Advanced Pre-Clinical Development of O2LineTM System for Type 1 Diabetes Cell Therapy

PROJECT SUMMARY Advanced pre-clinical development of O2Line™ system for type 1 diabetes cell therapy The overall goal of this program is to advance preclinical development of a safe, anti-fibrotic, high capacity, and oxygenated cell encapsulation device (termed as the O2line™ system) for type 1 diabetes (T1D) cell replacement therapy. Transplantation of human cadaveric islets and more recently human stem cell- derived insulin-producing cells (hSC-beta cells) has shown that cell replacement therapy can be curative and provide better glycemic control for T1D patients than even the most advanced insulin therapies (i.e. closed-loop insulin delivery systems). Thus, cell therapies have the potential to provide a much better quality of life both in the short term (decreased burden) and long term (decreased diabetes complications). However, delivering the cells safely, effectively and without immunosuppression remains a daunting challenge. Cell encapsulation approaches seek to provide long-lasting treatment for large numbers of T1D patients without the risks and costs of immunosuppression and loose transplanted allogeneic cells. While substantial advancements have been made, the bottleneck remains the lack of safe, long-term functional and clinically practical encapsulation and delivery systems. Among the challenges are: (1) insufficient access to vasculature or oxygen limiting cell viability and overall capacity; and (2) foreign body responses and fibrotic reactions against the encapsulation material or device. To address these challenges, we (Co- founders of Persista Bio: Dr. Tempelman of Giner, Inc. and Dr. James Flanders, Dr. Beum Jun Kim and Dr. Minglin Ma of Cornell University) combine our expertise and integrate our best innovative technologies (implantable electrochemical oxygen generator and core-shell nanofibrous cell capsule) to develop a clinically translatable O2line™ system. This system, if successful, will be able to deliver a curative dose of insulin-producing cells by addressing the issues of oxygen deficiency, fibrotic reactions and immunoprotection. In the O2line™ approach, oxygen is generated constitutively and in situ by the electrolytic conversion of small quantities of tissue water into hydrogen and oxygen by an implantable electrochemical oxygen generator (iEOG), a technology perfected over many years for organ preservation and in vivo use by the Tempelman team. The oxygen generated from this module is delivered in a controllable manner to a core-shell, anti-fibrotic nanofibrous cell capsule developed and optimized by the Ma lab for almost a decade. This proposed development and preclinical demonstrations will lay the foundation required to attract funding for commercial product development and clinical translation.