4D Molecular Therapeutics, Inc. · NASDAQ:FDMT

4D Molecular Therapeutics — Technical Presentation (July 2023)

15 slides from 4D Molecular Therapeutics's technical presentation, July 2023

  1. Slide 1: 4D-150 Phase 1/2 Trial in Wet AMD: Interim 9-Month Results

    A Phase 1/2 Clinical Trial Evaluating 4D-150, a Dual-transgene Intravitreal Gene Therapy in Patients with Wet Age-Related Macular Degeneration: Interim 9-Month Results Christine N. Kay, M.D. Arshad M. Khanani,Vrinda S. Hershberger, Allen Hu, David A. Eichenbaum, Glenn J. Jaffe, Carol Chung, Somayeh

  2. Slide 2: Disclosures

    Disclosures Atsena Therapeutics Belite Bio MeiraGTx/Janssen ▪ Consultant ▪ Investigator ▪ Investigator ▪ Stock options Biogen Gyroscope AGTC/Syncona ▪ Investigator ▪ Investigator ▪ Investigator 4D Molecular Therapeutics Kiora Pharmaceuticals Foundation Fighting Blindness ▪ Investigator ▪ Consultant

  3. Slide 3: 4D-150: Overview

    4D-150: Overview Dual-transgene, multi-targeted ▪ Primate-evolved retinotropic R100 capsid inhibition of VEGF pathways carrying a dual transgene payload o Aflibercept and VEGF-C RNAi VEGF-C RNAi 4D-150 ▪ Single-dose intravitreal administration Aflibercept DNA RNA (VEGF Trap) transcription ▪ Widespre

  4. Slide 4: Intravitreal 4D-150 Biodistribution: Therapeutic Levels of Aflibercept

    Intravitreal 4D-150 Biodistribution: Therapeutic Levels of Aflibercept RETINOTROPIC R100 VECTOR FACILITATES HIGH-LEVEL EXPRESSION WITHIN THE RETINA Aflibercept Concentration (NHP)* 4D-150–mediated Aflibercept Protein Expression Retina Aflibercept (ng/mL or g) Aqueous Choroid humor (AH) High Vitreous

  5. Slide 5: 4D-150 Phase 1/2 Clinical Trial

    4D-150 Phase 1/2 Clinical Trial OBJECTIVE: EVALUATE SAFETY, TOLERABILITY, AND CLINICAL ACTIVITY Study Design Key Inclusion Criteria* Dose Exploration Dose Expansion ▪ Age ≥50 years ▪ CNV secondary to AMD 3x1010 vg/eye 3x1010 vg/eye (n=5) (n=20) ▪ ≥25 (~20/320) and ≤78 (~20/32) ETDRS letters† 1x1010

  6. Slide 6: Baseline Characteristics

    Baseline Characteristics ANALYSIS POPULATION: ALL ENROLLED PARTICIPANTS (N=15) 3x1010 vg/eye 1x1010 vg/eye 6x109 vg/eye Total Characteristic (N=5) (N=5) (N=5) (N=15) Mean ±SE age, years 79 ±3.9 79 ±4.1 76 ±4.9 78 ±4.0 Female, n (%) 5 (100) 3 (60) 3 (60) 11 (73) Race, n (%) White 5 (100) 5 (100) 4 (8

  7. Slide 7: Ophthalmic Examination

    Ophthalmic Examination NO SUN OR NEI GRADE ≥1+ WBC, FLARE, OR HAZE Anterior Chamber Cells Anterior Chamber Flare Vitreous Cells Vitreous Haze Topical corticosteroid 0 (none) Cohort 1 2+ Patient 1 pc Tpc Tpc Tpc 0.5+ (trace) 3x1010 vg/eye Patient 2 1+ Patient 3 * Tpc 2+ Patient 4 3+ Patient 5 4+ Coho

  8. Slide 8: Intraocular Pressure (IOP)

    Intraocular Pressure (IOP) Study Eye Fellow Eye Study Eye Mean IOP 3x1010 vg/eye TCS >30 mm Hg 35 Patient 1 22–30 mm Hg Patient 2 11–21 mm Hg 30 Patient 3 8–10 mm Hg Patient 4 6–7 mm Hg Mean ±SE IOP (mm Hg) Patient 5 0–5 mm Hg 25 1x1010 vg/eye TCS 20 Patient 1 Patient 2 15 Patient 3 Patient 4 Patien

  9. Slide 9: Anti-VEGF Injections at Week 36

    Anti-VEGF Injections at Week 36 UP TO 81% REDUCTION IN ANNUALIZED ANTI-VEGF INJECTION RATE Aflibercept Ranabizumb Ranibizumab Bevacizumab 4D-150 Anti-VEGF Annualized Brolucizumab Faricimab Study visits Injection-free Injection Rate Cohort 1 1 3x1010 vg/eye 2 3 4/5 (80%) (–)81% 4 5 Cohort 2 1 1x1010

  10. Slide 10: Anti-VEGF Injections at Week 36

    Anti-VEGF Injections at Week 36 4 OF 4 (100%) EVALUABLE PARTICIPANTS INJECTION-FREE AT HIGHEST DOSE (3x1010 vg/EYE) Aflibercept Ranibizumab Ranabizumb Bevacizumab 4D-150 Brolucizumab Faricimab Study visits 3x1010 vg/eye 1 Durable 2 injection-free: 3 4 4/4 (100%) 5 Non evaluable* 1x1010 vg/eye 1 2 3

  11. Slide 11: Visual and Anatomic Outcomes

    Visual and Anatomic Outcomes STABLE VISUAL ACUITY AND CENTRAL SUBFIELD THICKNESS THROUGH WEEK 36 Best Corrected Visual Acuity Central Subfield Thickness 100 600 90 Mean ±SE BCVA (ETDRS letters) 80 500 * –4.6 ±2.9 70 Mean ±SE CST (mm) +3.6 ±1.6 400 +35±32 mm 60 –23±34 mm * * –3.8 ±4.0 –92±49 mm 50 30

  12. Slide 12: Aqueous Humor Aflibercept Concentrations (Week 12)

    Aqueous Humor Aflibercept Concentrations (Week 12) AH Aflibercept Concentration 400 n=4 n=4 n=3 ▪ Detectable aflibercept in AH is consistent with predicted therapeutic concentrations of 4D-150 Mean ±SEM AH AFLB, ng/mL in the retina 300 ▪ Dose-related aflibercept concentrations observed in aqueous hu

  13. Slide 13: Case Study

    Case Study 89-YEAR-OLD FEMALE (3x1010 vg/eye) CST (mm) 200 0 -54 -52 -50 -48 -46 -44 -42 -40 -38 -36 -34 -32 -30 -28 -26 -24 -22 -20 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 65 letters 80 (change, +5) 600 505 mm 60 CST (µm) 60 letters 400 13 prior anti-VEGF

  14. Slide 14: Conclusions

    Conclusions ▪ Intravitreal administration of 4D-150 to adults with wet AMD was safe and generally well tolerated at doses ranging from 6x109 to 3x1010 vg/eye through Week 36 o No dose-limiting toxicities and no 4D-150–related serious adverse events o 14/15 participants experienced no intraocular inf

  15. Slide 15: Acknowledgments

    Acknowledgments Veeral Sheth, M.D. University Retina and Macula Associates Arshad Khanani, M.D. Sierra Eye Associates Allen Hu, M.D. Cumberland Valley Retina Consultants Joel Pearlman, M.D. Retina Consultants Glenn Jaffe, M.D. Duke University Dante Pieramici, M.D. California Retina Consultants Sunil

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