Introduction: Sigilon Therapeutics is developing an allogeneic cell therapy for the treatment of type 1 diabetes (T1D), in partnership with Eli Lilly and Company.  In T1D, the insulin-secreting beta cells within the pancreatic islets are attacked by the immune system resulting in dysregulation of glucose metabolism.

Method: We differentiated human induced pluripotent stem cells to generate stem cell-derived islets (SC-islets), which contain the glucose-responsive, insulin-secreting beta cells that are missing in T1D patients.  The SC-islets were encapsulated in alginate hydrogel spheres to produce our drug product candidate, SIG-002.  Sigilon’s Shielded Living Therapeutics™ platform technology uses Afibromer™ alginate spheres that are designed to mitigate the foreign body response to biomaterials and to protect the SC-islets from the patient’s immune system, thereby avoiding the need for immunosuppression. 

Results: Our differentiation protocol reproducibly generated SC-islets that contained a high percentage of beta cells, high insulin content, and demonstrated glucose-regulated insulin secretion.  SIG-002 showed glycemic regulation in a diabetes mouse model.  Assessment of the foreign body response to SIG-002 in vitro and in a humanized mouse model demonstrated that Afibromer alginate mitigated foreign body response-induced pericapsular fibrotic overgrowth by preventing macrophage attachment.

Conclusion: We have shown that SIG-002 is efficacious and that Afibromer alginate mitigates the foreign body response.  With these encouraging preclinical data, we have laid the foundation for achieving our goal of developing a functional cure for T1D.