A single arm, open label, clinical study of cryopreserved autologous CD34+ cells transduced with lentiviral vector containing human ARSA cDNA, for the treatment of early onset Metachromatic Leukodystrophy (MLD)

Metachromatic Leukodystrophy (MLD)

Gross motor function measure (GMFM) score at 24 months post gene therapy

GMFM score post gene therapy at multiple visits over time; • Clinical efficacy at 24 months post gene therapy and multiple visits over time, as measured by: a) Gross Motor Function Classification (GMFC)- MLD score b) Neurological Examinations c) Assessment of Nerve Conduction Velocity (NCV) d) Evaluation of Brain Magnetic Resonance (MR) imaging assessments / parameters (e.g. Modified Loes Score) e) Neurocognitive assessments, • %LV positive clonogenic progenitors in bone marrow (BM) at Day 30 post-gene therapy and at multiple visits over time • Vector copy number (VCN) (in BM mononuclear cells) at Day 30 post-gene therapy and at multiple visits over time • VCN (in peripheral blood [PB] mononuclear cells) at Day 60 post-gene therapy and at multiple visits over time, • The following at Day 60 post-gene therapy and at multiple visits over time: i) Arylsulfatase A (ARSA) activity in Total Peripheral blood mononuclear cells (PBMCs) ii) ARSA activity in PB CD15+ cells iii) ARSA activity in PB CD14+ cells • ARSA activity in cerebral spinal fluid (CSF) at Day 90 post-gene therapy and at multiple visits over time, • Safety and tolerability as measured by adverse events (AEs) reporting; • Conditioning regimen related toxicity and AEs • Non-conditioning related AEs, • Hematological recovery, defined as reconstitution of absolute neutrophil count (ANC) > 500 neutrophils/ µL, associated with evidence of BM recovery (i.e. no hypocellular marrow) by day +60 • Incidence and titers of antibodies against ARSA • Absence of malignancy or abnormal clonal proliferation due to insertional oncogenesis • Absence of Replication Competent Lentivirus (RCL)

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