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 JUNE 2020

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Develop and launch the first curative

targeted cellular therapies for patients with autoimmune diseases

Cabaletta overview Engineering and

developing CAAR T products to treat B cell-mediated autoimmune diseases Leveraging commercially approved CART19 technology though Penn partnership Pursuing targets where there is a biologic opportunity for cure with the CABA platform First mover

advantage developing highly specific targeted cell therapy for autoimmune diseases Preclinical pipeline led by MuSK-CAART for myasthenia gravis with IND filing anticipated in 2H211 IND-enabling studies ongoing with in vivo preclinical data presented

at 2020 American Academy of Neurology Manufacturing validation on track with CMO partner to initiate in 2H20 Issued U.S. patent on lead clinical program with emerging robust IP portfolio Issued CAAR T product patent covers all or any part of the

relevant human antigens (DSG3 and DSG1) Lead clinical program, DSG3-CAART, in mucosal pemphigus vulgaris (mPV) patients DesCAARTes trial ready to launch with clinical acute tolerability (8 day) data from initial cohort by 1H211 Multiple

clinical sites engaged across the U.S. supported by validated manufacturing partnership with Penn Fast Track and Orphan Drug Designations granted in 1H20 Cash runway into at least 3Q22 with $131 million in cash at March 31, 2020 1 Assumes lifting of

current COVID-19-related restrictions and no future restrictions due to subsequent COVID-19 resurgence

CAR T Therapy CAAR T Therapy Our

scientific platform leverages CAR T technology Chimeric AutoAntibody Receptor T cell CABA CAAR T Chimeric Antigen Receptor T cell Kymriah

CABA (Cabaletta Approach for Selective

B cell Ablation) platform 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 DSG3-CAART MuSK-CAART

Indication Program Discovery1

Preclinical Phase 1 Phase 2 Phase 32 Mucosal Pemphigus Vulgaris DSG3-CAART Mucocutaneous Pemphigus Vulgaris DSG3/1-CAART MuSK Myasthenia Gravis MuSK-CAART Hemophilia A w/ FVIII Alloantibodies FVIII-CAART Pipeline addressing multiple disease targets

1 In our discovery stage, we perform epitope mapping and optimize CAAR construct and design. 2 May not be required if Phase 2 is a registrational clinical trial.

DSG3-CAART for patients with mucosal

Working to meet an unmet need for

patients Overview of Pemphigus Vulgaris Image credit: D@nderm 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. Kushner, Carolyn J., et al. "Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus." JAMA dermatology (2019).

Jancin, Bruce. "Rituximab bests mycophenolate in pemphigus vulgaris," Dermatology News, Nov 2019, Vol. 50:11, p. 2.; Press Release, Roche, 14 Oct 2019. Mucosal PV1 25% of U.S. pemphigus vulgaris Mucocutaneous PV1 75% of U.S. pemphigus

vulgaris http://www.danderm-pdv.is.kkh.dk/atlas/3-157.html http://www.dermis.net/bilder/CD008/550px/img0042.jpg 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 Disease Incidence 350 US / 600 EU 1,050 US / 1,800 EU Disease Prevalence 4,250 US / 6,250 EU 12,750 US / 18,750 EU Current Treatment Landscape Broad immunosuppression Modestly

effective Poorly tolerated B cell depletion with rituximab2,3,4 Offers transient remission Majority of responders relapse Chronic B cell depletion with rituximab 5.4% annual risk of severe infection Up to 1.9% lifetime risk of fatal

DSG3-CAART encompasses all known

pathogenic epitopes 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, 62G2C11, 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 data INDICATOR RESULTS In vitro off-target toxicity No specific cytotoxicity at clinically relevant cell numbers vs

FcgR-expressing cells No interactions confirmed 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

Study Endpoint & Objectives

Primary Endpoint: Adverse Events, including Dose Limiting Toxicity 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 has agreed, that we will share data from cohort A to inform a discussion on the optimal design of cohort C. According to FDA guidance, the submission of cohort A data is

not gating to planned enrollment in cohort B. Open-label study to determine the maximum tolerated dose & fractionation of DSG3-CAART Part Cohort # Subjects A - Dose Escalation Fractionated infusion at increasing dose levels A1-A4 3 (+3)

per cohort B - Dose Consolidation Consolidating selected dose fractions into a single infusion B1-B2 3 (+3) per cohort C - Expansion1 Expanded subject enrollment at final selected dose C ~12 Total ~30 (+18) Age: 18 Inadequately

managed by standard immunosuppressive therapies Confirmed diagnosis Active disease Anti-DSG3 antibody positive Rituximab in last 6 months Prednisone > 0.25mg/kg/day Other autoimmune disorder requiring immunosuppressive therapies Recent

investigational treatment ALC < 1,000 at screening Major Inclusion Criteria Major Exclusion Criteria SCREENING PERIOD FOLLOWED (2-4 WEEKS) TREATMENT PERIOD (1-3 WEEKS) Next Patient

Safety assessed acutely and at 3

months, with ability to measure CAAR T engagement by 6 months DesCAARTes clinical trial assessments and timeframes Spindler, Volker, et al. "Mechanisms causing loss of keratinocyte cohesion in pemphigus." Journal of Investigative Dermatology

