Slide 1: Safety and efficacy of CABA-201 in IMNM and SLE from RESET trials
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-Myositis™ and RESET-SLE™ clinical trials Saira Sheikh1; Tahseen Mozaffar2; Vimal Derebail1; Natalie Grov
Slide 2: Disclosures
Disclosures Author Disclosures David J. Chang Employee: Cabaletta Bio Saira Sheikh Consultant: AstraZeneca; Biogen; Cabaletta Bio; GSK Tahseen Mozaffar Advisor or Review Panel Member, Grant/Research Support: Amicus; AnnJi; Argenx; Astellas Gene Therapy; AstraZeneca; Janssen; Sanofi; Spark Therapeuti
Slide 3: Autoimmune Disease Patients Face Substantial Unmet Medical Needs
Autoimmune Disease Patients Face Substantial Unmet Medical Needs Safety and efficacy of CABA-201• 17 NOV 2024 Myositis Chronic inflammation often leads to permanent tissue damage1 Progressive weakness, pain, dysphagia, and extramuscular manifestations are also common5 Systemic lupus erythematosus Sy
Slide 4: What are Chimeric Antigen Receptor (CAR) T Cells?
What are Chimeric Antigen Receptor (CAR) T Cells? Safety and efficacy of CABA-201• 17 NOV 2024 Image adapted from C&EN Oncology 2018.1 Preparation: Standard lymphodepleting preconditioning regimen T cell source: A patient’s own T cells 1 Leukapheresis: T cells collected from blood 2 Viral vector T c
Slide 5: RESET Clinical Program for CABA-201, a CD19-directed CAR T
AChR-Ab, acetylcholine receptor antibody; CABA, Cabaletta Approach to B cell Ablation; CAR, chimeric antigen receptor; RESET, REstoring SElf-Tolerance. Cabaletta Bio: CABA-201. Available at: www.cabalettabio.com/pipeline/caba-201 (accessed October 2024). Trial Preclinical Phase 1/2 Pivotal RESET-Myo
Slide 6: RESET Program: Key Inclusion and Exclusion Criteria
RESET™ Program: Key Inclusion and Exclusion Criteria ANA, antinuclear antibody; anti-dsDNA, anti-double strand DNA antibodies; ASyS, antisynthetase syndrome; CAR, chimeric antigen receptor; DM, dermatomyositis; HSCT, hematopoietic stem cell transplantation; IIM, idiopathic inflammatory myopathy; IMN
Slide 7: RESET Clinical Trials Have Consistent Design Principles
RESET™ Clinical Trials Have Consistent Design Principles1 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 Stu
Slide 8: Baseline Characteristics: First Patients in the RESET Program
Baseline Characteristics: First 8 Patients in the RESET™ Program Safety and efficacy of CABA-201• 17 NOV 2024 All patients had active, refractory disease and most had failed B cell-targeting therapies RESET-Myositis™ RESET-Myositis Patient / Cohort IMNM-1 IMNM-2 DM-1 Age, sex 33 M 60 M 57 M Disease
Slide 9: Baseline Characteristics: First Patients in the RESET Program
Baseline Characteristics: First 8 Patients in the RESET™ Program Safety and efficacy of CABA-201• 17 NOV 2024 RESET-Myositis™ RESET-Myositis Patient / Cohort IMNM-1 IMNM-2 DM-1 Age, sex 33 M 60 M 57 M Disease duration ~2 years ~4 years ~4 years Autoantibodies SRP HMGCR SAE Baseline Disease activity*
Slide 10: Baseline Characteristics: First Patients in the RESET Program
Baseline Characteristics: First 8 Patients in the RESET™ Program Safety and efficacy of CABA-201• 17 NOV 2024 RESET-Myositis™ RESET-Myositis Patient / Cohort IMNM-1 IMNM-2 DM-1 Age, sex 33 M 60 M 57 M Disease duration ~2 years ~4 years ~4 years Autoantibodies SRP HMGCR SAE Baseline Disease activity*
Slide 11: Baseline Characteristics: First Patients in the RESET Program
Baseline Characteristics: First 8 Patients in the RESET™ Program Safety and efficacy of CABA-201• 17 NOV 2024 RESET-Myositis™ RESET-Myositis Patient / Cohort IMNM-1 IMNM-2 DM-1 Age, sex 33 M 60 M 57 M Disease duration ~2 years ~4 years ~4 years Autoantibodies SRP HMGCR SAE Baseline Disease activity*
Slide 12: Baseline Characteristics: First Patients in the RESET Program
Baseline Characteristics: First 8 Patients in the RESET™ Program *Baseline disease activity = activity before preconditioning. † 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 kinas
Slide 13: Incidence and Severity of Adverse Events
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 Safety and efficacy of CABA-201• 17 NOV 2024 Incidence and Severi
Slide 14: Incidence and Severity of Adverse Events
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 SLE-1 SLE-2 SLE-3 None Grade 1 None None
Slide 15: Incidence and Severity of Adverse Events
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 SLE-1 SLE-2 SLE-3 None Grade 1 None None
Slide 16: Incidence and Severity of Adverse Events
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 LN-1 None Grade 1 N
Slide 17: Incidence and Severity of Adverse Events
