In autoimmunity and immune-mediated disorders, fields long dominated by chronic immunosuppression and symptom management, Tr1X Bio (pronounced “Tricks Bio”) bet big on long-term immune tolerance powered by regulatory T (Treg) cell therapy that can be mass-produced, and it appears that their strategy has paid off. At the 2026 ASTCT/CIBMTR Tandem Meetings, Tr1X presented first-in-human clinical data for TRX103, an allogeneic, off-the-shelf type 1 regulatory T cell (Tr1) therapy, a Treg subtype important for immune tolerance dampening, marking what it says is the first clinical proof of biology for this cell type delivered in an allogeneic format.
“This is really the first of its kind,” David de Vries, co-founder and CEO of Tr1X Bio, told Inside Precision Medicine. “It’s the first time Tr1 biology has been demonstrated in humans with an allogeneic cell therapy. That mechanism had been hypothesized, shown in mice, and demonstrated with autologous Tr1 cells. What we’ve de-risked today is that we can do it off the shelf.”
Why allogeneic Tr1 cells?
Tr1X was founded just over four years ago with a singular goal of moving away from chronic treatment or symptom suppression to permanent cure and remission of autoimmune and inflammatory diseases. This led de Vries down a decision tree with several key nodes.
The first decision was to match Tr1X Bio’s mission to an immunotherapy modality, either antibodies or cells. B-cell depletion in autoimmune diseases has a well-established and partially effective mechanism of action, as demonstrated by anti-CD20 biologics such as rituximab, which are widely used across B-cell–driven conditions and remain the only approved therapy for primary progressive multiple sclerosis due to their demonstrated efficacy. Cell therapy offers additional advantages over antibodies, including improved tissue accessibility (such as lymph nodes, spleen, brain, and spinal cord) and deeper, more comprehensive B-cell depletion, which may better enable immune reset toward naïve, non–autoantibody-producing B cells. Putting the choice into simpler terms, de Vries said, “Cells can go where antibodies cannot—into tissues, lymph nodes, the spleen, and in our case, the brain and spinal cord. That accessibility gives you greater depth of depletion.”
The next decision was made based on the cell type. While there has been some therapeutic success in the glowingly competitive space of using chimeric antigen receptor (CAR) T cells in treating autoimmune diseases, de Vries and Tr1X went with Tregs. But they didn’t just choose the same Treg as most of their competitors, which tend to use Foxp3+ Tregs, such as Sonoma Biotherapeutics, co-founded by 2025 Nobel Prize in Physiology or Medicine winner Fred Ramsdell, PhD. “What we focused on specifically is a subset of regulatory cells called type one regulatory T cells, or Tr1 cells,” de Vries said. “They’re different from your traditional canonical FoxP3 Tregs that a lot of our friends and colleagues are working on.”
Foxp3+ Tregs and Tr1 have complementary (but not opposing) roles in immune tolerance—the body’s mechanism for avoiding attacking its own healthy cells and tissues, distinguishing “self” from “non-self.” An extremely reductionist view of how these two cell types work is that Foxp3+ Tregs are a non-specific “on switch” and Tr1s “dial the knob” to a more focused antigen-specific response. In healthy individuals, Tr1 cells play a quiet but essential role, responsible for producing regulators of immune responses to the antigens we encounter in everyday life. “Food, bee venom, house dust mites, and cat dander… Tr1 cells keep the immune system in check and prevent attack of self when you encounter all these antigens,” explained de Vries.
To understand the function of these cell types at a more mechanistic level requires looking into the cell lineage and suppressive mechanism. The work by Ramsdell and Nobel Prize co-awardees Shimon Sakaguchi, MD, PhD, and Mary E. Brunkow, PhD, centered around the discovery of Tregs and establishing Foxp3 as their master regulatory gene, revealing how immune tolerance is maintained and enabling transformative therapies for autoimmunity, transplantation, and cancer. FoxP3+ Tregs are derived from the thymus for self-antigen tolerance or peripherally during inflammation that uses contact-dependent mechanisms and suppressive cytokines. Tr1 cells are induced only in the periphery and are characterized by plastic, context-dependent immune suppression mainly via cytokines. Expanding on the importance of these differences, de Vries said, “First, [Tr1] cells are not primed from birth. These are adaptive cells. They adapt over time based on antigen stimulation. Second, they are potent anti-inflammatory cells, and third, they secrete extremely high levels of IL-10, which is a suppressive cytokine and their main mode of action.”
Another aspect that influenced the decision to go with allogeneic Tr1 cells has to do with what de Vries views as limitations of autologous T cell therapies. “It demonstrates proof of safety and signs of efficacy, but it’s not a commercial product,” said de Vries. “I still need chemo. I still see cytokine release storm (CRS) and neurotoxicity. And it’s still really expensive to make.” De Vries believes the allogeneic Tr1 approach at Tr1X addresses these concerns, with an improved safety profile and immense cost reduction. “It’s allogeneic, so the cost of goods is a lot lower than autologous, and we don’t need standard preconditioning,” de Vries said. “Instead of causing CRS and Immune effector cell-associated neurotoxicity syndrome (ICANS), I’m actually reducing inflammation as part of the product profile.”
