Important Update on CAR-T Trials in Autoimmune Disease

MSU wants to update our community about important recent safety developments involving

CAR-T clinical trials for autoimmune diseases, including trials involving people with myositis.

Novartis – rap-cel (YTB323)

Novartis has temporarily paused screening, enrollment and treatment in its immunology and

neuroscience trials of rapcabtagene autoleucel (rap-cel/YTB323), a CD19-directed CAR-T

therapy, including its study in idiopathic inflammatory myopathies.

In information provided to the patient community, Novartis stated that the pause followed

notification of serious immune effector cell-associated hemophagocytic syndrome (IEC-HS)

events. The company is reviewing the clinical and safety data with independent Data Monitoring

and Steering Committees and is sharing information with global health authorities. Novartis has

indicated that it cannot provide additional details while the review is ongoing.

Separately, Novartis has confirmed to news organizations that three patients experienced serious

IEC-HS and that complications from these events resulted in fatal outcomes. Novartis is

conducting a comprehensive review to better understand what occurred and determine

appropriate next steps.

The company has stated that this is a temporary pause and not a discontinuation of the rap-cel

program. Patients who have already received treatment will continue to be monitored through

their clinical trial teams.

What is IEC-HS?

IEC-HS is a recognized but uncommon and potentially serious complication of CAR-T and other

immune-effector-cell therapies, previously observed primarily in patients receiving CAR-T for

blood cancers (e.g., myeloma).

It is a hyperinflammatory reaction in which activation of the immune system can become

excessive and affect multiple organs. It can be associated with high or rapidly rising ferritin,

abnormalities in blood counts and clotting, liver inflammation and, in severe cases, organ

dysfunction.

IEC-HS is related to, but distinct from, the better-known cytokine release syndrome (CRS) that

can occur following CAR-T treatment. IEC-HS can be treated, particularly when identified early,

but severe cases can be life-threatening. Each center has a protocol for treatment of adverse

effects.

At this time, we do not know why these serious events occurred in the Novartis autoimmune

program, and it would be premature to assume that the same risk applies to other CAR-T

products.

Bristol Myers Squibb – zola-cel

Bristol Myers Squibb (BMS) has provided MSU with additional information regarding the voluntary pause of its autologous CD19 CAR-T program involving zolacabtagene autoleucel (zola-cel).

BMS explained that when the program moved from Phase 1 to Phase 2, changes were made to the manufacturing process to improve scalability. During the subsequent Phase 2 lupus study, BMS observed an increased rate of immune effector cell-associated neurotoxicity syndrome

(ICANS) compared with its Phase 1 experience and voluntarily paused the zola-cel clinical programs while it investigated the finding.

According to BMS, its analysis has now identified the change in manufacturing process as the

root cause of the increased ICANS rate. BMS reported that these ICANS events were reversible and resolved without clinical sequelae.

The company is now working with the FDA and other global health authorities to return to a manufacturing process that more closely aligns with the process used during Phase 1. BMS

indicated that it will provide additional information about timing after those regulatory discussions.

BMS also clarified an important distinction from the recent Novartis safety events. BMS has

previously reported one Grade 1 IEC-HS event, but stated that IEC-HS was not the reason for

the zola-cel clinical trial pause.

The pause applies to BMS’s autologous zola-cel program and did not affect its allogeneic or in-

vivo CAR-T programs.

Cabaletta – RESET-Myositis continues

Because many members of our community are following the RESET-Myositis trial, MSU

contacted Cabaletta Bio directly regarding the status of its investigational CD19 CAR-T therapy,

rese-cel.

Cabaletta confirmed to MSU that:

• RESET-Myositis continues to enroll patients.
• The FDA has not requested Cabaletta to pause enrollment in any rese-cel clinical trial.
• More than 90 patients with autoimmune diseases have now received a single, weight-based
• dose of rese-cel across the RESET program.
• According to Cabaletta, no cases of IEC-HS of any grade have been observed to date with res-cel.

Cabaletta also noted that rese-cel uses a well-characterized 9-day manufacturing process similar

to manufacturing approaches used for established oncology CAR-T products and the academic

CD19 CAR-T experience at Erlangen University.

RESET-Myositis continues to recruit participants, including patients with dermatomyositis

(DM).

What does this mean for patients?

These developments are important, but they should not be interpreted as evidence that all CAR-T

trials for autoimmune disease have the same safety concerns.

CAR-T therapies being studied by different companies are different investigational products.

They may differ in their CAR design, manufacturing process, dose, patient population and othercharacteristics. We do not yet know which factors contributed to the events now under investigation.

The experience also illustrates why clinical trials include intensive safety monitoring and

independent review committees. Pausing enrollment while unexpected safety findings are

investigated is an important part of that process.

CAR-T remains a promising but still investigational approach for myositis and other

autoimmune diseases and continued careful evaluation of both benefits and risks is essential.

MSU will continue communicating directly with companies and investigators involved in

myositis CAR-T research and will update our community as additional information becomes

Information current as of September 4, 2026