NAGLU

HYOGO, Japan--(BUSINESS WIRE)-- MEDIPAL HOLDINGS CORPORATION (TSE 7459 “MEDIPAL”) and JCR Pharmaceuticals Co., Ltd. (TSE 4552 “JCR”) today announced the completion of the regulatory review by the Pharmaceuticals and Medical Devices Agency (PMDA) for the clinical trial notification for the phase I/II study of JR-446, a blood-brain barrier-penetrating α-N-acetylglucosaminidase, for the treatment of mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome type B), a devastating and ultra-rare lysosomal storage disorder. MPS IIIB affects an estimated 500 to 1,000 individuals worldwide1, causing severe central nervous system symptoms. Despite the dire need, there are currently no approved treatments available for this condition. JR-446, developed using JCR’s proprietary J-Brain Cargo® technology, has shown promising preclinical results in addressing the symptoms of this challenging disorder. In September 2023, MEDIPAL and JCR secured a license to commercialize JR-446 overseas and partnered to develop and commercialize it in Japan, targeting MPS IIIB2. With the regulatory review now complete, we plan to start the clinical trial in Japan in the first half of FY2024 (April to September). This collaboration highlights the commitment of MEDIPAL and JCR to pioneer treatments for ultra- rare diseases. By advancing therapies like JR-446, we aim to bring hope to patients and their families, while enhancing corporate value and contributing to a society where everyone can live with physical and mental well-being. About Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B) Mucopolysaccharidosis type IIIB, or Sanfilippo syndrome type B, is an autosomal recessive disease caused by pathogenic mutations in the NAGLU gene, encoding a lysosomal enzyme involved in the degradation of heparan sulfate. With the accumulation of heparan sulfate in the central nervous system in the brain, individuals with this condition present rapid neurological decline, including sleep disorders, loss of speech, and behavioral changes, which may significantly affect the quality of life of patients and their families. About MEDIPAL HOLDINGS CORPORATION MEDIPAL is a holding company which controls, administers and supports the operating activities of companies in which it holds shares in the Prescription Pharmaceutical Wholesale Business; the Cosmetics, Daily Necessities and OTC Pharmaceutical Wholesale Business; and the Animal Health Products and Food Processing Raw Materials Wholesale and Related Business, and conducts business development for the MEDIPAL Group. For more information, visit About JCR Pharmaceuticals Co., Ltd. JCR is a global specialty pharmaceuticals company dedicated to advancing treatments for rare and genetic diseases. With nearly 50 years of expertise in Japan, we are expanding to the US, Europe, and Latin America. Our innovative therapies address conditions like growth disorder, MPS II, Fabry disease, acute graft-versus-host disease, and renal anemia. We are also developing treatments for rare diseases like MPS I, MPS II, MPS IIIA and B, and more. Our core values of reliability, confidence, and persistence drive our mission to enhance global medical progress. For more information, visit . References 1 Based on data from the Ministry of Health, Labour and Welfare’s public research and JCR’s own investigations. 2 Reference: Press release on the licensing agreement for JR-446 between MEDIPAL and JCR (September 28, 2023). This news release is intended to provide the latest information on two companies businesses to shareholders and other investors, and members of the press. The information on pharmaceutical products (including those under development) in this document is not intended for advertising, providing medical advice or other such purposes. The English version of this document is a translation of the Japanese original and is provided for information purposes only. While reasonable efforts have been made to provide an accurate translation, no liability is assumed by MEDIPAL and JCR for any errors, omissions, or ambiguities in the translation. In the event of any inconsistency or conflict between the English version and the Japanese original, the Japanese original shall prevail.

