Tr1x gets OK for first-in-human trial of TRX319 for progressive MS
Developer also receives $50M in financing to advance cell therapy
The U.S. Food and Drug Administration (FDA) has given Tr1x the green light to launch a first-in-human clinical trial of TRX319, a cell therapy candidate designed to restore immune balance in people with progressive forms of multiple sclerosis (MS).
With FDA clearance now granted for its investigational new drug (IND) application, Trix said it plans to begin Phase 1/2a clinical testing of TRX319 early next year. The company also has obtained $50 million in financing, which will support the upcoming trial as well as an ongoing clinical trial in Crohn’s disease.
“We are pleased to receive IND clearance for TRX319 and to advance our second program into the clinic in early 2026,” David de Vries, cofounder and CEO of Tr1x, said in a company press release.
For de Vries, “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.”
MS is caused by self-reactive antibodies that target the myelin sheath, a fatty covering around nerve fibers. This triggers inflammation and results in myelin and nerve cell damage, eventually leading to a range of MS symptoms. Antibodies, including self-reactive ones, are produced by immune cells called B-cells.
CAR T-cell therapies take advantage of immune T-cells and their ability to mount immune attacks against specific targets, leading to their elimination. The approach involves modifying T-cells in the lab to produce a chimeric antigen receptor, or CAR — a man-made receptor that binds to specific proteins on the surface of target cells.
TRX-319 aims to restore immune balance in progressive MS
Unlike other CAR T-cell therapies that use T-cells from patients, TRX319 is allogeneic, meaning it sources T-cells from healthy donors. These T-cells are modified to produce a CAR that targets CD19, a protein found on B-cells, and mimic the function of type 1 regulatory (Tr1) T-cells, which maintain immune balance by controlling excessive inflammation.
The T-cells in TRX319 are expanded and stored before being infused into patients, creating a so-called off-the-shelf product, or one that doesn’t need to be developed for a specific patient.
By targeting and eliminating B-cells, TRX319 is expected to restore immune balance, prevent autoimmune attacks, and slow — or even stop — progression of the disease, according to Tr1x.
Bruce Cree, MD, PhD, a professor in MS in the department of neurology at the University of California, San Francisco noted that this is a novel strategy.
“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,” Cree said.
In preclinical tests, TRX319 showed it could reach the central nervous system — the brain and spinal cord — where MS causes damage to nerve cells. TRX319 eliminated CD19-positive B-cells and released IL-10, a molecule that helps control inflammation and is produced in high amounts by Tr1 T-cells.
Via its action on IL-10, the therapy reduces the activation of self-reactive T-cells as well as microglia, the brain resident immune cells that are thought to play a key role in disease progression in the absence of relapses, the company noted.
The exploration of new approaches, such as this first-in-human study … is timely and important. … I look forward to studying TRX319 in this dose-escalation trial to further understand the potential of this cell therapy
Jennifer Graves, MD, PhD, head of neuroimmunology at the University of California, San Diego noted that “progressive MS remains a major clinical challenge — patients can accumulate disability outside of relapses, and therapeutic options are limited.”
The open-label Phase 1/2a trial is expected to open at multiple locations. Its primary goal is to assess how safe and well tolerated TRX319 is at increasing doses. Secondary and exploratory measures include pharmacological studies and changes in clinical disability and biomarkers.
“The exploration of new approaches, such as this first-in-human study of an allogeneic CAR-Tr1 [T-cell] therapy that carefully evaluates its potential with clear safety and pharmacodynamic objectives is timely and important,” said Graves, who also serves as vice chair of human clinical research at the university.
“I look forward to studying TRX319 in this dose-escalation trial to further understand the potential of this cell therapy,” Cree added.
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