4D Molecular Therapeutics, Inc 8-K, filed Jan 11, 2022
4D Molecular Therapeutics, Inc. (FDMT)
About this 8-K
4D Molecular Therapeutics, Inc filed this 8-K on January 11, 2022, reporting on events of January 10, 2022.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 9.01: Financial statements and exhibits
UNITED STATES
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Washington, D.C. 20549
FORM
CURRENT REPORT
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| Item 7.01 | Regulation FD Disclosure |
On January 10, 2022, 4D Molecular Therapeutics, Inc. (the “Company”) provided a corporate presentation relating to its research and development programs by posting a corporate presentation to the investor section of the Company’s website at: https://ir.4dmoleculartherapeutics.com. The Company’s corporate presentation is attached hereto as Exhibit 99.1.
The furnishing of the attached presentation is not an admission as to the materiality of any information therein. The information contained in the slides is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”) and other public announcements that the Company has made and may make from time to time by press release or otherwise. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases or through other public disclosures. For important information about forward looking statements, see the slide titled “Legal Disclaimer” in Exhibit 99.1 attached hereto.
The information in this Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the presentation attached as Exhibit 99.1 to this Current Report shall not be incorporated by reference into any filing with the SEC made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Corporate Presentation of 4D Molecular Therapeutics, Inc. dated January 10, 2022. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| 4D MOLECULAR THERAPEUTICS, INC. | ||||||
| Date: January 11, 2022 | By: | /s/ August J. Moretti | ||||
| August J. Moretti | ||||||
| Chief Financial Officer | ||||||
Exhibit 99.1 Harnessing the Power of Directed Evolution for Targeted Gene Therapies Corporate Presentation | January 2022 © 2021 4D Molecular Therapeutics. All Rights Reserved.
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 operations, future financial position, prospects, plans, and objectives of management, are forward looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward looking statements, although not all forward looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in these forward looking statements, and you should not place undue reliance on these forward looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward looking statements. In addition, the forward looking statements included in this Presentation represent our views as of the date of this Presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward looking statements in the future, we specifically disclaim any obligation to do so. These forward looking statements should not be relied upon as representing our views as of any date subsequent to the date of this Presentation. This Presentation discusses our product candidates that are under preclinical study and in clinical trials, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of our product candidates for the therapeutic use for which they are being studied. This Presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. This Presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities. © 2021 4D Molecular Therapeutics. All Rights Reserved. 2
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 Vectors & 3 Therapeutic Areas PIPELINE CLINICAL 5 Clinical Candidates DEVELOPMENT STRATEGY Fully Integrated Biopharmaceutical Company © 2021 4D Molecular Therapeutics. All Rights Reserved. 3
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 FULL POTENTIAL OF GENE THERAPY BY HARNESSING THE POWER OF DIRECTED EVOLUTION © 2021 4D Molecular Therapeutics. All Rights Reserved. 4
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 Prize have no affiliation with 4DMT. © 2021 4D Molecular Therapeutics. All Rights Reserved. 5
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 peptide insertion Random point mutagenesis DNA shuffled CAPSID LIBRARY PACKING CAP GENE © 2021 4D Molecular Therapeutics. All Rights Reserved. 6
