Manufacturing Clinical-Grade Cell Capsule of O2Line(TM) Implant System for T1D

PROJECT SUMMARY Manufacturing Clinical-Grade Cell Capsule for O2Line™ Implant System for T1D Our ultimate goal for this program is to develop the manufacturing process for the cell capsule of the Persista Bio™ O2line™ system, an advanced oxygenated cell encapsulation system targeting Type 1 diabetes (T1D) treatment. The system features high capacity, fibrosis mitigation, long-term efficacy, immunosuppression-free operation, donor-independence, and full implantability with minimally invasive procedures. For T1D treatment, current insulin pumps face limitations in achieving long-term, physiologically responsive glycemic control. While islet transplantation, an alternative option, has shown promising results, it remains dependent on donor availability and requires lifelong immunosuppression. In comparison, cell encapsulation therapy offers a physiological response to blood glucose levels and protects against immune system attacks. The technology involves encapsulating cells in a hydrogel or a semipermeable nanoporous device, facilitating the diffusion of nutrients and insulin, while also providing a barrier against immune cells. It has advanced significantly, addressing previous issues and moving towards clinical trials. However, major hurdles remain in the field, including oxygen deficiency and foreign body reactions. Oxygen deficiency arises from low oxygen solubility and insufficient vasculature at the implantation site, impacting cell viability and glucose responsiveness, thus limiting cell density and device longevity. Foreign body reactions, typically stemming from the materials used, further exacerbate these issues, affecting device performance and oxygen availability. To tackle these challenges, Persista Bio Inc. was established to integrate innovative technologies from Prof. Ma at Cornell University and Giner Inc. The O2line™ system combines a core-shell nanofibrous cell encapsulation design with fibrosis-mitigating modifications from the Ma lab for safe and efficient cell delivery, and Giner’s implantable electrochemical oxygen generator (iEOG), which controllably converts tissue water into hydrogen and oxygen. This integration has been successfully developed and tested for efficacy in small animals. The focus of this proposal is to advance the manufacturing of the cell capsule component of the O2line™ system. By partnering with a GMP electrospinning provider, we will develop a consistent, large-scale production process. This work will serve as a crucial step toward achieving commercial production and preparing for clinical trials. For this PAR-24-131 Small Business Transition Grant for New Entrepreneurs, the PI puts forth objectives for his career development focusing on transitioning into an entrepreneurial role with principal investigator responsibilities. He has guidance from two highly experienced mentors and has designed a career development plan for Phase I and beyond, which includes: VC due diligence, investor presentations, grant writing, and entrepreneurship courses.