GALC

Designation grants access to enter the Innovative Licensing and Access Pathway (ILAP) Five patients treated with FBX-101 show positive safety and efficacy results, including significant improvements in motor function Forge’s CMO, Dr. Maria Escolar, to present updated FBX-101 clinical data during the Advanced Therapies 2024 conference in London March 19-20 Designation provides opportunities for further global acceptance of Forge’s manufacturing process and facility through additional reviews and inspections COLUMBUS, Ohio--(BUSINESS WIRE)-- Forge Biologics, a member of Ajinomoto Bio-Pharma Services and a leading manufacturer of genetic medicines, today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA), the healthcare regulatory body of the United Kingdom (UK), granted Innovation Passport designation to the Company’s novel AAV gene therapy program, FBX-101, to enter the Innovative Licensing and Access Pathway (ILAP). FBX-101 was created for the treatment of patients with Krabbe disease, a rare neurodegenerative disease that is usually fatal in untreated patients by age two. The ILAP is intended to accelerate regulatory and market access interactions in the UK. Maria Escolar, M.D., Forge’s Chief Medical Officer, will discuss the significance of achieving this regulatory designation and present a poster on updated data from REKLAIM, an early phase clinical trial for FBX-101, during the Advanced Therapies 2024 conference being held in London, March 19-20, 2024. “Considering the rapid progression of Krabbe disease in young patients and the positive results we’ve observed in the REKLAIM trial, we are pleased to receive the Innovation Passport designation which will enable Forge to further accelerate the clinical development of FBX-101,” stated Dr. Escolar. “ILAP was created to provide access to tools to decrease the time to market and facilitate patient access to medicines in the UK for life-threatening or seriously debilitating conditions.” The REKLAIM clinical trial is evaluating the safety and efficacy of FBX-101 in patients with infantile and late infantile Krabbe disease. Children assessed in REKLAIM have received intravenous FBX-101 in addition to the current standard of care, hematopoietic stem cell transplantation (HSCT). Clinical data demonstrate that FBX 101 has been well tolerated and has an excellent safety pro the treatment of five patients. Results show improvements in motor function in all patients, the most meaningful clinical outcome for this disease. FBX-101 has been granted Orphan Drug Designation and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA), allowing Forge to advance and expedite the development of FBX-101 as the leading worldwide gene therapy for patients with Krabbe disease. In the US, the FDA has granted FBX-101 Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation. ILAP is intended to accelerate regulatory and market access interactions in the UK for patient populations with significant need, leading to accelerated patient access to novel therapies. It also provides access to a range of UK development services and tools, including frequent MHRA interactions, accelerated Marketing Authorization Application (MAA) assessment, a Target Development Profile, expanded licensing routes, and more, creating a roadmap for advancement of therapies through regulatory approval. Regulatory review by the MHRA through ILAP provides opportunities for further global acceptance of Forge’s manufacturing process and facility though additional reviews and inspections, including Compliance Readiness Inspections that provide custom and pragmatic supervisory and licensing inspections specific to the GMP guidelines. Through this designation Forge has expanded global regulatory experience to include interactions with the MHRA in the UK. This access to global health authority resources will enable an added level of assurance to clients utilizing Forge’s CDMO services with integrated regulatory support. About Krabbe Disease Krabbe disease is a rare neurodegenerative disease affecting about 1-2.5 in 100,000 people in the US. Krabbe disease is caused by autosomal recessive mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine. Without functional GALC, psychosine accumulates to toxic levels in cells, specifically in cells insulating the nerves in the brain and peripheral nervous system, causing rapid demyelination. Krabbe disease initially manifests in young patients as irritability, developmental delay, and progressive muscle weakness. Symptoms rapidly advance to difficulty swallowing, breathing, and regression of neurodevelopment followed by seizures, vision and hearing loss. Infantile Krabbe disease (0-12 months of age at onset) usually leads to death in untreated patients by two years of age. Late Infantile patients (12-36 months of age at onset) usually die by the age of six. The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death. About FBX-101 FBX-101 was developed to treat children with Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is delivered intravenously after HSCT infusion. The vector delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system and has shown to functionally correct the central and peripheral neuropathy, improve myelination and gross motor function, and significantly prolong lifespan in animal models. This approach also has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies and extend the duration of gene transfer. About the REKLAIM Trial REKLAIM is a nonblinded, non-randomized, early phase dose escalation clinical trial currently enrolling children with asymptomatic infantile and symptomatic late infantile Krabbe disease to investigate the safety and efficacy of a single intravenous infusion of FBX-101 administered more than 21 days after HSCT, the current standard of care. Data from extensive natural history subjects will be used to compare as the control group. More information on the REKLAIM trial can be found online at . About Forge Biologics Forge Biologics, a member of Ajinomoto Bio-Pharma Services, is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company, enabling access to life-changing gene therapies by bringing them from concept to reality. Forge’s 200,000 square foot facility, the Hearth, is headquartered in Columbus, Ohio, and houses 20 custom-designed cGMP suites with 200,000L of manufacturing capacity. Forge’s end-to-end, scalable plasmid and AAV manufacturing services include research-grade manufacturing, process and analytical development, cGMP manufacturing, fill and finish, and integrated regulatory support to help accelerate the timelines of transformative medicines for patients with genetic diseases. To learn more, visit .

