8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of Earliest Event Reported): June 14, 2014

bluebird bio, Inc.

(Exact name of registrant as specified in its charter)

DELAWARE	001-35966	13-3680878
(State or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification No.)

150 Second Street Cambridge, MA	02141
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code (339) 499-9300

Not Applicable

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 7.01 Regulation FD Disclosure

On June 16, 2014, bluebird bio, Inc. (“bluebird”) conducted an investor webcast summarizing clinical data from its HGB-205 clinical trial that was presented at an oral presentation at the 19^th European Hematology Association Congress in Milan, Italy on June 14, 2014. A copy of the presentation is being furnished as Exhibit 99.2 to this Report on Form 8-K.

The information in Item 7.01 of this Report on Form 8-K and Exhibit 99.2 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing

Item 8.01 Other Events

On June 14, 2014, issued a press release announcing clinical data from its HGB-205 clinical trial at an oral presentation at the 19^th European Hematology Association Congress in Milan, Italy on June 14, 2014. The full text of bluebird’s press release regarding the announcement is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description
99.1	Press release issued by bluebird bio, Inc. on June 14, 2014.
99.2	Investor presentation provided by bluebird bio, Inc. on June 16, 2014.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: June 16, 2014	bluebird bio, Inc.
	By:	/s/ Jason F. Cole
		Jason Cole
		Senior Vice President, General Counsel

EXHIBIT INDEX

Exhibit No.	Description
99.1	Press release issued by bluebird bio, Inc. on June 14, 2014.
99.2	Investor presentation provided by bluebird bio, Inc. on June 16, 2014.

EX-99.1

Exhibit 99.1

NEWS RELEASE

bluebird bio Reports Rapid Transfusion Independence in Beta-Thalassemia Major Patients Treated with its LentiGlobin Product Candidate

First two patients in the HGB-205 Study achieved transfusion independence within two weeks of an autologous transplant with bluebird’s lentiviral gene therapy

CAMBRIDGE, MA, June 14, 2014 – bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases, today released initial positive clinical data from its HGB-205 clinical study of its LentiGlobin BB305 product candidate in beta-thalassemia major subjects at the 19^th Annual Congress of the European Hematology Association (EHA) in Milan, Italy.

“We are gratified that the improvements we introduced into the BB305 lentiviral vector design and manufacturing process appear to have translated into clinical results that we believe support the potential for our LentiGlobin BB305 gene therapy to transform the lives of patients with beta-thalassemia major,” stated David Davidson, M.D., bluebird bio’s Chief Medical Officer. “We are encouraged by the early and high-level production of corrected beta^AT87Q-globin and the rapid onset of transfusion independence in these initial subjects, as well as the absence of any gene therapy related adverse events. We look forward to providing additional data from this study and our ongoing multi-center Northstar Study later this year.”

The principal investigator of the HGB-205 Study, Marina Cavazzana, M.D delivered an oral presentation at the EHA Congress entitled “Improving gene therapy for beta-thalassemia major: initial results from Study HGB-205” on June 14, 2014 at 04:15 pm CET (10:15 am EDT). The presentation included data from the prior LG001 Clinical Study and the ongoing HGB-205 Study.

Summary of the clinical data presented at EHA were:

LG001 Clinical Study

• Clinical update provided on two subjects treated in the prior LG001 Study (subjects 3 and 4) using the prior lentiviral HPV569 product candidate

• Subject 3 remains blood transfusion independent 72 months after being transplanted with the lentiviral HPV569 product candidate

• Subjects 3 and 4 are producing 2.7 g/dL and 0.4 g/dL of therapeutic beta^A-T87Q-globin post-transplant, respectively

• No drug product related adverse events were reported in the LG001 Study.

HGB-205 Clinical Study

• Clinical data were presented on two subjects (subjects 1 and 2), both with beta-thalassemia major and the Beta E/Beta 0 genotype who were treated using the new lentiviral vector BB305

• At 4.5 months following autologous transplant subject 1 had a total hemoglobin of 10.1 g/dL of which 6.6 g/dL was therapeutic beta^AT87Q-globin, and at 2 months post-transplant subject 2 had a total hemoglobin of 11.6 g/dL of which 4.2 g/dL was beta^AT87Q-globin

• Subjects 1 and 2 received their last blood transfusion on day 10 and 12, respectively, post-transplant and both subjects remain blood transfusion independent

• Vector copy number in the drug product for subjects 1 and 2 were 1.5 and 2.1, respectively; multiple times higher than the drug product vector copy numbers reported in the prior LG001 Study (VCN 0.6 and 0.3 for Subjects 3 and 4, respectively)

• No drug product related adverse events were reported, and the integration site analysis performed on subject 1 at the 3-month time point showed polyclonal reconstitution.

