UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company 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).
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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. ☐
Item 7.01Regulation FD Disclosure.
On December 9, 2019, bluebird bio, Inc. (“bluebird”) conducted an investor webcast presenting updated clinical data for the LentiGlobin product candidate in the treatment of patients with transfusion-dependent β-thalassemia (HGB-204, HGB-207, and HGB-212), for the LentiGlobin product candidate in the treatment of patients with sickle cell disease (HGB-206), and for the bb21217 product candidate in the treatment of patients with relapsed-refractory multiple myeloma (CRB-402), as presented at the 61st Annual Meeting of the American Society of Hematology (“ASH”) in Orlando, Florida, as well as clinical data from KarMMa, a pivotal phase 2 study of idecabtagene vicleucel for the treatment of patients with relapsed and refractory multiple myeloma. A copy of the presentation is being furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in Item 7.01 of this Current 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 8.01Other Events.
On December 9, 2019, bluebird issued a press release announcing data presented at ASH of new data from ongoing studies of LentiGlobin gene therapy for β-thalassemia (betibeglogene autotemcel) in pediatric, adolescent and adult patients who have transfusion-dependent β-thalassemia (TDT),
Also on December 9, 2019, bluebird issued a press release announcing data presented at ASH from the ongoing Phase 1 clinical study of bb21217 (CRB-402) of its investigational next-generation anti-BCMA CAR T cell therapy being studied in patients with relapsed-refractory multiple myeloma.
The full text of bluebird’s press releases regarding these announcements are filed as Exhibits 99.2 and 99.3 to this Current Report on Form 8-K and are incorporated herein by reference.
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Financial Statements and Exhibits. |
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Description |
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99.1 |
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Investor presentation provided by bluebird bio, Inc. on December 9, 2019. |
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99.2 |
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99.3 |
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104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
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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 thereunto duly authorized.
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bluebird bio, Inc. |
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Date: December 10, 2019 |
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By: |
/s/ Jason F. Cole |
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Jason F. Cole |
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Chief Operating and Legal Officer |
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ASH 2019 december 9, 2019 Exhibit 99.1
These slides and the accompanying oral presentation contain forward-looking statements and information. The use of words such as “may,” “might,” “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 initiate or complete, clinical studies, the timing or likelihood of regulatory filings and approvals or the requirements that may be imposed, and the timing and likelihood of entering into contracts with payors for value-based payments over time or reimbursement approvals, and our commercialization plans for approved products 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
today’s agenda welcome Nick Leschly chief bluebird LentiGlobin for TDT data Dave Davidson, M.D. chief medical officer LentiGlobin for SCD data Mohammed Asmal, M.D., Ph.D. vice president, head of SGD clinical research bb21217 and KarMMa topline data Dave Davidson, M.D. chief medical officer Q&A Chip Baird, chief financial officer Philip Gregory, D. Phil., chief scientific officer Alison Finger, chief commercial officer
RADICAL CARE We care in a way that’s intense and truly sets us apart. WE RECODE FOR LIFE THIS IS PERSONAL Gene therapy is about saving lives one person at a time. And we are, each of us, personally all in. PIONEERS WITH PURPOSE We’re exploring new frontiers for the sake of patients.
We live by our non-negotiables
Key questions for today LentiGlobin TDT LentiGlobin SCD bb21217 Do the updated data in patients with non-β0/β0 genotypes reinforce the potential for patients to achieve and maintain transfusion independence (TI)? Do the emerging data in patients with β0/β0 genotypes suggest that these patients may achieve TI? With more patients and more follow up, are we continuing to see profound impact on important clinical manifestations of disease (VOEs, hemolytic anemia)? Do the laboratory tools we have developed conclusively demonstrate that LentiGlobin for SCD changes the fundamental pathophysiology of the sickle RBC? Does enriching 21217 drug product for memory-like t cells translate to greater T cell persistence and longer durations of response? ide-cel KarMMa Are KarMMa data supportive of ide-cel as a meaningful advance for patients and as a potential new standard of care for refractory multiple myeloma? Is the program on track for 1H:2020 filing?
Transfusion-Dependent β-Thalassemia (TDT) EU approval granted June 2019 US rolling BLA submission to begin by YE 2019 Studies ongoing: Northstar-2 (HGB-207) Northstar-3 (HGB-212) Long-term follow-up: LTF-303 program overview A severe, progressive, genetic disease that leads to severe anemia, lifelong transfusion dependence, unavoidable iron overload, serious comorbidities, and a shortened lifespan. Global prevalence estimated at ~288,0001 The U.S. prevalence of beta-thalassemia major is estimated at least 1,000 people2,3 European prevalence is variable by country ranging from <1,0004 patients in nonendemic countries, to ~6,5005 patients in endemic countries 1Biffi A. Gene Therapy as a Curative Option for beta-Thalassemia. N Engl J Med. 2018;378(16):1551-1552. 2SayaniFA, Kwiatkowski JL. Increasing prevalence of thalassemia in America: implications for primary care. Ann Med. 2015;47(7):592-604. 3Centers for Disease Control and Prevention. Living with thalassemia. 2018; https://www.cdc.gov/features/international-thalassemia/index.html. Accessed May 11, 2018. 4CarioH, StahnkeK, Sander S, KohneE. Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter β-thalassemia study. Ann Hematol. 2000;79(1):7-12. 5AngelucciE, AntmenAB, LosiS, Burrows N, BartiromoC, Hu XH. Direct medical care costs associated with β-Thalassemia care in Italy. Blood. 2017;130(Suppl 1):92-5599.
