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informational purposes only. This Presentation does not purport to be a prospectus, to be complete or to contain all of the information you may desire. Statements contained herein are made as of the date of this Presentation unless stated otherwise,
and this Presentation shall not under any circumstances create an implication that the information contained herein is correct as of any time after such date or that information will be updated or revised to reflect information that subsequently
becomes available or changes occurring after the date hereof. This Presentation may contain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and
financial conditions, and include, but are not limited to, express or implied statements regarding our current beliefs, expectations and assumptions regarding: our business, future plans and strategies for our CAAR T technology and CABA
platform; the progress and results of our DesCAARTes Phase 1 trial, including the significance and impact around the clinical and translational data updates from cohorts A1 through A4 of our DesCAARTes Phase 1 trial; the expected
timing and significance of the announcement of 28-day safety for cohort A5 and clinical and translational data for cohort A4 in mid-2022; the therapeutic potential and clinical benefits of our product candidates; the expectation that Cabaletta Bio
may improve outcomes for patients suffering from mucosal pemphigus vulgaris; our ability to continue progressing in cohort A5, including the planned addition of an enhanced manufacturing process in cohort A5e; our ability to escalate dosing as high
as 10 to 15 billion cells in cohort A6m or otherwise; our ability to advance dose escalation in the DesCAARTes Phase 1 trial at the current dose ranges for the current cohorts and any projected potential dose ranges for future cohorts, and to
optimize our targeted cell therapy; our ability to evaluate, and the potential significance of, the relationship between DSG3-CAART persistence and potential clinical responses in patients with mPV; our ability to safely retreat additional patients
and whether we will continue to observe a lack of immune-mediated clearance of DSG3-CAART cells after retreatment and repeat dosing of patients; our ability to successfully complete our preclinical and clinical studies for our product candidates,
including our ongoing Phase 1 DesCAARTes trial, our planned clinical trial of MuSK-CAART, including our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; the ability of
MuSK-CAART to target B cells that differentiate into antibody secreting cells, which produce autoantibodies against muscle-specific kinase; our ability to obtain and maintain regulatory approval of our product candidates, including our expectations
regarding the intended incentives conferred by and ability to retain Orphan Drug Designation and Fast Track Designation for DSG3-CAART for the treatment of pemphigus vulgaris and Fast Track Designation for MuSK-CAART to improve activities of daily
living and muscle strength in patients with MuSK antibody-positive myasthenia gravis; the further expansion and development of our modular CABA platform across a range of autoimmune diseases; our ability to contract with third-party suppliers
and manufacturers, implement an enhanced manufacturing process and further develop our internal manufacturing strategy, capabilities and facilities; our potential commercial opportunities, including value and addressable market, for our product
candidates; our expectations regarding our use of capital and other financial results; and our ability to fund operations through the third quarter of 2023. Words such as, but not limited to, "look forward to," "believe,"
"expect," "anticipate," "estimate," "intend," "plan," "would," "should" and "could," and similar expressions or words, identify forward-looking
statements. Various risks, uncertainties and assumptions could cause actual results to differ materially from those anticipated or implied in our forward-looking statements. Such risks and uncertainties include, but are not limited to, risks related
to the success, cost, and timing of our product candidate development activities and preclinical studies and clinical trials, risks related to our ability to demonstrate sufficient evidence of safety, efficacy and tolerability in our preclinical and
clinical trials of DSG3-CAART and MuSK-CAART, the risk that signs of biologic activity or persistence may not inform long-term results, the risk that persistence observed with effective CART-19 oncology studies in combination with lymphodepletion is
not indicative of, or applicable to, clinical responses in patients with mPV, risks related to clinical trial site activation or enrollment rates that are lower than expected, our ability to protect and maintain our intellectual property position,
risks related to our relationship with third parties, uncertainties related to regulatory agencies' evaluation of regulatory filings and other information related to our product candidates, our ability to retain and recognize the intended
incentives conferred by any Orphan Drug Designation and Fast Track Designations, the risk that any one or more of our product candidates will not be successfully developed and commercialized, the risk that the results of preclinical studies or
clinical studies will not be predictive of future results in connection with future studies, the impact of COVID-19 on the timing, progress, interpretability of data, and results of ongoing or planned clinical trials and risks relating to as a
result of extraordinary events or circumstances such as the COVID-19 pandemic, and any business interruptions to our operations or to those of our clinical sites, manufacturers, suppliers, or other vendors resulting from the COVID-19 pandemic or
similar public health crisis. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any
forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give
no assurance that such expectations will prove to be correct. Accordingly, you are cautioned not to place undue reliance on these forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any
such forward-looking statements. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ materially from those contained in the forward-looking statements, see
the section entitled "Risk Factors" in our most recent annual report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the Securities and Exchange Commission. Certain
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Develop and launch the first curative
targeted cellular therapies for patients with autoimmune diseases
Cabaletta overview CRS -
Cytokine release syndrome; ICANS - Immune effector cell-associated neurotoxicity syndrome; SAE - Serious adverse event Mueller, Karen Thudium, et al. "Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia
and chronic lymphocytic leukemia." Blood, The Journal of the American Society of Hematology 130.21 (2017): 2317-2325. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J
Med. 2019;380(1):45-56. doi:10.1056/NEJMoa1804980 The range of persistence observed with anti-CD19 CART therapy in oncology has not been confirmed to be necessary or sufficient for clinical responses in patients with mPV. Includes five disclosed
product candidates and two undisclosed pipeline disease targets in our pipeline. Developing highly specific CAAR T products to treat B cell-mediated autoimmune diseases Cell therapy pipeline4 targeting diseases that affect over 80,000 U.S. patients
MusCAARTes trial in patients with MuSK myasthenia gravis on track to initiate in 2022 DesCAARTes trial in patients with mucosal pemphigus vulgaris (mPV) ongoing Favorable safety profile for DSG3-CAART demonstrated in cohorts A1 through
A4 at doses up to 2.5 billion cells No CRS, ICANS, dose-limiting toxicities or related SAEs observed in any patient in cohorts A1 to A4 Dose-dependent increase in DSG3-CAART persistence observed in cohorts A1 to A4, as presented at 25th Annual ASGCT
Conference Cohort A4 persistence approached the lower end of the range seen with anti-CD19 CART with lymphodepletion in oncology1,2,3 Cohort A5 dosing up to 7.5 billion cells ongoing with multiple additional cohorts possible to enhance in vivo
DSG3-CAART exposure Cash runway through 3Q23 with $109.2M in cash and investments at the end of 1Q22
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 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 Oncology B Cell-Mediated Allo/Autoimmune Diseases CAR-T / CAAR-T T-reg, NK, TCR,
RBC, macrophage, TIL (7 programs under development) Note: Landscape for illustrative purposes only.
