4d Molecular Therapeutics, Inc. · NASDAQ:FDMT

4d Molecular Therapeutics — Investor Presentation (January 2022)

35 slides from 4d Molecular Therapeutics's investor presentation, Jan 11, 2022

  1. Slide 1: Harnessing the Power of Directed Evolution for Targeted Gene Therapies

    Exhibit 99.1 Harnessing the Power of Directed Evolution for Targeted Gene Therapies Corporate Presentation | January 2022 © 2021 4D Molecular Therapeutics. All Rights Reserved.

  2. 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

  3. Slide 3: Boldly Innovating to Unlock the Full Potential of Gene Therapy

    We are Boldly Innovating to Unlock the Full Potential of Gene Therapy for Millions of Patients ~120 Employees Emeryville Co-Founders COMPANY Kirn, MD & Schaffer, PhD GMP Facilities ~1 BILLION AAV Targeted & Evolved PLATFORM Directed Evolution synthetic capsid Vectors sequences Vector Modularity Lead

  4. Slide 4: Successes & Limitations of Conventional AAV

    Successes & Limitations of Conventional AAV OPPORTUNITY FOR TARGETED GENE THERAPY VECTORS & PRODUCTS SUCCESSES LIMITATIONS ▪ Limited Delivery ▪ Limited Transduction Narrow Focus on Niche Diseases ▪ Increased Inflammation and Toxicity ▪ Vulnerability to Neutralizing Antibodies OPPORTUNITY: UNLOCK THE

  5. Slide 5: Platform Solution: Therapeutic Vector Evolution

    Platform Solution: Therapeutic Vector Evolution INNOVATION BY DIRECTED EVOLUTION “…the most powerful biological design process…” – Frances Arnold, 2018 Nobel Prize in Chemistry* THERAPEUTIC DIRECTED AAV GENE VECTOR EVOLUTION THERAPY EVOLUTION *Dr. Arnold and the other investigators awarded the Nobel

  6. Slide 6: Platform Solution: ~1 Billion Synthetic Capsid Sequences

    Platform Solution: ~1 Billion Synthetic Capsid Sequences 40 DISTINCT LIBRARIES CONVENTIONAL CREATE ~1 BILLION SYNTHETIC AAV CAPSID 40 DISTINCT 4DMT AAV NATURALLY OCCURRING SEQUENCES BY DIVERSIFYING THE CAP GENE CAPSID LIBRARIES CAPSIDS Ancestral reconstruction Variable loop mutagenesis Random peptid

  7. Slide 7: Platform Solution: Compete for Target Vector Profile Fitness

    Platform Solution: Compete for Target Vector Profile Fitness THERAPEUTIC VECTOR EVOLUTION IDENTIFY DESIGN PACKAGE ADMINISTER COMPETITIVE SELECTION* LEAD DISEASE ORGAN(S)-SPECIFIC 4DMT AAV 4DMT AAV TARGET VECTOR PROFILE FITNESS VECTORS TARGET(S) TARGET VECTOR LIBRARIES LIBRARIES PROFILE From ~1 BILLI

  8. Slide 8: Modular Approach to Therapeutic Area Pipeline

    Modular Approach to Therapeutic Area Pipeline PRODUCT DESIGN & ENGINEERING FOR ACCELERATED DEVELOPMENT THERAPEUTIC AREA PIPELINE MODULAR PRODUCTS: NEW TRANSGENES, IN VIVO RARE AND LARGE DISEASES (NHP) CLINICAL LEAD CANDIDATE 1 VECTORS Replace CLINICAL Knock-down IND PROOF OF (e.g. RNAi) CONCEPT HUMA

  9. Slide 9: Pipeline: Clinical-Stage Product Candidates

    Pipeline: 5 Clinical-Stage Product Candidates THREE THERAPEUTIC AREAS, RARE & LARGE PATIENT POPULATIONS VECTOR PRODUCT PRODUCT LEAD Delivery CANDIDATE INDICATION OPTIMIZATION IND-ENABLING PHASE 1 / 2 PHASE 3 RIGHTS R100 OPHTHALMOLOGY Intravitreal 4D-125 XLRP 4D-110 CHM Wet AMD 4D-150 DME C102 CARDIO

