Leukodystrophy, Metachromatic

Ten presentations at ESGCT 2024 detail the therapeutic potential and applicability of the company’s platform in rare neurometabolic diseases and beyond Nature manuscript highlights clinical results supporting long-term durability and safety profile of genetically corrected hematopoietic stem and progenitor cells Research letter detailing results from the world’s first prospective, population-based newborn study for metachromatic leukodystrophy recently published in the New England Journal of Medicine LONDON and BOSTON, Oct. 23, 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 multiple data presentations and publications highlighting the transformative potential of HSC gene therapy and newborn screening. Ten presentations (three oral and seven posters) from across its hematopoietic stem cell (HSC) gene therapy portfolio will be featured at the European Society of Gene and Cell Therapy (ESGCT) 31st Annual Congress taking place October 22-25, 2024, in Rome, Italy. Featured data include several accepted abstracts and encore presentations detailing clinical, biochemical and other functional outcomes from across the company’s commercial- and clinical-stage neurometabolic portfolio in metachromatic leukodystrophy (MLD), the Hurler subtype of mucopolysaccharidosis type I (MPS-IH), and mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A. Pertaining to earlier-stage pipeline programs, company researchers will also highlight the potential of the platform beyond rare neurometabolic conditions, including: An oral presentation of preclinical proof-of-concept data showing the therapeutic potential of OTL-104 for NOD2-deficient Crohn’s disease, a severe and treatment-refractory form of the condition;A poster presentation outlining the potential of HSC gene therapy as a mechanism to deliver therapeutic antibodies across the blood-brain-barrier and into the central nervous system; andAnother poster presentation detailing the feasibility of utilizing HSC gene therapy to provide stable and targeted immunotherapy for autoimmune disorders through the ability of HSCs to differentiate into T regulatory (Treg) cells engineered to express chimeric antigen receptors (CAR). This approach combines the durability of HSC gene therapy with the suppressive activity of autoantigen-specific CAR-Treg cells. Details of the oral presentations are as follows (all times in CEST): Title: Stem cell gene therapy for Childhood Dementias – a Sanfilippo storyDate/Time: Wednesday, October 23 at 9:00 a.m.Presenter: Brian Bigger#INV20 Title: Haematopoietic stem cell gene therapy as a treatment for NOD2-deficient severe Crohn’s DiseaseDate/Time: Thursday, October 24 at 10:45 a.m.Presenter: Piv Sagoo#OR064 Title: Lentiviral haematopoietic stem cell gene therapy (atidarsagene autotemcel) for late juvenile Metachromatic leukodystrophy (MLD)Date/Time: Friday, October 25 at 12:00 p.m.Presenter: Valeria Calbi#OR099 Details of the poster presentations are as follows (all times in CEST): Title: Lentiviral ex vivo autologous HSC gene therapy as a tool to deliver therapeutic antibodies beyond the blood brain barrierDate/Time: Tuesday, October 22 from 7:30 to 9:00 p.m.Presenter: Chiara Recchi#P0309 Title: HSC-derived CAR-Treg gene therapy: a novel approach for the treatment of multiple sclerosisDate/Time: Tuesday, October 22 from 7:30 to 9:00 p.m.Presenter: Lily Du#P0293 Title: Biological properties and clonality of engineered hematopoietic stem/progenitor cells persisting long-term after gene therapyDate/Time: Wednesday, October 23 from 1:30 to 3:00 p.m.Presenter: Pamela Quaranta#P0412 Title: Atidarsagene autotemcel (autologous hematopoietic stem cell gene therapy) preserves cognition, language, and speech and slows brain demyelination and atrophy in early-onset metachromatic leukodystrophy Date/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Valeria Calbi#P0880 Title: Unveiling myeloid-mediated enzymatic correction of ARSA-deficient neural cells in hematopoietic stem cell gene therapy for Metachromatic LeukodystrophyDate/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Vasco Meneghini#P0898 Title: Hematopoietic Stem Cell Gene Therapy for Hurler Syndrome (OTL-203): interim skeletal, neurological and systemic outcomes Date/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Valeria Calbi#P0886 Title: Hematopoietic stem cell-based gene therapy in Mucopolysaccharidosis type I Hurler (OTL-203): focus on skeletal damage and cross-correction mechanismsDate/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Ludovica Santi#P1016 Nature manuscript elucidates sustained long-term reconstitution and lineage commitment of genetically corrected HSPCs In a paper published online today in Nature, titled “Long-term lineage commitment is modulated by the underlying disease in hematopoietic stem cell gene therapy patients,” researchers from the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) detail clinical results elucidating the long-term reconstitution, lineage commitment and the incidence of somatic mutations of genetically corrected hematopoietic stem and progenitor cells (HSPCs). In the study, researchers examined and compared hematopoietic reconstitution in 53 patients treated with Orchard’s current and former HSC gene therapy programs for three genetic diseases, including MLD (n=29), Wiskott-Aldrich syndrome (WAS; n=15), and β-thalassemia (β-Thal; n=9) with up to 8 years of follow-up (median 4 years), using vector integration sites as a surrogate of clonal identity. Based on the analysis, all patients had a polyclonal repertoire consistent with other lentiviral-based HSC gene therapy studies and previously reported clinical results. Importantly, no somatic mutations known to drive clonal hematopoiesis or myeloid cancer were found in any patient from the MLD cohort and no increase of somatic mutations was observed over time. Program-specific differences in the clonal complexity of the various lineages and the incidence of somatic mutations suggest an impact of the underlying disease biology on