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

Inclusion Criteria:

1. Men or women aged ≥ 18 years and ≤ 65 years (including boundary values) who signedinformed consent.

2. Meets the diagnostic criteria for familial hypercholesterolemia. When screening,there are mutations in the PCSK9 and/or ApoB and/or LDLR genes.

3. When screening, the weight should be ≥ 40kg, and the body mass index (BMI) should bebetween 18-30 kg/m2 (including boundary values).

4. During screening, subjects must meet the following laboratory standards: 5.1 Bloodroutine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin count (HGB) ≥ 90 g/dL; 5.2 Liver function: aspartateaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) < 2.0 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN; 5.3 Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN, and glomerular filtration rate (GFR)>60mL/min * 1.73m2; 5.4Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT), international standardized ratio (INR)<1.5 x ULN; 5.5 Low densitylipoprotein cholesterol (LDL-C) ≥ 4.21mmol/L, and fasting triglycerides<5.6mmol/L.

5. The subjects and their partners must take effective contraceptive measures duringthe participation in this study until 6 months after the end of the main study.

6. The subject must agree not to accept other lipid-lowering drugs for at least 28 daysafter receiving the investigational drug.

7. Voluntarily sign informed consent.

Exclusion Criteria:

1. Those who have used any prescription drugs that affect blood lipid metabolism withinat least 14 days before receiving the study drug (or within 7 half lives of thedrug, whichever is longer, applicable to small molecule/small nuclear acid drugs) orwithin 3 months (applicable to biological agents such as PCSK9 inhibitors), or whohave used any over-the-counter drugs that affect blood lipid metabolism within atleast 14 days before receiving the study drug (such as Chinese medicine/traditionalChinese patent medicines and simple preparations, vitamins, fish oil (>1000mg/day),drugs containing red koji rice or health products, etc.), (Exception of those whohave received stable non-cyclical hormone replacement therapy for more than 8 weeksand agree not to change the hormone treatment more than 28 days after the study drugadministration); individuals who have participated in clinical studies of otherlipid-lowering drugs and have accepted the investigational drugs within 6 monthsbefore the screening period.

2. Poorly controlled hypertensive patients who have receive conventional treatments (systolic blood pressure (SBP) ≥ 160mmHg and/or diastolic blood pressure (DBP) ≥ 100mmHg).

3. Poorly controlled diabetes patients (glycosylated hemoglobin>8.5%).

4. Individuals who are allergic to drugs or mRNA vaccine components contained in lipidnanoparticles (LNPs), or have experienced adverse reactions to LNP drug therapy,such as:

4.1 After receiving LNP drug treatment, ALT or AST>3.0 × ULN; 4.2 After receivingLNP drug treatment, INR>1.5 or APTT/d-dimer>1.5 × ULN; 4.3 Any infusion responsethat requires clinical intervention, slows down infusion rate, or stops LNP drugstreatment; 4.4 Any other adverse reactions that researchers believe are related tothe treatment of LNP drugs.

5. Within three months before the screening, individuals who smoke more than 5cigarettes per day or consume an equal amount of nicotine or nicotine substitutes.

6. Individuals with a history of alcohol abuse [consuming more than 14 units of alcoholper week (1 unit ≈ 360mL of beer or 45mL of 40% liquor or 150mL of wine)] within 3months before the screening; Individuals positive for alcohol breath test during thescreening or admission.

7. Grade III-IV heart failure defined by the New York Heart Association (NYHA), or leftventricular ejection fraction<50%, or prolonged QTc interval (>470ms in femalesand>450ms in males) found during the screening.

8. Suffering poorly controlled severe arrhythmia , such as recurrent and highlysymptomatic ventricular tachycardia with poorly drug controlled, atrial fibrillationwith rapid ventricular reaction, or supraventricular tachycardia within three monthsbefore the screening.

9. Myocardial infarction, unstable angina, percutaneous coronary intervention, coronaryartery bypass grafting, severe deep vein thrombosis or pulmonary embolism withinthree months before the screening; Cerebrovascular accidents occurring within 6months before the screening or planning for cardiac surgery or revascularizationduring the main study period.

10. Suffering from diseases that have a significant impact on blood lipid levels andcannot be controlled, such as nephrotic syndrome, severe liver disease, Cushing'ssyndrome, thyroid dysfunction, etc. (Individuals with hypothyroidism who haveundergone stable thyroid replacement therapy for ≥ 28 days before screening, havenormal TSH testing, and agree to maintain the dose of thyroid replacement drugsunchanged during the study can be considered to be enrolled).

11. Individuals who have donated more than 500 mL of blood within three months beforescreening.

12. Those who are unable or unwilling to accept the medication treatment required beforethe investigational treatment.

13. Patients who underwent antithrombotic treatment (such as warfarin, dabigatran, andapixaban) within 14 days prior to enrollment.

14. Those who are prone to bleeding or have a history of coagulation disorders (such ascirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome);

15. Patients with an expected survival period of less than 2 years.

16. Individuals who are known or suspected to have systemic viral, parasitic, or fungalinfections, or are expected to receive antibiotic treatment within 14 days afterscreening.

17. Hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or humanimmunodeficiency virus (HIV) antibody positive during the screening.

18. Individuals who have received liver, heart, or other solid organ transplantation,bone marrow transplantation within one year before the screening, or having atransplantation plan during the clinical trial.

19. Individuals with a history of malignant tumors within 5 years before the screening (excluding curative skin basal cell carcinoma, skin squamous cell carcinoma,cervical carcinoma in situ, low-grade prostate carcinoma in situ, and curativethyroid basal carcinoma in situ).

20. Individuals with a history of drug use within three years before the screening.

21. Pregnant or lactating women.

22. Patients with other systemic diseases such as the blood system, digestive system, orcentral nervous system (including cerebrovascular diseases and degenerativediseases) that the researchers believe will interfere with the evaluation or limitthe participation in the trial.

23. Severe mental diseases that researchers believe which cannot be fully controlled bythe medication treatment.

24. Those who are unwilling to follow the research procedures or are unwilling to fullycooperate.

25. Other situations that researchers believe not suitable to participate in theclinical trial.