  10. Slide 10: Cardiology Modular Vector C102: 4D-310 Fabry Disease

    CARDIOLOGY Modular Vector: C102 ▪ 4D-310: FABRY DISEASE © © 2 20 02 21 1 4 4D D M Mo ollecu ecullar ar T Th herap erapeu euti tics. cs. Al Alll R Riigh ghts R ts Reser eserved ved.. 10

  11. Slide 11: 4D-310 Product Design & C102 Target Vector Profile

    4D-310 Product Design & C102 Target Vector Profile INVENTED FOR LOW DOSE IV DELIVERY TO TARGET ORGANS INCLUDING HEART & HIGH SERUM AGA Patient with Fabry Disease Biodistribution to affected organs Blood vessel Delivery dysfunction to liver Cardiac dysfunction Ubiquitous GLA Kidney dysfunction Conven

  12. Slide 12: 4D-310 Competitive Advantages: Dual MOA Product Design

    4D-310 Competitive Advantages: Dual MOA Product Design DESIGNED FOR HIGH STABLE AGA EXPRESSION IN BLOOD, HEART & OTHER TARGET ORGANS ERT Gene Therapy AGA Enzyme PEGylated Autologous AAV MOA Product Design 4D-310 Infusions AGA Stem Cells Liver-directed Pharmacokinetics AGA: Systemic PK No chemotherap

  13. Slide 13: 4D-310 Study Design: Broad Enrollment Criteria

    4D-310 Study Design: Broad Enrollment Criteria OPEN-LABEL, PHASE 1/2 TRIAL IN ADULTS WITH CLASSIC & LATE-ONSET FABRY DISEASE KEY INCLUSION CRITERIA STUDY DESIGN ▪ Males≥ 18 years of age ▪ Pathogenic GLA mutation DOSE DOSE ESCALATION ▪ Classic OR Late-onset FD with LVH EXPANSION ▪ ERT-On, ERT-Off OR

  14. Slide 14: 4D-310 Baseline Patient Characteristics

    4D-310 Baseline Patient Characteristics: STUDY ENROLLED CLASSIC FABRY DISEASE PATIENTS WITH ANTI-AGA ANTIBODY POSITIVITY Patient 1 Patient 2 Patient 3 Age dosed with 4D-310 51 years 32 years 26 years Anti-AGA antibody titer 1 : 947 1 : 99,900 1 : 13,900 Disease classification Classic Classic Classic

  15. Slide 15: 4D-310 Mean Serum AGA Activity: >20-Fold Mean Normal

    4D-310 Mean Serum AGA Activity: >20-Fold Mean Normal ANTI-AGA ANTIBODY POSITIVE LOW & MID TITERS: PATIENTS 1 & 3 AGA ACTIVITY OVER TIME 300 Mean Serum AGA Activity: ▪ Patient 1: 248.1 nmol/hr/mL 2,506% 200 2,114% ▪ Patient 3: 209.3 nmol/hr/mL 100 Mean normal (9.9 nmol/hr/mL) 0 Patient 1 Patient 3 Se

  16. Slide 16: 4D-310 Mean Serum AGA Activity: Within Normal Range

    4D-310 Mean Serum AGA Activity: Within Normal Range AGA ANTIBODY POSITIVE HIGHEST TITER: PATIENT 2 (HIGHEST TITER OF ALL ENROLLED & SCREENED) Mean Serum AGA Activity: Serum lyso-Gb3: ▪ Patient 2: 5.7 nmol/hr/mL 150 30 4D-310 dosing 100 20 * 50 10 Mean normal (9.9 nmol/hr/mL) 58% 0 -6 -4 -2 0 2 4 6 8

  17. Slide 17: Summary of Interim Data: 4D-310 Ph 1/2 Clinical Trial

    Summary of Interim Data: 4D-310 Ph 1/2 Clinical Trial DATA CUT-OFF DATE: 10/12/21 ▪ 4D-310 demonstrated a manageable safety profile & no DLTs ▪ Clinical activity observed in all patients at all timepoints: o Mean AGA enzyme activity: o Within, or significantly above, the normal range in all three pa

