Ocular Therapeutix, Inc. · NASDAQ:OCUL
Ocular Therapeutix — 49th Annual Macula Society Meeting 2026
129 slides from Ocular Therapeutix's conference presentation, Feb 27, 2026
Slide 1: Redefining the Management of Neovascular AMD
Redefining the Management of Neovascular AMD February 27, 2026 49th Annual Macula Society Meeting | Coronado, CA
Slide 2: Forward-Looking Statements and Disclaimers
Forward-Looking Statements and Disclaimers Any statements in this presentation about future expectations, plans, and prospects for the Company, including statements regarding the development and regulatory status of the Company’s or its competitors’ product candidates, including statements regarding
Slide 3: Faculty
Faculty Mark R. Barakat, MD Dilsher S. Dhoot, MD Jeffrey S. Heier, MD Peter K. Kaiser, MD Founder and Director of Clinical Vitreoretinal Specialist, Chief Scientific Officer, Chief Development Officer, Research, Retina Macula Institute California Retina Consultants, Ocular Therapeutix, Inc. Ocular T
Slide 4: Disclosures
Disclosures Mark R. Barakat • Consultant: AbbVie Inc, Adverum, Alcon, Alkeus, Annexon Biosciences, Apellis, Astellas, Bausch and Lomb, Beacon, Biocryst, Boehringer Ingelheim, Celltrion, Cencora, Clearside, Eyepoint Pharma, Genentech, Glaukos, Harrow, Janssen, Kodiak Sciences, Ocular Thera peutix, Oc
Slide 5: Disclosures
Disclosures Peter K. Kaiser • Chief Development Officer for Ocular Therapeutix • Consultant: Abbvie, Alexion, Alkeus, Allgenesis, Alzheon, Amaros, Annexon Biosciences, Astellas, Augen Therapeutics, Aviceda, Bayer, Biogen Idec, Carl Zeiss Meditec, Celltrion Healthcare Co., Cognition Therapeutics, Com
Slide 6: Agenda
Agenda SOL-1 Phase 3 Trial Background Key Insights Trial Design Dilsher S. Dhoot, MD Adnan Tufail, MBBS, MD Jeffrey S. Heier, MD OTX-TKI Overview Efficacy Results Panel Discussion Peter K. Kaiser, MD Arshad M. Khanani, MD Safety Results Patricio G. Schlottmann, MD Cases Mark R. Barakat, MD 6
Slide 7: Background: Limitations of Current Standard of Care
Background Limitations of Current Standard of Care Dilsher S. Dhoot, MD 7
Slide 8: Treatment Burden Remains a Significant Unmet Need in nAMD
Treatment Burden Remains a Significant Unmet Need in nAMD INJECTION BURDEN up to 12 injections/yr for patients1 90% of patients require injection every 1-3 months2 up to 12 days off/yr for patients Frequent injections and visits and caregivers disrupt patients’ daily routines and activities3 1 2 3 4
Slide 9: Suboptimal Frequency of Injections Contribute to Declining Real-World Outcomes
Suboptimal Frequency of Injections Contribute to Declining Real-World Outcomes 1. Wykoff CC et al. Impact of anti-VEGF treatment outcomes using IRIS Registry (6-year analysis). Ophthalmology Science. 2024. 2. Monés J, et al. Ophthalmol Ther. 2023;12(2):589-602. 3. Ciulla TA, et al. Ophthalmol Retina
Slide 10: Second Generation nAMD Agents Extend Injection Intervals Incrementally
