bluebird bio Announces EU Conditional Marketing Authorization for ZYNTEGLO™ (autologous CD34+ cells encoding βA-T87Q-globin gene) Gene Therapy for Patients 12 Years and Older with Transfusion-Dependent β-Thalassemia Who Do Not Have β0/β0 Genotype

ZYNTEGLO is the first gene therapy approved for transfusion-dependent
β-thalassemia (TDT)

European marketing authorization for ZYNTEGLO follows the fastest
assessment of an advanced therapy medicinal product (ATMP) as part of
the European Medicines Agency’s Priority Medicines (PRIME) program

ZYNTEGLO is bluebird bio’s first gene therapy to gain regulatory approval

CAMBRIDGE, Mass.–(BUSINESS WIRE)–bluebird
bio, Inc. (Nasdaq: BLUE) announced
today that the European Commission (EC) has granted conditional
marketing authorization for ZYNTEGLO™ (autologous CD34+ cells encoding β^A-T87Q-globin
gene), a gene therapy for patients 12 years and older with
transfusion-dependent β-thalassemia (TDT) who do not have a β⁰/β⁰ genotype,
for whom hematopoietic stem cell (HSC) transplantation is appropriate
but a human leukocyte antigen (HLA)-matched related HSC donor is not
available. bluebird bio will continue the country-by-country
reimbursement process to help ensure access to ZYNTEGLO for appropriate
patients.

TDT is a severe genetic disease caused by mutations in the β-globin gene
that result in reduced or absent hemoglobin. In order to survive, people
with TDT maintain hemoglobin levels through lifelong chronic blood
transfusions. These transfusions carry the risk of progressive
multi-organ damage due to unavoidable iron overload. ZYNTEGLO is a
one-time gene therapy that addresses the underlying genetic cause of TDT
and offers patients 12 years and older who do not have a β⁰/β⁰ genotype
the potential to become transfusion independent, which once achieved is
expected to be life-long.

“EC approval of ZYNTEGLO is a milestone that represents the dedication
and commitment of clinical investigators, healthcare providers, patients
and their families, and our employees, all of whom have helped advance
this treatment from concept to an approved therapy,” said Nick Leschly,
chief bluebird. “Our first product approval is a humbling moment for all
of us at bluebird, and we look forward to continuing our work with the
TDT community and health systems to bring this important treatment to
patients.”

ZYNTEGLO was reviewed as part of the European Medicines Agency’s (EMA)
Priority Medicines (PRIME) and Adaptive Pathways programs, which support
medicines that may offer a major therapeutic advantage over existing
treatments, or benefit patients without treatment options. The PRIME and
Adaptive Pathway programs allowed for early and enhanced dialogue and
accelerated assessment of ZYNTEGLO, which was completed on the shortest
timetable for an advanced therapy medicinal product (ATMP) by the EMA to
date.

“As one of the investigators in the clinical studies of ZYNTEGLO, I have
witnessed firsthand the hope this gene therapy can provide to patients
and their families who have often been managing this disease and
transfusions for years, often for decades,” said Professor Franco
Locatelli, M.D., Ph.D., Professor of Pediatrics, Sapienza University of
Rome, Italy, and Director, Department of Pediatric Hematology/Oncology
and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome,
Italy. “This approval by the European Commission means we now have a
gene therapy for certain patients with TDT that has the potential to
transform lives by offering the possibility of a transfusion-free
future.”

ZYNTEGLO adds functional copies of a modified form of the β-globin gene
(β^A-T87Q-globin gene) into a patient’s own hematopoietic
(blood) stem cells (HSCs). This means there is no need for donor HSCs
from another person as is required for allogeneic HSC transplantation
(allo-HSCT). A patient’s HSCs are removed from the body through a
process called apheresis. These HSCs are taken to a lab where a
lentiviral vector is used to insert the β^A-T87Q-globin gene
into the patient’s HSCs. This step is called transduction. Before their
modified HSCs are returned through infusion, a patient receives
chemotherapy to prepare their bone marrow for the modified HSCs that now
carry the β^A-T87Q-globin gene. Once a patient has the β^A-T87Q-globin
gene they have the potential to produce HbA^T87Q, which is
gene therapy-derived-hemoglobin, at levels that eliminate or
significantly reduce the need for transfusions. Upon engraftment and
achievement of transfusion independence, effects of ZYNTEGLO are
expected to be life-long.

Due to the highly technical and specialized nature of administering gene
therapy in rare diseases, bluebird bio is working with select qualified
treatment centers that have expertise in stem cell transplant and
treating patients with TDT to provide ZYNTEGLO.

