This Phase IIB SBIR application is responsive to NHLBI RFA HL-13-016, "NHLBI SBIR Phase IIB Bridge Awards to Accelerate the Commercialization of Technologies for Heart, Lung, Blood and Sleep Disorders and Diseases (R44)". This RFA solicits work on "basic, applied, and clinical research on all product and service development related to the mission of the NHLBI... including cardiovascular complications of diabetes and obesity, ... and peripheral vascular diseases." Humaycte has developed a novel vascular graft that has shown excellent function in large animal models. The graft is made by culturing allogeneic human smooth muscle cells in a bioreactor to produce an engineered vascular tissue, which is then carefully decellularized. Vascular dialysis grafts that are 6 mm in diameter function well in a baboon model of arterio-venous grafting. In our Phase II proposal, our aim was the construction and testing of a prototype, disposable vascular graft bioreactor. In this Phase IIB proposal, we will build on our successful Phase II work, and we will develop a closed, FDA-compliant manufacturing system that can produce manufacturing batches of 100 grafts/unit, enabling production sufficient to support clinical trials and eventual commercialization. This Phase IIB application will also support a Phase I/II clinical trial examining the safety and efficacy of the engineered vascular graft for hemodialysis access. Manufacturing data from this system, combined with clinical data from our Phase I/II trial, will be submitted to the FDA. At the conclusion of this study, we will file a Special Protocol Assessment (SPA) in support of a Phase III trial in the U.S. on Humacyte's vascular grafts in hemodialysis patients. These grafts have the potential to decrease morbidity from graft-related complications in patients with end-stage renal disease, as well as other patients requiring arterial bypass grafts.
This Phase IIB SBIR application addresses a critical need in regenerative medicine: the development of scaled manufacturing systems that produce engineered tissues in a reproducible and economical fashion. This application also tests an engineered vascular graft in end-stage renal disease patients requiring hemodialysis access.