Slide 1: Corporate Presentation August 2021
Corporate Presentation August 2021 Exhibit 99.1
Slide 2: Disclaimer
Disclaimer The following presentation, including any printed or electronic copy of these slides, the talks given by the presenters, the information communicated during any delivery of the presentation and any question and answer session and any document or material distributed at or in connection wi
Slide 3: Develop and launch the first curative targeted cellular therapies for autoimmune diseases
Develop and launch the first curative targeted cellular therapies for patients with autoimmune diseases
Slide 4: Cabaletta overview
Cabaletta overview * 20M, 100M & 500M refers to the number of DSG3-CAART cells infused for patients in dosing cohorts 1-3, in millions. As of August 17, 2021. Assumes no dose-limiting toxicities are observed during cohort and uninterrupted enrollment occurs in the trial. Includes five disclosed prod
Slide 5: Our scientific platform leverages clinically validated CAR T technology
Our scientific platform leverages clinically validated CAR T technology CAR T Therapy Chimeric Antigen Receptor T cell Kymriah CAAR T product candidates are designed for selective and specific elimination of the pathogenic B cells CAAR T Therapy Chimeric AutoAntibody Receptor T cell CABA CAAR T CD13
Slide 6: Foundational CAR T technology clinically validated in B cell-mediated cancers
Foundational CAR T technology clinically validated in treating B cell-mediated cancers Cabaletta: Advancing targeted cell therapy to autoimmunity Marketed Pivotal Clinical Preclinical / Discovery Oncology B Cell-Mediated Allo/Autoimmune Diseases CAR-T / CAAR-T T-reg, NK, TCR, RBC, macrophage, TIL (7
Slide 7: Biologic opportunity in dozens of B-cell mediated autoimmune diseases
Biologic opportunity for cure or treatment may be possible in dozens of B-cell mediated autoimmune diseases* CABA platform may apply across a range of autoimmune diseases Pemphigus Vulgaris1,2,3 Pemphigus Foliaceus1,2,3 Epidermolysis Bullosa Acquisita3 Bullous Pemphigoid1,2,3 Lupus Nephritis3,4 Memb
Slide 8: Technology foundation enabling a portfolio of programs targeting B cell-mediated diseases
Technology foundation designed to enable a portfolio of programs targeting B cell-mediated diseases Modular platform with “plug-and-play” architecture Clinically validated engineered T cell platform is the foundational technology PLA2R-CAART PLA2R+ membranous nephropathy DSG3-CAART Mucosal pemphigus
Slide 9: CABA platform: Cabaletta Approach for Selective B cell Ablation
Epitope mapping to determine regions targeted by autoantibodies Optimize CAAR construct / design with the goal of selectively ablating reactive B cells Preclinical in vitro and in vivo testing to evaluate efficacy and safety Scientific, clinical and commercial assessment to inform product candidate
Slide 10: Pipeline
Therapeutic Area Indication Program Discovery2 Preclinical Phase 1 Phase 2/3 Dermatology Mucosal Pemphigus Vulgaris DSG3-CAART Mucocutaneous Pemphigus Vulgaris DSG3/1-CAART Neurology MuSK Myasthenia Gravis MuSK-CAART Nephrology PLA2R Membranous Nephropathy PLA2R-CAART Hematology Hemophilia A w/ FVII
Slide 11: Data from the DesCAARTes trial provides read-through to pipeline
Data from the DesCAARTes™ trial provides read-through to pipeline Clinical data Biologic Activity Indicators Manufacturing Strong operating partnership with Penn CVPF manufacturing organization Use of validated process from CAR T experience at Penn helps mitigate risk 100% success rate for DesCAARTe
Slide 12: DSG3-CAART for patients with mucosal pemphigus vulgaris
DSG3-CAART for patients with mucosal pemphigus vulgaris
Slide 13: DSG3 antibodies are necessary and sufficient to cause PV
DSG3 antibodies are widely considered to be necessary and sufficient to cause PV1 PV is an optimal lead indication for CAAR T therapy Spindler, Volker, et al. "Mechanisms causing loss of keratinocyte cohesion in pemphigus." Journal of Investigative Dermatology 138.1 (2018): 32-37. Schmidt, Enno, et
