Fondazione San Raffaele del Monte Tabor-Milano

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.

ISTANBUL and LONDON, and BOSTON, Oct. 07, 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 and Er-Kim, an international pharmaceutical company specializing in the commercialization of novel therapies, today announced the companies have signed an exclusive distribution agreement to commercialize Libmeldy® (atidarsagene autotemcel), the only approved therapy for eligible children with early-onset metachromatic leukodystrophy (MLD). Libmeldy aims to correct the underlying genetic cause of MLD, an ultra-rare, rapidly progressive, irreversible and ultimately fatal neurometabolic disease that affects approximately one in 100,000 live births based on existing literature. Under the agreement, Er-Kim will serve as the exclusive representative of Orchard to identify children eligible for treatment with Libmeldy in international markets across Turkey, Russia, Ukraine, and the Commonwealth of Independent States. Er-Kim will collaborate with Orchard Therapeutics to refer eligible children with early-onset MLD identified in these countries to an established European-based qualified treatment center. “The pharmaceutical and biotech industries have made notable strides in advancing gene therapies and we are thrilled to partner with Orchard Therapeutics to enable access to this important treatment in the region,” said Cem Zorlular, chief executive officer of Er-Kim. “Libmeldy is a potentially transformative therapy for eligible children with early-onset MLD who previously had no approved treatment options beyond supportive and end-of-life care. We are looking forward to working with Orchard and our counterparts in these territories that we specialize in to further implement bespoke approaches to deliver genetic medicines to eligible patients as soon as possible.” “MLD is a devastating disease for which there is evidence of a higher incidence rate in Turkish and Eurasian populations than those in the U.S. and Europe, which heightens our urgency to expand access mechanisms for Libmeldy in these regions,” said Robin Kenselaar, senior vice president and general manager of EMEA at Orchard Therapeutics. “With its extensive regional footprint and deep expertise in delivering specialty medicines to patients in need, we look forward to working with our new partners at Er-Kim to broaden access for eligible children and their families.” 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 LibmeldyLibmeldy® (atidarsagene autotemcel) aims to correct the underlying genetic cause of metachromatic leukodystrophy (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. Prior to treatment, patients must undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in Libmeldy. This approach has the potential to restore enzymatic function to stop or slow disease progression with a single treatment. Libmeldy is approved by the European Commission (EC), UK Medicines and Healthcare products Regulatory Agency (MHRA), and Swiss Agency for Therapeutic Products (Swissmedic). For more information, 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. About Er-KimEstablished in 1981, Er-Kim Pharmaceuticals stands at the forefront of biopharmaceutical innovation, partnering with over 40 global leaders to revolutionize patient care in key international markets. Our pioneering business models, tailored for sustainability and flexibility, have positioned us as a full-service solution, extending our reach to over 600 million patients through our fully-owned affiliates. With a dedicated team of over 280 professionals worldwide and revenues exceeding EUR 200M, Er-Kim is not just a partner but a trailblazer in healthcare, continually setting new standards in commercialization and patient access. For more information, please visit http://www.er-kim.com/. 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. ______________________________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/10.1177/0883073809341669

Genespire patched together a €46.6 million (about $52 million) funding round to get its lead gene therapy into the clinic in a few years. The Milan-based biotech, which employs nine people, said Wednesday that the Series B will fuel its mission to create a lentiviral vector-based gene therapy for children with methylmalonic acidemia, a rare genetic disease marked by disruptions to the breakdown of certain fats and amino acids. Also known as MMA, it can lead to muscular weakness, seizures, developmental delays, organ damage and even death. Other gene therapy startups have attempted but then abandoned efforts to develop treatments for the disease, including AstraZeneca’s LogicBio and Selecta Biosciences . There are no disease-modifying drugs, and treatment is currently addressed by diet modifications or sometimes liver transplants. Genespire’s work is based on research out of the San Raffaele Telethon Institute for Gene Therapy. The four-year-old biotech recently recruited former Lysogene CEO Karen Aiach-Pignet as its new chief executive after Lysogene shut down. It’s “a new page for me at a time when there have been a lot of ups and downs in the gene therapy space,” she said in an interview. “Probably more downs over the recent years.” Several gene therapy makers, including bluebird bio — which saw its sickle cell gene therapy Lyfgenia get approved last year — are struggling after interest in the once-bustling field has waned amid the broader biotech downturn and questions about the profitability of making these therapies. That said, new biotechs are still emerging, with plans to focus on neurodegenerative and CNS diseases , cancers and other areas. Aiach-Pignet joined Genespire after bringing Lysogene from the lab to Phase 3 with a gene therapy that missed the bar on improving cognitive development in Sanfilippo syndrome type A, a serious inherited neurodegenerative lysosomal storage disorder. Aiach-Pignet said a patient group called Blue Daisy has acquired the program. Sofinnova Partners, which had backed Lysogene, co-led Genespire’s Series B. XGEN Venture, CDP Venture Capital and Indaco Venture Partners SGR are also investors in Genespire. Aiach-Pignet said it is too soon to commit to a time frame for the Phase 1/2 study, though it is likely more than a year away, she said. The company still needs to coordinate the study with regulators and patient advocacy groups, according to the CEO. “Something that I really pay great attention to is the viewpoints, the experience, the expertise of patient groups,” Aiach-Pignet said. “The reason why I wanted to include them in the process is because we need to have a very robust clinical protocol, but we also need to have a protocol that makes sense for the patients and will make sense for the payers down the line.” Moderna is aiming for approval of its own experimental medicine for MMA by 2028. The biotech is in Phase 1/2 with an mRNA infusion treatment candidate known as mRNA-3705. Meanwhile, a BridgeBio subsidiary called CoA Therapeutics terminated a Phase 1 of its oral drug BBP-671 last year. Editor’s note: This story was updated to include additional information on Blue Daisy acquiring Lysogene’s gene therapy.