EX-99.1 2 d874885dex991.htm EX-99.1

Exhibit 99.1 CABA-201 Clinical and Translational Data from the RESET Phase 1/2 Trials NOVEMBER 2024 © 2024 Cabaletta Bio. All rights reserved.

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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 CABA-201, DSG3-CAART 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 CABA-201, ethe risk that signs of biologic activity or persistence may not inform long-term results, the risk that interim results do not always inform later results, the risk that piersistence 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 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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Today’s Agenda AGENDA TOPIC SPEAKER Steven Nichtberger, MD CABA-201 Overview Chief Executive Officer Lessons from Oncology: Expanding CAR T Carl H. June, MD Director of the Center for Cellular Immunotherapies, Penn Medicine Cell Therapies into Autoimmunity CABA-201 Clinical and Translational Data David Chang, MD, MPH, FACR TM Chief Medical Officer from the RESET Clinical Program Steven Nichtberger, MD Conclusions Chief Executive Officer Q&A 3

CABA-201: CD19-CAR T specifically designed for autoimmunity 1,3 Cabaletta’s CD19 binder with similar in vitro & in vivo activity to construct used in academic studies Clinical data reported by IASO using 4 licensed CD19 binder in oncology Fully human anti-CD19 binder Similar binding affinity & biologic activity to FMC63, 1,2 with binding to the same epitopes Fully human binder Evaluated as dual-CAR combined with CD22 binder with standard Flu/Cy preconditioning Data reported in ~20 patients to date 4-1BB costimulatory domain B cell leukemia and lymphoma in IIT in China Same co-stim. domain as used in academic studies CD3-ζ signaling domain Safety data supports autoimmune development 5 CABA-201 IIT – Investigator-initiated trial; Flu/Cy – Fludarabine/Cyclophosphamide 1. 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. 2. 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. 3. 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. 4. Evaluated as part of CT120, a dual-CD19xCD22 CAR T product candidate under development by Nanjing IASO Biotherapeutics, Co., Ltd. (IASO Bio). 5. Transmembrane domain in CABA-201 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 4 IFN-γ production in preclinical studies. The CD8α transmembrane domain is employed in tisagenlecleucel.

RESET clinical program for CABA-201, a CD19-directed CAR T Multiple autoimmune diseases evaluated in distinct disease cohorts across five clinical trials Phase 1/2 Pivotal Program Trial Preclinical Dermatomyositis Rheumatology Anti-synthetase syndrome Neurology RESET-Myositis IMNM Dermatology Contains cohort(s) without preconditioning Juvenile Myositis Pediatric Indication Lupus Nephritis FTD RESET-SLE CABA-201 Non-Renal SLE 4-1BB CD19-CAR T Skin + Organ Cohort RESET-SSc Skin Cohort AChR-Ab pos. gMG RESET-MG AChR-Ab neg. gMG 2 Mucocutaneous & mucosal pemphigus vulgaris RESET-PV RESET – REstoring SElf-Tolerance; IMNM – Immune-mediated necrotizing myopathy; SLE – Systemic lupus erythematosus; Ab – Antibody; AChR – Acetylcholine receptor; gMG – Generalized myasthenia gravis 5 1. FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, mucosal pemphigus vulgaris, and MuSK-Ab positive MG.

1 Expanding clinical site footprint across RESET program TM 16 patients enrolled and 10 patients dosed across RESET studies, with 40 actively recruiting U.S. sites TM • Clinical development expanding to Europe in 2025 with EMA CTA authorization for CABA-201 received for RESET-SLE • Gerwin Winter appointed as SVP and Head of International at Cabaletta Bio SLE sites Myositis sites SSc sites MG sites PV sites TM RESET Program Upcoming Milestone: q 2025: Data permitting, anticipate meeting with FDA regarding potential registrational trial designs for CABA-201 6 1. Data per clinicaltrials.gov as of November 12, 2024, as compared to companies with actively recruiting U.S. clinical sites for autoimmune cell therapy trials under company-sponsored INDs.