Completed studies of LentiGlobin for TDT reinforce long term durability of clinical outcomes Up to 5 years follow-up with stable HbAT87Q and total Hb 8/10 non-β0/β0; 3/8 β0/β0 remain TI as of data cut-off Reduction in liver iron content; cardiac iron remains stable in normal range as of data cut-off 21/23 patients treated 9/10 patients achieved transfusion independence (TI) Total unsupported Hb is near-normal in most patients as of data cut-off 13/18 patients treated 2/2 patients achieved transfusion independence HGB-204 Complete HGB-207 non-β0/β0 genotypes HGB-212 β0/β0 genotype or IVS-I-110 mutations Stable HbAT87Q and total Hb at up to 5+ years follow-up 3/4 non-β0/β0 remain TI as of data cut-off Substantial improvement in underlying dyserythropoiesis HGB-205 Complete
HGB-207: 90% (18/20) of patients with > 3 months follow-up are off pRBC transfusions Data as of 12 June 2019 Green indicates patient <12 years old at screening Hb (g/dL) at last visit The safety profile of LentiGlobin for TDT remains generally consistent with that of myeloablative busulfan conditioning. 1 12.5 2 9.3* 3 13.2 4 12.8 5 13.3 6 12.7 7 12.3 8 12.1 9 12.1 10 11.9 11 12.3 12 10.5 13 10.2 14 11.3 15 9.7 16 11.2 17 11.1 18 9.3 19 10.6 20 9.7* *Supported by transfusions
HGB-207: stable total Hb and gene therapy-derived HbAT87Q in the majority of patients Data as of 12 June 2019 *Last Hb before patient 2 restarted red blood cell transfusions. Hb, hemoglobin. Median total Hb values include Patient 2 who was on transfusions Median Hb (g/dL) M6 N=17 M9 N=14 M12 N=11 M18 N=8 M24 N=3 Total Hb 11.5 11.6 12.3 12.2 12.5 HbAT87Q 8.7 9.2 9.3 9.4 8.8 Months Post-LentiGlobin for TDT Infusion HGB-207 utilized a range of manufacturing process conditions as the commercial manufacturing process was defined
HGB-212: 9/11 patients with ≥ 6 months follow-up have been off transfusions for ≥ 3 months Data as of 30 September 2019 Hb, hemoglobin; RBC, red blood cell 13.2 10.4 14.2 7.8* 9.4 12.8 9.7 9.6* 10.0 11.1 8.3 9.8* 1 2 3 4 5 6 7 8 9 10 11 12 Genotype β0/β0 β0/IVS I-110 IVS I-110/IVS I-110 β0/β0 β0/IVS I-110 β0/β0 Green indicates patient <12 years old at screening Hb (g/dL) last visit *Supported by RBC transfusion Transfusion status in patients with ≥ 3 months follow-up Months Post-LentiGlobin for TDT Infusion Patients 1 and 2 achieved and maintained transfusion independence Weighted average Hb ≥ 9 g/dL without RBC transfusions for ≥ 12 months
HGB-212: HbAT87Q supports target total Hb in most patients with minimal endogenous HbA ≥ 3 months after treatment Data as of 30 September 2019 DP, drug product; Hb, hemoglobin; VCN, vector copy number Genotype β0/β0 β0/ IVS I-110 IVS I-110/ IVS I-110 IVS I-110/ IVS I-110 β0/β0 β0/ IVS I-110 β0/β0 β0/β0 β0/β0 β0/β0 β0/β0 β0/β0 DP/peripheral VCN 3.1/2.4 3.65/1.9 3.1/3.1 2.1/0.4 2.25/0.5 4.3/1.1 3.0/0.5 1.9/0.2 1.2/0.2 2.1/2.2 2.5/0.5 1.9/0.8 Month 6 Month 9 Month 12 M18 M3 HGB-212 utilized a range of manufacturing process conditions as the commercial manufacturing process was defined The safety profile of LentiGlobin for TDT remains generally consistent with that of myeloablative busulfan conditioning
50+ patients treated across program for LentiGlobin in TDT Completed HGB-204 and HGB-205 studies with up to 5+ years of data reinforce durability of treatment 90% of evaluable patients who do not have a β 0 / β 0 genotype achieved TI in HGB-207 study 9 of 11 patients with at least 6 months of follow-up in HGB-212 did not receive a transfusion for more than 3 months as of last follow-up Safety profile of LentiGlobin for TDT treatment is consistent with that of busulfan conditioning
Sickle Cell Disease (SCD) Plan to pursue development path based on hematological primary endpoint Phase 3 HGB-210 study to be open and enrolling patients by early 2020 HGB-206 target enrollment achieved program overview A serious, progressive, unpredictable, and debilitating genetic disease caused by abnormal sickle hemoglobin Results in chronic hemolytic anemia, repeated painful vaso-occlusive events and persistent vasculopathy that frequently leads to early morbidity and mortality Global annual birth incidence ~ 300,000 – 400,0001,2 U.S. prevalence estimated at 72,000 – 100,0003,4 Mean age of death in the U.S. is 44 years5 1Kato GJ, Piel FB, Reid CD, et al. Sickle cell disease. Nat Rev Dis Primers. 2018;4:18010. 2Piel FB, Patil AP, Howes RE, et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet. 2013;381(9861):142-151. 3Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 2010;38(4 Suppl):S512-521. 4CDC Data and Statistics on Sickle Cell Disease. https://www.cdc.gov/ncbddd/sicklecell/data.html 5Paulukonis et al, California’s Sickle Cell Data Collection Cohort, 2005-2015* ASH 2017*
Ongoing Phase 1/2, single arm, multi-center, U.S. study N=41 (Group C) Primary Endpoint: HbAT87Q and total Hb Key Secondary Endpoint: Reduction in severe VOEs ≥ 12 years of age - ≤ 50 years of age Phase 1/2, single-center in France N=7 (4 β-thalassemia) HGB-205 (Transfusion-dependent b-thalassemia & severe sickle cell disease) All thalassemia subjects dosed as of Sep 2015 2 year study duration; last β-thalassemia subject visit ≈Sep 2017 HGB-206 Group C Sickle Cell Disease, history of vaso-occlusive events (VOEs) over 24 months Currently Enrolled¥ N=49 LentiGlobin DP Infused N=17 Median follow-up: 10.9 months (min – max: 0.9 – 20.7) Plerixafor Mobilization & Apheresis N=30 Discontinued* N=3 Cell Collection Pending N=13 Ineligible N=6 DP Manufacture Completed N=25 Transplant Pending N=8 DP Manufacture Pending N=2 *1 withdrew consent, 1 discontinued due to investigator discretion, 1 mobilization failure; DP, drug product ¥ Currently active, not recruiting Data as of 26 August 2019 Expanding development program to evaluate LentiGlobin across SCD patient types and ages
