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bluebird bio Presents Updated Data from Phase 2/3 Starbeam Study of Investigational Lenti-D™ Gene Therapy for CALD and Initial Data from Observational Study ALD-103 of Allogeneic Hematopoietic Stem Cell Transplant in CALD at 2018 SSIEM


− Updated Efficacy and Safety Data Consistent with Previously
Reported Phase 2/3 Starbeam Results –

− General Agreement Reached on Regulatory Pathway for Lenti-D in the
U.S. and EU –

bio, Inc
. (NASDAQ:BLUE) announced updated results from the Phase
2/3 Starbeam study (ALD-102) of its investigational Lenti-D™ gene
therapy in boys 17 years of age and under with cerebral
adrenoleukodystrophy (CALD), and initial data from ALD-103, the ongoing
observational study of outcomes from allogeneic hematopoietic stem cell
transplant (allo-HSCT) in boys 17 years of age and under with CALD. The
data were presented today at the Society for the Study of Inborn Errors
of Metabolism (SSIEM) 2018 Symposium in Athens, Greece.

bluebird bio has also reached general agreement with the U.S. Food and
Drug Administration (FDA) and the European Medicines Agency (EMA) on the
clinical development program to support future marketing applications
for Lenti-D in CALD.

"Cerebral adrenoleukodystrophy is a genetic disease primarily affecting
young boys that causes progressive damage to the brain, leading to the
permanent loss of physical and cognitive function, and it is often
fatal," said David Davidson, M.D., chief medical officer, bluebird bio.
"The data we presented from our Phase 2/3 Starbeam study are consistent
with the results we have observed with Lenti-D to date, with the
additional follow-up showing durable lack of progression to major
functional disabilities (MFD) in boys who were MFD-free at 24 months
post-treatment. The data from the ALD-103 study highlight the increased
risks of mortality and morbidity in boys without a matched sibling donor
who undergo allogeneic HSCT. We look forward to working with the FDA and
EMA to advance our goal of delivering a gene therapy for patients with
this terrible disease."

Updated Results: Phase 2/3 Starbeam Study
Phase 2/3 Starbeam study has met its enrollment goal. All reported data
are as of April 25, 2018 and reflect a total study population of 31
patients. Of these 31 patients, 29 have received Lenti-D and the median
follow-up for all treated patients was 34 months (0.4 – 54 months).

The primary efficacy endpoint of the Phase 2/3 Starbeam study is the
proportion of patients who are alive and free of major functional
disabilities (MFD) at month 24. MFDs are six severe disabilities
commonly attributed to CALD and thought to have the most profound impact
on a patient's ability to function independently: loss of ability to
communicate, cortical blindness, need for tube feeding, total
incontinence, wheelchair dependence, and complete loss of voluntary

As previously reported in the New England Journal of Medicine
(October 2017), of the 17 patients treated with Lenti-D who completed 24
months of follow-up, 15 patients (88 percent) were alive and MFD-free.
One patient withdrew from the study, and one died following rapid
development of MFDs post-treatment. All patients who were MFD-free at 24
months (n=15) continued to be MFD-free. The median follow-up for the
initial group (n=17) was 41.4 months (13.4 - 54.0 months).

An additional 12 patients have received Lenti-D in the Phase 2/3
Starbeam study. While these patients have not reached the primary
endpoint of 24-month follow-up, there have been no MFDs reported as of
April 25, 2018. The median follow-up for this additional cohort of
patients is 4.2 months (0.4 – 11.7 months).

Secondary efficacy endpoint data for gadolinium-enhancement (GdE) and
Neurologic Function Scores (NFS) were also reported. GdE was assessed by
magnetic resonance imaging (MRI) every six months following transplant
up to 24-months, and then every 12 months. In the 15 patients who
completed 24 months of follow-up, 14 were negative for GdE as of their
last MRI. Eleven patients in the study had intermittent re-emergence of
GdE-positivity at various follow-up assessments, however, post-treatment
GdE positivity was markedly reduced in intensity and does not appear to
correlate with clinical outcome.

NFS was used to quantify the severity of neurologic dysfunction based on
15 symptoms. All patients had an NFS of ≤1 at time of Lenti-D treatment.
In 15 patients who met 24 months of follow up by April 25, 2018; 14 had
an NFS score ≤1 at their last follow-up visit, and one patient had an
increase in NFS from 1 to 2, due to vision impairment and non-febrile
seizures. One patient had rapid disease progression beginning early in
their participation in the study, resulting in multiple MFDs and an NFS
of 17 at last follow-up.

