MeiraGTx to present on genetic medicine, cell therapy at ESGCT 2025

MeiraGTx (MGTX) Holdin announced the Company will exhibit two posters at the European Society of Gene and Cell Therapy 2025 Annual Congress, which is being held from October 7-10, 2025, in Seville, Spain. Abstract Title: Novel AAV Capsids for Intravitreal Delivery Developed by Directed Evolution in Non-human Primate Eyes and Validated in Human Retinal Organoids: We performed an in vivo directed evolution capsid screen in non-human primates to identify novel capsids that target the back of the eye. This involved administering a diverse library of AAV capsid variants intravitreally into the eyes of NHPs. The library was constructed by generating a variety of AAV capsid variants through the insertion of random peptides at a specific site in the capsid. Specifically, a 7-mer peptide display library based on AAV2 was created, with a 7-mer peptide inserted at amino acid 588, flanked by a 5′ AAA linker and a 3′ AA linker. After administration, the fovea was excised, and retinal cells were harvested. By excluding the fovea, which most capsids readily transduce, we aimed to identify capsids with a broader transduction profile, extending to the perimacular region and beyond. Viral genomes were recovered and sequenced to identify the most efficient variants. By analysing the recovered viral genomes, we identified the top-performing capsids for further development. From a library of ~ 1E7 variants, the top-performing capsids were selected. These candidates were validated and compared head-to-head against AAV2.7m8 and the parental AAV2 in our human retinal organoid platform using live cell imaging, flow cytometry, histology, and single-cell RNA sequencing. We identified variants with significantly higher transduction efficiency compared to the parental serotype, AAV2, and AAV2.7m8. Deep transcriptional profiling using single-cell RNA sequencing demonstrated over 2-fold higher transduction efficiency of our novel capsids compared to AAV2.7m8. Top performers were further validated and characterized in human iPSC-derive RPE where our novel capsids showed higher transduction efficiency compared to other natural and engineered serotypes. In addition, in vivo studies in mice using absolute quantification of total retinal expression in intravitreally injected retinas, overall expression levels of our novel capsids were higher than AAV2.7m8. These novel AAV capsids have potential applications in treating various ocular diseases, including inherited retinal disorders and age-related macular degeneration. Their enhanced efficiency makes them exceptional candidates for gene therapy approaches requiring precise targeting of retinal cells and high overall levels of retinal transduction and expression. The ability to transduce a broad range of retinal cell types with high efficiency opens up new possibilities for treating complex retinal diseases that affect multiple cell types in the retina. Abstract Title: Scale-up of a Perfusion-Based AAV Manufacturing Process: Building upon prior development of MeiraGTx’s adeno-associated viral vector upstream manufacturing platform, this work presents the scale-up of our perfusion-based AAV production process to 40L bioreactors. MeiraGTx’s perfusion-based upstream process was optimized and modulated through the choice of transfection reagents, AAV production enhancers, and transfection parameters, in 250mL stirred tank reactors. Operating a perfusion-based process at bench-scale was found to increase volumetric VG yield by up to 120% and reduce plasmid DNA usage by up to 50%, without compromising on AAV productivity and product quality, resulting in a reduction in the cost-of-goods per dose of up to 2.2-fold. The work presented here focuses on the translation of bench-scale process parameters to the 40L manufacturing scale with a focus on maintaining process efficiency and product quality, to demonstrate a perfusion-based process as a viable approach for clinical and commercial AAV manufacturing.