First clinical data from Phase 1 dose-escalation study in patients undergoing HLA-mismatched hematopoietic stem cell transplantation (HSCT)

TRX103 demonstrated exceptional safety, accelerated immune reconstitution, and dose-dependent persistence and induction of Tr1 and FOXP3+ regulatory T cells.

All patients achieved successful engraftment and donor chimerism following transplantation

Tr1X, a clinical-stage autoimmune and inflammatory disease company developing Type 1 regulatory T (Tr1) cell therapies, today announced the first clinical data from its ongoing Phase 1 study of TRX103 in patients with hematologic malignancies undergoing HLA-mismatched hematopoietic peripheral stem cell transplantation (HSCT), presented at the 2026 ASTCT/CIBMTR Tandem Meetings.

The data represents the first clinical results for TRX103, an investigational, off-the-shelf engineered Tr1 cell therapy. This is the first demonstration that an engineered, allogeneic cell therapy can induce the patient's own immune system to generate protective regulatory T cells. This mechanism is designed to restore natural immune balance, supporting a potential shift away from lifelong pharmacologic immunosuppression.

Patients receiving mismatched transplants often face a prolonged period of immune deficiency, leaving them vulnerable to severe infections and relapse, even with current standards of care such as post-transplant cyclophosphamide. The data suggest that TRX103 can address this vulnerability by accelerating immune reconstitution and promoting a tolerogenic environment that may improve clinical outcomes including incidence and severity of Graft versus Host Disease (GvHD).

Across all evaluated dose levels, TRX103 was well tolerated, with no dose-limiting toxicities reported and no serious adverse events related to the product. All patients achieved successful engraftment and achieved full donor chimerism following transplantation. Pharmacokinetic analyses demonstrated dose-dependent persistence of TRX103 cells in circulation and significant increases in exposure between doses.

“Patients receiving mismatched transplants can remain immunologically vulnerable for weeks to months,” said Monzr M. Al Malki, MD, Principal Investigator and Professor at City of Hope. “In this early dose-escalation experience, TRX103 has shown a favorable safety profile alongside a compelling biologic signature, with dose-dependent persistence and early signals of rapid immune reconstitution. The induction of immune tolerance through the expansion of new regulatory T cells, together with the low incidence of severe infections at optimal doses, suggests the therapy is behaving as designed and is biologically active. We are encouraged by its potential in this setting, where more than half of patients still fail to achieve graft-versus-host disease-free, relapse-free survival.”

“The first clinical data from TRX103 provide important validation of Tr1 biology in humans using an allogeneic, off-the-shelf approach,” said David de Vries, CEO & Co-Founder, Tr1X. “Autologous Tr1 cells have shown clinical promise, but scalability and feasibility have limited their broader use. Our platform was designed to overcome these barriers while preserving the unique biological properties of Tr1 cells, and these early clinical results support the continued development of our Tr1-based therapies across multiple immune-mediated diseases.”

The data suggest that TRX103 helps the immune system recover faster and in a more optimal way after transplant than current standard approaches. Patients showed earlier recovery of CD4+ T cells, reaching healthy levels months sooner than typically seen with post-transplant cyclophosphamide, along with a marked increase in immune cells linked to tolerance. This coordinated immune reset, including higher levels of Tr1 cells, FOXP3 regulatory T cells and tolerogenic dendritic cells, supports the idea that TRX103 may reduce the need for long-term immunosuppressive drugs and restore immune tolerance.

A Differentiated, Scalable Tr1 Cell Therapy Platform

TRX103 is generated from T cells sourced from healthy donors which are then reprogrammed to achieve a Tr1 regulatory T cell phenotype. The product is manufactured in a fully closed, end-to-end process capable of yielding billions of cells per production run at a fraction of the cost of autologous cell therapies.

TRX103 is being evaluated across multiple Phase 1/2a clinical studies, including for the prevention of graft-versus-host disease (GvHD) in patients undergoing HLA-mismatched peripheral blood hematopoietic stem cell transplantation (HSCT), as well as for refractory inflammatory bowel disease and noninfectious uveitis. The company’s second program, TRX319, builds on this validated Tr1 regulatory cell platform by incorporating a CD19 CAR to enable a dual-mechanism approach and is currently being studied in a Phase 1/2a trial for patients with progressive forms of multiple sclerosis.

About TRX103

TRX103 is an investigational, allogeneic, off-the-shelf engineered T cell therapy generated from CD4+ T cells sourced from healthy donors. The cells are engineered to replicate the biological functions of Type 1 regulatory T (Tr1) cells, which play a central role in immune tolerance through IL-10–mediated regulation. TRX103 is being developed for the treatment of immune-mediated and inflammatory diseases.

About Tr1X

Tr1X is a privately held biotechnology company focused on engineering cures for autoimmune and inflammatory diseases. Founded by scientists involved in the discovery of Tr1 cells, the company is developing a pipeline of off-the-shelf allogeneic cell therapies designed to restore immune balance in diseases with high unmet medical need. Tr1X is backed by leading investors, including The Column Group, NEVA SGR, and Alexandria Venture Investments, and has received grant support from the California Institute for Regenerative Medicine (CIRM). For more information, visit www.tr1x.bio.

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