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 23, 2017

 

bluebird bio, Inc.

(Exact name of Registrant as Specified in Its Charter)

 

 

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 (see General Instructions A.2. below):

Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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Item 7.01    Regulation FD Disclosure

 

On June 23, 2017, bluebird bio, Inc. (“bluebird”) will be conducting meetings with investors in connection with its announcement of updated clinical data at the 22^nd Congress of the European Hematology Association.  As part of these meetings, bluebird will deliver the slide presentation furnished to this report as Exhibit 99.1 and which is incorporated by reference herein.

 

See Item 8.01 below, which is incorporated by reference herein.

 

The information in Item 7.01 of this Report on Form 8-K and Exhibit 99.1 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 23, 2017, bluebird issued two press releases announcing updated clinical data from the Northstar-2 and HGB-205 studies of its LentiGlobin product candidate in transfusion-dependent β-thalassemia and severe sickle cell disease, being presented at the 22^nd Congress of the European Hematology Association.  The full text of bluebird’s press releases regarding the announcements are filed as Exhibits 99.2 and 99.3 to this Current Report on Form 8-K and is incorporated herein by reference.

 

Item 9.01Financial Statements and Exhibits.

(d) Exhibits

 

 

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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.

 

 

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EXHIBIT INDEX

 

 

 

EHA 2017 June 23, 2017 NASDAQ: BLUE Exhibit 99.1

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. 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 our most recent quarterly report on Form 10-Q, as well as our subsequent filings 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. Forward Looking Statements

Our Vision: Make Hope a Reality TRUE BLUE BLUE MOJO OUR PATIENTS OUR PEOPLE

Our Strategic Intent Severe Genetic Diseases Hematopoietic Stem Cells (HSCs) Immunotherapy T Cells Late Stage (LentiGlobin, Lenti-D) Big Near Term Opportunities (SCD, Multiple Myeloma) Best Team (350+) Great Partners Truly Integrated Platform Transformative Product Focus “Tetris” R&D (Anti-Pure Play) Lentiviral Gene Delivery Pure, Potent, Reproducible, Scalable Global Manufacturing Platform Virus and Drug Product Genome Editing Platform MegaTALs

T H E G E N E T H E R A P Y P R O D U C T C O M P A N Y Products on the Market Programs Nearing Commercialization Additional Programs in the Clinic 2+ 4+ 2+ Patient Impact ∞ World-class Gene Therapy Platform and Integrated Global Capabilities

How Do We Get There? Data, Execution and Development in 2017 LentiGlobin, TDT and SCD Update @ ASH LentiGlobin, TDT Update @ EHA CRB-401 Study Data (bb2121) @ ASCO DATA EXECUTION Initiate HGB-212 Study of LentiGlobin Confirm LentiD, CALD Clinical/ Regulatory Path Preparations for TDT EU MAA Filing File Next Generation BCMA IND (bb21217) Advance & Further Validate Gene Editing Platform DEVELOPMENT Lenti-D CALD Update @TBD

CRB-401: All bb2121 Patients in Active Dose Cohorts Achieved an Objective Response, Duration up to 54 Weeks * High tumor burden (>50% bone marrow involvement) Includes unscheduled assessments. bb2121 has induced durable and deepening responses in a heavily pre-treated population (median 7 prior therapies) with relapsed/refractory multiple myeloma, including: 100% ORR, 73% VGPR or better, 27% CR (at doses > 50 x 106) MRD negative results in all evaluable patients (N=4) No disease progression in patients treated with doses > 50 x 106, with 1 patient past 1 year and 8 patients past 6 months To date, the safety profile of bb2121 has been manageable at all tested doses No DLTs The 2 reported events of grade 3 CRS resolved within 24 hours No grade 3/4 neurotoxicity reported Data Presented at ASCO 2017; Data Cutoff of May 4, 2017

