17 slides from 4d Molecular Therapeutics's conference presentation, September 2024
Slide 1: Extended Follow-Up in the PRISM Clinical Trial Evaluating 4D-150 in Adults with Neovascular AMD
Extended Follow-Up in the PRISM Clinical Trial Evaluating 4D-150 in Adults with Neovascular Age-related Macular Degeneration Arshad M. Khanani, M.D., M.A.,FASRS on behalf of PRISM Investigators Sierra Eye Associates, Reno, NV, USA University of Nevada, Reno School of Medicine, Reno, NV, USA
Slide 2: 4D-150: R100-based Intravitreal Genetic Medicine
4D-150: R100-based Intravitreal Genetic Medicine Retinotropic 100 Vector is Optimized to Penetrate ILM and Transduce All Layers of the Retina R100: Evolved AAV Vector EGFP Expression in Primate Retina Following IVT Injection of R100.EGRP ILM barrier Enhanced retinal penetration transduction Retina V
Slide 3: 4D-150 Dual-Transgene Payload of Aflibercept & VEGF-C RNAi
4D-150 is designed to deliver a dual-transgene payload of aflibercept & VEGF-C RNAi Expression • Steady state expression in VEGF-C RNAi 4D-150 approximately 8-12 weeks Aflibercept (VEGF Trap) DNA RNA transcription Protein translation PIGF VEGF-A VEGF-B VEGF-C VEGFR-1 VEGFR-2 VEGFR-3 Angiogenesis Vas
Slide 4: PRISM Study Design
PRISM Study Design 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) Randomized (n=21
Slide 5: 4D-150 PRISM Development Program: Severe to Broad Patient Population
4D-150 PRISM Development Program Started with the Most Severe and Moved to a Broad Patient Population Phase 1 Phase 2a Phase 2a Phase 2b “Severe” “Severe” “Severe” “Broad” 3E10 vg/eye 3E10 vg/eye Aflibercept 2mg Q8W 3E10 vg/eye (N=5) (N=20) (N=10) (N=30) Age, years (Mean ±SD) 79 ±8.7 77 ±8.0 80 ± 4.
Slide 6: Phase 1/2a: >80% Reduction in Annualized Anti-VEGF Injections at Week 52
Phase 1/2a: >80% Reduction in Annualized Anti-VEGF Injections at Week 52 in Severe Disease Cohorts (3E10 vg/eye) Aflibercept Ranibizumab Bevacizumab 4D-150 3E10 vg/eye Brolucizumab Faricimab Suppl. Aflibercept 4D-150 3E10 vg/eye (n=24) Anti-VEGF Injections (Week 52) Supplemental Injections* Study An
Slide 7: Phase 1/2a: Sustained Anatomic Control
Phase 1/2a (4D-150 3E10 vg/eye): Sustained Anatomic Control Pending additional follow-up 200 3E10 Injection-Free (n=10) 3E10 Total (n=24) AFLB Q8W (n=10) Mean ±SD Change from BL in CST (µm) 150 100 50 0 -50 -100 -150 -200 -250 Aflibercept arm receiving supplemental injections -300 -4 0 4 8 12 16 20
Slide 8: Phase 1/2a: Comparable Visual Acuity
Phase 1/2a (4D-150 3E10 vg/eye): Comparable Visual Acuity AFLB 2Q8 Pending additional follow-up 20 3E10 Injection-Free (n=10) 3E10 Total (n=24) Mean ±SD Change from BL in BCVA (ETDRS letters) AFLB Q8W (n=10) 15 10 5 0 -5 -10 -15 Aflibercept arm receiving supplemental injections -20 -4 0 4 8 12 16 20
Slide 9: Reduction in Treatment Burden in Severe Wet AMD Patients Through 52 Weeks
Reduction in Treatment Burden in Severe Wet AMD Patients Through 52 Weeks (Phase 3 Dose: 3E10 vg/eye) % Reduction in Annualized Injections % 0–1 Supplemental Injections % Supplemental Injection-free 83% 52% 44% Category 1 Severe Broad Category Phase 2 3 Category 1 Severe Broad Category Phase 2 3 Cat
Slide 10: Phase 2b: 70% Injection-free Over 52 Week Follow-up
Phase 2b (3E10 vg/eye): 70% Injection-free Over 52 Week Follow-up (Kaplan-Meier Estimate) Aflibercept Ranibizumab Supplemental aflibercept 4D-150 Faricimab Bevacizumab 3E10 vg/eye 4D-150 3E10 vg/eye (n=30) Supplemental Injections* Status Week 32 Week 52 Injection-free 73% 70% 0-1 injection 93% 80% *
Slide 11: Phase 2b: Sustained Anatomic Control
Phase 2b: Sustained Anatomic Control 200 3E10 Total (n=30) Data pending for some subjects 150 Mean ±SD Change from BL in CST (µm) 3E10 Injection-Free 100 (n=21) 50 15 3 -16 -10 -13 -17 -14 -12 0 -29 -23 -24 -37 -39 -39 13 -2 -50 -21 -15 -13 -23 -24 -32 -36 -30 -29 -26 -38 -38 -100 -150 -200 -250 -30
Slide 12: Phase 2b: Visual Acuity Improved and Stable
Phase 2b: Visual Acuity Improved and Stable 20 3E10 Total (n=30) 3E10 Injection-Free (n=21) Data pending for some subjects Mean ±SD Change from BL in BCVA (ETDRS letters) 15 10 4.1 4.9 4.5 3.7 3.7 4.0 3.5 3.1 3.8 5 2.9 1.7 1.8 1.9 3.6 4.1 2.7 2.9 2.7 3.1 2.8 2.8 2.8 0 0.7 1.3 1.2 0.1 -5 -7.0 -10 -7.
Slide 13: Treatment Burden in Broad Wet AMD Population Through 52 Weeks
Treatment Burden in Broad Wet AMD Population Through 52 Weeks (Phase 3 Dose: 3E10 vg/eye) % Reduction in Annualized Injections % 0–1 Supplemental Injections % Supplemental Injection-Free 89% 83% 80% 70% 52% 44% Category 1 Category 2 Category 1 Category 2 Category 1 Category 2 Severe Broad Severe Bro
Slide 14: 4D-150 Safety
4D-150 Safety No 4D-150–related serious adverse events All 4D-150 3E10 vg/eye-Treated Wet AMD Rate of 3E10 dose 4D-150–related intraocular inflammation: Patients (N=71) Wet AMD Highest SUN/NEI Score (4D-150–Related)* o 2.8% (2 of 71) had transient 1+VC at any timepoint 2.8% o 99% (70 of 71) comp
Slide 15: Case Study: Phase 1 (3E10 vg/eye)
Case Study: Phase 1 (3E10 vg/eye) 89-year-old female (13 anti-VEGF injections during prior 12 months)* Sustained Improvement in BCVA & CST While Supplemental Injection-free at 2 Years 4D-150 Week -26 Week 24 Week 72 BCVA: NA; CST: 483 µm BCVA: 65 letters; CST: 258 µm BCVA: 69 letters; CST: 253 µm 8
Slide 16: Key Takeaways Extended Follow-Up
TREATMENT BURDEN REDUCTION SEEN IN PRE-TREATED WET AMD PATIENTS Phase 1/2a – Severe disease with heavy pre-treatment • 83% reduction in injection burden at 52-weeks compared to year prior to enrollment Key Takeaways • 44% of patients remain injection-free at 52-weeks post 4D-150 administration
Slide 17: 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 Dulan