bluebird bio Announces Data Demonstrating First Four Patients with β-Thalassemia Major Treated with LentiGlobin™ are Transfusion-Free

Data Presented at ASH; Company to Host Investor Call on December 10

CAMBRIDGE, MA, USA I December 8, 2014 I bluebird bio, Inc. (Nasdaq: BLUE) today announced data from eight subjects treated with LentiGlobin BB305 drug product. In the first four subjects, each of whom had at least three months of follow up, treatment with LentiGlobin BB305 drug product resulted in sufficient hemoglobin production to reduce or eliminate the need for transfusion support among patients with beta-thalassemia major who would otherwise require chronic blood transfusions. These data include the first five subjects treated in bluebird bio’s ongoing Phase 1/2 Northstar (HGB-204) Study and the first three subjects from its HGB-205 study. These studies include the first subjects with the beta-0/beta-0 genotype of beta-thalassemia major treated with LentiGlobin BB305 drug product and the first subject with sickle cell disease treated with gene therapy. These data are being presented today at the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco.

“Beta-thalassemia major is a devastating disease that affects 40,000 newborn children globally every year, and the existing treatment options for these patients have significant side effects and limitations,” said Alexis A. Thompson, M.D., M.P.H., professor of pediatrics at Northwestern University Feinberg School of Medicine, director of the Comprehensive Thalassemia Program at Ann & Robert H. Lurie Children’s Hospital of Chicago and lead investigator of the Northstar Study, who presented the data in an oral presentation. “Data from the Northstar Study presented today further demonstrate the potential for a one-time gene therapy treatment to transform the lives of patients with beta-thalassemia major, including those with the most severe genotype of beta-thalassemia major, beta-0/beta-0, also known as Cooley’s Anemia.”

LentiGlobin BB305 drug product aims to treat beta-thalassemia major and severe sickle cell disease by inserting a fully functional human beta-globin gene into the patient’s own hematopoietic stem cells ex vivo and then transplanting those modified cells into the patient through infusion, also known as autologous stem cell transplantation.

“We are very encouraged to see that each of the first four beta-thalassemia major subjects treated with LentiGlobin who had at least three months of follow up is producing robust levels of beta-^T87Q-globin and is transfusion-free,” said David Davidson, M.D., chief medical officer, bluebird bio. “We are on track to complete patient enrollment for the Northstar and HGB-205 studies in 2015, and as the clinical data continue to mature, we will work closely with medical experts, patient communities and regulatory authorities to define the regulatory path forward for LentiGlobin.”

Northstar Study Data

The Northstar Study is an ongoing, open-label, single-dose, international, multicenter Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product for the treatment of subjects with beta-thalassemia major.As ofDecember 1, 2014, five subjects with beta-thalassemia major have undergone infusion with LentiGlobin BB305 drug product in the Northstar Study. The first two subjects treated in the Northstar Study are producing steadily increasing amounts of beta-^T87Q-globin and have been free from the need for transfusions for the past five months and three months, respectively. Three additional subjects have been infused, but it is too early to draw any meaningful conclusions on clinical efficacy.

*If more than one drug product was manufactured for a subject, the VCN of each drug product lot is quantified and the cell count is combined.

**Data includes two months of follow-up on safety only.

HGB-205 Study Data

HGB-205 is an ongoing, open-label, single-center Phase 1/2 study 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. As ofDecember 1, 2014, two subjects with beta-thalassemia major have undergone infusion with LentiGlobin BB305 drug product. Both of these subjects achieved rapid transfusion independence with near-normal hemoglobin levels, similar to what may be expected from a successful allogeneic transplant, and have been free from the need for transfusions for the past 12 months and nine months, respectively. The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment, but it is too early post-transplant to draw any meaningful conclusions on clinical efficacy.

*If more than one drug product was manufactured for a subject, the VCN of each drug product lot is quantified and the cell count is combined.

**Hemoglobin levels represent data from the six-month follow up visit. Nine-month visit hemoglobin data not yet available.

In both studies, treatment with LentiGlobin BB305 drug product has been well tolerated to date, with no gene therapy-related Grade 3 or greater adverse events observed. All integration site analyses that have been performed to date show a polyclonal reconstitution without any evidence of clonal dominance.

“Today’s data demonstrate the potential benefit of gene therapy across beta-hemoglobinopathies as we begin gaining insights into its therapeutic potential for patients with severe sickle cell disease,” said 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. “Sickle cell disease affects millions of people around the world, significantly impacting their quality of life. The only currently available curative treatment for sickle cell disease is an allogeneic hematopoietic stem cell transplant, which is not accessible to most patients due to lack of suitable donors, so we are eager to explore LentiGlobin’s potential as a one-time therapy.”

Investor Conference Call and Webcast Information

bluebird bio will host a conference call and webcast on Wednesday, December 10, 2014 at 8:00 am EST to review the data presented at ASH. The event will be webcast live and 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 and (315) 625-3227 from outside the United States.

About Beta-Thalassemia

Beta-thalassemia is an inherited blood disease that can cause severe anemia. Patients with beta-thalassemia cannot make enough of the beta-globin part of hemoglobin, the protein used by red blood cells to carry oxygen throughout the body. Approximately 40,000 children are born with a serious form of the disease every year, making it one of the most common genetic diseases in the world. In its most severe form, beta-thalassemia is fatal if not treated.

Treating beta-thalassemia includes frequent and lifelong blood transfusions, which deliver red blood cells to the body to correct the anemia. However, blood transfusions also cause excess iron to build up in the body, which can damage organs and cause additional issues, such as abdominal pain, weakness, fatigue, joint pain, endocrine dysfunction, liver cirrhosis and heart failure. Patients who receive ongoing blood transfusions must also receive treatment to remove the excess iron. The only currently available curative treatment option for beta-thalassemia is allogeneic hematopoietic stem cell transplant. However, these transplants are only offered to pediatric patients with matched sibling donors (occurring in less than 25 percent of all cases), due to the significant risk of transplant-related morbidity and mortality.

About the Northstar (HGB-204) Study

Northstar is an ongoing, open-label, single-dose, international, multicenter Phase1/2 study designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with beta-thalassemia major. The study is designed to enroll up to 15 subjects who will be evaluated for safety and efficacy post-transplant. For more information on the Northstar Study, please visit www.northstarstudy.com or clinicaltrials.gov using identifier NCT01745120.

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 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 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.

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 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 for the treatment of beta-thalassemia major, one in the United States, Australia and Thailand (the Northstar Study) and one in France (HGB-205). The Phase 1/2 HGB-205 study also allows enrollment of patient(s) with sickle cell disease, and bluebird bio has initiated 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.

SOURCE: bluebird bio