99% reduction in annualized rate of VOC + ACS in HGB-206 Group C patients with history of VOCs and ACS who had ≥ 6 months of follow-up *As previously reported, 1 non-serious Grade 2 VOC was observed in 1 patient ~3.5 months post-LentiGlobin treatment Investigator-reported adverse events of VOC or ACS are shown; *Patients with ≥ 4 VOC/ACS at baseline before Informed Consent and with ~ ≥ 6 months of follow-up post-DP infusion ACS, acute chest syndrome; VOCs, vaso-occlusive crises; DP, drug product 24 months prior to Informed Consent Duration (months) of Follow-Up Post DP Total number of events over 2 years post-DP Total number of events over 2 years pre-IC * Data as of 26 August 2019 95% confidence interval: 92.5-100% LentiGlobin for SCD treatment
Improving key markers of hemolysis in HGB-206 Group C patients following treatment with LentiGlobin for SCD Median (Q1, Q3) depicted; Dot-dash lines denote lower and upper limits of normal values; *Number of patients with data available; †Total bilirubin at last follow-up remains > 2-fold lower than at screening DP, drug product; LDH, lactate dehydrogenase Reticulocyte Counts Lactate Dehydrogenase Total Bilirubin N= 16 12 10 9 7 4 1 N= 16 12 10 9 7 4 N= 16 12 10 9 7 4 1 Data as of 26 August 2019
HGB-206 Group C patients at 6 months post-treatment produced consistent median levels of anti-sickling hemoglobin ranging from 44% - 59% (Month 6-21) Median Hb (g/dL) % represents median Hb fraction as % of total Hb; Hb, hemoglobin 38% 44% 34% 53% 54% 48% 50% 44% 52% 44% 53% 45% 59% 39% Median HbS ≤ 60% at ≥ 6 months post-LentiGlobin for SCD treatment Total Hb and HbAT87Q ranged from 9.3 – 15.2 g/dL and 2.7 – 9.0 g/dL, respectively, at last visit in patients with ≥ 6 months of follow-up Data as of 26 August 2019 11.2 11.7 11.7 11.5 15.2 11.4 11.2
On average, ≥ 70% of RBCs from patients treated with LentiGlobin for SCD contain βA-T87Q by month 6 Exploratory single RBC western assay performed on samples from 12 patients in Group C DP, drug product; RBCs, red blood cells; sc, single cell Mean is depicted - if N=1, data show technical replicates; *Pre-conditioning sample does not contain any βA-T87Q , signal is due to error rate of multiples Data as of 26 August 2019
Exploratory assay: high concentrations of T87Q achieved at the cellular level DP, drug product; Hb, hemoglobin; HPFH, hereditary persistence of fetal hemoglobin; MCH, mean corpuscular hemoglobin; RBC, red blood cells AS, sickle cell trait; HD, healthy donor; SS, sickle mutation on both HBB alleles Average pg Hb/RBC = (% HbAT87Q of total Hb/% RBCs containing bA-T87Q) x MCH *Calculated using 50% HbA/RBC for the lower end of the range and 60% HbA/RBC for the upper end of the range **Group C only; †HbF contribution to total Hb in these samples ranged from 28% – 42% 1. Steinberg MH et al., Blood. 2014;123(4):481-5. Propensity to sickle decreases over time post-gene therapy with LentiGlobin for SCD; Group C similar to trait Data as of 26 August 2019 HbAT87Q pg/RBC comparable to HbA pg/RBC in trait & HbF pg/RBC in HPFH % sickling for LentiGlobin-treated patients with ≥ 6M follow-up Group C only LentiGlobin-treated (Group C)
HGB-206 Group C: safety profile post-DP infusion generally consistent with myeloablative single-agent busulfan conditioning Non-hematologic Grade ≥ 3 AEs Post-DP infusion in ≥ 2 patients* N = 17 n (%) Febrile neutropenia 10 (58.8) Stomatitis 9 (52.9) Increased blood bilirubin 3 (17.6) Upper abdominal pain 2 (11.8) Increased alanine aminotransferase 2 (11.8) Increased aspartate aminotransferase 2 (11.8) Nausea 2 (11.8) Premature menopause 2 (11.8) Serious AEs Post-DP infusion in ≥ 2 patients N = 17 n (%) Nausea 2 (11.8) Vomiting 2 (11.8) Safety profile post-DP infusion is generally consistent with myeloablative single-agent busulfan conditioning No DP-related adverse events No cases of veno-occlusive liver disease No graft failure or deaths reported No vector-mediated RCL No evidence of clonal dominance No further cases of MDS have been observed across studies of LentiGlobin†§ *Hematologic AEs commonly observed post-transplantation have been excluded †As of June 2019 (HGB-205); 12 Jun 2019 (HGB-204, HGB-207), and 30 Sep 2019 (HGB-212) ▪One patient in Group A was reported to have MDS at ASH 2018. There was no evidence of LVV-mediated oncogenesis and the MDS SAE was considered unlikely related to LentiGlobin gene therapy. AE, adverse event; DP, drug product; RCL, replication competent lentivirus
Notable impact on underlying pathophysiology of SCD ACS, acute chest syndrome; VOCs, vaso-occlusive crises 99% reduction in annualized rate of VOC + ACS in Group C patients with history of VOCs and ACS who had ≥ 6 months of follow-up, with no reports of ACS or serious VOCs at up to 21 months post-treatment Continued improvement in key markers of hemolysis in Group C patients as of the data cut-off date Continue to pursue an accelerated development path based on hematological primary endpoint Group C patients at 6 months post-treatment produced consistent median levels of anti-sickling hemoglobin ranging from 44% - 59%
multiple myeloma ide-cel (bb2121): U.S. BLA submission planned for 1H:2020 KarMMa-2 and KarMMa-3 studies in earlier lines of therapy open and enrolling; Phase 1 study in newly-diagnosed multiple myeloma set for 2019 bb21217 CRB-402 Phase 1 study underway BCMA program overview An incurable type of blood cancer that arises from antibody producing cells in the bone marrow, resulting in anemia, kidney failure, infections and skeletal fractures. Second most common hematologic cancer1,2 In 2018, MM was diagnosed in nearly 160,000 patients worldwide and over 31,000 patients in the US. It is estimated that over 130,000 patients in the US are living with this disease. 1NCI SEER. https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed June 5, 2019. 2 Bray F, et al. CA Cancer J Clin. 2018;68(6):394-424
