4D Molecular Therapeutics, Inc. · NASDAQ:FDMT

4D Molecular Therapeutics — Technical Presentation (2025)

16 slides from 4D Molecular Therapeutics's technical presentation, 2025

  1. Slide 1: PRISM Phase 1/2 Study of 4D-150 in Wet AMD: 18-24 Months Extended Follow-Up

    PRISM Phase 1/2 Study of 4D-150 in Wet AMD: 18-24 Months Extended Follow-Up, First Time Results Carl C. Awh, MD, FASRS Tennessee Retina Nashville, TN On behalf of the PRISM investigators © 2025 4D Molecular © 2025 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. All Rights Reserved.

  2. Slide 2: Disclosures

    Disclosures ▪ Consultant: Bausch + Lomb, Genentech, Inc., Ocular Therapeutix, Zeiss; ▪ Investigator: 4D Molecular Therapeutics, Adverum,Allergan, Apellis,Astellas/AIRM,Aura, Aviceda, Chengdu Kanghong, Cognition, Eluminex, Genentech, Inc., Ionis, Kodiak Sciences, Mylan, NGM Bio, Ocular Therapeutix, O

  3. Slide 3: Adeno-associated Virus (AAV): Leading Platform for Retina Gene Therapy

    Adeno-associated Virus (AAV) Leading Platform for the Delivery of Retina Gene Therapy ITR ITR Rep Cap pA Replication/ Rep78 Viral capsid VP1 packaging Rep68 VP2 Rep52 VP3 Rep40 Advantages Limitations ▪ Non-pathogenic ▪ Broad, non-specific tropism ▪ Relatively low immunogenicity – Limited ability to

  4. Slide 4: Intravitreal AAV-based Retinal Gene Therapy

    Intravitreal AAV-based Retinal Gene Therapy Key Challenge: Retinal Cell Transduction Wild-type AAV Optimal AAV Vector Blocked by Limited retinal ILM barrier Enhanced retinal WT AAV penetration transduction barrier (ILM) transduction Retina Retina Heparan Inner sulfate retina Cytosol Vitreous Vitreou

  5. Slide 5: Therapeutic Vector Evolution

    Therapeutic Vector Evolution Directed Evolution-based Proprietary Vector Discovery Platform ▪ Define ideal vector profile (route of administration, dose, target cells, etc.) ▪ Multiple molecular biology techniques employed to generate massive genetic diversity WILD-TYPE & SYNTHETIC AAV AAV CAPSID EN

  6. Slide 6: Ideal Vector Creation Overcomes Many Limitations

    Ideal Vector Creation Overcomes Many Limitations In Vivo Directed Evolution in Animal Models What must the How do you create ideal vector do? the best vector? Be delivered at low doses via Candidate Capsid selection based on: intravitreal injection directly to vectors all layers of the retina Best r

  7. Slide 7: 4D-150: A Novel, R100-Based Dual-Transgene Investigational Gene Therapy

    4D-150: A Novel, R100-Based Dual-Transgene Investigational Gene Therapy Delivery Vehicle: AAV Capsid (R100) Dual Transgene Payload: 4D-150 1 2 R100 AAV Capsid Specifically Designed to: Be administered via routine intravitreal injection Cross vitreoretinal barriers Selectively transduce cells of the

  8. Slide 8: PRISM Phase 1/2 Clinical Trial

    PRISM Phase 1/2 Clinical Trial Evaluation of 4D-150 in Broad Range of nAMD Populations Cohort Phase 1 Dose Exploration Phase 2a Dose Expansion Phase 2b Population Extension Population Severe Disease Activity Severe Disease Activity Broad Population Dose Groups 3E10 vg/eye 3E10 vg/eye (n=5) (n=20) 3E

  9. Slide 9: 4D-150 in a Broad AMD Population: Phase 2b Results

    4D-150 in a Broad AMD Population: Phase 2b 18 Month Results Central Subfield Thickness 150 3E10 (n=30) 1E10 (n=15) Mean ±SD Change from BL in 100 50 CST (µm) 0 -50 -100 -150 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 Weeks 15 Best Corrected Visual Acuity Mean ±SD Change from BL in 1

  10. Slide 10: Mean Cumulative Number of Injections

    3E10 vs. 1E10 vg/eye: Consistent Dose Response in Mean Cumulative Supplemental Injections Through 1.5 Years 1.4 (77% reduction) 2.4 (73% reduction) 10 1.0 (83% reduction) 1.6 (82% reduction) Projected AFLB Q8W 9 9 Mean Cumulative Number of Injections 1E10 vg/eye (n=15) 8 Phase 3 dose (3E10 vg/eye, n

  11. Slide 11: Phase 2b Recently Diagnosed Subgroup 18 Month Results

    4D-150 in a Broad AMD Population: Phase 2b Recently Diagnosed (≤ 6 Months) Subgroup 18 Month Results Central Subfield Thickness 150 3E10 (n=15) 1E10 (n=11) Mean ±SD Change from BL in 100 50 CST (µm) 0 -50 -100 -150 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 Weeks 15 Best Corrected V

  12. Slide 12: Mean Cumulative Number of Injections

    3E10 vs. 1E10 vg/eye: Consistent Dose Response in Mean Cumulative Supplemental Injections Through 1.5 Years 1.4 (77% reduction) 2.1 (77% reduction) 0.3 (94% reduction) 0.7 (92% reduction) 10 Projected AFLB Q8W 9 9 1E10 vg/eye (n=11) Mean Cumulative Number of Injections Supplemental Injections 8 Phas

  13. Slide 13: 4D-150 Continues to be Well Tolerated

    4D-150 Continues to be Well Tolerated ▪ No 4D-150–related serious adverse events 4D-150 3E10 vg/eye (N=71)* ▪ No 4D-150–related hypotony, endophthalmitis, Highest SUN/NEI Score† occlusive/non-occlusive retinal vasculitis, or choroidal 2.8% effusions None 1+ ▪ 4D-150–related intraocular inflammation

  14. Slide 14: 4D-150 PRISM Phase 1/2 Update: 1.5- & 2-Year Follow-up

    4D-150 PRISM Phase 1/2 Update: 1.5- & 2-Year Follow-up ▪ Visual acuity & anatomic control maintained Consistent, Durable and ▪ Durable reduction in injection number across diverse wet AMD populations: Clinically Meaningful o 79% reduction in a recalcitrant population Clinical Activity o 82% reductio

  15. Slide 15: Global 4FRONT Phase 3 Wet AMD Program

    Global 4FRONT Phase 3 Wet AMD Program: Evaluating the Efficacy, Safety, and Durability of a Single IVT Injection of 4D-150 vs. Aflibercept 2mg Q8W Primary Demonstrate non-inferiority in the mean change in BCVA from baseline to Week 52 of a single Objective injection of 4D-150 compared to aflibercept

  16. Slide 16: Thank you!

    Thank you! © 2025 4D Molecular © 2025 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. All Rights Reserved.

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