Company to webcast in­­vestor event, Sunday, De­cem­ber 6 at 8:30 p.m. ET

Orlando, FL (Press Release) – bluebird bio, Inc. (NASDAQ:BLUE), a clin­i­cal-stage com­pany com­mit­ted to devel­op­ing poten­tially trans­for­ma­tive gene ther­a­pies for severe ge­netic dis­eases and T cell-based im­mun­o­therapies for cancer, an­nounced that pre-clinical data from its anti-BCMA on­col­ogy pro­gram were pre­sented by bluebird bio scientists at the 57th American Society of He­ma­tol­ogy Annual Meeting.

“We be­lieve the unique science and trans­la­tional gene ther­apy plat­forms we have built dif­fer­en­ti­ate bluebird bio in the on­col­ogy field and have the poten­tial to yield im­por­tant new ther­a­pies for patients living with can­cer. Our three on­col­ogy posters at ASH this year, covering crit­i­cal basic re­search, trans­la­tional and manu­factur­ing as­pects of our T cell on­col­ogy pipe­line, dem­onstrate the strength of our T cell immuno­therapy trans­la­tional science,” said Rob Ross, M.D., head of on­col­ogy, bluebird bio. “We are also ex­cited to see the first anti-BCMA clin­i­cal data from Dr. Jim Kochenderfer of the National Cancer Institute, which was high­lighted in yes­ter­day’s press release from ASH. We be­lieve these data provide excellent proof of concept for bb2121 and are pleased that Jim will serve as one of the prin­ci­pal in­ves­ti­ga­tors for our Phase 1 study of bb2121.”

Abstract #1893: Manufacturing an Enhanced CAR T Cell Product by Inhibition of the PI3K/Akt Pathway During T Cell Expansion Results in Improved In Vivo Efficacy of Anti-BCMA CAR T Cells

Overview and results, pre­sented by Molly Perkins, D.Phil., bluebird bio, in­clude:

• bluebird bio explored the potential for culture modifications to improve the therapeutic potential of CAR T cells without adding complexity to manufacturing. The company tested this hypothesis using CAR T cells specific to B cell maturation antigen (BCMA) manufactured using standard IL-2 culture with an inhibitor of PI3K added to the media, or with IL-7 and IL-15, in place of IL-2.
• In an in vivo aggressive lymphoma model, mice treated with anti-BCMA CAR T cells cultured only with IL-2 experienced no effect on tumor growth and succumbed to the tumors within two weeks after treat­ment; anti-BCMA CAR T cells grown in IL-7 and IL-15 also did not affect tumor growth. In contrast, mice treated with anti-BCMA CAR T cells cultured with IL-2 and an inhibitor of PI3K experienced com­plete and long-term tumor regression.
• In an in vivo multiple myeloma model, mice received a single administration of anti-BCMA CAR T cells cultured under various conditions; all treatment groups demonstrated tumor regression regardless of culture conditions. In a model of tumor relapse, two weeks after tumor clearance, surviving mice were re-challenged with the same multiple myeloma tumors on the opposite flank; only animals that had been treated with anti-BCMA CAR T cells cultured with the PI3K inhibitor were able to resist sub­se­quent tumor challenge.
• These data suggest that inhibition of PI3K during ex vivo expansion may generate a superior anti-BCMA CAR T cell product for clinical use; this approach could potentially apply to the manufacture of CAR T cell therapies against other oncology targets.

Abstract #3094: A Novel and Highly Potent CAR T Cell Drug Product for Treatment of BCMA-Expressing Hema­to­logical Malig­nan­cies

Overview and results, pre­sented by Alena Chekmasova, Ph.D., bluebird bio, in­clude:

• bluebird bio has developed a CAR targeting BCMA (bb2121) that consists of an extracellular single chain variable fragment scFv antigen recognition domain derived from antibodies to BCMA linked to CD137 (4-1BB) co-stimulatory and CD3zeta chain signaling domains.
• Based on receptor density quantification, bb2121 can recognize tumor cells expressing less than 1,000 BCMA molecules per cell.
• In a preclinical BCMA+ multiple myeloma xenograft model, a single IV administration of bb2121 anti-BCMA CAR T cells resulted in rapid and sustained elimination of the tumors with 100 percent survival, while a month-long course of anti-myeloma therapy Velcade® (bortezomib) only delayed tumor growth.
• Using flow cytometry and immunohistochemistry, bb2121 T cells were shown to rapidly target and infiltrate tumors, and T cell expansion was correlated with tumor regression.
• bb2121 anti-BCMA CAR T cells also induced xenograft regression and enhanced survival in a pre­clinical model of advanced Burkitt’s lymphoma.
• Taken together, these studies support the potential clinical application of bb2121 for the treatment of patients with tumors expressing BCMA.

Abstract #3243: Characterization of Lentiviral Vector Derived Anti-BCMA CAR T Cells Reveals Key Parameters for Robust Manufacturing of Cell-Based Gene Therapies for Multiple Myeloma

Overview and results, pre­sented by Graham W.J. Lilley, M.Sc., bluebird bio, in­clude:

• Successful personalized medicine will require robust and reproducible drug product manufacturing. A series of experiments were conducted to determine whether variations in anti-BCMA CAR surface expression resulted in changes in the activity of CAR T cells.
• T cells transduced with varying amounts of virus to yield different amounts of CAR surface expression were diluted with donor-matched untransduced cells to achieve a uniform population of T cells con­tain­ing 26 ± 4 percent anti-BCMA CAR T cells. When exposed to tumor, these CAR T cell popu­la­tions exhibited no difference in cytotoxicity against BCMA-expressing cells.
• All T cell productions easily achieved a level of anti-BCMA CAR expression that resulted in potent anti-BCMA activity, thus potency of the final drug product was shown to be independent of total anti-BCMA CAR expression on the cell surface.
• These data show that the bluebird bio T cell manufacturing process has the potential to overcome sig­nif­i­cant challenges associated with personalized medicine by reducing the effects of variability while maintaining potency in autologous cellular drug product manufacturing.

Investor Webcast In­for­ma­tion

bluebird bio will host an in­­vestor event that will be webcast live at 8:30 p.m. ET to­day, De­cem­ber 6, 2015, to discuss the ASH data and provide a brief overview of the science and clin­i­cal devel­op­ment plans sur­round­ing the gene ther­apy, genome edit­ing and immuno­therapy pro­grams. 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. The webcast will be avail­able for replay for 30 days on the com­pany website. 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 71438159.

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 childhood cerebral adreno­leuko­dystrophy, and its LentiGlobin® BB305 prod­uct can­di­date, cur­rently in three clin­i­cal stud­ies for the treat­ment of beta-thalassemia major 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 and focused on hema­to­logic malig­nan­cies. bluebird bio also has discovery re­search pro­grams uti­liz­ing megaTALs/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 Paris, France.

LentiGlobin and Lenti-D are trademarks of bluebird bio, Inc.

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 clin­i­cal poten­tial and manu­fac­tur­ing of the Com­pany’s anti-BCMA on­col­ogy pro­gram, in­­clud­ing its bb2121 prod­uct can­di­date. 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 pre­clin­i­cal ef­fi­cacy and safety data for our bb2121 prod­uct can­di­date will not be observed in our planned clin­i­cal stud­ies, 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 our clin­i­cal stud­ies, the risk that our col­lab­o­ration with Celgene Corpo­ra­tion 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.

Source: bluebird bio.