CS-206 in Patients With Sickle Cell Disease

Inclusion Criteria:

• Participants must be between 12 to 35 years old (inclusive). Participants or theirlegal guardians (for participants below 18 years old) must provide written informedconsent before any study-related procedures.

• Participants must have a Documented βS/βS, βS/β0 or βS/β+ genotype.

• Participants must have at least one of the following conditions

1. At least 2 occurrences of any of the following events within 2 years prior toscreening.

2. Acute pain crisis: requiring a visit to a medical facility andadministration of pain medications (opioids or intravenous NSAIDs) or redblood cell transfusions.

3. Acute chest syndrome: defined by the presence of a new pulmonaryinfiltrate on a chest X-ray, associated with pneumonia-like symptoms,including chest pain, fever, or respiratory distress.

4. Priapism lasting more than 2 hours and necessitating a visit to a medicalfacility for intervention.

5. Stroke or transient ischemic attack (TIA): confirmed by imaging studies (e.g., MRI or CT scan), including silent stroke, and overt stroke leadingto neurological deficits lasting >24 hours.

6. Presence of red cell alloimmunization (>2 antibodies) and the need for ongoingchronic transfusions.

7. Participants who have failed, not tolerated, refused the standard of care forSickle Cell Disease (SCD), or are unable to access the standard of care due tothe availability

8. Other situations deemed appropriate for hematopoietic stem cell transplantationaccording to the sickle cell anemia treatment guidelines, as determined by theinvestigator.

• Laboratory Parameters:

1. Documented Hemoglobin S (HbS) level ≥30% of total hemoglobin (Hb) concentrationprior to transfusion.

2. HbF at screening < 20%

• Participants must have a Karnofsky Performance Status (KPS for participants above 16years old, inclusive) or Lansky Play-Performance Scale (LPPS for participants below 16 years old) score of ≥70, indicating sufficient functional status to undergo theintervention.

• Willing to comply with the protocol requirements, use contraception as required,attend regular follow-up visits, and cooperate with examinations.

Exclusion Criteria:

• Female participants who are pregnant, breastfeeding, or planning pregnancy duringthe study period are excluded.

• Participation in another investigational drug trial within 30 days prior toscreening or within 5 half-lives (whichever is longer).

• Subjects who have received or are receiving luspatercept treatment within 3 monthsprior to screening.

• Subjects who have previously received any gene therapy for the disease.

• Subjects with a fully matched related donor who are already scheduled for allogeneichematopoietic stem cell transplantation.

• More than 10 unplanned hospitalizations or emergency visits within 12 months priorto screening, which the investigator believes are related to significant chronicpain rather than acute pain crisis (VOC).

• Severe liver dysfunction:

1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× theupper limit of normal (ULN) or:

2. International Normalized Ratio (INR) >1.5× ULN

• Severe renal impairment (creatinine clearance <30 mL/min/1.73 m²) are excluded.

• Subjects with HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), or Treponemapallidum infection during the screening period; those with active HBV or HCVinfection; or known tuberculosis or parasitic infection, etc. Excludes subjects withstable hepatitis B (HBV-DNA negative) after treatment and those cured of hepatitis C (HCV-RNA negative). Known active bacterial, viral, or fungal infections.

• Deemed unsuitable for autologous hematopoietic stem cell transplantation proceduresas determined by the investigator.

• Other situations deemed unsuitable for this study as determined by the investigator.