Patients with Inherited Metabolic Disorders (IMD) transplanted with MGTA-456, a CD34+ Expanded Cell Therapy Product, Show Rapid Engraftment in Preliminary Phase 2 Trial Results (P4.6-059)

Objective: To determine whether MGTA-456 improves engraftment, neutrophil recovery and outcomes in IMD transplant patients. Background: Hurler Syndrome, cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD) are fatal IMDs affecting the central nervous system treatable through allogeneic hematopoietic stem cell transplantation (HSCT). Cord blood (CB) is a preferred unrelated graft source in IMDs, however, prolonged neutropenia and graft failure remain challenges. MGTA-456 is a cell therapy product produced from CB using an aryl hydrocarbon receptor antagonist in a CD34+ expansion culture. As higher CD34+ doses improve engraftment in IMD patients, we hypothesize MGTA-456 may enhance neutrophil recovery and engraftment in IMD patients. Design/Methods: 12 patients will be enrolled with a diagnosis of Hurler, cALD, MLD, or GLD utilizing MGTA-456 produced from CB units matched at ≥ 6 of 8 HLA loci. The reduced toxicity transplant conditioning regimen consists of anti-thymocyte globulin, fludarabine (160 mg/m2 ) and targeted busulfan (21,000 to 22,000 μM/min/L−1) with cyclosporin/methylprednisolone immunoprophylaxis Results: Five patients have been treated per protocol to date. MGTA-456 contained a median 561-fold expansion of CD34+ cells with a median infused CD34+ cell dose of 110 × 106 cells/kg and median total nucleated cell dose of 26.4 × 107. The median duration of neutropenia was 1 day (range 0–9), in contrast to a historical median of 8 days. Myeloid chimerism was ≥98% donor on day +14 in evaluable patients. Two patients developed autoimmune cytopenia, a known complication in IMD patients after HSCT, assessed as unrelated to MGTA-456. Hurler and cALD disease-specific measures are being followed prospectively and will be reported. Conclusions: Treatment of IMD patients with MGTA-456 showed early and robust engraftment in all patients with marked reduction in days of neutropenia compared to a historical cohort. These preliminary data suggest MGTA-456 has the potential to improve IMD transplant-related outcomes. Disclosure: Dr. Orchard has received research support from Magenta Therapeutics. Dr. Raffel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Raffel has received compensation for serving on the Board of Directors of Magenta Therapeutics. Dr. Raffel holds stock and/or stock options in Magenta Therapeutics which sponsored research in which Dr. Raffel was involved as an investigator. Dr. Condon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Condon holds stock and/or stock options in Magenta Therapeutics. Dr. Monaghan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Monaghan holds stock and/or stock options in Magenta Therapeutics which sponsored research in which Dr. Monaghan was involved as an investigator. Dr. Braun has received research support from Magenta Therapeutics. Dr. Shanley has received research support from Magenta Therapeutics. Dr. Lund has received research support from Magenta Therapeutics. Dr. Gupta has received research support from Magenta Therapeutics. Dr. Boitano has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Boitano holds stock and/or stock options in Magenta Therapeutics which sponsored research in which Dr. Boitano was involved as an investigator. Dr. Cooke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Cooke holds stock and/or stock options in Magenta Therapeutics which sponsored research in which Dr. Cooke was involved as an investigator. Dr. Davis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Davis holds stock and/or stock options in Magenta Therapeutics, which sponsored research in which Dr. Davis was involved as an investigator. Dr. Wagner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Magenta Therapeutics. Dr. Wagner has received research support from Novartis.