Second Generation nAMD Agents Extend Injection Intervals Incrementally Over Previous Agents in the Real World Comparison of Intravitreal Injection Real World Use of Aflibercept 8 mg: Intervals (n=190)1 IRIS Registry Data2 10 Last Mean Dosing Interval (Weeks) Group Achieved Interval 8 7.64 6.18 Treat
Slide 11: Existing Literature Underestimates True Attrition in nAMD
Existing Literature Underestimates True Attrition in nAMD Themes in Attrition Literature Literature-Based Attrition Curve* Strict Inclusion Varying 100% Dataset applicability drops Criteria Limit considerably after Y3 Definitions of Relevance 88% Discontinuation Prior registry Ranging from 6-12 anal
Slide 12: Curated Retrospective Attrition Analysis Across Two National Registries
Curated Retrospective Attrition Analysis of Treatment-Naïve nAMD Eyes Across Two National Registries With Up to 7–9 Years of Follow-Up Period Study Vestrum Health Eyes: 202K IRIS Registry Eyes: 562K Jan 2015 - Jun 2025 Pts: 159K Jan 2016 - Dec 2024 Pts: 470K Up to 9 Year follow-up Up to 7 Year follo
Slide 13: Curated Retrospective Attrition Analysis Across Two National Registries
Curated Retrospective Attrition Analysis of Treatment-Naïve nAMD Eyes Across Two National Registries With Up to 7–9 Years of Follow-Up Period Study Vestrum Health Eyes: 202K IRIS Registry Eyes: 562K Jan 2015 - Jun 2025 Pts: 159K Jan 2016 - Dec 2024 Pts: 470K Up to 9 Year follow-up Up to 7 Year follo
Slide 14: Curated Retrospective Attrition Analysis Across Two National Registries
Curated Retrospective Attrition Analysis of Treatment-Naïve nAMD Eyes Across Two National Registries With Up to 7–9 Years of Follow-Up Period Study Vestrum Health Eyes: 202K IRIS Registry Eyes: 562K Jan 2015 - Jun 2025 Pts: 159K Jan 2016 - Dec 2024 Pts: 470K Up to 9 Year follow-up Up to 7 Year follo
Slide 15: High Real-World Discontinuation Highlights Unmet Need
High Real-World Discontinuation Highlights Unmet Need for Durable, Low-Burden nAMD Therapy Steepest Drop-Off in Years 1–2; Continued Decline Through Years 3–7+ Vestrum Health IRIS Registry* 100% 100% Proportion of Patients Remaining on Treatment Proportion of Patients Remaining on Treatment 80% 72%
Slide 16: Real-World Anti-VEGF Use Shows Fewer Injections Over Time
Real-World Anti-VEGF Use Shows Fewer Injections Over Time, Driving Initial Vision Gains Followed by Gradual Decline Injection Frequency Long-Term Visual Outcomes* 10 10 Mean Change in BCVA from Baseline 9 8.4 8 8 6 Mean Number of Injections 3.9 6.6 7 6.4 6.3 6.3 6.3 6.2 4 2.7 1.6 6 2 0.6 6.1 1.8 -0.
Slide 17: Persistent Dosing Could Provide for Sustained Visual Outcomes
Persistent Dosing Could Provide for Sustained Visual Outcomes, Emphasizing the Need for Therapies that Deliver Continuous, Consistent Treatment 20 Mean Change in BCVA from Baseline, Letters 15 Peak BCVA Maintained 10 5 0 -5 Peak BCVA Lost -10 Initiation Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year
Slide 18: Redefining nAMD Therapy: What can we do better?