LentiGlobin Clinical Studies NORTHSTAR (HGB-204) Phase 1/2 single-center study; all genotypes NORTHSTAR-3 (HGB-212) Phase 1/2 multicenter study; all genotypes HGB-205 (TDT and SCD) All 18 patients treated, with ≥ 6 months follow-up 2 patients have completed 2-year analysis HGB-206 (Severe SCD) 4 TDT patients treated, with 11 – 33 months follow-up Phase 3, global, multicenter study; non- β 0 / β 0 genotypes First study to use new manufacturing process N=15 adults and adolescents, and N=8 pediatric patients Phase 3, multicenter, global study; β 0 / β 0 genotypes N=15 adults, adolescents and pediatric patients Initiation planned for 2017 NORTHSTAR-2 (HGB-207) Open label, multicenter, U.S. based study N=29 adults

Key Questions Transfusion-Dependent β-thalassemia (TDT): Northstar-2 and HGB-205 With our new manufacturing process in Northstar-2, are we able to consistently manufacture drug product (DP) with higher vector copy number (VCN) and proportion of transduced cells? How do the early results from Northstar-2… Compare to the results seen in non-β0/β0 patients in HGB-204? Read through to β0/β0 patients? Read through to SCD patients? What can we learn from the HGB-205 TDT patients? Severe Sickle Cell Disease (SCD) How do the data from the HGB-205 patients compare to ASH 2016 data? What does HGB-205 teach us regarding the potential impact of the protocol and manufacturing changes made in HGB-206?

A Phase 3 Study to Evaluate Safety and Efficacy of LentiGlobin Gene Therapy for Transfusion-Dependent β-thalassemia in Patients with non-β0/β0 Genotypes: The Northstar-2 (HGB-207) Trial Mark C. Walters, Alexis Thompson, Suradej Hongeng, Janet L. Kwiatkowski, Franco Locatelli, John Porter, Martin Sauer, Adrian Thrasher, Isabelle Thuret, Evangelia Yannaki, Alexandria Petrusich, Mohammed Asmal EHA 2017 Abstract S814

Gene Therapy for Transfusion-Dependent β-thalassemia (TDT) Autologous gene therapy aims to correct TDT without the immunologic risks of allogeneic HSCT In Northstar (HGB-204) and HGB-205 phase 1/2 studies LentiGlobin BB305 gene therapy has eliminated transfusions in most patients with non-β0/β0 genotypes Patients with β0/β0 genotypes had a median 63% reduction in transfusion volume following treatment Key finding: Vector copy number (VCN) in drug product (DP) correlates with HbAT87Q production DP VCN in HGB-204 study was 0.3 – 1.5 copies/cell BB305 lentiviral vector

Northstar-2 (HGB-207) Study of LentiGlobin BB305 Gene Therapy Investigating efficacy and safety of LentiGlobin BB305 in adolescents and adults with TDT and non-β0/β0 genotypes Uses refined manufacturing process to yield higher DP VCNs Primary endpoint: proportion of patients who achieve “transfusion independence” (TI) TI = maintain an average Hb≥ 9 g/dL without RBC transfusions for ≥12 months Data as of June 2, 2017

Current Status of Northstar-2 Study Consented N=16 Ineligible  N=4* Stem Cell Mobilization complete N=6 Drug Product Manufacturing and Release Complete N=6 LentiGlobin Drug Product Infused N=3 (adult) First patient infused December 2016 Target: 15 treated patients (including ≥5 aged 12-17 years) Key enrollment criteria 12 to 50 years of age Non-β0/β0 genotype RBC requirement: ≥100 mL/kg/year (or ≥8 RBC transfusions/yr) for past 2 years Adequate organ function/performance status No previous stem cell transplant or gene therapy Transplant Pending N=3 As of June 2, 2017 *reasons for ineligibility: 2 withdrew consent, 2 screen failure due to liver biopsy findings

