EX-99.1 2 d916444dex991.htm EX-99.1

Corporate Presentation FEBRUary 2025 Exhibit 99.1

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 CAAR T technology; our ability to grow our autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from our research and translational insights; including those related to any similarly-designed constructs or dosing regimens; the anticipated market opportunities for rese-cel in patients with autoimmune diseases; the Company’s business plans and objectives; our expectations around the potential success and therapeutic and clinical benefits of rese-cel and our other product candidates, as well as our ability to successfully complete research and further development and commercialization of our drug candidates in current or future indications, including the timing and results of our clinical trials and our ability to conduct and complete clinical trials; expectation that clinical results will support rese-cel's safety and activity profile; our plan to leverage increasing clinical data and a unique development program for rese-cel; the clinical significance of the clinical data read-out at upcoming medical or scientific meetings; our belief that rese-cel has the potential to provide drug-free, durable meaningful clinical responses, through an immune reset, including the potential for achieving drug-free remission in patients with refractory myositis; the Company's advancement of separate Phase 1/2 clinical trials of rese-cel in patients with SLE, myositis, SSc and gMG and advancement of the RESET-PV and RESET-MS trials, including updates related to status, safety data, efficiency of clinical trial design and timing of data read-outs or otherwise; our ability to leverage our experience in autoimmune cell therapy; our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner and timing thereof, and advance the trial as planned in our Phase 1/2 clinical trials of rese-cel; the timing any planned regulatory filings for our development programs, including IND applications; the progress and results of our MusCAARTes™ Phase 1 trial, and impact around reported safety and clinical and translational data of cohorts from our MusCAARTes™ Phase 1 trial; Cabaletta's advancement of the whole blood manufacturing program to remove the burden of apheresis; statements regarding the timing of regulatory filings and interactions with regulatory authorities, including such authorities' review of safety information from our ongoing clinical trials and potential registrational pathway for rese-cel; our ability to successfully complete our preclinical and clinical studies for our product candidates, including our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; our ability to increase enrollment from our rapidly expanding clinical network in the RESET clinical trial program in the US and Europe; 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 Fast Track Designations for our product candidates; our ability to accelerate our pipeline to approval and launch and to develop meaningful therapies for patients, including in collaboration with academic and industry partners and the ability to optimize such collaborations on our development programs; our ability to contract with third-party suppliers and manufacturers and retain such manufacturers, whether due to legislative action or otherwise; to implement an enhanced manufacturing process and further develop our internal manufacturing strategy, capabilities and facilities; our ability to execute our manufacturing strategy to enable expansion of clinical supply and efficiently scale commercial supply for rese-cel; our potential commercial opportunities, including value and addressable market, for our product candidates. 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 studies and clinical trials of rese-cel and MuSK-CAART, the risk that the results observed with the similarly-designed construct, including, but not limited to, due to dosing regimen, are not indicative of the results we seek to achieve with rese-cel, the risk that signs of biologic activity or persistence may not inform long-term results, the risk that persistence observed with effective CD19-CAR T 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 demonstrate sufficient evidence of safety, efficacy and tolerability in its preclinical studies and clinical trials of rese-cel; risks that modifications to trial design or approach may not have the intended benefits and that the trial design may need to be further modified; our ability to protect and maintain our intellectual property position, risks related to our relationships 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 Designations and Fast Track Designations, risks related to regulatory filings and potential clearance, 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, and risks related to volatile market and economic conditions and public health crises. 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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 and subsequent 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. 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Develop and launch the first curative targeted cellular therapies for patients with autoimmune diseases