  18. Slide 18: Ophthalmology Modular Vector R100

    OPHTHALMOLOGY Modular Vector: R100 ▪ 4D-125: XLRP ▪ 4D-150: wAMD/DME ▪ 4D-110: CHOROIDEREMIA © © 2 20 02 21 1 4 4D D M Mo ollecu ecullar ar T Th herap erapeu euti tics. cs. Al Alll R Riigh ghts R ts Reser eserved ved.. 18

  19. Slide 19: Ophthalmology: R100 Structure & Target Vector Profile

    Ophthalmology: R100 Structure & Target Vector Profile INTRAVITREAL DELIVERY FOR RETINAL DISEASES Blocked by Limited retinal barrier (e.g., ILM) transduction Conventional Retina naturally Retina occurring Heparan Inner vectors Cytosol sulfate retina Vitreous Vitreous body body Naturally occurring cap

  20. Slide 20: Ophthalmology: 4D-125 for XLRP

    Ophthalmology: 4D-125 for XLRP Photoreceptor- specific RPGR PROMOTER TRANSGENE HIGH UNMET MEDICAL NEED EPIDEMIOLOGY: US & EU-5 PRODUCT DESIGN ▪ Monogenic: X-linked (RPGR)▪ Vector: R100 ▪ ~24,000 prevalence ▪ Blinding: periphery to center▪ Transgene: RPGR ▪ NO FDA APPROVED ▪ Promoter: Photoreceptor-s

  21. Slide 21: 4D-125 Study Design

    4D-125 Study Design OPEN-LABEL, PHASE 1/2 TRIAL IN ADULTS WITH XLRP KEY INCLUSION CRITERIA STUDY DESIGN ▪ Male ≥18 years of age DOSE ESCALATION DOSE EXPANSION ▪ Hemizygous RPGR mutation COHORT 1 COHORT 2 EXPANSION ▪ Clinical diagnosis of non-syndromic retinitis pigmentosa 3E11 vg/eye 1E12 vg/eye 1E1

  22. Slide 22: 4D-125 XLRP Biomarker Data: Preliminary Evidence of Activity

    4D-125 XLRP Biomarker Data: Preliminary Evidence of Activity BASELINE TO LAST VISIT; N=2 EVALUABLE & WITH AT LEAST 6 MONTHS FOLLOW-UP Optical Coherence Tomography (OCT) Microperimetry Microperimetry [Ellipsoid Zone Area – % Change] [Mean Retinal Sensitivity (dB)] [# of Loci with ≥ 7dB Improvement] P

  23. Slide 23: Summary of 4D-125 Interim Phase 1/2 Clinical Data

    Summary of 4D-125 Interim Phase 1/2 Clinical Data ▪ 4D-125 well-tolerated with no dose-limiting toxicities, serious adverse events or chronic inflammation ▪ Evidence of clinical activity observed in the treated eye vs. the untreated eye in evaluable patients (2/2 pts) on three clinical activity endp

  24. Slide 24: Ophthalmology: 4D-150 for Wet AMD & DME

    Ophthalmology: 4D-150 for Wet AMD & DME HIGH UNMET MEDICAL NEED EPIDEMIOLOGY: US PRODUCT DESIGN ▪ Frequent Injections▪ Vector: R100 ▪ Wet AMD: ~200,000/yr incidence ▪ Patient / Physician Adherence ▪ Transgene 1: Aflibercept ▪ DME: ~1.2M prevalence Issues ▪ Transgene 2: VEGF-C RNAi ▪ $9.7 Billion 201

  25. Slide 25: Ophthalmology: 4D-150 Efficacy in NHP CNV Model

    Ophthalmology: 4D-150 Efficacy in NHP CNV Model 100% SUPPRESSION OF CNV INCLUDING AT LOWEST DOSE OF 1E11 VG/EYE 2 wks 4 wks 16/168 0/491 15 10/84 ▪ 100% suppression of CNV, 10 ▪ Including at lowest dose of 1E11 vg/eye 6/84 ▪ Day 42 ocular assessments prior to laser: o 1E11 vg / eye, no uveitis or re

  26. Slide 26: 4D-150 Study Design

    4D-150 Study Design PHASE 1/2 DOSE-ESCALATION FOLLOWED BY RANDOMIZED DOSE EXPANSION STUDY DESIGN DOSE EXPANSION DOSE ESCALATION KEY INCLUSION CRITERIA ▪ ≥ 50 years of age COHORT 4 4D-150 DOSE 1 2:2:1 ▪ Diagnosed with CNV secondary to AMD 1E12 vg/eye TBD n = 3-6 n = 20 ▪ Anti-VEGF treatment: minimum

