bluebird bio Presents Long-Term Efficacy and Safety Data from Clinical Studies of LentiGlobin® Gene Therapy for Transfusion-Dependent β-Thalassemia (TDT) at 24th European Hematology Association (EHA) Congress

Up to 3.8 years of transfusion independence in Phase 1/2 Northstar
(HGB-204) study in patients with TDT who do not have a β⁰/β⁰
genotype

Four of five evaluable patients achieved transfusion independence in
ongoing Phase 3 Northstar-2 (HGB-207) study of patients with TDT who do
not have a β⁰/β⁰
genotype

In patients who were free from transfusions for at least three months
total hemoglobin levels were 10.2–13.6 g/dL in the ongoing Phase 3
Northstar-3 (HGB-212) study in patients with TDT who have a β⁰/β⁰
genotype or IVS-I-110 mutation

CAMBRIDGE, Mass.–(BUSINESS WIRE)–bluebird
bio, Inc. (Nasdaq:BLUE) announced updated results from the completed
Phase 1/2 Northstar (HGB-204) study, and new data from the Phase 3
Northstar-2 (HGB-207) and Phase 3 Northstar-3 (HGB-212) clinical studies
of its LentiGlobin^® gene therapy for patients with
transfusion-dependent β-thalassemia (TDT), at the 24th European
Hematology Association (EHA) Congress in Amsterdam, the Netherlands.

“The maturing data from our clinical studies of LentiGlobin for TDT show
that patients across genotypes are able to achieve and maintain
transfusion independence with stable production of gene
therapy-derived-hemoglobin, HbA^T87Q, extending for years,”
said David Davidson M.D., chief medical officer, bluebird bio. “In
patients who achieve transfusion independence, we have observed
decreased liver iron concentration over time and improved markers of
erythropoiesis, demonstrating the transformative disease-modifying
potential of gene therapy for patients with TDT.”

TDT is a severe genetic disease caused by mutations in the β-globin gene
that result in reduced or absent hemoglobin (Hb). In order to survive,
people with TDT maintain Hb levels through lifelong chronic blood
transfusions. These transfusions carry the risk of progressive
multi-organ damage due to unavoidable iron overload.

LentiGlobin for β-thalassemia addresses the underlying genetic cause of
TDT by adding 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). Once a patient has the β^A-T87Q-globin gene, they
have the potential to produce HbA^T87Q, which is gene
therapy-derived-Hb, at levels that eliminate or significantly reduce the
need for transfusions.

bluebird bio’s clinical development program for LentiGlobin in TDT
includes studies across patient genotypes, including those who do not
have a β⁰/β⁰ genotype as well as those with a β⁰/β⁰
genotype.

“Patients living with β-thalassemia who have a β⁰/β⁰
genotype or an IVS-I-110 mutation typically have low levels of
endogenous hemoglobin,” said Andreas Kulozik, M.D., Ph.D., Heidelberg
University Hospital, Heidelberg, Germany. “Transfusion independence is a
goal for the treatment of TDT, regardless of genotype. Early results
from the ongoing Phase 3 study in patients with a β⁰/β⁰
genotype or an IVS-I-110 mutation show gene therapy-derived-hemoglobin
significantly contributes to improved total hemoglobin levels.”

Northstar (HGB-204)

The results reported for the completed Phase 1/2 Northstar (HGB-204)
study reflect data as of December 13, 2018; of the 18 patients in the
study, 10 patients do not have a β⁰/β⁰ genotype
and eight have a β⁰/β⁰ genotype. All 18 patients
have completed the two-year study and enrolled in the long-term
follow-up study, LTF-303.

Eight of 10 treated patients who do not have a β⁰/β⁰ genotype
achieved transfusion independence (TI), meaning they had not received a
transfusion for at least 12 months or more and maintained a weighted
average Hb ≥9 g/dL.

These eight patients had a median weighted average Hb during TI of 10.3
g/dL (min–max: 9.3–13.2 g/dL) and continued to maintain TI for up to 45
months. The patient follow-up period is calculated from infusion of
LentiGlobin to the last study visit.

In patients who have a β⁰/β⁰ genotype, three of
the eight achieved TI and maintained a median weighted average Hb
ranging from 9.5–10.1 g/dL for a median duration of 16.4 months (min–max:
16.1–20.8 months).

An exploratory assessment was conducted to assess liver iron
concentration (LIC) in the 11 patients from the Northstar study who
achieved TI. Increased iron levels are a consequence of frequent
transfusions. High iron levels can cause organ damage, which many
patients with TDT are at risk of and must manage through chelation
regimens.