Planning to leverage increasing clinical data and unique development program for rese-cel1 2025: Pursuing an efficient path to approval CRS, cytokine release syndrome; DM – dermatomyositis; DORIS – definition of remission in SLE; ICANS, immune effector cell-associated neurotoxicity syndrome; LN – lupus nephritis; PK – pharmacokinetic; PD – pharmacodynamic; SLE – systemic lupus erythematosus; TIS – total improvement score. resecabtagene autoleucel; CABA-201 As of Jan 8, 2025. As of Feb 13, 2025. Golder, et al. Lupus. 2018;27(3): 501-506 Unique development strategy designed to accelerate time to approval and launch Compelling clinical efficacy with favorable safety profile & deep B cell depletion Multiple near-term catalysts including clarity on potential path to approval Multiple disease-specific trials with a common design allow for generation of disease-specific efficacy data with shared safety database Weight-based dose, single infusion; supported by clinical & translational data2 Industry-leading clinical network: 50 active US and European sites 26 patients enrolled Enrolling ~1 pt/week since Nov. 20243 Deepening clinical efficacy data over-time with immunosuppressant and steroid-free outcomes2: DORIS remission in 3 SLE patients Complete renal response in 1st LN pt Major TIS response in 1st DM patient Favorable safety profile in 1st 10 patients 90% either no CRS or Grade 1 CRS 90% no ICANS Deep systemic B cell depletion observed in the periphery and confirmed in the tissue in scleroderma patient by lymph node biopsy Meeting scheduled with FDA to align on registrational trial designs in 1H25 for rese-cel Enroll and complete dosing in multiple disease-specific cohorts in 2025 Present clinical data on rese-cel at medical meetings throughout 2025, including data evaluating rese-cel without preconditioning Patients are seeking a drug-free, symptom-free life which is rarely achieved despite current therapies; physicians also prioritize prevention of end-organ damage4

RESET clinical program has disease-specific cohorts designed to evolve directly into registrational studies Innovative clinical strategy with potential for accelerated regulatory path Program1 Trial Preclinical Phase 1/2 Pivotal Rese-cel (CABA-201) 4-1BB CD19-CAR T RESET-Myositis™ CARTA Chimeric Antigen Receptor T cells for Autoimmunity RESET-SLE™ RESET-SSc™ RESET-MG™ RESET-MS™ RESET-PV™ Dermatomyositis Antisynthetase syndrome Immune-mediated necrotizing myopathy Lupus Nephritis Non-Renal SLE Skin + Organ Cohort AChR-Ab neg. gMG AChR-Ab pos. gMG Skin Cohort Rheumatology Neurology Dermatology FTD Mucocutaneous & mucosal pemphigus vulgaris Contains cohort(s) without preconditioning Juvenile Myositis Pediatric Indication RESET™ – REstoring SElf-Tolerance; Ab – Antibody; AChR – Acetylcholine receptor; gMG – Generalized myasthenia gravis; MS – Multiple sclerosis; SLE – Systemic lupus erythematosus Additional pipeline candidate includes MuSK-CAART for MuSK-Ab positive MG, currently being evaluated in a Phase 1 trial. FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, mucosal pemphigus vulgaris, MuSK-Ab positive MG, and multiple sclerosis. Progressive MS Relapsing MS

Chimeric Antigen Receptor T Cells for Autoimmunity (rese-cel)

~150 autoimmune patients have been dosed with a range of autologous CAR T constructs (industry & academia)1 Autologous CAR T is potentially transformational for autoimmunity IIM – idiopathic inflammatory myopathy; MG – Myasthenia gravis; MS – Multiple sclerosis; SPS – Stiff person syndrome; SSc – Systemic sclerosis. Note: ‘Other’ indications includes CIDP, IgG4-related disease, ANCA-associated vasculitis, NMOSD, Lambert Eaton myasthenic syndrome, autoimmune encephalitis. 1. Data as of November 2024 (ACR Convergence 2024) based on Cabaletta Bio literature review across industry and academia. 2. Abstract 1749: Safety and Long-term Efficacy of CD19-CAR T-cell Therapy in 30 Patients with Autoimmune Disease. ACR Convergence 2024. Compelling immunosuppressant-free clinical responses observed across many autoimmune diseases, durable for up to 4 years Clinical recurrences observed in <5% of ~150 treated patients IIM patient relapsed after 12+ months of drug-free remission No evidence of CD19 escape or failure Patient treated with BCMA-CAR T & now in remission2 ~150 Patients Treated (by Disease) Type of CAR T Construct Efficacy Observations1 Safety Observations1 Among ~150 autoimmune patients dosed with cell therapy, frequency and severity of CRS/ICANS events were considerably lower than those observed in cancer patients <2% Gr 3+ CRS & Gr 3+ ICANS events observed Vaccine titers stable with CD19-CAR T mono-targeting therapy insufficient data with CD19xBCMA-CAR T 31% 60% 8%

