Exhibit 99.1
Corporate Presentation JANUARY 2025 © 2025 Cabaletta Bio. All rights reserved.
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 may enable achieving drug-free, durable meaningful clinical responses, through an immune reset; 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 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 MusCAARTe Phase 1 trial, and impact around reported safety and clinical and translational data of cohorts from our MusCAARTe Phase 1 trial; Cabaletta’s advancement of the whole blood manufacturing program as a potential replacement for apheresis, as well as its potential alignment with FDA in connection thereto; expectation that clinical results will support rese-cel’s safety and activity profile; 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 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. 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 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. 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
3 2025: Realizing our vision by defining an efficient path to approval Planning to leverage increasing clinical data and unique development program for rese-cel (resecabtagene autoleucel; CABA-201) Compelling clinical efficacy Unique development strategy Multiple near-term catalysts with favorable safety profile designed to accelerate time including clarity on potential & rapidly growing enrollment to approval and launch path to approval • Compelling clinical efficacy data in • Multiple disease-specific cohorts with a • Plan to meet with FDA to align on active, refractory autoimmune patients1 common design allow for a potentially registrational trial design in 1H25 • Favorable safety profile in first 10 accelerated path to approval with broad • Enroll and complete dosing in multiple patients dosed, 90% experienced either evaluation of autoimmune indications disease-specific cohorts in 2025 no CRS or grade 1 (fever) CRS and • One weight-based dose administered as • Present clinical data on rese-cel at 90% experienced no ICANS a single infusion; dose supported by medical meetings throughout 2025, clinical & translational data1 • Immunosuppressant-free outcomes including data evaluating rese-celobserved with patients discontinuing all • Industry-leading clinical network without preconditioning immunosuppressants from rese-cel with 44 active clinical sites and growing in infusion through follow up period1 the US and Europe2 Patients are seeking a drug-free, symptom-free life which is rarely achieved despite current therapies; physicians also prioritize prevention of end-organ damage3 1. 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 Convergence 2024. 2. Clinicaltrials.gov as of December 31, 2024 4 3. Golder, et al. Lupus. 2018;27(3): 501-506
Innovative clinical strategy with potential for accelerated regulatory path RESET clinical program has disease-specific cohorts designed to evolve directly into registrational studies Program1 Trial Preclinical Phase 1/2 Pivotal Dermatomyositis Rheumatology Antisynthetase syndrome RESET-Myosit Neurology Immune-mediated necrotizing myopathy Dermatology Juvenile Myositis Contains cohort(s) without preconditioning Pediatric Indication Lupus Nephritis RESET-SLE Rese-cel FTD Non-Renal SLE (CABA-201) Skin + Organ Cohort RESET-SSc 4-1BB CD19-CAR T Skin Cohort AChR-Ab pos. gMG RESET-MG AChR-Ab neg. gMG RESET-MS Relapsing MS Progressive MS RESET-PV Mucocutaneous & mucosal pemphigus vulgaris RESET – REstoring SElf-Tolerance; Ab – Antibody; AChR – Acetylcholine receptor; gMG – Generalized myasthenia gravis; MS – Multiple sclerosis; SLE – Systemic lupus erythematosus 1. Additional pipeline candidate includes MuSK-CAART for MuSK-Ab positive MG, currently being evaluated in a Phase 1 trial. 2. FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, mucosal pemphigus vulgaris, MuSK-Ab positive MG, and multiple sclerosis. 5
Chimeric Antigen Receptor T Cells for Autoimmunity (rese-cel) 6
Rese-cel: CD19-CAR T specifically designed for autoimmunity Cabaletta rese-cel binder with similar in vitro & in vivo activity to construct used in academic studies1,3 Rese-cel product design & clinical / translational data Fully human anti-CD19 binder 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 4-1BB costimulatory domain Same weight-based dose as in academic studies • Potential to provide immune reset based on CD3-ζ signaling domain initial clinical and translational data5 Rese-cel4 Initial patients treated with rese-cel have shown compelling clinical responses with safety data that supports autoimmune development6 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. 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. 5. 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. 6. 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 7 Erythematosus from the RESET-MyositisTM and RESET-SLETM Clinical Trials. ACR 2024.