LIC was measured at baseline and then every 12 months after treatment
with LentiGlobin. Patients reinitiated iron chelation therapy at a
median of 13 months after LentiGlobin infusion (min–max: 2–16 months).
Over time, LIC began to decrease in all 11 patients with the largest
decrease observed in patients who had 48 months of data available (n=4).
A median 56 percent reduction (min–max: 38–83 percent) was reported in
these four patients.

Northstar-2 (HGB-207) Efficacy

As of December 13, 2018, 20 patients who do not have β⁰/β⁰
genotypes have been treated in the Phase 3 Northstar-2 study. Patient
age ranged from 8–34 years, with five pediatric (<12 years) and 15
adolescent/adult (≥12 years) patients.

Four of five evaluable patients achieved TI and maintained a median
weighted average Hb of 12.4 g/dL (min–max: 11.5–12.6 g/dL). These four
patients continued to maintain TI for a median duration of 13.6 months
(min–max: 12–18.2 months) at the time of the data cut off.

Thirteen of 14 patients with at least three months of follow-up were
free from transfusions for at least three months. Total Hb levels in
these patients ranged from 8.8–13.3 g/dL at the time of the last study
visit. HbA^T87Q levels were stable over time in patients who
were free from transfusions; at Month 6 (n=10) median HbA^T87Q
was 9.5 g/dL and at Month 12 (n=7) median HbA^T87Q was 9.3
g/dL.

An exploratory analysis was conducted with bone marrow from seven
patients with 12 months of follow-up after treatment. The samples were
evaluated for cellularity and myeloid to erythroid ratio. A low myeloid
to erythroid ratio is a key feature of dyserythropoesis, or abnormal
bone marrow red blood cell (RBC) production, characteristic of patients
with TDT. In these seven patients, all of whom had stopped chronic
transfusions, an increase in the myeloid to erythroid ratio was
observed, suggesting improvement in RBC production.

Northstar-3 (HGB-212) Efficacy

As of April 12, 2019, 11 patients with TDT and a β⁰/β⁰
genotype or an IVS-I-110 mutation had been treated in the Phase 3
Northstar-3 study.

The one patient evaluable for TI achieved and maintained it and had a
total Hb of 13.6 g/dL at the Month 16 follow-up.

Five patients had stopped transfusions for at least three months and had
Hb levels of 10.2–13.6 g/dL at the time of the last study visit (5 – 16
months post-treatment). Of these patients, all of those who reached six
months of follow-up (n=4) had HbA^T87Q levels of at least 8
g/dL.

LentiGlobin for TDT Safety

Non-serious adverse events (AEs) observed during clinical studies that
were attributed to LentiGlobin for TDT 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 LentiGlobin for TDT.

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.

As of the data cut off dates stated above, a total of 49 pediatric,
adolescent and adult patients with TDT and a non-β⁰/β⁰ or
β⁰/β⁰ genotype, including patients with
IVS-I-110 mutations, have been treated with LentiGlobin for TDT in the
Northstar, Northstar-2 and Northstar-3 studies.

About LentiGlobin for β-Thalassemia

The European Commission (EC) granted conditional marketing authorization
for LentiGlobin for TDT, to be marketed as ZYNTEGLO® (autologous CD34+
cells encoding β^A-T87Q-globin gene) gene therapy, for
patients 12 years and older with 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.

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). 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 lifelong.

The EMA previously granted Priority Medicines (PRIME) eligibility and
Orphan Medicinal Product designation to ZYNTEGLO for the treatment of
TDT. ZYNTEGLO is also part of the EMA’s Adaptive Pathways pilot program,
which is part of the EMA’s effort to improve timely access for patients
to new medicines.

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

LentiGlobin for TDT continues to be evaluated in the ongoing Phase 3
Northstar-2 and Northstar-3 studies and the long-term follow-up study
LTF-303. For more information about the ongoing clinical studies, visit www.northstarclinicalstudies.com
or clinicaltrials.gov
and use identifier NCT01745120 for Northstar (HGB-204), NCT02906202 for
Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212) and
NCT02633943 for LTF-303.

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. 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 LentiGlobin for TDT will not continue or be
repeated in our ongoing or planned clinical trials of LentiGlobin for
TDT; the risk that the current or planned clinical trials of LentiGlobin
for TDT will be insufficient to support future regulatory submissions in
the U.S. and EU or additional marketing authorizations; 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 LentiGlobin for TDT. 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]