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 BILLION Dose synthetic AAV capsid Route sequences in 40 Tissue target R100 distinct libraries Antibody resistance Retina (IVT) TVP: Retina C102 Non-human primate (NHP) Cardiac (IV) TVP: Cardiac A101 TVP: Lung Lung (Aerosol) *Capsid library placed under varying selective pressures // Actual number of selection rounds varies by target © 2021 4D Molecular Therapeutics. All Rights Reserved. 7
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 HUMAN CELL & DISEASE MODELS Transgene: Replace Therapeutic protein © 2021 4D Molecular Therapeutics. All Rights Reserved. 8
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 CARDIOLOGY IV Fabry 4D-310 Disease A101 PULMONOLOGY Aerosol Cystic 4D-710 Fibrosis © 2021 4D Molecular Therapeutics. All Rights Reserved. 9
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
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 Conventional PROMOTER TRANSGENE naturally occurring vectors Enhanced biodistribution PRODUCT DESIGN to affected organs ▪ Vector: C102 ▪ Transgene: GLA (encodes AGA enzyme) Enhanced Blood vessel delivery dysfunction ▪ Promoter: Ubiquitous to heart Cardiac dysfunction Kidney dysfunction 4D-310 © 2021 4D Molecular Therapeutics. All Rights Reserved. 11
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 chemotherapy/ bone + + – + + marrow ablation AGA: Heart, Kidney, – – – – + Blood Vessels Production in Target Cells AGA: Intracellular production – – – – + Avoid Anti-AGA Ab Abbreviations: Ab, antibodies; AGA, aspartylglucosaminidase; AAV, adeno-associated virus; ERT, enzyme replacement therapy; IV, intravenous; n.a., not applicable. © 2021 4D Molecular Therapeutics. All Rights Reserved. 12
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 ERT-naïve COHORT 2 ▪ Anti-AGA Ab status positive OR negative 3E13 vg/kg n = 3 DOSE COHORT 1 KEY EXCLUSION CRITERIA EXPANSION 1E13 vg/kg n = 3-6 n = 3 ▪ High titer anti-4D-310 NAb (>1:1,000) COHORT 2 ▪ High titer anti-AGA NAb titer (>1:25,000) 3E12 vg/kg ▪ eGFR <45 mL/min/1.73m2 n = 3 ▪ LVEF <45% (Echo) SRT Meeting PRIMARY ENDPOINT ASSESSMENT SCHEDULE: BIOMARKERS ▪ Incidence & severity of adverse events KEY SECONDARY ENDPOINTS ▪ Serum AGA Activity: change from baseline ▪ Cardiac - Imaging & Functional: change from baseline Biomarker Assessment (Mayo Clinic) © 2021 4D Molecular Therapeutics. All Rights Reserved. 13
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 Serum AGA activity (nmol/hr/mL) 0.42 0.00 0.30 ERT experience Yes Yes Yes ERT status ERT-ON ERT-OFF ERT-ON Serum lyso-Gb3 (ng/mL) 6.28 101.00 8.78 Mutation c.1023A>C (p.E341D) c.708G>T (p.W236C) c.974G>A (p.G325D) Reference range: • Serum AGA activity: 4.44-27.42 nmol/hr/mL • Serum Lyso-Gb3: < 1.0 ng/mL © 2021 4D Molecular Therapeutics. All Rights Reserved. 14
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 Serum AGA activity: mean normal = 9.9 nmol/hr/ml; normal range: 4.44 – 27.42 nmol/hr/mL © 2021 4D Molecular Therapeutics. All Rights Reserved. 15 AGA Activity (nmol/hr/mL)
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 10 12 14 0 Patient 2 Weeks Serum AGA activity: mean normal = 9.9 nmol/hr/ml; normal range: 4.44 – 27.42 nmol/hr/mL; © 2021 4D Molecular Therapeutics. All Rights Reserved. 16 AGA Activity (nmol/hr/mL) Serum lyso-Gb3 (ng/mL)
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 patients o Levels correlated with baseline anti-AGA antibody titers o Serum lyso-Gb3 substrate decreased significantly in patient with elevated pre-treatment lysoGb3 (entered study OFF-ERT) o Serum lyso-Gb3 substrate remained low following discontinuation of ERT in BOTH patients who entered study ON-ERT © 2021 4D Molecular Therapeutics. All Rights Reserved. 17
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
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 capsid Eye cross section Eye cross section Inner retina PhotoreceptorsRPE Overcome Enhanced retinal barrier (e.g., ILM) transduction R100 R100 Abbreviations: ILM, inner limiting membrane; RPE, retinal pigment epithelium. © 2021 4D Molecular Therapeutics. All Rights Reserved. 19
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-specific THERAPY STATUS: DIFFERENTIATION Ongoing Phase 1/2 Clinical Trial Intravitreal (IVT) Transduces Entire Retinal Surface Fast Track Designation IVT Routine & Safe EXPECTED MILESTONE: All Stages Ongoing Enrollment at 1E12 vg/eye © 2021 4D Molecular Therapeutics. All Rights Reserved. 20
