4D Molecular Therapeutics, Inc. · NASDAQ:FDMT

4D Molecular Therapeutics — Investor Presentation (August 2024)

77 slides from 4D Molecular Therapeutics's investor presentation, August 2024

1. Slide 1: Harnessing the Power of Directed Evolution for Genetic Medicines

   Harnessing the Power of Directed Evolution for Targeted, Next-Generation Genetic Medicines Corporate Presentation | August 2024 © 2024 4D Molecular © 2024 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. 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: Leading Clinical Stage Next Generation AAV Company

   Leading Clinical Stage Next Generation AAV Company Mission: Become a Fully Integrated Biopharma Company Boldly Innovating to Unlock the Full Potential of Genetic Medicines for Millions of Patients DIRECTED MODULAR ~1 BILLION PLATFORM EVOLUTION Proprietary Capsid Sequences Customized & Evolved Vector

4. Slide 4: Platform Solution: Therapeutic Vector Evolution

   Platform Solution: Therapeutic Vector Evolution Innovation Through Nobel Prize-Winning Technology for Biologics “…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

5. Slide 5: Successes & Limitations of Conventional AAV

   Successes & Limitations of Conventional AAV Opportunity For Targeted Genetic Medicine Vectors & Products SUCCESSES LIMITATIONS ▪ Limited Delivery ▪ Limited Transduction ▪ Increased Inflammation Narrow Focus on Niche and Toxicity Diseases ▪ Vulnerability to Neutralizing Antibodies OPPORTUNITY: UNLOCK

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

   Platform Solution: ~1 Billion Synthetic Capsid Sequences Step 1: Create Massive Diversity in Highly Diverse and Distinct Libraries CONVENTIONAL CREATE ~1 BILLION SYNTHETIC AAV CAPSID HIGHLY DIVERSE AND NATURALLY OCCURRING SEQUENCES BY DIVERSIFYING THE CAP GENE DISTINCT 4DMT AAV CAPSIDS CAPSID LIBRAR

7. Slide 7: Platform Solution: Target Vector Profile Fitness Competition

   Platform Solution: Target Vector Profile Fitness Competition Steps 2 & 3: 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

8. Slide 8: Unlocking the Full Potential of Genetic Medicines: Multiple Large Market Opportunities

   Unlocking the Full Potential of Genetic Medicines: Multiple Large Market Opportunities VECTOR / PRODUCT ESTIMATED RESEARCH IND- PRODUCT DELIVERY CANDIDATE INDICATION PREVALENCE CANDIDATE ENABLING P HA S E 1/ 2 P HA S E 3 R I G HT S Wet AMD ~3M U.S./EUMM 4D-150 DME ~5M U.S./EUMM OPHTHALMOLOGY 4D-125

9. Slide 9: Large Market Ophthalmology

   Large Market Ophthalmology Modular Vector: R100 ▪ 4D-150: Wet AMD & DME ▪ 4D-175: Geographic Atrophy © 2024 4D Molecular © 2024 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. All Rights Reserved.

10. Slide 10: R100 is Designed for Low Dose Intravitreal Delivery for Retinal Diseases

    R100 is Designed for Low Dose Intravitreal Delivery for Retinal Diseases R100 Capsid Efficient Intravitreal Delivery to the Retina Overcome Enhanced retinal barrier (e.g., ILM) transduction Capsid base Peptide insertions Point mutations (internal) Modular Vector Platform for Genetic Medicines to Tre

11. Slide 11: Wet AMD is the First of Four Large Market Retina Indications

    Wet AMD is the First of Four Large Market Retina Indications for 4DMT ~7.6 Million Patients in U.S. Ongoing 4D-150 Trials Future opportunities 3.4M 4.2M 2024 U.S. Prevalence ~2.6M* ~1.7M ~1.7M ~1.6M wet AMD DME Moderate-Severe NPDR GA Lead Program 4D-150 4D-175 Market Scope 2023 Retinal Pharmaceutic

12. Slide 12: Current Bolus Anti-VEGF Therapies for Wet AMD Do Not Preserve Vision

    Current Bolus Anti-VEGF Therapies for Wet AMD Do Not Preserve Vision Long-Term Vision Loss Over Time in the Real World with Current Standard of Care1 +4 +3.0 Therapeutic Objective: Long-term Vision Preservation Change in VA,ETDRS Letters +2 +1.2 Change from Baseline 0 -0.4 -1.8 -2 -3.1 -4 -4.6 Initi