We anticipate reporting additional data from the HGB-205 Study and from our ongoing Northstar Study in late 2014.

Conference Call and Webcast

bluebird bio will host a conference call at 8:00 am EDT on Monday, June 16, 2014 to discuss the initial results from its HGB-205 Study. Investors may listen to the webcast of the conference call live on the “Calendar of Events” section of bluebird bio’s website, www.bluebirdbio.com. Alternatively, investors may listen to the call by dialing: (844) 825-4408 from locations in the U.S. and (315) 625-3227 from outside the U.S. The webcast replay will be available for at least 72 hours following the call.

About beta-thalassemia

Beta-thalassemia major is a rare hereditary blood disorder caused by a genetic abnormality of the beta globin gene resulting in defective red blood cells. Symptoms of beta-thalassemia include severe anemia and splenomegaly. It is estimated that about 288,000 patients with beta-thalassemia are alive, of which an estimated 15,000 live in the United States and Europe. The majority of beta-thalassemia patients have beta-thalassemia major.

About the HGB-205 Study

The phase 1/2 study is designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with beta-thalassemia major and severe sickle cell disease. The study is designed to enroll up to seven subjects. Subjects will be followed to evaluate safety and blood transfusion requirements post-transplant. In sickle cell disease patients only, efficacy will also be measured based on the number of vaso-occlusive crises or acute chest syndrome events.

For more information on the HGB-205 Study, please visit www.clinicaltrials.gov using identifier NCT02151526.

About bluebird bio, Inc.

bluebird bio is a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases. bluebird bio has two clinical-stage programs in development. The most advanced product candidate, Lenti-D, is in a recently-initiated phase 2/3 study, the Starbeam Study, for the treatment of childhood cerebral adrenoleukodystrophy (CCALD), a rare, hereditary neurological disorder affecting young boys. The next most advanced product candidate, LentiGlobin, is currently in two phase 1/2 studies, one in the US (the Northstar Study) and one in France (HGB-205), for the treatment of beta-thalassemia major. The phase 1/2 HGB-205 study also allows enrollment of patient(s) with sickle cell disease, and bluebird bio is planning a separate U.S. sickle cell disease trial (HGB-206).

bluebird bio also has an early-stage chimeric antigen receptor-modified T cell (CAR-T) program for oncology in collaboration with Celgene Corporation.

bluebird bio has operations in Cambridge, Massachusetts and Paris, France. For more information, please visit www.bluebirdbio.com

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 potential efficacy and safety of the Company’s LentiGlobin product candidate, the Company’s plans with respect to LentiGlobin and its other product candidates and anticipated clinical and business milestones and announcements for 2014. In addition it should be noted that the data for LentiGlobin announced from the HGB-205 study at the EHA Congress are preliminary in nature and the HGB-205 trial is not completed. These data may not continue for these subjects or be repeated or observed in ongoing or future studies involving our LentiGlobin product candidate, including the HGB-205 Study, the Northstar Study or the HGB-206 study in sickle cell disease. 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 preliminary results from our clinical trials will not continue or be repeated in our ongoing clinical trials, the risk that previously conducted studies involving similar product candidates will not be repeated or observed in ongoing or future studies involving current product candidates, the risk of cessation or delay of any of the ongoing or planned clinical studies and/or our development of our product candidates, the risk of a delay in the enrollment of patients in the Company’s clinical studies, the risk that our collaboration with Celgene will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and

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 quarterly report on 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.

Availability of other information about bluebird bio

Investors and others should note that we communicate with our investors and the public using our company website (www.bluebirdbio.com), our investor relations website (http://www.bluebirdbio.com/investor-splash.html), including but not limited to investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference calls and webcasts. You can also connect with us on Twitter @bluebirdbio, LinkedIn or our YouTube channel. The information that we post on these channels and websites could be deemed to be material information. As a result, we encourage investors, the media, and others interested in bluebird bio to review the information that we post on these channels, including our investor relations website, on a regular basis. This list of channels may be updated from time to time on our investor relations website and may include other social media channels than the ones described above. The contents of our website or these channels, or any other website that may be accessed from our website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Investor Relations:

Richard E. T. Smith, Ph.D.

bluebird bio, Inc

(339) 499-9382

Media Contact:

Dan Budwick

Pure Communications, Inc.

