NGGT006 Gene Therapy for Homozygous Familial Hypercholesterolemia

Inclusion Criteria:

• Voluntarily sign informed consent form;

• Male or female, 12 ≤ age ≤ 55 years (first patient≥ 18 years), diagnosed ashomozygous familial hypercholesterolemia with genetic confirmation of two mutantalleles of the LDL receptor (LDLR) gene;

• AAV8 neutralizing antibodies can be negative or reduced to negative levels throughmethods such as plasma exchange.

• Untreated LDL-C ≥10 mmol/L (386mg/ dL) or treated LDL-C ≥7 mmol/L (270mg/ dL)together with cutaneous or tendon xanthoma before age 18 years;

• Had been on stable medication for ≥30 days if receiving lipid-lowering therapy (or ≥60 days if receiving alirocumab or evolocumab) prior to screening and not scheduledfor addition of new drugs or dose adjustments during the study;

• Agreed to follow a low-fat diet and comply with all study procedures;

• Agreed to maintain a similar exercise volume and intensity to baseline during thestudy period;

• Agreed to maintain good lifestyle habits;

• No history of alcohol abuse or alcohol dependence (diagnosed as F10 in ICD-10 code);

• No sexual activity for 14 days prior to administration and negative serum pregnancytest in female participants;

• Participants of childbearing potential agreed to use highly effective contraceptionfor at least 365 days from administration of NGGT006;

• No plan of stent implantation within 3 months.

Exclusion Criteria:

• Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV) or syphilis test;

• Clinically significant abnormalities in liver function test: alanineaminotransferase (ALT) ≥2 × upper limit of normal (ULN) and/or aspartateaminotransferase (AST) ≥2 × ULN;

• Baseline blood pressure ≥160/100 mmHg (1 repeat measurement is allowed);

• Uncontrolled myocardial infarction or heart failure, or had surgery plan within 1year;

• Diabetes diagnosed within 3 months or with poor control (HbA1c ≥9%);

• Acute or chronic kidney failure;

• Hemoglobin (Hb) ≥120g/L (male), Hb ≥110 (female);

• Abnormal platelet counts or morphology;

• History or laboratory tests suggestive of thrombosis;

• Had contraindications to glucocorticoid (e.g., epilepsy, severe schizophrenia,active peptic ulcer);

• Life expectancy less than 1 year;

• With malignant tumors;

• Liver fibrosis or liver cancer;

• Previous gene therapy treatment;

• Hypersensitivity to AAV or cortisone or immunosuppressants (sirolimus, rituximab,tacrolimus);

• Participation in any other clinical trial within 3 months;

• History of stent implantation within 1 month or myocardial infarction within 3months;

• Breastfeeding females;

• Any other condition that may not be appropriate for the study in the opinion of theInvestigator.