Slide 1: IMMUNE Reset: The potential of CAR T cell therapy to transform autoimmune disease treatment
IMMUNE Reset: The potential of car t cell therapy to transform the treatment of patients with autoimmune disease Exhibit 99.3
Slide 2: Symposium Speakers
Symposium Speakers Drs Georg Schett and Carl June are members of Cabaletta Bio’s Scientific Advisory Board. David J. Chang, MD, MPH, FACR Chief Medical Officer Cabaletta Bio Philadelphia, PA Carl H. June, MD Director of the Center for Cellular Immunotherapies Penn Medicine Philadelphia, PA Georg Schet
Slide 3: Agenda
8:15 am-8:20 am 8:20 am-8:35 am 8:35 am-8:50 am 8:50 am-9:15 am 9:15 am-9:30 am Welcome and introductions David J. Chang, MD, MPH, FACR Evolving the potential of chimeric antigen receptor (CAR) T cell therapies to autoimmunity Carl H. June, MD Resetting the immune system of patients with autoimmune
Slide 4: Learning Objectives
Learning Objectives Learn about the history of CAR T cell therapies in oncology and their potential in autoimmunity Review the role of B cells in autoimmune disease and the potential for CD19-CAR T cell therapy to transform treatment Understand the potential of CD19-CAR T cell therapy to reset the i
Slide 5: Evolving the Potential of CAR T Cell Therapies to Autoimmunity
Evolving the Potential of Chimeric Antigen Receptor (CAR) T Cell Therapies to Autoimmunity
Slide 6: What Are Chimeric Antigen Receptor (CAR) T Cells?
Engineered T cells that combine the targeting ability of antibodies with the cell-killing machinery of T cells What Are Chimeric Antigen Receptor (CAR) T Cells? CD, cluster of differentiation; HLA, human leukocyte antigen. June CH, Sadelain M. N Engl J Med. 2018;379;64-73. T CELL RECEPTOR CHIMERIC A
Slide 7: Personalized Manufacturing of CAR T Cells
Personalized Manufacturing of CAR T Cells C&EN Oncology. Accessed June 10, 2024. https://cen.acs.org/pharmaceuticals/oncology/Controlling-CAR-T-scientists-plan/96/i19. Image adapted from C&EN Oncology 2018. T cell source: A patient’s own T cells 1 Leukapheresis: T cells collected from blood 2 Viral
Slide 8: Considerations and Efficacy Outcomes of CAR T in Cancer
Personalized cell therapy product that behaves as a ‘living drug’ by fully eliminating target cells in the body1 Considerations and Efficacy Outcomes of CAR T in Cancer FDA, US Food and Drug Administration. 1. Holzinger A, Abken H. Pharmacology. 2022;107(9-10):446-463. 2. Pietrobon V, et al. Int J M
Slide 9: Common Adverse Events Associated With CAR T Cell Therapy
Familiarity with CAR T-associated AEs has increased in oncology, enabling potential outpatient administration Common Adverse Events Associated With CAR T Cell Therapy AE, adverse event; BiPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; CRS, cytokine release syndrome
Slide 10: Potential Adverse Events After CAR T Cell Therapy in Cancer
Potential Adverse Events After CAR T Cell Therapy in Cancer 1. Bonifant CL, et al. Mol Ther Oncolytics. 2016;3:16011. 2. Verdun N, Marks P. N Eng J Med. 2024;390(7):584-586. 3. Adkins S. J Adv Pract Oncol. 2019;10(suppl 3):21-28. 4. FDA. Accessed June 10, 2024. https://www.fda.gov/vaccines-blood-bio
Slide 11: Differences in CD19-CAR T Constructs
Product in lymphoma studya Costim domain CRS ICANS Requiring tocilizumab Requiring steroids All Gr Gr ≥3 All Gr Gr ≥3 Axicabtagene ciloleucel4 CD28 93% 13% 64% 28% 43% 27% Brexucabtagene autoleucel5 CD28 91% 15% 63% 31% 59% 22% Tisagenlecleucel6 4-1BB 58% 22% 21% 12% 14% 10% Lisocabtagene maraleucel
Slide 12: Success of CAR T in Oncology Established Over Decades
Significant experience with CAR T in B cell cancers provided the foundation for autoimmune application Success of CAR T in Oncology Established Over Decades 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