Hypothesis: Increasing long-lived, memory-like T Cell subsets in the drug product may result in enhanced persistence of functional anti-BCMA CAR T cells in vivo TN cell TSCM cell TCM cell TEM cell TEFF cell Terminally Differentiated No Self Renewal Short-lived bb21217: PI3K inhibition during manufacturing drives increase in long-lived, memory-like T cells T Cell Plasticity Self Renewal Long-lived
300 × 106 n=6 Phase 1 dose-escalation study in heavily pretreated and refractory patient population continues to enroll BCMA, B-cell maturation antigen; IMiD, immunomodulatory imide drugs; MRD, minimal residual disease; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor; R/R, relapsed/refractory. cPer International Myeloma Working Group Criteria. 3 + 3 dose escalation 450 × 106 n=6 150 × 106 n=12 Primary endpoints: AEs, DLTs Other endpoints: Responsec, PFS, OS, MRD, CAR+ T cell expansion and persistence Manufacturing Success Rate 100%* CAR+ T cell dose Expansion 300 × 106 n=8 450 × 106 n=6 Data as of 4 September 2019 *3 patients required 1 re-manufacturing run Expansion Ongoing at 450 N ≈ 74 R/R MM ≥3 prior regimens Prior IMiD and PI required In escalation only ≥50% BCMA expression required In expansion only αCD38 exposure and refractory to last line required
Baseline patient characteristics and treatment history Confidential : DRAFT Data as of 4 September 2019 Characteristic bb21217-Treated (N=38) Median (min, max) age, y 62 (33, 74) Male, n (%) 21 (55) Time since initial diagnosis, y Median (min, max) 5.5 (1.0, 13.5) ECOG PS, n (%) 0 1 2 12 (32) 24 (63) 2 (5) ISS stagea, n (%) I II III Unavailable 11 (29) 7 (18) 10 (26) 10 (26) High-risk cytogenetics, n (%) del(17p), t(4;14), t(14;16) Unknown 13 (34) 1 (3) ECOG PS, Eastern Cooperative Oncology Groups performance status; IMiD, immunomodulatory imide drugs; ISS, International Staging System; mAb, monoclonal antibody; PI, proteasome inhibitor; SCT, stem cell transplantation. bNumber of antimyeloma regimens, including autologous SCT. Characteristic bb21217-Treated (N=38) Median (min, max) no. prior regimensb 6 (3, 17) Prior autologous SCT, n (%) 0 1 >1 7 (18) 22 (58) 9 (24) Prior therapies, n (%) Exposed Refractory IMiD agent Any Lenalidomide Pomalidomide 38 (100) 38 (100) 35 (92) 30 (79) 30 (79) 22 (58) PI Any Bortezomib Carfilzomib 38 (100) 36 (95) 32 (84) 33 (89) 21 (55) 25 (66) αCD38 antibodies Any Daratumumab 36 (95) 35 (92) 29 (76) 28 (74) Cumulative PI/IMiD PI/IMiD/αCD38 antibodies 38 (100) 36 (95) 29 (76) 24 (63)
Safety profile consistent with CAR T experience Confidential : DRAFT Data as of 4 September 2019 CRSc occurred in 25 patients (66%) Median (min, max) time to onset was 3 d (1, 20) Generally adequately managed with tocilizumab (n=10) and tocilizumab plus corticosteroids (n=4) 1 fatal CRS event associated with grade 3 neurotoxicity at the 450 × 106 dose occurred after 15 days of follow-up Neurotoxicityd of grade 3 or higher occurred in 3 patients 2 grade 3 events and 1 previously reported grade 4 event Median (min, max) time to onset of neurotoxicity was 7 d (3, 24) 7 grade 3/4 infections reported 19 patients (50%) experienced ≥1 SAE AE, adverse event, SAE, serious AE, CMV, cytomegalovirus aAEs and SAEs after first documented progression are excluded bIncludes SOC infections and infestations, one case each of anal abscess, bacteraemia, CMV colitis, device related infection, escherichiabacteraemia, pneumococcal bacteraemia, pneumococcal sepsis and pneumonia; CRS, cytokine release syndrome;. cCRSuniformly graded according to Lee et al., Blood2014;124:188-195 occurring after bb21217 infusion and before disease progression. dEvents selected as CAR T neurotoxicity on the case report form occurring within 90 days after bb21217 infusion. Grade, n (%) Total all grades N 1 2 3 4 5 CRS 150 × 106 300 × 106 450 × 106 12 14 12 4 (33) 4 (29) 4 (33) 3 (25) 3 (21) 5 (42) 1 (8) 0 0 0 0 0 0 0 1 (8) 8 (67) 7 (50) 10 (83) Neurotoxicity 150 × 106 300 × 106 450 × 106 12 14 12 1 (8) 1 (7) 1 (8) 1 (8) 2 (14) 0 0 1 (7) 1 (8) 1 (8) 0 0 0 0 0 3 (25) 4 (29) 2 (17) Grade 3/4 AEs in >2 Patientsa, n (%) Grade 3/4 (N=38) Neutropenia 31 (82) Leukopenia 21 (55) Thrombocytopenia 21 (55) Anemia 19 (50) Lymphopenia 13 (34) Hypophosphatemia 8 (21) Infectionb 7 (18) Hyponatremia 5 (13) Febrile neutropenia 4 (11)
Data as of 4 September 2019 CAR+ T Cells N Median follow up (min, max) 150 × 106 12 17.6 mo (12, 23) 300 × 106 14 4.0 mo (2, 10) 450 × 106 12a 3.3 mo (<1, 6) Months CR, complete response; MRD, minimal residual disease; PD, progressive disease; sCR, stringent complete response; VGPR, very good partial response. a One patient ongoing at the time of the data extraction missed their 2-month visit and another was in VGPR but is reported as a PR owing to a missed assessment. + Death To date, no progression in patients with confirmed response at the 300 x 106 and 450 x 106 dose cohorts; mDOR of 11.1 months at 150 x 106 dose
Data as of 4 September 2019 Confirmed Response Duration by Dosea DOR, duration of response; MRD, minimal residual disease; NE, not estimable; PD, progressive disease; PR, partial response; sCR/CR, stringent complete response/complete response; VGPR, very good partial response. aPatients with ≥2 months of follow up or PD/death within 2 months. Response confirmed by a consecutive response of the same category or better. bPatients with ≥PR and ≥1 valid post-baseline MRD assessment by Adaptive next-generation sequencing. 150x106 dose 6 neg at 10-6 and 1 neg at 10-5, 300x106 dose 4 neg at 10-6 and 1 at 10-5, 450x106 2 neg at 10-6 and 2 at 10-5. CAR+ T Cells: 150 × 106 (n=12) 300 × 106 (n=14) 450 × 106 (n=7) Median follow-up (min, max) 17.6 mo (12, 23) 4.0 mo (2, 10) 3.3 mo (<1, 6) Confirmed responsea, n (%) sCR/CR VGPR PR Total 4 (33) 6 (50) 0 10 (83) 0 4 (29) 2 (14) 6 (43) 1 (14) 2 (29) 1 (14) 4 (57) Median time to first response (min, max), mo 1.0 (1.0, 1.9) 1.0 (1.0, 1.0) 1.2 (1.0, 1.8) MRD status in bone marrowb Evaluable responders, n MRD negative, n 7 7 6 5 4 4 Confirmed responses across dose cohorts
