Tr1X Doses First Patient in Proof of Concept GvHD Trial for TRX103 Therapy

Tr1X, Inc., a biopharmaceutical company specializing in the development of engineered Treg and CAR-Treg cell therapies, has announced a significant milestone. The company has successfully dosed the first patient in its TRX103-01 proof of concept trial aimed at preventing Graft versus Host Disease (GvHD) and improving outcomes for patients with hematologic malignancies undergoing mismatched hematopoietic stem cell transplantation (HSCT). Notably, this marks the first use of an allogeneic engineered Type 1 Treg (Tr1) cell therapy in clinical trials.

The primary objective of this study is to evaluate the safety, pharmacokinetics, and pharmacodynamics of TRX103. Secondary goals include fostering immune tolerance to prevent GvHD and enhancing HSCT outcomes. The initial patient experienced no serious adverse events, and the multi-center dose escalation trial continues to enroll participants, with additional preliminary safety and effectiveness data expected by the fourth quarter of 2024.

TRX103 is a pioneering Type 1 Treg (Tr1) cell therapy tailored for patients with autoimmune and inflammatory disorders, particularly those undergoing HSCT. Unlike conventional treatments, TRX103 is an off-the-shelf, engineered cell therapy designed to minimize inflammation, prevent harmful T cell proliferation, and reset the immune system. Tr1 cells possess unique properties such as traveling to inflamed tissues and lymph nodes, lowering inflammatory cytokines, controlling harmful T cell responses, and establishing immune tolerance.

Compared to other cell therapies like effector CAR-T cells, TRX103 Treg cells offer promising treatment options for autoimmune diseases with potentially fewer side effects and without the need for lymphodepletion. These cells are naturally shielded from the immune system, which enhances their persistence and reduces the risk of dangerous immune responses.

Maria Grazia Roncarolo, Co-founder, President, and Head of Research and Development at Tr1X, highlighted the significance of this achievement: "The first patient to receive an allogeneic engineered Tr1 cell therapy, TRX103, is a substantial milestone for our company, our scientists, and the broader field of cell and gene therapy. This is a crucial step in advancing our pipeline. We believe our allogeneic Tr1 Treg and CAR-Treg therapies can surpass the limitations of current treatments by controlling harmful T cells and B cells and creating immune tolerance, potentially curing a wide array of autoimmune and inflammatory disorders."

The TRX103-01 study leverages academic research demonstrating the safety and efficacy of Tr1 Treg cell therapies for various autoimmune and inflammatory conditions, including the prevention of GvHD and treatment of severe inflammatory bowel disease. The company has successfully produced sufficient clinical doses from its initial manufacturing runs using its proprietary closed process to treat up to 36 patients with a one-time infusion of TRX103.

Looking ahead, Tr1X plans to file an Investigational New Drug (IND) application for TRX103 for treatment-refractory Crohn’s Disease in the latter half of 2024. TRX103 is an investigational allogeneic off-the-shelf engineered T cell product derived from CD4+ cells from healthy donors. These CD4+ cells are engineered to function as Tr1 regulatory T cells, known as TRX cells. Multiple preclinical studies have shown TRX103 to be both tolerable and effective, with the potential to reset the immune system to a healthy state. This therapy also aims to overcome major limitations of current cell therapies for autoimmune diseases, such as limited persistence and side effects including cytokine release syndrome (CRS) and neurotoxicity.

Tr1X is a private biotechnology firm dedicated to curing immune-mediated and inflammatory diseases. Founded by industry experts, including the discoverers of Tr1 cells, the company is advancing a pipeline of off-the-shelf allogeneic cell therapies to address and potentially cure autoimmune diseases with high unmet medical needs. The company is backed by prominent investors such as The Column Group, NEVA SGR, and Alexandria Venture Investments, and has received additional grant support from the California Institute for Regenerative Medicine (CIRM).