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 LN-1 None Grade 1 N
Slide 18: Consistent and Complete B cell Depletion by Day 15
Consistent and Complete B cell Depletion by Day 221 B cell depletion & CABA-201 expansion through Day 30 Safety and efficacy of CABA-201• 17 NOV 2024 PK, pharmacokinetic; PD, pharmacodynamic * Pre-infusion B-cell levels were measured at pre-preconditioning for all subjects other than IMNM-2 where ap
Slide 19: RESET-Myositis: Early Efficacy Data Following CABA-201 Infusion
RESET- Myositis™: Early Efficacy Data Following CABA-201 Infusion ‡ As of Nov 1, 2024 CAR; chimeric antigen receptor; CDASI-A, Cutaneous Dermatomyositis Disease Area and Severity Index – Activity; CK, creatinine kinase; DM, dermatomyositis; GC, glucocorticoid; HCQ, hydroxychloroquine; IMNM, immune-m
Slide 20: RESET-Myositis: Efficacy Data Following CABA-201 Infusion
TIS Major Moderate Minor None RESET- Myositis™: Efficacy Data Following CABA-201 Infusion ‡ As of Nov 1, 2024 CDASI-A, Cutaneous Dermatomyositis Disease Area and Severity Index – Activity; CK, creatinine kinase; DM, dermatomyositis; GC, glucocorticoid; HCQ, hydroxychloroquine; IMNM, immune-mediated
Slide 21: RESET-SLE: Efficacy Data in SLE Following CABA-201 Infusion
26 8 SLE-1 Class V LN 10 4 SLE-2 8 2 SLE-3 Discontinued GC, MMF, HCQ Discontinued AZA, HCQ Discontinued HCQ, MMF, BEL Increased DNA binding Low complement Proteinuria Hematuria Vasculitis Leukopenia Pleurisy Pyuria SLEDAI-2K SLEDAI-2K SLEDAI-2K RESET-SLE™: Efficacy Data in SLE Following CABA-201 Inf
Slide 22: RESET-SLE: Efficacy Data in LN Following CABA-201 Infusion
22 SLEDAI-2K 8 RESET-SLE™: Efficacy Data in LN Following CABA-201 infusion Safety and efficacy of CABA-201• 17 NOV 2024 ‡ As of Nov 1, 2024 ANI, anifrolumab; dsDNA, double-stranded DNA; HCQ, hydroxychloroquine; LN, lupus nephritis; MMF, mycophenolate mofetil; RESET, REstoring SElf-Tolerance; SLE, sy
Slide 23: LN-1 Patient: ICANS Event Timeline
Safety and efficacy of CABA-201• 17 NOV 2024 Day -4: Fever/worsening anemia (resolved in 3 days) Day -7 to -5: Preconditioning Day -18: Fever/relapsing pericardial effusion (resolved in 1 day) LN-1 Patient : ICANS Event Timeline 24-year-old female with SLE for ~2 years and with active class III LN A
Slide 24: LN-1 Patient: ICANS Event Timeline
Safety and efficacy of CABA-201• 17 NOV 2024 Day 1: CABA-201 infusion Day 9: Grade 1 CRS Day 10: Grade 4 ICANS Arousable; unable to speak Subclinical seizure activity on EEG No evidence of elevated intracranial pressure or cerebral edema Day 12: ICANS fully resolved Managed with standard therapies D
Slide 25: LN-1 Patient: ICANS Event Timeline
Safety and efficacy of CABA-201• 17 NOV 2024 Day 1: CABA-201 infusion Day 9: Grade 1 CRS Day 10: Grade 4 ICANS Arousable; unable to speak Subclinical seizure activity on EEG No evidence of elevated intracranial pressure or cerebral edema Day 12: ICANS fully resolved Managed with standard therapies D
Slide 26: LN-1 Patient Outcome: Months Post-Treatment
Safety and efficacy of CABA-201• 17 NOV 2024 LN-1 Patient Outcome: 4 Months Post-Treatment Patient 4 Months Follow-up* Off all immunosuppressants‡ Prednisone 8mg/day; taper ongoing SLEDAI-2K: 22 à 8 UPCR (mg/mg): 7.22 à 0.63 Compelling clinical response since discontinuation of all immunosuppressant
Slide 27: LN-1 Patient Outcome: Months Post-Treatment
Safety and efficacy of CABA-201• 17 NOV 2024 LN-1 Patient Outcome: 4 Months Post-Treatment “Overall, I feel much better than I felt before CABA-201 therapy. I have much more energy, I have significantly less joint pain and inflammation, my proteinuria has improved, I no longer have any mouth sores,
Slide 28: RESET-SSc: Emerging Efficacy Data
RESET-SSc™: Emerging Efficacy Data - 42 days post infusion ‡ As of Nov 1, 2024 patient is not taking immunosuppressants or steroids mRSS, modified Rodnan Skin Score; RESET, REstoring SElf-Tolerance; SSc, systemic sclerosis Cabaletta Bio: Data on file. 1. Khanna D, et al. J Scleroderma Relat Disord.
Slide 29: Summary from Clinical and Translational Data on the First Patients
Summary from Clinical and Translational Data on the First 8 Patients Safety and efficacy of CABA-201• 17 NOV 2024 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
Slide 30: Acknowledgements
Patients and caregivers involved in the RESET™ clinical program Site investigators and staff involved with these patients from the RESET™ clinical program Mayo Clinic, Rochester University of California, Davis University of California, Irvine University of Michigan University of North Carolina Cabal