Confirmed responders show increased CAR T cell expansion and durable persistence Confidential : DRAFT Data as of 4 September 2019 Month 3 6 12 18 Detectable vectora, n 13 8 2 2 No. at riskb 15 10 4 2 Median VCN Over Time by Dose Vector Copies/μg gDNA Months After bb21217 Infusion P value based on a 2 sided Wilcoxon rank sum test. BL, baseline; gDNA, genomic DNA; IQR, interquartile range; LLOQ, lower limit of quantification; VCN, vector copy number. a includes detectable but not measurable. b includes VCN data for patients until PD,includes 1 patient who received subsequent chemotherapy before progression. Error bars for median VCN represent IQR Nonresponders (n=13) Peak VCN by Response P=0.0007 Vector Copies/μg gDNA Confirmed Responders (n=20)
Proportion LEF1+ t cells Proprortion CD57+ t cells Enrichment for memory-like T cells is associated with robust CAR T expansion and lack of progression by month 6 Patients with a higher proportion of memory-like T cells in bb21217 drug product have significantly better peak expansion A higher proportion of memory-like T cells is associated with numerically less progression by M6 CD57 CD27 LEF1 CCR7 High memory-like T Cells 1/7 progressed Intermediate 1/5 progressed High CD57 4/6 progressed No PD by M6 PD by M6 bb21217 Drug Product Enriched For Memory-Like T Cells Memory-Like T Cells Associated With Peak CAR T Expansion Memory-Like T Cells in Drug Product Associated With Lack of Progression at M6a −1.5 −1 −0.5 0 0.5 1 1.5 Exhaustion Memory PD by M6 M6, month 6; PBMC, peripheral blood mononuclear cell in apheresis product; PD, progressive disease; VCN, vector copy number. A Responding Patients with biomarker data who had either PD or a month 6 visit confirming absence of PD, 1 patient with continued stable disease at M6 included. Proportion CD57 Proportion LEF1 VCN, Copies/μg gDNA VCN, Copies/μg gDNA Data as of 4 September 2019
Emerging data supports memory T cell hypothesis Confidential : DRAFT Safety profile consistent with known toxicities of CAR T-cell therapies Demonstrated association between enrichment in 21217 manufacturing process and robust CAR-T cell expansion Dose escalation is complete. Continue to evaluate safety and efficacy at recommended phase 2 dose of 450 x 10 6 dose Confirmed responses achieved across all doses Detectable CAR-T cells at 18 months for patients remaining in response with greater than 20 months follow up
KarMMa topline data readout
Heavily pretreated population 94% refractory to anti-CD38, 84% triple refractory All patients were refractory to their last treatment (progression during or within 60 days of last therapy) Deep and durable responses across dose levels mPFS of >11mo at the 450 x 106 dose Durability is consistent across doses Safety consistent with the Ph1 data Gr ≥ 3 CRS and iiNT were reported in <6% of subjects at each target dose CRS and iiNT of any grade occurred in 83.6% and 18% of patients, respectively 300 x 106 (n=70) 450 x 106 (n=54) SoC All Doses (n=128) 150 x 106 CAR+ T cells (N=4) 300 x 106 CAR+ T cells (N=70) 450 x 106 CAR+ T cells (N=54) All Doses CAR+ T cells (N=128) ORR, n (%) 2 (50.0) 48 (68.6) 44 (81.5) 94 (73.4) CR/sCR, n (%) 1 (25.0) 20 (28.6) 19 (35.2) 40 (31.3) Median DoR, mo --- 9.9 11.3 10.6 iiNT: investigator identified neurotoxicity Ide-cel is being developed in collaboration with Bristol-Myers Squibb ide-cel (bb2121): Positive Pivotal Data
Advancing ide-cel (bb2121) into earlier lines of multiple myeloma Multiple Myeloma NDMM Study KarMMa-3 (BB2121-MM-003) KarMMa-2 (BB2121-MM-002) KarMMa (BB2121-MM-001) phase 3 phase 2 phase 1 registration-enabling trial in late line met primary and secondary endpoints front line setting Phase 1 study starting in 2019 3rd line+ phase 3 study open 2nd line phase 2 study open lines of therapy Planned 1H:2020 regulatory submission
closing
bbb at ASH 2019: LentiGlobin TDT LentiGlobin SCD bb21217 Patients achieving and maintaining TI across genotypes Launch progressing in EU Clinical impact underscored by impact on underlying disease Program gradually expanding Indication of hypothesis bearing out Further investigation underway bb2121 Topline data support 1H:2020 regulatory submission Development path in earlier lines of therapy progressing
thank you
bluebird bio Presents New Data Demonstrating Long-Term Transfusion Independence and Safety for LentiGlobin™ Gene Therapy for β-thalassemia (betibeglogene autotemcel) at 61st ASH Annual Meeting and Exposition
More than four years of durable transfusion independence (TI), stable total hemoglobin (Hb) levels and reduced liver iron concentrations in completed Phase 1/2 Northstar (HGB-204) study in patients who do not have a β0/β0 genotype
Ninety percent of evaluable patients who do not have a β0/β0 genotype achieved TI, with median average total Hb levels of 12.2 g/dL in Phase 3 Northstar-2 (HGB-207) study
In ongoing Phase 3 Northstar-3 (HGB-212) study in patients with β0/β0 genotype or IVS-I-110 mutation, the two patients evaluable for TI achieved it with Hb levels of 13.2 g/dL and 10.4 g/dL at last visit
Nine of 11 patients with at least six months of follow-up in HGB-212 have not had a transfusion for at least three months
CAMBRIDGE, Mass.— (BUSINESS WIRE)— December 9, 2019 - bluebird bio, Inc. (Nasdaq: BLUE) announced new data from ongoing studies of LentiGlobin™ gene therapy for β-thalassemia (betibeglogene autotemcel) in pediatric, adolescent and adult patients who have transfusion-dependent β-thalassemia (TDT), including results from the Phase 3 Northstar-3 (HGB-212) study in patients with a β0/β0 genotype or IVS-I-110 mutation, and the Phase 3 Northstar-2 (HGB-207) study in patients who do not have a β0/β0 genotype. These data, as well as updated results reflecting up to five years of follow-up from the completed Phase 1/2 Northstar (HGB-204) study, were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.
