POLARIS: A Phase 1, Single Dose, Open-label Study of GNTI-122 in Adults With Recently Diagnosed Type 1 Diabetes (T1D)

This is a 78-week single arm, multi center, Phase 1 study to evaluate the safety, tolerability, cellular kinetics, and biomarker changes in C-peptide over time of GNTI-122 in adult participants with recently (within 180 days of Screening) diagnosed T1D. GNTI-122 is an investigational cell therapy manufactured from a participant's own blood cells and is intended to help correct an imbalance of certain types of cells found in patients with Type 1 Diabetes (T1D).

After assessment of eligibility, participants who qualify for the study will be enrolled sequentially in 1 of 3 cohorts. Cohorts 1 and 2 are safety run-in cohorts (n=3 participants per cohort) in which each participant receives a single dose of GNTI 122 alone; Cohort 1 receives a low dose 1 of GNTI-122 and Cohort 2 receives a high dose of GNTI-122. Cohort 3 includes 10 participants that will receive a single high dose of GNTI-122 in combination with rapamycin (with a target trough concentration [Ctrough] of 3 to 6 ng/mL), which may extend the survival of GNTI-122. Participants will remain at the clinical site for observation for at least 4 hours after administration of GNTI-122.

Safety and tolerability assessments over the 78-week study include: vital signs, 12-lead electrocardiograms, physical examinations, clinical laboratory evaluations, monitoring of adverse events and concomitant medications. Risks to participants will be minimized by the incorporation of sentinel dosing (i.e., at least 28 days of safety assessments between first and second participant and at least 14 days between the second and third participant in Cohorts 1 and 2, and at least 14 days between the first and second participant and the second and third participant in Cohort 3) and the evaluation of safety and tolerability by a Safety Review Committee with at least 14 days of safety assessments (i.e., laboratory values and adverse event reporting) after 3 participants are dosed in Cohort 1 and Cohort 2. Disease markers (e.g., MMTT-stimulated C-peptide, HbA1c) and pharmacodynamic activity (e.g., lymphocyte subsets and phenotypes, effector T cell responses to islet antigens ex vivo, T1D autoantibodies) will be monitored serially throughout the study.

In Cohort 3, rapamycin concentrations will be measured periodically to ensure levels are in the target range of Ctrough level between 3 and 6 ng/mL.

Per Health Authority guidelines (Food and Drug Administration) for gene therapy products or advanced medicinal products, all participants treated with GNTI-122 who complete or discontinue from this study must be monitored for specific toxicities for a total of 15 years (semi-annually or annually), irrespective of their response to GNTI-122. This will be addressed in a separate protocol of a long-term follow-up study of these participants.