Slide 13: Considerations for CAR T Therapy in Cancer and Autoimmunity
Factors that predict adverse events and relapse are minimized in autoimmune diseases1 Considerations for CAR T Therapy in Cancer and Autoimmunity 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. Pr
Slide 14: Key Takeaways
Key Takeaways CAR T cells are engineered T cells that are designed to combine the targeting ability of antibodies with the cell-killing machinery of T cells1 Key learnings from oncology have the potential to accelerate the adoption of CAR T cell therapy for autoimmune disease2,3 Differences in CD19-
Slide 15: Resetting the Immune System of Patients With Autoimmune Disease
Resetting the Immune System of Patients With Autoimmune Disease
Slide 16: B Cells Play a Central Role in the Pathogenesis of Autoimmune Diseases
B Cells Play a Central Role in the Pathogenesis of Autoimmune Diseases B cells contribute to autoimmunity through a variety of mechanisms1,2 Autoantibody production Antigen presentation T cell co-stimulation Production of proinflammatory cytokines While circulating B cells are sensitive to depletion
Slide 17: Current Therapies for B Cell Driven Autoimmune Disease Rarely Achieve Drug-Free Remission
Current Therapies for B Cell Driven Autoimmune Disease Rarely Achieve Drug-Free Remission 1. Schett G, et a. Ann Rheum Dis. 2024. PMID: 38777374. 2. Bucci, L. et al. Nat Med. 2024; PMID 38671240. Current challenges Despite good peripheral B cell depletion, bispecific and antibody-based B cell target
Slide 18: Emerging Academic Evidence of CD19-CAR T in Autoimmunity
Emerging Academic Evidence of CD19-CAR T in Autoimmunity CK: creatinine kinase; Flu/Cy, fludarabine/cyclophosphamide; LN, lupus nephritis; SLE, systemic lupus erythematosus; SLEDAI-2K, systemic lupus erythematosus disease activity index 2K. Müller F, et al. N Engl J Med. 2024;390(8):687-700. 15 pati
Slide 19: CD19-CAR T Cells Can Result in Targeted B Cell Depletion
Preconditioning results in transient WBC decrease, though B cell depletion is sustained CD19-CAR T Cells Can Result in Targeted B Cell Depletion WBC, white blood cell. Müller F, et al. N Engl J Med. 2024;390(8):687-700. Circulating CAR T cell numbers after CD19-CAR T treatment (N=15) CD19-CAR T cell
Slide 20: Reconstitution With Naïve B Cells Within Months
Reconstitution With Naïve B Cells Within 7 Months1 BL, baseline; FU, follow-up; Ig, immunoglobulin; IIM, idiopathic inflammatory myopathy; RC, reconstitution. 1. Müller F, et al. N Engl J Med. 2024;390(8):687-700. 2. Mackensen, Andreas A, et al. Nature Medicine. 2022;28(10):1-9. B cell reconstitutio
Slide 21: Long-term Efficacy Outcomes With CD19-CAR T Cells
Patients maintained off immunosuppressive therapies, suggesting an ‘immune reset’ is possible Long-term Efficacy Outcomes With CD19-CAR T Cells Figures adapted from Müller F, et al. 2024. C3, complement component 3; EUSTAR-AI, European Scleroderma Trials and Research Group activity index; dsDNA, dou
Slide 22: Initial HMGCR IMNM Patient Treated With CD19-CAR T
Preliminary academic data suggests potential slower IMNM improvement due to muscle-predominant disease1,2 Initial HMGCR IMNM Patient Treated With CD19-CAR T1 MMT8 Units 120 100 80 60 0 50 100 150 81-year-old woman with HMGCR IMNM Myositis subtype involving primarily muscle Manifestations may affect
Slide 23: Safety & Tolerability of CD19-CAR T in Autoimmunity
AE profile consisted primarily of fever in 4-1BB costimulatory domain-containing CD19-CAR T Safety & Tolerability of CD19-CAR T in Autoimmunity1 a2 patients (1 SLE, 1 myositis) had preexisting hypogammaglobulinemia due to previous rituximab exposure b1 patient had preexisting hypogammaglobulinemia.
