Clinical Exploration Trial of YOLT-101 in the Treatment of Familial Hypercholesterolemia (FH)

Inclusion Criteria:

1. Male or female, aged 18 to 75 years inclusive, at the time of signing informedconsent.

2. Meets the diagnostic criteria for familial hypercholesterolemia.

3. At screening, there is a mutation in the PCSK9 and/or ApoB and/or LDLR gene.

4. At screening, weight is ≥40kg, and Body Mass Index (BMI) is >18kg/m^2.

5. At screening, subjects must meet the following laboratory criteria:

5.1 Hematology: Absolute Neutrophil Count (ANC) ≥1.5×10^9/L, Platelet (PLT) ≥100×10^9/L, Hemoglobin (HGB) ≥90 g/dL; 5.2 Liver Function: AspartateAminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) <2.0×Upper Limit of Normal (ULN), Total Bilirubin (TBIL) ≤1.5×ULN; 5.3 RenalFunction: Serum Creatinine (Cr) ≤1.5×ULN, and Glomerular Filtration Rate (GFR) >60mL/min*1.73m^2; 5.4 Coagulation Function: Prothrombin Time (PT), ActivatedPartial Thromboplastin Time (APTT), International Normalized Ratio (INR) <1.5×ULN; 5.5 Fasting Triglycerides <5.6mmol/L.

6. On moderate intensity or higher statin therapy (statin treatment stable for 4 weeks)with LDL-C ≥2.6mmol/L; for those with evidence of atherosclerosis, LDL-C ≥1.8mmol/L. (Evidence of atherosclerosis includes: 1. History of myocardial infarction, angina,coronary artery revascularization, non-embolic ischemic stroke or transient ischemicattack, intermittent claudication; 2. Presence of advanced subclinicalatherosclerosis: Coronary artery calcium score > 100 Agatston units, or above the 75th percentile for age and sex; or coronary artery CT angiography showing stenosis > 50%, or multiple vessels with non-obstructive plaques.)

7. Subjects and their partners must use effective contraceptive measures during thestudy period and for at least 6 months after the end of the main study.

8. Voluntarily sign informed consent.

Exclusion Criteria:

1. Within at least 14 days (or 5 half-lives of the drug, whichever is longer, for smallmolecule/small nucleic acid drugs) or 2 months (for biological agents such as PCSK9inhibitors) or 1 year (for PCSK9 small nucleic acid drugs) before accepting thestudy medication, those who have used prescription drugs that affect lipidmetabolism other than statins, or those who have used any non-prescription drugsaffecting lipid metabolism within at least 14 days before accepting the studymedication (such as traditional Chinese medicine/patent Chinese medicine, vitamins,fish oil (>1000mg/day), drugs or health products containing red yeast rice, etc.;except for those who have been on stable non-cyclic hormone replacement therapy formore than 8 weeks and agree not to change the treatment plan for at least 28 daysafter receiving the trial medication); those who are currently participating inother clinical studies of lipid-lowering drugs and have used study medication.

2. Patients with poorly controlled hypertension (systolic blood pressure (SBP) ≥160mmHgand/or diastolic blood pressure (DBP) ≥100mmHg).

3. Patients with poorly controlled diabetes (glycated hemoglobin >8.5%).

4. Those allergic to drugs or components of LNP-mRNA vaccines contained in lipidnanoparticles (LNP), or those who have experienced adverse reactions due toLNP-based drug treatment, such as: 4.1 After receiving LNP-based drug treatment, ALTor AST > 3.0×ULN; 4.2 After receiving LNP-based drug treatment, INR > 1.5 orAPTT/d-dimer > 1.5×ULN; 4.3 Any infusion reaction that requires clinicalintervention or slows down or stops the infusion of LNP-based drug treatment; 4.4Any other adverse reactions deemed related to LNP-based drug treatment by theinvestigator.

5. Within 3 months before screening, those who smoke more than 5 cigarettes per day orconsume an equivalent amount of nicotine or nicotine replacement products.

6. Within 3 months before screening, those with a history of alcohol abuse [consumingmore than 14 units of alcohol per week (1 unit ≈ 360mL beer or 45mL of liquor with 40% alcohol or 150mL of wine)]; or those who test positive for alcohol breathresearch at screening or admission.

7. At screening, those with New York Heart Association (NYHA) defined class III-IVheart failure, or left ventricular ejection fraction <50%, or prolonged QTc interval (females >470ms, males >450ms).

8. Within 3 months before screening, those with poorly controlled severe arrhythmias,such as recurrent and highly symptomatic ventricular tachycardia, rapid ventricularresponse atrial fibrillation, or supraventricular tachycardia that is not wellcontrolled with medication.

9. Within 3 months before screening, those with myocardial infarction, unstable angina,percutaneous coronary intervention, coronary artery bypass grafting, severe deepvein thrombosis, or pulmonary embolism; those who have had a cerebrovascularaccident within 6 months before screening or plan to undergo cardiac surgery orrevascularization during the main study period.

10. Those with diseases that significantly affect lipid levels and are uncontrollable,such as nephrotic syndrome, severe liver disease, Cushing's syndrome, thyroiddysfunction, etc. (those with hypothyroidism before screening who have been onstable thyroid replacement therapy for ≥28 days, with normal TSH testing, and agreeto maintain the thyroid replacement drug dose unchanged during the study may beconsidered for inclusion).

11. Those who have donated more than 500 mL of blood within 3 months before screening.

12. Those who cannot or are unwilling to accept the required medication treatment planbefore treatment.

13. Those who have undergone antithrombotic treatment (such as warfarin, dabigatran,apixaban) within 14 days before enrollment.

14. Those with a history of easy bleeding or coagulation disorders (such as livercirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome).

15. Those with an expected survival of less than 2 years.

16. Those known or suspected to have systemic viral, parasitic, or fungal infections, orthose expected to receive antibiotic treatment within 14 days after screening.

17. Those who test positive for hepatitis B surface antigen (HBsAg) or hepatitis C virusantibody (HCV Ab) or human immunodeficiency virus (HIV) antibody at screening.

18. Those who have undergone liver, heart, or other solid organ transplantation or bonemarrow transplantation within 1 year before screening or plan to undergotransplantation during the trial period.

19. Those with a history of malignant tumors within 5 years before screening (except forcured basal cell carcinoma of the skin, squamous cell carcinoma of the skin,cervical carcinoma in situ, low-grade prostatic intraepithelial neoplasia, and curedbasal cell carcinoma of the thyroid).

20. Those with a history of drug abuse within 3 years before screening.

21. Women who are pregnant or breastfeeding.

22. Those with other hematopoietic system, digestive system, or central nervous system (including cerebrovascular diseases, degenerative diseases) diseases that theinvestigator believes will interfere with evaluation or limit participation in thetrial.

23. Those with severe mental illnesses that the investigator believes cannot beadequately controlled by drug treatment.

24. Those unwilling to comply with the research procedures or unwilling to fullycooperate.

25. Other situations deemed by the investigator as not suitable for participation inclinical trials.