As of the data cutoff presented today, 52 pediatric, adolescent and adult patients with TDT who do not have a β0/β0 genotype or have a β0/β0 genotype have been treated with LentiGlobin for β-thalassemia in the Northstar, Northstar-2 and Northstar-3 studies.
“The results from our clinical studies of LentiGlobin for β-thalassemia support its potential benefits and consistent safety profile across a broad range of TDT genotypes and patient populations, including pediatric patients, with the longest duration of follow-up now extending beyond five years,” said David Davidson, M.D., chief medical officer, bluebird bio. “Importantly, patients have achieved and maintained transfusion independence, with improvements in multiple markers of bone marrow red blood cell production, as well as reductions in iron overload. These outcomes demonstrate the long-term disease-modifying potential of LentiGlobin for people living with TDT.”
TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.
LentiGlobin for β-thalassemia was designed to address the underlying genetic cause of TDT by adding functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). bluebird bio’s clinical development program for LentiGlobin for β-thalassemia includes studies across patient genotypes, including those who do not have a β0/β0 genotype, as well as those with a β0/β0 genotype.
“Blood transfusions, while necessary, result in unavoidable iron overload, which can cause multi-organ damage. These infusions also have an impact on patients and their families’ lives,” said Ashutosh Lal, M.D., UCSF Benioff Children’s Hospital, Oakland, Calif. “It’s encouraging to see that adult, adolescent and pediatric patients with various genotypes in the LentiGlobin for β-thalassemia clinical trials have achieved and continue to maintain transfusion independence.”
Northstar (HGB-204) Efficacy
As of June 12, 2019, data from up to five years (median 44.9; min–max: 34.8–61.3 months) of follow-up from the completed Phase 1/2 Northstar (HGB-204) study show durable transfusion independence (TI) and stable HbAT87Q levels in patients who achieved TI. TI is defined as weighted average Hb ≥ 9 g/dL without red blood cell (RBC) transfusions for more than 12 months.
Eight of 10 treated patients who did not have a β0/β0 genotype achieved and continued to maintain TI for up to 51.3 months as of the data cutoff, with a median weighted average Hb during TI of 10.3 g/dL. Transfusion volumes were reduced by 79% and 52% in the two patients who did not achieve TI.
In patients who have a β0/β0 genotype (n=8), three of eight achieved and continued to maintain TI with a current duration up to 30.4 months as of the data cutoff, and a median weighted average Hb during TI of 9.9 g/dL.
Among patients who achieved TI, a decrease in markers of iron burden, including liver iron concentration, serum ferritin and transferrin saturation, were observed over time. Liver iron concentrations began to decrease in eight of the 11 patients who achieved TI, with the largest decrease observed in patients who had 48 months of data available (n=7). A median 44% reduction (min–max: 17%–83%) was reported in these seven patients.
Northstar-2 (HGB-207) Efficacy
As of June 12, 2019, 21 of 23 patients were treated and have been followed for a median of 11.6 months. These patients ranged in age from 8 to 34 years, including six pediatric (<12 years) and 15 adolescent/adult (≥12 years) patients. Three patients with more than 24 months of follow-up are enrolled in the long-term follow-up study LTF-303.
Ninety percent (9/10) of patients evaluable for TI had achieved it, with median weighted average Hb levels of 12.2 g/dL (min–max: 11.4–12.8 g/dL) during TI. All nine patients continued to maintain TI for a median duration of 15.2 months (min–max: 12.1–21.3 months) as of the data cutoff.
Ninety percent (18/20) of patients with at least five months of follow-up had not received a transfusion for at least 3.5 months and total Hb was near normal in most, with the median total Hb at Months 6, 12 and 18 at 11.5 (n=17), 12.3 (n=11) and 12.2 g/dL (n=8), respectively. HbAT87Q levels were stable over time: 8.7 g/dL at Month 6; 9.3 g/dL at Month 12; and 9.4 g/dL at Month 18.
In an exploratory analysis, bone marrow from nine patients who had reached 12 months of follow-up and were transfusion independent was evaluated for myeloid to erythroid ratio. A low myeloid to erythroid ratio is a key feature of abnormal bone marrow RBC production that is characteristic of patients with TDT.
In all nine patients, an increase in the myeloid to erythroid ratio was observed, suggesting improvement in bone marrow RBC production. A trend toward normalization of soluble transferrin receptor, a marker of RBC production, and reticulocyte counts, a marker of hemolysis or RBC destruction, was also observed. The trend toward normalization in RBC production supports the disease-modifying potential of LentiGlobin for β-thalassemia for patients with TDT.