Slide 24: Key Takeaways
Key Takeaways Academic Data Demonstrates Drug-free and Durable Responses in Patients With Myositis, SLE and SSc 1. Müller F, et al. N Engl J Med. 2024;390(8):687-700. 2. Mackensen, Andreas A, et al. Nat Med. 2022;28(10):1-9. Case series provides preliminary support for the feasibility, efficacy and
Slide 25: Unlocking the Potential of CD19-CAR T Cell Therapy in Myositis and Lupus
Unlocking the Potential of CD19-CAR T Cell Therapy in Myositis and Lupus
Slide 26: REstoring SElf-Tolerance (RESET) Development Program
Designed to replicate and expand on the academic clinical data that generated interest in the field REstoring SElf-Tolerance (RESET™) Development Program PK, pharmacokinetics; PD, pharmacodynamics, SAEs: serious adverse events 1.Peng, BinghaoJ, et al. Presented at: American Society Gene and Cell The
Slide 27: Phase 1/2 Myositis Study for CABA-201
Phase 1/2 Myositis Study for CABA-2011 CY, cyclophosphamide; EULAR/ACR, European Alliance of Associations for Rheumatology/America College of Rheumatology; FLU, fludarabine; HSCT, hematopoietic stem cell transplantation. TIS, Total Improvement Score. 1. ClinicalTrials.gov. Accessed June 10, 2024. ht
Slide 28: Phase 1/2 Lupus Study for CABA-201
Phase 1/2 Lupus Study for CABA-2011 ANA, antinuclear antibody; SELENA-2K, Systemic Lupus Erythematosus Disease Activity Index-2K. 1. ClinicalTrials.gov. Accessed June 10, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06121297. Key inclusion criteria Age ≥18 to ≤65 with an SLE diagnosis (2019
Slide 29: Metrics To Assess Outcomes of B Cell Depletion In Autoimmunity
Indicates data being presented for either or both of the first two patients in the RESET™ clinical program. aFlow phenotyping data; confirmatory analyses ongoing. 1. Illustrative graphic, adapted from Taubmann J, et al. OPO141. Abstract presented at: EULAR; May 31, 2023; Milan, Italy. 2. Müller F, e
Slide 30: IMNM: High Unmet Need & Limited Therapeutic Options
IMNM: High Unmet Need & Limited Therapeutic Options1 DM, dermatomyositis; EMA, European Medicines Agency; ESRD, end-stage renal disease; IMNM, immune-mediated necrotizing myopathy; HMGCR: HMG-CoA reductase 1. Suh J, et al. Muscle Nerve. Published online May 27, 2024. doi:10.1002/mus.28114. 2. Khoo T
Slide 31: SLE: Variable Disease Course & Limited Treatments
SLE: Variable Disease Course & Limited Treatments1-6 LN, lupus nephritis. 1. Tian J, et al. Ann Rheum Dis. 2023;82(3):351-356. 2. Hoover PJ, Costenbader KH. Kidney Int. 2016;90(3):487-92. 3. Benlysta. Package insert. GSK; 2018. 4. Saphnelo. Package Insert. AstraZeneca. 2021. 5. Hahn BH, et al. Arthr
Slide 32: Baseline Characteristics of First Two Patients in RESET Trials
Both patients had refractory disease, including to B cell-targeting antibodies & other agents Baseline Characteristics of First Two Patients in RESET Trials aBaseline=pre-preconditioning visit. bDisease manifestations were according to Myositis Disease Activity Assessment Tool (MDAAT) and SLEDAI-2K
Slide 33: CABA-201 was Well-tolerated in Initial Patients
No CRS, ICANS or infections reported through follow-up perioda CABA-201 was Well-tolerated in Initial Patients aData cut-off as of 28 May 2024. bProtocol requires a minimum of 4-day hospitalization for monitoring. cPI-directed taper from 10mg daily prednisone. dGrade 4 leukopenia, neutropenia and ly
