CS-101 in Patients With β-thalassemia

A Clinical Study Evaluating the Safety and Efficacy of Autologous Peripheral Blood Hematopoietic Stem and Progenitor Cells (CS-101) Modified by Ex Vivo Base Editing to Induce γ-Globin Production in Treating Patients With β-Thalassemia

The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of CS-101 in treating β-thalassemia.

CS-101 is an autologous CD34+ cell suspension, edited by in vitro base editing technology, which modifies the BCL11A binding site in HBG promoter, so that it loses the ability to bind to BCL11A, which can re-induce the production of γ-globin chain and increase the concentration of fetal hemoglobin(HbF) in the blood, compensating for the function of missing adult hemoglobin HbA to achieve clinical cure. The therapy addresses two major challenges in the current treatment of the disease: lack of matching donors and graft-versus-host diseases in allogeneic hematopoietic stem cell transplantation.

Inclusion Criteria:

• 6 to 35 years old(inclusive) male or female subjects at the time of informed consenting Diagnosis of β-thalassemia, genotypes include but are not limited to β+β0，βEβ0，β0β0, etc History of at least≥8 units/year of packed RBC transfusions in the prior 12 months prior to the screening period Generally in good condition, Karnofsky performance score≥60 points for subjects≥16 years old at the time of autologous hematopoietic stem cell collection, or Lansky Play-Performance score≥60 points for subjects under 16 years old, or equivalent clinical evaluation as the investigator site's common practice

Exclusion Criteria:

• Treatment with other investigational medications or other experimental interventions 30 days prior to signing informed consent or within 6 half-lives of the drug, whichever is longer.

Subjects who have received or are receiving thalidomide and/or Luspatercept, when their drug-drug interaction on the efficacy and safety of CS-101 cannot be ruled out, unless at least there are 3 test results showing the total hemoglobin level before transfusion is below 9g/dL in the past 6 months before screening.

Previously received allogeneic hematopoietic stem cell transplantation or gene(edited) therapy.

Subjects have available related fully matching donors and are eligible and prepared for allogeneic hematopoietic stem cell transplantation.

Those with active infections, including but not limited to: HIV, hepatitis B, hepatitis C, cytomegalovirus, Epstein-Barr virus and treponema pallidum test positive, or known tuberculosis, parasitic infection, etc. who are judged by the investigator to be unsuitable to participate in this study.

Echocardiography results with ejection fraction below 45%. Advanced liver disease, defined as：

Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) or:

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

MRI during the screening period showed heavy iron overload and is judged by the investigator to be unable to participate in the study.