Lessons from Oncology: Expanding CAR T Cell Therapies into Autoimmunity 7

Success of CAR T in oncology established over decades B cell cancer experience with CAR T informs use in autoimmune patients 1987 1994 2003 2017 1 First CAR design First report of CAR T cells First anti-CD19 First CAR T cell therapy approved by FDA 2 5 7 killing tumor cells in mice CAR reported (tisagenlecleucel) 1994 1998 2004 2021 First clinical trial of First CD28- First 4-1BB- Early report of CAR T cell CAR T for HIV costimulated CAR costimulated CAR therapy for autoimmune 3 4 6 8 initiated reported reported disease in humans 9 • Multiple types of cell therapies are in Phase 1/2 studies, with the majority being autologous CAR T cell therapy 10 • ~800 ongoing CAR T trials, with the majority in the US and China Experience in oncology has established foundation for application in autoimmune disease 1. Kuwana Y, et al. Biochem Biophys Res Commun. 1987;149(3):960-968. 2. Moritz D, et al. Proc Natl Acad Sci USA. 1994;91:4318-4322. 3. Roberts MR, et al. Blood. 1994;84(9):2878-2889. 4. Krause A, et al. J Exp Med. 1998;188:619-626. 5. Brentjens RJ, et al. Nat Med. 2003;101(4):1637-1644. 6. Imai C, et al. Leukemia. 2004;18:676-684. 7. O’Leary MC, et al. Clin Cancer Res. 2019;25(4):1142-146. 8. Mougiakakos D, et al. N Engl J Med. 2021;385(6):567-569. 9. Krishnamurthy A, et al. Wells Fargo, November 2017. 10. Clinicaltrials.gov. Accessed November 14, 2024. 8 https://clinicaltrials.gov/search?intr=chimeric%20antigen%20receptor.

Considerations for CAR T therapy in cancer and autoimmunity 1 Factors that predict adverse events and relapse differ in patients with autoimmune diseases Cancer Autoimmune disease Risk of side effects related to target B cell burden (including 1-5 CAR CRS and ICANS) T cell Healthy cells Risk of treatment failure due to Necrotic 1,2 cell mutational load (antigen escape) Cancer cells T reg Risk of permanent B cell aplasia 2 Fibroblast due to prior bone marrow damage TME Diseased cell Risk of environmental barriers Cancer (DLBCL) Healthy B cells for CAR T cell infiltration 7 ~10 trillion cells 300 billion cells Anticipated risk of 1-5 1,6 High risk Lower Risk suboptimal outcomes 1 Images adapted from Baker DJ, et al. 2023. TME, tumor microenvironment. 1. Baker DJ, et al. Nature. 2023;619(7971):707-715. 2. Sterner RC, Sterner RM. Blood Cancer J. 2021;11(4):69. 3. Breyanzi. Prescribing information; 2024. 4. Yescarta. Prescribing information; 2024. 5. 9 Kymriah. Prescribing information; 2022. 6. Müller F, et al. N Engl J Med. 2024;390(8):687-700. 7. Sender, R et al. PNAS 2023 e2308511120.

