DSG3-CAART / Cabaletta Bio - LARVOL DELTA

Correlative findings following DSG3-CAART infusion with and without preconditioning in patients with Pemphigus Vulgaris (DesCAARTesTM trial) (ESGCT 2024) - No abstract available

Clinical • Dermatology • Immunology • Pemphigus Vulgaris

A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris (RESET-PV) (clinicaltrials.gov) - P1 | N=55 | Recruiting | Sponsor: Cabaletta Bio | N=39 ➔ 55 | Trial completion date: Sep 2026 ➔ Jan 2029 | Trial primary completion date: Sep 2026 ➔ Jan 2029

Enrollment change • Trial completion date • Trial primary completion date • Dermatology • Immunology • Pemphigus Vulgaris

Correlative findings following DSG3‐CAART infusion with and without preconditioning in patients with Pemphigus Vulgaris (DesCAARTes study) (ESGCT 2023) - P1 | "We examined an additional patient cohort utilizing a preconditioning regimen consisting of intravenous immune globulin (IVIG) to reduce potentially neutralizing autoantibodies and cyclophosphamide (Cy) to reduce leukocytes, followed by an infusion of 2.5x109 DSG3-CAART cells (n = 3)...To date, there is no clear pattern of change in anti-DSG3 autoantibody levels across dosing cohorts despite increases in DSG3-CAART cell exposure. These data support continued exploration of DSG3-CAART with more aggressive preconditioning regimens including the addition of fludarabine for mPV patients."

Clinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Neutropenia • Pain • Pemphigus Vulgaris

Correlative Findings Following DSG3-CAART Infusion with and without Combination Preconditioning Therapy in Patients with Pemphigus Vulgaris (DesCAARTes Study) (ASGCT 2023) - P1 | "Furthermore, in subjects receiving combination therapy, transient (< 2 weeks) leukopenia and neutropenia were observed but without lymphopenia. These data suggest that combination therapy with IVIG and cyclophosphamide enhances DSG3-CAART persistence and activation and support continued exploration of DSG3-CAART for mPV patients."

Clinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Neutropenia • Pain • Pemphigus Vulgaris

Oxford Biomedica expands agreement with Cabaletta Bio; adding new viral vector programme for CD19-CAR T therapies (Oxford Biomedica Press Release) - "Oxford Biomedica plc...announces that it has expanded its License and Supply Agreement ('LSA') with Cabaletta Bio, Inc...a Philadelphia-based clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies for patients with autoimmune diseases. This follows on from the LSA announced in January 2022 and adds CD19 as a new target. Oxford Biomedica initially licensed its LentiVector^® platform to Cabaletta Bio for their lead product candidate, DSG3-CAART. The agreement has now been extended to grant a non-exclusive license to Cabaletta under Oxford Biomedica’s LentiVector^® platform IP for their CAR-T programme, CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy."

Licensing / partnership • Immunology • Systemic Lupus Erythematosus

Cabaletta Bio Reports First Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "Cabaletta will present an invited, oral presentation on the CD19-CAR T approach in SLE in addition to preclinical data from its CABA-201 program and updated clinical and translational data from its DSG3-CAART product candidate in poster presentations at the ASGCT 26th Annual Meeting, which is being held at the Los Angeles Convention Center in Los Angeles, CA from May 16-20, 2023."

Preclinical • Immunology • Lupus • Pemphigus Vulgaris • Systemic Lupus Erythematosus

Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV) (clinicaltrials.gov) - P1 | N=39 | Recruiting | Sponsor: Cabaletta Bio | N=30 ➔ 39

Enrollment change • Dermatology • Immunology • Pemphigus Vulgaris

Characterization of DSG3-CAART cells prior to & following adoptive transfer in mucosal Pemphigus Vulgaris (ESGCT 2022) - No abstract available

Dermatology • Immunology • Pemphigus Vulgaris

A Phase 1 trial of DSG3-CAART cells in mucosal-dominant pemphigus vulgaris patients: preliminary data (EADV 2022) - No abstract available

Clinical • Late-breaking abstract • P1 data • Dermatology • Immunology • Pemphigus Vulgaris

A Phase 1 Trial of Targeted DSG3-CAART Cell Therapy in Mucosal-Dominant Pemphigus Vulgaris (mPV) Patients: Early Cohort Data (ASGCT 2022) - P1 | "Prior medications included prednisone (9), rituximab (6) and mycophenolate (6). Early cohort data from the first-in-human trial of DSG3-CAART, a novel investigational precision cell therapy for the autoimmune disease mPV, demonstrate that DSG3-CAART was well-tolerated with no CRS/neurotoxicity or clinically relevant AEs. Dose-dependent increase in persistence indicates that DSG3-CAART cells were not eliminated by soluble anti-DSG3 Ab; peak persistence in cohort 3 was 10-1000x lower than observed with CART therapy in B cell cancers, likely due to differences in target frequency and lymphodepletion. The favorable DSG3-CAART safety profile and absence of DLTs allow the study to evaluate higher doses and a manufacturing enhancement, intended to increase in vivo presence of DSG3-CAART, to reach deep and durable remission for mPV patients without generalized immunosuppression."