hematopoietic reconstitution. These findings add to the compendium of evidence supporting the long-term durability and safety profile of Orchard’s HSC gene therapy portfolio. Results from the world’s first prospective, population-based NBS study for MLD published in NEJM A research letter detailing results from the world’s first prospective, population-based newborn screening (NBS) study for MLD was published in the September 18, 2024, issue of the New England Journal of Medicine (NEJM). The aim of the study, which was conducted in Hannover, Germany, was to evaluate the technical feasibility of MLD NBS and to develop and implement a comprehensive care pathway to provide prompt confirmatory diagnostics, clinical assessment, subtype prediction, clinical follow-up, and treatment. Dried blood spot samples from the first 109,259 newborns were tested in a three tier, high-throughput screen based on increased sulfatide levels, reduced ARSA enzyme activity and ARSA gene sequencing. Three newborns were identified as screen positive and were confirmed to have MLD and referred for pre-symptomatic treatment. The screening algorithm and comprehensive clinical care pathway represents a novel diagnostic and treatment paradigm for MLD, with the potential to significantly alter clinical practice by reducing morbidity and mortality in children with MLD by enabling pre-symptomatic treatment. 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 and deliver novel medicines and treatments 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 with high unmet medical needs, such as bone & mineral, intractable hematological diseases/hemato oncology, and rare diseases. A shared commitment to our values, to sustainable growth, and to making people smile unites us across the globe. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com.

Seven young boys treated with bluebird bio’s gene therapy for a rare neurological disease have been diagnosed with blood cancer months or years after treatment, according to data published on Wednesday in the New England Journal of Medicine . Researchers have long known that therapies developed with lentiviral vectors could, in some cases, cause cancer, but they have been seeking to understand why Skysona comes with a seemingly greater risk. The cases may relate to the design of the lentiviral vector used in the treatment, scientists hypothesize. Bluebird’s eli-cel was approved in 2022 under the brand name Skysona to treat cerebral adrenoleukodystrophy, also known as CALD. The condition mostly affects young boys and progresses rapidly without treatment, leading to neurological decline or death. Skysona was approved in 2022 with a black box warning for hematologic malignancy, and the FDA updated its label in April to disclose that there had been six cases of the cancer out of 67 patients dosed in clinical studies. An additional case has been diagnosed since then, according to new data published in NEJM. The patients received Skysona when they were between 5 and 13 years old, with the cancer diagnoses occurring 14 to 92 months later, according to the data. In an editorial published alongside the data, Cynthia Dunbar, a hematologist at the NIH’s National Heart, Lung and Blood Institute, wrote that more cases may appear over time. “Unfortunately, I think she’s right,” Christine Duncan, lead author of the NEJM study and Boston Children’s Hospital senior physician, told Endpoints News. “ Patients are being followed very closely. The families are being very educated. They all know about all of these cases.” Duncan and her team hypothesized that the cases may have been driven by the design of the lentiviral vector used in Skysona. CALD is caused by a mutation in a gene called ABCD1. Skysona works by using a lentivirus to insert a functioning form of the ABCD1 gene. Skysona’s lentiviral vector was designed with the use of a viral promoter, intended to help drive strong expression of the gene. But a risk of that type of promoter is oncogenesis, or driving the development of cancer, Duncan explained. “We’re relatively confident that that promoter in the design of the vector is driving this,” she said. “The question then is, in my mind, is it driving it alone, or are there other factors that contribute?” Duncan noted that patients in one study, ALD-102, which has reported only one case of hematologic cancer, received a stronger chemotherapy regimen as part of preparation for treatment than another study, ALD-104, which reported the other six cases. But at this time, it remains unclear whether that made a difference, or whether other factors were involved. “Is it a combination of conditioning regimen and the vector?” she asked. “We can’t know for certain.” Duncan added that the risk-benefit analysis for Skysona may vary from patient to patient. Some patients may be eligible for allogeneic stem cell transplant, but that process comes with its own risks — and just 20% of CALD patients have an available matched donor, according to the NEJM editorial. “We recognize that families of children diagnosed with CALD face urgent treatment decisions, and bluebird is committed to ensuring that treating physicians have access to the most up-to-date safety information to support informed decision making,” bluebird said in a statement. Leaving CALD untreated is the greatest risk, Duncan said. “Both allogeneic stem cell transplant, so the traditional therapy, and gene therapy, they both have things that are good about them, they both have things that are bad about them. And for any individual patient, it’s not the same scale,” Duncan said. “At the end of the day, I think it is very valuable, very important that families have choices that they can personalize with their caregivers and their providers.” Researchers noted there have been no cases of lentivirus-caused cancer reported with bluebird’s sickle cell and beta thalassemia therapy, which used a different lentiviral vector called BB305, and none with Orchard Therapeutics’ metachromatic leukodystrophy therapy Lenmeldy. Lei Lei Wu contributed reporting.

