4D Molecular Therapeutics, Inc. · NASDAQ:FDMT
4D Molecular Therapeutics — ASRS 2024
13 slides from 4D Molecular Therapeutics's conference presentation, Jul 15, 2024
Slide 1: Phase 2 Population Extension Cohort in the PRISM Clinical Trial Evaluating 4D-150
Phase 2 Population Extension Cohort in the PRISM Clinical Trial Evaluating 4D-150 in Adults with Neovascular Age-related Macular Degeneration Raj K. Maturi, M.D. Retina Partners Midwest, Carmel, IN Assistant Professor Indiana University School of Medicine © 2023 4D Molecular Therapeutics. All Rights
Slide 2: 4D-150 Dual-Transgene Intravitreal Gene Therapy
4D-150 Dual-Transgene Intravitreal Gene Therapy ▪ Primate-evolved intravitreal R100 capsid carrying a dual-transgene payload VEGF-C RNAi o Aflibercept & VEGF-C RNAi 4D-150 ▪ Single-dose intravitreal administration Aflibercept (VEGF Trap) DNA RNA transcription ▪ Widespread delivery to all major regio
Slide 3: PRISM Phase 1/2 Study Design
PRISM Phase 1/2 Study Design Evaluation of 4D-150 in a Broad Range of Wet AMD Populations Phase 1 Dose Exploration Phase 2 Dose Expansion Phase 2 Population Extension 3x1010 vg/eye 3x1010 vg/eye (n=5) (n=20) 3x1010 vg/eye Sequential (n=30)* 1x1010 vg/eye 2:2:1 1x1010 vg/eye enrollment (n=5) Randomiz
Slide 4: PRISM Phase 2 Population Extension Study Design
PRISM Phase 2 Population Extension Study Design Phase 2 Population Extension Corticosteroid* Study assessment† Scheduled aflibercept injection 4D-150 (Day 1) 4D-150 3x1010 vg/eye (n=30) 4D-150 (Day 1) 4D-150 1x1010 vg/eye (n=15) -1 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Week Key Endpoints Supplement
Slide 5: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics Population Extension Cohort 3x1010 vg/eye 1x1010 vg/eye Total (N=30) (N=15) (N=45) Mean ±SD age, years 77 ±7.7 78 ±8.6 77 ±7.9 Female, n (%) 20 (67) 6 (40) 26 (58) Race, n (%) White 30 (100) 14 (93) 44 (98) Asian 0 1 (7) 1 (2) Mean ±SD BCVA, ETDRS letters 71
Slide 6: Safety and Tolerability
Safety and Tolerability Interim Analysis (Week 24) ▪ 4D-150 was safe and generally well tolerated ▪ No 4D-150–related serious adverse events ▪ No hypotony, endophthalmitis, retinal vasculitis, choroidal effusions, or retinal artery occlusions ▪ Intraocular inflammation analysis: o 1x1010 vg/eye: mod
Slide 7: Ophthalmic Examination
Ophthalmic Examination Population Extension Cohort (Week 24) Anterior Chamber Cells* Vitreous Cells* Corticosteroid† None 4D-150 Trace 3x1010 vg/eye 1+ (n=30) 2+ 3+ 4+ ▪ 3x1010 vg/eye: – 30/30 completed steroid regimen on schedule X X PC – 0/30 restarted 4D-150 ▪ 1x1010 vg/eye: 1x1010 vg/eye – 13/15
Slide 8: Anti-VEGF Injections (Week 24)
Anti-VEGF Injections (Week 24) Up to 91% Reduction in Annualized Anti-VEGF Injection Rate 4D-150 Aflibercept Ranibizumb Bevacizumab Faricimab Suppl. Aflibercept Mean annualized rate: 0.9 4D-150 Post Week 4* 3x1010 vg/eye (n=30) 89% reduction in annualized anti-VEGF injection rate 93% ≤1 injection 77
Slide 9: Best Corrected Visual Acuity (BCVA)
Best Corrected Visual Acuity (BCVA) 3x1010 vg/eye: Durable Improvement in Visual Acuity Through Week 24 4D-150 (Day 1) 15 Average (95% CI): Weeks 20/24 4D-150 (3x1010 vg/eye) +3.5 (1.1, 5.8) Adjusted mean (95% CI) change in BCVA 4D-1503E10 4D-150 3x10(n=30) 10 vg/eye (n=30) 4D-150 (1x1010 vg/eye) –2
Slide 10: Central Subfield Thickness (CST)
Central Subfield Thickness (CST) 3x1010 vg/eye: Stable Anatomic Control Through Week 24 4D-150 (Day 1) 200 Average (95% CI): Weeks 20/24 Adjusted mean (95% CI) change in CST 150 4D-1503E10 4D-150 3x10(n=30) 10 vg/eye (n=30) 4D-150 (3x1010 vg/eye) –9.2 (–30.8, 12.4) 4D-1501E10 4D-150 1x10(n=15) 10 vg
Slide 11: Supplemental Injection-free Participants
Supplemental Injection-free Participants 3x1010 vg/eye: Durable Improvement in Visual Acuity and Sustained Reduction in CST Average, Weeks 20/24 3x1010 vg/eye: +3.5 (1.0, 5.9) BCVA 15 4D-150 3x1010 vg/eye (n=23) No Rescue- 3E10 (n=23) 1x1010 vg/eye: +2.9 (–1.7, 7.6) Adjusted mean (95% CI) change in
Slide 12: Summary and Conclusions
Summary and Conclusions ▪ 4D-150 was safe and well tolerated through 24 weeks in individuals with wAMD and moderate disease activity o No 4D-150–related SAEs o No hypotony, endophthalmitis, retinal vasculitis, choroidal effusions, or retinal artery occlusions o 3x1010 vg/eye: 30/30 completed prophyl
Slide 13: Acknowledgments
Acknowledgments Murtaza Adam Victor Gonzalez Fuad Makkouk Carol Chung Colorado Retina Associates Valley Retina Institute Austin Clinical Research, 4D Molecular Therapeutics, Inc Englewood, CO McAllen,TX Austin,TX Emeryville, CA Suhail Alam Jeffrey Heier Joel Pearlman Somayeh Honarmand Barnet Dulaney