4d Molecular Therapeutics, Inc. · NASDAQ:FDMT
4d Molecular Therapeutics — Retina Society 2024
14 slides from 4d Molecular Therapeutics's conference presentation, September 2024
Slide 1: Interim Results from the PRISM Phase 1/2 Clinical Trial of Intravitreal 4D-150
Interim Results from the PRISM Phase 1/2 Clinical Trial Evaluating Intravitreal 4D-150 in Adults with Neovascular Age-related Macular Degeneration David A. Eichenbaum, M.D. Retina Vitreous Associates of Florida, St Petersburg, FL USF Health Morsani College of Medicine, Tampa, FL © 2024 4D Molecular
Slide 2: Disclosures
Disclosures* Investigator: 4DMT, Aerie/Alcon, Alexion, Allegenesis, Annexion, Aviceda, Bayer, EyeBio, EyePoint, Gemini, Genentech, Gyroscope, Ionis, Janssen, Kodiak, Kyowa Kirin, Mylan, NGM, Novartis, Ocular Therapeutix, OcuTerra, Opthea, ONL, RecensMedical, Regeneron, Regenxbio, Roche, Stealth, Uni
Slide 3: Key Takeaways
Key Takeaways PRISM Phase 2 Clinical Trial Interim Results ▪ 4D-150: dual-transgene intravitreal gene therapy o Evolved retinotropic AAV vector, dual-transgene payload (aflibercept,VEGF-C RNAi) ▪ PRISM Phase 1/2 clinical trial: Evaluation of 4D-150 in a broad wet AMD population ▪ PRISM Phase 2 inter
Slide 4: 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 and VEGF-C RNAi 4D-150 ▪ Single-dose intravitreal administration Aflibercept DNA RNA (VEGF Trap) transcription ▪ Widespread delivery to all major reg
Slide 5: PRISM Phase 1/2 Clinical Trial
PRISM Phase 1/2 Clinical Trial Evaluation of 4D-150 in a Broad Range of Wet AMD Populations Phase 1 Dose Exploration Phase 2a Dose Expansion Phase 2b 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) Rand
Slide 6: Study Design
Study Design Phase 2 Dose Expansion and Population Extension Cohorts Phase 2a Dose Expansion Key Eligibility Criteria Prophylactic corticosteroid Study assessment Scheduled aflibercept injection ▪ ≥6 anti-VEGF injections during 4D-150 4D-150 3x1010 vg/eye prior 12 months 4D-150 4D-150 1x1010 vg/eye
Slide 7: Baseline Characteristics (Phase 2)
Baseline Characteristics (Phase 2) Broad Range of Disease Activity and Anti-VEGF Injection Burden Dose Expansion Population Extension 4D-150 4D-150 Aflibercept 4D-150 4D-150 3×1010 vg/eye 1×1010 vg/eye 2 mg Q8W 3×1010 vg/eye 1×1010 vg/eye (N=20) (N=21) (N=10) (N=30) (N=15) Mean ±SD age, years 77 ±8.
Slide 8: PRISM Phase 2 Interim Results
PRISM Phase 2 Interim Results 4D-150 3×1010 vg/eye (Phase 3 Dose) Anterior Chamber Cells* Vitreous Cells* Corticosteroid† X X None Dose Trace Expansion 1+ (n=19) 2+ 3+ PC 4+ X X X X Population ▪ No clinically significant Extension inflammation (n=30) ▪ 100% (49/49) completed prophylactic steroid reg
Slide 9: Anti-VEGF Injections (Week 24)
Anti-VEGF Injections (Week 24) 4D-150 3×1010 vg/eye: 89% Reduction in Annualized Anti-VEGF Injection Rate 4D-150 89% reduction in annualized Aflibercept Brolucizumab Ranibizumb Faricimab Bevacizumab Suppl. Aflibercept anti-VEGF injection rate 84% ≤1 injection 63% injection free 89% reduction in annu
Slide 10: Best Corrected Visual Acuity (BCVA)
Best Corrected Visual Acuity (BCVA) 4D-150 3×1010 vg/eye: Stable Visual Acuity Through Week 24 20 Aflibercept (n=10) Aflibercept 2 mg Q8W (n=10) Adjusted mean (95% CI) change 15 4D-150 3E10 4D-150 3x10 vg/eye (n=20) 10 vg/eye (n=20) BCVA (ETDRS letters) 10 Dose Expansion 4D-150 1E10 4D-150 1x10 vg/e
Slide 11: Central Subfield Thickness (CST)
Central Subfield Thickness (CST) 4D-150 3×1010 vg/eye: Stable Anatomic Control Through Week 24 150 Aflibercept (n=10) Aflibercept 2 mg Q8W (n=10) 4D-150 3E10 4D-150 3x10 vg/eye (n=20) 10 vg/eye (n=20) Adjusted mean (95% CI) 100 4D-150 1E10vg/eye 4D-150 1x10 10 vg/eye (n=21) (n=21) Dose Expansion cha
Slide 12: Case Study: Population Extension Anti-VEGF Injections in Prior 6 Months
Case Study Population Extension (4D-150 3×1010 vg/eye): 4 Anti-VEGF Injections in Prior 6 Months CST (m) 200 0 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 100 500 4D-150 4D-150 BCVA (ETDRS letters) +6 400 80 CST (m) 300 60 -156 Scheduled aflibercept injection 200 Scheduled aflibercept injection No supple
Slide 13: Summary and Conclusions
Summary and Conclusions ▪ PRISM Phase 1/2 clinical trial o Broad wet AMD population with a wide range of disease activity and anti-VEGF treatment burden ▪ Phase 2 interim results (Week 24)—3×1010 vg/eye: o 4D-150 was safe and well tolerated • No 4D-150–related serious adverse events and no clinicall
Slide 14: Acknowledgments
Acknowledgments Murtaza Adam Sunil Gupta Raj Maturi Carol Chung Colorado Retina Associates Retina Specialty Institute Midwest Eye Institute 4D Molecular Therapeutics, Inc Englewood, CO Pensacola, FL Indianapolis, IN Emeryville, CA Suhail Alam Jeffrey Heier Fuad Makkouk Somayeh Honarmand Barnet Dulan