CD34

One-time treatment with Lenmeldy has shown the potential to restore enzymatic function to stop or slow disease progression, with up to 12 years of follow-up (median 6.76 years)TOKYO and LONDON and BOSTON, March 18, 2024 (GLOBE NEWSWIRE) -- Orchard Therapeutics, recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe, today announced the U.S. Food and Drug Administration (FDA) has approved Lenmeldy™ (atidarsagene autotemcel), formerly known as OTL-200, for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ)—collectively referred to as early-onset—metachromatic leukodystrophy (MLD). “The FDA approval of Lenmeldy opens up tremendous new possibilities for children in the U.S. with early-onset MLD who previously had no treatment options beyond supportive and end-of-life care,” said Bobby Gaspar, M.D., Ph.D., co-founder and chief executive officer of Orchard Therapeutics. “MLD is a rapidly progressing, life-limiting and ultimately fatal rare disease that has a devastating impact on afflicted children and their families. This achievement is the culmination of decades of research and development in partnership with our academic and clinical collaborators at the San Raffaele-Telethon Institute for Gene Therapy. I want to express my sincere gratitude to the patients and families who participated in our clinical trials as well as to the broader MLD community—we would not be here today without your contributions and support.” Dr. Gaspar continued, “I am also incredibly proud of the entire team at Orchard for their tireless effort to make this moment possible, and we look forward to ensuring broad and sustainable access to this remarkable innovation for eligible patients in need.” MLD is a rare, fatal genetic disorder caused by a mutation in the gene responsible for encoding the enzyme arylsulfatase A (ARSA) leading to neurological damage and developmental regression due to the accumulation of fats called sulfatides in the brain and other areas of the body which, when not broken down, damage the central nervous system over time. In its most severe form, babies develop normally but in late infancy start to rapidly lose the ability to walk, talk and interact with the world around them. These children eventually deteriorate into a vegetative state, which may require 24-hour intensive care, and the majority pass away within five years of disease onset, creating an enormous emotional and financial burden on the family. Lenmeldy aims to correct the underlying genetic cause of MLD by inserting one or more functional copies of the human ARSA gene ex vivo (outside the body) into the genome of a patient’s own hematopoietic stem cells (HSCs) using a lentiviral vector. The genetically repaired cells are infused back into the patient, where, once engrafted, they differentiate into multiple cell types, some of which migrate across the blood-brain barrier into the central nervous system and express the functional enzyme. This approach has the potential to restore enzymatic function to stop or slow disease progression with a single treatment. “This is a momentous occasion and I commend the FDA for recognizing the clinical impact Lenmeldy has on this cruel disease,” said Barbara Burton, M.D., attending physician, genetics, genomics and metabolism at the Ann & Robert H. Lurie Children’s Hospital of Chicago. “For too long, my colleagues and I have consoled families at their most vulnerable times—usually following an arduous diagnostic odyssey, coping with a dire prognosis and being told there were no treatments, and then having to watch their young child slip away. With this approval, we are now one significant step closer to ensuring future generations of children, families and healthcare professionals no longer need to experience first-hand the terrible manifestations this disease has on untreated patients.” “As a mother who lost a child to MLD, it is difficult to articulate how much of a watershed moment this is for patients, families and advocates,” said Maria Kefalas, Ph.D., co-founder of the Calliope Joy Foundation and a founding member of Cure MLD. “I, and so many others in our community, have made it our life’s work to end the horror caused by MLD so other families may not have to face the same terrible fate as ours. Today, we are closer than ever to making that vision a reality, but there’s still more work to be done. With the first therapy for this childhood disease now approved, we must act urgently and collaboratively to enable universal newborn screening for MLD in the U.S. so babies with these pathogenic mutations can be diagnosed and referred for appropriate treatment before the onset of symptoms.” Lenmeldy was granted Priority Review in September 2023. It was previously given both Rare Pediatric Disease (RPD) and Regenerative Medicine Advanced Therapy (RMAT) designations from FDA. In connection with the approval, Orchard Therapeutics received a Priority Review Voucher (PRV), which will be transferred to GSK in accordance with the terms of the original licensing agreement. Orchard Therapeutics will provide more details about the launch of Lenmeldy in the U.S. through a separate announcement this week. Overview of Clinical Development Program and Results