Hydroxycarbamide

SOMERVILLE, Mass.--( BUSINESS WIRE )--bluebird bio, Inc. (Nasdaq: BLUE) today announced new and updated data from LYFGENIA™ (lovotobegligene autotemcel, or lovo-cel) gene therapy for patients with sickle cell disease who have a history of vaso-occlusive events (VOEs). The data will be presented at the 66 th American Society of Hematology (ASH) Annual Meeting and Exposition in an oral presentation on Sunday, December 8 at 9:30 a.m. Pacific Time and a poster presentation on Sunday, December 8 at 6 p.m. Pacific Time. As of July 2024, 70 patients were treated across the full lovo-cel clinical development program, with follow-up beyond 9 years in the earliest treated patients. “ Data presented at ASH demonstrate that the potentially transformative benefits of LYFGENIA are sustained through additional long-term follow-up and consistent across sub-populations, including patients with overt stroke, not studied in any other clinical development program of gene therapy for sickle cell disease.” said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “ These data continue to distinguish LYFGENIA as the most deeply studied gene therapy for sickle cell disease, with the most patients treated, longest follow-up, and broadest range of clinical presentations evaluated across the field.” Updated efficacy data continue to support sustained, transformational impact on VOE burden and hematologic markers of disease An update on clinical response to lovo-cel in patients living with sickle cell disease focused on 58 patients who received lovo-cel in the HGB-206 Group C (n=36) and HGB-210 (n=22) studies, following enhancements to the manufacturing and treatment protocols, will be presented in Oral Presentation #511: An Update on Lovotibeglogene Autotemcel (lovo-cel) Clinical Trials for Sickle Cell Disease (SCD) and Analysis of Early Predictors of Response to Lovo-cel. Median follow-up time was 47.7 months (4.0 years), with 15 study participants having 5 or more years of follow-up. Stacy Rifkin-Zenenberg, DO, Hackensack Meridian Health said: “ These data demonstrate that the significant clinical benefits of lovo-cel for people living with sickle cell disease are durable through continued long-term follow-up. Additionally, the number of patients treated, and duration of follow-up, has enabled detailed exploration of the pharmacology and mechanism of action of LVV gene therapy for sickle cell disease, providing even greater support that one-time treatment with lovo-cel has the potential to permanently address the underlying cause of sickle cell disease.” As of the July 2024 cutoff date, all patients continued to have stable production of anti-sickling adult hemoglobin after infusion through last follow-up (median >40% HbA T87Q ) and total Hb at last visit was 12.4 (6.6, 15.1) g/dL and was stable without transfusion support post engraftment. VOEs and severe vaso-occlusive events (sVOEs) were eliminated or significantly reduced in all patients. Specific findings include: 36/38 (94.7%) of evaluable patients achieved complete resolution of severe VOEs (sVOE-CR) in the 6-18 months post infusion, maintained for a median (min, max) of 42.3 months (12.2, 70.5). 33/38 (86.8%) of evaluable patients achieved complete resolution of VOEs (VOE-CR), maintained for a median (min, max) of 42.4 (12.2, 70.5) months. 10/10 (100%) pediatric patients achieved complete resolution of VOEs and sVOEs. The safety profile of the lovo-cel treatment regimen was generally consistent with underlying sickle cell disease and the known effects of myeloablative conditioning. There were no cases of graft failure or graft-versus-host disease (GVHD), no vector-related complications, and no insertional oncogenesis. For complete safety information please refer to the U.S. Prescribing Information noted below. Data from patients with sickle cell disease and a history of overt stroke show no recurrence of stroke following treatment with lovo-cel The first focused analysis of the clinical impact of lovo-cel on patients with sickle cell disease with a history of stroke, including overt stroke, will be presented in Poster Presentation #3576: Participants with a History of Stroke in Lovotibeglogene Autotemcel (lovo-cel) Clinical Trials. Data showed that patients with a history of overt stroke remained stable without recurrent stroke up to 9 years post-treatment (n=6), with median follow-up of 6.5 years. Jennifer Jaroscak, MD, Director, Pediatric Non-Malignant Transplant, Medical University of South Carolina, said “ We are extremely pleased to report that no study participants with a history of overt or silent stroke experienced recurrent strokes following treatment with lovo-cel gene therapy, despite discontinuing transfusions. This finding is remarkable, as these patients face an exceedingly high risk of subsequent strokes, and transfusions alone provide only modest protection against secondary strokes. These data are unique in the field as lovo-cel is the only gene therapy for sickle cell disease with data on patients with a history of stroke.” Overt ischemic stroke is a devastating complication of sickle cell disease and requires lifelong chronic transfusions or allogeneic hematopoietic stem cell transplantation, which carry significant risk of complications. One in four patients living with sickle cell disease have a stroke by age 45. Other clinical outcomes in patients with a history of stroke—including expression of gene therapy derived anti-sickling