Safety and Efficacy Study of NGGT002 in PKU Adult Subjects

Inclusion Criteria:

• Voluntarily sign informed consent form;

• Male and female subjects with diagnosis of PKU caused by confirmed phenylalaninehydroxylase(PAH) mutation according to the "Clinical Practice Guidelines forPhenylketonuria, 2020 Edition";

• Age ≥ 18 years;

• Blood phenylalanine (Phe) concentration ≥ 600 μmol/L at least once within 2 yearsprior to screening, with one measurement confirmed within six months of enrollment;

• Subjects are able to maintain their baseline diet throughout the study (regardlessof dietary phenylalanine restriction), and willingness to follow the instruction ofinvestigators to manage the diet for the duration of the trial;

• Subjects are required to obtain approval from the investigator prior to the use ofany concomitant medications during the study period;

• Willingness and capable per Investigator opinion to comply with study procedures andrequirements;

• Female participants of childbearing potential must have abstained from unprotectedsexual intercourse for at least 14 days prior to dosing, and must have a documentednegative serum hCG test between Day -7 and Day 0. All participants must be willingto use a highly effective method of contraception for at least 12 months followingNGGT002.

Exclusion Criteria:

• Anti-AAV8 neutralizing antibody>1:10

• Prior gene therapy

• Positive hepatitis B virus surface antigen, hepatitis C virus antibody, anti-humanimmunodeficiency virus antibody or treponema pallidum-specific antibody

• Hepatic function abnormal: alanine aminotransferase (ALT) or aspartateaminotransferase (AST) > 1.5 × ULN; alkaline phosphatase (ALP) > 1.5 × ULN; totalbilirubin (TBil) > 1.5 × ULN; international normalized ratio (INR) > 1.3

• Hematology values outside of the normal range (Hemoglobin < 110 g/L (male), < 100g/L (female), white blood cells < 3.0 × 10^9/L, neutrophils < 1.5 × 10^9/L, plateletcounts < 100 × 10^9/L;

• Hemoglobin A1c > 6%, or fasting glucose > 6.1 mmol/L;

• Clinically significant abnormalities in vital signs, physical examination findings,laboratory tests, or other assessments that, in the Investigator's judgment, aredeemed unsuitable for study enrollment;

• Any contraindications to corticosteroid use or conditions potentially worsened bycorticosteroids, as assessed by the Investigator, including but not limited tohypersensitivity to glucocorticoids, epilepsy, recent or unresolved bone fractures,ongoing wound healing, uncontrolled infections, or clinically significantosteoporosis;

• Subjects with a history of allergy to human serum albumin;

• All types of past and current malignancy;

• Severe diseases in the cardiovascular, respiratory, digestive tract, endocrine,kidney, blood, nervous, mental and other systems before screening;

• Subjects with history of live diseases, such as hepatitis, liver cirrhosis, livercancer or other serious liver diseases;

• Subjects who participated in other clinical trails and took drugs within 3 monthsbefore screening;

• Other conditions that the Investigators deemed inappropriate for enrollment.