138.1 (2018): 32-37. To be potentially incorporated in future protocol amendments or trials after discussion with FDA. Key Risks Context and Mitigating Strategies Options to Consider2 CRS / Neurotoxicity Product designed to kill <1% of B cells

Low initial dose with fractionation No lymphodepletion Manage with standard protocols Soluble antibody Fractionated dosing designed to mitigate against potential toxicity Pretreat w/ plasmapheresis or IVIG Limit soluble anti-DSG3 antibody inclusion

criteria Insufficient efficacy / CAAR T engraftment Wide cell dose range planned Consider increased dose and/or preconditioning / lymphodepletion Disease flare with medication taper Limit dose of corticosteroid use to enroll Local / oral steroids;

plasmapheresis Skin toxicity from cross-reactivity No preclinical signals Local / oral steroids; plasmapheresis New autoimmune disorder or worsening Patients with active autoimmune disorders requiring immunosuppressants excluded Autoimmune therapies

as needed Up to Wk -18 Wk -18 to -1 Day -7 to -3 Pre-infusion visit CAART INFUSION Day 8 Acute safety data 3 Months Primary safety endpoint 6 Months Evidence of target engagement 3 Years Efficacy 15 Years Long-term follow-up Declining anti-DSG3

titers1 Assuming selective B cell ablation in 2-4 weeks, serum IgG (half-life ~3 weeks) should fall within 6 months Key efficacy measures DSG3 antibody titer (ELISA)1 Disease activity (clinical) Steroid / immunosuppressive use 8-10 weeks from

screening to infusion

Preclinical data suggests soluble

antibodies can partially activate or inhibit DSG3 CAAR T cells1 Soluble antibodies may alter the dynamics of DSG3-CAART proliferation Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of

autoimmune disease." Science 353.6295 (2016): 179-184. Antibodies derived from a hybridoma model. Non-transduced T cell. CFSE (carboxyfluorescein diacetate succinimidyl ester) is a dye used in flow cytometric monitoring that reduces in

intensity as it is distributed in actively dividing cells. Non-dividing cells will retain more CFSE dye. Soluble anti-DSG3 induces CAART cell proliferation Inhibitory antibodies reduce but do not prevent DSG3-CAART target engagement Increased target

engagement Decreased target engagement EC1-4 vs. PV Ab #12 EC1-4 vs. PV Ab #22 NTD3 vs. PV Ab #12 NTD3 vs. PV Ab #22 Cell division Increased T cell division compared to response to normal human IgG 4 Observations

Data suggest preconditioning may not

be necessary to drive responses beyond leukemia / lymphoma Recent MM patient data showed non-significant differences in ORR and rate of cytokine release syndrome in patients receiving CART-BCMA with and without lymphodepletion1 Studies from three

clinical trials for patients with HIV showed CAR T cells were detected in 98% of samples tested for at least 11 years after infusion Potential activating effect of soluble antibody on engraftment and function is a key consideration in autoimmune

patients Multiple infusions, higher dose, and cytokine support may offer more tolerable approach for autoimmune patients Past successes in HIV and multiple myeloma without preconditioning plus differences in patient populations are relevant1,2

Preconditioning regimens in CAAR T cell therapy may not be required Cohen, Adam D., et al. "B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma." The Journal of Clinical Investigation 129.6

(2019). Scholler, John, et al. "Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells." Science translational medicine 4.132 (2012): 132ra53-132ra53. Gattinoni et al. "Removal of homeostatic

cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells." The Journal of Experimental Medicine 202(7):907-912 Wang, Shu and Plautz "Host lymphodepletion augments T cell adoptive

immunotherapy through enhanced intratumoral proliferation of effector cells: Cancer Research 65(20): 9547-54. Lymphodepletion Mechanism Oncology Autoimmunity Reduction of T cell growth cytokine sinks3 + + Depletion of suppressor cells4 + -

- Lymphodepletion mechanism unlikely to apply + Lymphodepletion mechanism likely to apply

Key clinical trial milestones and

data readouts Evaluate safety by dosing cohort Acute safety data to be evaluated at 8 days post-infusion Primary endpoint data at 3 months Spindler V, Eming R, Schmidt E, et al. Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus. J Invest

Dermatol 2018;138:32-7. Target engagement during dose escalation to be evaluated DSG3 antibody is necessary and sufficient to cause mPV (per consensus document1) DSG3 antibody half-life ~3 weeks Potential evidence of reduction of anti-DSG3 levels

may be observed within 6 months Clinical responses including mucosal lesion response and absence of recurrence may take longer

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 submit an IND after review of safety and target engagement data from DSG3-CAART DSG3/1 CAART for mucocutaneous PV (mcPV) 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. DSG1-CAART and DSG3-CAART both demonstrated specific cytotoxicity in vitro Together, DSG1-CAART and DSG3-CAART demonstrated cytotoxicity

towards anti-DSG3 and anti-DSG1 B cells EC1 EC2 EC3 EC4 Transmembrane Domain Cytoplasmic tail % of PV sera targeting each domain1 98% 26% 9% 4% 7% EC5 EC1 EC2 EC3 EC4 CD137 CD3z DSG1 DSG1 CAAR

MuSK-CAART for 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