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Key Takeaway: Corporate Presentation june 2021 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

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Corporate Presentation june 2021
Disclaimer The following presentation,
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Develop and launch the first curative
targeted cellular therapies for patients with autoimmune diseases
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 Preclinical pipeline led by MuSK-CAART for myasthenia gravis - IND filing planned in 2H21 PLA2R-CAART pre-IND meeting with FDA anticipated in 2H21 for PLA2R positive 1 membranous nephropathy patients Product portfolio2 currently
targeting diseases that affect over 80,000 patients in the US Issued U.S. patent on lead clinical program with emerging differentiated IP portfolio First issued CAAR T product patent covers all or any part of the relevant human antigens (DSG3 and
DSG1) Phase 1 DesCAARTesTM trial ongoing for patients with mucosal pemphigus vulgaris (mPV) No DLTs or any clinically relevant toxicities observed in the 1st 28 days following infusion for all 3 patients in the 1st cohort DSG3-CAART cells were
detected at low levels via qPCR in both patients evaluated to date 20M cell dose without lymphodepletion and in the presence of circulating anti-DSG3 antibodies within patients Target engagement data from cohort 1, and acute safety data from the 1st
3 cohorts anticipated this year1 Cash runway through at least 4Q22 with $102M in cash and investments as of March 31, 2021 Assumes no dose-limiting toxicities are observed during cohort and uninterrupted enrollment occurs in the trial. Includes five
disclosed product candidates and two undisclosed pipeline disease targets in our pipeline through expansion of our Sponsored Research Agreement with the University of Pennsylvania.
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 AUTOANTIGEN (e.g. DSG3, MuSK ) CD137 (4-1BB) Costimulatory Domain CD3-Zeta Signaling Domain HEALTHY B CELL
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-Mediated Allo/Autoimmune Diseases CAR-T / CAAR-T T-reg, NK, TCR, RBC, macrophage, TIL PLA2R-CAART (MN)
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 Membranous Nephropathy1,2,3 Goodpasture's Syndrome1,2,3,4 Myasthenia Gravis1,2,3,5 Neuromyelitis Optica3 Chronic Inflammatory Demyelinating Polyneuropathy1.2 Anti-NMDAR Encephalitis3 Lambert-Eaton Syndrome5 Immune Thrombocytopenic
Purpura3 Thrombotic Thrombocytopenic Purpura1,2,3 Antiphospholipid Syndrome4,5 Autoimmune Hemolytic Anemia3 Rheumatoid Arthritis2,3,4 Systemic lupus erythematosus3,4,5 ANCA-Associated Vasculitis3,4,5 Myositis5 Type 1 Diabetes3 Graves'
Disease3,5 Hashimoto's Disease5 * Illustrative list of diseases where biologic opportunity for cure or treatment may be possible. Koneczny, Inga. "Update on IgG4-mediated autoimmune diseases: new insights and new family members." Autoimmunity
Reviews (2020): 102646. Huijbers, Maartje G., et al. "IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders." Annals of the New York Academy of Sciences 1413.1 (2018): 92. Ludwig, Ralf J., et al. "Mechanisms of
autoantibody-induced pathology." Frontiers in immunology 8 (2017): 603. Suurmond, Jolien, and Betty Diamond. "Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity." The Journal of clinical investigation 125.6 (2015):
2194-2202. Xiao, Ze Xiu, Joseph S. Miller, and Song Guo Zheng. "An updated advance of autoantibodies in autoimmune diseases." Autoimmunity Reviews (2020): 102743. Dermatology Nephrology Neurology Hematology Rheumatology Endocrinology
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 vulgaris MuSK-CAART MuSK+ myasthenia gravis DSG3/1-CAART Mucocutaneous pemphigus vulgaris Swapping the extracellular domain, or autoantigen, creates new product candidates FVIII-CAART Hemophilia A with FVIII inhibitors
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 development Vector & Clinical Cell manufacturing Clinical trials CABA (Cabaletta Approach for Selective B cell Ablation) platform DSG3 CAART MuSK CAART PLA2R CAART FVIII CAART DSG3/1 CAART Current stage of pipeline
We believe the initial
DesCAARTes data begins to de-risk the platform Data from the DesCAARTes trial provides read-through to pipeline As of June 1, 2021. Acute safety in patients with mPV Future Data: Target engagement Manufacturing success in clinical
trial 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 DesCAARTes trial manufacturing through June 1, 2021 No DLTs or any
clinically relevant toxicities observed in initial cohort through 28 days DSG3-CAART was detected at low levels via qPCR in both patients evaluated to date 20M DSG3-CAART cell dose administered without lymphodepletion In patients with soluble
circulating anti-DSG3 antibodies Second dosing cohort is at 100M DSG3-CAART cells Two cohorts higher than 100M cells are currently planned as well, if necessary We believe biologic activity is present if DSG3 Ab titers consistently reduced by
>20% More robust anti-DSG3 titer decline expected with greater target engagement Many variables to modify and strategies to maximize target engagement
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/ FVIII Alloantibodies FVIII-CAART Pipeline1 includes multiple disease targets where cure is possible Two additional undisclosed disease targets added to our pipeline portfolio through expansion of our Sponsored Research Agreement with
the University of Pennsylvania are not shown. In our discovery stage, we perform epitope mapping and optimize CAAR construct and design. Current pipeline includes 7 programs targeting diseases affecting >80,000 patients in the US
DSG3-CAART for patients with mucosal
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 al. "Novel ELISA systems for antibodies to desmoglein 1 and 3." Experimental dermatology 19.5 (2010): 458-463. Joly, Pascal, et al. "First-line rituximab combined with short-term prednisone versus prednisone alone for the
treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial." The Lancet 389.10083 (2017): 2031-2040. Mouquet, Hugo, et al. "B-cell depletion immunotherapy in pemphigus: effects on cellular and humoral
immune responses." Journal of Investigative Dermatology 128.12 (2008): 2859-2869. Hammers, Christoph M., et al. "Persistence of anti-desmoglein 3 IgG+ B-cell clones in pemphigus patients over years." Journal of Investigative Dermatology 135.3
(2015): 742-749. Ohyama, Bungo, et al. "Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2-based swapped molecules." Journal of investigative dermatology 132.4 (2012): 1158-1168.
Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease." Science 353.6295 (2016): 179-184. Serum anti-DSG3 antibodies are 98 - 100% sensitive and specific2 1 The DSG3 CAAR has
published animal model proof-of-concept validation7 5 Depletion of B cells by rituximab3 or antibody by plasmapheresis transiently improves clinical disease 2 The B cell repertoire and antigenic epitopes on DSG1/3 are well understood6, and formed
the basis for DSG3 and DSG1 CAAR designs 4 Incomplete B cell depletion by rituximab leads to PV recurrences, with identical disease-causing B cell clones4,5 3 anti- dsg anti- dsg
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 versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial." The Lancet 389.10083 (2017): 2031-2040. Werth, Victoria P., et al. "Rituximab
versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris." New England Journal of Medicine (2021). Rituximab label, 08/2020 revision. Kushner, Carolyn J., et al. "Factors Associated With Complete Remission After Rituximab Therapy for
Pemphigus." JAMA dermatology (2019). Tony, Hans-Peter, et al. "Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)." Arthritis research & therapy
13.3 (2011): 1-14. Current Treatment Landscape Broad immunosuppression3,6 Modestly effective Poorly tolerated Rituximab plus steroids (~3,500 mg/yr)4 Response: ~40% of patients achieved a 16-week period with no lesions or medicines during 1 yr4,5
22% annual serious adverse event (SAE) rate4 4-9%3,4,5 annual risk of severe infection in PV Real world data indicate: Transient remission ~ 70% CROT6: ~30% relapse in 1 year6 >50% relapse within 2 years6 ~30% never achieve CROT6 ~1.9% lifetime
risk of fatal infection7 CROT = 8+ weeks without lesions while off systemic therapy http://www.danderm-pdv.is.kkh.dk/atlas/3-157.html http://www.dermis.net/bilder/CD008/550px/img0042.jpg Mucosal PV1 25% of U.S. pemphigus vulgaris Mucocutaneous PV2
75% of U.S. pemphigus vulgaris Associated Antibody Anti-DSG3 Anti-DSG3 + Anti-DSG1 Clinical Signs Painful blisters of the mucous membranes (mouth, nose, larynx, esophagus, eyes, genitalia, rectum) Blisters on orifices and skin US Disease Prevalence
3,250 to 4,750 9,750 to 14,250
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 2-based swapped molecules." Journal of investigative dermatology 132.4 (2012): 1158-1168. Antibodies that target the specific extracellular domain are shown below each extracellular domain. EC5 directed
antibodies are not known to be pathogenic DSG3-CAART Costimulatory Domains anti-EC4 P2C1, P5D4, P5B6, P3A6, P5E4 2 anti-EC3 AK18 2 anti-EC2 PVB28, AK19 2 anti-EC1 AK23, Px43, Px44, 6G2C11, F779 2 EC1 EC2 EC3 EC4 Transmembrane Domain Cytoplasmic tail
% of PV sera targeting each domain1 91% 71% 51% 19% 12% EC5 EC1 EC2 EC3 EC4 CD137 CD3z DSG3 Protein
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 confirmed interactions with human membrane proteins In vivo off-target toxicity No off-target effects detected at clinically relevant doses Anti-DSG3 autoantibody titer Serologic remission' -
dose-dependent elimination of anti-DSG3 B cells and antibodies CAAR T cell engraftment Dose-dependent increase in CAAR-positive cells observed via flow cytometry Tissue blistering Histologic remission' - no blistering of oral
mucosa Anti-DSG3 hybridoma outgrowth Significantly delayed outgrowth despite soluble anti-DSG antibodies Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease." Science 353.6295
(2016): 179-184. 2. Lee, Jinmin, et al. "Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris." The Journal of Clinical Investigation (2020).
Study Endpoint & Objectives
Primary Endpoint: Adverse Events, including Dose Limiting Toxicity (DLT) DLTs include any grade 3 or 4 CRS or neurotoxicity, or any grade 2 CRS or neurotoxicity that failed to improve to Grade 1 or baseline within 7 days Secondary
Objectives: DSG3 ELISA titer changes, rate of/time to/duration of remission, manufacturing success rate, CAAR T expansion/persistence DesCAARTes : Phase 1 clinical trial in mucosal-dominant PV (mPV) patients FDA has requested, and the Company
Last updated: Jun 3, 2021