San Diego-based Tr1X, Inc. has secured an $8 million grant from the California Institute for Regenerative Medicine (CIRM) to advance its ongoing Phase 1/2a clinical trial of TRX103, a novel engineered Tr1 regulatory T cell therapy designed to prevent graft-versus-host disease (GvHD) in blood cancer patients undergoing mismatched stem cell transplants.
This latest funding follows a previous $4 million CIRM grant awarded to Tr1X in early 2024, which supported late-stage preclinical research that helped bring TRX103 into human trials. The company has already reported positive initial persistence and safety data from the first two patient cohorts, with additional data expected later in 2025.
Maria Grazia Roncarolo, MD, co-founder, president and head of R&D at Tr1X, who is leading the clinical trial, emphasized the significance of this development: "With CIRM's support, TRX103 has rapidly advanced from promising preclinical findings into clinical trials, bringing us closer to transforming mismatched stem cell transplants into safer, life-saving options."
The Clinical Challenge of GvHD
Graft-versus-host disease remains one of the most serious complications of allogeneic hematopoietic stem cell transplantation, occurring when donor immune cells recognize the recipient's tissues as foreign and mount an immunological attack. This can lead to significant morbidity and mortality, affecting organs including the skin, liver, and gastrointestinal tract.
Current standard treatments for GvHD rely heavily on broad immunosuppression, which can leave patients vulnerable to life-threatening infections and potentially compromise the effectiveness of cancer treatments. Additionally, many patients lack access to perfectly matched donors, limiting their transplant options.
TRX103: A Novel Approach to Immune Regulation
TRX103 represents a fundamentally different approach to preventing GvHD. It is an allogeneic, off-the-shelf engineered T cell product generated from CD4+ cells sourced from healthy donors. These cells are engineered to mimic the function of type 1 regulatory (Tr1) cells, which naturally suppress immune responses.
The ongoing Phase 1/2a trial is enrolling patients at leading stem cell transplant centers across the United States. The study design involves treating patients receiving mismatched or haploidentical transplants with a single infusion of TRX103.
"By harnessing the unique power of engineered Tr1 cells, our goal is to prevent graft-versus-host disease, improve immune reconstitution and induce tolerance to host cells—therefore expanding access to curative therapies for patients who urgently need them," Dr. Roncarolo explained.
Broader Therapeutic Potential
Beyond GvHD prevention, Tr1X is also evaluating TRX103 in a separate Phase 1/2a trial for patients with treatment-refractory Crohn's Disease, highlighting the potential broader applications of this cell therapy platform in autoimmune and inflammatory conditions.
Preclinical studies have demonstrated that TRX103 is both tolerable and effective, with the potential to reset the immune system to a healthy state. Importantly, the therapy may overcome major limitations of current cell therapies for autoimmune diseases, including limited persistence and serious side effects such as cytokine release syndrome and neurotoxicity.
Expanding Access to Curative Therapies
Dr. Roncarolo highlighted the broader implications of this research: "This trial represents a hope for all of us transplanters—not only for better outcomes but also for a future where effective, personalized treatments like hematopoietic stem cell transplant become accessible to all patients, regardless of donor match."
The potential impact of TRX103 extends beyond individual patient outcomes to the broader healthcare system. By potentially reducing the incidence and severity of GvHD, the therapy could decrease hospitalization rates, lower the need for intensive immunosuppressive regimens, and ultimately improve quality of life for transplant recipients.
About Tr1X
Tr1X is a clinical-stage private biotechnology company focused on developing curative cell therapies for autoimmune and inflammatory diseases. The company was founded by scientists who discovered Tr1 cells and develops off-the-shelf, allogeneic Treg and CAR-Treg therapies engineered for improved safety, scalability, and accessibility.
The company's approach aims to eliminate the need for standard lymphodepletion while enabling durable restoration of immune tolerance. Tr1X is supported by investors including The Column Group, NEVA SGR, and Alexandria Venture Investments, alongside grant funding from CIRM.
With its innovative platform technology, Tr1X is working to transform treatment paradigms from lifelong disease management to permanent cures for patients with autoimmune and inflammatory conditions.