Redefining nAMD Therapy: What can we do better? Match treatment Provide Enable long- Lower treatment to real-world continuous VEGF acting disease burden adherence suppression control Therapies must Sustained control Fewer visits and work even when Avoid the cycle of without frequent injections may p
Slide 19: OTX-TKI: The Science Behind the Therapy
OTX-TKI The Science Behind the Therapy Peter K. Kaiser, MD 19
Slide 20: Current Anti-VEGF Therapies Selectively Target Only Extracellular VEGF
Current Anti-VEGF Therapies Selectively Target Only Extracellular VEGF Aflibercept Faricimab Ang2 Ranibizumab Bevacizumab VEGF-A VEGF-A Brolucizumab VEGF-B VEGF-C VEGF-C Current Anti-VEGF agents act PIGF VEGF-E VEGF-D extracellularly by binding selective ligands, like VEGF-A, Extracellular preventin
Slide 21: Tyrosine Kinase Inhibitors Act Intracellularly to Inhibit Receptor Signaling
Tyrosine Kinase Inhibitors Act Intracellularly to Inhibit Receptor Signaling VEGF-A VEGF-A VEGF-B VEGF-C VEGF-C Tyrosine Kinase Inhibitors (TKI) PIGF VEGF-E VEGF-D bind at the intracellular tyrosine kinase domains of VEGF receptors, inhibiting ATP binding Extracellular and preventing activation of p
Slide 22: AssayQuant Kinome Tree
AssayQuant Kinome Tree Independent, Quantifiable, Simultaneous Evaluation of Inhibition Activity of TKI drugs Kinome Tree AssayQuant Kinome tree is an independent, standardized visualization of kinase profiling data 1 Each kinase receptor is a node with color intensity reflecting magnitude of inhibi
Slide 23: AssayQuant Kinome Tree
AssayQuant Kinome Tree Critically important to understand testing conditions to interpret Kinome Tree Inhibition Kinome Tree ATP competes with TKI drugs for receptor binding Apparent % inhibition depends on ATP + drug concentration Adapted from AssayQuant. 1 AssayQuant is an independent, standardize
Slide 24: AssayQuant Kinome Tree
AssayQuant Kinome Tree Critically important to understand testing conditions to interpret Kinome Tree Inhibition Kinome Tree ATP competes with TKI drugs for receptor binding Apparent % inhibition depends on ATP + drug concentration ATP Testing Levels Drug Testing Levels Low ATP levels reduce competi
Slide 25: AssayQuant Kinome Tree
AssayQuant Kinome Tree Always look for testing conditions when evaluating claims about receptor inhibition Kinome Tree ATP competes with TKI drugs for receptor binding Apparent % inhibition depends on ATP + drug concentration ATP Testing Levels Drug Testing Levels Low ATP levels reduce competition S
Slide 26: Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor
Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor • 2nd generation TKI, approved in 2012 (Inlyta, Pfizer) for treatment of advanced renal cell carcinoma • Axitinib’s high potency and selectivity relates to its interaction inside the pocket of the kinase receptor domain combined with its interac
Slide 27: Axitinib: Highly Selective, Very Potent Pan-VEGFR Inhibitor
Axitinib: Highly Selective, Very Potent Pan-VEGFR Inhibitor IC50 Values with Cell Phosphorylation (nM)1 Percent Inhibition of Phosphorylation3 Axitinib - VEGFR2 Vorolanib - VEGFR2 100 120 Percent Inhibition of Phosphorylation 110 Lower IC50 values indicate higher 100 potency VEGFR-2 90 10 VEGFR-2 2.
Slide 28: Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor
Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor Independent AssayQuant Kinome Tree Analysis Kinome Tree Axitinib Sunitinib Vorolanib At physiologic ATP concentrations and therapeutic TKI concentrations, axitinib*: VEGFR 1/2/3: >90% inhibition 1,2 VEG FR3 VEG FR3 VEG FR3 VEG FR2 VEG FR2 VEG FR
Slide 29: AssayQuant Independent Potency Comparison Among TKIs
