bluebird bio, Inc. (Nasdaq: BLUE) announced today that new and updated data from its investigational gene and cell therapy programs for multiple myeloma, sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) will be presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, December 7 - 10.

bluebird bio will present updated safety and efficacy data from the ongoing Phase 1 clinical study (CRB-402) of bb21217. bb21217 is an investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy being studied, in partnership with Celgene, in patients with relapsed/refractory multiple myeloma (RRMM).

In addition, data from clinical studies of LentiGlobin™ gene therapy for β-thalassemia, including results up to 61 months from the long-term follow-up study (LTF-303) and updated results from the completed Phase 1/2 Northstar (HGB-204) study, will be presented at ASH. The company will also present new data from the ongoing Phase 3 Northstar-2 (HGB-207) study in pediatric, adolescent and adult patients who do not have a β0/β0 genotype and from the ongoing Phase 3 Northstar-3 (HGB-212) study in pediatric, adolescent and adult patients who have β0/β0 genotype or an IVS-I-110 mutation at both alleles of the β-globin gene.

New data from the company’s Phase 1/2 HGB-206 study of LentiGlobin gene therapy for SCD will include additional patients treated in the study and updated data for those previously reported. The company will also present data from exploratory assays designed to assess the relationship between drug product characteristics and red blood cell physiology in patients treated with LentiGlobin for SCD.

Updated Data from Ongoing Phase 1 Clinical Study (CRB-402) of bb21217

Updated Results from an Ongoing Phase 1 Clinical Study of bb21217 Anti-BCMA CAR T Cell Therapy
Presenting Author: Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood Cancers, Nashville, Tenn.
Date & Time: Oral #927, Monday, December 9, 2019, 6:45 p.m. ET

bb21217, an investigational BCMA-targeted CAR T cell therapy being developed in partnership with Celgene, is one of bluebird bio's lead oncology programs. bb21217 uses the idecabtagene vicleucel CAR molecule (formerly referred to as bb2121) and is manufactured with a process intended to increase the in vivo persistence of CAR T cells.

This presentation will include updated data from the Phase 1 CRB-402 study, the first-in-human study of bb21217 in patients with RRMM, designed to assess the primary endpoint of safety as well as other pre-defined endpoints including efficacy and pharmacokinetics measurements. CRB-402 is a two-part (dose escalation and dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with RRMM with a projected final enrollment of 74 patients.

Data in the abstract include results as of the data cutoff date of April 20, 2019 for 22 patients who have received bb21217 at three dose levels (12 at 150 x 106 CAR+ T cells; six at 300 x 106 CAR+ T cells; and four at 450 x 106 CAR+ T cells). These patients had a median of seven prior lines of therapy (min-max: 4 – 17 lines), 18 patients had a prior autologous stem cell transplant, 19 patients received daratumumab and 13 patients received prior treatment with bortezomib, lenalidomide, carfilzomib, pomalidomide and daratumumab.

As of the data cutoff, the adverse events observed were consistent with known toxicities of CAR T therapies. Thirteen of 22 patients developed cytokine release syndrome (CRS); five Grade 1, seven Grade 2, and one Grade 3 case. All 13 patients responded to supportive care, tocilizumab and/or corticosteroids. Five of 22 patients developed neurotoxicity; one Grade 1, two Grade 2, one Grade 3 (vertigo/dizziness), and one Grade 4 (encephalopathy, previously reported). For the one patient previously reported with Grade 4 neurotoxicity, Grade 3 CRS was also reported, and both have resolved.

Eighteen patients were evaluable for clinical response with > two months of follow-up or progressive disease within two months. Eighty-three percent (n=15/18) of evaluable patients demonstrated clinical response per the International Myeloma Working Group Uniform Response Criteria for multiple myeloma. As of the data cutoff, with the median follow-up after bb21217 infusion of five months (min-max: <1 – 18 months), nine patients remained in response, including two patients with ongoing response at 15 and 18 months.

Evidence of myeloma in the bone marrow, known as minimal residual disease, was undetectable by next-generation sequencing at a sensitivity level of 10-5 or better in all responders who had evaluable bone marrow samples (n=10) at Month 1. CAR T cell persistence was observed in six of eight patients evaluable at six months and in two of two patients evaluable at 12 months.