Overview of the Northstar-2 Study Process Patient Treatment Centralized Manufacturing Pre-infusion Conditioning Stem Cell Collection Transduced Stem Cells Infused Select CD34+ cells + Cryopreserve, test and release DP 2 years follow-up Extension study (13 years) Up to 15 years total follow-up Immune System Reconstitution Transduce using new manufacturing process LentiGlobin BB305 manufacturing busulfan myeloablation mobilization (with G-CSF/ plerixafor) + apheresis

Northstar-2 Patient Characteristics N=3 treated patients to date Patient 1 2 3 Age (years) 20 20 22 Gender F F F Genotype β0/βE β0/βE IVS-I-5 (G>C) Pre-Treatment pRBC Transfusions (mL/kg/year)1 162.5 192.9 158.7 Liver Iron Concentration (mg/g) (normal range <1.1 mg/g) 18.8 19.6 1.4 Cardiac T2* (msec) (normal range >20 msec)2 42.5 45.3 36.3 Splenectomy N N Y As of June 2, 2017 1 Garbowski, M. W. et al (2014). Journal of Cardiovascular Magnetic Resonance, 16:40 2 Carpenter, J. P et al (2011). Circulation, 123:1519-1528

Initial Safety Summary & Treatment-related Parameters N=3 treated patients Patient 1 2 3 VCN in Drug Product1 2.9 2.4 3.2, 2.4 Vector positive cells 77% 53% 77%, 82% CD34+ Cell Dose (x106/kg) 7.0 13.6 8.1 Busulfan AUC (μM*min)2 4286 4337 4562 Neutrophil engraftment, study day3 25 24 19 Platelet engraftment, study day4 44 45 35 Follow up (months) 6 3 2 Patient 1 2 3 Follow up 6 months 3 months 2 months Adverse events none Hypotension (SAE; Grade 3) Epistaxis (Grade 3) Mucositis (Grade 3) Grade ≥3 non-hematologic AEs 1, 2 No significant veno-occlusive disease (VOD) of the liver or infections post-treatment No drug product-related AEs As of June 2, 2017 Hematological values typically decreased post-transplant are not shown All AEs are reported from Day -8 to date of last contact (2-6 months) As of June 2, 2017 VCN: vector copy number (vector copies per diploid genome) Estimated average daily busulfan exposure over four days ANC ≥ 500 for 3 consecutive days Unsupported platelet count ≥ 20,000/µL

Improved Manufacturing Process Yields Higher Drug Product Vector Copy Number and Proportion of Transduced Cells Vector copy number (VCN) in drug product Proportion of CD34+ cells transduced median 0.7 median 3.0 median 32% median 77% DP VCN for initial 6 subjects manufactured in Northstar-2 consistently higher than 18 subjects in Northstar Northstar: median 0.7 (0.3 – 1.5) Northstar-2 to date: median 3.0 (2.4 – 4.0) Increased DP VCN in Northstar-2 reflects higher proportion of transduced cells (% vector positive) Northstar: median 32% (range 17% – 58%) Northstar-2 to date: median 77% (range 53% – 90%) * Samples from EU manufacturing pending vector positive analysis *

First Patient Treated in Northstar-2 with 6 Months Follow-up has Achieved Normal Total Hemoglobin After Discontinuing Transfusions 13.3 Last RBC transfusion: Day 33 4.8 7.1 9.5 HbAT87Q HbF HbA2 HbA HbE 4.2 2.2 1.1 Medians in non-β0/β0 genotypes (N=10) (data as of Sept 2016) 9.7 * N=6 patients in Northstar study with HbE genotype * * *

VCN over time Patient 1 Patient 2 Patient 3 Northstar (non-β0/β0 patients only*) HbAT87Q levels over time HbAT87Q in Patients Treated in Northstar-2 Match or Exceed HbAT87Q in Patients Achieving Early Transfusion Independence in Northstar DP lots for patients pending transplant Transfusion independent Not yet TI evaluable Northstar-2 *Northstar data as of ASH 2016 DP lots for treated patients