Potential adverse events after CAR T cell therapy in cancer Physician experience in oncology has established algorithms for routine management of common AEs 1 CRS/ICANS assessment parameters Measures alterations in speech, Fever orientation, handwriting, attention, ICE score 2 & receptive aphasia Hypogamma- CRS events globulinemia Consciousness with ICANS CRS Hypotension Graded 1–4 Graded 1–4 Seizure depending on depending on severity & severity & manifestations manifestations and/or Motor findings Hypoxia Cytopenias & neutropenias, ICANS events increasing risk of ICP/cerebral edema infection Managing CRS & ICANS events 3 • CRS: Tocilizumab +/- steroids & supportive care 4 • ICANS: Steroids, supportive care and anti-seizure medications when appropriate 5-8 • Seizure prophylaxis is a routine part of some CAR T therapy administration protocols 9 10 11 Image adapted from Bonifant CL, et al. 2016, Verdun N and Marks P. 2024, Adkins S, et al. 2019. AE, adverse event; CAR, chimeric antigen receptor; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell encephalopathy; ICP, intracranial pressure 1. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25(4):625–638. 2. Herr MM, et al. Biol Blood Marrow Transplant. 2020;26(11):e271–e2744. 3. Zhang Y, et al. J Clin Med. 2023;12(19):6124. 4. Jain MD, et al. Blood. 2023;141(20):2430–2442. 5. The EBMT/EHA CAR-T Cell Handbook. Available at: www.ebmt.org/sites/default/files/2022-02/2022_Book_TheEBMTEHACAR-TCellHandbook.pdf (accessed 10 October 2022). 6. Pensato U, et al. J Neurol. 2023;270(5):2659–2673. 7. Pensato U, et al. Neurol Sci. 2024;45(8):4007–4014. 8. Mackensen A, et al. Nat Med. 2022;28(10):2124–2132. 9. Bonifant CL, et al. Mol Ther Oncolytics. 2016;3:16011. 10. Verdun N, Marks P. N Eng J Med. 2024;390(7):584-586. 11. Adkins S. J Adv Pract Oncol. 2019;10(suppl 3):21-28.

CABA-201 Clinical and Translational Data TM from the RESET Clinical Program 11

Autoimmune disease patients face substantial unmet medical needs 1-4 Despite therapies with chronic broad immunosuppression, mortality is increased, and quality of life is reduced* Systemic lupus Myositis Systemic sclerosis erythematosus 6 • Chronic inflammation often leads to • Progressive, multi-organ damage • Progressive skin and organ fibrosis, which 1 permanent tissue damage often leads to irreversible lung, cardiac and 2 • ~40% develop lupus nephritis with 25% risk kidney damage 7,8 • Progressive weakness, pain, dysphagia, and of death or ESKD within 10 years extramuscular manifestations are also 9 • Average survival from diagnosis is ~12 years 5 common Patients are seeking a drug-free, symptom-free life; 10 physicians also prioritize prevention of end-organ damage *Compared with the general population ESKD, end-stage kidney disease 1. Lundberg IE, et al. Nat Rev Dis Primers. 2021;7(1):86. 2. Allanore Y, et al. Nat Rev Dis Primers. 2015;1:15002. 3. Zen M, et al. Eur J Intern Med. 2023;112:45–51. 4. Refai RH, et al. Sci Rep. 2024;14(1):5234. 5. Suh J, Amato AA. Muscle Nerve. 2024;70(2):166–172. 6. Murimi-Worstell IB, et al. BMJ Open. 2020;10(5):e031850. 7. Anders HJ, et al. 12 Nat Rev Dis Primers. 2020;6(1):7. 8. Hoover PJ, Costenbader KH. Kidney Int. 2016;90(3):487–492. 9. Mayes MD. Rheum Dis Clin North Am. 2003;29(2):239-254. 10. Golder, et al. Lupus. 2018;27(3): 501-506

TM Key inclusion and exclusion criteria in RESET clinical program Designed to evaluate the safety and tolerability of CABA-201 in subjects with active, refractory disease​ 1–3 Key inclusion criteria Evidence of active disease despite prior or current treatment with standard of care RESET-Myositis RESET-SLE RESET-SSc • Age ≥18 and ≤65 with an SLE diagnosis • Age ≥18 and ≤75 with a diagnosis of IIM • Positive ANA or anti-dsDNA at screening • Age ≥18 and ≤70 with a limited or diffuse (ASyS, DM, or IMNM) • SLE (non-renal): active, moderate to severe SSc diagnosis • Presence of at least one MSA SLE, SLEDAI-2K ≥8; pure class V LN patients • Evidence of significant skin, pulmonary, eligible for this cohort • JIIM: Age ≥6 and ≤17 with presence of at least renal, or cardiac involvement one MSA or MAA • LN: active, biopsy-proven LN class III or IV (± class V) 1–3 Key exclusion criteria B cell-depleting agent within prior 3-6 months; Previous CAR T therapy and/or HSCT • Presence of kidney disease other than LN • Cancer-associated myositis • Severe lung or cardiac impairment • Current symptoms of severe, progressive, or • Significant lung or cardiac impairment uncontrolled pulmonary or cardiac disease 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; MSA, myositis-specific antibodies; SLEDAI-2k, SLE disease activity index 2000; SSc, systemic sclerosis. 1. ClinicalTrials.gov. Available at: www.clinicaltrials.gov/study/NCT06121297 (accessed October 2024). 13 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).

