Cartesian Therapeutics, Inc. · NASDAQ:RNAC

Cartesian Therapeutics — 6th European CAR T-Cell Meeting 2024

22 slides from Cartesian Therapeutics's conference presentation, Feb 26, 2024

  1. Slide 1: 1

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  2. Slide 2: mRNA CAR-T in Myasthenia Gravis

    mRNA CAR-T in Myasthenia Gravis 6th edition of the European CAR T-cell Meeting February 26, 2024 James F Howard Jr, MD Professor of Neurology, Medicine & Allied Health Departments of Neurology, Medicine & Allied Health The University of North Carolina at Chapel Hill Department of Clinical Sciences (

  3. Slide 3: Howard Disclosures

    Howard Disclosures (26 February 2024) Research Support Consulting / Advisory Boards (e.g. Directors & (active & within 2 years) Services (within 2 years) Advisory) (active) • Ad Scientiam • Alexion Pharmaceuticals • Alexion gMG Scientific • Alexion Pharmaceuticals • argenx BV Advisory Board, (Chair)

  4. Slide 4: Myasthenia Gravis

    Myasthenia Gravis  Chronic, antibody dependent, complement mediate autoimmune neuromuscular disorder  Characterized by variable fluctuating muscle weakness and exertional muscle fatigue  Multiple effector antibodies targeting  acetylcholine receptor AChR,~83%),  muscle specific kinase (MuSK, ~8

  5. Slide 5: Neuromuscular Transmission

    Neuromuscular Transmission Mechanisms of Synaptic Block Functional Blockade of AChR Antigenic Modulation of AChR 5 Conti-Fine, BM et al. The Journal of Clinical Investigation, (2006):116 (11) 2843-54. doi:10.1172/JCI29894

  6. Slide 6: Myasthenia Gravis: Complement Activation

    Myasthenia Gravis Complement Activation Basal Lamina Post MAC Junctional Membrane  Anti-AChR antibodies bind to the AChR and initiate the complement cascade via activation of the C1 complex  The product of the complement cascade is the membrane attack complex (MAC / TCC) 6 Howard JF et al, Exp Opi

  7. Slide 7: Conventional engineered cell therapy uses DNA, which can lead to toxicity

    Conventional engineered cell therapy uses DNA, which can DNA transduced CAR-T associated with: lead to toxicity and increased patient burden  Cytokine release syndrome (CRS)  Neurotoxicity and parkinsonism  Effector function of cell therapy engineered with  Cytopenia (from pre-treatment chemo) D

  8. Slide 8: Cartesian's mRNA approach to expand reach of cell therapy

    Cartesian’s mRNA approach is designed to expand the Expectation for cells to be administered at the therapeutic but sub-toxic doses reach of potent cell therapy products to address potential Descartes-08 has been administered to 66 patients with autoimmune diseases and cancer1 autoimmune indications

  9. Slide 9: Descartes-08 believed to be first mRNA CAR-T in autoimmune disease

    Descartes-08 believed to be the first mRNA CAR-T in clinical development for autoimmune disease  Engineered by transfection of autologous CD8+ T cells with mRNA encoding BCMA-directed CAR  Typical lot processed for infusion within ~3 weeks  Observed to enhance killing and suppression of inflammat

  10. Slide 10: MG-001 Descartes-08 (Phase 2; NCT04146051)

    mRNA CAR-T MG-001 Descartes-08 (Phase 2; NCT04146051) Patient eligibility Part 1  MG-ADL > 6 Identify safe dose  MGFA Clinical Class II-IV Part 2  Stable medication dosing > 8 wks (n = 3) Determine optimal dosing prior to infusion Complete schedule Part 3  4-week washout for biologics (n = 11) P

  11. Slide 11: MG-001 Descartes-08, Part 2 (NCT04146051)

    mRNA CAR-T MG-001 Descartes-08, Part 2 (NCT04146051) Phase 1b/2a Open Label Key Inclusion/Exclusion Criteria  MGFA Clinical Class II-IV  MG-ADL  6  AChR Ab+ or AChR Ab−  Stable SOC Primary endpoint  Type and frequency of AEs at the MTD administered at 3 different schedules Secondary endpoints

