ViaCyte is a company developing a stem cell-based therapy for diabetes. The therapy is a combination product, called VC-01™, comprised of human embryonic stem cell (hESC)-derived pancreatic beta cell precursors (PEC-01™ cell product), encapsulated within the Encaptra® drug delivery system (ENCAPTRA device). After implantation, the precursor cells mature into endocrine cells that secrete insulin and other hormones in a regulated manner to control blood sugar levels in animal models of diabetes. hESC are the renewable starting material for cell manufacturing; they are directed to differentiate to PEC-01 cell product using scalable processes. The retrievable ENCAPTRA device is designed to contain cells and to protect cells from immune attack. The goal is to develop a product that will provide insulin independence, reduce diabetes-related complications, and eliminate the need for chronic immunosuppressant drugs.

This CIRM award is focused on product safety. An important nonclinical safety assessment of this combination product therapy is the evaluation of its tumorigenicity, i.e., its capacity to form tumors. Upon transplantation into animal models, undifferentiated hESC can generate a teratoma, a tumor that is akin to a particular type of germ cell tumor that can form in humans. Accordingly, to the extent that undifferentiated hESC could potentially remain in the differentiated PEC-01 cell product, these could potentially give rise to a teratoma. Prior to this award, it was unclear whether teratomas will form when undifferentiated hESC are implanted within the ENCAPTRA device and if so, what threshold dose of hESC in PEC-01 would be required to produce a teratoma.

ViaCyte received this award to develop methods to assess teratoma potential with in vivo and in vitro assays, and to mitigate potential tumorigenicity risk by ensuring integrity of the encapsulation delivery device. ViaCyte has investigated a standardized assay to measure the presence of hESC in PEC-01 cell product, and preliminary tumorigenicity studies of VC-01 were completed with safe outcomes. With these data in hand, definitive IND-enabling tumorigenicity studies were designed and initiated to include in a package that will be submitted to the FDA as ViaCyte seeks approval to test the product in human clinical trials. A large assurance of safety is provided by confining the transplanted cells within the device and by the ability to retrieve the product. To demonstrate that the ENCAPTRA device will be effective in containing implanted cells in a patient, ViaCyte has also developed assays and performed studies to ensure the integrity of the ENCAPTRA device. Collectively, the data from these studies will form a compelling package to demonstrate the safety of the VC-01 product so that clinical trials can be initiated with the goal of developing a game-changing cell therapy for diabetes.