5 4 3 2 1 0 Dose of Indicated Population (x 106 cells/kg) Transduced Primitive Stem Cell Population Northstar-2 Patient 2: Phenotypic Profile of CD34+ Cells is Atypical Disproportionate number of lymphoid cells results in lower proportion of primitive stem cells available for transduction With the improved manufacturing process, the patient still achieved a transduced stem cell dose on par with transfusion independent HGB-204 patients 40 30 20 10 0 % of Total Dose Committed Lymphoid Progenitors

Summary and Next Steps The improved manufacturing process in Northstar-2 consistently yields higher DP VCNs and proportions of cells transduced Initial results show that the 3 patients treated to date have achieved in vivo VCN and HbAT87Q production as good or better than patients achieving transfusion independence in the first Northstar study No LentiGlobin-related AEs reported in Northstar-2 with 2 - 6 months follow-up AE profile of LentiGlobin continues to appear similar to autologous HCT with myeloablative busulfan Data on vector insertion pattern with higher DP VCN is pending HGB-212 β0/β0 genotypes Phase 3, multi-center, global study N=15 adults, adolescents and pediatric patients Initiation planned for 2017 Northstar-2 Summary Next Steps

HGB-205: Transfusion-Dependent Thalassemia (TDT)

HGB-205: Study Status Patients consented & enrolled N=8 Cell collection and drug product manufacture complete N=7 Conditioning and drug product infusion complete N=7 Ineligible N=1 Follow-up after drug-product infusion for 7 treated patients (4 TDT, 3 SCD) Median: 23.4 months range: 3.4 – 42.2 months As of June 2, 2017

HGB-205 TDT: Patient and Drug Product Characteristics and Safety 1201 1202 1203 1206 Age at Enrollment (yrs) 18 16 19 17 Genotype β0/βE β0/βE homozygous IVS1 nt 110 G>A β0/βE Pre-Treatment pRBC Transfusions (mL/kg/yr)1 139 188 176 189 VCN in Drug Product2 1.5 2.1 0.8 1.1 CD34+ Cell Dose (x106/kg) 8.9 13.6 8.8 12.0 Busulfan AUC (average, μM*min) 4,967 5,212 4,670 4,930 Follow-up (months) 42.2 39.0 23.4 20.4 1mean pRBC requirement per year, over the past 2 years prior to consent; 2VCN = number of vector copies per diploid genome Adverse events generally consistent with myeloablative conditioning No drug-product related non-hematologic AEs or SAEs No replication competent lentivirus (RCL) detected to date No evidence of insertional mutagenesis

HGB-205 TDT: Stable Peripheral VCN Over Time and Durable HbAT87Q Production VCN over Time HbAT87Q Levels over Time

HGB-205 TDT: Consistent and Durable Transfusion Independence Up to 3.5 Years 11.3 8.3 12.9 11.4 Total Hb* *Hemoglobin (g/dL) at most recent study visit + Discontinued iron chelation and transitioned to therapeutic phlebotomy: Patients 1201 (started Aug. 2016), 1202 (started Nov. 2015), 1206 (started Oct. 2016)

HGB-205: Sickle Cell Disease (SCD)

ASH 2016: 8% to 48% Anti-Sickling Hemoglobin at Last Follow Up 12 12 9 9 6 6 9 48% Anti-Sickling Hb 30.0% 14.2% 18.3% 22.8% 16.5% 7.9% 21 18.7% 1301 1303 1304 1306 1308 1309 1310 1204 12 12 9 9 6 9 6 21 Follow up (Months) Data as of Sept 9, 2016 [HGB-205] and Nov 9, 2016 [HGB-206]

ASH 2016: Vector Copy Number (VCN) in Drug Product and Peripheral Blood Vector copy number (VCN; per diploid genome) VCN drop from drug product to peripheral blood in HGB-206 Peripheral blood VCN over time 1204 Data as of Sept 9, 2016 [HGB-205] and Nov 9, 2016 [HGB-206]