  27. Slide 27: Ophthalmology: 4D-110 for Choroideremia

    Ophthalmology: 4D-110 for Choroideremia Ubiquitous CHM PROMOTER TRANSGENE HIGH UNMET MEDICAL NEED EPIDEMIOLOGY: US & EU-5 PRODUCT DESIGN ▪ Monogenic: X-linked (CHM)▪ Vector: R100 ▪ ~13,000 prevalence ▪ Blinding: periphery to center▪ Transgene: CHM ▪ NO FDA APPROVED ▪ Promoter: Ubiquitous THERAPY DIF

  28. Slide 28: Key Takeaways for 4D-110 Clinical Data

    Key Takeaways for 4D-110 Clinical Data TOLERABILITY @3E11 VG/EYE ASSOCIATED WITH CLINICAL ACTIVITY ▪ 3E11 vg/eye dose (Cohort 1): o Well-tolerated & no DLT or SAE o Clinical activity vs control eyes (FAF Area) ▪ 1E12 vg/eye dose (Cohort 2): o AE consistent with REP1 transgene product over-expression

  29. Slide 29: Pulmonology Modular Vector A101: 4D-710 Cystic Fibrosis

    PULMONOLOGY Modular Vector: A101 ▪ 4D-710: CYSTIC FIBROSIS © © 2 20 02 21 1 4 4D D M Mo ollecu ecullar ar T Th herap erapeu euti tics. cs. Al Alll R Riigh ghts R ts Reser eserved ved.. 29

  30. Slide 30: 4D-710 Product Design & A101 Target Vector Profile

    4D-710 Product Design & A101 Target Vector Profile AEROSOL DELIVERY FOR LUNG DISEASES Potential Barriers Limited Transduction of Airway Cells BRONCHIAL AIRWAY Patient Nebulizer Defensins Lungs Ubiquitous microCFTR Antibodies Conventional PROMOTER TRANSGENE LUNGS naturally occurring vectors Mucus Epi

  31. Slide 31: Pulmonology: 4D-710 Aerosol Delivery in NHP

    Pulmonology: 4D-710 Aerosol Delivery in NHP WIDESPREAD TRANSDUCTION IN NHP AIRWAYS & ALVEOLI Trachea Bronchi Alveoli Vehicle 4D-710 Lung Genome 46/48 (qPCR) (95.8%) 4D-710 mRNA 44/48 (RT-qPCR) (91.7%) © 2021 4D Molecular Therapeutics. All Rights Reserved. 31

  32. Slide 32: 4D-710 Study Design

    4D-710 Study Design OPEN-LABEL, PHASE 1/2 TRIAL KEY INCLUSION CRITERIA STUDY DESIGN ▪ ≥18 years of age ▪ Diagnosis of CF lung disease including: DOSE ESCALATION DOSE EXPANSION o Bi-allelic mutations in the CFTR gene COHORT 1 COHORT 2 EXPANSION o CFTR modulator therapy: 1E15 vg 2E15 vg TBD n = 3-6 n

  33. Slide 33: Milestones & Financials

    MILESTONES & FINANCIALS © © 2 20 02 21 1 4 4D D M Mo ollecu ecullar ar T Th herap erapeu euti tics. cs. Al Alll R Riigh ghts R ts Reser eserved ved.. 33

  34. Slide 34: Expected Milestones & Cash Runway

    Expected Milestones & Cash Runway CASH POSITION & RUNWAY GUIDANCE PH 1/2 DOSE-ESCALATION ON-GOING 4D-150 $227M 4D-125 PH 1/2 DOSE-EXPANSION ON-GOING Cash, cash equivalents and marketable 4D-110 PH 1/2 DOSE-EXPANSION ON-GOING securities as of the end of Q3 2021 $111M 1Q22 – UPDATED INTERIM CLINICAL D

  35. Slide 35: Thank You

    THANK YOU 5858 Horton Street, Suite 455 Emeryville, California 94608 (510) 505-2680 | info@4DMT.com 4DMT.com © 2021 4D Molecular Therapeutics. All Rights Reserved.

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