The FDA approval of Lenmeldy is based on data from 37 pediatric patients with early-onset MLD, enrolled in two single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the gene therapy and compared with natural history data. All treated patients were administered Lenmeldy and subsequently monitored at Ospedale San Raffaele in Milan, Italy. With more than 12 years of follow-up in the earliest treated patients (median 6.76 years), treatment with Lenmeldy significantly extended overall survival and resulted in the preservation of motor function and cognitive skills in most late infantile MLD patients past ages at which untreated patients showed severe cognitive and motor impairments. Lenmeldy also resulted in the preservation of motor function and cognitive skills in some early juvenile MLD patients which is not expected when compared to untreated patients. The most common non-laboratory adverse reactions (incidence ≥ 10%) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%). The most common laboratory abnormalities were: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%). Please see below for additional details and Important Safety Information. About MLDMLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births based on existing literature. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.i About LenmeldyLenmeldy™ (atidarsagene autotemcel), formerly known as OTL-200, is the only approved therapy in the U.S. for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early-symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). For additional details about Lenmeldy, please refer to the full Prescribing Information. In Europe, Lenmeldy is known as Libmeldy®, where it has been approved by the European Commission (EC), UK Medicines and Healthcare products Regulatory Agency (MHRA), and Swiss Agency for Therapeutic Products (Swissmedic). For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website. The program was originated by and developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. It was licensed by Orchard Therapeutics from GSK in 2018. INDICATION LENMELDYTM (atidarsagene autotemcel) is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Thrombosis and Thromboembolic Events:Treatment with LENMELDY may increase the risk of thrombosis and thromboembolic events. A child with PSEJ MLD died after experiencing a left hemisphere cerebral infarction secondary to a thrombotic event in a large blood vessel approximately 1 year after treatment with LENMELDY. Evaluate the risk factors for thrombosis prior to and after LENMELDY infusion according to best clinical practice. Consider monitoring D-dimer levels after LENMELDY treatment. Encephalitis:Treatment with LENMELDY may increase the risk of encephalitis. A child with ESEJ developed a serious event of encephalitis after treatment with LENMELDY. The etiology of this event is unclear but attribution to LENMELDY cannot be ruled out. Treatment with LENMELDY may trigger a relapsing-remitting pattern of disease progression. No other events related to encephalitis have been reported during the clinical development of LENMELDY. Monitor children for signs or symptoms of encephalitis after LENMELDY treatment. Serious Infection:In the period between start of conditioning and within 1 year after LENMELDY treatment, severe Grade 3 infections occurred in 39% of all children (21% bacterial, 5% viral, 5% bacterial and viral or bacterial and fungal, and 8% unspecified). Grade 3 febrile neutropenia developed within 1 month after LENMELDY infusion in 82% of children. In the event of febrile neutropenia, monitor for signs and symptoms of infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated. Monitor children for signs and symptoms of infection after myeloablative conditioning and LENMELDY infusion and treat appropriately. Administer prophylactic antimicrobials according to best clinical practice. Veno-Occlusive Disease:Three children (8%) treated in clinical trials of LENMELDY developed veno-occlusive disease (VOD) with one Grade 4 SAE and two Grade 3 AEs. None of these three events met Hy’s Law criteria. Monitor children for signs and symptoms of VOD including liver function tests in all children during the first month after LENMELDY infusion. Consider prophylaxis for VOD with an anti-thrombotic such as defibrotide or ursodeoxycholic acid based on risk factors for VOD and best clinical practice. Delayed Platelet Engraftment (DPE):DPE has been observed with LENMELDY treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in children with prolonged thrombocytopenia. In clinical trials of LENMELDY, 4 (10%) children had delayed platelet engraftment after day 60 (range day 67-109), with 3 children requiring platelet transfusions until engraftment occurred. Patients should be informed of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding until platelet engraftment and recovery are achieved. Neutrophil Engraftment Failure: There is a potential risk of neutrophil engraftment failure after treatment with LENMELDY. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a child treated with LENMELDY, provide rescue treatment with the unmanipulated back-up collection of CD34+ cells. Insertional Oncogenesis: There is a potential risk of LVV-mediated insertional oncogenesis after treatment with LENMELDY. Children treated with LENMELDY may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) annually and integration site analysis as warranted for at least 15 years after treatment with LENMELDY. In the event that a malignancy occurs, contact Orchard Therapeutics at 1-888-878-0185 for reporting and to obtain instructions on collection of samples for testing. Hypersensitivity Reactions: The dimethyl sulfoxide (DMSO) in LENMELDY may cause hypersensitivity reactions, including anaphylaxis which is potentially life-threatening and requires immediate intervention. Hypersensitivity including anaphylaxis can occur in children with and without prior exposure to DSMO. Monitor for hypersensitivity reactions during infusion and after infusion. Anti-Retroviral Use: Children should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization, or for the expected duration of time needed for the elimination of the medications. Anti-retroviral medications may interfere with the manufacturing of LENMELDY. If a child requires antiretrovirals for HIV prophylaxis, initiation of LENMELDY treatment should be delayed until confirmation of a negative test for HIV. Interference With Serology Testing: Due to the likelihood of a false-positive test for HIV, children who have received LENMELDY should not be screened for HIV infection using a PCR-based assay. USE IN SPECIFIC POPULATIONS Females and Males of Reproductive Potential Pregnancy TestingAs a precautionary measure, a negative serum pregnancy test must be confirmed prior to the start of mobilization, and reconfirmed prior to conditioning procedures, and before administration of LENMELDY in females of childbearing potential. Contraception Consult the Prescribing Information of the mobilization and conditioning agents for information on the need for effective contraception. Males capable of fathering a child and females of childbearing age should use an effective method of contraception from start of mobilization through at least 6 months after administration of LENMELDY. InfertilityThere are no data on the effects of LENMELDY on fertility. Data are available on the risk of infertility with myeloablative conditioning. In clinical trials of LENMELDY, seven children (50% of females) developed ovarian failure. Advise children of the option to cryopreserve semen or ova before treatment, if appropriate. For additional safety information, please see the full Prescribing Information. About Orchard TherapeuticsOrchard Therapeutics, a Kyowa Kirin company, is a global gene therapy leader focused on ending the devastation caused by genetic and other severe diseases by discovering, developing, and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease with a single treatment. Founded in 2015, Orchard’s roots go back to some of the first research and clinical developments involving HSC gene therapy. Our team has played a central role in the evolution of this technology from a promising scientific idea to a potentially life-transforming reality. Today, Orchard is advancing a pipeline of HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist. For more information, please visit www.orchard-tx.com. About Kyowa KirinKyowa Kirin aims to discover novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients affected by a severe or rare disease. A shared commitment to our values, to sustainable growth, and to making people smile unites us across our four regions – Japan, Asia Pacific, North America, and EMEA/International. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com.______________________________iMahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature. Journal of Child Neurology 2010, DOI: http://doi.org.libproxy1.nus.edu.sg/10.1177/0883073809341669

SOMERVILLE, Mass.--(BUSINESS WIRE)-- bluebird bio, Inc. (NASDAQ: BLUE) (“bluebird bio”) today announced it has signed its first Medicaid outcomes-based agreement for LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel) with the state of Michigan. LYFGENIA is a one-time gene therapy approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events (VOEs). Approximately 50 percent of individuals living with sickle cell disease in the U.S. are insured by Medicaid. “Our commercial approach is built on the principle that people with sickle cell disease insured through Medicaid deserve the same timely access to gene therapy as patients with other forms of insurance,” said Tom Klima, chief commercial & operating officer, bluebird bio. “We are extremely pleased to have reached this agreement with Michigan Medicaid and with the momentum behind our reimbursement negotiations across the board just months following approval, which underscores payers’ shared commitment to equitable access and understanding of the value that LYFGENIA can bring to people living with sickle cell disease, their caregivers, and the healthcare system.” bluebird is an established leader in developing and implementing innovative, value-based contracting approaches. The Company has designed outcomes-based contract options unique to LYFGENIA that offer payers meaningful risk sharing tied to VOE-related