April 16, 2024 -- Jaya Biosciences, Inc. (“JayaBio” or “the Company”), a privately held early-stage life-sciences company developing CNS-directed gene therapies for unmet needs in the neurodegenerative diseases, reported preclinical data at the 45th Annual Meeting of the Society for Inherited Metabolic Disorders (SIMD), a leading research conference on inherited metabolic diseases, including lysosomal diseases. During a podium presentation, Jaya Biosciences’ scientific founder and science advisory board chair, Professor Mark Sands, reported on recently updated human genetic analyses suggesting that heterozygous loss-of-function mutations in lysosomal enzyme genes are enriched in Alzheimer’s disease (AD) patients. This new analysis generated from a much larger whole genome sequence database confirmed their previous human genetic findings from a smaller whole exome database. Professor Sands presented in vivo data that validated several of the genes identified in the human AD cases and identified two additional lysosomal enzyme genes that affect amyloid-beta (Aβ) processing in heterozygous animals. Finally, CNS-directed, AAV-mediated gene therapy with JB111 (the Company’s lead therapy) was shown to ameliorate the biochemical, histological, and clinical signs of disease in an animal model of PPT1-associated AD (5xFAD harboring a heterozygous mutation in the PPT1 gene). “We are pleased to see that the additional genetic analyses corroborated our initial findings of lysosomal dysfunction in Alzheimer’s disease,” said Pawel Krysiak, President and CEO of JayaBio. “The updated preclinical data we presented continue to show the high potential of targeting PPT1 haploinsufficiency in Alzheimer’s and support the necessity for a paradigm shift in the strategy for AD therapy development. Our team is committed to further advancing JayaBio’s platform targeting the upstream effector lysosomal pathway in an effort to address an enormous unmet need in neurodegenerative diseases.” The following talk was presented at the 45th SIMD Annual Meeting: Title: Haploinsufficiency of lysosomal enzymes and Alzheimer’s disease Date and Time: Mon, April 15th, 2024 at 5:00 PM ET Session: Science Session 4 Presenter (In-person): Prof. Mark Sands, Washington University School of Medicine, St. Louis, MO Human genetic analysis suggests that heterozygous loss-of-function mutations in lysosomal enzyme genes are enriched in Alzheimer’s patients. Heterozygosity of five different lysosomal enzyme genes (PPT1, NAGLU, GALC, IDUA, GUSB) significantly affects amyloid precursor protein (APP) processing and favors pro-amyloidogenic pathway. PPT1 haploinsufficiency greatly exacerbates Aβ plaque formation and significantly reduces the life span of the 5xFAD mouse model of AD. CNS-directed, AAV-mediated PPT1 gene therapy significantly increases the life span of 5xFAD/PPT1+/- mice. “The updated human genetic data confirmed that heterozygous deleterious mutations in a subset of lysosomal genes are enriched in patients with Alzheimer’s disease,” said Prof. Mark Sands. “Together with previously reported gene dosage effects of these mutations on Aβ processing, it underscores the utility of targeting lysosomal genes haploinsuficiencies in neurodegenerative diseases and adds to the evolving understanding regarding the status of lysosomal enzyme gene defects carriers. Especially considering that our lead therapy, the CNS-directed AAV-mediated PPT1 gene therapy, dramatically improved the clinical signs in a mouse model of AD.” “We continue to be encouraged by the positive preclinical results from our JB111 gene therapy study in PPT1-associated Alzheimer’s model and look forward to translating our strong animal proof of concept to IND-enabling toxicology and clinical studies,” added Dr. Neal Goodwin, Co-founder and Chief Scientific Officer of JayaBio. For more information about the 45th SIMD Annual Meeting, please go to SIMD2024 Meeting. The abstract will also be made available on JayaBio’s corporate website. Lysosomes are subcellular organelles responsible for the normal degradation and turnover of cellular components and aggregation-prone proteins. Deficits in the autophagy-lysosomal pathway (ALP) result in protein aggregation, the generation of toxic protein species, and accumulation of dysfunctional organelles, which are hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).1 Lysosomal degradation plays a critical role, as the degradation of autophagosomal cargo cannot proceed without successful fusion to an available and functional lysosome.2 Lysosomal function declines with age and likely contributes both to the aging process itself as well as the development of age-related diseases such as neurodegenerative diseases and cancer.2,3 Emerging evidence suggest that defects in certain lysosomal enzyme genes are associated with various neurodegenerative diseases such as Parkinson’s Disease4, Frontotemporal Dementia5, and Alzheimer’s Disease.6 1. Martini-Stoica H, et al., (2016) Trends Neurosci 39(4):221-234 2. Levine B, Kroemer G, (2019) Cell 176(1-2):11-42 3. Hansen M, et. al., (2018) Nature Rev Mol Cell Biol, 19(9):579-593 4. Sidransky E, et al., (2009) N Engl J Med 361(17):1651-61. 