Mucopolysaccharidosis I

Pictured: BioMarin headquarters in California/iSto iStock , Sundry Photography The biotech beat Wall Street’s third-quarter revenue forecast by 6%, driven by increased uptake of its achondroplasia drug Voxzogo. However, William Blair downgraded BioMarin’s shares to market perform due to a “lack of near-term catalysts” and uncertainty around Voxzogo’s potential revenue growth. BioMarin Pharmaceuticals on Tuesday announced $746 million in total revenue in the third quarter , 28% year-over-year growth driven by the continued strong uptake of its therapies for rare genetic diseases. The biotech beat consensus estimates, surpassing Wall Street’s expected Q3 revenue of $703 million by 6%. BMO Capital Markets analyst Kostas Biliouris in an investor note attributed BioMarin’s strong performance to the continued growth of its achondroplasia medicine Voxzogo, with sales of $190 million jumping 54%. There are now over 3,800 patients on Voxzogo, according to BioMarin, up from around 3,500 in the second quarter . Still, Wall Street anticipated Voxzogo generating $195 million for BioMarin in Q3, a bar the company missed by 3%. Roctavian, a gene therapy approved in June 2023 for hemophilia A , brought in $7 million in the quarter, in line with the analyst consensus. And while its relative contribution to BioMarin’s total Q3 revenue is low, Roctavian presents a high-growth opportunity for the biotech with 600% sales growth versus the same period the year prior. Biliouris said that this “continued uptake” of Roctavian reflects the company’s efforts to focus on the U.S., Italy and Germany markets, potentially paving the way for hitting around $60 million in revenue for the gene therapy by 2025. Truist Securities analyst Joon Lee also credited BioMarin’s Sanofi-partnered enzyme replacement therapy Aldurazyme for its Q3 beat. Sales of Aldurazyme, indicated for mucopolysaccharidosis I, jumped 407% in the quarter bringing in $71 million and beating the consensus expectation of $30 million by $137%. Encouraged by its strong Q3 showing—and by the continued growth of its products—BioMarin on Tuesday raised its full-year 2024 revenue guidance to between $2.79 billion and $2.825 billion. The biotech previously expected a range of $2.75 billion to $2.825 billion this year. Despite BioMarin’s promising outlook for 2024, Lee warned about impending competitive pressure on Voxzogo. Last month, Ascendis Pharma revealed strong pivotal data for its investigational drug TransCon CNP, also known as navepegritide, which showed significant improvements in annual growth velocity in children with achondroplasia. Ascendis is gearing up for a regulatory filing for TransCon CNP in the first quarter of 2025. “In light of better-than-expected data, we’re left to wonder what further impact competition from TransCon-CNP may have on BioMarin’s mid- to long-term guidance,” Lee said. Likewise, William Blair analyst Sami Corwin in a note to investors said that despite the Q3 beat, her firm downgraded shares of BioMarin to market perform. “We do not think its clinical pipeline will be a source of significant value creation in the near term,” according to Corwin. “Voxzogo remains the key top-line growth driver for the company, but the threat of competition could erode its revenue growth and market share.”

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.

- Preclinical Data Demonstrate Potential to Deliver an AAV Gene Therapy Using JCR’s Proprietary J-Brain Cargo ® Technology to Treat Central Nervous System Diseases - HYOGO, Japan--(BUSINESS WIRE)-- JCR Pharmaceuticals Co., Ltd. (TSE 4552; Chairman and President: Shin Ashida; “JCR”) announced today that the Company presented preclinical data from its novel adeno-associated virus (AAV) gene therapy research programs in a poster session at the European Society of Gene and Cell Therapy (ESGCT) 31 st Annual Congress, being held October 22-25, 2024, in Rome, Italy. JCR leverages its proprietary J-Brain Cargo ® (JBC) technology for the delivery of adeno-associated virus (AAV) gene therapy to the body and the brain to potentially address the central nervous system (CNS) symptoms by crossing the blood-brain barrier (BBB). “These findings illustrate the potential for applying our proprietary JBC technology as a vehicle to deliver gene therapy across the blood-brain barrier to potentially treat diseases in the central nervous system,” said Hiroyuki Sonoda, Ph.D., Director, Senior Managing Executive Officer, and Executive Director, Research Division at JCR Pharmaceuticals. “This approach has the potential to unlock new therapeutic options for conditions that have historically been challenging to treat. The results from these preclinical studies indicate that the uptake of the gene therapy using our proprietary JBC technology was substantially higher than with AAV9 and a reduction in tropism to the liver, thereby enhancing the safety of AAVs for human-use. We are committed to advancing innovative solutions that address unmet medical needs, and this research marks a crucial step forward.” JCR showcased the following presentation: Incorporation of transferrin receptor binder into AAV enables efficient brain delivery for treatment of genetic CNS diseases (P0133) Presenter: Yuhei Ashida (JCR Pharmaceuticals) The AAV vector leveraging the JBC technology transduced cells in the CNS more efficiently than a conventional AAV9 vector in mice and monkeys. When the modified vector was applied to mouse models of genetic CNS diseases, efficient reduction of toxic substances, histopathological improvements of the brain, improvements of behavioral tests, and greatly improved survival were observed. In addition, a JBC-AAV molecule with additional modifications showed dramatically reduced liver transduction. These results suggest that JCR’s JBC-AAV has the potential to be a promising tool for gene therapy of CNS diseases. Researchers noted the potential advantages of using JBC technology to deliver the AAV gene therapy to the CNS. The JBC-AAV capsid has versatility to fine-tune affinity and uptake. In addition, the capsid has a simple manufacturing scheme and stable production yields. About the European Society of Gene and Cell Therapy (ESGCT) Established in 1992, the European Society of Gene and Cell Therapy (ESGCT) seeks to support scientists and clinicians working in the fields of gene and cell therapy and to promote awareness and understanding of gene and cell therapy and the vast amount of related research in Europe. For more information, please visit . About the J-Brain Cargo ® Platform Technology JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo ® , to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGO ® (INN: pabinafusp alfa) and was approved in Japan for the treatment of a lysosomal storage disorder. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 49-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. JCR strives to expand the possibilities for patients while accelerating medical advancement at a global level. Our core values – reliability, confidence, and persistence – benefit all our stakeholders, including employees, partners, and patients. For more information, please visit . Cautionary Statement Regarding Forward-Looking Statements This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future. Contacts Investors & Media: JCR Pharmaceuticals Co., Ltd. Corporate Communications ir-info@jp.jcrpharm.com