This study is ongoing to evaluate the potential safety and efficacy of treatment with bb21217, and updated results, including early clinical and CAR T cell persistence data, will be shared at the ASH conference.

Multiple Myeloma Presentations at ASH

Markers of Initial and Long-Term Responses to Idecabtagene Vicleucel (Ide-Cel; bb2121) in the CRB-401 Study in Relapsed/Refractory Multiple Myeloma
Presenting Author: Ethan G. Thompson, Ph.D., Celgene, Seattle, Wash.
Date & Time: Poster #4328, Monday, December 9, 2019, 6:00 – 8:00 p.m. ET

Updated Results from an Ongoing Phase 1 Clinical Study of bb21217 anti-BCMA CAR T Cell Therapy
Presenting Author: Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood Cancers, Nashville, Tenn.
Date & Time: Oral #927, Monday, December 9, 2019, 6:45 p.m. ET

SCD Presentations at ASH

The Relationships Between Target Gene Transduction, Engraftment of HSCs and RBC Physiology in Sickle Cell Disease Gene Therapy
Presenting Author: Melissa Bonner, Ph.D., bluebird bio, Cambridge, Mass.
Date & Time: Oral #206, Saturday, December 7, 2019, 2:15 p.m.

Exploring the Drivers of Clinical Benefit in Initial Patients Treated in the HGB-206 Study of LentiGlobin for Sickle Cell Disease (SCD) Gene Therapy
Presenting Author: Mark Walters, M.D., Benioff Children’s Hospital, Oakland, Calif.
Date & Time: Poster #2061, Saturday, December 7, 2019, 5:30 – 7:30 p.m.

Resolution of Sickle Cell Disease Manifestations in Patients Treated with LentiGlobin Gene Therapy: Updated Results from the Phase 1/2 HGB-206 Group C Study
Presenting Author: Julie Kanter, M.D., University of Alabama at Birmingham, Birmingham, Ala.
Date & Time: Poster #990, Saturday, December 7, 2019, 5:30 – 7:30 p.m.

TDT Presentations at ASH

Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Transfusion-Dependent β-Thalassemia Treated at the Bambino Gesù Children’s Hospital, Rome, Italy
Presenting Author: Pietro Merli, M.D., IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
Date & Time: Poster #969, Saturday, December 7, 2019, 5:30 – 7:30 p.m.

Northstar-3: Interim Results from a Phase 3 Study Evaluating LentiGlobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Either a β0 or IVS-I-110 Mutation at Both Alleles of the HBB Gene
Presenting Author: Ashutosh Lal, M.D., UCSF Benioff Children’s Hospital, Oakland, Calif.
Date & Time: Oral #815, Monday, December 9, 2019, 5:30 p.m.

Northstar-2: Updated Safety and Efficacy Analysis of LentiGlobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Non-β0/β0 Genotypes
Presenting Author: Alexis Thompson, M.D., MPH, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Ill.
Date & Time: Poster #3543, Monday, December 9, 2019, 6:00 – 8:00 p.m.

Long-Term Clinical Outcomes of LentiGlobin Gene Therapy for Transfusion-Dependent β-Thalassemia in the Northstar (HGB-204) Study
Presenting Author: Janet Kwiatkowski, M.D., MSCE, Children's Hospital of Philadelphia, Philadelphia, Pa.
Date & Time: Poster #4628, Monday, December 9, 2019, 6:00 – 8:00 p.m.

Routine Management, Healthcare Resource Use and Patient/Caregiver-Reported Outcomes of Patients with Transfusion-Dependent β-Thalassaemia in the United Kingdom: A Mixed Methods Observational Study
Presenting Author: Farrukh Shah, MBBS, FRCP, FRCPath, M.D., Whittington Hospital, London, U.K.
Date & Time: Poster #3550, Monday, December 9, 2019, 6:00 – 8:00 p.m.

SCD and TDT Presentation at ASH

Results from the Completed HGB-205 Trial of LentiGlobin for β-Thalassemia and LentiGlobin for Sickle Cell Disease Gene Therapy
Presenting Author: Elisa Magrin, Ph.D., Necker Children’s Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Date & Time: Poster #3358, Sunday, December 8, 2019, 6:00 – 8:00 p.m.

Abstracts outlining bluebird bio’s accepted data at ASH will be available on the ASH conference website at 9 a.m. EST today.