Tr1X's Multiple Sclerosis Cell Therapy TRX319 Cleared for US Trial

The FDA has cleared an investigational new drug (IND) application for Tr1X's TRX319, an allogeneic chimeric antigen receptor (CAR)-engineered type 1 regulatory (Tr1 Treg) cell therapy intended to treat progressive multiple sclerosis (MS).¹

In light of the IND clearance, Tr1X intends to go forward with plans for a phase 1/2a dose-escalation clinical trial, which it expects to launch early next year. According to Tr1X, TRX319 is intended to restore immune balance via active anti-inflammatory signaling, T-cell regulation, and targeted B-cell control. The planned multicenter, open-label study will primarily focus on safety, but will also include evaluation of pharmacodynamics, clinical disability, and biomarkers. Tr1X highlighted findings from preclinical research on TRX319 indicating its ability to suppress key proinflammatory cytokines and to penetrate the central nervous system in a “robust” manner. Additionally, the preclinical TRX319 data demonstrated CD19-specific cytotoxicity and IL-10–associated regulatory activity across self-reactive T-cells and activated microglia.

“An approach that targets B-cell biology while actively modulating inflammatory signaling within a regulatory cell-therapy framework is a distinct and promising hypothesis in progressive MS,” Bruce Cree, MD, PhD, MAS, the George A. Zimmermann endowed professor in multiple sclerosis in the Department of Neurology at the University of California San Francisco, said in a statement.¹ “I look forward to studying TRX319 in this dose-escalation trial to further understand the potential of this cell therapy.”

Alongside the IND clearance announcement, Tr1X also announced that it has received $50 million in venture financing that will support its clinical trial activities for both TRX319 and TRX103, an investigational allogeneic regulatory T-cell (allo-Treg) therapy that the company is developing for treatment-refractory Crohn disease (CD) and for the prevention of graft versus host disease (GvHD) in patients undergoing HLA-mismatched hematopoietic stem cell transplantation.^1,2 TRX103 is currently being evaluated in separate phase 1 clinical trials for the aforementioned CD (NCT06721962) and GvHD prevention (NCT06462365) indications. Tr1X stated that the financing pushes forward its cash runway into the year after next.

“We are pleased to receive IND clearance for TRX319 and to advance our second program into the clinic in early 2026,” David de Vries, MPhil, the cofounder and CEO of Tr1X, said in a statement.¹ “We are also encouraged by early safety, pharmacokinetic/pharmacodynamic, and clinical signals from our ongoing TRX103 studies in refractory CD and mismatched hematopoietic stem cell transplant, and we plan to share initial data from these trials in the coming months. This financing further underscores investor confidence in our differentiated allogeneic Tr1 and CAR-Tr1 Treg strategy, the progress and data generated to date, and our continued capital efficiency.”

The first patient’s dosing in the GvHD prevention trial for TRX103 was announced in July of last year.³ The company stated at the time that this patient was the first to have received an allogeneic engineered type 1 Treg (Tr1) therapy in any clinical trial. Tr1X also noted that it had completed manufacturing of doses of TRX103 in sufficient quantity for the entire study, which is ultimately intended to enroll up to 36 patients.

“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 July 2024 statement.³ “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.”

Notably, Tr1X is not alone in exploring the potential of engineered Treg cell therapy, as the lab of David Rawlings, MD, the director of the Center for Immunity and Immunotherapies at Seattle Children's Research Institute, is conducting research on the development of antigen-specific engineered regulatory T-cells (EngTregs) for autoimmune disease.⁴ In a 2023 interview with CGTLive®, Rawlings discussed his lab’s work.

REFERENCES
1. Tr1X announces FDA clearance of IND application for TRX319, a first-in-class allogeneic CAR-TR1 Treg cell therapy for progressive multiple sclerosis, and $50 million in additional financing. News release. Tr1X, Inc. October 14, 2025. Accessed October 15, 2024. https://www.globenewswire.com/news-release/2025/10/14/3166144/0/en/Tr1X-Announces-FDA-Clearance-of-IND-Application-for-TRX319-a-First-in-Class-Allogeneic-CAR-Tr1-Treg-Cell-Therapy-for-Progressive-Multiple-Sclerosis-and-50-Million-in-Additional-Fin.html
2. 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 October 15, 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#
3. 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 October 15, 2025. 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#
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 15, 2025. https://www.seattlechildrens.org/research/featured-research/asgct-2023/