Periodic Reporting for period 1 - TRACTION (Transcription Factor Gene Therapy for Bradyarrhythmias)
Periodo di rendicontazione: 2023-01-01 al 2023-12-31
At the centre of TRACTION is BradyTx-01, a ground-breaking gene therapy medicinal product (GTMP) developed by PacingCure, specifically engineered to combat life-threatening cardiac pacing dysfunctions. This innovative treatment reprograms regular cardiomyocytes into pacemaker cells, finely controlling therapeutic gene overexpression via adeno-associated virus (AAV)-mediated gene transfer. Termed the "biological pacemaker", BradyTx-01 will cure cardiac pacing disorders, enhance cardiac function and adapt to metabolic demands, via a minimally invasive delivery method and potentially with lifelong efficacy.
In partnership with AUMC under the TRACTION project, our goal is to advance AAV-mediated gene therapy by validating its efficacy in relevant preclinicial disease models. Concomitantly, we're developing a large-scale manufacturing process to provide gene therapy vectors at scale for preclinical validation. Moreover, within TRACTION BradyTx-01's technology-product-market fit will be actively refined, evaluating regulatory strategies, conducting health technology assessments, and further defining PacingCure’s business strategy.
The TRACTION project serves as the catalyst for BradyTx-01's progression, guiding toward clinical trials and eventual commercialization, transforming PacingCure into a fully operational, investment-ready entity poised to make a substantial impact in cardiac care.
In partnership with AUMC under the TRACTION project, our goal is to advance AAV-mediated gene therapy by validating its efficacy in relevant preclinicial disease models. Concomitantly, we're developing a large-scale manufacturing process to provide gene therapy vectors at scale for preclinical validation. Moreover, within TRACTION BradyTx-01's technology-product-market fit will be actively refined, evaluating regulatory strategies, conducting health technology assessments, and further defining PacingCure’s business strategy.
The TRACTION project serves as the catalyst for BradyTx-01's progression, guiding toward clinical trials and eventual commercialization, transforming PacingCure into a fully operational, investment-ready entity poised to make a substantial impact in cardiac care.
Towards reaching the overall objectives of TRACTION, work performed in year one of the project has been carried out, as planned, in the six pre-defined work packages.
Work package one centres around identifying the most potent reprogramming vector to induce a pacemaker phenotype, establishing a robust long-term pacemaker phenotype in mice after in vivo gene transfer and validating long-term efficacy and safety. We have optimized the GTMPs by implementing cardiac specific promoters and confirmed in vivo functionality and safety. Furthermore, we designed, produced and validated GTMPs using vector variants for increased gene therapy dosing specificity.
Work package two deals with generating non-GMP AAV vectors for porcine testing and establishing optimized process protocols for efficient scale-up towards GMP production of the lead GTMP. We have established a bioreactor-based manufacturing process to scale up production from small scale petri dish-based production to a scale that supports studies in pigs. Extensive quality control was performed to ensure that the AAV produced in the bioreactor is of comparable quality to that produced at a small scale and to inform further process development.
Work package three is about assessing safety and efficacy of GTMP in a preclinical disease model and validation of delivery of GTMP in utero in a preclinical disease model. We have established procedures and protocols to reliably generate the pre-clinical disease model, necessary to assess clinically relevant efficacy and safety of our GTMP.
Work package four focuses on developing regulatory strategies and integrate input obtained in regulatory meetings into overall GTMP development and evaluation of the properties, effects and/or impacts of our technology to set the stage for effective clinical and commercial development. We have assessed and analysed the unmet clinical need regarding the target indication. Technology profiles were drafted, delineating the intended positioning of the GTMP for an external audience. These profiles aimed to elucidate the clinical characteristics, mechanism of action, indicated usage, and administration procedures. The primary objective of these documents was to illustrate how the GTMP had the potential to enhance the prevailing "standard of care".
Work package five is about defining the optimal business scenario for market deployment and commercialization, developing an investment-ready business proposition and transition into an operational and investment-ready spin-off and facilitating interest and funding for route-to-market. After extensive debate and evaluation with our advisors, we designed a favourable business model that aims to leverage PacingCure’s intellectual property rights (IPR) and proprietary know-how.
Finally, work package six deals with project management ensuring the project tasks are executed and project objectives are realized timely and within budget and ensuring the project activities and its outcomes align with all elements of the selected business strategy. We have coordinated TRACTION scientifically, administratively and financially as planned and in agreement with all partners to meet project goals and avoid barriers.
Work package one centres around identifying the most potent reprogramming vector to induce a pacemaker phenotype, establishing a robust long-term pacemaker phenotype in mice after in vivo gene transfer and validating long-term efficacy and safety. We have optimized the GTMPs by implementing cardiac specific promoters and confirmed in vivo functionality and safety. Furthermore, we designed, produced and validated GTMPs using vector variants for increased gene therapy dosing specificity.
Work package two deals with generating non-GMP AAV vectors for porcine testing and establishing optimized process protocols for efficient scale-up towards GMP production of the lead GTMP. We have established a bioreactor-based manufacturing process to scale up production from small scale petri dish-based production to a scale that supports studies in pigs. Extensive quality control was performed to ensure that the AAV produced in the bioreactor is of comparable quality to that produced at a small scale and to inform further process development.
Work package three is about assessing safety and efficacy of GTMP in a preclinical disease model and validation of delivery of GTMP in utero in a preclinical disease model. We have established procedures and protocols to reliably generate the pre-clinical disease model, necessary to assess clinically relevant efficacy and safety of our GTMP.
Work package four focuses on developing regulatory strategies and integrate input obtained in regulatory meetings into overall GTMP development and evaluation of the properties, effects and/or impacts of our technology to set the stage for effective clinical and commercial development. We have assessed and analysed the unmet clinical need regarding the target indication. Technology profiles were drafted, delineating the intended positioning of the GTMP for an external audience. These profiles aimed to elucidate the clinical characteristics, mechanism of action, indicated usage, and administration procedures. The primary objective of these documents was to illustrate how the GTMP had the potential to enhance the prevailing "standard of care".
Work package five is about defining the optimal business scenario for market deployment and commercialization, developing an investment-ready business proposition and transition into an operational and investment-ready spin-off and facilitating interest and funding for route-to-market. After extensive debate and evaluation with our advisors, we designed a favourable business model that aims to leverage PacingCure’s intellectual property rights (IPR) and proprietary know-how.
Finally, work package six deals with project management ensuring the project tasks are executed and project objectives are realized timely and within budget and ensuring the project activities and its outcomes align with all elements of the selected business strategy. We have coordinated TRACTION scientifically, administratively and financially as planned and in agreement with all partners to meet project goals and avoid barriers.