SA FasL engineered human islets as a novel product for the treatment of type diabetes

PROJECT SUMMARY
Type diabetes T D is a chronic autoimmune disorder that affects of population worldwide Exogenous
insulin treatment is the standard of care for T D but often negatively affects the quality of life and is ineffective
in preventing recurrent hyperglycemia episodes and chronic complications Recent studies show that human
islet allografts can restore long term normoglycemia and insulin independence protect from severe
hypoglycemia and slow progression of microvascular lesions in immunosuppressed T D patients However
immune rejection and continuous use of immunosuppression to control rejection are two major limitations
of clinical islet transplantation Standard immunosuppression is ineffective in achieving long term graft survival
and also has significant adverse effects on the graft and graft recipients Therefore the development of novel
approaches to prevent rejection of islet grafts without chronic immunosuppression is a significant goal
FasCure Therapeutics is focused on the development of biologics with desired immune modulatory
activities for targeted indications The Company has exclusive rights to a portfolio of proprietary novel immune
inhibitory ligands as components of an immunomodulatory platform for prevention and treatment of
autoimmune diseases and graft rejection The Company s lead therapeutic platform includes islets engineered
with a novel form of Fas ligand immunomodulatory protein SA FasL T cells are the main culprits of T D as
well as allogeneic islet graft rejection T cells upregulate Fas receptor on their surface following antigen
activation and become sensitive to Fas FasL mediated apoptosis Importantly FasL induced apoptosis plays
an important role in T cell homeostasis and tolerance to self antigens As such SA FasL has significant
potential for the induction of tolerance to auto and alloantigens Consistent with this notion the transient
display of SA FasL protein on pancreatic islets have shown robust efficacy in overcoming immune rejection in
various allogeneic and xenogeneic rodent transplantation models The major goals of this phase I STTR
application is to i assesses the feasibility of engineering human islets with SA FasL protein without
negatively impacting their function and ii test the efficacy of SA FasL engineered islets in overcoming
rejection in a humanized mouse model in the absence of continuous immunosuppression If feasibility
and efficacy are shown in the humanized mouse model the SA FasL engineered human islets will be further
developed as a novel product in a Phase II STRR application for translation into clinic PROJECT NARRATIVE
Type diabetes T D is a chronic autoimmune disorder that affects more than of the population
worldwide Insulin as a standard treatment has major long term complications therefore the development of
novel approaches to prevent and treat T D is a significant therapeutic goal The primary objective of this
proposal is to engineer human pancreatic islets with an immunomodulatory biologic and test the efficacy of
engineered islets in preventing rejection and treating diabetes in a humanized mouse model If effective this
approach will have immediate and important implications for the use of allogeneic islets for the treatment of
T D in humans