Cabaletta rese-cel binder with similar in vitro & in vivo activity to construct used in academic studies1,3 Rese-cel: CD19-CAR T specifically designed for autoimmunity Peng, Binghao J, et al. “Preclinical specificity and activity of CABA-201, a fully human 4-1BB containing CD19 CAR T therapy for treatment-resistant autoimmune disease.” Poster presented at: American Society Gene and Cell Therapy 26th Annual Meeting; 2023 May 19; Los Angeles, CA. Dai, Zhenyu, et al. "Development and functional characterization of novel fully human anti‐CD19 chimeric antigen receptors for T‐cell therapy." Journal of Cellular Physiology 236.8 (2021): 5832-5847. Müller, Fabian, et al. "CD19 CAR T-Cell Therapy in Autoimmune Disease—A Case Series with Follow-up." New England Journal of Medicine 390.8 (2024): 687-700. Maschan, Michael, et al. “Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients.” Nature Communications 12, 7200 (2021) Transmembrane domain in rese-cel is CD8α vs. TNFRSF19 (Troy) utilized in the academic construct. The two transmembrane domains have not been shown to have a significant difference in function or IFN-γ production in preclinical studies. The CD8α transmembrane domain is employed in tisagenlecleucel. Volkov, Jenell, et al. “Case study of CD19 CAR T therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis phase I/II trial.” Molecular Therapy 32.11 (2024): 3821-3828. Abstract 1733: Safety and Efficacy of CABA-201, a Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy in Patients with Immune-Mediated Necrotizing Myopathy and Systemic Lupus Erythematosus from the RESET-MyositisTM and RESET-SLETM Clinical Trials. ACR 2024. Rese-cel product design & clinical / translational data 4-1BB costimulatory domain with fully human binder Binder with similar affinity & biologic activity to academic FMC63 binder while binding to the same epitopes1,2 Same weight-based dose as in academic studies Potential to provide immune reset based on initial clinical and translational data5 Initial patients treated with rese-cel have shown compelling clinical responses with safety data that supports autoimmune development6 Fully human anti-CD19 binder 4-1BB costimulatory domain CD3-z signaling domain Rese-cel4

Broad portfolio with six RESET trials designed to address high unmet need and realize the potential of rese-cel RESET™ program addressing several autoimmune markets SLE – Systemic lupus erythematosus; DM – Dermatomyositis; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis; MS – multiple sclerosis; ESRD – End-stage renal disease; PV – pemphigus vulgaris SSc gMG PV ~90k ~55k ~15k Middle age onset common Progressive skin & organ fibrosis with lung, cardiac, renal damage Average survival of 12y Bimodal age of onset Profound weakness that can be disabling Risk for myasthenic crises, with respiratory failure Phase 1/2 Trials Rheum Neuro Derm No Flu/Cy Pure autoantibody & B-cell mediated autoimmune disease Characterized by painful blisters & erosions SLE ~160-320k Affects young women & people of color ~40% with lupus nephritis, which carries ~25% risk of death or ESRD within 10y > > > Myositis ~70k Typical onset middle age Only FDA-approved therapy is IVIg in DM High mortality due to lung & cardiac involvement > MS ~750k Chronic inflammation, axon loss, cognitive impairment, and irreversible neurologic damage > ~85k ~150k ~60k ~100k ~550k ~20k U.S. Prevalence EU Prevalence

Rese-cel Clinical & Translational Data

Designed to evaluate the safety and tolerability of rese-cel in subjects with active, refractory disease​ Key inclusion and exclusion criteria in RESETTM clinical program ASyS, antisynthetase syndrome; CAR, chimeric antigen receptor; DM, dermatomyositis; HSCT, hematopoietic stem cell transplantation; IIM, idiopathic inflammatory myopathy; JIIM, juvenile idiopathic inflammatory myopathy; LN, lupus nephritis; MAA, myositis-associated antibody; SLEDAI-2k, SLE disease activity index 2000; SSc, systemic sclerosis. 1. ClinicalTrials.gov. Available at: www.clinicaltrials.gov/study/NCT06121297 (accessed October 2024). 2. ClinicalTrials.gov. Available at: www.clinicaltrials.gov/study/NCT06328777 (accessed October 2024). 3. ClinicalTrials.gov. Available at: www.clinicaltrials.gov/study/NCT06154252 (accessed October 2024). RESET-SLE™ Diagnosis of SLE (SLE or LN) Age ≥18 and ≤65 Positive ANA or anti-dsDNA at screening SLE (non-renal): active, moderate to severe SLE, SLEDAI-2K ≥8; pure class V LN eligible LN: active, biopsy-proven LN class III or IV (± class V) RESET-Myositis™ Diagnosis of IIM (ASyS, DM, or IMNM) Age ≥18 and ≤75 Presence of at least one myositis antibody JIIM: Age ≥6 and ≤17 with presence of at least one MSA or MAA Diagnosis of SSc limited or diffuse Age ≥18 and ≤70 Evidence of significant skin, pulmonary, renal, or cardiac involvement RESET-SSc™ Evidence of active disease despite prior or current treatment with standard of care Key inclusion criteria1–3 Key exclusion criteria1–3 B cell-depleting agent within prior 3-6 months; Previous CAR T therapy and/or HSCT Presence of kidney disease other than LN Current symptoms of severe, progressive, or uncontrolled pulmonary or cardiac disease Cancer-associated myositis Significant lung or cardiac impairment Severe lung or cardiac impairment Anticipate enrolling and completing dosing in multiple disease-specific cohorts in 2025; similarly designed RESET-MG™ Phase 1/2 trial enrolling