Slide 34: CABA-201 Expansion in Anticipated Range
CABA-201 exhibited anticipated profile of expansion and contraction1-5 CABA-201 Expansion in Anticipated Range aResponse appears to be consistent with published data of cryopreserved CAR T products as well as the expansion profile of BCMA-CAR T products in patients with multiple myeloma, in which th
Slide 35: Systemic B Cell Depletion With CABA-201
Complete B cell depletion achieved by day 15 on flow cytometry & maintained in context of WBC recovery Systemic B Cell Depletion With CABA-201 aNadir of lymphocyte count following fludarabine and cyclophosphamide administration estimated based on respective product labels.1,2 WBC, white blood cell.
Slide 36: Immunologic Effects of CABA-201
Immunologic Effects of CABA-201 IMNM #1 CABA-201 pharmacokinetics CABA-201 pharmacodynamics IFNγ peak prior to peripheral CABA-201 peak suggests tissue-resident B cell cytotoxicity Systemic B cell depletion triggers BAFF to encourage bone marrow B cell repopulation IFN�� T cells Preconditioning CABA
Slide 37: CK Reduction & Clinical Improvement Observed in SRP IMNM
Antibody reduction & clinical improvement in disease activity as anticipated with follow-up of 12 weeks CK Reduction & Clinical Improvement Observed in SRP IMNM aData cut-off as of 28 May 2024. bLuminex assay developed and performed by Cabaletta Labs. cQualitative commercial assay (Myositis Antigen
Slide 38: Early Efficacy Signals in Non-Renal SLE
Trend toward improvement in disease manifestations with follow up of 4 weeksb Early Efficacy Signals in Non-Renal SLEa Vasculitis, arthritis and hematuria resolved within 4 weeks despite discontinuation of all therapies at infusion other than ongoing taper from prednisone 10mg per day aPatient in no
Slide 39: CABA-201 Effects on Vaccine & Infection Antibody Titers
CABA-201 Effects on Vaccine & Infection Antibody Titers Titers preserved post-infusion, with no reported infections in the duration of follow-up perioda aData cut-off as of 28 May 2024. IMNM #1 SLE #1 Streptococcus pneumoniae HSV1 Influenza A G4 EA (H1N1) Sars-CoV-2 Epstein-Barr virus (EBV) Bordetel
Slide 40: B Cell Repopulation with Naïve B Cells
Initial patient phenotyping data consistent with potential immune system reset; confirmatory analyses ongoing B Cell Repopulation with Naïve B Cells Note: Flow plot gating reflects CD19+ CD20+ live lymphocytes. aPatient received multiple courses of rituximab, with most recent dose approximately 9 mo
Slide 41: Key Takeaways
Key Takeaways 1. Müller F, et al. N Engl J Med. 2024;390(8):687-700. 2. Castle Phase 1/2 basket study. CABA-201: Designed for autoimmune patients to optimize the potential product profile of CD19-CAR T Safety: In the first 2 patients (IMNM & SLE), CABA-201 was well-tolerated No CRS, ICANS or infecti
Slide 42: Questions & Answers
Questions & Answers
Slide 43: Visit Booth S18-19 for additional engagement with Cabaletta Bio
You are invited to stop by at Booth S18-19 for additional engagement with Cabaletta Bio! Please use the EULAR app to complete an evaluation form To learn more, please visit CabalettaBio.com & contact us at clinicaltrials@cabalettabio.com