13. Slide 13: 4D-150 Solution: Designed to Preserve Vision

    4D-150 Solution: Designed to Preserve Vision by Addressing the Limitations of Current Wet AMD Therapeutic Regimens Aqueous Concentrations Following Bevacizumab Injections1* Vision Loss Over Time 166% VEGF-A Due to Limitations of Limited durability & 91% VEGF-C Current Standard of high treatment burd

14. Slide 14: Goal of Continuous Retinal Expression of Anti-VEGF is to Reduce Retinal Anatomy Variability

    Goal of Continuous Retinal Expression of Anti-VEGF is to Reduce Retinal Anatomy Variability Oscillating Peak-Trough Anti-VEGF Concentrations Can Central Subfield Thickness (CST) Variability Lead to Variability in CST Predicts Legal Blindness in Wet AMD1 100 HR 2.90 (p=0.002) 0 reservation vision pre

15. Slide 15: Products with Incremental Improvements in Durability Have Become Commercial Blockbusters

    Products with Incremental Improvements in Durability & Reduction in Treatment Burden Have Become Commercial Blockbusters Reduction in Injections Peak WW Annual Sales In-Office IVT “Treat & Extend” Landscape in Wet AMD vs. (All Indications, Eylea Q8W* Consensus6) 4D-150 Designed to provide continuous

16. Slide 16: Potential Multi-billion Annual Revenue Opportunity for 4D-150 in Wet AMD

    Potential Multi-billion Annual Revenue Opportunity for 4D-150 in Broad Wet AMD Patient Population in the U.S. if Approved Market Unlocked Through Potential Wet AMD U.S. Opportunity Adoption Across Key Patient Segments Estimated in 2035 ~$10B annual* Logistically and/or compliance 1% share High burde

17. Slide 17: Strong & Accelerating Enrollment Rates

    Significant Investigator & Patient Interest Following Clinical Data Drove Strong & Accelerating Enrollment Rates 139 Patients Treated with 4D-150 Patients 4D-150 To-Date Enrolled per Month ~14 ~9 ~2 Phase Phase 1 1 Phase 2Phase 2 Dose Expansion Phase Phase 2 Population 2 & Alternate Extension Dose E

18. Slide 18: Key Highlights from 4D-150 Interim Data Presented at ASRS

    Key Highlights from 4D-150 Interim Data Presented at ASRS 1.1 STRONG CLINICAL ACTIVITY DEMONSTRATED IN BROAD WET AMD DISEASE ACTIVITY POPULATION: Planned Phase 3 Population 2.2 DEMONSTRATED DURABLE CLINICAL ACTIVITY 3.3 CONTINUES TO BE SAFE & WELL-TOLERATED: In Both Wet AMD & DME 4.4 PROVIDES FURTHE

19. Slide 19: 4D-150 Continues to be Safe and Well Tolerated in Wet AMD & DME

    4D-150 Continues to be Safe and Well Tolerated in Wet AMD & DME (N=139) No Significant Inflammation in Patients Treated with Planned Phase 3 Dose & Durezol Regimen Highest SUN/NEI Score Observed (4D-150–Related)* All Doses & Steroid Regimens Planned Phase 3 Dose & Range of Maximum Follow-up† Tested†

20. Slide 20: Phase 2 Cohorts Designed to Evaluate 4D-150 in Wet AMD

    Phase 2 Cohorts Designed to Evaluate 4D-150 in Wet AMD Patients With Severe or Broad Disease Activity Population: Severe & High Treatment Burden Broad Disease Activity Cohort: Dose Expansion Population Extension 3E10 vg/eye 3E10 vg/eye (n=20) (n=30) 2:2:1 Sequential 1E10 vg/eye 1E10 vg/eye Randomize

21. Slide 21: Phase 2 Cohorts Enrolled Wet AMD Patients With Severe or Broad Disease Activity

    Phase 2 Cohorts Enrolled Wet AMD Patients With Severe or Broad Disease Activity 10 + Phase 2 Dose Expansion 8 Actual Anti-VEGF Injections Mean CST: ~440 μm Actual Injections*: ~10 (prior 12 months) 6 4 Phase 2 Population Extension Mean CST: ~330 μm 2 Actual Injections*: ~4.4 0 200 225 250 275 300 32