5. Baker M, et al., (2006) Nature, 442(7105):916-9 6. Lopergolo D, et al., (2023) J Med Genet, Epub ahead of print JB111, Jaya Biosciences’ lead therapy, is an experimental CNS-directed AAV9-mediated PPT1 gene therapy currently being developed for neurodegeneration associated with PPT1 haploinsufficiency (carrier status for loss-of-function mutations in palmitoyl protein thioesterase-1 gene or PPT1 heterozygosity). JB111 showed very promising results in the animal model of PPT1-associated Alzheimer’s disease (5XFAD mouse harboring PPT1 heterozygous allele). Single intracerebroventricular (ICV) injection of JB111 resulted in a significantly increased life span and improved cognitive performance. Jaya Biosciences is a privately held pre-clinical stage life sciences company developing CNS-directed gene therapies for genetically defined neurodegenerative diseases, including Alzheimer's, Parkinson’s, and frontotemporal dementia. Jaya’s platform is based on the groundbreaking discovery that carriers of loss-of-function mutations in genes for lysosomal enzymes have an increased risk of neurodegeneration, including early onset of symptoms. Jaya Biosciences’ team, proven in drug development and commercialization of lysosomal targets and gene therapies, is dedicated to addressing unmet needs in neurodegeneration and adding value to patient and medical communities worldwide. Jaya’s mission is to fulfill a promise of victory over neurodegeneration by identifying and targeting the relevant pathways involved in the etiology of these debilitating diseases. For more information, please visit www.jayabio.com The content above comes from the network. if any infringement, please contact us to modify.

- Study results highlight potential utility of targeting lysosomal genes to treat neurodegenerative diseases, including Alzheimer’s - SOUTH SAN FRANCISCO, Calif., Feb. 12, 2024 (GLOBE NEWSWIRE) -- Jaya Biosciences, Inc. (“JayaBio” or “the Company”), a privately held early-stage life-sciences company developing CNS-directed gene therapies to address unmet needs in genetically defined neurodegeneration, reported non-clinical data at the 20th Annual WORLDSymposium™, a leading research conference on lysosomal diseases. During a late-breaking news platform presentation, Jaya Biosciences’ scientific founder, Prof. Mark Sands, reported preliminary human genetic analysis suggesting that heterozygous loss-of-function mutations in lysosomal enzyme genes are enriched in Alzheimer’s patients, as well as preclinical efficacy results in the animal model of Alzheimer’s disease (AD) for JB111, the Company’s lead therapy. “We are thrilled to showcase a new paradigm for the treatment of genetically defined neurodegeneration at the 20th WORLDSymposium™,” said Pawel Krysiak, President and CEO of JayaBio. “The preclinical data we presented demonstrate a tremendous promise of targeting PPT1 haploinsufficiency in Alzheimer’s disease. Development of an effective treatment for Alzheimer’s has been elusive for decades and nearly 7 million Americans are the testament to the size of the unmet medical need. This underscores the necessity for a shift in the strategy for Alzheimer’s therapy development. Our team has identified and validated a number of genes as potential targets for the upstream effector lysosomal pathway, and JayaBio will build its clinical programs upon this groundbreaking foundation of scientific data.” The following talk was presented at the 20th WORLDSymposium™: Title: Haploinsufficiency of lysosomal enzymes and Alzheimer’s disease Date and Time: Friday, Feb. 9, 2024 at 9:00 AM PT (12:00 PM ET) Session: Late-Breaking Science Presenter (In-person): Prof. Mark Sands, Washington University School of Medicine, St. Louis, MO Preliminary human genetic analysis suggests that heterozygous loss-of-function mutations in lysosomal enzyme genes are enriched in Alzheimer’s patients. Heterozygosity of five different lysosomal enzyme genes (PPT1, NAGLU, GALC, IDUA, GUSB) significantly affects amyloid precursor protein (APP) processing and favors pro-amyloidogenic pathway. Heterozygosity of PPT1 and NAGLU