RESET program addressing several autoimmune markets Broad por ith six RESET trials designed to address high unmet need and realize the potential of rese-cel Phase 1/2 TrialsNo Flu/Cy Myositis SLE SSc gMG MS PV Typical onset middle age Affects young women & Middle age onset Bimodal age of onset Chronic inflammation, Pure autoantibody &Only FDA-approved people of color common axon loss, cognitive B-cell mediated therapy is IVIg in DM Progressive skin & Profound weakness that impairment, and ~40% with lupus can be disabling autoimmune disease High mortality due to nephritis, which carries organ fibrosis with lung, irreversible neurologic Risk for myasthenic Characterized by painful lung & cardiac ~25% risk of death or cardiac, renal damage damage crises, with respiratory blisters & erosions involvement ESRD within 10y Average survival of 12y failure U.S. Prevalence ~68k ~160-320k ~88k ~55k ~750k ~13k EU Prevalence ~85k ~150k ~60k ~100k ~550k ~21k Rheum Neuro Derm SLE – Systemic lupus erythematosus; DM – Dermatomyositis; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis; MS – multiple sclerosis; 8 ESRD – End-stage renal disease; PV – pemphigus vulgaris
Industry-leading clinical site footprint across RESE program1 +1 SLE site in Europe SLE sites Myositis sites Juvenile myositis sites SSc sites MG sites PV sites 21 patients enrolled2 across the RESETTM studies, with 44 actively recruiting clinical sites in the US & Europe 1. Data per clinicaltrials.gov as of December 31, 2024, as compared to companies with actively recruiting U.S. clinical sites for autoimmune cell therapy trials under company-sponsored INDs. 2. As of December 31, 2024. 9
Rese-cel Clinical & Translational Data (Based on Presentation at ACR Convergence 2024) 10
Key inclusion and exclusion criteria in RESETTM clinical program Designed to evaluate the safety and tolerability of rese-cel in subjects with active, refractory disease Key inclusion criteria1–3 Evidence of active disease despite prior or current treatment with standard of care RESET-Myosit 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 (ASyS, DM, or IMNM) • Age ≥18 and ≤70 with a limited or diffuse • SLE (non-renal): active, moderate to severe SSc diagnosis • Presence of at least one myositis antibody SLE, SLEDAI-2K ≥8; pure class V LN patients • Evidence of significant skin, pulmonary, • JIIM: Age ≥6 and ≤17 with presence of at least eligible for this cohort renal, or cardiac involvement one MSA or MAA • LN: active, biopsy-proven LN class III or IV (± class V) 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 • Cancer-associated myositis • Current symptoms of severe, progressive, or • Severe lung or cardiac impairment • Significant lung or cardiac impairment uncontrolled pulmonary or cardiac disease Anticipate enrolling and completing dosing in multiple disease-specific cohorts in 2025; similarly designed RESET-MG Phase 1/2 trial enrolling ASyS, antisynthetase syndrome; CAR, chimeric antigen receptor; DM, dermatomyositis; HSCT, hematopoietic stem cell trans on; 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). 11 3. ClinicalTrials.gov. Available at: www.clinicaltrials.gov/study/NCT06154252 (accessed October 2024).
Baseline characteristics of first 8 patients in the RESE program All patients had active, refractory disease and most had failed B cell-targeting therapi RESET-Myositi RESET-SLE RESET-SSc SLE-1† SSc-Skin-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 Baseline 130 126 131 26 10 8 22 42 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 Screening MMF, HCQ Other prior CYC, BEL, VOC, MSC, RTX, ANI, RTX, IVIG RTX, MMF, MTX IVIG GC, MTX BEL, LEF HCQ therapies TAC BEL, ADA, MTX GC dose at 5 5 20 10 7 n/a 20 n/a 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. 12 Cabaletta Bio: Data on file.