hemoglobin (HBA T87Q ), improvements in total hemoglobin, and impact on other hematologic markers—were consistent with those patients’ respective study populations (HGB-206 Group A and HGB-206 Group C). The analysis also included 21 patients who had evidence of silent stroke based on available MRI data at screening. In this cohort there were no reports of recurrent overt or silent stroke among patients with follow-up MRIs, with a median 3.5 years follow-up (.48, 6.88 years). Silent ischemic stroke adversely affects neurocognitive function and is associated with increased risk of overt stroke. It occurs in an estimated 39% of patients with sickle cell disease. Safety findings for participants with a history of overt stroke did not differ from that in the overall treatment group. No increase in hypertension, bleeding issues, prolonged thrombocytopenia or catheter-related thromboses were observed. As previously reported, cases of acute myeloid leukemia were observed in two patients from the HGB-206 Group A cohort who were treated with an earlier version of the therapy prior to enhancements to the treatment and manufacturing processes. Both patients died due to aforementioned leukemia. About LYFGENIA™ (lovotibeglogene autotemcel) or lovo-cel LYFGENIA is a one-time ex-vivo lentiviral vector gene therapy approved for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events (VOEs). LYFGENIA works by adding a functional β-globin gene to patients’ own hematopoietic (blood) stem and progenitor cells (HSPCs). Durable production of adult hemoglobin with anti-sickling properties (HbAT87Q) is possible following successful engraftment. HbAT87Q has a similar oxygen-binding affinity to wild-type HbA, limits sickling of red blood cells and has the potential to reduce VOEs. The Phase 1/2 HGB-206 study of LYFGENIA is complete and the Phase 3 HGB-210 study evaluating LYFGENIA is ongoing. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for patients with sickle cell disease who have been treated with LYFGENIA in bluebird bio-sponsored clinical studies. Indication LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events (VOEs). Limitations of Use Following treatment with LYFGENIA, patients with α-thalassemia trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions. LYFGENIA has not been studied in patients with more than two α-globin gene deletions. Important Safety Information Boxed WARNING: HEMATOLOGIC MALIGNANCY Hematologic malignancy has occurred in patients treated with LYFGENIA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through integration site analysis at Months 6, 12, and as warranted. Hematologic Malignancy Hematologic malignancy has occurred in patients treated with LYFGENIA (Study 1, Group A). At the time of initial product approval, two patients treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A) developed acute myeloid leukemia (AML). One patient with α-thalassemia trait (Study 1, Group C) has been diagnosed with myelodysplastic syndrome (MDS). The additional hematopoietic stress associated with mobilization, conditioning, and infusion of LYFGENIA, including the need to regenerate the hematopoietic system, may increase the risk of a hematologic malignancy. Patients with sickle cell disease have an increased risk of hematologic malignancy as compared to the general population. Patients treated with LYFGENIA may develop hematologic malignancies and should have lifelong monitoring. Monitor for hematologic malignancies with a complete blood count (with differential) at least every 6 months for at least 15 years after treatment with LYFGENIA, and integration site analysis at Months 6, 12, and as warranted. In the event that a malignancy occurs, contact bluebird bio at 1-833-999-6378 for reporting and to obtain instructions on collection of samples for testing. Post-Marketing Long Term Follow-Up Study: Patients who intend to receive treatment with LYFGENIA are encouraged to enroll in the study, as available, to assess the long-term safety of LYFGENIA and the risk of malignancies occurring after treatment with LYFGENIA by calling bluebird bio at 1-833-999-6378. The study includes monitoring (at pre-specified intervals) for clonal expansion. Delayed Platelet Engraftment Delayed platelet engraftment has been observed with LYFGENIA. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia. Two patients (4%) required more than 100 days post treatment with LYFGENIA to achieve platelet engraftment. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with LYFGENIA. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 0.5 × 109 cells/L obtained on different days by Day 43 after infusion of LYFGENIA. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with LYFGENIA, provide rescue treatment with the back-up collection of CD34+ cells. Insertional Oncogenesis There is a potential risk of lentiviral vector-mediated insertional oncogenesis after treatment with LYFGENIA. Hypersensitivity Reactions Allergic reactions may occur with the infusion of LYFGENIA. The dimethyl sulfoxide (DMSO) or dextran 40 in LYFGENIA may cause hypersensitivity reactions, including anaphylaxis. Anti-retroviral Use Patients should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization and until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells. Hydroxyurea Use Patients should not take hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed. If hydroxyurea is administered between mobilization and conditioning, discontinue 2 days prior to initiation of conditioning. Iron Chelation Drug-drug interactions between iron chelators and the mobilization process and myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of mobilization or conditioning. Do not administer myelosuppressive iron chelators (e.g., deferiprone) for 6 months post-treatment with LYFGENIA. Non-myelosuppressive iron chelation should be restarted no sooner than 3 months after LYFGENIA infusion. Phlebotomy can be used in lieu of iron chelation, when appropriate. Interference with PCR-based Testing Patients who have received LYFGENIA are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a possible false-positive PCR assay test result for HIV. Therefore, patients who have received LYFGENIA should not be screened for HIV infection using a PCR-based assay. Adverse Reactions The most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia. Three patients died during LYFGENIA clinical trials; one from sudden cardiac death due to underlying disease and two from acute myeloid leukemia who were treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A). Pregnancy/Lactation Advise patients of the risks associated with myeloablative conditioning agents, including on pregnancy and fertility. LYFGENIA should not be administered to women who are pregnant, and pregnancy after LYFGENIA infusion should be discussed with the treating physician. LYFGENIA is not recommended for women who are breastfeeding, and breastfeeding after LYFGENIA infusion should be discussed with the treating physician. Females and Males of Reproductive Potential A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before LYFGENIA administration. Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra-uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of LYFGENIA. Advise patients of the options for fertility preservation. Please see full Prescribing Information for LYFGENIA including Boxed WARNING and Medication Guide . About bluebird bio, Inc. bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days. Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers. With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward. bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding the therapeutic potential of LYFGENIA. Such forward-looking statements are based on historical performance and current expectations and projections about bluebird’s future 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 bluebird’s control and could cause bluebird’s future goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. 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, 2023, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC. These risks and uncertainties include, but are not limited to: the risk that the efficacy and safety results from bluebird’s prior and ongoing clinical trials will not continue or be seen in the commercial context; the risk that there is not sufficient patient demand or payer reimbursement to support continued commercialization of LYFGENIA; the risk of insertional oncogenic or other safety events associated with lentiviral vector, drug product, or myeloablation, including the risk of hematologic malignancy; and the risk that bluebird’s products, including LYFGENIA, will not be successfully commercialized. 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.

SOMERVILLE, Mass.--( BUSINESS WIRE )--bluebird bio, Inc. (Nasdaq: BLUE) today announced updated data from patients with beta-thalassemia who require regular blood transfusions treated with betibeglogene autotemcel (beti-cel, approved commercially as ZYNTEGLO™) in clinical studies. The data was presented today at the 66 th American Society of Hematology (ASH) Annual Meeting and Exposition. “ Updated follow-up data of up to 10 years showed that patients treated with beti-cel in clinical trials experienced durable transfusion independence and normal or near-normal hemoglobin, regardless of genotype and age, and a continued favorable safety profile”, said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “ We are deeply grateful for the ongoing commitment of our investigators, patients, and study participants. Our collective efforts are not only advancing the field of gene therapy but also providing new hope and possibilities for individuals with severe genetic diseases." “ Data at ASH demonstrate the durability of beti-cel through 10 years of long-term follow-up, giving additional confidence in that the transformational outcomes observed in parent studies are sustained over time,” said Alexis Thompson, MD, MPH, Chief of the Division of Hematology at Children’s Hospital of Philadelphia, which is a Qualified Treatment Center for ZYNTEGLO. “ These long-term data demonstrate beti-cel’s continued positive impact on iron management outcomes over time, which can help inform treatment decisions by clinicians who are now using this therapy in the real-world setting.” Betibeglogene Autotemcel (beti-cel) Gene Addition Therapy results in durable Hemoglobin A (HbA) Production with up to 10 Years of Follow-Up in Participants with Transfusion-Dependent β-Thalassemia (Poster #2194) Long-term outcomes with beti-cel in adult and pediatric patients with TDT were presented in a poster session. The data focused on 63 adult and pediatric study participants who had received beti-cel in a Phase 1/2 or Phase 3 study. Two participants had 10 years of follow-up, and 51 (81.0%) participants had 5 or more years of follow-up. Additionally, iron