The primary safety endpoint of the Phase 2/3 Starbeam study is the
proportion of patients who experienced grade ≥2 acute graft-versus-host
disease (GvHD) or chronic GvHD by 24 months post-treatment. No acute or
chronic GvHD has been reported post-Lenti-D treatment as of April 25,
2018. There has been no graft failure, insertional oncogenesis or
replication competent lentivirus detected. The safety profile of Lenti-D
is generally consistent with myeloablative conditioning with busulfan
and cyclophosphamide. Three adverse events (AE) have been deemed
potentially related to treatment with Lenti-D and include BK-mediated
viral cystitis (grade 3), tachycardia (grade 1), and vomiting (grade 1).

"As a physician who treats boys with CALD, I see its devastating effects
on young children and families," said Professor Paul Gissen, Consultant
in Pediatric Metabolic Diseases at Great Ormond Street Hospital, London,
United Kingdom, and an investigator in the Phase 2/3 Starbeam study.
"Data from the Phase 2/3 Starbeam study suggest that Lenti-D, which
utilizes a child's own cells and does not require a matched donor, may
be a potential treatment for CALD."

Initial Results from ALD-103 Study
has been successfully used to treat CALD but may be associated with
adverse immunologic complications. The ongoing observational study
ALD-103 is designed to assess safety and efficacy outcomes of this
treatment option in boys 17 years of age or younger with CALD.

As of April 25, 2018, 41 pediatric patients were enrolled in the ALD-103
study and had undergone allo-HSCT. Thirty-one patients received cells
from unrelated donors and 10 received cells from a related donor. The
median baseline NFS for the group was 0.0 (min – max, 0.0 - 4.0). The
median Loes score, a 34-point scale that measures the location and
extent of demyelination through MRI, was 3.0 (min – max, 0.0 - 16.0).
Twenty-five patients had early cerebral disease, defined as having
evidence of cerebral disease established by GdE positivity or Loes score
≥0.5, Loes score ≤9.0, and NFS ≤1.

Initial results were in line with safety and efficacy outcomes reported
in the literature for allo-HSCT in patients with CALD. Two-year
Kaplan-Meier estimates of MFD-free survival post-allo-HSCT, were 78
percent for patients with early disease (n=25) and 71 percent for all
patients (n=41).

Transplant-related mortality was defined as death due to any
transplantation-related cause other than disease progression. There were
six transplant-related deaths at one year (14.6 percent); none of these
patients had a matched sibling donor. Engraftment failure was reported
in five patients (12 percent); none of these patients had a matched
sibling donor and all received a second transplant.

Of the 41 patients who received allo-HSCT, 34 percent (n=14) experienced
either grade ≥2 acute GvHD or chronic GvHD.

Lenti-D Data at SSIEM
Presentation: Lenti-D hematopoietic stem cell gene therapy for cerebral
adrenoleukodystrophy: safety and efficacy outcomes from an ongoing Ph
2/3 trial

Presenter: Paul Gissen, MBChB, Ph.D., FRCPCH, Pediatric
Metabolic Diseases at Great Ormond Street Hospital, London, United
Date & Time: Wednesday, September 5, 2018, 9:00
– 10:30 a.m. EEST (2:00 – 3:30 a.m. EDT)

Oral Presentation: An observational study of patients with cerebral
adrenoleukodystrophy (CALD) treated with allogeneic hematopoietic stem
cell transplant

Presenter: Robert Chiesa, M.D., Pediatric Bone Marrow
Transplantation at Great Ormond Street Hospital, London, United Kingdom
& Time:
Wednesday, September 5, 2018, 9:00 – 10:30 a.m.
EEST (2:00 – 3:30 a.m. EDT)

Regulatory Progress for Lenti-D in Cerebral

bluebird bio reached general
agreement with the FDA and EMA on the clinical development program to
support future marketing applications for Lenti-D in the treatment of

The primary efficacy endpoint in the Phase 2/3 Starbeam study is the
proportion of patients at month 24 who achieve MFD-free survival. This
endpoint will be compared to a clinically meaningful benchmark that is
based on literature and data collected in ALD-101, a retrospective
analysis that assessed the natural history of CALD as well as outcomes
from allo-HSCT treatment in patients with CALD.