Protocol and Process Changes to Potentially Improve Outcomes in SCD Patients Hypoxic, inflamed marrow Pre-harvest transfusions to reduce marrow inflammation, hypoxia Low yield harvest Additional changes to manufacturing process to increase cell dose Poor transduction New manufacturing process Inadequate myeloablation Increased exposure to myeloablative agent Apheresis (vs. Bone Marrow) Utilize Plerixafor for mobilization and collection

HGB-205 SCD: Patient and Drug Product Characteristics 1204 1207 1208 Age at Enrollment (yrs) 13 16 21 Genotype βS/βS βS/βS βS/β0 Busulfan AUC (average, μM*min) 4,841 5,022 5,447 CD34+ Cell Dose (x106/kg) 5.6 4.7 3.0 VCN in Drug Product1 1.0/1.2 0.7/1.0 0.8/0.5 Follow-up (months) 31.7 6.1 3.4 Neutrophil engraftment2 Day + 38 + 27 +32 Platelet engraftment3 Day + 92 + 51 +39 1. VCN: number of vector copies per diploid genome; 2. Absolute neutrophil count [AUC] ≥ 500 cells/μL for 3 consecutive days; 3. Unsupported platelet count ≥ 50,000/µL for 3 consecutive measures.

HGB-205 SCD: Durable Effect in Patient 1204 Total Hb 12.4 g/dL VCN 2.3 HbA (transfused) HbS 48% HbA2 2% HbF <1% HbAT87Q 50%

HGB-205 SCD: Safety and Clinical Status in Severe SCD Patients Adverse events generally consistent with myeloablative conditioning No drug-product related non-hematologic AEs or SAEs No replication competent lentivirus (RCL) detected to date No evidence of insertional mutagenesis Patient 1204 One episode of acute gastroenteritis at 30 months post-treatment, with vomiting and 2 days of fever up to 40°C, followed by a vaso-occlusive crisis (VOC) and was hospitalized HbAT87Q and peripheral blood VCN levels have remained stable (HbAT87Q  6.1 g/dL, VCN 2.3 at 30 months) Patient 1207 Pre-treatment history of frequent episodes of VOC and acute chest syndrome (ACS) despite hydroxyurea prior to beginning regular transfusions. Experienced an episode of ACS 6 months post-treatment and was hospitalized. HbAT87Q continues to increase with 1.8 g/dL at 6 months.

SCD: Transfused Patients Have More Stable VCN HGB-206 (Process 1) HGB-205 (Process 0) * Dotted lines represent transfused patients

SCD HbAT87Q Production Higher in Transfused Patients HGB-206 (Process 1) HGB-205 (Process 0) Data from transplant and other literature argue that as little as 3g/dL (~30%) of anti-sickling hemoglobin and gene marking as low as 20% could potentially achieve a disease-modifying effect * Dotted lines represent transfused patients

1204 1207 1208 50% 48% 20% 61% 15% 15% 39% 16% HbAT87Q HbF HbS HbA (transfused) HbA2 HGB-205 SCD: Levels of Anti-sickling Hemoglobin (HbAT87Q + HbF) Above 30%

Evolution of LentiGlobin in SCD – More To Come at ASH 2017 HGB-206 Process 1 HGB-206 Updated Protocol HGB-206 (Apheresis) Low/Med Low Low No High Medium High Yes High High High Yes HGB-205 High Medium Medium Yes Transfusions (Pre-Treatment) Conditioning Total Cell Dose Transduction (VCN & % Transduced) Planned Cell Source Shift Cell Source: Apheresis (Apheresis simplifies cell harvest and facilitates higher cell doses) Cell Source: Bone Marrow

Closing

Key Questions Transfusion-Dependent β-thalassemia (TDT): Northstar-2 and HGB-205 With our new manufacturing process in Northstar-2, are we able to consistently manufacture drug product (DP) with higher vector copy number (VCN) and proportion of transduced cells? How do the early results from Northstar-2… Compare to the results seen in non- β0/ β0 patients in HGB-204? Read through to β0/ β0 patients? Read through to SCD patients? What can we learn from the HGB-205 TDT patients? Severe Sickle Cell Disease (SCD) How do the data from the HGB-205 patients compare to ASH 2016 data? What does HGB-205 teach us regarding the potential impact of the protocol and manufacturing changes made in HGB-206?