Consistent and deep B cell depletion by Day 221 In patients with >3-month follow-up, B cell repopulation with naïve cells started as early as 8 weeks 1st 150 days: B cell depletion / repopulation & 1st 30 days: B cell depletion & rese-cel expansion rese-cel expansion 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 PK, pharmacokinetic; PD, pharmacodynamic 13 * 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
Incidence and severity of adverse events in the first 8 patients* RESET-Myositi 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 Related SAEs (Grade)§ Fever (1) None None None None None None ¶ None (excluding CRS and ICANS) Pancytopenia (4) **Prior to infusion1, LN-1 patient experienced acute, febrile inflammatory events & highly elevated pro-inflammatory cytokines that continued after treatment, suggesting a possible occult infection; supportive data from TCR clonal sequencing2. ICANS event resolved completely with standard therapies. *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. ¶Consistent with “Prolonged Cytopenias,” which is a labeled warning and precaution for approved oncology CAR T products. 1. MIP-1β, IL-27 2. 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; ICANS, immune effector cell-associated neurotoxicity syndrome; PE, pulmonary embolism; SAE, serious adverse event 14 Cabaletta Bio: Data on file.
RESET-Myositis : Efficacy data following rese-cel infusion 1st known adult DM pati ed with CAR T demonstrated compelling early response off immunosuppressants‡ DM patient demonstrated a major TIS response at Day 29 & Disease activity & improvement measures st 1 IMNM patient showed a moderate TIS response at Week 24 5000 CK (N=3) 100 TIS (N=3) Discontinued all (U/L) 4000 90 immunosuppressants 3000 80 Major CK 70 2000 1000 60 0 TIS 50 Moderate Baseline Day 29 Week 8 Week 12 Week 16 Week 20 Week 24 40 MMT-8 (N=3) 30 Normal strength Minimal 150 20 8 140 10—None MMT 130 0 120 110 Baseline Day 29 Week 8 Week 12 Week 16 Week 20 Week 24 IMNM-1 IMNM-2 Discontinued: MTX IVIG MMF, HCQ IMNM-1 IMNM-2 DM-1 Initial clinical responses in IMNM are consistent with published data1; response kinetics seem to differ among myositis subtypes ‡ As of Nov 1, 2024 15 Cabaletta Bio: Data on file. 1. Schett, G. ‘CAR-T Cell Therapy: “The Future is Now.”’ 5th Global Conference on Myositis. iMyoS. Pittsburgh, PA.
RESET-SL : Efficacy data in SLE following Rese-cel infusion All 3 SLE patients onstrated 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 2K GC, MMF, HCQ 2K AZA, HCQ 2K HCQ, MMF, BEL — 15—15 SLEDAI SLEDAI 15 SLEDAI 10 10 8 10 10 8 dsDNA 5 Low complement 5 4 5 2 Proteinuria dsDNA (Class V LN) Low complement 0 0 0 Baseline Week 24 Baseline Day 29 Baseline Day 29 Clinical Criteria Laboratory Criteria Increased Vasculitis Pleurisy Rash DNA binding Proteinuria Pyuria Arthritis Alopecia Low complement Hematuria Leukopenia 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. 16 Cabaletta Bio: Data on file.
RESET-SL : Outcomes in first LN following rese-cel infusion LN-1 demonstrat ed improvement of proteinuria off all immunosuppressants, continuing steroid taper‡ UPCR decreased from 7.22 to 0.63 mg/mg at Week 16 1st LN patient SLEDAI reduced by 14 points at Week 16 Discontinued all Proteinuria SLEDAI-2K immunosuppressants 30 8 7 7.22 25 22 6 dsDNA Discontinued 5 20 Complement ANI, VOC, MMF, HCQ 4 2K Rash at Baseline (mg/mg)— 15 Pyuria 3 2 UPCR SLEDAI 10 Proteinuria 8 1 0.63 Alopecia Hematuria 0 5 Rash Arthritis Proteinuria 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. 17 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 Baseline mRSS score by body area1 Overall mRSS score1 Day 42 mRSS score by body area1 Baseline Day 22 Day 42 mRSS 42 38 36 • Modified Rodnan Skin Score (mRSS): a measure of skin thickness in SSc across 17 body areas, with a maximum score of 511 0 None 0 None • Used as an outcome measure in SSc clinical 1 Mild trials as a surrogate for disease activity, 1 Mild severity and mortality1 2 Moderate 2 Moderate 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 18 Cabaletta Bio: Data on file. 1. Khanna D, et al. J Scleroderma Relat Disord. 2017;2(1):11–18.