status was assessed in study participants who achieved TI and discontinued chelation therapy. Results showed that majority of participants treated with beti-cel achieved TI. All participants achieved platelet and neutrophil engraftment. Specific findings showed: Of 63 patients, 52 (90.2% in Phase 3 studies and 68.2% in Phase 1/2 studies) achieved TI. All except one patient maintained TI through last follow-up. The median weighted average hemoglobin during TI was 10.2 mg/dL for Phase 1/2 studies and 11.2 mg/dL for Phase 3 studies. Achievement and maintenance of TI and median weighted average hemoglobin were similar across ages and genotypes. Study participants treated with beti-cel who achieved and maintained TI demonstrated effective restoration of iron homeostasis over time and reduced iron management burden. Among participants who achieved TI, improvements in serum ferritin and liver iron concentration were sustained through month 60. 28/37 (75.7%) study participants who achieved TI in Phase 3 studies are no longer undergoing iron chelation therapy. Both adult and pediatric health-related quality of life scores (HRQoL) remained above the normative population mean up to 60 months. All 26 participants who achieved TI and completed a questionnaire reported an overall benefit with beti-cel. The safety profile was consistent with known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. None of the study participants had a fatal event. No beti-cel–related serious adverse events were reported more than 2 years after infusion through last follow-up. No malignancies, insertional oncogenesis or vector-derived replication-competent lentivirus were reported in any study participants. Beti-cel was approved by the FDA in August 2022 and is commercially available in the United States as ZYNTEGLO. About ZYNTEGLO® (betibeglogene autotemcel) or beti-cel ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy approved for the treatment of beta-thalassemia in adult and pediatric patients who require regular red blood cell transfusions. ZYNTEGLO works by adding functional copies of a modified form of the beta-globin gene (β A-T87Q- globin gene) into a patient’s own hematopoietic (blood) stem and progenitor cells to enable the production of a modified functional adult hemoglobin (HbA T87Q ). Once a patient has the β A-T87Q- globin gene, they have the potential to increase ZYNTEGLO-derived adult hemoglobin (HbA T87Q ) and total hemoglobin to normal or near normal levels that can eliminate the need for regular red blood cell (RBC) transfusions. Indication ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions. Important Safety Information Delayed Platelet Engraftment Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Risk of Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells. Risk of Insertional Oncogenesis There is a potential risk of LVV mediated insertional oncogenesis after treatment with ZYNTEGLO. Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted. In the event that a malignancy occurs, contact bluebird bio at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing. Hypersensitivity Reactions Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis. Anti-retroviral and Hydroxyurea Use Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells. Interference with Serology Testing Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR‑based assay. Adverse Reactions The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia. Drug Interactions Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates. Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate. Pregnancy/Lactation Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility. ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician. ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician. Females and Males of Reproductive Potential A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration. Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO. Advise patients of the option to cryopreserve semen or ova before treatment if appropriate. Please see full Prescribing Information for ZYNTEGLO . About bluebird bio, Inc. bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days. Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers. With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward. bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding the therapeutic potential of ZYNTEGLO. Such forward-looking statements are based on historical performance and current expectations and projections about bluebird’s future 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 bluebird’s control and could cause bluebird’s future goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. 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, 2023, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC. These risks and uncertainties include, but are not limited to: the risk that the efficacy and safety results from bluebird’s prior and ongoing clinical trials will not continue or be seen in the commercial context; the risk that there is not sufficient patient demand or payer reimbursement to support continued commercialization of ZYNTEGLO; the risk of insertional oncogenic or other safety events associated with lentiviral vector, drug product, or myeloablation, including the risk of hematologic malignancy; and the risk that bluebird’s products, including ZYNTEGLO, will not be successfully commercialized. 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.