exacerbate amyloid–beta (Aß) plaque formation, increase insoluble Aß40 and Aß42, and significantly decrease the life span of the 5xFAD mouse model of AD. CNS-directed, AAV-mediated gene therapy significantly increases the life span and improves cognitive function of 5xFAD/PPT1+/- mice. “These data strongly suggest that heterozygous deleterious mutations in a subset of lysosomal genes are enriched in patients with Alzheimer’s disease and there is a nearly perfect gene dosage effect of these mutations on Aß processing in five different mouse models,” said Prof. Mark Sands, Jaya Biosciences’ Scientific Founder and Science Advisory Board Chair. “Furthermore, CNS-directed AAV-mediated gene therapy complemented the haploinsufficiency of our lead target gene, palmitoyl protein thioesterase-1 (PPT1), and dramatically improved the clinical signs in a mouse model of AD. Collectively, these findings challenge the old dogma that carriers of lysosomal enzyme gene defects are normal throughout life and provides a conceptual and practical framework to treat neurodegeneration associated with these heterozygous mutations.” “We are very encouraged by the positive preclinical results from our JB111 gene therapy study in PPT1-associated Alzheimer’s model,” added Dr. Neal Goodwin, Co-founder and Chief Scientific Officer of JayaBio. “We believe that having demonstrated strong animal proof of concept for JB111 supports raising additional capital and proceeding forward to IND-enabling toxicology and clinical studies.” For more information on how to access the live streamed events, presentations, and Q&A sessions, please go to WORLDSymposium™. The abstract will also be made available on JayaBio’s corporate website. About Autophagy-Lysosomal Pathway in Neurodegeneration Lysosomes are subcellular organelles responsible for the normal degradation and turnover of cellular components and aggregation-prone proteins. Deficits in the autophagy-lysosomal pathway (ALP) result in protein aggregation, the generation of toxic protein species, and accumulation of dysfunctional organelles, which are hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).1 Lysosomal degradation plays a critical role, as the degradation of autophagosomal cargo cannot proceed without successful fusion to an available and functional lysosome.2 Lysosomal function declines with age and likely contributes both to the aging process itself as well as the development of age-related diseases such as neurodegenerative diseases and cancer.2,3 Emerging evidence suggest that defects in certain lysosomal enzyme genes are associated with various neurodegenerative diseases such as Parkinson’s Disease4, Frontotemporal Dementia5, and Alzheimer’s Disease.6 1. Martini-Stoica H, et al., (2016) Trends Neurosci 39(4):221-234 2. Levine B, Kroemer G, (2019) Cell 176(1-2):11-42 3. Hansen M, et. al., (2018) Nature Rev Mol Cell Biol, 19(9):579-593 4. Sidransky E, et al., (2009) N Engl J Med 361(17):1651-61. 5. Baker M, et al., (2006) Nature, 442(7105):916-9 6. Lopergolo D, et al., (2023) J Med Genet, Epub ahead of print About JB111 JB111, Jaya Biosciences’ lead therapy, is an experimental CNS-directed AAV9-mediated PPT1 gene therapy currently being developed for neurodegeneration associated with PPT1 haploinsufficiency (carrier status for loss-of-function mutations in palmitoyl protein thioesterase-1 gene or PPT1 heterozygosity). JB111 showed very promising results in the animal model of PPT1-associated Alzheimer’s disease (5XFAD mouse harboring PPT1 heterozygous allele). Single intracerebroventricular (ICV) injection of JB111 resulted in a significantly increased life span and improved cognitive performance. About Jaya Biosciences, Inc. Jaya Biosciences is a privately held pre-clinical stage life sciences company developing CNS-directed gene therapies for genetically defined neurodegenerative diseases, including Alzheimer's, Parkinson’s, and frontotemporal dementia. Jaya’s platform is based on the groundbreaking discovery that carriers of loss-of-function mutations in genes for lysosomal enzymes have an increased risk of neurodegeneration, including early onset of symptoms. Jaya Biosciences’ team, proven in drug development and commercialization of lysosomal targets and gene therapies, is dedicated to addressing unmet needs in neurodegeneration and adding value to patient and medical communities worldwide. Jaya’s mission is to fulfill a promise of victory over neurodegeneration by identifying and targeting the relevant pathways involved in the etiology of these debilitating diseases. For more information, please visit Investor/Media Contact: Jaya Biosciences Inc. info@jayabio.com