Individual trials in myositis, SLE, and SSc share common elements of preconditioning, dose, and study design RESETTM clinical trials have consistent design principles1 †Follow up period encompasses 15 years in total, aligned to regulatory guidance for CAR T cell therapies. AE, adverse event; CABA, Cabaletta Approach to B cell Ablation; FLU, fludarabine; CY, cyclophosphamide; PBMC, peripheral blood mononuclear cell; PD, pharmacodynamics; PK, pharmacokinetics; RESET, REstoring SElf-Tolerance; SLE, systemic lupus erythematosus; SSc, systemic sclerosis. Cabaletta Bio: Data on file; 1. Peng BJ, et al. Mol Ther Methods Clin Dev. 2024;32(2):101267. Leukapheresis and CABA-201 production Preconditioning Single infusion of CABA-201 Weight-based dosing 1×106 cells/kg Day 1 Primary endpoint: Incidence and severity of AEs T cells isolated from patient’s own PBMCs (autologous CAR T) Day 29 Study follow-up through Year 3† Screening Additional Endpoints Clinical efficacy measuring: Drug-free responses Validated study-specific endpoints PK/PD analysis: CABA-201 expansion B cell depletion B cell repopulation Adverse events & safety Biomarker analysis, including autoantibody levels FLU 25 mg/m2 x 3 days CY 1000 mg/m2 x 1 day Day -5 to Day -3

All patients had active, refractory disease and most had failed B cell-targeting therapies Baseline characteristics of first 10 patients in the RESET™ program *Baseline disease activity = activity before preconditioning. #Prednisone/prednisone equivalent dose †SLE-1 had class V LN; inclusion criteria for LN cohort requires class III/IV LN. ‡SLE-4 initiated 20 mg/day of prednisone after screening and before leukapheresis, tapered to 2.5mg by latest follow-up of week 8 and discontinued as of data cut. ADA, adalimumab; ANI, anifrolumab; AZA, azathioprine; BEL, belimumab; BRX, brentuximab vedotin; CK, creatinine kinase; CYC, cyclophosphamide; dsDNA, double-stranded DNA; GC, glucocorticoid; HCQ, hydroxychloroquine; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IVIG, intravenous immunoglobulin; LEF, leflunomide; MMF, mycophenolate mofetil; MMT-8, manual muscle testing 8; mRSS, modified Rodnan skin score; MSC, mesenchymal stem cell; MTX, methotrexate; RESET, REstoring SElf-Tolerance; RNA P III, RNA polymerase III; RTX, rituximab; SAE, small ubiquitin-like modifier activating enzyme; SLEDAI-2K, SLE disease activity index 2000; SRP, signal recognition particle; TAC, tacrolimus; U/L, units per liter; UPCR, urinary protein-to-creatinine ratio; VOC, voclosporin, y, years. Cabaletta Bio: Data on file. RESET-Myositis™ RESET-Myositis Patient / Cohort IMNM-1 IMNM-2 DM-1 Age, sex 33 M 60 M 57 M Disease duration (y) ~2 ~4 ~4 Autoantibodies SRP HMGCR SAE Baseline Disease activity* MMT-8 130 126 131 CK (U/L) 617 4725 94 Therapies at Screening GC, MTX GC, IVIG GC, MMF, HCQ Other prior therapies RTX, IVIG RTX, MMF, MTX IVIG GC dose at Screening (mg/day)# 5 5 20 RESET-SLE™ SLE-1† Class V LN SLE-2 SLE-3 SLE-4 LN-1 LN-2 26 M 36 F 44 F 37 F 24 F 35 F ~6 ~17 ~9 ~10 ~2 ~8 dsDNA dsDNA dsDNA dsDNA dsDNA dsDNA SLEDAI-2K 26 10 8 8 22 14 UPCR (mg/mg) 1.08† n/a n/a n/a 7.22 4.85 HCQ, GC, MMF GC, AZA HCQ, MMF, BEL HCQ‡ HCQ, GC, MMF, ANI, VOC MMF CYC, BEL, VOC, TAC HCQ, MTX, ANI, BEL, MSC, RTX, ADA GC, MTX MTX, BEL BEL, LEF HCQ, GC, AZA, RTX 10 7 n/a n/a‡ 20 N/A RESET-SSc™ SSc-Skin-1 Severe skin cohort 66 F ~2 RNA P III mRSS 42 MMF, BRX HCQ N/A