Bringing & Valuing Hope Go TRUE BLUE We Must Make Hope a Reality

 

Exhibit 99.2

 

bluebird bio Announces Early Data from Phase 3 Northstar-2 (HGB-207) Study of LentiGlobin^TM Drug Product at European Hematology Association (EHA) Annual Meeting

 

 

CAMBRIDGE, Mass., June 23, 2017 – bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for serious genetic diseases and T cell-based immunotherapies for cancer, announced early interim data from the ongoing Northstar-2 (HGB-207) Phase 3 clinical study of LentiGlobin drug product in patients with transfusion-dependent β-thalassemia (TDT) and non-β⁰/β⁰ genotypes. These data will be presented by Mark Walters, M.D., UCSF Benioff Children’s Hospital, Oakland, California, in an oral session on Sunday, June 25 at the European Hematology Association (EHA) Annual Meeting in Madrid, Spain.

 

“Northstar-2 is our first study to utilize our improved LentiGlobin drug product manufacturing process to increase the drug product vector copy number and percent of cells transduced. The first patient treated in this study exemplifies the promise of gene therapy, discontinuing blood transfusions approximately a month after treatment and achieving a normal level of total hemoglobin production at six months post-treatment,” said David Davidson, M.D., chief medical officer, bluebird bio. “These early results suggest that the improved manufacturing process results in consistently higher drug product vector copy numbers (VCN) and lentiviral vector positive (LVV+) cells, which is correlated with higher production of HbA^T87Q and ultimately may address known patient-to-patient variability.”

 

“Although early, these data add to the growing body of clinical evidence that indicate that LentiGlobin may offer a transformative benefit for patients with TDT,” said Alexis Thompson, MD, MPH, Ann & Robert H. Lurie Children’s Hospital of Chicago, Illinois and a primary investigator on the study. “Patients with TDT are dependent on a burdensome cycle of transfusion and chelation, and for these patients, gene therapy with

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LentiGlobin may offer a long-term solution with a one-time therapy that alleviates many of the complications of the current treatment paradigm.”

 

A Phase 3 Study to Evaluate Safety and Efficacy of LentiGlobin Gene Therapy for Transfusion-Dependent β-thalassemia in Patients with non-β⁰/β⁰ Genotypes: The Northstar-2 (HGB-207) Trial (Abstract S814)

 

The Northstar-2 Study is an ongoing, open-label, single-dose, international, multicenter Phase 3 study designed to evaluate the safety and efficacy of LentiGlobin drug product for the treatment of patients with TDT and non-β⁰/β⁰ genotypes. As of June 2, 2017, drug product had been manufactured for six patients. The median DP VCN for these patients was 3.0 (range: 2.4 – 4.0), compared to a median DP VCN of 0.7 (range: 0.3 – 1.5) in Northstar. Results in treated patients, aged 20-22 years, as of June 2, 2017, include:

 

 

 

Webcast Information

bluebird bio will host a live webcast at 8:00 a.m. ET on Friday, June 23, 2017. The live webcast can be accessed under "Calendar of Events" in the Investors and Media section of the company's website at www.bluebirdbio.com. Alternatively, investors may listen to the call by dialing (844) 825-4408 from locations in the United States or (315) 625-3227 from outside the United States. Please refer to conference ID number 39917037.

 

About Northstar-2 (HGB-207)

Northstar-2 is a Phase 3, global, multi-center study designed to evaluate the safety and efficacy of LentiGlobin drug product in patients with transfusion-dependent beta-thalassemia and non-β⁰/β⁰ genotypes. For this study, the manufacturing process by which

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the patient’s cells are transduced with the LentiGlobin viral vector has been improved, with the intent of increasing vector copy number and the percentage of cells successfully transduced.