“We welcome European Commission authorization for the first gene therapy
for TDT. This achievement means the TDT community now has another
treatment option that may provide new hope for people living with TDT
who have been managing their disease through chronic transfusions,” said
Dr. Androulla Eleftheriou, Thalassemia International Federation
Executive Director. “Undoubtedly, this is not the end of the road, but
merely the beginning, and TIF is ready to collaborate with all involved
stakeholders to help ensure accessibility for as many appropriate
patients as possible.”

The conditional marketing authorization is valid in all 28 member states
of the EU as well as Iceland, Liechtenstein and Norway.

Data Supporting Clinical Profile of ZYNTEGLO

The conditional marketing authorization is supported by efficacy, safety
and durability data from the Phase 1/2 HGB-205 study and the completed
Phase 1/2 Northstar (HGB-204) study as well as available data from the
ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies,
and the long-term follow-up study LTF-303, as of the data cut off of
December 13, 2018.

Data from Phase 1/2 HGB-205 showed that 75 percent (n=3/4) of patients
who do not have a β⁰/β⁰ genotype achieved
transfusion independence, meaning they had not received a transfusion
for at least 12 months or more and maintained weighted hemoglobin ≥9
g/dL. In the Phase 1/2 Northstar study, 80 percent (n=8/10) of patients
who do not have a β⁰/β⁰ genotype achieved
transfusion independence.

These 11 patients (three from HGB-205 and eight from Northstar)
continued to maintain transfusion independence, which at the time of
data cut off was for a duration of 21–56 months.

Five patients in Northstar-2 were evaluable for transfusion
independence. Of these five, 80 percent (n=4/5) achieved transfusion
independence.

Non-serious adverse events (AEs) observed during clinical trials that
were attributed to ZYNTEGLO were hot flush, dyspnoea, abdominal pain,
pain in extremities and non-cardiac chest pain. One serious adverse
event (SAE) of thrombocytopenia was considered possibly related to
ZYNTEGLO.

Additional AEs observed in clinical studies were consistent with the
known side effects of HSC collection and bone marrow ablation with
busulfan, including SAEs of veno-occlusive disease.

For details, please see the Summary of Product Characteristics (SmPC).

ZYNTEGLO continues to be evaluated in the ongoing Phase 3 Northstar-2
and Northstar-3 studies and the long-term follow-up study LTF-303.

In addition to Priority Medicines (PRIME) designation, ZYNTEGLO received
an Orphan Medicinal Product designation from the EC for the treatment of
β-thalassemia intermedia and major, which includes TDT.

The U.S. Food and Drug Administration granted ZYNTEGLO Orphan Drug
status and Breakthrough Therapy designation for the treatment of TDT.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From
our Cambridge, Mass., headquarters, we’re developing gene therapies for
severe genetic diseases and cancer, with the goal that people facing
potentially fatal conditions with limited treatment options can live
their lives fully. Beyond our labs, we’re working to positively disrupt
the healthcare system to create access, transparency and education so
that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. We’re putting
our care and expertise to work across a spectrum of disorders by
researching cerebral adrenoleukodystrophy, sickle cell disease,
transfusion-dependent β-thalassemia and multiple myeloma using three
gene therapy technologies: gene addition, cell therapy and
(megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and
Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO and LentiGlobin are trademarks of bluebird bio.

The full common name for ZYNTEGLO: A genetically modified autologous
CD34+ cell enriched population that contains hematopoietic stem cells
transduced with lentiviral vector encoding the β^A-T87Q-globin
gene.

Forward-Looking Statements

This release contains “forward-looking statements” within the meaning of
the Private Securities Litigation Reform Act of 1995, including
statements regarding the Company’s plans and expectations for the
commercialization for ZYNTEGLO™ (autologous CD34+ cells encoding β^A-T87Q-globin
gene, formerly LentiGlobin™ in TDT) to treat TDT, and the potential
implications of clinical data for patients. 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: the risk that the
efficacy and safety results from our prior and ongoing clinical trials
of ZYNTEGLO will not continue or be repeated in our ongoing or planned
clinical trials of ZYNTEGLO; the risk that the current or planned
clinical trials of ZYNTEGLO will be insufficient to support regulatory
submissions or marketing approval in the US, or for additional patient
populations in the EU; the risk that the production of HbA^T87Q may
not be sustained over extended periods of time; and the risk that we may
not secure adequate pricing or reimbursement to support continued
development or commercialization of ZYNTEGLO following regulatory
approval. 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.

Contacts

bluebird bio
Investors:
Elizabeth Pingpank, 617-914-8736
[email protected]
or
Media:
Catherine
Falcetti, 339-499-9436
[email protected]