CABA platform 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
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 currently in discovery stage are not shown in our pipeline portfolio. 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 U.S.
DSG3-CAART for patients with mucosal
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. Amagai, Masayuki,
et al. "Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic." The Journal of clinical investigation 90.3 (1992): 919-926. EC5 directed antibodies are not known to be pathogenic3
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
Trial in patients with mPV
evaluating up to 750x dose range (20M up to 10-15B cells) DesCAARTes Phase 1 study of DSG3-CAART1 Phase 1 Trial (NCT04422912). 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 enrollment in part B. Cohort progression following A5 (e.g. A5e or A6m) is to be prioritized according to emerging data and discussions with
the FDA, as applicable. Cohort A5e reflects an enhanced manufacturing process designed to amplify the already present cell subtypes in the product in order to potentially improve product potency and trafficking. Cohort A6m reflects a multi-dose
regimen where patients will receive a total of 10 to 15 billion cells. Orphan Drug Designation Fast Track Designation DSG3-CAART INFUSION TREATMENT & FOLLOW-UP PERIOD Next Patient Part A Cohorts2,3 Subjects Dose* A1 3 (+3) 20M A2 3 (+3) 100M A3
3 (+3) 500M A4 3 (+3) 2.5B A5 3 (+3) 5.0B to 7.5B A5e4 3 (+3) 5.0B to 7.5B A6m5 3 (+3) 10B to 15B Age: 18, confirmed diagnosis Inadequately managed by standard immunosuppressive therapies Confirmed diagnosis Active disease Anti-DSG3 antibody
positive Recent rituximab Prednisone > 0.25 mg/kg/day Other autoimmune disorder requiring immunosuppressive therapies Recent investigational treatment ALC < 1,000 at screening Major Inclusion Criteria Major Exclusion Criteria Screening
Apheresis White blood cells (including T cells) are collected T cells lentivirally transduced with DSG3 CAAR DSG3 CAAR T cell expansion DSG3 CAAR T cells are infused into the patient Adjunctive immunosuppressants are stopped; prednisone tapered to
low dose prior to infusion Primary objective: Determine the maximum tolerated dose of DSG3-CAART Primary endpoint: Adverse events, including dose-limiting toxicities (DLTs), related to DSG3-CAART within 3 months of infusion Secondary objectives:
Manufacturing success rate DSG3-CAART persistence Anti-DSG3 antibody titer changes Concomitant medication changes Clinical disease activity score changes Up to 750-fold dose escalation * 20M, 100M, 500M, 2.5B, 5.0B to 7.5B and 10B to 15B refers to
the number of DSG3-CAART cells infused for patients in dosing cohorts A1 to A (M - millions; B - billions).
Safety assessed acutely, at 28 days
& at 3 months, with data on biologic activity within 6 months DesCAARTes clinical trial assessments & current timeframes * Clearance of 28-day observation window without DLTs required to initiate next dosing cohort. 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 This information represents data that we believe can be used to inform potential efficacy endpoints in future
clinical development. Spindler, Volker, et al. "Mechanisms causing loss of keratinocyte cohesion in pemphigus." Journal of Investigative Dermatology 138.1 (2018): 32-37. Up to Wk -18 Wk -18 to -1 Day -7 to -3 Pre-infusion visit 3 Years Efficacy 15
Years Long-term follow-up 3 Months Primary safety endpoint 8-10 weeks from screening to infusion DSG3-CAART INFUSION Day 28 safety data Infusion of DSG3-CAART in context of circulating soluble DSG3 antibody Other safety measures CRS / neurotoxicity
Other adverse events Early evaluations of efficacy include1: Persistence of DSG3-CAART detected via qPCR DSG3 antibody titer changes (targeting sustained reduction) Change in mPV therapy and/or new systemic rescue therapy Disease activity changes
based on clinically validated scales e.g. PDAI, ODSS Primary safety endpoint at 3 months Potential for disease flare during planned steroid taper +/- discontinuation of immuno-suppressive medications for mPV DLT observation window* 6 Months Biologic
Activity Data Data expected within 6 months of completion for each cohort Day 28 Day 8 Acute safety data
Favorable safety profile at all
reported doses of DSG3-CAART, including the 2.5B cell dose cohort No DLTs observed to date in first 4 cohorts of DesCAARTes trial * 20M, 100M, 500M, 2.5B, 5.0B to 7.5B and 10B to 15B refers to the number of DSG3-CAART cells infused for