22. Slide 22: Wet AMD is a Heterogenous Patient Population

    Wet AMD is a Heterogenous Patient Population with a Wide Range of Anti- VEGF Need Real World Injection Frequency1 Moderate to High burden: ~20% to ~60% 14% 14% 13% 11% 9% 10% % of eyes treated 7% 6% 5% 4% 3% 3% 2% 1 2 3 4 5 6 7 8 9 10 11 12 13 Real World Number of Injections (Yr 1) 1. Adapted from C

23. Slide 23: Phase 2 Population Extension Cohort Treatment Schema & Endpoints

    Phase 2 Population Extension Cohort Treatment Schema & Endpoints Design Finalized ~Mid-2023: Population Extension Cohort Study Schema 1) Patient safety during gene expression ramp-up (maximizes by week 8-12) 2) Similar to expected Phase 3 design (and precedents) Landmark Local Corticosteroid* Analys

24. Slide 24: Baseline Characteristics Showed Dose Arms are Well Balanced

    Baseline Characteristics Showed Dose Arms are Well Balanced 3E10 vg/eye 1E10 vg/eye Total (N=30) (N=15) (N=45) Mean ±SD age, years 77 ±7.7 78 ±8.6 77 ±7.9 Mean ±SD BCVA, ETDRS letters 71 ±9.9 73 ±8.8 72 ±9.5 Mean ±SD CST (central subfield thickness), m 336 ±135.0 314 ±70.8 329 ±117.1 Mean ±SD time

25. Slide 25: Robust Anti-VEGF Treatment Burden Reduction Observed through 24 Weeks

    Robust Anti-VEGF Treatment Burden Reduction Observed through 24 Weeks Patients Receiving Planned Phase 3 Dose of 3E10: 77% Injection-Free & 93% Had 0–1 Injection Aflibercept Ranibizumb Bevacizumab Faricimab Suppl. Aflibercept Overall: 4D-150 89% reduction in annualized 3E10 vg/eye anti-VEGF injectio

26. Slide 26: Planned Phase 3 Dose Demonstrated Higher BCVA Gains

    Planned Phase 3 Dose Demonstrated Higher BCVA Gains That Were Maintained Over Time, Including in Injection-Free Patients Mean Change Mean Absolute Average (95% CI): Baseline Weeks 20/24 Week 24 3E10 vg/eye: Total 71 +3.5 (1.1, 5.8) 75 4D-150 3E10 (n=30) 3E10 vg/eye: Total (n=30) 3E10 vg/eye: Injecti

27. Slide 27: Planned Phase 3 Dose Demonstrated Sustained Anatomic Control

    Planned Phase 3 Dose Demonstrated Sustained & Greater Anatomic Control Without Fluctuations, Including in Injection-Free Patients 200 (n=30) Total (n=30) 4D-150 3E10 vg/eye: Adjusted mean (95% CI) change in CST Mean Change Mean Absolute 150 4D-150 4D-150 3E10 3E10 inj-free vg/eye: (n=23) Injection-f

28. Slide 28: Patient Case Highlighting the Benefit of a Single Injection of 4D-150 3E10

    Patient Case Highlighting the Benefit of a Single Injection of 4D-150 3E10: BCVA & CST Improved and Maintained Over Time and Injection-free Patient received 4 prior anti-VEGF injections (bevacizumab) in last 6 months CST (m) 200 0 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 4D-150 100 4D-150 500 BCVA (ETD

29. Slide 29: Randomized Phase 2 Dose Expansion Treatment Schema & Endpoints

    Randomized Phase 2 Dose Expansion Treatment Schema & Endpoints: 4D-150 at Doses of 3E10 & 1E10 vg/eye vs. Aflibercept Q8 Week Control Topical corticosteroid taper† Landmark Analysis Aflibercept 4D-150 (Day -7) (Day 1) 4D-150 3E10 vg/eye (n=20) 4D-150 1E10 vg/eye (n=21) Aflibercept 2 mg (n=10) 0 4 8

30. Slide 30: Baseline Characteristics: Severe Disease Activity & High Treatment Burden

    Baseline Characteristics: Wet AMD Patients with Severe Disease Activity & High Treatment Burden 3E10 vg/eye 1E10 vg/eye Aflibercept Total (n=20) (n=21) (n=10) (N=51) 77 ± 7.7 Mean ±SD age, years 77 ± 8.0 77 ± 8.6 80 ± 4.1 (range: 57–92) Mean ±SD time since diagnosis, years 4.0 ± 3.0 2.9 ± 2.2 1.9 ±