 

The target enrollment of the study is 15 adult and adolescent patients and 8 pediatric patients. The study’s primary endpoint is the proportion of treated subjects who meet the definition of "transfusion independence," defined as total hemoglobin levels of at least 9g/dL without any red blood cell (RBC) transfusions for a continuous period of at least 12 months at any time during the study.

 

About TDT

Transfusion-dependent β-thalassemia (TDT), also called β-thalassemia major or Cooley’s anemia, is an inherited blood disease that can be fatal within the first few years of life if not treated.

 

Despite advances in the supportive conventional management of the disease, which consists of frequent and lifelong blood transfusions and iron chelation therapy, there is still a significant unmet medical need, including the risk for significant morbidity and early mortality. Currently, the only advanced treatment option for TDT is allogeneic hematopoietic stem cell transplant (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft vs. host disease and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.

About bluebird bio, Inc.

With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ product candidate, currently in four clinical studies for the treatment of transfusion-dependent β-thalassemia, and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in 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. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline.

 

bluebird bio has operations in Cambridge, Massachusetts, Seattle, Washington and Europe.

 

 

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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 research, development, manufacturing and regulatory approval plans for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia, and whether the manufacturing process changes for LentiGlobin will improve outcomes of patients with transfusion-dependent ß-thalassemia. 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 risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin will not continue or be repeated in our ongoing, planned or expanded clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing process will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, 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.

 

 

Contact:

Investors:

bluebird bio, Inc.

Manisha Pai, 617-245-2107

mpai@bluebirdbio.com

 

Media:

bluebird bio, Inc.

Elizabeth Pingpank, 617-914-8736

epingpank@bluebirdbio.com

 

                                          

 

Exhibit 99.3

 

bluebird bio Presents New Data from HGB-205 Study of LentiGlobin^TM Drug Product in Patients with Transfusion-Dependent β-Thalassemia (TDT) and Severe Sickle Cell Disease (SCD) at European Hematology Association (EHA) Annual Meeting

 

 

CAMBRIDGE, Mass., June 23, 2017 – bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for serious genetic diseases and T cell-based immunotherapies for cancer, announced new data from the ongoing HGB-205 clinical study evaluating its LentiGlobin gene therapy product candidate in patients with transfusion-dependent β-thalassemia (TDT) and severe sickle cell disease (SCD).

 

These data will be presented by Elisa Magrin, Ph.D., Necker Children’s Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France in a poster session on Saturday, June 24 at the European Hematology Association (EHA) Annual Meeting in Madrid, Spain. Marina Cavazzana, M.D., Ph.D., Professor of Medicine at Paris Descartes University and Research Director at the Centre for Clinical Research in Biotherapy, Necker Hospital, and at the Institute of Genetic Diseases, Imagine, Paris, France, is the primary investigator of the HGB-205 study.

 

“HGB-205 was designed as a proof-of-concept study to initially assess the feasibility of treatment with LentiGlobin gene therapy in patients with TDT and severe SCD. Results from this study to date demonstrate the potential for durable treatment effect of LentiGlobin, with stable HbA^T87Q production through 3.5 years of follow-up and sustained clinical benefit,” said David Davidson, M.D., chief medical officer, bluebird bio. “The two most recently treated patients with SCD, both of whom show rising HbA^T87Q production, illustrate the potential benefit of some of the protocol modifications that we have made in our separate HGB-206 study in SCD. As with Patient 1204, the first patient with SCD treated in HGB-205, these two patients received a more stringent busulfan conditioning regimen and regular blood transfusions prior to stem cell harvest. Longer follow-up will be required to determine their eventual HbA^T87Q production and clinical outcome, but it is encouraging that their in vivo VCN shows evidence of early

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stabilization at a higher level compared to the initial cohort of patients in HGB-206. It is also important to note that in our HGB-206 study, these modifications are further supplemented with manufacturing process improvements and evaluation of plerixafor for stem cell mobilization, which we believe may further optimize patient outcomes.”