(973) 271-6085

EX-99.2

Making Hope A Reality

Nasdaq : BLUE

June 16, 2014

Exhibit 99.2

Forward Looking Statement

2

These slides and the accompanying oral presentation contain forward-looking statements and

information.  The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,”

“anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and

other similar expressions are intended to identify forward looking statements.  For example, all

statements we make regarding the initiation, timing, progress and results of our preclinical and

clinical studies and our research and development programs, our ability to advance product

candidates into, and successfully complete, clinical studies, and the timing or likelihood of

regulatory filings and approvals are forward looking. The data for LentiGlobin are preliminary

in nature and the HGB-205 trial is not completed. These data may not continue for these

subjects or be repeated or observed in ongoing or future studies involving our LentiGlobin

product candidate, including the HGB-205 Study, the Northstar Study or the HB-206 Study in

sickle cell disease.  All forward-looking statements are based on estimates and assumptions by

our management that, although we believe to be reasonable, are inherently uncertain.  All

forward-looking statements are subject to risks and uncertainties that may cause actual results

to differ materially from those that we expected. These statements are also subject to a

number of material risks and uncertainties that are described in the our most recent quarterly

report on Form 10-Q, as well as our subsequent fillings with the Securities and Exchange

Commission.  Any forward-looking statement speaks only as of the date on which it was

made.  We undertake no obligation to publicly update or revise any forward-looking statement,

whether as a result of new information, future events or otherwise, except as required by law.

Summary -

Key Messages

Potential for one-time transformative treatments for severe

genetic and orphan diseases

Encouraging

clinical

data

in

beta-thalassemia

major

patients

Promising

proof

of

concept

data

in

CCALD

patients

Industrialized

platform

across

people,

production,

development and deployment

Disruptive

product

platform

with

broad

product

and

deal

potential

Industry

leading

team

and

culture

funded

for

success

3

bluebird Pipeline

CNS Diseases

Hematologic/Solid Tumors

Lenti-D

LentiGlobin™

CAR-T Cells

Undisclosed

Worldwide

Oncology

Hematologic Diseases

Products

Early Pipeline

Research

Worldwide

Worldwide

Global Celgene

Collaboration

4

Program Area

Preclinical

Phase I/II

Phase II/III

Rights

b-thalassemia/SCD (France) –

HGB-205 Study**

b-thalassemia (U.S.) –

Northstar Study**

Sickle Cell Disease (U.S.) –

HGB-206 Study

* The Phase II/III Starbeam Study is our first clinical study of our current Lenti-D viral vector and product candidate. 

** The Phase I/II HGB-205 and Northstar Studies are our first clinical studies of our current LentiGlobin viral vector and product candidate.

Childhood Cerebral ALD – Starbeam Study*

5

IMPROVING GENE THERAPY FOR

-THALASSEMIA MAJOR: INITIAL

RESULTS FROM STUDY HGB-205

M. Cavazzana, JA Ribeil*, E. Payen*, F. Suarez, O. Negre, Y. Beuzard, F. Touzot, R.

Cavallesco, F. Lefrere, S. Chretien, P. Bourget, F. Monpoux, C. Pondarre, B. Neven, F.

Bushman, M. Schmidt, C. von Kalle, L. Sandler, S. Soni, B. Ryu, R. Kutner, G. Veres,

M. Finer, S. Blanche, O. Hermine, S. Hacein-Bey-Abina, P. Leboulch

*these authors contributed equally

Epidemiology of hemoglobin disorders

6

The hemoglobinopathies are the most prevalent monogenetic disorders in the world –

7% of global population carry an abnormal hemoglobin gene

Between 300,000 –

400,00 babies are born each year with a serious hemoglobin

disorder

•

>40,000 with   -thalassemia major/HbE    -thalassemia

•

>200,000 with sickle cell disease

Adapted from Williams and Weatherall 2012 and  March of Dimes, 2006

b

b

-thalassemia major is a serious disease potentially

amenable to gene therapy

7

Only curative approach is allogeneic HSCT, but complicated by:

difficulty in finding well-matched donors

graft versus host disease

prolonged immunosuppression

At EHA we report data from two clinical trials of ex-vivo

gene

therapy in subjects with b-thalassemia major

Study

Lentiviral vector

Current status

1 (LG001)

HPV569

Study closed, update presented today

2 (HGB-205)

BB305

Enrolling, initial results on first 2

subjects presented today

Identical study design for both gene therapy trials

•

Key eligibility:

•

b-Thalassemia major (

100 mls pRBCs/kg/year)

•

Subjects with severe sickle cell disease are also eligible; none

treated to date

•

No HLA-matched sibling donor

HSC

mobilization

then apheresis

Myeloablation

with IV

busulfan

Infusion

Follow-up

CD34+ cells

selection

Cryopreserve

Lentiviral

vector

transduction

8

HPV569 lentiviral vector used in Study 1

9

Globin production is under transcriptional control of an

erythroid-specific promoter and enhancer

R

U5

HIV U3

RRE

cPPT

pA

gag

3’enh/pA

Globin LCR

U3

R

A-T87Q

-globin allows for monitoring of protein levels produced using

HPLC

Human

-globin

gene

A-T87Q

cHS4 insulators

Study 1 –

characteristics of included subjects

•

No AEs related to drug product, including no RCL nor malignancy

10

Subject

Outcome

1

Not treated

2

Low number of stem cells infused, no engraftment,

received rescue cells

3

Engrafted, 6 years follow-up

4

Engrafted, 2 years follow-up

Subject 3

Subject 4

Age

18

22

Genotype

b

0

/

b

0

/

CD34

+

VCN

0.6

0.3

CD34

+

cell dose (x 10

6

/kg)

4.9*

4.3

*Subject 3 source of CD34+ cells was bone marrow

E

E

b

b

Study 1 : hemoglobin concentrations

11

•

Subject

3:

stable

levels

of

b

A-T87Q

–globin

beginning

at

Month

18,

transfusion

independent

by

Month

12.

Producing

2.7

g/dL

of

b

A-T87Q

-globin

at

6

years.

•

Subject

4:

minimal

levels

of

b

A-T87Q

-globin

post-treatment,

transfusion

dependent.

Producing

0.4

g/dL

of

b

A-T87Q

-globin

at

2

years.

Months post treatment

9.8

8.6

10.5

8.0

8.0

8.9

8.9

9.2

8.7

8.3

8.2

8.1

7.8

9.0

8.8

7.9

8.1

7.3

8.4

8.6

7.1

7.1

BB305 lentiviral vector used in Study 2

12

•

Improvements made in vector design, vector

manufacturing process, and drug product manufacturing,

including:

Study 2:

Study 1:

•

CMV promoter to drive vector production (aim to increase

vector titer)

•

cHS4  insulator elements were removed (aim to increase vector

titer, potency, and stability)

Improvements in BB305 vector design and manufacturing

process increase transduction efficiency in vitro

13

•

Mean VCN was 2-

to 3-fold higher in transduced human CD34

+

cells

•

b

A-T87Q

–globin was produced at a 2-fold higher level in differentiated

erythroid lineage cells

Study 2 : characteristics of included subjects (to date)

14

Subject 1

Subject 2

Age at Enrollment

18

16

Genotype

b

0

/b

E

b

0

/b

E

CD34

+

VCN

1.5

2.1

CD34

+

cell dose (x 10

6

/kg)

8.9

13.6

Study 2 :  Safety

15

Subject 1

Subject 2

Follow up  period

4.5 months

2 months

Day of neutrophil engraftment

ANC > 500/µL

Day  13

Day  15

Day of platelet engraftment

Unsupported platelet count > 20,000/µL

Day  17

Day 24

Non-laboratory    Grade 3 AEs

Mucositis

1

Mucositis

SAEs occurring     Day 0

None

None

Insertion site analysis

At 3 Months: highly

polyclonal (>1000), no

clonal dominance

Not yet available

1

Subject 1201 had an asymptomatic Grade 3 AST, ALT and GGT elevation from Days 23-90 

•

No AEs related to drug product, including no RCL nor malignancy

Study 2 vs. Study 1: VCN in peripheral blood leucocytes

16

Months post infusion

CD34+

VCN

Study 1

Study 2

In first 12 months, VCN in PBLs for Study 1

subjects were between 0.02 and 0.04

In

study

2,

early

and

high

production

of

A-T87Q

-globin

resulting

in

rapid transfusion-independence at near normal Hb levels in both

patients

17

•

Subject 1: producing 6.6 g/dL of b

A-T87Q

-globin  at 4.5 months

•

Subject 2: producing 4.2 g/dL of b

A-T87Q

-globin  at 2 months

Kinetics of  

A-T87Q

expression and transfusion

independence

18

Study 2

Study 1

•

In Study 2, rapid production of therapeutic globin (weeks as opposed to one

year)

