Cabaletta Bio's CAR-T Trial Faces Setback, but Analysts Remain Optimistic

Cabaletta Bio, a biotechnology company focused on developing novel therapies for autoimmune diseases, has reported a grade 3 toxicity event in its ongoing phase 1/2 trial of resecabtagene autoleucel (rese-cel), an autoimmune CAR-T therapy. Despite this setback, industry analysts remain confident in the treatment's potential.

Toxicity Event Details

A patient with systemic sclerosis (SSc) experienced immune effector cell-associated neurotoxicity syndrome (ICANS) nine days after receiving rese-cel. The patient exhibited a "transient period of confusion" but remained arousable throughout the event, with no cerebral edema, seizures, or motor dysfunction reported. Cabaletta stated that the ICANS resolved rapidly following dexamethasone treatment, and the patient was discharged without further symptoms.

The company attributed the adverse event to a protocol deviation, as the patient had reported a fever three days before rese-cel infusion, but this information was not communicated to the medical monitor. In response, Cabaletta has proposed tightening oversight of patients' pre-infusion fever status.

Analyst Reactions and Trial Progress

William Blair analysts described the ICANS case as "disappointing" but emphasized that it "underscores that the peri-infusion management of autoimmune disease patients is critical in minimizing the likelihood of severe safety events." They suggested that the event could have been prevented if the protocol had been followed correctly.

Despite the setback, analysts remain encouraged by the early efficacy data across multiple indications. They noted that all patients are now off immunosuppressants, with some appearing to be in or trending toward drug-free disease remission.

Cabaletta reported that 33 patients had received rese-cel across the RESET program trials as of March 14, with an average enrollment rate of one patient per week. The company plans to present clinical and translational data at the EULAR 2025 Congress in Spain this June.

Future Outlook and Market Response

Cabaletta CEO Steven Nichtberger expressed optimism about the RESET clinical program, citing "robust physician and patient interest" following the presentation of data demonstrating potentially transformative clinical responses after a single weight-based dose of rese-cel.

The company is preparing to meet with the FDA to discuss registrational trial designs for myositis, which affects approximately 70,000 patients in the United States. However, investor reaction to the toxicity event was less positive, with Cabaletta's stock dropping 15% on Tuesday, closing at $1.17.

As CAR-T therapy expands from oncology into immunology, Cabaletta's progress in this field will be closely watched by industry observers and potential competitors in the coming months.