AssayQuant Independent Potency Comparison Among TKIs Tyrosine Kinase Inhibitor Potency (% Inhibition) Evaluated at physiologic ATP levels (1mM) & Drug Concentrations (1µM)* Axitinib Vorolanib Sunitinib TK Receptors1,2 Most Potent VEGFR, PDGFR TKI Derivative of Sunitinib Development in retina termina
Slide 30: AssayQuant Independent Potency Comparison Among TKIs
AssayQuant Independent Potency Comparison Among TKIs Tyrosine Kinase Inhibitor Potency (% Inhibition) Evaluated at physiologic ATP levels (1mM) & Drug Concentrations (1µM)* Axitinib Vorolanib Sunitinib TK Receptors1,2 Most Potent VEGFR, PDGFR TKI Derivative of Sunitinib Development in retina termina
Slide 31: Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor
Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor Independent AssayQuant Kinome Tree Analysis Kinome Tree Axitinib Sunitinib Vorolanib At physiologic ATP concentrations and therapeutic TKI concentrations, axitinib*: VEGFR 1/2/3: >90% inhibition 1 VEG FR3 VEG FR3 VEG FR3 VEG FR2 VEG FR2 VEG FR2
Slide 32: AssayQuant Independent Potency Comparison Among TKIs
AssayQuant Independent Potency Comparison Among TKIs Tyrosine Kinase Inhibitor Potency (% Inhibition) Evaluated at physiologic ATP levels (1mM) & Drug Concentrations (1µM)* Axitinib Vorolanib Sunitinib TK Receptors1,2 Most Potent VEGFR, PDGFR TKI Derivative of Sunitinib Development in retina termina
Slide 33: Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor
Axitinib: Highly Selective, Potent Pan-VEGFR Inhibitor Independent AssayQuant Kinome Tree Analysis Kinome Tree 1,2 Axitinib Sunitinib Vorolanib At physiologic ATP concentrations and therapeutic TKI concentrations*: No meaningful JAK1 or TIE2 inhibition1 VEG FR3 VEG FR3 VEG FR3 VEG FR2 VEG FR2 VEG FR
Slide 34: AssayQuant Independent Potency Comparison Among TKIs
AssayQuant Independent Potency Comparison Among TKIs Tyrosine Kinase Inhibitor Potency (% Inhibition) Evaluated at physiologic ATP levels (1mM) & Drug Concentrations (1µM)* Axitinib Vorolanib Sunitinib TK Receptors1,2 Most Potent VEGFR, PDGFR TKI Derivative of Sunitinib Development in retina termina
Slide 35: Hydrogel-Based Platform Widely Utilized
Hydrogel-Based Platform Widely Utilized Other Medical Specialties Hydrogel in Ophthalmology Neurosurgery DuraSeal® Dural Sealant System1 Vascular Surgery MYNXGRIP® Vascular Closure Device 2 Interventional Radiology Nellix® Endovascular Aneurysm Sealing System3 Urology SpaceOAR 4 Ocular applications
Slide 36: OTX-TKI: Axitinib via Hydrogel Allows for Tunable Sustained Release
OTX-TKI: Axitinib via Hydrogel Allows for Tunable Sustained Release AXITINIB ELUTYX TECHNOLOGY Multi-target Tyrosine Kinase Inhibitor (TKI) Bioresorbable, Sustained Drug Delivery Highly selective pan VEGF inhibitor 1 Proprietary hydrogel Highly potent TKI2 Versatile, biocompatible, tunable platform
Slide 37: OTX-TKI is Designed to Release Axitinib and Maintain Intraocular Drug Levels
OTX-TKI is Designed to Release Axitinib and Maintain Intraocular Drug Levels Over Time with Complete Bioresorption Axitinib concentrations in the retina and choroid/RPE following a single OTX-TKI over 9 months in NHPs1 Axitinib Concentration (ng/g) Rapid, continuous and consistent axitinib delivery1
Slide 38: Histology of Ocular Tissues Demonstrates Axitinib Elution
Histology of Ocular Tissues Demonstrates Axitinib Elution with No Inflammatory Cells Microscopic Findings Histology of Ocular Tissues from 0.7 mg OTX-TKI White, refractile, basophilic, 5002 5603 granular axitinib in the vitreous No inflammatory cells in vitreous, retina, or AC 500 um 1000 um 5002 56
Slide 39: Comparison of Hydrogel vs Other Retinal Polymer Implants