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 1E12 vg/eye n = 3 n = 3 n = 6-12 ▪ Measurable ellipsoid zone line (EZL) on macular SD-OCT DSMC review ▪ Microperimetry: o>1 nonzero point (dose-escalation) OR o≥1dB mean retinal sensitivity (dose-expansion) ASSESSMENT SCHEDULE PRIMARY ENDPOINT ▪ Incidence & severity of adverse events KEY SECONDARY ENDPOINTS Biomarkers assessed by Independent Reading Center ▪ EZ Area (SD-OCT): Change from baseline over time vs contralateral non-injected control eye ▪ Microperimetry: Change from baseline in visual field sensitivity & # loci improving >7dB over 12 months vs contralateral non-injected control eye © 2021 4D Molecular Therapeutics. All Rights Reserved. 21
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] Patient Last Assessment Treated Eye Untreated Eye Treated Eye Untreated Eye Treated Eye Untreated Eye 11 Cohort 1 (3×10 vg/eye) 1 Month 12 -1.0% -2.1% Not Evaluable Not Evaluable Not Evaluable Not Evaluable 2 Month 12 Not Evaluable -10.7% -0.3 Not Evaluable 0 Not Evaluable 3 Month 9 -12.4% -16.2% +1.65 +0.25 +6 +1 12 Cohort 2 (1×10 vg/eye) 4 Month 6 Not Evaluable Not Evaluable Not Evaluable Not Evaluable Not Evaluable Not Evaluable 5 Month 6 -20.2% -28.7% +0.90 +0.10* +3 0* 6 Month 9 Not Evaluable -7% Not Evaluable Not Evaluable Not Evaluable Not Evaluable *Month 4 – Patient 5 unable to fixate in untreated eye at m6 © 2021 4D Molecular Therapeutics. All Rights Reserved. 22
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 endpoints ▪ Continuing enrolling patients at high dose (1E12 vg/eye) in expansion cohort, including less advanced patients ▪ Fast Track Designation received from FDA © 2021 4D Molecular Therapeutics. All Rights Reserved. 23
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 2019 global sales ▪ Incomplete Responders ▪ Promoter: Ubiquitous DIFFERENTIATION STATUS: Intravitreal (IVT) Ongoing Phase 1/2 Clinical Trial Transduces Entire Retina Surface EXPECTED MILESTONE: IVT Routine & Safe Ongoing Enrollment in Dose Escalation 4 Distinct Mechanisms-of-action © 2021 4D Molecular Therapeutics. All Rights Reserved. 24
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 retinal abnormalities 5 o 3E11 & 1E12 vg / eye, mild to moderate uveitis in a minority of NHP; no retinal abnormalities * * * * * * o Tapered 28-day steroid regimen 0/83 0/81 0/84 0/84 0/78 0/81 0 Vehicle 1E11 3E11 1E12 *p<0.05 4D-150 (vg/eye) © 2021 4D Molecular Therapeutics. All Rights Reserved. 25 Grade IV CNV lesions (%)
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 6 injections last 12 mo ▪ Disease responsive to anti-VEGF treatment COHORT 3 4D-150 DOSE 2 3E11 vg/eye TBD n = 3-6 n = 20 PRIMARY ENDPOINT ▪ Incidence and severity of adverse events COHORT 2 Aflibercept 1E11 vg/eye 2mg n = 3-6 n = 10 KEY SECONDARY ENDPOINTS COHORT 1 ▪ Rescue Aflibercept Injections: # over time vs pre-treatment 3E10 vg/eye n = 3-6 DSMC review © 2021 4D Molecular Therapeutics. All Rights Reserved. 26
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 DIFFERENTIATION STATUS: Intravitreal (IVT) Ongoing Phase 1/2 Clinical Trial Transduces Entire Retinal Surface EXPECTED MILESTONE: IVT Routine & Safe Ongoing Enrollment at 3E11 vg/eye All Stages © 2021 4D Molecular Therapeutics. All Rights Reserved. 27
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 (no association with inflammation) ▪ Dose expansion at 3E11 vg/eye dose (n= 6 total) © 2021 4D Molecular Therapeutics. All Rights Reserved. 28
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
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 Epithelium PRODUCT DESIGN ▪ Vector: A101 Overcome Potential Barriers Enhanced Transduction of Airway Cells ▪ Transgene: microCFTR ▪ Promoter: Ubiquitous TVP: Lungs A101 Abbreviations: TVP, Target Vector Profile © 2021 4D Molecular Therapeutics. All Rights Reserved. 30
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
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 = 3-6 n = 12 • Ineligible OR DSMC review • Received modulator therapy but discontinued due to adverse effects or lack of efficacy PRIMARY ENDPOINT ▪ Incidence & severity of adverse events KEY SECONDARY ENDPOINTS ▪ Percent Predicted FEV : change from baseline 1 © 2021 4D Molecular Therapeutics. All Rights Reserved. 32
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
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 DATA 4D-310 (WORLD SYMPOSIUM 2022) Net proceeds from October 2021 follow- on public offering $338M proforma 4D-710 1H22 – PH 1/2 FIRST PATIENT DOSED Cash, cash equivalents & marketable securities expected to fund operations into 2H24 © 2021 4D Molecular Therapeutics. All Rights Reserved. 34
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