- 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

Data from Krabbe patients treated with hematopoietic stem cell transplantation (HSCT) and FBX-101 gene therapy in clinical trials continue to demonstrate safety and efficacy post-FBX-101 systemic administration Five patients have received FBX-101, all of whom were identified by newborn screening CEO Timothy J. Miller, Ph.D., is slated to comment during the public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) to reinforce the importance of the addition of Krabbe Newborn Screening to the national Recommended Newborn Screening Panel (RUSP) on Tuesday, January 30, 2024 Dr. Maria Escolar, Chief Medical Officer, will present updated FBX-101 clinical data as a late-breaking oral presentation on Friday, February 9, 2024, during the 10:30 a.m. ET session at the WORLD Symposium in San Diego, California COLUMBUS, Ohio--(BUSINESS WIRE)-- Forge Biologics (Forge), a member of Ajinomoto Bio-Pharma Services and a leading manufacturer of genetic medicines, announced a clinical update today on five patients with Krabbe disease that have received FBX-101, an AAV gene therapy, after hematopoietic stem cell transplantation (HSCT). Timothy J. Miller, Ph.D., CEO and President of Forge Biologics, will provide comments during the open period at the public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) on Tuesday, January 30, 2024, in support of adding Krabbe disease to the Recommended Uniform Screening Panel (RUSP). Krabbe disease is caused by mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, damaging cells that myelinate and insulate the nerves in the brain and peripheral nervous system, causing rapid demyelination and eventual death. Infantile Krabbe patients, often not diagnosed until after significant disease manifestations have occurred, typically die by the age of two if not treated by HSCT before symptoms are observed. Previously published data have demonstrated that patients with Krabbe treated with HSCT demonstrate increased lifespan and stabilization of neurodegenerative disease in the central nervous system. FBX-101, an investigational adeno-associated viral (AAV) gene therapy, has been designed to address the peripheral nerve disease not corrected by HSCT. Data recently presented at the European Society for Gene and Cell Therapy (ESGCT) demonstrated that FBX-101 provided to Krabbe patients identified through newborn screening who also received HSCT demonstrated increased GALC expression, reduced psychosine levels, normalized motor function, and corrected brain white matter growth. “Inclusion of Krabbe disease on the RUSP would extend Krabbe Newborn Screening to eight additional states, based on RUSP alignment legislation, ensuring that nearly 70% of all newborns in the United States are screened for this devastasting disease,” said Dr. Miller. “That would mean the potential of identifying dozens of babies every year, based on published incidence, who could receive the opportunity of life-saving treatments such as transplant and newly developing treatments like gene therapy.” The responsibility of the committee members of the ACHDNC is to provide the Secretary of Health and Human Services with recommendations, advice, and information to enhance, expand, or improve the ability of the Secretary to reduce mortality and morbidity from heritable disorders—such as Krabbe disease—in newborns and children. In early 2023, Krabbe disease came up for the second time (previously in 2010) to the ACHDNC for a vote to be added to the RUSP—a vote which ended in a tie of seven members voting approve, and seven members voting not to approve, something that had never happened before and has been a focus of multiple advocacy group efforts requesting a re-vote. As a result, after a year of patient and foundation advocacy, Krabbe disease is again being voted on for potential inclusion on the RUSP. “For infantile Krabbe patients, the alternative of not being able to receive a treatment such as a transplant is 100% chance of death,” said Lesa Brackbill, Director of Advocacy at Leukodystrophy Newborn Screening Action Network (LDNBS), whose daughter Victoria died from Krabbe disease in 2016. “The risk-to-benefit approach of identifying patients as early as possible in their genetic disease to help provide their children any relief, justifies the addition of Krabbe to