A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Subjects With Transfusion-Dependent β-Thalassemia, Who Have a β0/β0 Genotype

Inclusion Criteria:

- Subjects ≤50 years of age at the time of consent or assent (as applicable), and able
to provide written consent (adults, or legal guardians, as applicable) or assent
(adolescents or children). Provided that the DMC has approved enrolling subjects
younger than 5 years of age, subjects younger than 5 years of age may be enrolled if
they weigh a minimum of 6 kg and are reasonably anticipated to be able to provide at
least the minimum number of cells required to initiate the manufacturing process.

- Diagnosis of TDT with a history of at least 100 mL/kg/year of packed red blood cells
(pRBCs) in the 2 years preceding enrollment (all subjects), or be managed under
standard thalassemia guidelines with ≥8 transfusions of pRBCs per year in the 2 years
preceding enrollment (subjects ≥12 years).

- Clinically stable and eligible to undergo HSCT.

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

Exclusion Criteria:

- Presence of a mutation characterized as other then β0 (e.g., β+, βE, βC) on at least
one HBB allele.

- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2),
hepatitis B virus (HBV), or hepatitis C (HCV).

- A white blood cell (WBC) count <3×10^9/L, and/or platelet count <100×10^9/L not
related to hypersplenism.

- Uncorrected bleeding disorder.

- Any prior or current malignancy.

- Prior HSCT.

- Advanced liver disease.

- 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.

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

- Any other condition that would render the subject ineligible for HSCT, as determined
by the attending transplant physician or investigator.

- Prior receipt of gene therapy.

- Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception
for fertile subjects.

- A known and available HLA-matched family donor.

- Any contraindications to the use of G-CSF and plerixafor during the mobilization of
hematopoietic stem cells and any contraindications to the use of busulfan and any
other medicinal products required during the myeloablative conditioning, including
hypersensitivity to the active substances or to any of the excipients.