Clinical Study of DTX301 AAV- Mediated Gene Transfer for Ornithine Transcarbamylase(OTC) Deficiency

Key Inclusion Criteria:

• Confirmed clinical diagnosis of late-onset OTC deficiency with historicaldocumentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia inthe presence of elevated plasma glutamine, low citrulline, and elevated spot urineorotic acid), or molecular testing (ie, OTC analysis)

• Free from symptomatic hyperammonemia and has not required emergent activeintervention for hyperammonemia within 4 weeks before screening/baseline

• If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for ≥ 4 weeks prior to screening

• If on a protein-restricted diet, must be on a stable total daily protein intake thatdoes not vary more than 20% for ≥ 4 weeks prior to screening

• From the time written informed consent through Week 128, females of childbearingpotential and fertile males must consent to use highly effective contraception. Iffemale, agree not to become pregnant. If male, agree not father a child or donatesperm

Key Exclusion Criteria:

• Significant hepatic inflammation or cirrhosis

• Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening by the 2021CKD-EPI creatinine-based formula (Inker et al., 2021) for patients ≥ 18 years of ageor the Schwartz bedside formula (Schwartz and Work, 2009) for patients < 18 years ofage

• Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection,documented by current use of antiviral therapy for HBV or HCV or by hepatitis Bsurface antigen (HBsAg) or HCV RNA positivity

• Active infection (viral or bacterial)

• Detectable pre-existing antibodies to the AAV8 capsid

• Presence or history of any condition that, in the view of the Investigator, wouldinterfere with participation, pose undue risk, or would confound interpretation ofresults

• Participation (current or previous) in another gene transfer study

Note: Additional inclusion/exclusion criteria may apply, per protocol