the Safety and Efficacy Evaluation of HGI-002 Injection in Patients With Transfusion-Dependent α-Thalassemia

Inclusion Criteria:

1. Aged 12-35 years (inclusive), ICF can be provided by the patient and/or legalguardian;

2. Definitively α- thalassemia diagnosed with severe TDT without genotype restriction,and a valid test report can be provided;

3. Average transfusion volume > 100 mL/kg/year or transfusion frequency > 8 times/yearwithin 2 years prior to enrollment, or has been definitively diagnosed with TDT;

4. At least 3 months of full volume transfusion (verification of blood transfusionrecords can be provided) prior to screening, and Hb is maintained at ≥ 9.0 g/dL;

5. Ferritin load < 3000 μg/L, cardiac and liver iron indicates moderate or lesser ironoverload; records of iron chelation treatments within 3 months before screening (including prescription or receipt) can be provided;

6. Acceptable organ functions (including heart, liver, kidney, lung and coagulationfunctions), stable disease condition, and suitable for busulfan pre-treatment andhematopoietic stem cell (HSC) transplantation as judged by the investigator;

7. Meets follow-up requirements, adheres to treatment arrangements, and is able toreturn to the hospital regularly to undergo various examinations within 2 yearsafter reinfusion of HGI-002 injection.

Exclusion Criteria:

1. Patients with fully HLA-matched donors;

2. Received allogeneic transplantation, which needs to be weighed and evaluated by anexpert committee; received other gene therapies;

3. Have previously undergone splenectomy;

4. Uncorrected bleeding disorder;

5. Uncontrolled epilepsy and mental illness;

6. Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months priorto enrollment;

7. Psychoactive substance abuse, drug or alcohol abuse within 6 months prior toenrollment;

8. Patients with pulmonary hypertension who have not been given effective intervention;

9. Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment;

10. Positive for anti-RBC antibodies in antibody screening;

11. Positive for hepatitis B surface antigen (HBsAg) and HBV DNA copy number > upperlimit of normal (ULN) (HBV DNA test not required for patients negative for HBsAg),positive for hepatitis C virus (HCV) antibody, positive human immunodeficiency virus (HIV), or positive for Treponema pallidum antibody (TP-Ab) (subjects who arepositive for the antibody due to vaccination can be enrolled). In certain clinicalenvironments/regions, subjects who are positive for other tests can also be excludedfrom the trial, such as, human lymphocytic virus-1 (HTLV-1) or -2 (HTLV-2),tuberculosis, and toxoplasmosis.

12. Has or has had malignant tumors or myeloproliferative disease or immunodeficiencydisease;

13. Immediate family member with or suspected of having a familial cancer (including butnot limited to hereditary breast and ovarian cancers, nonpolyposis colorectalcancer, and adenomatous polyposis);

14. Severe bacterial, viral, fungal or parasitic infection;

15. Other illnesses which render the subject unsuitable for participation (e.g., severeliver, kidney or heart disease); Definition of severe liver and kidney disease: a.Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin > 3 × ULN; b. Liver magnetic resonance imaging (MRI) indicates significantcirrhosis; c. Liver biopsy indicates cirrhosis, severe fibrosis or active hepatitis (liver biopsy is only performed when liver MRI indicates active hepatitis andsignificant fibrosis without evidence for cirrhosis); d. Creatinine clearance < 30%of normal;

16. WBC < 3 × 109/L and/or PLT < 100 × 109/L;

17. Has diabetes, abnormal thyroid functions or other endocrine disorder;

18. Participated in other interventional clinical studies within 4 weeks before thetrial;

19. Poor adherence or other conditions that renders the subject unsuitable forparticipation as judged by the investigator.