The primary safety endpoint in the Phase 2/3 Starbeam study is the
proportion of patients who experience grade ≥2 acute GvHD or chronic
GvHD at 24 months post treatment. Due to the potential increased risk of
immunologic complications when randomizing subjects with a less than
ideal HLA-matched donor to an allo-HSCT trial arm, an external control
approach has been adopted to establish the benefit-risk profile of

The safety results from the Phase 2/3 Starbeam study will be compared
with data collected from study ALD-103, a multinational, multi-site,
prospective and retrospective observational study designed to evaluate
outcomes of allo-HSCT in subjects with CALD aged 17 years or younger.

ALD-103 is running concurrently with ALD-102 and its study design is
consistent with ALD-102.

bluebird bio is conducting a long-term safety and efficacy follow-up
study (LTF-304) for patients who have participated in ALD-102 and were
treated with Lenti-D.

About Cerebral Adrenoleukodystrophy
(ALD) is a rare, X-linked metabolic disorder that is estimated to affect
one in 21,000 male newborns worldwide. ALD is caused by mutations in the ABCD1
gene that affect the production of adrenoleukodystrophy protein
(ALDP) and subsequently cause toxic accumulation of very long chain
fatty acids (VLCFAs) in the adrenal cortex and white matter of the brain
and spinal cord.

Approximately 35-40 percent of boys with ALD will develop cerebral ALD
(CALD), the most severe form of ALD. CALD is a progressive
neurogenerative disease that involves breakdown of myelin, the
protective sheath of the nerve cells in the brain that are responsible
for thinking and muscle control. Symptoms of CALD usually occur in early
childhood and progress rapidly, if untreated, leading to severe loss of
neurologic function, and eventual death, in most patients.

Currently, the only therapeutic option for patients with CALD is
allo-HSCT. Beneficial effects have been reported if allo-HSCT is
performed early in the course of CALD progression. Potential
complications of allo-HSCT, which can be fatal, include graft failure,
graft-versus-host disease, and opportunistic infections, particularly in
patients who undergo transplant with non-sibling matched donor cells.

Early diagnosis of CALD is important, as the outcome of treatment varies
with the clinical stage of the disease at the time of transplant.
Newborn screening for ALD is a critical enabler of early diagnosis and
successful treatment of ALD. In the United States, newborn screening for
ALD was added to the Recommended Universal Screening Panel in February
2016 but is currently active in only a limited number of states.

About bluebird bio, Inc.
With its lentiviral-based gene
therapies, T cell immunotherapy expertise and gene editing capabilities,
bluebird bio has built a pipeline with broad potential application in
severe genetic diseases and cancer.

bluebird bio's gene therapy clinical programs include investigational
treatments for cerebral adrenoleukodystrophy, transfusion-dependent
β-thalassemia, also known as β-thalassemia major, and severe sickle cell

bluebird bio's oncology pipeline is built upon the company's lentiviral
gene delivery and T cell engineering, with a focus on developing novel T
cell-based immunotherapies, including chimeric antigen receptor (CAR T)
and T cell receptor (TCR) therapies. The company's lead oncology
programs are anti-BCMA CAR T programs partnered with Celgene.

bluebird bio's discovery research programs include utilizing
meatal/homing endonuclease gene editing technologies with the potential
for use across the company's pipeline.

bluebird bio has operations in Cambridge, Massachusetts; Seattle,
Washington; Durham, North Carolina and Zug, Switzerland.

Lenti-D is a trademark of bluebird bio, Inc.

Forward-Looking Statements
This release contains
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995, clinical development and
anticipated regulatory approval pathways, and market potential of the
Company's Lenti-D product candidate to treat cerebral
adrenoleukodystrophy. Any forward-looking statements are based on
management's current expectations of future events and are subject to a
number of risks and uncertainties that could cause actual results to
differ materially and adversely from those set forth in or implied by
such forward-looking statements. These risks and uncertainties include,
but are not limited to, risks that the preliminary efficacy and safety
data for our Lenti-D product candidate from the Starbeam Study will not
continue or persist, the risk of cessation or delay of any of the
ongoing clinical studies and/or our development of Lenti-D, the risks
regarding future potential regulatory approvals of Lenti-D, including
the risk that the Starbeam Study will be insufficient to support
regulatory submissions or marketing approval in the US and EU, and the
risk that any one or more of our product candidates will not be
successfully developed, approved or commercialized. For a discussion of
other risks and uncertainties, and other important factors, any of which
could cause our actual results to differ from those contained in the
forward-looking statements, see the section entitled "Risk Factors" in
our most recent Form 10-Q, as well as discussions of potential risks,
uncertainties, and other important factors in our subsequent filings
with the Securities and Exchange Commission. All information in this
press release is as of the date of the release, and bluebird bio
undertakes no duty to update this information unless required by law.

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