Over 725,000 patients have end stage renal disease, with nearly 90% utilizing hemodialysis for renal replacement therapy. A functioning and durable vascular access is required, and an arteriovenous fistula (AVF) is preferred due to a lower rate of infections, thrombosis, and healthcare expenditures. However, after formation, approximately 60% of AVFs fail to mature, due to early intimal hyperplasia and inadequate vasodilation. At present, there are no effective therapies to promote vascular access maturation. The annual cost of treating vascular access dysfunction totals over $1 billion US dollars. Endomimetics has developed a nitric oxide (NO) releasing bionanomatrix gel (“AVF Gel”) that improves the maturation of AVFs by inhibiting intimal hyperplasia, enhancing vasodilation, and reducing inflammation. Through SBIR Phase I and II grant funding, this AVF Gel has been evaluated in both small and large animal models (rat and pig), demonstrating improved blood flow and inhibition of intimal hyperplasia. In this Phase IIB proposal, we propose Aims that will prepare Endomimetics to meet FDA requirements for Phase I clinical trials. These Aims include 1) Development of a manufacturing plan with AmbioPharm for large scale peptide synthesis and with Bioserv America for formulation, fill and finish, sterilization, and packaging that is consistent with FDA requirements and 2) Perform stability and biocompatibility evaluations of the AVF Gel in vitro and in vivo based on The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and International Organization for Standardization (ISO) guidelines. We are beginning the FDA review process, and an initial conversation with the FDA occurred on March 4, 2020, in which the FDA was consulted on future steps necessary to advance to Phase I clinical trials. Commercialization of the Endomimetics AVF Gel may provide significant improvement in the treatment of patients requiring dialysis.

Project Narrative Arteriovenous fistula (AVF) non-maturation occurs in 60% of hemodialysis patients receiving an AVF for hemodialysis. This results in significant morbidity and mortality due to suboptimal vascular access and increased risk of infection. Endomimetics, LLC has developed a novel AVF Gel that improves AVF maturation rates through a novel nitric oxide (NO) releasing, prohealing mechanism. The goal of this Phase IIB proposal is preparation for the FDA requirements in order to advance to Phase I clinical trials.