Comparison of Hydrogel vs Other Retinal Polymer Implants Implant Implant Dimensions Needle Matrix Degradation Polymer Implant Remnants (Full View) (Length x Diameter) Size & Release Byproduct at 12 Months 6mm x OZURDEX Lactic acid and Lasts >12 0.46mm* 22-gauge* glycolic acid† months ‡ Two implants
Slide 40: OTX-TKI is Designed for Seamless, Immediate Adoption
OTX-TKI is Designed for Seamless, Immediate Adoption Ideal Target Product Profile Pan-VEGF and PDGF inhibitory activity1 Axitinib has Best-in-class (TKI) Potency1 Best-in-class durability up to 12 months2 1. Gross-Goupil M, et al. Clin Med Insights Oncol. 2013;7:269-277. 2. Eichenbaum, DA, et al. Am
Slide 41: OTX-TKI is Designed for Seamless, Immediate Adoption
OTX-TKI is Designed for Seamless, Immediate Adoption Ideal Target Single Bioresorbable Product Profile Hydrogel Pan-VEGF and PDGF No remnants inhibitory activity1 after drug depletion3 Axitinib has Best-in-class Tunable hydrogel used (TKI) Potency1 in DEXTENZA3 Excellent safety profile Best-in-class
Slide 42: OTX-TKI is Designed for Seamless, Immediate Adoption
OTX-TKI is Designed for Seamless, Immediate Adoption Ideal Target Single Bioresorbable Optimizing Product Profile Hydrogel Retina Practices Pan-VEGF and PDGF No remnants Familiar IVT inhibitory activity1 after drug depletion3 injection with 25g needle5 Axitinib has Best-in-class Tunable hydrogel use
Slide 43: Trial Design
Trial Design Addressing Regulatory and Clinical Objectives Jeffrey S. Heier, MD 43
Slide 44: FDA Draft Guidance for Industry
FDA Draft Guidance for Industry 2023 Q1 New FDA Drug Development Guidance released U.S. Food and Drug Administration. Neovascular AMD: Developing Drugs for Treatment Guidance for Industry. 2023 Q1, quarter 1 44
Slide 45: SOL-1 Trial is Designed to Align with FDA Guidance
SOL-1 Trial is Designed to Align with FDA Guidance FDA Guidance for Neovascular AMD Trials One comparator arm should have the same dosing schedule as the investigational drug1 Sham injections are not recommended due to inadequate masking2,3 1. U.S. Food and Drug Administration. Neovascular AMD: Deve
Slide 46: SOL-1 Trial is Designed to Align with FDA Guidance
SOL-1 Trial is Designed to Align with FDA Guidance FDA Guidance for Neovascular AMD Trials SOL-1 Trial Design One comparator arm should have the same Both study arms have the same dosing schedule as the investigational drug1 dosing schedule Sham injections are not recommended No sham injections in e
Slide 47: SOL-1 Trial is Designed to Align with FDA Guidance
SOL-1 Trial is Designed to Align with FDA Guidance FDA Guidance for Neovascular AMD Trials SOL-1 Trial Design One comparator arm should have the same Both study arms have the same dosing schedule as the investigational drug1 dosing schedule Sham injections are not recommended No sham injections in e
Slide 48: Special Protocol Assessment (SPA)
Special Protocol Assessment (SPA) Agreement with FDA on critical design elements and statistical analysis plan (SAP) to support approval With acceptance of SPA, study design, endpoints, and SAP cannot be changed Adhering to protocol is critical to ensuring trial will be considered adequate and well-
Slide 49: FDA Recommendation for Endpoints to Demonstrate Superiority
FDA Recommendation for Endpoints to Demonstrate Superiority ≥15-Letter Decrease Statistically significant smaller % of subjects with ≥15-letter decrease at 9 months or later ≥15-Letter Increase Statistically significant greater % of subjects with ≥15-letter increase at 9 months or later ≥15-Letter D
Slide 50: OTX-TKI Evaluated in a Superiority Trial for nAMD
