4d Molecular Therapeutics, Inc. · NASDAQ:FDMT
4d Molecular Therapeutics — ASGCT 2021
14 slides from 4d Molecular Therapeutics's conference presentation, 2021
Slide 1: 4D-150 Anti-Angiogenic AAV Gene Therapy for Wet AMD and DME in Non-Human Primates
A Multi-Mechanistic Anti-Angiogenic AAV Gene Therapy Product Candidate, 4D-150, for the Treatment of Wet Age-Related Macular Degeneration (Wet AMD) and Diabetic Macular Edema (DME): Intravitreal Biodistribution, Transgene Expression, Safety and Efficacy in Non-Human Primates Peter Francis1, Christia
Slide 2: Legal Disclaimer
Legal Disclaimer This Presentation contains forward looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Presentation, including statements regarding our clinical development plans, strategy, future operatio
Slide 3: Presenter Disclosures
Presenter Disclosures ▪ Chief Scientific Officer & a full-time employee at 4D Molecular Therapeutics, Inc. ▪ Inventor on patents and pending patent applications related to AAV capsid variants and AAV gene delivery. © 2020 4D Molecular Therapeutics. All Rights Reserved. 3
Slide 4: Disease Background & Current Treatment
Disease Background & Current Treatment DURABLE EXPRESSION BY AAV GENE THERAPY HOLDS PROMISE ▪ Wet Age-Related Macular Degeneration (wet AMD) ▪ Diabetic Macular Edema (DME) ▪ Both Associated With: o Retina swelling & edema o Bleeding o Reduced visual acuity ▪ Stimulated by VEGF family members: o A, B
Slide 5: 4D-150 for Wet AMD & DME
4D-150 for Wet AMD & DME DUAL TRANSGENE, INTRAVITREAL GENE THERAPY INHIBITING FOUR DISTINCT VEGF FAMILY MEMBERS HIGH UNMET MEDICAL NEED EPIDEMIOLOGY: US PRODUCT DESIGN ▪ Frequent Injections ▪ Wet AMD: ~200,000/yr incidence ▪ Vector: R100 ▪ Patient / Physician Adherence ▪ DME: ~1.2M prevalence ▪ Tran
Slide 6: 4D-150 Multi-Mechanistic Gene Therapy for Wet AMD & DME
4D-150 Multi-Mechanistic Gene Therapy for Wet AMD & DME DUAL TRANSGENE, INTRAVITREAL GENE THERAPY INHIBITING FOUR DISTINCT VEGF FAMILY MEMBERS © 2020 4D Molecular Therapeutics. All Rights Reserved. 6
Slide 7: 4D-150 Designed to Induce Regression of Neovascularization & For Resolution of Edema
4D-150 Designed to Induce Regression of Neovascularization & For Resolution of Edema © 2020 4D Molecular Therapeutics. All Rights Reserved. 7
Slide 8: R100 Structure & Target Vector Profile
R100 Structure & Target Vector Profile INTRAVITREAL DELIVERY FOR RETINAL DISEASES Blocked by Limited retinal barrier (e.g., ILM) transduction Conventional naturally Retina occurring vectors Heparan Inner sulfate retina Cytosol Naturally occurring Vitreous capsid body Eye cross section Inner retina P
Slide 9: R100 Vector Proof-of-Concept
R100 Vector Proof-of-Concept INTRAVITREAL TRANSDUCTION OF NHP RETINA & HUMAN RETINAL RPE CELLS VS AAV2 IN VITRO AAV2 R100 Eye cross section Retina Human RPE in vitro Vitreous body IVT in NHP in vivo © 2020 4D Molecular Therapeutics. All Rights Reserved. 9
Slide 10: Intravitreal 4D-150 Prototype: Stable Anti-VEGF Expression
Intravitreal 4D-150 Prototype: Stable Anti-VEGF Expression R100.ANTI-VEGF EXPRESSION THROUGH 6 AND 12 MONTHS 1E11 vg 1E12 vg Vehicle R100.anti-VEGF R100.anti-VEGF ▪ Laser-induced CNV 6 weeks after single IVT delivery of 4D- 150 prototype* ▪ Dose-related sustained anti-VEGF expression at 6 and 12 mon
Slide 11: Intravitreal 4D-150: Methods for NHP Preclinical Studies
Intravitreal 4D-150: Methods for NHP Preclinical Studies ACUTE BIODSTRIBUTION & LASER-INDUCED CNV STUDIES NHP ACUTE BIODISTRIBUTION NHP LASER-INDUCED CNV MODEL ▪ Eyes (N): 4 NHP eyes ▪ Eyes (N): 42 NHP eyes ▪ Dose (vg/eye): 1E12 o 14 per dose group ▪ Study Duration: 28 days ▪ Dose (vg/eye): ▪ Endpoi
Slide 12: Intravitreal 4D-150: NHP Acute Biodistribution Study
Intravitreal 4D-150: NHP Acute Biodistribution Study HIGH AFLIBERCEPT AND VEGF-C miRNA EXPRESSION; NO EVIDENCE OF UVEITIS OR RETINAL ABNORMALITY ▪ 4D-150 resulted in high levels of aqueous aflibercept ▪ miRNA copies detected across all retinas ▪ No evidence of uveitis or retinal abnormality Aqueous
Slide 13: Intravitreal 4D-150: Efficacy in NHP CNV Model
Intravitreal 4D-150: Efficacy in NHP CNV Model 100% SUPPRESSION OF CNV INCLUDING AT LOWEST DOSE OF 1E11 VG/EYE 2 wks 4 wks 15 16/168 0/491 Grade IV CNV lesions (%) 10/84 10 ▪ 100% suppression of CNV (grade IV lesions), 6/84 including at lowest dose of 1E11 vg/eye 5 ▪ Day 42 ocular assessments prior
Slide 14: 4D-150 Summary
4D-150 Summary DUAL-TRANSGENE, INTRAVITREAL GENE THERAPY INHIBITING FOUR DISTINCT VEGF FAMILY MEMBERS FOR WET AMD & DME ▪ Utilizes 4DMT’s targeted & evolved AAV vector R100 - invented for: o Routine intravitreal injection o Transgene expression across the entire surface area of the retina o Transgen