hospitalizations—a claims-based metric that is directly correlated with clinical benefit and aligned with study endpoints in the LYFGENIA clinical development program—with patients followed for three years. bluebird’s outcomes-based contract offering for State Medicaid Agencies was designed with direct input from government payers to specifically address the challenges they face in adapting to provide access to one-time, transformative treatments, and reflects the Company’s unmatched experience delivering gene therapies in the commercial setting. bluebird is in ongoing discussions with more than 15 Medicaid agencies representing 80 percent of Medicaid-insured individuals in the U.S. Additionally, bluebird has signed multiple outcomes-based agreements for LYFGENIA with national commercial payer organizations representing dozens of downstream plans and covering approximately 200 million U.S. lives. bluebird is also engaged with the Center for Medicare and Medicaid Innovation (CMMI) on its Cell and Gene Therapy Access Demonstration Model, which is anticipated to start in 2025. 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 cells (HSCs). 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 and 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. bluebird bio and LYFGENIA are registered trademarks of bluebird bio, Inc. All rights reserved. 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. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding the momentum around the Company’s launch of LYFGENIA and its ability to successfully partner with payers and CMMI. 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, 2022, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. These risks and uncertainties include, but are not limited to: delays and challenges in bluebird’s commercialization and manufacturing of its products; 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

Results include pharmacokinetic and pharmacodynamic data, and post-hoc subgroup analyses of the Phase 3 GENESIS trial Presentations on Thursday, February 22, 2024 in San Antonio, Texas TEL AVIV, Israel, Feb. 16, 2024 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ/TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, today announced that new post-hoc subgroup analyses and pharmacodynamic data will be presented on APHEXDA® (motixafortide) for CD34+ hematopoietic stem cell (HSC) mobilization in patients with multiple myeloma at the 2024 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT®) and the Center for International Blood and Marrow Transplant Research (CIBMTR®), taking place February 21-24, 2024, in San Antonio, Texas. Results include pharmacokinetics (PK) and pharmacodynamics (PD) data as well as post-hoc subgroup analyses from the Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim, compared to placebo plus filgrastim (G-CSF), for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Phase 1 study results demonstrated an extended PD effect with complete receptor occupancy by motixafortide starting at a concentration of 3nM. In the GENESIS trial, post-hoc subgroup analyses based on baseline characteristics and risk factors for impaired HSC mobilization demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients. Poster Presentations at the 2024 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the ASTCT and the CIBMTR. Henry B. González Convention Center, San Antonio, Texas Poster Session Details Poster: Number 537. See abstract. Title: Motixafortide Enables Consistent, Robust Hematopoietic Stem Cell Collection (HSC) across Populations with Increased Impaired HSC Mobilization: A Sub-Group Analysis of the Genesis Study Presenter: Zachary D. Crees, MD, Washington University School of Medicine in St. Louis Poster Session: Myeloma - Clinical Date: Thursday, February 22, 2024 Time: 6:45 PM - 7:45 PM Poster: Number 535. See abstract. Title: Prolonged CXCR4 Receptor Occupancy By Motixafortide Following a Single Subcutaneous Injection Is Associated with Extended Mobilization of CD34+ Cells in Peripheral Blood for > 24 Hours Presenter: Ella Sorani, PhD, BioLineRx Ltd Poster Session: Myeloma - Clinical Date: Thursday, February 22, 2024 Time: 6:45 PM - 7:45 PM About the GENESIS Trial GENESIS (NCT 03246529) is a 2-part, Phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim (G-CSF), compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study. The primary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session. About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. According to the American Cancer Society, in 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S.1 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections. About APHEXDA® APHEXDA (motixafortide) is a CXCR4 antagonist with long receptor occupancy (greater than 72 hours) that, in combination with filgrastim (G-CSF), enables mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplantation in patients with multiple myeloma.2 INDICATION AND IMPORTANT SAFETY INFORMATION INDICATION APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide. WARNINGS AND PRECAUTIONS Anaphylactic Shock and Hypersensitivity Reactions: Anaphylactic shock and hypersensitivity reactions have occurred. Premedicate