Slide 14: Current treatments require broad immunosuppression with safety risks and transient efficacy
Current treatments require broad immunosuppression associated with safety risks and transient efficacy Overview of Pemphigus Vulgaris Image credit: D@nderm. http://www.vgrd.org/archive/cases/2004/pv/DSCN4996%20copy.JPG Joly, Pascal, et al. "First-line rituximab combined with short-term prednisone ve
Slide 15: Inclusion of all disease-relevant epitopes enables one-size-fits-all approach for mPV
Inclusion of all disease-relevant epitopes enables a ‘one-size-fits-all’ approach for patients with mPV DSG3-CAART is designed to bind all known pathogenic autoantibodies Ohyama, Bungo, et al. "Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein
Slide 16: DSG3-CAART preclinical tolerability and target engagement
Tolerability Target Engagement No evidence of toxicity at clinically relevant doses with selective and specific target engagement DSG3-CAART preclinical data1,2 INDICATOR RESULTS In vitro off-target toxicity No specific cytotoxicity at clinically relevant cell numbers vs FcgR-expressing cells No con
Slide 17: DesCAARTes Phase 1 clinical trial in mPV patients
Phase 1 clinical trial in mucosal-dominant PV (mPV) patients DesCAARTes™: FDA has requested, and the Company has agreed, that we will share data from part A to inform a discussion on the optimal design of part C. According to FDA advice, the submission of part A data is not gating to planned enrollm
Slide 18: Safety assessed acutely, at days and at months, with biologic activity within 6 months
Safety assessed acutely, at 28 days and at 3 months, with data on biologic activity within 6 months DesCAARTes™ clinical trial assessments and timeframes * Clearance of 28-day observation window without DLTs required to initiate next dosing cohort. This information represents data that we believe ca
Slide 19: DSG3-CAART persistence observed via qPCR across cohorts
DSG3-CAART persistence observed via qPCR across cohorts No DLTs observed to date in 1st or 2nd cohorts of DesCAARTes™ trial As of August 17, 2021. No clinically meaningful adverse events in any subject to date1, enabling progression to cohort A3 with dose of 500M cells COHORT A1: 3 patients received
Slide 20: 100% manufacturing success rate for DSG3-CAART cells
100% success rate for manufacturing of DSG3-CAART cells in DesCAARTes™ trial to date1 Manufactured DSG3-CAART cells exhibit target elimination in vitro Manufacturing partnership with Penn is delivering necessary quality & capacity for the clinical trial requirements 2.5:1 1.25:1 0.625:1 0:1 (Target
Slide 21: Strategies for targeted cell therapy in autoimmune diseases
Dose of CAART cells 2 CAART cell expansion post-infusion 3 Circulating antibody titer 4 Range of strategies to consider for targeted cell therapy approaches in patients with autoimmune diseases Potential drivers of biologic activity in autoimmune disease Target cell population 0.1-1% of B cells are
Slide 22: Accelerating timelines for DesCAARTes trial
Expanding relationships with patient advocacy organizations Growing clinical site network with high investigator engagement Rapid cadence of trial recruitment may enable enrollment & dosing of first 4 cohorts by end of 20211 Accelerating timelines for DesCAARTes™ trial Assumes no dose-limiting toxic
Slide 23: DSG3/1 CAART for mucocutaneous PV
DSG3/1 CAARs designed for mcPV DSG3 and DSG1 autoantibodies Most severe and common form of PV (~75%) Mucosal blistering, plus skin erosion and blistering Managed with immune suppression, similar to mPV High risk of relapse Potential for hospitalizations and fatal infections Plan to submit an IND aft
Slide 24: MuSK-CAART for patients with MuSK myasthenia gravis
MuSK-CAART for patients with MuSK myasthenia gravis
Slide 25: High unmet need in MuSK myasthenia gravis
6.0 - 7.5% All known extracellular domains can be included in the CAAR design High unmet need in MuSK myasthenia gravis; a valuable CAAR target Hain, Berit, et al. "Successful treatment of MuSK antibody–positive myasthenia gravis with rituximab." Muscle & Nerve: Official Journal of the American Asso
