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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

Gene therapy being developed as a one-time treatment to address the underlying cause of the disease by inserting a functional copy of the human IDUA gene into a patient’s own hematopoietic stem cells HURCULES study to enroll 40 patients at clinical sites across the U.S. and Europe TOKYO, LONDON and BOSTON, Feb. 05, 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 first patient has been randomized at the M Health Fairview Masonic Children’s Hospital in a registrational trial evaluating the efficacy and safety of OTL-203, an investigational hematopoietic stem cell (HSC) gene therapy, in patients with the Hurler subtype of mucopolysaccharidosis type I (MPS-IH). The trial, referred to as HURCULES, compares treatment with OTL-203 to standard of care with allogeneic hematopoietic stem cell transplant (HSCT), and is expected to enroll 40 MPS-IH patients at sites across the U.S. and Europe. MPS-I is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme resulting in the accumulation of glycosaminoglycans (GAGs) in multiple organs, including the musculoskeletal and central nervous systems, as well as the heart, eyes, and ears. It is estimated to occur globally in 1 in 100,000 live births. Approximately 60 percent of children born with MPS-I have the most severe subtype, MPS-IH, also called Hurler syndrome, and rarely live past the age of 10 when untreated. Current treatment options for MPS-IH include allogeneic hematopoietic stem cell transplant (HSCT) and enzyme replacement therapy (ERT), both of which have significant limitations. “This is a substantial milestone in the development of OTL-203 as we work toward bringing an important new treatment option to children with MPS-IH and their families,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics. “Previously reported results from an earlier proof-of-concept study in patients showed robust metabolic correction, continued cognitive, motor, and physical development, as well as early improvements in skeletal, ocular and auditory health demonstrating that one-time treatment with OTL-203 has the potential to positively impact a broad range of clinical manifestations not fully addressed by the current standard of care.” In an earlier single-center proof-of-concept (PoC) study, eight patients diagnosed with MPS-IH were treated at Ospedale San Raffaele in Milan, Italy with investigational OTL-203 between July 2018 and December 2019. Throughout the follow-up period, a total of 26 serious adverse events (SAEs) were observed. The events were related to known complications of MPS-IH already present prior to treatment, protocol procedures or general illnesses of childhood, and all have resolved. One patient experienced an acute hypersensitivity reaction that was considered probably related to HSC gene therapy. OTL-203 has received Fast Track and Rare Pediatric Disease (RPD) designations from the U.S. Food and Drug Administration (FDA), as well as priority medicines (PRIME) status from the European Medicines Agency (EMA). The program was originated by, and initially developed in partnership with, the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) in Milan, Italy. “The complications associated with MPS-IH have a detrimental impact on patients’ quality of life, and while transplantation may help improve outcomes, it is associated with significant morbidity and mortality,” said Paul Orchard, M.D., a study investigator and professor in the Division of Pediatric Blood and Marrow Transplantation and Cellular Therapy Program at the University of Minnesota Medical School. “New options are needed to better address some of the more severe symptoms of the disease, such as neurocognitive function, growth and other skeletal issues. We look forward to working with the team at Orchard Therapeutics and other clinical sites around the world to facilitate enrollment in this study and characterize the potential clinical impact of OTL-203 on MPS-IH.” Currently, the University of Minnesota is actively recruiting patients with additional trial sites expected to begin recruitment in the coming months. Summary of Previous OTL-203 Clinical Results Interim results from the earlier PoC study published in The New England Journal of Medicine showed all patients had supraphysiological IDUA enzyme activity with an associated sustained decrease in GAG levels and stable cognitive performance post-treatment. In addition, all participants had progressed along expected growth percentiles of