Unique international partnership marks significant momentum for new gene therapy entity PHILADELPHIA, Oct. 8, 2024 /PRNewswire/ -- Today, GEMMA Biotherapeutics ("GEMMABio") – a new therapeutics company founded by gene therapy pioneer Dr. Jim Wilson – announced a major agreement with the Oswaldo Cruz Foundation ("Fiocruz"), a public health research institution that is part of the Ministry of Health of Brazil and has extensive experience in biomanufacturing. GEMMABio partnered with Fiocruz – which is the main supplier of immunobiologics, biopharmaceuticals and diagnostics to the Brazilian Ministry of Health – to sponsor research that will bring gene therapy treatments to the people of Brazil under the Sistema Único de Saúde (SUS), Brazil's publicly funded health care system. Fiocruz will fund up to $100 million, which will be used to conduct clinical research and manufacturing – ultimately securing approval for programs that will allow the country to increase distribution of rare disease treatments and at a more affordable cost. "By combining our resources and knowledge, this collaboration represents a major advancement in making gene therapies accessible to more patients quickly and at a fraction of the typical cost," said Dr. Wilson, who will serve as President and CEO of GEMMABio. "We are optimistic that this deal will serve as a global example for expanding access to advanced medical therapies as well as pursuing non-traditional ways to capitalize biotech companies." A key component of the partnership will involve tech transfer, replicating GEMMABio's manufacturing technologies and process so that the companies can collaborate on programs and production in Brazil and for Fiocruz to utilize with other sponsors and programs. The agreement will also fund clinical development activities in Brazil for six core programs, including GM1 gangliosidosis (GM1), Krabbe Disease, Metachromatic leukodystrophy (MLD), and three unnamed programs. In return for their financial support, Fiocruz will be able to license related treatments to supply the Brazilian public health system. "Brazil has the largest public health system in the world, offering health services and products to more than 200 million people. We are very proud to bring this innovation to the Brazilian system, a technology that was previously restricted to those with higher incomes, will now be accessible to the entire Brazilian population" said Marco Krieger, Vice President of Production and Innovation in Health, Fiocruz. About GEMMABio GEMMABio is a therapeutics company focused on speeding the research of and global access to life-changing advanced therapies for those living with rare diseases. The company will provide research and product development functions to bring gene therapy discoveries from the bench to the bedside faster and affordably. GEMMABio is led by gene therapy industry pioneer Jim Wilson and his team of experts, who previously conducted their work in academia. Wilson is also the Chairperson of Franklin Biolabs, a Contract Research Organization. The collective goal of the two affiliated companies is to translate innovative scientific work into clinical trials, to then commercialize and distribute the new therapies around the world to patients who need them most. For more information, please visit gemmabiotx.com. About Fiocruz The Oswaldo Cruz Foundation (Fiocruz) is the largest biomedical research institution in Latin America, which also produces vaccines, medicines and in vitro diagnostics (IVD) to supply the Unified Health System (SUS, acronym in Portuguese for the Brazilian public health system). Linked to the Brazilian Ministry of Health, the Foundation was created on May 25, 1900 to initially manufacture serums and vaccines against bubonic plague. Since then, the institution has experienced an intense trajectory, which is intertwined with the development of public health in Brazil. Currently, Fiocruz is installed in 10 states, in addition to the Federal District, and has an office in Maputo, capital of Mozambique, Africa. In addition to the institutes based in Rio de Janeiro, the Foundation maintains units in the Northeast, North, Southeast and South regions of Brazil, and offices in Ceará, Mato Grosso do Sul, Piauí and Rondônia. In total, there are 16 technical-scientific units, focused on teaching, research, innovation, assistance, technological development and extension in the field of health. For more information, visit . Contact: Scott Hoeflich [email protected] SOURCE GEMMA Biotherapeutics and Franklin Biolabs WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED