A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus

Through histology, the potential for functional engraftment of VC-01 combination product could be assessed in Cohort 1 subjects. Explanted sentinel units from subjects were processed and stained for markers identifying the number of graft cell nuclei (i.e., signifying the cells were viable). The percentage of viable graft cells in these explanted units were then compared to the percentage of viable graft cells from the pre-clinical (i.e., animal) models. These pre-clinical models are based on animal studies performed at ViaCyte (ref: internal study report). The data in Outcome Measure Data Table represent the % of viable graft cells present in the explanted sentinels compared to what was expected based on the animal model at Weeks 4, 8, 12, and 26 (e.g., At Week 4, there was an average of 18.27% viable graft cells in the participant's explants compared to what was expected based on the animal models).

Time frame: Weeks 4, 8, 12 and 26

Population: For each timepoint, explanted sentinel units containing PEC-01 cells from the 17 subjects were stained and evaluated for graft cell survival (i.e., viability). Not all subjects had units explanted at every timepoint, and units explanted that had de minimus graft cell survival (i.e., minimal, \< 500 cells, \< 4% of pre-clinical controls) could not be evaluated and were not included in the summary table.

Evaluation of clinical efficacy of VC-01 combination product in Cohort 2 subjects was intended by measuring C-peptide levels during a 4-hour Mixed Meal Tolerance Test (MMTT). Blood glucose and C-peptide data were collected from subjects at timepoints 0, 30, 60, 90, 120, 180, 240 minutes after ingestion of a meal (i.e., BOOST drink). These C-peptide data points could be used to create the AUC calculation. If the implanted units contained mature, insulin-producing cells, stimulated C-peptide levels would be expected to increase over the time course in reaction to the meal.

Time frame: To Week 26

Population: Stimulated C-peptide data from the MMTT showed every value from baseline and Week 26 samples at all timepoints to be undetectable (\<0.1 ng/mL) except for one subject for whom the AUC could be calculated. Analyzing the data was deemed futile because the number of surviving graft cells was noted as insufficient for establishing the biological critical mass. The change from baseline to Week 26 in AUC for this one subject is provided below.