Cabaletta Bio’s CAR-T cell therapy has eliminated the overreactive B cells of two patients with an autoimmune disease without preconditioning chemotherapy, pleasing investors and analysts while providing hope of a less toxic autoimmune treatment.
The two patients are enrolled in one of Cabaletta’s six RESET phase 1/2 trials testing resecabtagene autoleucel (rese-cel) in a suite of autoimmune diseases. This trial, RESET-PV, is studying rese-cel in patients with pemphigus vulgaris, a rare autoimmune disease that causes blisters on the skin, throat, genitals and elsewhere.
The B cells of a third patient were also depleted after treatment, though not completely, Cabaletta said. All three patients saw substantial improvements on the Pemphigus Disease Area Index, a measure of disease severity, in the month after rese-cel infusion. Rese-cel is an autologous treatment, meaning a patient’s T cells are extracted and modified in a lab to target B cells before being reinfused into the patient.
Rese-cel was generally well-tolerated, Cabaletta said in an Oct. 9 release. One patient developed a fever from grade 1 cytokine release syndrome, and another needed a course of steroids after a disease flare that arose when immunomodulators were discontinued. Besides being off all immunomodulators, the three patients are also tapering glucocorticoids.
Notably, Cabaletta reported no instances of immune effector cell-associated neurotoxicity syndrome (ICANS), a dangerous side effect that a patient in a different RESET trial developed after rese-cel treatment earlier this year.
Philadelphia-based Cabaletta shared the new findings in a late-breaking presentation at the 2025 European Society of Gene & Cell Therapy conference in Sevilla, Spain.
The biotech now plans to expand enrollment in the RESET-PV trial and then potentially up the dosage, while also pursuing regimens with no preconditioning in other RESET trials, Cabaletta Chief Medical Officer David Chang, M.D., said in the release.
“These data provide preliminary evidence that a single infusion of rese-cel without preconditioning can achieve complete B cell depletion and meaningful early clinical responses with a simplified regimen that can expand access to patients who may desire a treatment option without preconditioning,” Chang said.
Cabaletta’s stock price jumped from $2.40 per share to $3.25 after the data debut, with shares sitting at $2.71 as of 10 a.m. ET on Oct. 10.
“The ability to eliminate preconditioning would be a colossal differentiator and would significantly decrease the treatment burden for patients,” William Blair analyst Sami Corwin, Ph.D., wrote in an Oct. 10 note. While uncertainties like “the small cohort size, limited follow-up duration, absence of tissue-level B cell data to confirm depletion in lymph nodes and lack of data demonstrating class switching in repopulated B cells” exist, “the data are the most impressive early evidence to date for using CAR-T without cytotoxic preconditioning.”
The stock bump stands in contrast to Cabaletta's April announcement, when a patient in the biotech’s systemic sclerosis RESET trial suffered from grade 3 ICANS nine days after treatment. The patient experienced a “transient period of confusion,” the company said at the time, with the complication clearing up after treatment with dexamethasone. Cabaletta’s stock dipped 15% as a result, though analysts were less concerned.
“We believe the event could have been prevented,” William Blair analysts wrote in an April 1 note, agreeing with Cabaletta’s position that the adverse event was caused by a failure to follow proper trial protocol.