AAV-GBA-S1S3

- Preclinical data provide proof of concept for co-expression of GBA gene with the truncated S1S3 PTase to produce highly phosphorylated GCase (β-glucocerebrosidase) - - Company’s M012 gene therapy had high M6P content and enhanced binding to CI-MPR as compared to the enzyme produced without S1S3 PTase - - Results suggest that M012 AAV can enable effective cross-correction in the CNS, and M012 AAV is a potential novel gene therapy for Gaucher disease, including neuronopathic phenotypes - ST. LOUIS--(BUSINESS WIRE)-- M6P Therapeutics (“M6PT” or “the Company”), a privately held life sciences company developing next-generation enzyme replacement and gene therapies for lysosomal storage disorders (LSDs), today announced a poster presentation titled, “A novel AAV9 gene therapy for producing β-glucocerebrosidase enzyme with high mannose 6-phosphate content to treat Gaucher disease,” by Lin Liu, Ph.D., Director, R&D of M6P Therapeutics, at the 29th Annual Congress of the European Society of Gene and Cell Therapy (ESGCT). The Congress takes place in-person and virtually in Edinburgh, Scotland from Oct. 11-14, 2022 at the Edinburgh International Conference Centre. “The data from this preclinical study illustrate the potential of our AAV-GBA-S1S3 gene therapy candidate for the treatment of Gaucher disease, including neuronopathic phenotypes,” said Pawel Krysiak, President and CEO of M6P Therapeutics. “M012 is part of our pipeline of candidates leveraging a first-in-class co-expression S1S3 platform technology for the treatment of lysosomal storage disorders. Using our technology platform, we enhance mannose 6-phosphate content on lysosomal enzymes for both enzyme replacement and gene therapies, leading to improved enzyme uptake across target tissues.” Gaucher disease is a rare inherited metabolic disorder of defective lipid catabolism caused by deficient β-glucocerebrosidase (GCase) encoding by the GBA1 gene resulting in accumulation of glycosphingolipids in the periphery and central nervous system (CNS). Multiple recombinant human GCase enzyme replacement therapies have been approved to treat Gaucher disease type 1, but there are no effective treatments to address the neuronopathic manifestations for Gaucher disease types 2 and 3. Gene therapy could be a potential therapeutic approach to treat all three types of Gaucher disease. "In this study, gene copy and transcriptome analysis showed that the dosed novel M012 AAV vector enabled transduction of peripheral tissues and various regions of brain in wild-type mice post-intravenous injection,” said Dr. Liu. “We observed increased GCase enzyme activity with enhanced CI-MPR affinity in peripheral tissues of treated animals and noted strong GCase protein signal with broad distribution detected in M012 AAV vector-treated brain samples. These results strongly suggest that M012 AAV enables effective GCase cross-correction in the CNS. We look forward to sharing additional updates and data as the program progresses.” Presentation highlights from the poster include: Data from previous publications show that co-expression of truncated GlcNAc-1-phosphotransferase (designated as S1S3 PTase) greatly increases the levels of mannose 6-phosphate (M6P) on lysosomal enzymes, which enables efficient cellular uptake via the cation-independent mannose 6-phosphate receptor (CI-MPR) that is the broadly expressed on most cells including neurons and other cell types in the CNS The study demonstrated M6P Therapeutics’ ability to regulate and enhance M6P content on lysosomal enzymes for both enzyme replacement and gene therapies, which improves enzyme uptake across target tissues, restoring the enzymatic activity within this natural pathway The M012’s novel AAV gene therapy approach uses a dual promoter construct design for co-expression of GBA gene with the truncated S1S3 PTase to produce highly phosphorylated GCase as a potential treatment for Gaucher disease The produced hGCase with S1S3 PTase co-expression was shown to have high M6P content and enhanced binding to CI-MPR as compared to the enzyme produced without S1S3 PTase GCase uptake and distribution in the CNS was also evaluated by immunohistochemical staining About M6P Therapeutics M6P Therapeutics is a privately held, venture-backed biotechnology company developing the next-generation of targeted enzyme replacement and gene therapies for lysosomal storage disorders (LSDs). M6P Therapeutics’ proprietary co-expression S1S3 platform has the unique ability to enhance phosphorylation of lysosomal enzymes for both enzyme replacement and gene therapies, leading to improved biodistribution and cellular uptake of recombinant proteins and efficient cross-correction of gene therapy product. This can potentially lead to more efficacious treatments with lower therapy burden, as well as new therapies for currently untreated diseases. M6P Therapeutics’ team, proven in rare diseases drug development and commercialization, is dedicated to fulfilling the promise of enzyme replacement and gene therapies by harnessing the power of protein phosphorylation using its co-expression S1S3 platform. M6P Therapeutics’ mission is to translate advanced science into best-in-class therapies that address unmet needs within the LSD community. For more information, please visit: .