Cabaletta Bio (CABA) Presents Updated Interim Data DesCAARTes Phase 1 Trial

Cabaletta Bio, Inc. (Nasdaq: CABA) today presented updated clinical and translational data through 6 months of follow-up in cohorts A1 through A3, safety data through 3 months and persistence data through 1 month of follow-up in cohorts A1 through A4 from the DesCAARTes™ trial at the American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting being held in Washington, D.C. from May 16-19, 2022.

“At ASGCT, we presented updated interim data showing that DSG3-CAART has had a favorable safety profile with no dose limiting toxicities or cytokine release syndrome of any grade through cohort A4, which was a dose of 2.5 billion DSG3-CAART cells. In addition, we have observed a dose dependent increase in DSG3-CAART persistence, which at cohort A4 approached the lower end of the range that is observed in anti-CD19 CART oncology studies in combination with lymphodepletion,” said David Chang, M.D., Chief Medical Officer of Cabaletta. “These data continue to support the planned dose escalation in this trial and our conviction in the potential of this program. As we progress through additional cohorts of the study, we look forward to evaluating the relationship between DSG3-CAART persistence and potential clinical responses in patients with mPV along with the opportunity to explore higher doses and an enhanced manufacturing process to meet our goal of reaching deep, durable and potentially curative responses for these patients.”

Cabaletta’s DesCAARTes™ Phase 1 trial is an open-label, dose escalation, multi-center study of DSG3-CAART in adults with mucosal-dominant pemphigus vulgaris (mPV). The trial is designed to determine the maximum tolerated dose of DSG3-CAART in adult subjects with active, anti-DSG3 Ab positive, biopsy confirmed mPV that is inadequately managed by one or more standard therapies. The primary endpoint is incidence of adverse events (AEs), including dose-limiting toxicities (DLTs), such as cytokine release syndrome (CRS) and neurotoxicity, related to DSG3-CAART within three months of infusion. Secondary endpoints include CAART persistence (qPCR), anti-DSG3 Ab levels (ELISA) and disease activity (PDAI). The trial is currently in cohort A5 (5.0 to 7.5 billion cells) and is being conducted across multiple clinical sites throughout the United States. The Company plans to include two new additional dose cohorts – A5e (enhanced manufacturing process at 5.0 to 7.5 billion cells) and A6m (multi-dose regimen at 10 to 15 billion cells). The prioritization of cohorts following cohort A5 (e.g. A5e or A6m) is subject to evaluation of emerging data and discussions with the FDA, as applicable.

The updated interim DesCAARTes™ trial Phase 1 data included 12 treated subjects, four cohorts with three patients per cohort; nine having completed six months follow up after DSG3-CAART infusion. The posters as presented at ASGCT are available at https://www.cabalettabio.com/technology/posters-publications. The data show:

• No DLTs, CRS of any grade, or related serious AEs were observed in any subject within three months of DSG3-CAART infusion through cohort A4 (2.5 billion cells).
• There was a dose dependent increase in DSG3-CAART persistence through day 29 in cohorts A1 to A4, indicating that DSG3-CAART cells were not eliminated through immune-mediated rejection.
  • Persistence (AUC_d29 and C_max) in cohort A4 approached the lower end of the range that is observed in clinical trials of anti-CD19 CART combined with lymphodepletion in B-cell malignancies
• In cohorts A1 to A3:
  • Disease activity was clear or almost clear (PDAI 0-1) in 0/9 subjects at screening, 1/9 at pre-infusion, 2/9 at month one, 5/9 at month two, 3/9 at month three, 2/9 at month four, 3/9 at month five and 1/9 at month six after treatment.
  • Through six months post DSG3-CAART infusion, no clear pattern was observed in changes in anti-DSG3 Ab levels (ELISA) or disease activity (PDAI) in the low dose cohorts where the A3 dose (500 million cells) represents 6.7 to 10% of the ongoing cohort A5 dose (5.0 to 7.5 billion cells).
• One subject from cohort A1 was retreated with 500 million cells (the cohort A3 dose) and persistence in the subject was similar to the three subjects who were originally administered the cohort A3 dose, suggesting that there was not immune-mediated clearance of DSG3-CAART cells after retreatment and repeat dosing of patients is possible, if indicated.

Data presented on the company’s manufacturing process were as follows:

• In cohorts A1-A4, the manufacturing success rate was 100% with functional DSG3-CAART cells manufactured successfully from mPV patient apheresis material.
• Infused DSG3-CAART cells exhibited a stem cell or central memory phenotype with a strong positive correlation between the dose of gene modified T cells and post-infusion persistence to day 29.
• These data suggest that DSG3-CAART cells are not being eliminated by the pre-existing anti-DSG3 immunity present in mPV.

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