B cell repopulation with transitional naïve cells started as early as 2 months post-infusion Consistent and deep B cell depletion by Day 221 PK, pharmacokinetic; PD, pharmacodynamic * Pre-infusion B-cell levels were measured at pre-preconditioning for all subjects other than IMNM-2 where apheresis was used 1. Nunez et al. Correlative Studies of CABA-201 from the RESET-MyositisTM and RESET-SLETM Clinical Trials. Presented at ACR Convergence 2024. Abstract 0324 Peak expansion typically day 8 to 15; B cell depletion by day 22 B cell repopulation as early as 8 weeks post-infusion * B cell repopulation across all indications to date Rese-cel exhibited a PK/PD profile with peak expansion between Day 8 and 15 as expected, with a later 2nd peak for the first LN patient, suggestive of a possible occult infection1 SSc Myositis SLE & LN

Tissue resident depletion, consistent with the deep B cell depletion in circulation, observed via lymph node biopsy Lymph node B cell depletion 21 days post infusion in first SSc patient LN biopsies were from the left inguinal area using USG at U. Michigan by Dr. Khanna All Images are 20X magnification Baseline 21 days post-infusion T cells (CD3) B cells (CD20) B cells (CD19)

Incidence and severity of adverse events in the first 10 patients* *As of Jan 8, 2025; Primary endpoint is incidence and severity of adverse events through Day 29. †Graded per ASTCT Consensus Grading Criteria. Of these patients, DM-1, SLE-2, SLE-3, SLE-4, LN-2, and SSc-Skin-1 received medication for seizure prophylaxis. Tocilizumab was not administered for any cases of CRS. ‡Coded in System Organ Class of Infections and Infestations and meets seriousness criteria. §As assessed per FDA guidelines. ¶Consistent with “Prolonged Cytopenias,” which is a labeled warning and precaution for approved oncology CAR T products. MIP-1β, IL-27 Nunez et al. Correlative Studies of CABA-201 from the RESET-MyositisTM and RESET-SLETM Clinical Trials. Presented at ACR Convergence 2024. Abstract 0324 CRS, cytokine release syndrome; CY, cyclophosphamide; FLU, fludarabine; ICANS, immune effector cell-associated neurotoxicity syndrome; SAE, serious adverse event. Cabaletta Bio: Data on file. **Prior to infusion, LN-1 patient experienced acute, febrile inflammatory events & highly elevated pro-inflammatory cytokines1 that continued after treatment, suggesting a possible occult infection; supportive data from TCR clonal sequencing2. ICANS event resolved completely with standard therapies. RESET-Myositis™ Cohort IMNM DM Patient IMNM-1 IMNM-2 DM-1 CRS† None None None ICANS† None None None Serious infections‡ None None None Hypogammaglobulinemia None None None Related SAEs (Grade)§ (excluding CRS and ICANS) None None None RESET-SLE™ Non-renal SLE LN SLE-1 SLE-2 SLE-3 SLE-4 LN-1** LN-2 None Grade 1 None None Grade 1 None None None None None Grade 4 None None None None None None None None None None None Grade 2 None None None None None Fever (1) Neutropenic fever (1) Pancytopenia¶ (4) None RESET-SSc™ Severe Skin SSc-Skin-1 Grade 2 None None None None