healthy children and exhibited longitudinal growth that was considered within the normal range adjusted for age and gender. In subsequent follow-up, study investigators have observed progressive acquisition of fine and gross motor skills, as well as evidence of continued growth within normal range and improvements in skeletal health with a median follow-up of 3.78 years (range: 3.14 to 4.58 years) as of May 2023. In addition, Dr. Maria Ester Bernardo, clinical coordinator, pediatric clinical research unit at SR-TIGET and the principal investigator of the PoC study, detailed the first findings on other treatment outcomes, including ocular (eye) symptoms and auditory (hearing) function at the European Society of Cell and Gene Therapy (ESGCT) 30th Annual Congress. The presentation outlined favorable results for disease manifestations not fully addressed by the current standard of care and further highlights the potential of genetically repaired HSCs to migrate into and correct abnormalities in multiple tissues and organs. Throughout the PoC study, treatment with OTL-203 has been generally well-tolerated with a safety profile consistent with the selected conditioning regimen. The viral vector integration profile was comparable with other Orchard Therapeutics lentiviral-based HSC gene therapy studies, and all participants had a stable and highly polyclonal repertoire. As part of the study, ERT was discontinued at least three weeks prior to any patient receiving gene therapy, and none of those patients needed to re-start ERT post-treatment. Patients who entered the study with anti-IDUA antibodies present because of prior ERT treatment were no longer antibody positive within two months of treatment with OTL-203. About the HURCULES StudyHURCULES—a study name that combines the target indication HURler syndrome and HerCULES, the classical mythological character—is a multi-center, randomized, active controlled clinical trial designed to evaluate the efficacy and safety of OTL-203 in patients with MPS-IH compared to standard of care with allogeneic HSCT. A total of 40 patients with a confirmed diagnosis of MPS-IH who meet the study inclusion criteria are being randomized 1:1 to receive either OTL-203 or allogeneic HSCT. The study is powered to demonstrate superiority of OTL-203 over allogeneic HSCT. The primary endpoint, which will be measured at two years post-treatment, comprises a composite of clinically meaningful outcomes, including death, the need for rescue transplant, treatment failure, immunological complications, as well as severe cognitive and/or growth impairment. Secondary endpoints include biochemical markers, additional clinical assessments, as well as safety and tolerability. The company expects to activate six sites in the United States and Europe. For more information, please visit www.clinicaltrials.gov (NCT06149403). About MPS-IMucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to break down sugar molecules called glycosaminoglycans (GAGs). The accumulation of GAGs across multiple organ systems results in multiple symptomatic manifestations of the disease including severe neurocognitive impairment, skeletal deformities, cardiovascular and pulmonary complications, impaired motor function, loss of hearing and corneal clouding. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I. Approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome (MPS-IH), and rarely live past the age of 10 when untreated. Treatment options for MPS-I include hematopoietic stem cell transplant and enzyme replacement therapy, both of which have limitations, such as inadequate impact on some of the more severe manifestations of disease, as well as significant morbidity and mortality. At present, Newborn Screening (NBS) for MPS-I has been established in multiple geographies, including the United States and Europe. About OTL-203OTL-203 is an investigational hematopoietic stem cell gene therapy being developed for the treatment of MPS-IH. It uses a modified virus to insert a functional copy of the human IDUA gene into a patient’s cells. OTL-203 was originated by, and initially developed in partnership with, the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. OTL-203 has received Rare Pediatric Disease (RPD) and Fast Track designations from the U.S. FDA, as well as priority medicines (PRIME) status from the EMA. 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, as a vital part of Kyowa Kirin’s global business, Orchard continuing to advance 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: https://www.kyowakirin.com.

