Slide 1: Corporate Presentation August 2021
Corporate Presentation august 2021 Exhibit 99.2
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 Developing highly specific CAAR T products to treat B cell-mediated autoimmune diseases Where there is a biologic opportunity for deep and durable, perhaps curative, responses Leveraging a clinically validated CAR T product design and manufacturing process through Penn alliance Pr
Slide 5: 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: Advancing targeted cell therapy to autoimmunity
Foundational CAR T technology clinically validated in treating B cell-mediated cancers Cabaletta: Advancing targeted cell therapy to autoimmunity Marketed Pivotal Clinical Preclinical / Discovery DSG3-CAART (mPV) MuSK-CAART (MG) FVIII-CAART (Hem A w/ Inhibitor) DSG3/1-CAART (mcPV) Oncology B Cell-Me
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
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 development process
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: Initial DesCAARTes data begins to de-risk the platform
We believe the initial DesCAARTes™ data begins to de-risk the platform Data from the DesCAARTes™ trial provides read-through to pipeline Acute safety in patients with mPV Future Data: Target engagement Manufacturing success in clinical trial Strong operating partnership with Penn CVPF manufacturing
Slide 12: DSG3-CAART for patients with mucosal pemphigus vulgaris
DSG3-CAART for patients with mucosal pemphigus vulgaris
Slide 13: DSG3 antibodies 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
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
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: Tolerability and target engagement preclinical data
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 design
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 and at months, target engagement by 6 months
Safety assessed acutely (Day 8) and at 3 months, with data on potential target engagement by 6 months DesCAARTes™ clinical trial assessments and timeframes * Clearance of 28-day observation window without DLTs required to initiate next dosing cohort. Spindler, Volker, et al. "Mechanisms causing loss
Slide 19: Promising initial safety profile in first cohort
Promising initial safety profile for all 3 patients dosed with DSG3-CAART in the 1st trial cohort No DLTs observed to date in 1st cohort of DesCAARTes™ trial 1. As of August 4, 2021. Up to Wk -18 Wk -18 to -1 Day -7 to -3 Pre-infusion visit 6 Months Data on target engagement Day 8 Acute safety data
Slide 20: 100% manufacturing success rate for DSG3-CAART
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: No DLTs or clinically relevant toxicities in first three patients
No DLTs or clinically relevant toxicities in 1st three patients to date1 At a 20 million cell dose, in the absence of lymphodepletion Circulating anti-DSG3 antibodies present in all patients at infusion All patients in the 1st cohort have completed the 28-day DLT monitoring period DSG3-CAART was obs
Slide 22: Strategies to consider for targeted cell therapy in autoimmune disease
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 target engagement in autoimmune disease Target cell population 0.1-1% of B cells are
Slide 23: Accelerating timelines for DesCAARTes trial
Expanding relationships with patient advocacy organizations Growing clinical site network with high investigator engagement Strong interest by study sites, with three sites actively enrolling and many more working to open Accelerating timelines for DesCAARTes™ trial Assumes no dose-limiting toxiciti
Slide 24: DSG3/1 CAAR 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 potentially submi
Slide 25: MuSK-CAART for patients with MuSK myasthenia gravis
MuSK-CAART for patients with MuSK myasthenia gravis
Slide 26: 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 27: MuSK-CAART 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 28: MuSK-CAART 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 29: PLA2R-CAART for PLA2R-associated membranous nephropathy
PLA2R-CAART for patients with PLA2R-associated membranous nephropathy
Slide 30: Primary MN is an immune-mediated kidney disease
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 31: Opportunity for antigen-targeted therapy to address 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 32: 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 33: Manufacturing
Manufacturing Cabaletta Bio’
Slide 34: 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 35: 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 36: Corporate Summary
Corporate Summary Cabaletta Bio’
Slide 37: 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 38: Updated 2021 anticipated milestones
Updated 2021 anticipated milestones Milestone 1Q 2021 2Q 2021 3Q 2021 4Q 2021 DSG3-CAART: DesCAARTes™ Data 1st cohort1 2nd cohort1 3rd cohort1 MuSK-CAART Validate manufacturing process with CMO partner MuSK-CAART IND filing PLA2R-CAART Pre-IND meeting with FDA COMPLETED Acute Safety Target Engagemen
Slide 39: 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 Highly specific, targeted therapy designed to eliminate only pathogenic B cells Target engage
Slide 40: Corporate Presentation August 2021
Corporate Presentation August 2021