1st known adult DM patient dosed with CAR T demonstrated compelling early response off immunosuppressants* RESET-Myositis™: Efficacy data following rese-cel infusion *As of Jan 8, 2025. CDASI-A, Cutaneous Dermatomyositis Disease Area and Severity Index – Activity; CK, creatinine kinase; HCQ, hydroxychloroquine; MMF, mycophenolate mofetil; MMT-8, manual muscle testing 8; TIS, total improvement score; U/L, units per liter. Cabaletta Bio: Data on file. Maintenance of major response to treatment (TIS) in DM-1 shows potential for achieving drug-free remission in patients with refractory myositis Disease activity & improvement measures DM patient maintained a major TIS response at Week 12 CK (U/L) MMT-8 Normal strength CK DM-1 CDASI-A TIS Major Moderate Minimal None Discontinued all immunosuppressants MMF, HCQ Discontinued:

1st IMNM patient with longer follow up demonstrated continuing clinical response off immunosuppressants* RESET-Myositis™: Efficacy data following rese-cel infusion1 *As of Jan 8, 2025. †IMNM-1 Day 29 CK measurement was unavailable; Day 22 used. ‡IMNM-2 developed a PE at Day 38 with a prolonged hospitalization and recovery and received IVIG just after Week 12 visit and increased prednisone from 5 mg to 20 mg 2 weeks later. CK, creatinine kinase; HCQ, hydroxychloroquine; IVIG, intravenous immunoglobulin; MTX, methotrexate; MMF, mycophenolate mofetil; MMT-8, manual muscle testing 8; TIS, total improvement score; U/L, units per liter. 1. Cabaletta Bio: Data on file. 2. Schett, G. 'CAR-T Cell Therapy: "The Future is Now."' 5th Global Conference on Myositis. iMyoS. Pittsburgh, PA. Initial clinical responses in IMNM are consistent with published data;2 response kinetics seem to differ among myositis subtypes Disease activity & improvement measures 1st IMNM patient demonstrated continuing clinical response off immunosuppressants without flares at Week 40 TIS Major Moderate Minimal None MTX IVIG MMF, HCQ Discontinued all immunosuppressants Discontinued: CK (U/L) MMT-8 CK (N=3) Normal strength † † ‡

3 out of 4 SLE patients have achieved DORIS remission and 1st LN patient achieved CRR off all IS and steroids RESET-SLE™: Efficacy data following rese-cel infusion* *As of Jan 8, 2025 † Enrollment in the LN cohort requires class III/IV +/- V LN. SLE-1 had isolated class V LN and extra-renal SLE disease activity that met inclusion criteria for the non-renal cohort. Proteinuria contributed 4 SLEDAI-2K points at all assessments. ‡ SLEDAI-2K components at latest follow up: SLE-1: proteinuria-4, complement-2, dsDNA-2; SLE-3: dsDNA-2; SLE-4: dsDNA-2; LN-1: rash-2; LN-2: proteinuria-4, leukopenia-1, alopecia-2, complement-2, dsDNA-2 # SLE-4 and LN-1 had discontinued GC as of the data cut; as of the latest follow up SLE-4 was on 2.5mg/d of prednisone (week 8) and LN-1 was on 7mg/d of prednisone (week 24) CRR, complete renal response; DORIS, definition of remission in SLE; IS, immunosuppressant; LLDAS, lupus low disease activity state; N/A, not applicable; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000. Cabaletta Bio: Data on file SLE LN Patient SLE-1† SLE-2 SLE-3 SLE-4 LN-1 LN-2 Latest follow-up (weeks) 36 16 8 8 24 4 DORIS remission (at latest follow-up) ‒ ü ü ü ‒ ‒ LLDAS (at latest follow-up) ‒ ü ü ü ü ‒ SLEDAI-2K score‡ (baseline to latest follow-up) 26→8 10→0 8→2 8→2 22→2 14→11 Urine protein-creatinine ratio (baseline to latest follow-up) 1.08→0.55 N/A N/A N/A 7.22→0.45 4.85→2.56 Complete renal response (at latest follow-up) ‒ N/A N/A N/A ü ‒ Glucocorticoid-free# ü ü ü ü ü ü Immunosuppressant-free ü ü ü ü ü ü

