Abstract Details

Title 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

Topic Child Neurology and Developmental Neurology

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-059

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 x 10⁶ cells/kg and median total nucleated cell dose of 26.4 x 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.

Authors/Disclosures
Paul Orchard PRESENTER	No disclosure on file
Glen Raffel, MD, PhD (Magenta Therapeutics)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Troy Lund	No disclosure on file
Ashish Gupta, MD (University of Minnesota)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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