1 RESET clinical trials have consistent design principles Individual trials in myositis, SLE, and SSc share common elements of preconditioning, dose, and study design † Day 1 Day 29 Study follow-up through Year 3 Day -5 to Day -3 Leukapheresis Primary endpoint: Additional Endpoints Single infusion Screening and CABA-201 Preconditioning Incidence and of CABA-201 production severity of AEs • 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 T cells isolated from Weight-based 2 FLU 25 mg/m x 3 days autoantibody levels patient’s own PBMCs dosing 2 CY 1000 mg/m x 1 day 6 (autologous CAR T) 1×10 cells/kg Prophylactic tocilizumab is not currently TM used in the RESET protocols †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 14 Cabaletta Bio: Data on file; 1. Peng BJ, et al. Mol Ther Methods Clin Dev. 2024;32(2):101267.

Baseline characteristics of first 8 patients in the RESET program All patients had active, refractory disease and most had failed B cell-targeting therapies RESET-Myositis RESET-SLE RESET-SSc † SSc-Skin-1 SLE-1 Patient / Cohort IMNM-1 IMNM-2 DM-1 SLE-2 SLE-3 LN-1 Class V LN (severe skin cohort) Age, sex 33 M 60 M 57 M 26 M 36 F 44 F 24 F 66 F Disease duration ~2 years ~4 years ~4 years ~6 years ~17 years ~9 years ~2 years ~2 years Autoantibodies SRP HMGCR SAE dsDNA dsDNA dsDNA dsDNA RNA P III MMT-8 SLEDAI-2K mRSS 130 126 131 26 10 8 22 42 Baseline Disease activity* CK (U/L) UPCR (mg/mg) † 617 4725 94 1.08 n/a n/a 7.22 Therapies at GC, ANI, VOC, GC, MTX GC, IVIG GC, MMF, HCQ GC, MMF, HCQ GC, AZA, HCQ HCQ, MMF, BEL MMF MMF, HCQ Screening Other prior CYC, BEL, VOC, MSC, RTX, ANI, RTX, IVIG RTX, MMF, MTX IVIG GC, MTX BEL, LEF HCQ TAC BEL, ADA, MTX therapies GC dose at 5 5 20 n/a 10 7 n/a 20 Screening (mg/day) *Baseline disease activity = activity before pre-conditioning. † SLE-1 had class V LN; inclusion criteria for LN cohort requires class III/IV LN. ADA, adalimumab; ANI, anifrolumab; AZA, azathioprine; BEL, belimumab; CK, creatinine kinase; 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; RNA P III, RNA polymerase III; RTX, rituximab; SAE, small ubiquitin-like modifier activating enzyme; SRP, signal recognition particle; TAC, tacrolimus; U/L, units per liter; UPCR, urinary protein-to-creatinine ratio; VOC, voclosporin. 15 Cabaletta Bio: Data on file.