31. Slide 31: PRISM Met All Objectives Through 24 Weeks

    PRISM Met All Objectives in Wet AMD Patients with Severe Disease Activity & High Treatment Burden Through 24 Weeks Anti-VEGF Long Term Retinal Treatment Burden Durability Administration Safety Anatomical Reduction (3E10 vg/eye Control (3E10 vg/eye) from Phase 1) intravitreal Single, routine injecti

32. Slide 32: Robust Reduction in Treatment: 89% Reduction with High Dose 4D-150

    Robust Reduction in Treatment for Severe Disease Activity & High Treatment Burden Patients: 89% Reduction with High Dose 4D-150 Aflibercept Ranibizumb Bevacizumab 4D-150 Brolucizumab Faricimab Suppl. Aflibercept Overall: 4D-150 89% reduction in annualized 3E10 vg/eye anti-VEGF injection rate (n=20)

33. Slide 33: Stable Visual Acuity Equivalent to Standard Aflibercept

    Stable Visual Acuity Equivalent to Standard Aflibercept 30 Average difference (95% CI) vs. Aflibercept Total Aflibercept(n=10) Aflibercept 2 mg Q8W (n=10) Adjusted mean (95% CI) change in ETDRS letters 20 4D-150 (3E10 vg/eye) –1.8 (–1.0, 4.1) Population 4D-1503E10 4D-150 3E10vg/eye vg/eye(n=20) (n=2

34. Slide 34: Stable Visual Acuity With and Without Supplemental Injections

    Stable Visual Acuity Equivalent to Standard Aflibercept With and Without Supplemental Injections 30 Average difference (95% CI) vs. Aflibercept Injection-free Aflibercept (n=10) Aflibercept 2 mg Q8W (n=10) Adjusted mean (95% CI) change in ETDRS letters 4D-150 (3E10 vg/eye) +0.4 (–5.2, 6.1) 20 4D-150

35. Slide 35: Sustained Reduction in CST and Anatomic Control Compared to Aflibercept

    Sustained Reduction in CST and Anatomic Control Compared to Aflibercept Average difference (95% CI) vs. Aflibercept 200 Total 150 Aflibercept(n=10) Aflibercept 2 mg Q8W (n=10) 4D-150 (3E10 vg/eye) –8.3 (–92.6, 76.0) Adjusted mean (95% CI) Population change in CST (µm) 100 4D-1503E10 4D-150 3E10vg/ey

36. Slide 36: Sustained Reduction in CST With and Without Supplemental Injections

    Sustained Reduction in CST and Anatomic Control Compared to Aflibercept With and Without Supplemental Injections 200 Average difference (95% CI) vs. Aflibercept Injection-free Aflibercept Aflibercept 2(n=10) mg Q8W (n=10) 4D-150 (3E10 vg/eye) –30.8 (–125, 63.2) 150 Adjusted mean (95% CI) change in C

37. Slide 37: Outcomes Under Preliminary Phase 3 Eligibility Criteria

    Vision and CST Outcomes Under Preliminary Phase 3 Eligibility Criteria* Supports Advancement to Phase 3 25 Aflibercept (n=6) Average 20 Anti-VEGF Injections Adjusted 15 4D-150 3E10 vg/eye (n=16) (Weeks 20 & 24) ∆ vs A L B mean 10 +3.3 ±95% CI 5 10 0 change in -5 9.6 BCVA 90% -10 Preliminary Phase 3

38. Slide 38: Phase 1 Patients Remain Injection-free Through ~2 to 2.5 Years

    3 Patients from Phase 1 Treated with 4D-150 3E10 vg/eye Remain Injection- free Through ~2 to 2.5 Years with Strong Disease Control 4D-150 Anti-VEGF Injections (3E10 vg/eye) Aflibercept Ranibizumb Visits Supplemental Aflibercept Participant 1 Participant 3 Participant 4 -52 -48 -44 -40 -36 -32 -28 -2

39. Slide 39: Planned 4D-150 Phase 3 Registrational Trials in Wet AMD

    Planned 4D-150 Phase 3 Registrational Trials in Wet AMD ▪ Primary Endpoint: Noninferiority (BCVA) 4D-150 3E10 vg/eye vs. aflibercept Preliminary 2mg Q8 weeks Phase 3 Design ▪ Study Size: ~450 patients per study, two studies ▪ Target Population: broad wet AMD disease activity ▪ Increased collaboratio

