4D Molecular Therapeutics, Inc. · NASDAQ:FDMT
4D Molecular Therapeutics — ARVO 2023
17 slides from 4D Molecular Therapeutics's conference presentation, April 2023
Slide 1: 4D-150 Phase 1/2 Trial in Wet AMD: Interim 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 Results Arshad M. Khanani, M.D., M.A.,FASRS* Vrinda S. Hershberger, Christine N. Kay, Allen Hu, David A. Eichenbaum, Glenn J. Jaffe, Carol Chung, So
Slide 2: Disclosures
Disclosures o Consultant: Abbvie, Adverum Biotechnologies, Aerie Pharmaceuticals, AGTC, Aldebaran Therapeutics, Allergan, Apellis Pharmaceuticals, Arrowhead, Pharmaceuticals, Aviceda Therapeutics, Bausch & Lomb, BroadWing Bio, Clearside, 4D Molecular Therapeutics, Exgenesis, Eyepoint Pharmaceuticals
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
Slide 4: Intravitreal 4D-150 Biodistribution
Intravitreal 4D-150 Biodistribution 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 Low humor (VH) Aqueous Vitreous Re
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 3E10 vg/eye 3E10 vg/eye (n=5) (n=20) ≥25 (~20/320) and ≤78 (~20/32) ETDRS letters† 1E10 vg/eye
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
Slide 7: Overall Safety Summary
Overall Safety Summary 24 WEEKS OF FOLLOW-UP: 4D-150 SAFE AND WELL TOLERATED No dose-limiting toxicities No 4D-150–related SAEs 4D-150–related TEAEs (n=2) o 3x1010 vg/eye group: pigmented anterior chamber cells (mild, n=1), mixed vitreous cells (mild, n=1) No eyes with SUN or NEI Grade ≥1+ W
Slide 8: 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 steroid 2+ Tr 0 (none) Cohort 1 Patient 1 pc pc 0.5+ (trace) 3x1010 vg/eye Patient 2 1+ Patient 3 *** ** 2+ Patient 4 3+ Patient 5 4+ Cohort 2 Patient
Slide 9: Intraocular Pressure (IOP)
Intraocular Pressure (IOP) Study Eye Fellow Eye Study Eye Mean IOP 3x1010 vg/eye TCS Patient 1 >30 mm Hg 35 22–30 mm Hg Patient 2 11–21 mm Hg Patient 3 8–10 mm Hg 30 Patient 4 6–7 mm Hg Mean ±SE IOP (mm Hg) Patient 5 0–5 mm Hg 25 1x1010 vg/eye TCS Patient 1 20 Patient 2 Patient 3 15 Patient 4 Patien
Slide 10: Anti-VEGF Injections at Week 24
Anti-VEGF Injections at Week 24 UP TO 84% REDUCTION IN ANNUALIZED ANTI-VEGF INJECTION RATE Aflibercept Ranabizumb Ranibizumab Bevacizumab Brolucizumab Faricimab Visits 4D-150 Anti-VEGF Annualized Injection-free Injection Rate Cohort 1 1 3x1010 vg/eye 2 3 4/5 (–)84% 4 5 Cohort 2 1 1x1010 vg/eye 2 3 2
Slide 11: Visual and Anatomic Outcomes
Visual and Anatomic Outcomes STABLE VISUAL ACUITY AND CENTRAL SUBFIELD THICKNESS THROUGH WEEK 24 Best Corrected Visual Acuity Central Subfield Thickness 100 600 90 Mean ±SE BCVA (ETDRS letters) 80 500 –1.2 ±4.2 70 Mean ±SE CST (µm) +3±25 µm +1.4 ±3.5 400 60 +38±37 µm –78±49 µm 50 –4.0 ±4.5 300 40 20
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
Slide 13: Clinical Assessments Through Week 36
Clinical Assessments Through Week 36 3x1010 vg/eye DOSE COHORT Anti-VEGF Injections 1 2 3 4/5 (80%) participants 4 anti-VEGF injection-free 5 -56 -52 -48 -44 -40 -36 -32 -28 -24 -20 -16 -12 -8 -4 0 4 8 12 16 20 24 28 32 36 Week Injection not per protocol. Best Corrected Visual Acuity Central Subfi
Slide 14: Safety Assessments Through Week 36
Safety Assessments Through Week 36 3x1010 vg/eye DOSE COHORT Ophthalmic Exam Intraocular Pressure (IOP) Anterior Anterior Vitreous Vitreous Chamber Cells Chamber Flare Cells Haze Study Eye Fellow Eye Topical steroid 1 2+ Tr pc pc Tr Tr pc pc Patient 1 2 Patient 2 3 * Tr pc Patient 3 4 Patient 4 5 Pa
Slide 15: Case Study
Case Study 89-YEAR-OLD FEMALE (3x1010 vg/eye) 200 CST (µm) 0 -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 80 65 letters 600 505 µm 60 CST (µm) 60 letters 400 BCVA 40 Prior 12 months: 13 anti-VEGF injections* 200 260 µ
Slide 16: Conclusions
Conclusions Intravitreal administration of 4D-150 in patients with wet AMD was safe and generally well tolerated at doses ranging from 6x109 to 3x1010 vg/eye through Week 24 o No dose-limiting toxicities and no 4D-150–related serious adverse events o 14/15 participants with no intraocular inflamma
Slide 17: 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