MGTA-456 in Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

This phase 2 study is designed to evaluate the safety and efficacy of MGTA-456 after
myeloablative conditioning to induce rapid and sustained hematopoietic engraftment with
replacement of the specific protein product missing or defective in the patient with an IMD.
The study aims to enhance the efficacy of umbilical cord blood transplantation (UCBT), to
preserve neurodevelopment in patients with selected IMDs. Since MGTA-456 offers increased
numbers of HSCs over standard UCB, it is expected to reduce the risks of prolonged
neutropenia and thrombocytopenia and graft failure, and potentially transplant-related
mortality (TRM). Patients with Hurler syndrome (also referred to as mucopolysaccharidosis-1H
(MPS-1H)), cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy (MLD) or
globoid cell leukodystrophy (GLD) (also referred to as Krabbe disease) could be eligible for
this study.

Inclusion Criteria:

- Diagnosed with Hurler syndrome, metachromatic leukodystrophy (MLD), globoid cell
leukodystrophy (GLD or Krabbe) or cerebral adrenoleukodystrophy (cALD)

- Adequate organ function

- Availability of eligible donor material

Exclusion Criteria:

- Availability of a matched-related donor who is not a carrier of the same genetic
defect

- Active infection at screening

- Prior myeloablative conditioning

- History of human immunodeficiency virus (HIV) infection