Northstar-3 (HGB-212) Efficacy
As of September 30, 2019, 13 patients (eight β0/β0, two β0/IVS-I-110, three homozygous IVS-I-110 genotypes) were treated and had a median follow-up of 8.8 months (min–max: 2.5–20.0 months). Median age at enrollment was 17 years of age (min–max: 7–33 years); four patients were under 12 years of age.
Two patients had at least 12 months of follow-up and were evaluable for TI. Both patients, one patient with a β0/β0 genotype and one pediatric patient with a β0/IVS-I-110 genotype, achieved TI, and continued to maintain it with Hb levels of 13.2 g/dL and 10.4 g/dL, respectively, at last visit.
In addition, nine of 11 patients with at least six months of follow-up did not receive a transfusion for more than three months as of last follow-up. In these patients, total Hb levels ranged from 8.3–14.2 g/dL at last visit.
LentiGlobin for β-thalassemia Safety
Non-serious adverse events (AEs) observed during the HGB-204, HGB-207 and HGB-212 clinical studies that were attributed to LentiGlobin for β-thalassemia were hot flush, dyspnoea, abdominal pain, pain in extremities, thrombocytopenia, leukopenia, neutropenia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for β-thalassemia for TDT.
Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.
With more than five years of follow-up to date, there have been no new unexpected safety events, no deaths, no graft failure and no cases of vector-mediated replication competent lentivirus or clonal dominance. In addition, there have been no new reports of veno-occlusive liver disease (VOD) as of the data cutoff presented at ASH.
About LentiGlobin for β-Thalassemia (betibeglogene autotemcel)
The European Commission granted conditional marketing authorization for LentiGlobin for β-thalassemia, to be marketed as ZYNTEGLO™ (autologous CD34+ cells encoding βA-T87Q-globin gene) gene therapy, for patients 12 years and older with TDT who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.
TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.
LentiGlobin for β-thalassemia adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.
The conditional marketing authorization for ZYNTEGLO is only valid in the 28 member states of the EU as well as Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).
The U.S. Food and Drug Administration granted LentiGlobin for β-thalassemia Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.
By the end of 2019, bluebird bio plans to initiate rolling submission of a Biologics Licensing Application (BLA) of LentiGlobin for β-thalassemia in the U.S. for the treatment of patients with TDT who do not have a β0/β0 genotype. bluebird bio is engaged with the FDA in discussions regarding the requirements and timing of the various components of the rolling BLA submission and, subject to these ongoing discussions, the company is currently planning to complete the BLA submission in the first half of 2020.
LentiGlobin for β-thalassemia continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).
bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for β-thalassemia. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, we’re developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, we’re working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.
bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, β-thalassemia and multiple myeloma, using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.
Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.
ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of bluebird bio, Inc.
The full common name for ZYNTEGLO: A genetically modified autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced with lentiviral vector encoding the βA-T87Q-globin gene.
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 views with respect to the potential for LentiGlobin to treat transfusion-dependent β-thalassemia (TDT). 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 to treat TDT will not continue or be repeated in our ongoing or planned clinical trials or in the commercial context, risks that the current or planned clinical trials of our product candidates will be insufficient to support future regulatory submissions or to support marketing approval in the US, the risk that the ability to submit and obtain approval of a BLA is ultimately an FDA review decision and the FDA may impose additional requirements before we can submit or obtain approval of a BLA, or before we are able to treat patients in the commercial context, 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.
Investors:
Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com
or
Media:
Catherine Falcetti, 617-583-3411
cfalcetti@bluebirdbio.com
Exhibit 99.3
bluebird bio and Bristol-Myers Squibb Present Updated Data from Ongoing Phase 1 Study of BCMA-Targeted CAR T Cell Therapy bb21217 in Relapsed/Refractory Multiple Myeloma at 61st ASH Annual Meeting and Exposition
Safety profile consistent with known toxicities of CAR T therapies
CAR T persistence observed in 8/10 evaluable responders at Month 6 and 2/2 evaluable responders at Month 18
CAMBRIDGE, Mass., & PRINCETON, NJ – December 9, 2019 – bluebird bio, Inc. (Nasdaq: BLUE) and Bristol-Myers Squibb (NYSE: BMY) announced updated safety and efficacy results from the ongoing Phase 1 study (CRB-402) of bb21217, an investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy being studied in patients with relapsed/refractory multiple myeloma (R/RMM). The data were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.
bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the idecabtagene vicleucel (ide-cel; bb2121) CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention to increase the in vivo persistence of CAR T cells.
“Early data from the CRB-402 study in heavily pre-treated patients (median of six prior lines) with relapsed/refractory multiple myeloma demonstrate the potential for durable responses following bb21217 CAR T cell treatment, with a median duration of response of 11.1 months at the 150 x 106 CAR+ T cell dose level,” said David Davidson, M.D., chief medical officer, bluebird bio. “Consistent with the hypothesis underlying the bb21217 program that memory-like phenotype T cells may survive longer in vivo, we have observed durable CAR T cell persistence in evaluable patients (n=2/2) with ongoing response at up to 18 months following treatment. We are continuing to recruit additional patients in the study and performing ongoing assessments of the functional persistence of bb21217, as well as its potential correlation to durability of response.”
CRB-402, the first in-human study of bb21217 in patients with R/RMM, is 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, open-label, multi-site Phase 1 study of bb21217 in adults with R/RMM with a projected final enrollment of 74 patients. The dose escalation part of CRB-402 is complete, and the dose expansion part of the study is ongoing.
“The data of CRB-402 provide additional support that targeting BCMA with a CAR T therapy could be beneficial in treating relapsed/refractory multiple myeloma, particularly for heavily pre-treated patients,” said Kristen Hege, M.D., Senior Vice President, Hematology/Oncology and Cell Therapy, Early Clinical Development for Bristol-Myers Squibb. “We have observed durable responses with bb21217 in this study and look forward to further results.”
“One of the challenges in treating patients with relapsed/refractory multiple myeloma is that they often become resistant to currently available therapies and response durations generally shorten with each subsequent therapy,” said presenting author Jesus G. Berdeja, M.D., Sarah Cannon Center for Blood Cancers, Nashville, Tennessee. “In this heavily-treated patient population, we are encouraged by the results with bb21217 treatment in this ongoing study.”
