Tr1 Treg Therapy to be Evaluated in Trial for Crohn Disease
TRX103 is also being evaluated for the prevention of graft versus host disease (GvHD) in patients undergoing HLA-mismatched HSCT.
Florian Rieder, MD
Credit: Cleveland Clinic
The FDA has cleared Tr1X’s investigational new drug (IND) application for its cell therapy TRX103 for the potential treatment of Crohn disease (CD).1
“Despite the advances in biological and targeted therapies in Crohn disease, many of our patients do not achieve remission or relapse on treatment. This suggests a therapeutic ceiling for current anti-inflammatory therapies and novel approaches are needed,” Florian Rieder, MD, Vice Department Chair and codirector, Inflammatory Bowel Diseases (IBD) Section, Cleveland Clinic, said in a statement.1 “TRX103 is a novel and exciting Tr1 Treg cell therapeutic that combines anti-inflammatory and immunomodulating activities. It has the potential to reset the immune system to improve long-term outcomes for these patients.”
Tr1X is an allogeneic engineered Tr1 Treg cell therapy designed to reduce inflammation, promote tissue healing and repair, and reset immune homeostasis in the gut of patients with inflammatory bowel diseases, including CD. The therapy consists of T cells generated from CD4+ cells sourced from healthy donors that are engineered to become cells that mimic the function of Tr1 regulatory T cells, called TRX cells. Tr1 cells are able to traffic to inflamed tissues and lymph nodes, lower inflammatory cytokines, control harmful T cell responses, and create immune tolerance potentially without the need for lymphodepletion.
The IND clearance allows Tr1X to initiate a phase 1/2a, dose escalation and confirmation study of TRX103. The study will evaluate the safety, tolerability, and clinical activity of TRX-103 in participants with moderate to severe CD that has failed 3 or more advanced therapies.
READ MORE: Direct Biologics’ Phase 1 Clinical Trial Seeks to Treat Crohn Disease With Extracellular Vesicles
“Tr1 Tregs were first validated preclinically in animal models of inflammatory bowel disease, where they demonstrated their important anti-inflammatory and immunomodulatory effects,” Maria Grazia Roncarolo, MD, President and Head, R&D, Tr1X, added.1 “It is a full-circle moment for us to be able to test these allogeneic engineered Tr1 cells for the first time in the setting of Crohn’s disease, and to prove their importance in restoring and maintaining gut homeostasis for the benefit of patients worldwide.”
TRX103 is also being evaluated in a phase 1 clinical trial (NCT06462365) for the potential treatment for the prevention of graft versus host disease (GvHD) in patients undergoing HLA-mismatched hematopoietic stem cell transplantation. The trial dosed its first participant in July 2024.2
The first patient has cleared the trial’s safety period successfully, with no serious adverse events, and further enrollment is ongoing. Tr1X anticipates reporting initial safety and efficacy results from the multicenter, dose-escalation trial by the fourth quarter of this year.
“This first patient to receive an allogeneic engineered Tr1 cell therapy, TRX103, is a significant achievement for our company, our scientists, and the field of cell and gene therapy,” Roncarolo said in a statement at that time.2 “This is a key step in advancing our pipeline. We believe our allogeneic Tr1 Treg and CAR-Treg therapies can overcome the limitations of current treatments by controlling harmful T-cells and B-cells and creating immune tolerance, potentially curing a wide range of autoimmune and inflammatory disorders.”