40. Slide 40: Phase 2 Study Evaluating 4D-150 in Diabetic Macular Edema

    Phase 2 Study Evaluating 4D-150 in Diabetic Macular Edema, a 2nd Large Market Indication Randomized, Active-Controlled, Double-Masked Phase 2 Key Inclusion Criteria Part 1 – Dose Confirmation Part 2 – Expansion ▪ Type I or II diabetes mellitus with macular thickening secondary to DME involving the c

41. Slide 41: Geographic Atrophy is a Large and Growing Retinal Disease

    Geographic Atrophy is a Large and Growing Retinal Disease, CFH Dysfunction & Activation of the Complement Pathway Implicated Classical Lectin Alternative pathway pathway pathway Geographic Atrophy (GA) Antibody-antigen Serum lectin binding Spontaneous hydrolysis complex to mannose residues of C3 on

42. Slide 42: 4D-175 Solution: Intravitreal Gene Therapy for Geographic Atrophy

    4D-175 Solution: Intravitreal Gene Therapy for Geographic Atrophy Biological Rationale 4D-175: sCFH-Transgene Payload ▪ Clinically validated retinotropic AAV vector (R100) ▪ Codon-optimized sequence encoding a highly Promoter (Ubiquitous) Transgene (sCFH) functional, shortened form of human compleme

43. Slide 43: Short-form Complement Factor H is Highly Functional Compared to Full-Length

    Short-form Complement Factor H (sCFH) is Highly Functional Compared to Full-Length Transgene Design Pharmacological Activity Heparin Binding C3b Cleavage Full-length Human CFH1 3 sCFH NT Control Heparin binding CFH Heparin C3b binding CFH + + + - + - Supernatant sCFH C3b binding binding C3d binding

44. Slide 44: Target sCFH Levels Reached in Non-Human Primate Study

    Target sCFH Concentration Levels Reached in Non-Human Primate Ocular Pharmacodynamics and Tolerability Study 4D-175 sCFH Ocular Biodistribution 4D-175 Safety and Tolerability Aqueous Humor* Ocular Distribution‡ Fluorescein Angiography Intraocular Pressure (IOP) 40 Vehicle (n=3) NHP 2502 (1.5x1011 vg

45. Slide 45: Rapidly Advancing Development in Large Market Ophthalmology

    Rapidly Advancing Development in Large Market Ophthalmology VECTOR PRODUCT EPIDEMIOLOGY DELIVERY CANDIDATE INDICATION (PREVALENCE) PHASE 1 PHASE 2 PHASE 3 MILESTONES ✓ 24-week Ph 2 Dose Expansion (N=51) ✓ 24-week Ph 2 Pop. Extension (N=45) ▪ Sep 24 4D-150 Development Day: Interim longest available f

46. Slide 46: Pulmonology

    PULMONOLOGY Modular Vector: A101 ▪ 4D-710: Cystic Fibrosis Lung Disease ▪ 4D-725: Alpha-1 Antitrypsin Deficiency Lung Disease © 2024 4D Molecular © 2024 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. All Rights Reserved.

47. Slide 47: A101: Next-Gen Aerosolized Genetic Medicine Vector for Pulmonology

    A101: Next-Gen Aerosolized Genetic Medicine Vector for Pulmonology Prior aerosol gene therapy trials failed to achieve Aerosolized A101-Based Genetic Medicines transgene expression in lung1,2; potential limitations:  Poor mucus penetration Overcome Potential Barriers Enhanced Transduction of Airway

48. Slide 48: CF Lung Disease Has High Unmet Medical Need Despite Modulators

    CF Lung Disease Has High Unmet Medical Need Despite Modulators Disease Burden Epidemiology ▪ Dysfunctional cystic fibrosis transmembrane ▪ ~105,0004,5 prevalence worldwide: conductance regulator (CFTR) protein → o ~40,000 prevalence in U.S. alone inability to transport chloride at the apical membran

49. Slide 49: Highest Unmet Need in ~35K People with Cystic Fibrosis

    Highest Unmet Need in ~35K People with Cystic Fibrosis 4D-710 has the Potential to Treat Cystic Fibrosis Lung Disease Regardless of Genetic Variant Cystic Fibrosis Population WW Population Segment Estimated People Ineligible for CFTR modulators ~10k study population 10% Intolerant to CFTR modulators

