polyTregs / National Institute of Allergy and Infectious Diseases - LARVOL DELTA

The ProTreg21 Protocol: Phase I/IIa Regulatory T cell Therapy Clinical Trial in Deceased-Donor Kidney Transplantation. (PubMed, Kidney360) - "ProTreg21 will establish whether Treg02 can be manufactured and administered safely following deceased donor kidney transplantation and will provide exploratory data to inform subsequent efficacy trials."

Journal • P1/2 data • Cardiovascular • Infectious Disease • Oncology • Transplant Rejection • Transplantation

GNTI-932: A Targeted, Scalable, and Hypoimmune Allogeneic Engineered Treg therapy for the treatment of Inflammatory Bowel Disease. (IMMUNOLOGY 2026) - "Introduction/Rationale: Autologous polyclonal regulatory T cell (Treg) therapies hold promise for treating autoimmune and inflammatory bowel disease (IBD), but face challenges with specificity, stability, cost, long manufacturing times, inconsistent quality, and logistical complexity...GNTI-932 integrates four innovations: gut-specific targeting via synthetic binding receptors; stable Treg phenotype by FOXP3 overexpression in bulk CD4⁺ T cells; a rapamycin-inducible IL-2 signaling complex (CISC) supporting in vivo stability and purity; and immune evasive engineering (IEE) combining HLA class I/II knockout with a proprietary NK cell inhibitor to prevent rejection. In vitro, GNTI-932 showed a characteristic Treg phenotype (CD25, CTLA-4, LAP, GARP), suppressed effector CD4⁺ T cells, secreted no proinflammatory cytokines, and resisted allo-rejection. GNTI-932 is a novel, hypoimmune, antigen-specific, off-the-shelf immunotherapy for restoring tolerance in IBD, designed to be..."

IO biomarker • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • CTLA4 • FOXP3 • IL2 • IL2RA

cePolyTregs in Islet Transplantation (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: University of Alberta | N=11 ➔ 0 | Trial completion date: May 2026 ➔ May 2025 | Active, not recruiting ➔ Withdrawn | Trial primary completion date: May 2026 ➔ May 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

PolyTreg Immunotherapy in Islet Transplantation (clinicaltrials.gov) - P1 | N=11 | Completed | Sponsor: University of Alberta | Active, not recruiting ➔ Completed | N=18 ➔ 11

Enrollment change • Trial completion • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

PolyTreg Immunotherapy in Islet Transplantation (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: University of Alberta | Trial completion date: Oct 2024 ➔ Jan 2025

Trial completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

TASK: Treg Therapy in Subclinical Inflammation in Kidney Transplantation (clinicaltrials.gov) - P1/2 | N=32 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=14 ➔ 32

Enrollment change • Inflammation • Transplantation

PolyTreg Immunotherapy in Islet Transplantation (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: University of Alberta | Trial completion date: May 2024 ➔ Oct 2024 | Trial primary completion date: Aug 2022 ➔ Aug 2024

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

cePolyTregs in Islet Transplantation (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Alberta | Trial completion date: May 2024 ➔ May 2026 | Trial primary completion date: May 2024 ➔ May 2026

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

cePolyTregs in Islet Transplantation (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Alberta | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

TASK: Treg Therapy in Subclinical Inflammation in Kidney Transplantation (clinicaltrials.gov) - P1/2 | N=14 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Inflammation • Transplantation

Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Completed ➔ Terminated; Lack of recruitment, ongoing and new feasibility issues, and the impact of the coronavirus infectious disease 19 (COVID-19) pandemic

Trial termination • Dermatology • Immunology • Pemphigus Vulgaris • CD4 • IL2RA • IL7R

Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Pemphigus Vulgaris • CD4 • IL2RA • IL7R

TASK: Treg Therapy in Subclinical Inflammation in Kidney Transplantation (clinicaltrials.gov) - P1/2 | N=14 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammation • Transplantation

Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus (clinicaltrials.gov) - P1; N=4; Active, not recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); N=12 ➔ 4; Trial completion date: Sep 2021 ➔ Jan 2023; Trial primary completion date: Sep 2021 ➔ Jan 2021

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Dermatology • Dermatopathology • Immunology • Pemphigus Vulgaris

Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS) (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: Jeffrey Bluestone | N=18 ➔ 4 | Trial completion date: Nov 2022 ➔ Mar 2022 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2022 ➔ Mar 2022; Decrease in COVID-19 cases made further enrollment infeasible.

Enrollment change • Preclinical • Trial completion date • Trial primary completion date • Trial termination • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

cePolyTregs in Islet Transplantation (clinicaltrials.gov) - P1 | N=11 | Recruiting | Sponsor: University of Alberta | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

PolyTreg Immunotherapy in Islet Transplantation (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: University of Alberta | Trial completion date: Dec 2022 ➔ May 2024

Trial completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

cePolyTregs in Islet Transplantation (clinicaltrials.gov) - P1 | N=11 | Not yet recruiting | Sponsor: University of Alberta | Initiation date: May 2022 ➔ Aug 2022

Trial initiation date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

PolyTreg Immunotherapy in Islet Transplantation (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: University of Alberta | Recruiting ➔ Active, not recruiting | Trial completion date: May 2022 ➔ Dec 2022 | Trial primary completion date: Apr 2022 ➔ Jul 2022

Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

TASK: Treg Therapy in Subclinical Inflammation in Kidney Transplantation (clinicaltrials.gov) - P1/2 | N=14 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=30 ➔ 14 | Trial completion date: Jun 2022 ➔ Jun 2023 | Trial primary completion date: Jun 2022 ➔ Jun 2023

Enrollment change • Trial completion date • Trial primary completion date • Immunology • Inflammation • Transplantation

Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience. (PubMed, Front Immunol) - "We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020)...Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production."

Journal

T1DM Immunotherapy Using Polyclonal Tregs + IL-2 (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Jeffrey Bluestone; Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD8

Tregs for the Treatment of Acute Respiratory Distress Syndrome (ARDS) Associated With COVID-19 (regARDS) (clinicaltrials.gov) - P1/2; N=18; Recruiting; Sponsor: Jeffrey Bluestone

New P1/2 trial • Preclinical • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

T1DM Immunotherapy Using Polyclonal Tregs + IL-2 (clinicaltrials.gov) - P1; N=16; Active, not recruiting; Sponsor: Jeffrey Bluestone; Trial completion date: Dec 2021 ➔ Aug 2021

Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD8

TASK: Treg Therapy in Subclinical Inflammation in Kidney Transplantation (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: Oct 2021 ➔ Jun 2022; Trial primary completion date: Oct 2021 ➔ Jun 2022

Trial completion date • Trial primary completion date • Immunology • Inflammation • Renal Disease • Transplantation