Cartesian Therapeutics, Inc. · NASDAQ:RNAC
Cartesian Therapeutics — 2024 MGFA Scientific Session at AANEM
21 slides from Cartesian Therapeutics's conference presentation, Oct 15, 2024
Slide 1: Safety and efficacy of BCMA-directed mRNA CAR T-cell therapy in generalized myasthenia gravis
Safety and efficacy of BCMA-directed mRNA CAR T- cell therapy in generalized myasthenia gravis 2024 MGFA Scientific Session October 15, 2024 Tuan Vu, Hacer Durmus Tekce, Michael Rivner, Sheetal Shroff, Thomas Ragole, Bennett Myers, Mamatha Pasnoor, George Small, Chafic Karam, Mithila Vullaganti, Ama
Slide 2: COI Disclosures
COI Disclosures • Consultant and/or on speaker bureaus for Alexion/AstraZeneca Rare Disease, Amgen, argenx, CSL Behring, Dianthus, ImmunAbs, Johnson & Johnson, and Takeda. • Research or grant support related to myasthenia gravis from Alexion/AstraZeneca Rare Disease, Amgen, argenx, Cartesians, COUR,
Slide 3: Myasthenia gravis is a rare, progressive autoimmune disease with significant unmet need
Myasthenia gravis is a rare, progressive autoimmune disease with significant unmet need Characterized by debilitating fatigue and muscle weakness >120,000 Patients in the U.S. and EU Limbs Respiratory Ocular Facial Significant unmet need remains Current treatments require chronic or frequent adminis
Slide 4: mRNA engineering may expand the reach of potent cell therapy products
mRNA engineering may expand the reach of potent cell therapy products to address potential autoimmune indications mRNA Cell Therapy Conventional CAR T-Cell Therapy No Lymphodepleting Chemotherapy Required Requires Lymphodepleting Chemotherapy No requirement for cell proliferation → no expected need
Slide 5: Descartes-08 is designed for dual action targeting two BCMA+ cell populations
Descartes-08 is designed for dual action, precisely targeting two key BCMA+ cell populations involved in a spectrum of autoimmune diseases • Descartes-08 is designed to target BCMA, a surface antigen expressed on plasma cells/plasmablasts and plasmacytoid dendritic cells PLASMA CELLS (PCs) AND PLASM
Slide 6: Descartes-08 is an autologous BCMA-directed mRNA CAR-T in clinical development for gMG
Descartes-08 is an autologous BCMA-directed mRNA CAR-T in clinical development for gMG Engineered by transfection of autologous CD8+ T cells with mRNA encoding anti-BCMA CAR Typical lot processed for infusion within ~3 weeks Granted U.S. FDA orphan and RMAT designations for generalized myasthenia gr
Slide 7: Phase 2 study of Descartes-08 in MG (NCT04146051)
Phase 2 study of Descartes-08 in MG (NCT04146051) Part 1 Patient eligibility Identify safe dose Part 2 • Non-MuSK gMG (n = 3) Determine • MG-ADL > 6 optimal dosing • MGFA Class II-IV Complete schedule Part 3 • Stable medication dosing > 8 wks prior (n = 11) Phase 2b to infusion comparing • 4-week wa
Slide 8: Phase 2b trial: double-blind, placebo-controlled trial of Descartes-08 in myasthenia gravis
Phase 2b trial: double-blind, placebo-controlled clinical trial of Descartes- 08 in patients with myasthenia gravis Leukapheresis & Randomization Descartes-08 Cell Processing Days -59 to -10 1:1 Open Label Follow-Up Month 4, Month 6, Month 9, Month 12 Blinded Dosing Unblinding Six weekly doses of De
Slide 9: 14 patients received Descartes-08 and 12 received placebo in primary efficacy dataset
14 patients received Descartes-08 and 12 patients received placebo in the pre-specified primary efficacy dataset 36 patients enrolled 31 5 Per Protocol Population excluded 1 2 2 18 13 Early drop-out Ineligible Not evaluated Randomized to Randomized to Descartes-08 placebo 26 mITT Population • Modifi
Slide 10: Baseline characteristics: highly symptomatic patient population with severe disease
Baseline characteristics: highly symptomatic patient population with severe disease Descartes-08 Placebo Total Mean age, years (SD) 56.7 (16.7) 60 (13.4) 58.2 (15.0) Female 10 (71%) 6 (50%) 16 (62%) Male 4 (29%) 6 (50%) 10 (38%) Weight Mean weight, kg (SD) 94.1 (20.7) 104.0 (26.6) 98.7 (23.7) White,