50. Slide 50: Phase 1/2 Designed to Identify Doses for Late-Stage Development

    Phase 1/2 Designed to Identify Doses for Late-Stage Development Generate Safety, Biomarker & Clinical Activity Data to Inform Selection of Phase 2 & 3 Dose Phase 1 (Dose Exploration) Phase 2 (Dose Expansion) Primary Objectives: ppFEV1 Eligibility Criteria: 50% to 100% ppFEV1 Eligibility Criteria: ▪

51. Slide 51: AEROW Enrolled Participants Baseline Characteristics

    AEROW To-Date Enrolled pwCF Ineligible or Intolerant to Modulators with a Broad Range of Disease Activity, 5 with Pre-Existing Immunity to A101 2E15 vg 1E15 vg 5E14 vg 2.5E14 vg Participant # 1 2 3 4 1 2 3 1 2 1 Age, y 37 27 32 69 36 24 20 42 39 25 Sex Female Male Female Female Male Male Female Fema

52. Slide 52: Aerosolized 4D-710 Was Well Tolerated

    Aerosolized 4D-710 (Up to 1E15 vg) Was Well Tolerated 4D-710-Related Adverse Events None Grade 1 Grade 2 Grade 3 Grade 4 1E15 vg 1 2 3 5E14 vg 1 2 2.5E14 vg 1 Month (post dose): 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 ▪ Administration of aerosolized 4D-710 well tolerated o

53. Slide 53: Dose-dependent CFTRΔR RNA Expression Following 4D-710

    Dose-dependent CFTR∆R RNA Expression Following 4D-710 Administration CFTRR RNA (ISH): mean % (+) airway epithelial cells 80 ▪ Dose-dependent CFTRR mRNA Mean % (+) epithelial cells 60 expression in bronchial epithelial 53 cells 40 40 ▪ No CFTRR mRNA expression 27 observed in commercial non-CF and

54. Slide 54: Widespread 4D-710–Mediated CFTR Protein Expression

    Widespread 4D-710–Mediated CFTR Protein Expression at All Doses and in All Participants CFTR (+) Epithelial Cells (IHC) CFTR Staining Intensity (IHC)* 99.3 98.3 100 300 277 100 94 Mean % (+) epithelial cells 250 224.9 Mean intensity score* 80 204.9 200 60 150 44.2 150 40 100 18.4 47 20 50 19 0 0 2E1

55. Slide 55: Widespread & Consistent CFTR Protein Expression: 100% of Samples

    Widespread & Consistent CFTR Protein Expression: 100% of Samples 4D-710 Treated 2E15 vg 1E15 vg 5E14 vg 2.5E14 vg Participant 1 Participant 2† Participant 3 Participant 4 Participant 1 Participant 2† Participant 3 Participant 1 Participant 1 Pending Not sampled Not sampled Pending Interstitial stain

56. Slide 56: CFTR Protein Expression Observed in Multiple Airway Cell Types

    CFTR Protein Expression Observed in Multiple Airway Cell Types CFTR Protein Expression (IHC) Following Administration of 4D-710: Secretory, Ciliated & Basal Cells CFTR Protein Expressed in Multiple Cell Types* Localization to Apical Region† Cross section Longitudinal (1) Basal cells (2) Goblet cells

57. Slide 57: Pre-existing A101 Immunity and Transgene-mediated Protein Expression

    Pre-existing A101 Immunity and Transgene-mediated Protein Expression Pre-existing A101 Immunity Did NOT Affect CFTRR RNA or CFTR Protein Expression CFTR Expression According to Baseline Anti-A101 Antibodies ns ns Pre-existing Anti-A101 Capsid Antibodies 80 ns 150 300 CFTRdR ISH % Positive Positive

58. Slide 58: ppFEV1 Improvement at 12 Months in Two of Three Participants

    Two of Three Participants with Mild to Moderate ppFEV1 Impairment at Baseline Showed Improvement at 12 Months 2E15 vg 2x1015 vg (Pt 2) Participant 2 2E15 vg 2x1015 (Pt 3) vg Participant 3 1E15 vg 1x1015 vg Participant (Pt 2) 2 90 86 +6 ▪ Three participants had a 80 80 4D-710 (2x1015 vg) 74 baseline