First-in-human Tr1 clinical data
The last step in the decision tree for Tr1X involves matching the cell type to the clinical indication. While Foxp3+ Tregs are the “classic” choice for immune suppression, Tr1 cells are often viewed as superior candidates for addressing graft-versus-Host Disease (GvHD) therapy because they can preserve the graft-versus-Leukemia (GvL) effect—the ability of the donor’s immune system to still kill cancer cells. Fittingly, the clinical data presented by Tr1X Bio is for their lead program, TRX-103 hematologic malignancies undergoing HLA-mismatched hematopoietic peripheral stem cell transplantation (HSCT). 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 the incidence and severity of GvHD.
According to de Vries, this trial is intended to tease out several key questions: Is TRX-103 safe, tolerable, and functionally equivalent to their natural Tr1 counterparts? De Vries said, “Is TRX-103 safe and tolerable across all doses? yes. We’ve also demonstrated that we’re suppressing inflammation and T cell proliferation and also inducing new Tregs that the patients are making themselves.”
What we’ve proven today with our allogeneic version is that they induce the patient’s own body to make new Tregs,” de Vries said. “That restores homeostasis. You get new FoxP3+ Tregs and new Tr1 Tregs generated endogenously.”
If these Tregs can prove to be durable, then de Vries and Tr1X Bio may have something quite promising on their hands. “In theory, this can be one-and-done or very infrequent,” de Vries said. “You’re not dosing every four or eight weeks. You get a window of drug-free remission. I don’t want to call it a cure yet—but the promise is there.” With additional engineering, de Vries said that Tr1 cells can be applied to Crohn’s disease, multiple sclerosis, and potentially many other inflammatory and autoimmune conditions.
That’s where the second clinical product, TRX319, comes in. TRX319 adds another layer of engineering: a CD19 CAR. “If you wanted to design from scratch for immunology and inflammation, you’d want a Treg safety profile first and foremost,” de Vries said. “And then you’d want the ability to suppress T cells and deplete B cells.” As a CAR Treg, TRX319 does just that. “We have dual B cell depletion and Treg-driven anti-inflammatory and T cell suppression activity,” he said. The product is headed into progressive multiple sclerosis, where B-cell-targeting biologics like anti-CD20 antibodies have already demonstrated efficacy. The clean safety profile observed with TRX103, de Vries said, provides confidence to advance TRX319. “The first product has shown us that the safety profile is absolutely clean, and that allows us to move forward.”
“Walking hand-in-hand with the FDA”
The starting material for Tr1X is CD4+ T cells from healthy third-party donors that are reprogrammed into Tr1-like regulatory cells. It’s lead program TRX103 uses a lentiviral vector to permanently reprogram the cells, converting the CD4+ T cells to a very stable phenotype. The lentivirus allows permanent insertion and differentiation over a two- to three-week process into this Tr1 phenotype. That permanence is deliberate. “FoxP3+ Tregs have historically shown that in stressful inflammatory environments, they can revert to effector T cells,” de Vries said. “We wanted permanent reprogramming. What we’ve shown is that even in highly pro-inflammatory conditions—high TNF, high IL-6—the cells keep their phenotype and function. They keep secreting high levels of IL-10. They keep doing what you want them to do.”
Everything at Tr1X is planned out with manufacturing in mind. “Everything we do is off the shelf. We design for scale from the start,” said de Vries. “Tregs are notoriously hard to grow and expand, so we asked: can we manufacture these cells at scale? Can we get the cost of goods closer to a complex biologic than an autologous cell therapy while preserving the innate biology we want?” For Tr1X, manufacturing is not an afterthought. “CMC and lot release criteria are always top of mind,” de Vries said. “We do all our process development and optimization in-house, then manufacture with a CDMO partner.” The process is closed, automated, and consistent. “We’ve already done five GMP-grade batches of TRX103, and it’s incredibly consistent—purity, identity, viability, even potency,” he said. “We already have a potency assay in Phase I/II, which is pretty rare for a cell therapy.”
That consistency has resonated with regulators. “The FDA has asked us to show lack of batch-to-batch variability,” de Vries said. “That’s much more of a problem in autologous therapy. Because we don’t have donor-dependent lots, the process is very consistent.” Scalability is built in. “If we needed to treat 10,000 patients today, we could do it by putting more units in a room. We’re already close to being commercially ready.” Another key point pertains to safety expectations, which in autoimmune disease are fundamentally different from oncology. “In cancer, you’re staring down mortality, so the bar is lower,” de Vries said. “In immunology and inflammation, there’s tremendous morbidity and quality-of-life impact, but the bar for safety is much higher.” Having checked off these safety and manufacturing boxes, TRX103 has landed orphan drug designation, further streamlining regulatory interactions. “We’re walking hand-in-hand with the FDA,” de Vries said.
De Vries frames the newly presented data as both a scientific milestone and a starting point. “This is the first clinical proof of biology for allogeneic Tr1 cells,” he said. “But the underlying technology has broad applications beyond stem cell transplants.” Looking ahead, de Vries sees 2026 as a pivotal year. “It’s an exciting year for Tr1X,” he said. “We’re going to have data readouts across the entire pipeline. This is hopefully the first of many data drops that continue to confirm this compelling biology.” Ultimately, the company’s ambition remains unchanged from its founding. “We hope this is starting to pave the way toward durable remission,” de Vries said. “If not a cure.”
