Tr1X Doses First Patient in Trial Evaluating Allogeneic Treg Therapy TRX103 for GvHD Prevention

Tr1X has dosed the first patient in a phase 1 clinical trial (NCT06462365) evaluating TRX103, an investigational allogeneic regulatory T-cell (allo-Treg) therapy, for the prevention of graft versus host disease (GvHD) in patients undergoing HLA-mismatched hematopoietic stem cell transplantation.¹

Tr1X reported that the first patient has cleared the trial’s safety period successfully, having experienced no serious adverse events. As such, enrollment activities for the trial are ongoing. The company stated that this patient is the first to have received an allogeneic engineered type 1 Treg (Tr1) therapy in any clinical trial. Tr1X also noted that it has completed manufacturing of doses of TRX103 in sufficient quantity for the entire study, which is ultimately intended to enroll up to 36 patients. The company additionally announced that it anticipates reporting initial safety and efficacy results from the multicenter, dose-escalation trial by the fourth quarter of this year.

Notably, Tr1X also plans to evaluate the allo-Treg therapy in other indications beyond GvHD, and stated that it expects to submit an investigational new drug (IND) application for TRX103 in treatment-refractory Crohn disease to the FDA before the end of 2024. According to the company website’s pipeline page, TRX103 is also in IND-enabling studies for other undisclosed indications outside of GvHD and inflammatory bowel disease.² Furthermore, in addition to TRX103, the company is also developing TRX319, an allogeneic polyclonal chimeric antigen receptor (CAR) Treg therapy, for the treatment of multiple B-cell mediated autoimmune diseases. TRX319 is currently in IND-enabling studies.

“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,” Maria Grazia Roncarolo, MD, the cofounder, president, and head of research and development at Tr1X, said in a statement.¹ “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.”

The IND for the phase 1 trial was originally cleared by the FDA in April 2024.³ TRX103 consists of CD4+ T-cells derived from healthy donors that have been engineered to replicate the functionality of Tr1 Tregs. According to Tr1X, the allo-Treg therapy is expected to have the potential to reset the immune system to a healthy state based on the results of preclinical research with disease models. Preclinical research additionally demonstrated that the allo-Treg therapy was tolerable. Tr1X expects that TRX103 may have several potential advantages over some other cell therapies for autoimmune disease with regard to persistence and the potential for adverse events like cytokine release syndrome and neurotoxicity.¹

Tr1X is not the only entity currently studying the potential of engineered Treg cell therapy to treat autoimmune disease. In 2023, CGTLive® spoke with David Rawlings, MD, the director of the Center for Immunity and Immunotherapies at Seattle Children's Research Institute, about his lab’s preclinical research on the development of antigen-specific engineered regulatory T-cells (EngTregs).⁴ These EngTregs are derived from autologous CD4 T-cells and are genetically modified to maintain the Treg cell phenotype continuously and to target a specific antigen. In the interview found below, Rawlings discussed the engineering techniques his lab has been researching and how they might help to overcome issues holding back the therapeutic potential of Treg cells.

REFERENCES
1. Tr1X announces first patient dosed in proof of concept GvHD trial evaluating TRX103, a first-in-class type 1 Treg (tr1) cell therapy. News release. Tr1X, Inc. July 10, 2024. Accessed July 11, 2024. https://www.globenewswire.com/en/news-release/2024/07/10/2911048/0/en/Tr1X-Announces-First-Patient-Dosed-in-Proof-of-Concept-GvHD-Trial-Evaluating-TRX103-a-First-in-Class-Type-1-Treg-Tr1-Cell-Therapy.html#
2. Our Programs. Tr1X. Website. Accessed July 11, 2024. https://www.tr1x.bio/our-programs
3. Tr1X announces FDA clearance of first investigational new drug application for TRX103, an allogeneic regulatory t-cell therapy to treat autoimmune diseases. News release. Tr1X, Inc. April 10, 2024. Accessed April 15, 2024. https://www.prnewswire.com/news-releases/tr1x-announces-fda-clearance-of-first-investigational-new-drug-application-for-trx103-an-allogeneic-regulatory-t-cell-therapy-to-treat-autoimmune-diseases-302112587.html
4. Seattle Children’s Researchers Share Progress at American Society of Gene and Cell Therapy Annual Meeting. Website. Seattle Children’s Research Institute. Accessed October 12, 2023. https://www.seattlechildrens.org/research/featured-research/asgct-2023/