OR03-6 Further Clinical Evaluation of Stem Cell-Derived Islet Replacement Therapy (VC-02) Demonstrates Production of C-Peptide with Improvements in Glycemic Control Parameters in Multiple Patients with Type 1 Diabetes and Hypoglycemia Unawareness

VC-02 combination product (PEC-Direct) is a clinical-stage regenerative medicine therapy being developed for patients with type 1 diabetes and hypoglycemia unawareness intended to restore homeostatic glycemic control. It is comprised of stem cell-derived pancreatic progenitors (PEC-01) loaded into a macroencapsulation device that facilitates the in-growth of blood vessels into the device lumen, supporting the maturation and differentiation of the graft into hormone-positive islet cells comprising glucose-responsive beta cells. Initial data from one patient (2021, Keymeulen) demonstrated clinically-relevant levels of stimulated C-peptide and corresponding improvements in glycemic control within six months after subcutaneous implantation. These improvements now include a time-in-range consistently >90% and a persistent HbA1C <7%.Enrollment of additional patients with negligible C-peptide levels in the ongoing VC02-101 study implanted with the same device configuration has now resulted in multiple patients demonstrating C-peptide levels ≥0.3 ng/mL. All patients are challenged with a mixed-meal tolerance test at baseline and post-implantation to detect and monitor increases in plasma C-peptide levels. In some cases, the increased C-peptide levels are observed to occur as soon as two months post-implant with subsequent increases resulting as the patients progress further into the treatment period as high as 0.4 ng/mL by five months with additional time points at longer periods of exposure pending. This progressive rise in beta cell function is consistent with preclinical findings showing time-dependent differentiation of the pancreatic progenitors into beta cells and subsequent increases in beta cell mass.The increases in plasma C-peptide levels also correlate with trends toward improved glycemic control parameters. Relative to baseline levels, improvements are observed in time-in-range data captured from continuous glucose monitoring, as well as substantial decreases in HbA1C by as much as 1.5%. These positive trends also correlate with decreases in the amount of exogenous insulin required by as much as 70%. Importantly, these data and observations have been obtained at separate clinical sites involving different surgeons, indicating that the achievement of functional engraftment of PEC-Direct is reproducible with proper product handling, surgical training, and patient compliance with an adjunctive immunosuppression regimen. These data provide further proof-of-concept that continued optimization of PEC-Direct can result in a functional cure for T1D. Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.