Incidence and severity of adverse events in the first 8 patients* RESET-Myositis RESET-SLE RESET-SSc Cohort IMNM DM Non-renal SLE LN SSc – Severe Skin Patient IMNM-1 IMNM-2 DM-1 SLE-1 SLE-2 SLE-3 LN-1 SSc-Skin-1 † CRS None None None None Grade 1 None Grade 1 Grade 2 † ICANS None None None None None None Grade 4 None ‡ Serious infections None None None None None None None None Hypogammaglobulinemia None None None None None None Grade 2 None § Fever (1) Related SAEs (Grade) None None None None None None None ¶ (excluding CRS and ICANS) Pancytopenia (4) Back Pain (3) Neutropenia (4) § Unrelated SAEs (Grade) None None None None None None # PE (4) (FLU/CY related) *As of Nov 1, 2024; Primary endpoint is incidence and severity of Adverse Events through Day 29. †Graded per ASTCT Consensus Grading Criteria. Of these patients, only DM-1, SLE-2, SLE-3, 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. #Patient with Factor V Leiden heterozygosity (increased risk for thrombosis), recent intravenous immunoglobulin treatment, history of myocardial infarction, recent hospitalization for back pain & fatigue with decreased mobility. Undetectable CABA-201 levels since Day 22. Event occurred at Day 38 and was reported as PE leading to cardiac arrest, followed by successful pulmonary artery thrombectomy. ¶Consistent with “Prolonged Cytopenias,” which is a labeled warning and precaution for approved oncology CAR T products. CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; PE, pulmonary embolism; SAE, serious adverse event 16 Cabaletta Bio: Data on file.

1 Consistent and complete B cell depletion by Day 22 In patients with >3-month follow-up, B cell repopulation with naïve cells started as early as 8 weeks B cell depletion/repopulation & CABA-201 expansion B cell depletion & CABA-201 expansion through Day 30 through Day 150 CABA-201 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 PK, pharmacokinetic; PD, pharmacodynamic 17 * Pre-infusion B-cell levels were measured at pre-preconditioning for all subjects other than IMNM-2 where apheresis was used TM TM 1. Nunez et al. Correlative Studies of CABA-201 from the RESET-Myositis and RESET-SLE Clinical Trials. Presented at ACR Convergence 2024. Abstract 0324

RESET-Myositis : Early efficacy data following CABA-201 infusion st ‡ 1 known adult DM patient dosed with CAR T demonstrated compelling early response off immunosuppressants Disease activity & improvement measures DM patient demonstrated a major TIS response at Day 29 CK CDASI-A TIS 1000 25 Discontinued all 100 immunosuppressants 800 90 9 600 80 400 70 Baseline Day 29 200 DM-1 60 0 Baseline Day 29 Week 8 Week 12 Week 16 Week 20 Week 24 50 40 MMT-8 Normal strength 30 150 20 140 10 0 130 120 Baseline Day 29 Week 8 Week 12 Week 16 Week 20 Week 24 DM-1 DM-1 MMF, HCQ Discontinued: ‡ As of Nov 1, 2024 18 CDASI-A, Cutaneous Dermatomyositis Disease Area and Severity Index – Activity; TIS, total improvement score; U/L, units per liter. Cabaletta Bio: Data on file. CK (U/L) MMT-8 TIS None Minor Moderate Major

RESET-Myositis : Efficacy data following CABA-201 infusion st ‡ 1 IMNM patient with longer follow up demonstrated continuing response off immunosuppressants without flares st Disease activity & improvement measures 1 IMNM patient showed a moderate TIS response at Week 24 TIS (N=3) CK (N=3) 100 5000 Discontinued all 90 immunosuppressants 4000 80 3000 70 2000 60 1000 50 0 Baseline Day 29 Week 8 Week 12 Week 16 Week 20 Week 24 40 30 MMT-8 (N=3) Normal strength 150 20 140 10 130 0 120 110 IMNM-1 IMNM-2 DM-1 Baseline Day 29 Week 8 Week 12 Week 16 Week 20 Week 24 Discontinued: MTX IVIG MMF, HCQ IMNM-1 IMNM-2 DM-1 1 Initial clinical responses in IMNM are consistent with published data ; response kinetics may differ among myositis subtypes ‡ As of Nov 1, 2024 19 Cabaletta Bio: Data on file. 1. Schett, G. 'CAR-T Cell Therapy: The Future is Now. ' 5th Global Conference on Myositis. iMyoS. Pittsburgh, PA. CK (U/L) MMT-8 TIS None Minor Moderate Major