•

Both subjects in Study 2 have near-normal hemoglobin levels without

transfusion support (neither subject has required a transfusion post-

engraftment)

RBC transfusion Independence

Subject 3

Subject 1

Subject 2

Study

1

LG001

2

HGB-205

2

HGB-205

Vector

HPV569

BB305

BB305

Day of last

transfusion

Month 12

Day 10

Day 12

Duration since last

transfusion

>5 years

>125 days

>48 days

Months post treatment

Conclusions

19

•

BB305 lentiviral vector and improved manufacturing process produce superior

transduction efficiency as compared with HPV569

•

With BB305 lentiviral vector in Study 2, neither subject has received a transfusion since

the second week post transplantation

•

Production of b

A-T87Q

-globin has been rapid and clinically significant resulting in near-

normal hemoglobin levels

•

Initial safety profile is consistent with autologous transplantation, without gene-therapy

related adverse events, and with polyclonal reconstitution in the first subject

•

These data demonstrate that early transfusion independence (within weeks of

transplantation) with near-normal levels of hemoglobin can be achieved with ex-vivo

gene therapy using BB305 lentiviral vector in subjects with b

0

/b

E

-thalassemia major

Evidence for why BB305 globin may work for sickle cell

disease

•

BB305 globin incorporates an anti-

sickling amino acid that is found in

fetal hemoglobin (glutamine at

position 87) 

•

Anti-sickling activity of b

A-T87Q

-globin

has been demonstrated in a mouse

model of SCD (Science 2001)

•

Elevated fetal hemoglobin from

hereditary persistence of fetal

hemoglobin (HPFH) or treatment

with hydroxurea has shown clinical

benefit

F

L

T

V

F

L

Q

polymerization

destabilization

20

V

Ongoing Studies using BB305 lentiviral vector

21

Study

Centers

Indication

Planned

subjects

Current Status

HGB-205

(trial reported

today)

1 in France

7

4 subjects enrolled

2 subjects treated to

date

Northstar Study

(HGB-204)

4 in US

1 in Australia

1 in Thailand

15

6 subjects enrolled

1 subject treated to

date

HGB-206

3-6 planned,

all in US

Severe sickle cell

disease

8

Open IND, pending

initiation

b- thalassemia

major and severe 

sickle cell disease

b- thalassemia

major

Recent and Upcoming News Flow

Enroll first SCD patient in 

HGB-205 or HGB-206 (2014)

Preliminary Thal Northstar &

HGB-205 data (late 2014)

Various clinical publications

Signed global Oncology

collaboration with Celgene

Completed IPO

Initiated phase II/III Starbeam

Study

Initiated two phase I/II Thal

studies  (Northstar & HGB-

205)

First patient transplanted in

Starbeam Study

First patient transplanted in

Thal HGB-205 study

2013

2013

22

Complete enrollment of

Starbeam Study

Complete enrollment

Thal Northstar & HGB-

205

Preliminary SCD data

2015

2015

2014

2014

First patient transplanted in

Northstar Study

File IND for sickle cell disease

(SCD) study

Preliminary Thal HGB-205

data at EHA

Q&A

Backups

Study 1 (LG001) : Safety

•

No AEs related

to drug product, including no RCL nor malignancy

Subject 3

Subject 4

Follow-up  period

6 years

2 years

Day of neutrophil engraftment

ANC > 500/µL

Day  27

Day 19

Day of platelet engraftment

Unsupported platelet count > 20,000/µL

Day  40

Day 130

Non-laboratory    Grade 3 AEs

None

Mucositis, metrorrhagia,

epistaxis, mouth bleeding

SAEs occurring    Day 0

None

Thrombocytopenia

Insertion site analysis

Multiple clones  (25-50

detected at each timepoint),

including HMGA2,  many

observed repeatedly over

the following 5 years

Polyclonal (90-200 clones

detected at each timepoint)

reconstitution without

clonal dominance at Year 1

Subject 3 (LG001) : prominence of HMGA2 clone

decreasing over time

•

By Year 5, SPATS2 and ZZEF1 have replaced HMGA2 as the most common clones

identified by LAM-PCR

•

In

spite

of

decrease

in

HMGA2

clone,

therapeutic

effect

has

been

maintained

•

No hematological or clinical effects of the HMGA2 clone have been noted in over

6 years of follow-up

Months

0

5

10

15

20

0

10

20

30

40

50

60

70

vector-modified

cells

HMGA2-

modified cells