the RUSP. Newborn screening for Krabbe will help enhance the efforts of all parents, industry partners, and treatment providers’ ceaseless search for cures.” Additionally, Maria Escolar, M.D., Chief Medical Officer, will present updated FBX-101 clinical data during the 20th Annual WORLD Symposium in San Diego, California, on February 9, 2024 at 10:30 a.m. ET. Dr. Escolar’s late-breaking oral presentation is titled, “REKLAIM, the novel phase 1b clinical trial of FBX-101 (AAVrh10.galc) intravenously administered after UCBT for the treatment of infantile Krabbe disease.” The session will also be available on demand for registered attendees February 14 to March 14, 2024. For more details on the conference, please visit: . “We continue to be encouraged by the safety and efficacy observed in FBX-101 treated patients,” stated Dr. Escolar. “The window of treatment for patients with Krabbe disease is very narrow and newborn screening is a critical step for these babies to benefit from any treatment, but unfortunately newborn screening for this devastating and quickly progressing disease is still only available in a handful of states. Dr. Miller’s comments to the ACHDNC will reflect the urgency physicians have been trying to convey for this patient community.” About Krabbe Disease Krabbe disease is a rare neurodegenerative disease affecting about 1-2.5 in 100,000 people in the U.S. Krabbe disease is caused by autosomal recessive mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, specifically in cells that make myelin insulating the nerves in the brain and peripheral nervous system, resulting in rapid demyelination. Krabbe disease initially manifests in young patients as irritability, feeding difficulties, increased muscle tone and developmental delay. Symptoms rapidly advance to difficulty breathing, and regression of neurodevelopment followed by seizures, vision and hearing loss. Infantile Krabbe disease (0-12 months of age at onset) usually leads to death in untreated patients by two years of age. Late Infantile patients (12-36 months of age at onset) usually die by the age of six. The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes when performed prior to symptom onset. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death. Early diagnosis is key for treating patients with Krabbe disease before symptoms are evident and significant neurological damage has occurred. Currently, 11 states in the U.S. are conducting newborn screening for Krabbe disease. Infants who screen positive due to insufficient GALC activity undergo psychosine testing and mutation analysis to confirm the diagnosis and determine which infants need immediate treatment because they are at high risk to progress. More details can be found at . About FBX-101 FBX-101 was developed to treat children with Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is delivered intravenously after HSCT. The vector delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy associated with Krabbe, improve myelination and gross motor function, and significantly prolong lifespan in animal models. This is a novel approach that has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies (without transplantation). HSCT has normal GALC and provides an immune system that does not recognize GALC as an antigen. The FDA has granted FBX-101 Fast Track Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and the EMA has granted FBX-101 Orphan Drug Designation and Priority Medicines (PRIME) designation. FBX-101 investigation use is currently being evaluated for new subjects in the REKLAIM clinical trial (NCT05739643). More information on the REKLAIM trial can be found online at . About Forge Biologics Forge Biologics, a member of Ajinomoto Biopharma Services, is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company enabling access to life-changing gene therapies by bringing them from concept to reality. Forge’s 200,000 square foot facility, the Hearth, is headquartered in Columbus, Ohio, and houses 20 custom-designed cGMP suites. Forge’s end-to-end, scalable plasmid and AAV manufacturing services include research-grade manufacturing, process and analytical development, cGMP manufacturing, fill and finish, and regulatory consulting support to help accelerate the timelines of transformative medicines for patients with genetic diseases. To learn more, visit .