Magenta Therapeutics Presents Clinical and Preclinical Data on MGTA-456 Cell Therapy in Best Abstracts Sessions at Transplant and Cellular Therapy (TCT) Annual Meeting
-- Additional follow-up on patients with cerebral adrenoleukodystrophy (cALD) treated with MGTA-456 in Phase 2 study in inherited metabolic disorders (IMDs) shows persistent resolution of brain inflammation on MRI and stable Loes disease scores --
-- Additional follow-up on patients with Hurler syndrome treated with MGTA-456 in Phase 2 IMD study shows correction of enzyme deficiency and decrease in toxic metabolites --
--Three presentations highlighted by TCT among best abstracts and best pediatric abstracts --
MGTA-456 is a cell therapy designed to provide a high dose of
hematopoietic stem cells that are well-matched to the patient. The
Company plans to enroll 12 patients in the ongoing Phase 2 study in
inherited metabolic disorders, which include cALD, metachromatic
leukodystrophy and globoid cell leukodystrophy. The study previously
enrolled patients with Hurler syndrome. The primary endpoint of the
study is engraftment after transplantation. Both short- and long-term
disease specific outcomes are also being collected. Data from the first
five evaluable patients treated in this study were highlighted in an
oral presentation in the Pediatric Best Abstracts Session by
In a separate oral presentation in the Best Pediatric Abstracts Session,
“Inherited metabolic disorders are rare diseases that cause progressive
damage to multiple organs, including the brain, and are often fatal.
Stem cell transplant is the only disease-modifying treatment option but
delivering sufficient doses of stem cells has been a persistent
Robust Engraftment with MGTA-456, a CD34+ Expanded Cell Therapy Product in Patients with Inherited Metabolic Disorders (IMD): Preliminary Phase 2 Trial Results
Key results, as of
Transplant success outcomes:
Five of five evaluable patients treated with MGTA-456 met the primary
endpoint of successful engraftment by day 42 following the transplant
- In recent historical cohorts of patients undergoing regular cord blood transplantation with identical pre-transplant conditioning, up to 32% did not engraft at comparable time points.
The patients treated with MGTA-456 had minimal neutropenia, lasting
for a median of 1 day.
- In the historical cohort, neutropenia lasted for a median of 8 days.
Early evidence of disease benefit:
The two patients with cALD showed resolution of gadolinium enhancement
on MRI, an indicator of brain inflammation, by day 28 post-transplant,
and the resolution persisted at the most recent patient visits (Day
180 post-transplant and Day 100 post-transplant, respectively).
- Durable resolution of gadolinium enhancement is correlated with long-term disease benefit in patients with cALD.
- The Loes score, a method for quantifying the severity of brain abnormalities and atrophy found on MRI, remained stable in both patients as of the most recent patient visits.
Patients with Hurler syndrome achieved normal levels of blood
leukocyte IDUA enzyme, the enzyme that is deficient in untreated
patients with Hurler syndrome. This suggests that transplant with
MGTA-456 is beginning to affect the disease in these patients.
- Normalization of blood leukocyte IDUA enzyme after transplant has been significantly associated with improvement in disease.
- Patients with Hurler syndrome showed a marked decline in urine total glycosaminoglycan (GAG) levels as of the Day 100 post-transplant patient visit. This is correlated with improved long-term disease outcomes.
- Two treatment-related adverse events were observed: one grade 1 vomiting and one grade 3 nausea, both of which were transient.
Preclinical Data, MGTA-456 Stem Cell Expansion Program
MGTA-456, a First-in-Class Cell Therapy with High Doses of CD34+ CD90+ Cells, Enhances Speed and Level of Human Microglia Engraftment in the Brains of NSG Mice
Key results presented by
- Stem cell transplant is a standard of care in inherited metabolic disorders, and engraftment of microglial cells, which produce the deficient enzyme in the brain, after transplant is crucial for successful outcomes in patients.
- NSG mice were transplanted with MGTA-456 or unexpanded cord blood after being conditioned with total body irradiation or either high- or low-dose busulfan, and engraftment of microglial cells in the brain was measured.
- In sublethally-irradiated animals, MGTA-456 led to an 11-fold increase in hematopoietic engraftment and a 24-fold increase in microglial engraftment in the brain (p<0.001, n=8 mice) relative to standard of care, with histology consistent with engrafting microglia in the brain.
- In busulfan-conditioned animals, MGTA-456 led to a 25-fold increase in hematopoietic engraftment and a 60-fold increase in microglial engraftment in the brain relative to controls (p<0.001, n=8 mice).
- MGTA-456 led to faster microglial engraftment: a 28-fold increase in microglial engraftment was demonstrated as early as 2 weeks post-transplant with MGTA-456 (p<0.001, n=8 mice). The number of engrafting hematopoietic cells in the periphery correlated with number of engrafting microglia in the brain (p<0.0001).
- Subpopulations of MGTA-456 were evaluated to determine the source of microglial engraftment. Only CD34+CD90+ cells, but not CD34+CD90- or CD34- cells, led to brain engraftment, consistent with the subpopulation of cells that result in hematopoietic engraftment following transplant of unexpanded cells (Radtke et al., Sci Trans Med 2017 and Goncalves et al., Blood 2017 130:659).
- These data demonstrate that in preclinical models microglial engraftment is faster and greater in recipients of MGTA-456 even after lower dose busulfan conditioning, that microglial engraftment correlates with peripheral blood recovery, and that microglia cells are derived from CD34+CD90+ cells.
MGTA-456 Contains Large Numbers of CD34+CD90+ Hematopoietic Stem Cells Which Contain the NSG Engraftment Activity and Correlate with Time to Neutrophil Recovery Following Transplant into Patients with Hematologic Malignancy
Key results, presented by
- To date 41 evaluable patients have been treated with MGTA-456 (36 with blood cancers; 5 with inherited metabolic disorders), and all have engrafted at a significantly faster rate than historical controls.
- Magenta scientists sought to fully characterize the expanded CD34+ cell fraction of MGTA-456 phenotypically and functionally and identify the cell population that correlates with time to neutrophil recovery.
- MGTA-456 was found to contain large doses of CD34+CD90+ hematopoietic stem cells and progenitors, which are responsible for successful engraftment in mouse models.
- The dose of CD34+CD90+ cells was also found to have the strongest correlation with faster time to neutrophil recovery in patients.
- Of the 36 patients with blood cancers treated with MGTA-456, 100% of patients engrafted in a median of 14 days, with 67 percent overall survival at 2 years in this high-risk disease setting.
A Phase 2 study of MGTA-456 in patients with blood cancers is ongoing
University of Minnesota.
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Manisha Pai, Vice President, Communications & Investor Relations