonemia OR b) an ammonia level <100 µmol/L within the 4 week period preceding
the Screening visit.

4. On stable dose of ammonia scavenger therapy for ≥4 weeks.

5. Males and all females of childbearing potential must be willing to use effective
contraception at the time of administration of gene transfer and for the 52 weeks
following administration of DTX301

Exclusion Criteria:

1. Screening or Baseline (Day 0) ammonia level ≥100 µmol/L or signs and symptoms
indicative of hyperammonemia during the 4-week period preceding Day 0

2. Liver transplant, including hepatocyte cell therapy/transplant.

3. History of liver disease

4. Serum creatinine >2.0 mg/dL.

5. Participation in another investigational medicine study (including another gene
transfer trial) within 3 months of Screening

6. History of a malignancy for which the subject has received treatment in the past 2
years except for prostate cancer treated with watchful waiting or surgically removed
non-melanoma skin cancer.