Maria Grazia Roncarolo believes her company could redefine treatments for conditions like multiple sclerosis (MS), Crohn’s disease, and other autoimmune diseases.

Closer to Cures

Dr. Roncarolo, co-founder, president, and head of R&D at San Diego-based Tr1X Bio, said in a recent presentation that her company is modifying the patient’s own immune system to calm cells attacking the body’s tissues. This approach could treat a variety of autoimmune diseases.

The company currently focuses on graft-versus-host disease, progressive multiple sclerosis (MS), refractory Crohn’s disease, and autoimmune uveitis.

Autoimmune diseases occur when the body’s immune system goes off track and attacks healthy cells. While treatments exist, no cures exist. It’s estimated that about 1 in 10 people worldwide have one or more of the 80+ known autoimmune diseases, including conditions such as MS, Crohn’s, type 1 diabetes, and rheumatoid arthritis.

“When I started my work in immuno-mediated diseases, we had almost nothing,” Dr. Roncarolo said. “We had steroids, cyclosporin, little else. Over the past 30 years, we’ve developed a whole array of biological drugs, which is fantastic. But none of these drugs bring a cure.”

Tr1X wants to change that

Over the last few years, the company has received three awards from the California Institute for Regenerative Medicine (CIRM).

The first award supported preclinical development of engineered T-cells with immune-calming regulatory properties. The second award supported their subsequent use in a clinical trial to evaluate whether it can prevent graft-versus-host disease in patients receiving a mismatched hematopoietic stem cell transplant. Their most recent award from earlier this year supports a clinical trial using a further modification of the engineered regulatory T-cells to treat progressive MS.

In a “Closer to Cures” presentation to the CIRM board, Dr. Roncarolo outlined how she hopes the company’s approach could redefine autoimmune disease treatment.

“So, our goal is very ambitious,” she said. “It’s to go from therapy to cure and restore health. How do we want to do that? We use engineered regulatory T-cells.”

Reprogramming regulatory T-cells

The company’s approach involves harvesting immune cells from healthy donors and converting these cells into a type of T-cell known as type 1 regulatory T-cells (Tr1 cells).

These normally help calm the overactive, damaging immune response characteristic of autoimmune disease. In addition, as part of the body’s infectious tolerance response, these modified regulatory T-cells can “teach” the patient’s own non-engineered immune cells the proper calming signal to prevent ongoing damage to healthy tissue. This, in turn, enables the patient’s own immune system to heal itself.

“We infuse engineered regulatory T cells, made from healthy donors, that suppress the harmful cells and teach the patient’s own immune system to stop attacking itself,” Roncarolo said during the presentation.

Graft versus host disease

The company first tested its engineered cells in blood cancer patients who need a lifesaving mismatched donor stem cell transplant, aiming to reduce a severe side effect of this treatment: graft-versus-host disease. Graft-versus-host disease arises when the donor immune cells attack recipient tissues.

This multi-center trial was conducted at Stanford and City of Hope in Duarte, Fred Hutchinson Cancer Center in Seattle, Dana-Farber Cancer Institute in Boston, and the University of Minnesota. It is now fully enrolled.

The engineered regulatory T-cells proved safe, with patients achieving successful engraftment; Tr1X Bio’s approach shortened the time it takes patients to rebuild their immune system with the transplanted modified cells. Normally, it can take up to 100 days, but Tr1X Bio data suggest their approach cuts that timeline in half. This means that the window of vulnerability to serious infections and relapse is reduced.

Encouragingly, the team also gathered compelling evidence that it can restore natural immune balance in patients, raising the possibility of using engineered regulatory T-cells to reduce the incidence of GvHD and shift away from the need for taxing pharmacologic immune suppression.

Tr1X is also leveraging the same therapeutic in autoimmune diseases including Crohn’s disease and autoimmune uveitis. Infusing an affordable, “off-the-shelf” cell therapy that restores immune tolerance by homing to sites of inflammation, suppressing unwanted inflammatory effects, and boosting regulatory T-cell production could represent a significant advance in treating a variety of autoimmune conditions.

Progressive Multiple Sclerosis

Building on earlier work, the company is now testing an updated form of genetically modified regulatory T cells to treat progressive MS.

About 65,000 people in the U.S. live with progressive MS. Immune cells cross the blood‑brain barrier and attack myelin, the protective coating around nerves. Without myelin, nerve fibers deteriorate, leading to irreversible loss of mobility, sensation, and coordination. Other symptoms include fatigue, difficulty walking, muscle stiffness, and cognitive changes.

Current treatments may slow progression by targeting inflammation, but no cure exists. Most people eventually lose mobility and require supportive care.

The new Tr1X therapy adds a chimeric antigen receptor, or CAR, to engineered regulatory T cells. The CAR lets these cells target and eliminate harmful B cells while preserving regulatory T cells’ tolerogenic functions, including dampening inflammation in the brain. This approach parallels CAR T therapies used in cancer. This approach offers a slightly different take on CAR T therapies used to find and kill cancer cells. (Learn more about this approach, called CAR T-cell therapy, in this post.)

“The idea is that these cells will suppress active disease, remove pathogenic cells, and reset the immune system to a healthy, tolerant state,” Roncarolo said.

“I’m not a scientist, but I live with MS,” said CIRM board member Marguerite Casillas, who has had the disease for 23 years. “Thank you for tackling so many tough questions.”

Quest for cure

For her part, Roncarolo—who led academic labs and major research institutions, including at Stanford, before co‑founding and leading R&D at Tr1X Bio—said her focus remains unchanged.

“I have spent my entire professional life in quest of a cure,” she told the Board, adding that CIRM’s support has been essential.

“California leads the world in cell and gene therapy because of CIRM,” Roncarolo said. “Searching for a definitive cure carries high risk, and commercial investors rarely engage until assets are de‑risked. CIRM provides the critical bridge that lets us demonstrate early safety and efficacy. On behalf of our team, our academic collaborators, and the patients we serve, thank you for your support.”