RESET-SLE : Efficacy data in SLE following CABA-201 infusion ‡ All 3 SLE patients demonstrated clinical responses off immunosuppressants; first patient completed steroid taper SLE-1 (Class V LN) SLE-2 SLE-3 30 30 30 26 25 25 25 20 20 20 Discontinued Discontinued Discontinued AZA, HCQ GC, MMF, HCQ HCQ, MMF, BEL 15 15 15 10 10 10 8 8 10 dsDNA 4 5 5 Low complement 5 2 dsDNA Proteinuria Low complement (Class V LN) 0 0 0 Baseline Week 24 Baseline Day 29 Baseline Day 29 Clinical Criteria Laboratory Criteria Increased Proteinuria Pyuria Vasculitis Pleurisy Rash DNA binding Arthritis Low complement Hematuria Leukopenia Alopecia No clinical symptoms on SLEDAI-2K through latest follow up, including SLE-1 with isolated Class V LN (non-renal cohort) with persistent proteinuria as expected ‡ As of Nov 1, 2024 SLEDAI-2k, SLE disease activity index 2000. 20 Cabaletta Bio: Data on file. SLEDAI-2K SLEDAI-2K SLEDAI-2K

RESET-SLE : Efficacy data in LN following CABA-201 infusion ‡ LN-1 demonstrated marked improvement of proteinuria off all immunosuppressants, continuing steroid taper st UPCR decreased from 7.22 to 0.63 mg/mg at Week 16 1 LN patient SLEDAI reduced by 14 points at Week 16 Discontinued all Proteinuria SLEDAI-2K immunosuppressants 30 8 7.22 7 25 22 6 dsDNA 5 20 Discontinued Complement ANI, VOC, MMF, HCQ Rash 4 15 Pyuria 3 2 Proteinuria 10 8 1 Alopecia 0.63 Hematuria 0 5 Rash Proteinuria Arthritis 0 Baseline Week 16 LN-1 LN-1 proteinuria markedly improved by Week 8 with alopecia/rash as the remaining clinical manifestations at Week 16 after discontinuing all immunosuppressants & continuing prednisone taper ‡ As of Nov 1, 2024 SLEDAI-2k, SLE disease activity index 2000; UPCR, urinary protein-to-creatinine ratio. 21 Cabaletta Bio: Data on file. UPCR (mg/mg) SLEDAI-2K

ICANS event timeline in first LN patient Patient with recent fever in setting of acute and severe inflammation • 24-year-old female with SLE for ~2 years and with active class III LN • Active, severe (SLEDAI-2K = 22; UPCR = 7.22 mg/mg) refractory disease despite 5 systemic treatments* for SLE at screening Day 1: Day -7 to -5: CABA-201 infusion Pre-Conditioning Pre-infusion period Post-infusion period Day -4: Fever/worsening Day 9: Grade 1 CRS Day 12: ICANS fully resolved anemia (resolved in 3 days) • Managed with standard therapies Day -18: Fever/relapsing Day 10: Grade 4 ICANS • Arousable; unable to speak pericardial effusion • Subclinical seizure activity on EEG (resolved in 1 day) • No evidence of elevated intracranial pressure or cerebral edema ‡ Patient had acute, febrile inflammatory events & highly elevated pro-inflammatory cytokines pre-infusion that 1 continued after treatment, suggesting a possible occult infection; supportive data from TCR clonal sequencing *Therapies at Screening: glucocorticoids, anifrolumab, voclosporin, mycophenolate mofetil, hydroxychloroquine ‡MIP-1β, IL-27 22 TM TM Cabaletta Bio: Data on file. 1. Nunez et al. Correlative Studies of CABA-201 from the RESET-Myositis and RESET-SLE Clinical Trials. Presented at ACR Convergence 2024. Abstract 0324

