A Study Evaluating the Safety and Efficacy of the LentiGlobin® BB305 Drug Product in Beta-Thalassemia Major Subjects

Subject participation for this study will be 2 years. Subjects who enroll in this study will
be asked to participate in a subsequent long-term follow up study that will monitor the
safety and efficacy of the treatment they receive for up to 13 years post-transplant.

Inclusion criteria:

- Subjects between 12 and 35 years of age, inclusive, at the time of consent/assent, and
able to provide written consent/assent, if applicable.

- Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or
≥8 transfusions of pRBCs per year for the prior 2 years.

- Eligible for allogeneic bone marrow transplant.

- Treated and followed for at least the past 2 years in a specialized center that
maintained detailed medical records, including transfusion history.

Exclusion criteria:

- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).

- A white blood cell (WBC) count <3 × 109/L, and / or platelet count <100 × 109/L if not
due to hypersplenism.

- Uncorrected bleeding disorder.

- Any prior or current malignancy or myeloproliferative or immunodeficiency disorder.

- Immediate family member with a known or suspected Familial Cancer Syndrome (including
but not limited to hereditary breast and ovarian cancer syndrome, hereditary
non-polyposis colorectal cancer syndrome and familial adenomatous polyposis).

- Receipt of an allogeneic transplant.

- Advanced liver disease, including persistent aspartate transaminase (AST), alanine
transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver
biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.

- Kidney disease with a calculated creatinine clearance <30% normal value.

- Uncontrolled seizure disorder.

- Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for
hemoglobin).

- A cardiac T2* <10 ms by magnetic resonance imaging (MRI).

- Any other evidence of severe iron overload that, in the Investigator's opinion,
warrants exclusion.

- Clinically significant pulmonary hypertension, as defined by the requirement for
ongoing pharmacologic treatment or the consistent or intermittent use of supplemental
home oxygen.

- Participation in another clinical study with an investigational drug within 30 days of
Screening.

- Any prior or current malignancy or myeloproliferative disorder.

- Prior receipt of gene therapy.