– Six abstracts accepted for presentation –
– Interim data on LentiGlobin in beta-thalassemia show six of six
evaluable non-β0/β0
patients are transfusion-independent as of
– Median production of corrected HbAT87Q
globin: 5.2 g/dL among patients of all genotypes followed
for at least six months in HGB-204 study, as of
– Patient with sickle cell disease from HGB-205 study producing 51.5% anti-sickling hemoglobin at nine months post-treatment –
– Company will discuss ASH abstract data in a conference call today at 8:30 a.m. ET–
“Our expanding clinical experience with LentiGlobin continues to show
promising clinical benefit in patients with beta-thalassemia major and
severe sickle cell disease,” said
“The three accepted oncology abstracts represent the great progress we
have made building our immuno-oncology business,” said
LentiGlobin Presentations
Update of Results from the Northstar Study (HGB-204): A Phase 1/2 Study of Gene Therapy for Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector (LentiGlobin BB305 Drug Product) (Abstract #201)
Presenter:
Date:
Abstract
Results, as of
- Seven subjects have been monitored for at least six months post-infusion: three of the β0/β0 genotype and four of the non-β0/β0 genotype.
- The median level of HbAT87Q expression among these seven subjects is 5.2 g/dL (range 1.9 to 8.2 g/dL), with total hemoglobin ranging from 8.5 to 11.1 g/dL at last visit.
- All four non-β0/β0 subjects have been transfusion-free for at least 90 days, with a median of 287 days transfusion-free (range: 171 to 396 days).
- Two of the β0/β0 subjects have received a single transfusion post-discharge, and one remains transfusion-dependent.
- All subjects engrafted.
- The safety profile was consistent with autologous transplantation. No Grade 3 or higher drug-product related adverse events have been observed, and there is no evidence of clonal dominance after a median follow-up of 198 days (range: 65 to 492 days).
Outcomes of Gene Therapy for Severe Sickle Disease and Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector (Abstract #202)
Presenter: Marina Cavazzana, M.D., Ph.D., Hôpital Universitaire
Necker – Enfants Malades,
Date:
Abstract Results, as of
- The subject with severe SCD is producing approximately 51.5% anti-sickling hemoglobin (48 percent HbAT87Q, 1.8 percent HbF, 1.7 percent HbA2) at nine months post-infusion.
- The subject with severe SCD remains free of transfusions.
- The subject with severe SCD has not had a post-treatment hospitalization for a disease-related event despite ceasing chronic transfusions on Day +88.
- Both subjects with beta-thalassemia major have remained transfusion-free for at least 15 months post-infusion, with consistent expression of HbAT87Q – both subjects are β0/βE genotype.
- One additional subject with beta-thalassemia major had one month follow-up post-infusion.
- No subject has experienced a drug product-related adverse event, and there is no evidence of clonal dominance.
Initial Results from Study HGB-206: A Phase 1 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the LentiGlobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease (Abstract #3233)
Presenter:
Date:
Abstract
Results, as of
- LentiGlobin BB305 drug product has been manufactured for 2 subjects with severe SCD and 1 subject has been infused.
- The safety profile has been consistent with autologous transplantation, with no Grade 3 or higher drug product-related adverse events.
bb2121 Presentations
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 (Abstract #1893)
Presenter:
Date:
Abstract Results, as of
- In an in vivo aggressive lymphoma model, mice treated with anti-BCMA CAR T cells cultured with IL-2 and an inhibitor of PI3K experienced complete and long-term tumor regression; 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 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 model 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 be used in manufacture of other anti-tumor CAR therapies.
A Novel and Highly Potent CAR T Cell Drug Product for Treatment of BCMA-Expressing Hematological Malignancies (Abstract #3094)
Presenter: Alena Chekmasova, Ph.D., bluebird bio,
Date:
Abstract Results, as of
- bluebird bio has developed a chimeric antigen receptor (CAR) targeting BCMA (bb2121) that consists of 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 800 BCMA molecules per cell.
- In a BCMA+ MM xenograph model, treatment with bb2121 resulted in rapid and sustained elimination of the tumors and 100 percent survival.
Characterization of Lentiviral Vector Derived Anti-BCMA CAR T Cells Reveals Key Parameters for Robust Manufacturing of Cell-Based Gene Therapies for Multiple Myeloma (Abstract #3243)
Presenter:
Date:
Abstract Results, as of
- Successful personalized medicine will require robust and reproducible cell 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.
- The potency of the final drug product was shown to be independent of total anti-BCMA CAR expression on the cell surface.
- T cells transduced with varying MOIs 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.
- These data show that our manufacturing platform has been optimized to overcome significant challenges associated with personalized medicine by reducing the effects of variability while maintaining potency in autologous cellular drug product manufacturing.
Investor Conference Call and Webcast Information
bluebird
bio will host a conference call and webcast at
About bluebird bio, Inc.
With its lentiviral-based gene
therapy and gene editing capabilities, bluebird bio has built an
integrated product platform with broad potential application to severe
genetic diseases and T cell-based immunotherapy. bluebird bio’s clinical
programs include Lenti-D™ product candidate currently in a
Phase 2/3 study, called the Starbeam Study, for the treatment of
childhood cerebral adrenoleukodystrophy, and LentiGlobin®
BB305 product candidate, currently in three clinical studies: a global
Phase 1/2 study, called the Northstar Study, for the treatment of
beta-thalassemia major; a single-center Phase 1/2 study in
bluebird bio has operations in
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 potential efficacy and safety of the Company’s LentiGlobin BB305
product candidate in subjects with beta thalassemia major and severe
sickle cell disease, including statements concerning the production of
HbAT87Q and the reduced or eliminated need for
transfusion support for the study subjects with beta thalassemia major,
statements regarding the potential efficacy and safety of the Company’s
bb2121 product candidate, statements concerning the Company’s future
plans with respect to LentiGlobin, bb2121 and its other product
candidates. It should be noted that the data announced for LentiGlobin
are preliminary in nature and the
View source version on businesswire.com: http://www.businesswire.com/news/home/20151105005770/en/
Source: bluebird bio
bluebird bio, Inc.
Manisha Pai, 617-245-2107
mpai@bluebirdbio.com
or
Pure
Communications, Inc.
Dan Budwick, 973-271-6085