Achieving ‘immune system reset’ may predict long-term durability Autologous CAR T is the only modality to date that has facilitated an immune system reset in autoimmune patients CAR T & B cell levels1 CD19-CAR T Cells Following treatment with autologous CD19-CAR T, 6 pts with 12+ mo. of drug-free remission, as reported by Erlangen group2 Healthy B Naïve cells B cells Autoreactive B cells Infusion 1 mo. 3 mo. 6 mo. 12+ mo. B cell maturation Memory B cell Pre-plasma/ process3 plasma cell B cell precursors How to detect a true immune system reset4 Naïve 1) Naïve B cell repopulation documented by flow B cell cytometry and longitudinal sequencing of BCR Pre-B cell Early Naïve Mat α (Transitional) B + / -β cell 2) Deep transient B cell depletion in all tissues with Periphery lymph node biopsy confirming depletion Bone marrow 1. Illustrative graphic, adapted from Taubmann, J., et al. “OP0141 Long Term Safety and Efficacy Of CAR-T Cell Treatment in Refractory SLE-Data from the First Seven Patients.” (2023): 93-94. 2. 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. 19 3. Image adapted from Cambier JC, et al. Nat Rev Immunol. 2007;7(8):633-643. 4. Proposed mechanism for immune reset based on Cabaletta knowledge and assessment in the field
Rese-cel Product/Process Innovations & Indication Expansion
Securing & expanding our leadership in autoimmune cell therapy Several innovations to prioritize patient experience, expand access and address scale in autoimmune disease Product/Process Innovations in development Evaluating rese-cel in PV without preconditioning Both published data and experience with legacy CAART platform 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 Advancing whole blood program to remove the burden of apheresis3 Minimizing the requirement for inpatient stay 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 1. 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). 2. Poster P0744: Clinical and translational findings following MuSK-CAART infusion without preconditioning in patients with Myasthenia Gravis (MuSCAARTesTM trial). ESGCT 2024. 21 3. Abstract 1372: Autologous CD19 CART Manufacturing from Whole Blood Collection for the Treatment of Autoimmune Disease. ASGCT 2024.
Manufacturing strategy – securing reliable supply then innovating Staged approach allows for efficient allocation of capital while leveraging experienced partners Clinical & Commercial Supply: Innovative Manufacturing: Penn, CDMOs & CABA Process Scale-Up & Reduced COGs • Penn has reliably provided timely product for years • Expanded partnerships for automated manufacturing • WuXi partnership provides additional rese-cel supply • Advancing paths to commercial-ready manufacturing: • Continuous focus on address scale: Expansion of CDMO partnerships for pivotal supply • Further closing and automating our commercial process • Advancing Cellares technology assessment program Partnered wit ier for vector • Evaluating whole blood process to eliminate apheresis • Future consi operated facility • Opportunity for strategic partnership(s) 22
Corporate Summary
Cabaletta Bio leadership Track record of operational success evaluating & developing novel cell therapy candidates in autoimmunity LEADERSHIP TEAM Steven Nichtberger, M.D. Samik Basu, M.D. Gwendolyn Binder, Ph.D. David J. Chang, M.D., M.P.H., FACR Arun Das, M.D. Michael Gerard President, CEO & Chairman Chief Scientific Officer President, Science & Technology Chief Medical Officer Chief Business Officer General Counsel Heather Harte-Hall Anup Marda Nicolette Sherman Gerwin Winter Sarah Yuan Chief Compliance Officer Chief Financial Officer Chief HR Officer Head of International Chief Technology Officer SCIENTIFIC ADVISORY BOARD Aimee Payne, M.D., Ph.D. Michael C. Milone, M.D., Ph.D. Co-Founder and Co-Chair Co-Founder and Co-Chair Brian Daniels, M.D. Georg Schett, M.D. Carl June, M.D. Jay Siegel, M.D. From Fortune. Iain McInnes, Ph.D., FRCP, FRSE, FMedSci Drew Weissman, M.D., Ph.D. ©2024 Fortune Media IP Limited. All rights reserved. Used under license. 24
Cabaletta’s Anticipated Key Milestones for 2025 1H25 2025 2025 2025 Plan to meet with Present clinical data Enroll and complete Present additional FDA to align on evaluating rese-cel dosing in multiple clinical & translational registrational trial without preconditioning disease-specific data on rese-cel at designs for rese-cel from the RESET-PVTM cohorts from the medical or scientific trial RESETTM clinical meetings development program 25
Corporate Presentation JANUARY 2025 © 2025 Cabaletta Bio. All rights reserved.