As of the September 4, 2019 cutoff date, data include results for 38 treated patients. Twenty-four patients received bb21217 in the dose escalation cohort at three dose levels (12 at 150 x 106 CAR+ T cells; six at 300 x 106 CAR+ T cells; and six at 450 x 106 CAR+ T cells). Fourteen additional patients received bb21217 in the dose expansion cohort at two dose levels (8 at 300 x 106 CAR+ T cells and 6 at 450 x 106 CAR+ T cells). The patients had a median of six prior lines of therapy (min – max; 3 – 17 lines) and 82% had at least one prior autologous stem cell transplant. High-risk cytogenetics were reported in 34% of patients and 95% of patients received prior treatment with an anti-CD38 antibody. All patients treated in CRB-402 (n=38) had previously received at least three prior lines of therapy, including an immunomodulatory agent and proteasome inhibitor. The enrollment criteria for the dose expansion cohort required all enrolled patients (n=14) to be refractory to their last prior line of therapy and have previously received an anti-CD38 antibody.
Safety Results
As of the data cutoff, the adverse events observed with bb21217 were consistent with known toxicities of CAR T therapies, regardless of dose level.
Of the 38 treated patients, the most common Grade 3/4 toxicities include neutropenia (82%), leukopenia (55%), thrombocytopenia (55%), anemia (50%), lymphopenia (34%), hypophosphatemia (21%), hyponatremia (13%) and febrile neutropenia (11%). Grade 3/4 infections were reported in seven patients (18%).
Twenty-five of 38 patients (66%) developed bb21217-related cytokine release syndrome (CRS); 12 Grade 1, 11 Grade 2, one Grade 3 and one Grade 5 (death). The fatal CRS event occurred at the 450 x 106 CAR+ T cells dose level, after 15 days of follow-up. Nine of 38 (24%) patients developed neurotoxicity; three Grade 1, three Grade 2, two Grade 3 (one with vertigo/dizziness and one with encephalopathy) 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.
Efficacy Results
As of the data cutoff, 33 of the 38 patients were evaluable for clinical response as defined per the International Myeloma Working Group Uniform Response Criteria for multiple myeloma.
Twelve patients were evaluable in the 150 x 106 CAR+ T cells cohort, with a median follow-up of 17.6 months (min – max; 12 – 23 months). Ten of 12 (83%) evaluable patients (defined as treated patients with ≥ two months of response data or progressive disease/death/lost to follow-up within <=2 months) in the 150 x 106 CAR+ T cells cohort demonstrated clinical response, including four with a stringent complete response (sCR) or complete response (CR), and six with a very good partial response (VGPR). Among the ten confirmed responders, the median duration of response was 11.1 months (95% Confidence Interval (CI); 3.3 – not estimable).
As of the data cutoff, follow-up within the two higher dose cohorts (300 x 106 and 450 x 106 CAR+ T cells) remains early and none of the confirmed responders have experienced disease progression. In the 300 x
106 CAR+ T cells cohort, 14 patients were evaluable for response and six of the 14 (43%) evaluable patients demonstrated clinical response, including four with a VGPR and two with a partial response (PR), with a median follow-up of four months (min – max; 2 – 10 months). In the 450 x 106 CAR+ T cells cohort, seven patients were evaluable for response and four of the seven (57%) evaluable patients demonstrated clinical response, including one with a sCR, two with a VGPR and one with a PR, with a median follow-up of 3.3 months (min – max; <1 – 6 months).
Evidence of myeloma in the bone marrow, known as minimal residual disease (MRD), was undetectable by next-generation sequencing at a sensitivity level of 10-5 in 94% (n=16/17) of all confirmed responders who had evaluable bone marrow samples (patients with > PR and > 1 valid post-baseline MRD assessment).
As of the data cutoff, CAR T cell persistence was observed in eight of ten patients with ongoing response and evaluable at six months, and two out of two patients with ongoing response and evaluable at 18 months.
The dose expansion part of the CRB-402 study is ongoing to further recruit patients and explore bb21217 at the 450 x 106 CAR+ T cells dose cohort, assess functional persistence of bb21217 and durability of response.
About bb21217 for Multiple Myeloma
bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention to increase the in vivo persistence of CAR T cells bb21217 is being developed in partnership between bluebird bio and Bristol-Myers Squibb.
The clinical development program for bb21217 includes the ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study of bb21217 in patients with R/RMM, designed to assess safety, pharmacokinetics, efficacy and duration of effect. CRB-402 is a two-part (completed dose escalation and ongoing dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with R/RMM with a projected final enrollment of 74 patients. For more information visit: clinicaltrials.gov using identifier NCT03274219.
bb21217 is not approved for any indication in any geography.
About Multiple Myeloma
Multiple myeloma is a cancer of certain cells in the blood, called plasma cells. The cause of multiple myeloma is not known, and currently there is no cure. However, there are a number of treatment options available that can lead to response. For some people with multiple myeloma, response can last many years. Patients who have already been treated with some available therapies but continue to have progression of their disease have “relapsed” and “refractory” multiple myeloma, meaning their cancer has reoccurred after they have received initial treatments. Patients with relapsed and refractory multiple myeloma have fewer treatment options.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, we’re developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs,
we’re working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.
bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, β-thalassemia and multiple myeloma, using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.
Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.
bluebird bio is a trademark of bluebird bio, Inc.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Bristol-Myers Squibb: Advancing Cancer Research
At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.
Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.
Bristol-Myers Squibb Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results,
goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that bb21217 may not achieve its primary study endpoints or receive regulatory approval for the indication described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate for such indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol-Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
Bluebird bio Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that bb21217 may not achieve its primary study endpoints or receive regulatory approval for the indication described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate for such indication described in this release will be commercially successful, and that the collaboration with Bristol-Myers Squibb may not continue or be successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K for the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, bluebird bio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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For Bristol-Myers Squibb
Investors:
Tim Power, 609-252-7509
Timothy.Power@bms.com
or
Media:
Rose Weldon, 609-252-3345
Rose.Weldon@bms.com
media@bms.com
For bluebird bio
Investors:
Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com
or
Media:
Victoria von Rinteln, 617-914-8774
vvonrinteln@bluebirdbio.com