 

“We are beginning to see evidence of the long-term durability of benefit from treatment with LentiGlobin, with some TDT patients even transitioning off of chelation therapy,” said Prof. Cavazzana. “It is exciting to see the outcome in the patient with TDT with the longest follow-up in HGB-205, who has gone from years of regular transfusions to 3.5 years without a single blood transfusion after a one-time treatment with LentiGlobin gene therapy.”

 

Update on the First Patients with Severe Hemoglobinopathies Treated with LentiGlobin Gene Therapy (HGB-205) (Abstract P631)

 

Presenter: Elisa Magrin, Ph.D., Necker Children’s Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

Poster Session Date & Time: Saturday, June 24, 5:30 – 9:00 p.m. CEST

Location: Poster area (Hall 7)

 

HGB-205 is an ongoing, open-label, single-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product in the treatment of patients with TDT and severe SCD. Four patients with TDT and three patients with severe SCD have undergone infusion with LentiGlobin drug product in this study as of June 2, 2017.

 

TDT:

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SCD:

 

Webcast Information

bluebird bio will host a live webcast at 8:00 a.m. ET on Friday, June 23, 2017. The live webcast can be accessed under "Calendar of Events" in the Investors and Media section of the company's website at www.bluebirdbio.com. Alternatively, investors may listen to the call by dialing (844) 825-4408 from locations in the United States or (315) 625-3227 from outside the United States. Please refer to conference ID number 39917037.

 

About TDT

Transfusion-dependent β-thalassemia (TDT), also called β-thalassemia major or Cooley’s anemia, is an inherited blood disease that can be fatal within the first few years of life if not treated.

 

Despite advances in the supportive conventional management of the disease, which consists of frequent and lifelong blood transfusions and iron chelation therapy, there is still a significant unmet medical need, including the risk for significant morbidity and early mortality. Currently, the only advanced treatment option for TDT is allogeneic hematopoietic stem cell transplant (HSCT). Complications of allogeneic HSCT include a

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significant risk of treatment-related mortality, graft failure, graft vs. host disease and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.

 

About SCD

Sickle cell disease (SCD) is an inherited disease caused by a mutation in the beta-globin gene that results in sickle-shaped red blood cells. Common complications include anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life and sometimes, early death.

 

Where adequate medical care is available, common treatments for patients with SCD largely revolve around prevention of infection and management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced treatment for SCD is allogeneic HSCT. Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, GvHD and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.

About the HGB-205 Study
HGB-205 is an ongoing, open-label Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product in the treatment of subjects with TDT and SCD. The study enrolled seven subjects who will be followed to evaluate safety and transfusion requirements post-transplant. Among patients with sickle cell disease 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 clinicaltrials.gov using identifier NCT02151526.

About bluebird bio, Inc.

With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ product candidate, currently in four clinical studies for the treatment of transfusion-dependent β-thalassemia, and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in 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. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline.

 

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bluebird bio has operations in Cambridge, Massachusetts, Seattle, Washington and Europe.

 

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 research, development, manufacturing and regulatory approval plans for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia and severe sickle cell disease, including statements whether the manufacturing process changes for LentiGlobin will improve outcomes of patients with transfusion-dependent ß-thalassemia and severe sickle cell disease and the potential long-term durable treatment effect of LentiGlobin. 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 risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin will not continue or be repeated in our ongoing, planned or expanded clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing process or the HGB-206 clinical trial protocol will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, 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.

 

 

Contact:

Investors:

bluebird bio, Inc.

Manisha Pai, 617-245-2107

mpai@bluebirdbio.com

 

Media:

bluebird bio, Inc.

Elizabeth Pingpank, 617-914-8736

epingpank@bluebirdbio.com