Outcomes in first LN patient 4 months post-treatment Compelling clinical response since discontinuation of all immunosuppressants, continuing steroid taper Patient Month 4 Follow-up* ‡ • Off all immunosuppressants • Prednisone 8mg/day; taper ongoing • SLEDAI-2K: 22 à 8 “Overall, I feel much better than I felt before CABA-201 therapy. I • UPCR (mg/mg): 7.22 à 0.63 have much more energy, I have significantly less joint pain and inflammation, my proteinuria has improved, I no longer have any mouth sores, and I am getting back to my normal self! At 25 years old, my kidneys were not functioning properly and continued to get worse despite all of the strong medications I was on. I had multiple occurrences of fluid around my heart. CABA-201 has put a stop to that and has allowed my body to heal. Although I faced complications afterwards, I believe the improvement that I have seen in both my numbers and how I feel, was far worth it. If I had the choice, I would choose to receive CABA-201 again…. ” - LN-1 patient at 4 months post-therapy *As of Nov 1, 2024 ‡Therapies at Screening: glucocorticoids, anifrolumab, voclosporin, mycophenolate mofetil, hydroxychloroquine 23 Cabaletta Bio: Data on file.

Emerging efficacy data 42 days post infusion in first SSc patient Early disease improvements in face and hands after discontinuation of disease-specific medication 1 1 1 Baseline mRSS score by body area Overall mRSS score Day 42 mRSS score by body area Baseline Day 22 Day 42 mRSS 42 38 36 • Modified Rodnan Skin Score (mRSS): a measure of skin thickness in SSc across 17 1 body areas, with a maximum score of 51 0 None 0 None • Used as an outcome measure in SSc clinical trials as a surrogate for disease activity, 1 Mild 1 Mild 1 severity and mortality Moderate 2 Moderate 2 3 Severe 3 Severe ‡ Early clinical data in SSc-Skin-1 indicate potential emergence of a drug-free clinical response ‡ As of Nov 1, 2024 patient is not taking immunosuppressants or steroids 24 Cabaletta Bio: Data on file. 1. Khanna D, et al. J Scleroderma Relat Disord. 2017;2(1):11–18.

Conclusions 25

Summary from clinical & translational data on the first 8 patients • CABA-201 appears to have a favorable risk-benefit profile • In patients with recent fever or infections, delaying CAR T infusion should be considered • CABA-201 provided compelling efficacy in highly active and refractory autoimmune patients through the follow-up period • Initial data support the potential for drug-free clinical responses • All patients discontinued all immunosuppressants • SLE patients with longer follow-up: steroid taper completed or ongoing (prednisone 8mg/day) 1 • The PK/PD data support the current dose of CABA-201 TM TM 26 1. Nunez et al. Correlative Studies of CABA-201 from the RESET-Myositis and RESET-SLE Clinical Trials. Presented at ACR Convergence 2024. Abstract 0324

Realizing the vision to transform autoimmune disease treatment 2025: Meet with FDA on potential registrational CABA-201 trial designs 2H24: Additional 1H25: clinical data in Initial clinical Executing IND specific clinical myositis & SLE data in MG program to potentially accelerate at ACR 2024 path to regulatory approval Engineered CABA-201 Initial clinical • No requirement for dose escalation data in SSc at specifically for use in • Independent, parallel 6-patient cohorts ACR 2024 autoimmune patients • Increased enrollment observed at • Leveraging insights from industry-leading 40 US clinical sites 1 academic clinical data Innovations in development Securing efficient & scalable commercial manufacturing Advancing whole blood program to replace apheresis Cash runway FDA fast track designation granted Enrolling PV trial of CABA-201 without preconditioning 2 into 1H26 for CABA-201 in multiple indications SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; PV – Pemphigus vulgaris; ACR 2024 – American College of Rheumatology 2024 annual meeting from November 14-19, 2024. 1. 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. The construct utilized in these studies has a similar design to 27 CABA-201, sharing the 4-1BB costimulatory domain, but is a different construct. 2. FDA Fast Track Designation received in dermatomyositis, SLE, lupus nephritis and systemic sclerosis.

Q&A 28