Slide 26: MuSK-CAART showed in vitro selective and specific target engagement
Additional in vitro studies demonstrated no confirmed off-target toxicity observed with MuSK-CAART to date MuSK-CAART showed in vitro selective & specific target engagement1 https://cabalettabio.com/technology/posters-publications. NTD = non transduced T cell control against the same target cells Ta
Slide 27: MuSK-CAART demonstrated specific in vivo target engagement
MuSK-CAART eliminated anti-MuSK target cells2 in an animal model where CART19 cells were a positive control MuSK-CAART demonstrated specific in vivo target engagement1 https://cabalettabio.com/technology/posters-publications. Target cells represent a B cell tumor line (CD19 positive) that has been m
Slide 28: PLA2R-CAART for patients with PLA2R-associated membranous nephropathy
PLA2R-CAART for patients with PLA2R-associated membranous nephropathy
Slide 29: Primary MN is an immune-mediated kidney disease with anti-PLA2R antibodies
Primary MN is an immune-mediated kidney disease with anti-PLA2R antibodies in ~75% of patients Preclinical stage CAART program in membranous nephropathy PLA2R+ MN is attractive for CAAR development Single pass transmembrane protein with distinct immunogenic regions Epitopes are well-defined IgG4-dom
Slide 30: Opportunity for antigen-targeted therapy to address significant unmet need
Opportunity to develop antigen-targeted therapy to address significant unmet need Changing treatment paradigm highlights the role of B cells in disease High unmet need despite B cell-depleting therapies Rituximab increasing 1st line for medium to high-risk pts 1/3 cure; 1/3 relapse; 1/3 fail1 Relaps
Slide 31: Potential addressable market for PLA2R-CAART
Potential addressable market for PLA2R-CAART Confidential Eligible population prevalence of ~4,000 to 8,000 patients & annual incidence of ~700 to 1,400 patients ~3,300 ~2,475 ~1,860 ~1,400 Rituximab-eligible 700 patients Relapsed/ refractory to rituximab ~20,000 ~15,000 ~11,000 ~8,000 Rituximab-eli
Slide 32: Manufacturing
Manufacturing Cabaletta Bio’
Slide 33: Three-stage manufacturing strategy
Three-stage approach allows for efficient allocation of capital while leveraging experienced partners Manufacturing strategy Penn-sponsored CD19 CAR IND CMC data has been cross-referenced in DSG3-CAART IND to provide additional data reflecting alignment. Stage 3: Cabaletta Facility Commercialization
Slide 34: Clinically validated CART19 manufacturing process mitigates risks
Utilizing a clinically validated CART19 cell manufacturing process mitigates risks Cross referenced Penn CART19 IND including CMC process1 Penn process, not Novartis process, avoiding Kymriah release challenges2 Engineering runs have demonstrated efficient manufacture of DSG3-CAART cells from PV pat
Slide 35: Corporate Summary
Corporate Summary Cabaletta Bio’
Slide 36: Leadership team and Scientific Advisory Board
SCIENTIFIC ADVISORY BOARD Leadership team Aimee Payne, M.D., Ph.D. Co-Founder and Co-Chair Michael C. Milone, M.D., Ph.D. Co-Founder and Co-Chair Jay Siegel, M.D. LEADERSHIP TEAM Steven Nichtberger, M.D. President, CEO & Chairman Anup Marda Chief Financial Officer Arun Das, M.D. Executive Director B
Slide 37: Cabaletta today
Cabaletta today Leveraging a clinically validated CAR T platform as a novel approach to treating autoimmune diseases aiming to provide: Deep and durable responses, potentially cures, for autoimmune patients and An exceptional safety profile, based on Highly specific, targeted therapy designed to eli
Slide 38: Anticipated near-term milestones
Anticipated near-term milestones Milestone 1Q 2021 2Q 2021 3Q 2021 4Q 2021 1Q 2022 DSG3-CAART: DesCAARTes™ Data 1st cohort (20M)2 2nd cohort (100M)2 3rd cohort1 (500M)2 4th cohort1 (2.5B)2 MuSK-CAART Validate manufacturing process with CMO partner MuSK-CAART IND filing PLA2R-CAART Pre-IND interactio
Slide 39: Corporate Presentation AUGUST 2021
Corporate Presentation AUGUST 2021