Objective
We have a clinical grade cell line that is specifically designed to support genetic engineering. We will edit and engineer this line using our proprietary technologies to make stem cells that can be used to make tissues that will not require a patient receiving the tissues to be immune-suppressed. This will be the first of its kind raw material and will be the foundation for a completely new product that can help many people, and especially Type 1 diabetics who could receive a stem cell derived islet therapy made from these cells.
Background Rationale
Since the discovery of insulin in 1921 by Drs. Banting and Best and the first person treated with animal derived insulin in 1922 several stepwise and incremental improvements have dramatically improved insulin availability and delivery. In 1980, insulin therapy for diabetes moved from pig and bovine insulin products to E.coli derived recombinant human insulin . The pairing of this new source of insulin with the first commercially available insulin pump in 1979 were significant improvements to old multiple shots of animal insulin. Additional improvements over the next 35 years led to portable insulin delivery devices paired with wearable computerized glucose sensing culminating in the first hybrid closed loop glucose monitoring and delivery system from Medtronic in 2015. Closed loop glucose monitoring and insulin delivery technology has since eliminated or greatly reduced the need for insulin injections besides that delivered by pump.
Still, these mechanical and external therapeutic systems must rely on synthetic insulin. Compared to biologic glucose regulation, even the best mechanical exogenous systems are relatively ineffective at achieving and maintaining optimal glycemic control since they cannot fully replicate the finely tuned endogenous system of insulin secretion and other pancreatic hormones in response to fluctuating blood sugar levels in the fasted and fed states. Furthermore, in some patients, exogenous administration of insulin does not eliminate wide swings in glucose levels, alternatively resulting in hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar). Hypoglycemic unawareness, otherwise known as “brittle diabetes”, is particularly dangerous in children, the elderly, or infirm patients, and especially at night when it can be deadly. There is currently no treatment available for brittle diabetes in the most high risk populations like children or those at risk of cancer or infection.
There is only one way to make this possible: deliver a functional graft of pancreatic tissue that does not require chronic immune-suppresion. We intend to make the first commercially available, pluripotent stem cells for use as a raw material to make pancreatic islet like tissues for treating insulin dependent diabetes.
Description of Project
Recent advances in islet replacement therapy, including the FDA approval of Lantidra and the promising clinical development of Vertex's VX-880, offer hope for individuals with Type 1 Diabetes (T1D). However, these therapies require life-long chronic immunosuppression severely restricting patient eligibility and lifestyle due to the significant increased risk of cancer and opportunistic infection. These limitations of immunosuppression prevent adoption of a widely applicable islet therapy cure for the majority of T1D patients, and other forms of insulin dependent diabetes.
Our company has developed a patented and transformative solution: genetically pre-engineered pluripotent stem cells (PSCs) designed to serve as a universal raw material to make therapeutic cells and tissues, such as beta islet organoids. Crucially, our approach enables allogeneic transplantation without the need for chronic immunosuppression. This is achieved through proprietary licensed technologies including iACT (inducing allogeneic cell tolerance) factors engineered into healthy, young PSCs, paired with the unique drug-inducible FailSafe safety mechanism for eliminating any unwanted growing cells post-transplantation. Published proof-of-concept studies using prototype cells demonstrated successful differentiation, in vivo persistence in allogeneic settings without immunosuppression, and effective in vivo removal of growing cells if needed via FailSafe.
We are requesting Breakthrough T1D support to make a well-characterized, ready-to-use product (a pluripotent stem cell line) that can be used to manufacture stem cell derived islets. This critical resource will enable efficient manufacturing of an "off-the-shelf" islet replacement therapy designed for allogeneic use without chronic immunosuppression, thereby addressing a major unmet need and significantly broadening access to a potential cure for Type 1 Diabetes.
Anticipated Outcome
Within one year we will have a fully manufactured and tested cell line that can be used in further manufacturing of stem cell derived islets
Relevance to T1D
This is the doorway to one of the largest changes in treatment of insulin dependent diabetes since the discovery of insulin and the adoption of closed loop insulin pumps. Unlike exogenous insulin, islets made from this raw material and used to treat Type 1 diabetes, would effectively be like a cure. No chronic immune-suppresion with the paired risk of cancer of deadly infections, no finger sticks, no worrying about low glucose levels overnight; simply the ability to live life without always worrying .