PPT1

- Data presented highlight the potential utility of targeting lysosomal genes to treat neurodegenerative diseases, including Alzheimer’s -SOUTH SAN FRANCISCO, Calif., April 09, 2024 (GLOBE NEWSWIRE) -- Jaya Biosciences, Inc. (“JayaBio” or “the Company”), a privately held early-stage life-sciences company developing gene therapies to address unmet needs in genetically defined neurodegeneration, presented promising non-clinical data for a novel treatment approach in Alzheimer’s disease at the 23rd Annual Needham Virtual Healthcare Conference. JayaBio’s President and CEO, Pawel Krysiak, reviewed the rationale for targeting the autophagy-lysosomal pathway and discussed the Company’s lead program, JB111, including its strong animal proof-of-concept data and near-term development milestones. “We are grateful for the opportunity to share a new paradigm for the treatment of genetically defined neurodegeneration with the investor community at the 23rd Annual Needham Virtual Healthcare Conference,” said Pawel Krysiak, President and CEO of JayaBio. “The preclinical update we presented demonstrates a tremendous promise of targeting PPT1 haploinsufficiency in Alzheimer’s disease, and with the right funding in place, we could transition this program into the clinic within 3 years. Given the size of the unmet need and the strong potential of our platform, we hope to attract experienced investors to support JayaBio’s progress and help us develop life-changing therapies for genetically defined neurodegeneration, including Alzheimer’s disease.” The following talk was presented at the 23rd Annual Needham Virtual Healthcare Conference: Title: Jaya Biosciences: New Paradigm for Genetically-Defined Neurodegenerative DiseasesDate and Time: Mon, Apr 8 at 11:45-12:25 PMSession: Track 3Presenter (virtual): Pawel Krysiak, President & CEO, Jaya Biosciences Inc.Needham Moderator: James Diamond About The 23rd Annual Needham Virtual Healthcare ConferenceThis fully virtual conference features fireside chats and presentations from leading public and private companies in the Biopharma, Medtech, Diagnostics and Digital Health sectors as well as thematic panel discussions. 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 www.jayabio.com Investor/Media Contact: Jaya Biosciences Inc.info@jayabio.com

- 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

Genfit now has three candidates aimed at acute-on-chronic liver failure. Genfit has added a third liver failure candidate to its portfolio courtesy of a licensing deal with Seal Rock Therapeutics potentially worth up to 100 million euros ($107 million) in biobucks. The asset in question is an injectable form of Seal Rock’s ASK1 inhibitor SRT-015, for which Genfit has secured the rights in liver disease. France-based Genfit has its sights set on entering the clinic with the candidate in the second half of next year, with a proof-of-concept study in acute-on-chronic liver failure (ACLF) penciled in for 2025. Apoptosis signal-regulating kinase 1 (ASK1) is a member of the MAP kinase family. Inhibiting ASK1 has been shown to block lipopolysaccharide-associated hyperinflammatory response as well as reduce the release of proinflammatory cytokines, reduce fibrosis and protect macrophage mitochondrial function, Genfit explained in the postmarket release yesterday. Animal models and clinical trials have already shown benefits of this mechanism across a wide range of organ diseases, including of the kidney, liver, brain and cardiopulmonary system, the biotech added. These drugs haven’t always lived up to the hype, however. Gilead’s ASK1 inhibitor selonsertib flunked a couple of phase 3 trials in nonalcoholic steatohepatitis, the same condition for which Seal Rock had been developing SRT-015. Eyeing an ACLF market estimated to total $4 billion in the U.S. and five major European countries alone, the Seal Rock deal means Genfit now has three candidates targeting this space. Those include VS-01, which is in a phase 2 trial for adults with ACLF grades 1 and 2 and ascites, as well as NTZ, which has completed a pair of phase 1 studies in renal and hepatic impairment. Genfit is now readying NTZ for a phase 2 in ACLF. Genfit CEO Pascal Prigent said today’s licensing agreement “marks an additional milestone in the execution of our development strategy in liver diseases with high unmet medical needs.” “ACLF is a complex disorder that will likely require the combination of different approaches and with this acquisition, we continue to strengthen our leadership in this indication,” Prigent added. “Considering its liver-centric activity, the potential for multi-organ benefits and the breadth of evidence supporting further development in ACLF, we strongly believe in the potential of SRT-015.” While no upfront payment was mentioned in the release, Seattle-based Seal Rock is in line for up for 100 million euros in regulatory, clinical and commercial milestone payments alongside tiered royalties. Genfit’s remaining therapeutic pipeline includes the dual PPAR agonist elafibranor, which is undergoing late-stage studies for primary biliary cholangitis and has been licensed by Ipsen. There's also GNS561, a PPT1 inhibitor that has previously completed a phase 1 trial and is now being developed for bile duct cancer, and VS-02, a preclinical urease inhibitor the biotech hopes to progress for hepatic encephalopathy.