Three oral presentations and seven posters highlight transformative potential of HSC gene therapy and newborn screening to address severe neurometabolic diseasesBOSTON and LONDON, Feb. 02, 2024 (GLOBE NEWSWIRE) -- Orchard Therapeutics, a global gene therapy leader recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe, today announced 10 presentations from across its neurometabolic portfolio will be featured at the 20th Annual WORLDSymposium™ taking place February 4-9, 2024, in San Diego, California. Featured presentations include updated neurocognitive and biochemical results from an ongoing proof-of-concept study of investigational OTL-201 in mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A, with median follow-up now extending to 2.75 years (ranging from 24 to 39 months). Additional data highlights include several accepted abstracts detailing newborn screening efforts to support the timely and accurate diagnosis of metachromatic leukodystrophy (MLD), as well as an encore presentation showcasing long-term results from an updated integrated analysis of 39 patients with MLD treated with investigational OTL-200, which comprises key components of the clinical data package of the Biologics License Application (BLA) currently under Priority Review by the U.S. Food and Drug Administration. In addition to the data presentations outlined below, the company will also host a sponsored symposium on Monday, February 5, at 11:45 a.m., titled “Momentum, Leadership & Diagnosis: Changing the paradigm for MLD,” featuring expert speakers from different regions sharing their knowledge and experience to establish new standards and advance newborn screening through interdisciplinary collaboration. Oral presentation details are as follows (all times in PST; * denotes corresponding poster): Title: Clinical outcomes and sustained biochemical engraftment following ex-vivo autologous stem cell gene therapy for Mucopolysaccharidosis Type IIIA*Date/Time: Wednesday, February 7 at 8:12 a.m.Presenter: Simon Jones Title: Atidarsagene autotemcel (autologous hematopoietic stem cell gene therapy) preserves cognitive and motor development in early-onset metachromatic leukodystrophy with up to 12 years follow-up*Date/Time: Wednesday, February 7 at 8:24 a.m.Presenter: Francesca Fumagalli Title: Results of Prospective Newborn Screening for Metachromatic leukodystrophy in Germany and AustriaDate/Time: Friday, February 9 at 8:36 a.m.Presenter: Petra Oliva Poster presentation details are as follows (all times in PST; * denotes corresponding oral presentation): Title: A UK-based pre-pilot newborn screening study for Metachromatic Leukodystrophy identified a late infantile caseDate/Time: Tuesday, February 6 from 3:00-5:00 p.m.Presenting Author: Teresa WuPoster #: 349 Title: Atidarsagene autotemcel (autologous hematopoietic stem cell gene therapy) preserves cognitive and motor development in early-onset metachromatic leukodystrophy with up to 12 years follow-up*Date/Time: Wednesday, February 7 from 3:00-5:00 p.m.Presenting Author: Francesca FumagalliPoster #: 092 Title: Lentiviral hematopoietic stem cell gene therapy (atidarsagene autotemcel) for late juvenile Metachromatic leukodystrophy (MLD)Date/Time: Wednesday, February 7 from 3:00-5:00 p.m.Presenter: Francesca FumagalliPoster #: 096 Title: Compassionate use of lentiviral gene therapy for metachromatic leukodystrophyDate/Time: Wednesday, February 7 from 3:00-5:00 p.m.Presenting Author: Paul OrchardPoster #: 250 Title: Design of a multi-center randomized active controlled phase 3 clinical trial (HURCULES) evaluating the safety and efficacy of OTL-203 in patients with MPS-IH versus standard of care with allogeneic hematopoietic stem cell transplantationDate/Time: Wednesday, February 7 from 3:00-5:00 p.m.Presenting Author: Paul OrchardPoster #: 249 Title: Clinical outcomes and sustained biochemical engraftment following ex-vivo autologous stem cell gene therapy for Mucopolysaccharidosis Type IIIA*Date/Time: Wednesday, February 7 from 3:00-5:00 p.m.Presenting Author: Simon JonesPoster #: 166 Title: Cost-effectiveness framework by tandem mass spectrometry (TMS) for newborn screening of Metachromatic Leukodystrophy (MLD) in the United States (US)Date/Time: Thursday, February 8 from 3:00-5:00 p.m.Presenting Author: Karen BeanPoster #: 030 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 Kirin Kyowa 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 and rare diseases. 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: https://www.kyowakirin.com.