Development

Cabaletta Bio's CD19 CAR-Tshows early promise in Phase I/II trial for pemphigus vulgaris

Cabaletta Bio (Nasdaq: CABA) reported early clinical data for rese-cel (resecabtagene autoleucel) administered without preconditioning in pemphigus vulgaris, with interim findings from four patients at the lowest dose cohort showing drug-free clinical responses in two of four patients through six months of follow-up, the company said at the ASGCT 2026 Annual Meeting in Boston.

In the RESET-PV Phase I/II trial (NCT04422912), all four patients had been dosed and completed at least 24 weeks of follow-up as of April 2, 2026, with baseline Pemphigus Disease Area Index (PDAI) Total Activity scores ranging from 22 to 83. All four patients exhibited clinically meaningful reductions in PDAI scores by week four. Three of the four patients achieved complete peripheral B-cell depletion, and those three patients showed the most pronounced clinical improvements; the two patients who maintained drug-free responses through six months were among this group. Serum levels of anti-DSG3 and anti-DSG1 antibodies declined in parallel with PDAI improvements. On safety, rese-cel was generally well tolerated at this dose level, with no dose-limiting toxicities and no immune effector cell-associated neurotoxicity syndrome reported; one patient experienced transient fever classified as grade 1 cytokine release syndrome.

The RESET-PV study is an open-label, Phase I/II dose-escalation trial enrolling patients with active pemphigus vulgaris, with a planned enrollment of 40 patients across multiple dose cohorts. The data presented at ASGCT 2026 reflect only the first four patients treated at the lowest preconditioning-free dose — the same dose used across the broader RESET program with preconditioning — and the results remain early and descriptive. The company did not disclose the trial's primary endpoint, and no formal statistical analysis was reported for this cohort. The next dose cohort is actively enrolling, with higher-dose preconditioning-free data from RESET-PV anticipated in the second half of 2026.

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Rese-cel is an autologous CAR-T cell therapy engineered with a fully human CD19 binder and a 4-1BB co-stimulatory domain, designed to deplete CD19-positive B cells with the stated goal of inducing durable immune tolerance in autoimmune disease. In pemphigus vulgaris, pathogenic autoantibodies directed against desmoglein 3 and desmoglein 1 — produced by autoreactive B-cell clones — drive the blistering phenotype, making deep B-cell depletion a mechanistically relevant approach. The preconditioning-free regimen, if validated at higher doses, could broaden the setting in which rese-cel is administered beyond specialized CAR-T centers, potentially including outpatient and community infusion settings, though that remains speculative at this stage. Cross-trial comparisons are limited by differences in study design, duration, and patient populations, but efgartigimod (Vyvgart, argenx), which targets the neonatal Fc receptor to reduce pathogenic IgG levels, completed a Phase III trial in pemphigus and represents an approved mechanistic benchmark in the autoantibody-driven disease space.


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