Slide 11: Prior and ongoing treatments: heavily pre-treated patient population
Prior and ongoing treatments: heavily pre-treated patient population Descartes-08 Placebo Total Pyridostigmine 9 (64%) 8 (67%) 17 (65%) Previous myasthenia Prednisone 8 (57%) 6 (50%) 14 (54%) gravis therapies Other immunosuppressants 8 (57%) 9 (75%) 17 (65%) (standard of Complement inhibitor 3 (21%)
Slide 12: Trial met primary endpoint with statistical significance
Trial met primary endpoint with statistical significance • Responders in pre-specified analysis observed to have ~3x greater improvements than clinically meaningful* in the AChR Ab+ patients • Data support advancement to Phase 3 Proportion of MG Composite Responders (≥5-point reduction) at Month 3 O
Slide 13: In overall population, significant improvements in MG-ADL and MGC at month 3
In overall populaton, statistically significant improvements in MG-ADL and MGC were observed at month 3 in Descartes- 08 vs. placebo treated patients • Non-responders (n=4) • 1 LRP4+ MG non-responder at Month 3 onward • 1 non-responder at Month 3 onward • 1 responded during open label follow-up • 1
Slide 14: In AChR Ab+ patients, significant improvements in MG-ADL, MGC, and QMG vs placebo
In AChR Ab+ patients, Descartes-08 demonstrated statistically significant improvements in MG-ADL, * MGC, and QMG scores vs. ** placebo Statistically significant improvement in Descartes-08 compared to placebo at Month 3 seen across MGC (p=0.002), MG-ADL (p=0.012) and QMG (p=0.029). Placebo responses
Slide 15: Placebo group score reductions driven by responses in seronegative subjects
In the placebo treated group, score reductions in measures of disease activity was driven by responses in seronegative subjects Seronegative AChR Abᐩ Mean change from baseline in AChR Abᐩ (n=9) and seronegative (n=3) participants randomized to placebo (mITT population) 14
Slide 16: Deep and durable responses observed in Descartes-08 responders
Deep and durable responses observed in Descartes-08 responders through Month 6 Results consistent with Phase 2a open-label trial findings Mean decrease from Baseline in MG esponders (participants who achieved a ≥5-point reduction in MGC at 15 Month 3, n=10. Month 4 n=5, Month 6 n=3.
Slide 17: Observed safety results support outpatient administration
Descartes-08 (n=19) Placebo (n=17) Grade 1 Grade 2 Grade 3 Grade 1 Grade 2 Grade 3 Headache 6 (32%) 4 (21%) 2 (12%) 3 (18%) Chills 7 (37%) 4 (21%) 1 (6%) Nausea 2 (11%) 5 (26%) 2 (12%) 2 (12%) Observed safety results Fever 6 (32%) 3 (17%) 1 (6%) 0 (0%) 0 (0%) * Fatigue 5 (26%) 1 (5%) 1 (6%) support
Slide 18: Anti-AChR Ab titer, relative
Approximately 15% reduction in AChR antibody titer at Month 3 is in-line with Phase 2a data Phase 2a data 2.0 Anti-AChR Ab titer, relative Descartes-08 Placebo 1.5 +37.9% 1.0 -14.8% 0.5 0.0 -30 1 29 57 85 Day * Average reduction (±SEM) in AChR antibody in participants Individual Anti-AChR antibody t
Slide 19: Descartes-08 does not deplete broader antibody repertoire or decrease vaccine titers
Descartes-08 does not deplete broader antibody repertoire or decrease vaccine titers for common viruses No significance change in Ig at No significant change in common vaccine titers at primary end point (D85) vs. Day 11 primary end point (Day 85) relative to Day 12 IgG IgG 1.5 Relative to Baseline
Slide 20: Summary
Six once-weekly doses of Descartes-08 were associated with a significantly greater proportion of MGC responders than placebo at Month 3 Responses were greater than clinically meaningful and durable at last follow-up (up to 6 months) Safety data supports outpatient administration with 1hr post-infusi
Slide 21: Thank you
Thank you Special thanks to patients, their caregivers and the entire MG-001 study team 20
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