59. Slide 59: 4D-710 (1E15 vg): Durable Improvement in CFQ-R-R Score

    4D-710 (1E15 vg): Durable Improvement in CFQ-R-R Score CFQ-R Respiratory Symptom Score Mean Change in CFQ-R-R Score 100 14 * 89 89 CFQ-R Respiratory Symptom Score 90 * 12 11.1 83 83 83 * 83 Respiratory Symptom Score 80 78 78 78 Mean change in CFQ-R 72 72 72 72 10 70 8.4 8.4 8.4 61 8 7.4 * 60 56 6 50

60. Slide 60: Totality of Data Supports 1E15 vg as Intended Phase 2 Dose

    Totality of Clinical & Biomarker Data To-date Supports 1E15 vg as Intended Phase 2 Expansion Dose, 5E14 vg Dose Pending Additional Follow-Up 2E15 vg 1E15 vg 5E14 vg 2.5E14 vg Dose Selection Criteria: Target Profile (n=4) (n=3) (n=1) (n=1) CFTR∆R RNA expression (ISH) ≥15% cells1,2     CFTR protei

61. Slide 61: Preliminary Registration Path for 4D-710

    Preliminary Registration Path for 4D-710 for Treatment of People with CF Who are Modulator-Ineligible/-Intolerant Preliminary Phase 3 Design Accelerated Approval N= ~60-80 Additional FDA/EMA discussions to follow pwCF with low baseline ppFEV1 Population additional AEROW clinical and lung (planned ~4

62. Slide 62: Pulmonology Pipeline Key Expected Milestones

    Pulmonology Pipeline Key Expected Milestones VECTOR PRODUCT EPIDEMIOLOGY IND- EXPECTED UPCOMING DELIVERY CANDIDATE INDICATION (PREVALENCE) ENABLING PHASE 1/2 PHASE 3 MILESTONES Cystic Fibrosis Lung Disease ✓ Phase 1 interim update (N=10) ~15K (modulator ▪ Mid-2025 Interim data update WW ineligible /

63. Slide 63: Cardiology

    CARDIOLOGY Vector: C102 ▪ 4D-310: Fabry Disease Cardiomyopathy © 2024 4D Molecular © 2024 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. All Rights Reserved.

64. Slide 64: C102 & 4D-310 Designed for Low Dose IV Delivery to the Heart

    C102 & 4D-310 Designed for Low Dose IV Delivery to the Heart Cardiac disease is the most common cause of Intravenous C102-Based Genetic Medicines death (75%)1 in Fabry disease 4D-310 C102 Vector: C102 (cardiac Current therapies do not adequately address targeting evolved AAV) Fabry-related cardiovas

65. Slide 65: 4D-310 Unique MOA Well-Differentiated Versus ERT & Genetic Medicines

    4D-310 Unique MOA Well-Differentiated Versus ERT & Genetic Medicines for Fabry Disease Cardiomyopathy ERT (Blood) Genetic Medicine AGA Enzyme PEGylated AGA AAV-mediated 4D-310 MOA Product Design Infusions Liver-directed Normal Pharmacokinetics Time of dose AGA Delivery Lifelong Through the Bloodstre

66. Slide 66: Phase 1/2 Open Label Clinical Trials: 4D-310 for Fabry Disease Cardiomyopathy

    Phase 1/2 Open Label Clinical Trials: 4D-310 for Fabry Disease Cardiomyopathy Geography U.S. multicenter (Currently on Clinical Hold) Taiwan & Australia multicenter Patient Population Male or female adults; classic or late onset Fabry disease; cardiac involvement* (on or off ERT) 4D-310 Dose 1E13 vg

67. Slide 67: Cardiac Assessments: Multiple Diverse Endpoints

    Cardiac Assessments: Multiple Diverse Endpoints Study Assessment Method Time Points Transgene delivery & expression, Gb3 accumulation Cardiac Biopsy* Weeks 6, 26 Exploratory endpoint (INGLAXA 2) Cardiac contractility (global longitudinal strain) Echocardiogram† Months 6, 9, 12, 18, 24 FDA-recommende

68. Slide 68: Baseline Patient Characteristics

    Baseline Patient Characteristics INGLAXA 1 INGLAXA 2 Characteristic Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Disease classification Classic Classic Classic Late onset Late onset Late onset GLA variant c.1023A>C c.708G>T c.974G>A c.671A>G IVS4+919 G>A c.644 A>G Serum AGA activity,