Clinical • P1 data • Dermatology • Immunology • Infectious Disease • Inflammation • Oncology • Pain • Pemphigus Vulgaris

Characterization of DSG3-CAART Cells Prior to & Following Adoptive Transfer in Mucosal Pemphigus Vulgaris (ASGCT 2022) - "The current standard of care for mPV includes broadly immunosuppressive therapies (corticosteroids, MMF, & rituximab) that are not curative, require chronic administration & have risks of serious or life-threatening infection. DSG3-CAART cells are a novel investigational precision cellular therapy being evaluated in a first in human study in autoimmune disease. We have shown that functional DSG3-CAART cells can be manufactured successfully from mPV patient apheresis material. In the absence of lymphodepletion, engrafted 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."

Dermatology • Immunology • Infectious Disease • Oncology • Pain • Pemphigus Vulgaris • CCR7 • CD8

[VIRTUAL] Chimeric Autoantibody Receptor (CAAR) T Cells as a Precision Therapy for Antigen-Specific B Cell Depletion in PLA2R Membranous Nephropathy (KIDNEY WEEK 2021) - P1 | "B cell depletion with rituximab is an effective strategy for treatment of primary MN...We have shown that autoantigen-based chimeric autoantibody receptor (CAAR) T cells cause DSG3-specific B cell depletion in animal models of mucosal pemphigus vulgaris (mPV) without detectable off-target toxicity, which has led to a phase 1 trial of DSG3-CAART in mPV (NCT04422912)...Membrane proteome arrays screened with PLA2R CAAR extracellular domains did not identify off-target interactions. Conclusion CAAR T cells represent a novel strategy for targeted B cell depletion in PLA2R MN and may ultimately prove to be valuable for the treatment for a broad range of antibody-mediated diseases."

Chronic Kidney Disease • Dermatology • Glomerulonephritis • Immunology • Nephrology • Oncology • Pemphigus Vulgaris • Renal Disease • Transplantation • TNFRSF9

Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris. (PubMed, J Clin Invest) - "Toxicology screens using primary human cells and high-throughput membrane proteome arrays did not identify off-target cytotoxic interactions. These preclinical data guided the trial design for DSG3-CAART and may help inform CAART preclinical development for other antibody-mediated diseases."

Journal • Complement-mediated Rare Disorders • Dermatology • Dermatopathology • Immunology • Pemphigus Vulgaris

[VIRTUAL] Preclinical rationale for a first-in-human trial to evaluate the safety and preliminary efficacy of desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) for mucosal pemphigus vulgaris (SID 2020) - "In vitro screening of a panel of primary human cells with DSG3-CAART and high-throughput screening of a commercial membrane protein array with the soluble DSG3 CAAR ectodomain did not identify productive interactions with desmosomal or other off-target proteins. Collectively, these studies have informed the clinical design of a first-in-human trial of DSG3-CAART for mucosal PV and may facilitate the preclinical development of future CAART therapies for other antibody-mediated diseases."

P1 data • Complement-mediated Rare Disorders • Dermatology • Dermatopathology • Immunology • Pemphigus Vulgaris • IFNG

Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV) (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Cabaletta Bio; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Complement-mediated Rare Disorders • Dermatology • Dermatopathology • Immunology • Pemphigus Vulgaris

Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV) (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: Cabaletta Bio

Clinical • New P1 trial • Complement-mediated Rare Disorders • Dermatology • Dermatopathology • Immunology • Pemphigus Vulgaris

Antigen-specific B cell depletion with desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) for targeted therapy of mucosal pemphigus vulgaris (IMMUNOLOGY 2020) - "High-throughput screening of a membrane protein array with soluble DSG3 CAAR did not identify verifiable off-target toxicities. These preclinical studies have enabled a first-in-human clinical trial of DSG3-CAART in mucosal pemphigus vulgaris and provide a foundation that may inform the preclinical development of future CAAR T cell therapies for antigen-specific B cell depletion in other autoantibody-mediated diseases."