  12. Slide 12: MG-001 Descartes-08 Group 2; n=7

    MG-001 Descartes-08 Group 2; n=7 Clinically Meaningful Improvement Clinically Meaningful Improvement Clinically Meaningful Improvement Data are mean score improvement (point) and 95% Confidence Interval (light blue shading). Granit V etal. Lancet Neurol 2023 v22 p578 NCT04146051 12

  13. Slide 13: Descartes-08 was observed to be safe and well-tolerated in MG

    Part 2: all Part 2: Part 2: Part 2: Part 1 Descartes-08 Grade* (n=3) groups (n=11) group 1 (n=3) group 2 (n=7) group 3 (n=1) Hand numbness 2 1 (33%) 0 0 0 0 was observed to Headache 1 1 (33%) 5 (45%) 1 (33%) 3 (43%) 1 (100%) Muscle soreness 1 1 (33%) 1 (9%) 0 1 (14%) 0 be safe and Nausea 1 1 (33%) 4

  14. Slide 14: Descartes-08 observed to induce deep and durable clinical improvement in MG

    Descartes-08 observed to induce deep and durable clinical improvement in MG  Notable magnitude and duration of response across all 4 standard MG severity scales  Responses appear to deepen after completing treatment at Week 6  Positive twelve-month follow- up data from Phase 2a study Manuscript s

  15. Slide 15: Descartes-08 observed to induce deep and durable clinical improvement in MG

    Descartes-08 observed to induce deep and durable clinical improvement in MG  Notable magnitude and duration of response across all 4 standard MG severity scales  Responses appear to deepen after completing treatment at Week 6  Positive twelve-month follow- up data from Phase 2a study Manuscript s

  16. Slide 16: Measures of Disease Severity at Week 12

    MG-001 Descartes-08 Measures of Disease Severity at Week 12 Granit V etal. Lancet Neurol 2023 v22 p578 16

  17. Slide 17: Lasting reductions in autoantibody titers consistent with clinical responses

    MG-001 Descartes-08 Lasting reductions in autoantibody titers are consistent with the observed clinical responses and mechanism of action Manuscript submitted for peer review; pre-print available at medRxiv.org. Anti-AChR Antibody titers of all participants who received six once-weekly infusions and

  18. Slide 18: Retreated patients experienced rapid improvement in clinical scores

    MG-001 Descartes-08 Retreated patients experienced rapid improvement in clinical scores which was ongoing at last follow-up (Month 18 and Month 20) Retreatment patient 1 Experienced worsening of symptoms to baseline at Month 12 AChR-Ab pos, Failed AZA, Ecu, Pred, Thymex Retreatment patient 2 Experie

  19. Slide 19: Changes in anti-meningococcal antibody titers and immunoglobulin levels over 12 months

    MG-001 Descartes-08 Changes in anti-meningococcal antibody titers and total immunoglobulin levels over 12 months Manuscript submitted for peer review; pre-print available at medRxiv.org. Quantitative immunoglobulin levels and anti-meningococcal antibody titers of all participants who received six on

  20. Slide 20: Phase 2b randomized, placebo-controlled study

    Descartes-08 in MG Phase 2b randomized, placebo-controlled study Informed Consent/Screening (Days -61 to -12) Plan to treat ~30 patients PRIMARY ENDPOINT Screening (Days -60 to -11)  Proportion of MG Composite responders (≥5-point Leukapheresis & Cell Processing (Days -59 to -10) reduction) at Day

  21. Slide 21: Summary

    mRNA CAR-T Summary  mRNA CAR-Ts have potential to overcome the multiple challenges of DNA CAR-Ts – Ability to treat in outpatient setting – No lymphodepletion – Produces multiple cycles from one apheresis – Limited adverse event profile with no CRS, ICANS or severe infection to date  Expectation f

  22. Slide 22: Thank You!

    Thank You! Any questions? [email protected] University of North Carolina at Chapel Hill 22

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