69. Slide 69: Cardiac Biopsy: Robust & Durable Transgene Expression in Cardiomyocytes

    Cardiac Biopsy: Robust & Durable Transgene Expression in Cardiomyocytes ▪ Single participant with repeated cardiac biopsy 25 Week 6 (Weeks 6 & 26)* mRNA expression 20 Week 26 16.2 15 ▪ No inflammation 9.8 10 ▪ Paired analysis of biopsies demonstrated 5 4.3 2.6 widespread transduction & durable trans

70. Slide 70: Cardiac Biopsy: Reduction in Gb3 Substrate Accumulation

    Cardiac Biopsy: Reduction in Gb3 Substrate Accumulation in Cardiomyocytes Mean Gb3 Inclusion Body Ultra-high resolution electron microscopy & Volume per Cardiomyocyte image analysis used to identify cardiomyocytes & quantify the volume of Gb3 inclusions1 1200 1000 1058 Mean volume (m3) 800 15% Redu

71. Slide 71: Global Longitudinal Strain: Ventricular Function Improved or Stable

    Global Longitudinal Strain: Ventricular Function Improved or Stable in All Evaluable Participants Change from Baseline (%) Patient Baseline (Screening) Month 6 Month 12 Month 24 1 ‒17.10 Borderline ‒1.1 ‒2.5 ‒2.9 3 ‒18.83 Low normal ‒0.5 ‒3.3 ‒2.8 2* ‒22.17 Normal na ‒1.1 na MCID=1.5%2 5 ‒21.95‡ Nor

72. Slide 72: Cardiopulmonary Exercise Testing: Durable Improvement in Peak VO2

    Cardiopulmonary Exercise Testing: Durable Improvement in Peak VO2 in 3 of 4 Evaluable Participants Change from Baseline Patient Measurement Baseline Month 6 Month 12 Month 24 mL/kg/min +2.0† +7.8† 1 na nc* (% predicted) (+6.3)† (+24.6)† mL/kg/min 14.0 +7.0 2‡ na na (% predicted) (33.0) (+17.0) MCID=

73. Slide 73: KCCQ: Improved or Stable QoL in All Evaluable Participants

    Kansas City Cardiomyopathy Questionnaire (KCCQ): Improved or Stable QoL in All Evaluable Participants +10.4 +12.5 +5.2 Clinical 100 100 100 100 98.4 +4.7 97.9 100 100 100 100 97.9 +1.1 93.8 92.2 92.7 Summary Absolute Score 80 +5.7 87.5 Baseline Month 9 Score 60 59.9 65.6 Month 12 Month 24 40 20 0 Pa

74. Slide 74: Variability in Serum Biomarkers, No Correlation with Cardiac Outcomes

    Considerable Inter- and Intrasubject Variability in Serum Biomarkers, No Correlation with Cardiac Outcomes Serum AGA 4 Activity 3 Cardiac Outcomes (Patient 2) Log serum AGA activity (nmol/hr/mL) 2 Outcome Baseline Month 12 Change 1 Peak VO2 (mL/kg/min) 14.0 21.0 +7.0 Patient 1 0 Patient 2 * Peak VO2

75. Slide 75: Program Expectations & Cash Position

    Program Expectations & Cash Position ©© 2024 4D4D 2024 Molecular Therapeutics. Molecular AllAll Therapeutics. Rights Reserved. Rights Reserved. 75

76. Slide 76: Strong Cash Balance to Execute Through Key Near-Term Expected Milestones

    Strong Cash Balance to Execute Through Key Near-Term Expected Milestones Large Market 4D-150 1) Interim longest available follow up data through up to 2.5 years from PRISM Phase 1/2 cohorts Ophthalmology DEVELOPMENT DAY (September 2024) 2) Final wet AMD Phase 3 clinical trial design update  24-week

77. Slide 77: Thank You

    THANK YOU 5858 Horton Street, Suite 455 | Emeryville, California 94608 (510) 505-2680 | [email protected] IR.4DMT.com | LinkedIn © 2024 4D Molecular © 2024 4DTherapeutics. Molecular Therapeutics. All Rights Reserved. All Rights Reserved.

4D Molecular Therapeutics — Investor Presentation (August 2024) on 6ix