Improvements in skin across multiple body areas and in lung function, after discontinuing immunosuppressants* RESET-SSc™: efficacy data in first SSc patient post rese-cel infusion1 *As of Jan 8, 2025 patient is not taking immunosuppressants or steroids. DLCO, % predicted diffusing capacity for carbon monoxide; FVC, % predicted forced vital capacity; mRSS, modified Rodnan Skin Score (measure of skin thickness in SSc across 17 body areas, with a maximum score of 51. Used as an outcome measure in SSc clinical trials as a surrogate for disease activity, severity, and mortality)2. 1. Cabaletta Bio: Data on file. 2. Khanna D, et al. J Scleroderma Relat Disord. 2017;2(1):11–18. Early clinical data in SSc-Skin-1 indicate potential emergence of a drug-free clinical response* 0 1 2 3 None Mild Moderate Severe 0 1 2 3 None Mild Moderate Severe Baseline mRSS score by body area1 Week 12 mRSS score by body area1 Overall mRSS score1 Baseline Week 12 DLCO 70% 85% FVC 91% 97% Pulmonary function tests

Rese-cel Product/Process Innovations & Indication Expansion

Several innovations to enhance patient experience, expand access and address scale in autoimmune disease Securing & expanding our leadership in autoimmune cell therapy 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). Poster P0744: Clinical and translational findings following MuSK-CAART infusion without preconditioning in patients with Myasthenia Gravis (MuSCAARTesTM trial). ESGCT 2024. Abstract 1372: Autologous CD19 CART Manufacturing from Whole Blood Collection for the Treatment of Autoimmune Disease. ASGCT 2024. Product/Process Innovations in development Minimizing the requirement for inpatient administration and follow-up Advancing whole blood program to remove the burden of apheresis3 Evaluating rese-cel in PV without preconditioning Published data and CAART platform experience suggest that preconditioning may not be necessary in autoimmune patients1,2 As a well-defined autoantibody-mediated disease, PV is a potentially ideal evaluation setting Expected to present clinical data from the RESET-PV trial in 2025 IND application cleared for RESET-MS trial in patients with multiple sclerosis (MS) RESET-MS is a Phase 1/2 dose-escalation study in relapsing MS and progressive MS FDA has granted Fast Track Designation to rese-cel for the treatment of relapsing MS and progressive MS

Staged approach allows for efficient allocation of capital while leveraging experienced partners Manufacturing strategy – securing reliable supply then innovating Innovative Manufacturing: Scale-Up, Reduce COGs & Improve Patient Experience Clinical & Commercial Supply: Penn, CDMOs & CABA Process Clinical Supply: Penn has reliably provided timely product for years WuXi partnership provides additional and expanded global rese-cel supply Advancing Commercial-readiness Efforts: Commercial-ready drug product tech transfer process expected to be completed with Lonza as early as 2H25 Partnered with commercial supplier for vector Opportunity for additional manufacturing partners Expanded partnerships for automated manufacturing Completing Cellares technology assessment program Evaluating whole blood process to eliminate apheresis

Corporate Summary

Track record of operational success evaluating & developing novel cell therapy candidates in autoimmunity Cabaletta Bio leadership LEADERSHIP TEAM Anup Marda Chief Financial Officer Nicolette Sherman Chief HR Officer Michael Gerard General Counsel Steven Nichtberger, M.D. President, CEO & Chairman Heather Harte-Hall Chief Compliance Officer Gwendolyn Binder, Ph.D. President, Science & Technology SCIENTIFIC ADVISORY BOARD Aimee Payne, M.D., Ph.D. Co-Founder and Co-Chair Michael C. Milone, M.D., Ph.D. Co-Founder and Co-Chair Carl June, M.D. Jay Siegel, M.D. Brian Daniels, M.D. Drew Weissman, M.D., Ph.D. Iain McInnes, Ph.D., FRCP, FRSE, FMedSci Georg Schett, M.D. David J. Chang, M.D., M.P.H., FACR Chief Medical Officer Samik Basu, M.D. Chief Scientific Officer Arun Das, M.D. Chief Business Officer From Fortune. ©2024 Fortune Media IP Limited. All rights reserved. Used under license. Sarah Yuan Chief Technology Officer Gerwin Winter Head of International

Cabaletta’s Anticipated Key Milestones for 2025 Present rese-cel clinical & translational data at medical and scientific meetings 2025 Enroll and complete dosing in multiple disease-specific RESETTM cohorts 2025 Present clinical data evaluating rese-cel with no preconditioning from the RESET-PVTM trial 2025 Align with FDA on registrational trial designs for rese-cel 1H25

Corporate Presentation february 2025