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 —

(NASDAQ:MGTA), a clinical-stage biotechnology company
developing novel medicines to bring the curative power of stem cell
transplant to more patients, today announced that the Company presented
Phase 2 clinical data and preclinical research on its MGTA-456 program
at the TCT annual meeting.

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 Paul
Orchard, M.D., Medical Director, Inherited Metabolic & Storage Disease
Bone Marrow Transplantation Program, University of Minnesota.

In a separate oral presentation in the Best Pediatric Abstracts Session,
Kevin Goncalves, Ph.D., Magenta Therapeutics, highlighted data
demonstrating that the high stem cell doses in MGTA-456 accelerate and
improve engraftment of human microglia in the brains of transplanted
mice. Tony Boitano, Ph.D., Magenta Therapeutics, presented a third data
set in the TCT Meeting Best Abstracts session demonstrating that
MGTA-456 contains large doses of the stem cells responsible for
engraftment, which are also correlated with rapid neutrophil recovery in
patients following transplant.

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
challenge,” said John Davis, M.D., M.P.H., chief medical officer,
Magenta Therapeutics. “MGTA-456 provides patients with a large number of
stem cells to help overcome these challenges, and we are pleased that
all five evaluable patients treated with MGTA-456 thus far have met the
primary endpoints with robust and consistent engraftment. Further, in
patients with Hurler syndrome, the production of normal levels of enzyme
was associated with reduction in toxic disease-related metabolites. In
patients with cALD, we have seen persistent decrease in brain
inflammation as measured by imaging. These are early signs that MGTA-456
may provide disease-modifying clinical benefit to these patients.”

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 January 30th, 2019, presented by Paul
Orchard, M.D., University of Minnesota:

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

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
  • 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

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 Kevin Goncalves, Ph.D., Magenta Therapeutics:

  • 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 Tony Boitano, Ph.D., Magenta Therapeutics:

  • 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
    at the University of Minnesota.

About Magenta Therapeutics
Headquartered in Cambridge,
Mass., Magenta Therapeutics is a clinical-stage biotechnology company
developing novel medicines for patients with autoimmune diseases, blood
cancers and genetic diseases. By creating a platform focused on critical
areas of unmet need, Magenta Therapeutics is pioneering an integrated
approach to allow more patients to receive one-time, curative therapies
by making the process more effective, safer and easier.

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regarding Magenta’s future expectations, plans and prospects, including
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that constitute forward-looking statements under the Private Securities
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statements are based only on facts and factors currently known by
Magenta. As a result, you are cautioned not to rely on these
forward-looking statements. These and other risks concerning Magenta’s
programs and operations are described in additional detail in its
registration statement on Form S-1, its Quarterly Report on Form 10-Q
and its other filings made with the Securities and Exchange Commission
from time to time. Any forward-looking statement made in this press
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forward-looking statement, whether as a result of new information,
future developments or otherwise.


Magenta Therapeutics:
Manisha Pai, Vice President, Communications &
Investor Relations

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