all patients with a triple drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor approximately 30-60 minutes prior to each dose of APHEXDA. Administer APHEXDA in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions. Monitor patients for 1 hour following APHEXDA administration and manage reactions promptly. Patients receiving negative chronotropic drugs (e.g., beta-blockers) may be more at risk for hypotension in the event of a hypersensitivity reaction and these drugs, when appropriate, should be replaced with non-chronotropic drugs. Injection Site Reactions: Injection site reactions (73%) including pain (53%), erythema (27%), and pruritus (24%) have occurred. Severe reactions occurred in 9% of patients. Premedicate with an analgesic premedication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments post-dose, as needed. Tumor Cell Mobilization in Patients with Leukemia: For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia. Leukocytosis: Administering APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use. Potential for Tumor Cell Mobilization: When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied. Embryo-fetal Toxicity: Based on its mechanism of action, APHEXDA can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating treatment with APHEXDA and advise use of effective contraception during treatment and for 8 days after the final dose. ADVERSE REACTIONS The most common adverse reactions (incidence >20%) in patients treated with APHEXDA were injection site reactions [73%, including pain (53%), erythema (27%), pruritus (24%)]; pruritus (38%); flushing (33%); back pain (21%). USE IN SPECIFIC POPULATIONS Pregnancy: Please see the important information in Warnings and Precautions under Embryo-fetal Toxicity. Lactation: There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Advise females that breastfeeding is not recommended during treatment with APHEXDA and for 8 days after the final dose. Pediatric Use: The safety and effectiveness of APHEXDA have not been established in pediatric patients. Please see the accompanying full Prescribing Information. About BioLineRx BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases. The company's first approved product is APHEXDA® (motixafortide) with an indication in the U.S. for stem cell mobilization for autologous transplantation in multiple myeloma. BioLineRx is advancing a pipeline of investigational medicines for patients with sickle cell disease, pancreatic cancer, and other solid tumors. Headquartered in Israel, and with operations in the U.S., the company is driving innovative therapeutics with end-to-end expertise in development and commercialization, ensuring life-changing discoveries move beyond the bench to the bedside. Learn more about who we are, what we do, and how we do it at , or on Twitter and LinkedIn.  Forward Looking Statement Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These include statements regarding management's expectations, beliefs and intentions regarding, among other things, the potential benefits of APHEXDA, the execution of the launch of APHEXDA and the plans and objectives of management for future operations and expectations and commercial potential of motixafortide, as well as its potential investigational uses. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials, and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; whether BioLineRx's collaboration partners will be able to execute on collaboration goals in a timely manner; whether the clinical trial results for APHEXDA will be predictive of real-world results; whether early stage clinical trial results, or pre-clinical results, will be predictive of, or repeatable in, later clinical trials; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates, including the degree and pace of market uptake of APHEXDA for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients; whether access to APHEXDA is achieved in a commercially viable manner and whether APHEXDA receives adequate reimbursement from third-party payors; BioLineRx's ability to establish, operationalize and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for and ability to access sufficient additional financing, including any unexpected costs or delays in the commercial launch of APHEXDA; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; the impact of the political and security situation in Israel on BioLineRx's business; and the impact of the COVID-19 pandemic, the Russian invasion of Ukraine, the declared war by Israel against Hamas and the military campaigns against Hamas and other terrorist organizations, which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 22, 2023. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law. American Cancer Society. Key Statistics About Multiple Myeloma. Atlanta, Ga: American Cancer Society; 2024. APHEXDA. Prescribing Information. BioLineRx Ltd; 2023. Contacts: United States John Lacey BioLineRx [email protected] Israel Moran Meir LifeSci Advisors, LLC [email protected] ©BioLineRx USA, Inc. 2024. All Rights Reserved. APHEXDA® is a registered trademark of BioLineRx Ltd. All names and trademarks are property of their respective owners. Logo - SOURCE BioLineRx Ltd.