Preliminary results demonstrate engraftment with minimal neutropenia with MGTA-456, a CD34+expanded cord blood (CB) product in patients transplanted for inherited metabolic disorders (IMD)

Abstract

Mucopolysaccharidosis type IH (Hurler Syndrome), metachromatic leukodystrophy (MLD), globoid cell leukodystrophy (GLD) and cerebral adrenoleukodystrophy (cALD) are progressive diseases treatable with allogeneic hematopoietic stem cell transplantation (HSCT). While cord blood is a common stem cell source, it may be associated with prolonged neutropenia and graft failure. MGTA-456 is a cell therapy produced from a single CB unit using an aryl hydrocarbon receptor antagonist in a 15-day expansion culture of CD34+cells. In previous studies, patients with hematologic malignancies demonstrated a median 324-fold expansion of CD34+cells, and the time to neutrophil recovery was significantly reduced by a median of 9 days compared to historical controls. As higher CD34+doses have been correlated with improved engraftment and outcomes in inherited metabolic disease patients, we initiated a Phase 2, open-label trial to enroll up to 12 patients with a diagnosis of MPS1, cALD, MLD, and GLD utilizing CB units matched at ≥6 of 8 HLA loci using allele-based typing. The HSCT regimen consists of anti-thymocyte globulin (days -9 to -6), fludarabine (days -5 to -2) and busulfan (days -5 to -2), with cyclosporin and methylprednisolone as graft vs. host disease prophylaxis. In four patients treated thus far, a marked expansion of CD34+cells (median 482-fold) was observed. Two patients had no days of neutropenia and 2 patients had 1 and 4 days respectively, in contrast to a mean of 7.8 days in a historical Minnesota cohort (N=27) with identical conditioning. Donor myeloid chimerism (≥98%) was achieved by day +14 in all patients. One patient developed autoimmune cytopenia, a known complication unrelated to MSGT 456, resulting in death at day +143. Based on these promising data, MGTA-456 has potential to improve hematopoietic cell recovery and transplant-related outcomes in patients undergoing HSCT for patients with Inherited metabolic disorders.