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 an

Corporate Presentation december 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 document or material distributed at or in

connection with the presentation (collectively, the "Presentation") has been prepared by Cabaletta Bio, Inc. ("we," "us," "our," "Cabaletta" or the "Company") and is made for

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 CAR T technology and CABA platform; the

progress and results of our DesCAARTes Phase 1 trial, including our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; the expected announcement of additional biologic

activity data for the third dose cohort in the first quarter of 2022 as well as 28-day safety data for the fourth dose cohort in the first quarter of 2022; the therapeutic potential and clinical benefits of our product candidates; our ability to

successfully complete our preclinical and clinical studies for our product candidates, including our ongoing Phase 1 DesCAARTesTM trial, MuSK-CAART study and other discovery programs; our ability to obtain and maintain regulatory approval of our

product candidates, including our planned IND submission for our MuSK-CAART program; our plans to conduct a pre-IND meeting with the FDA for PLA2R-CAART in the fourth quarter of 2021; 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 during 2021; and our ability to fund operations through at least

the first 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, 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, 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 information contained in this Presentation

relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date

of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. The Company is the owner of various trademarks, trade

names and service marks. Certain other trademarks, trade names and service marks appearing in this Presentation are the property of third parties. Solely for convenience, the trademarks and trade names in this Presentation are referred to without

the and TM symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

Develop and launch the first curative

targeted cellular therapies for patients with autoimmune diseases

Cabaletta overview * 20M, 100M, 500M,

2.5B and 5.0B to 7.5B refers to the number of DSG3-CAART cells infused for patients in dosing cohorts 1 to 4 (M - millions; B - billions). As of December 12, 2021. Assessment of patient status to date based on evaluation of disease

activity scores, DSG3 autoantibody levels and need for new systemic rescue therapy or change in prior mPV medications. This patient received systemic therapies within 9 months of DSG3-CAART infusion, which may have impacted clinical scores and DSG3

levels, both of which improved between screening and infusion. 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. Developing highly specific CAAR T products to treat B cell-mediated autoimmune diseases Where there is a biologically clear opportunity for deep and durable, perhaps curative, responses Leveraging a clinically

validated CAR T product design and manufacturing process through Penn alliance DesCAARTesTM trial dosing patients with mucosal pemphigus vulgaris (mPV) at 2.5B cell dose No DLTs or clinically relevant AEs observed to date1 following completion of

first 3 dose cohorts (20M, 100M & 500M cells) Without lymphodepletion but in the presence of circulating anti-DSG3 antibodies No clear indications of biologic activity from low dose cohorts (at 1/125th and 1/25th of current 2.5B cohort) within

3-6 months post infusion 20M dose cohort2 - 2 patients worsening and 1 patient improving3, possibly due to prior systemic therapy +/- impact of DSG3-CAART 100M dose cohort2 - 1 patient stable, 1 patient stable then increasing disease

activity, 1 patient worsening Dose dependent increase in DSG3-CAART persistence in 500M dose cohort relative to 1st 2 low dose cohorts throughout 28 days post infusion Based on safety data observed to date1 and FDA communications dating to 1H21,

additional cohorts are planned to evaluate: Increased doses, consolidated fractions, and subject to a protocol amendment, an enhanced manufacturing process Cohort A5 (5.0B to 7.5B cells) expected to initiate4 without delay, following 28-day safety

data in 2.5B cell cohort A4 in 1Q222 Preclinical pipeline led by MuSK-CAART for myasthenia gravis - IND submission planned in 4Q21 PLA2R-CAART pre-IND interaction with FDA anticipated in 4Q21 for PLA2R positive primary membranous nephropathy

patients Product portfolio5 currently targeting diseases that affect over 80,000 patients in the US Cash runway through at least 1Q23 with $119.3M in cash and investments as of September 30, 2021

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)

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 Vulgaris**1,2,3 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. **Diseases in red represent current, disclosed targets of our CABA platform 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

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

Data from the DesCAARTes

trial provides read-through to pipeline Clinical data 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

DesCAARTes trial manufacturing to date1 No DLTs or any clinically relevant toxicities observed to date1 in the first 3 cohorts Without lymphodepletion, but in the presence of circulating anti-DSG3 antibodies Dose-dependent increase in

DSG3-CAART persistence in 500M cohort Relative to first 2 low dose cohorts and throughout 28 days following infusion No clear biologic activity signals from low dose cohorts at 1/125 and 1/25 of 2.5B dose cohort We are evaluating: Persistence of

DSG3-CAART detected via qPCR Change in level of DSG3 antibodies (targeting persistent reduction) Change in mPV therapy and absence of new systemic rescue therapy Change in disease activity based on clinically validated scales (e.g. PDAI, ODSS) As of

December 12, 2021 Biologic Activity Indicators

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

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