OTX-TKI Evaluated in a Superiority Trial for nAMD Compares a Single Multicenter, Double- Designed to Assess Safety OTX-TKI (0.45 mg) Dose Masked, Randomized and Efficacy, including to a Single Aflibercept Parallel-Group Trial Durability, of OTX-TKI (2 mg) Dose ClinicalTrials.gov. identifier: NCT0622
Slide 51: SOL-1 Eligibility and Enrollment Criteria
Eligibility and Enrollment Criteria Key Inclusion Criteria Week -8 -4 Study visit SOL-1 Screening Enrollment Criteria Screening Visit (Week -8) Treatment naïve CNV due to nAMD BCVA ≥54 ETDRS letters (~20/80 Snellen equivalent) CSFT of ≤500 μm ClinicalTrials.gov. identifier: NCT06223958 CNV, choroida
Slide 52: SOL-1 Eligibility and Enrollment Criteria
Eligibility and Enrollment Criteria Key Inclusion Criteria Week -8 -4 Aflibercept 2 mg Study visit SOL-1 Aflibercept 2 mg Aflibercept 2 mg Loading Enrollment Criteria Screening Visit (Week -8) Treatment naïve CNV due to nAMD BCVA ≥54 ETDRS letters (~20/80 Snellen equivalent) CSFT of ≤500 μm Clinical
Slide 53: SOL-1 Eligibility and Enrollment Criteria
Eligibility and Enrollment Criteria Key Inclusion Criteria Week -8 -4 R 1:1 Aflibercept 2 mg OTX-TKI* (0.45 mg) Study visit SOL-1 OTX-TKI 0.45 mg Aflibercept (2 mg) Randomization (Day 1) Enrollment Criteria Randomization Criteria Screening Visit (Week -8) Baseline Visit (Day 1) Treatment naïve CNV d
Slide 54: Direct Comparison: OTX-TKI and Aflibercept
Direct Comparison: OTX-TKI and Aflibercept Primary Data Endpoint Readout Week -8 -4 R 1:1 0 4 8 12 16 20 24 28 32 36 40 44 48 52 OTX-TKI* (0.45 mg) Aflibercept (2 mg) Loading Randomization Monthly Visits (Day 1) OTX-TKI (0.45 mg) Aflibercept (2 mg) Study visit Primary Endpoint (Week 36) Proportion o
Slide 55: Direct Comparison: OTX-TKI and Aflibercept
Direct Comparison: OTX-TKI and Aflibercept Primary Data Safety Endpoint Readout Follow-up** Week -8 -4 R 1:1 0 4 8 12 16 20 24 28 32 36 40 44 48 52 … 76 … OTX-TKI* (0.45 mg) End of year 2 Aflibercept (2 mg) Loading Randomization Monthly Visits (Day 1) OTX-TKI (0.45 mg) Aflibercept (2 mg) Study visit
Slide 56: Rescue Treatment Criteria and Execution
Rescue Treatment Criteria and Execution Rescue Treatment Criteria BCVA loss ≥15 ETDRS letters from baseline due to nAMD OR New macular hemorrhage that would likely lead to irreversible vision loss if left untreated in the opinion of the investigator after discussion with Medical Monitor ClinicalTria
Slide 57: Rescue Treatment Criteria and Execution
Rescue Treatment Criteria and Execution Rescue Treatment Criteria BCVA loss ≥15 ETDRS letters from baseline due to nAMD OR New macular hemorrhage that would likely lead to irreversible vision loss if left untreated in the opinion of the investigator after discussion with Medical Monitor Trial Conduc
Slide 58: Disclaimer: OTX-TKI is investigational
Disclaimer The following presentations discuss OTX-TKI - an investigational product candidate that has not been approved by the FDA or any other regulatory body; safety and effectiveness have not been established
Slide 59: Efficacy Results
Efficacy Results Key Outcomes through Week 52 Arshad M. Khanani, MD 59
Slide 60: Subject Disposition
Subject Disposition Randomized N=344 OTX-TKI 0.45 mg Aflibercept 2 mg N=172 N=172 60
Slide 61: Subject Disposition
Subject Disposition Strong subject retention maintained through Week 52 Randomized N=344 OTX-TKI 0.45 mg Aflibercept 2 mg N=172 N=172 Discontinued before Week 52 (n=11) Discontinued before Week 52 (n=5) • Adverse event (n=1) • Adverse event (n=2) • Subject withdrew consent* (n= 6) • Subject withdrew
Slide 62: Baseline Demographics
Baseline Demographics Treatment groups were well matched at baseline OTX-TKI 0.45 mg Aflibercept 2 mg Demographics N = 172 N = 172 Age, years, mean (SD) 75.7 (8.3) 76.3 (7.4) Sex, n (%) Female 103 (59.9) 108 (62.8) Ethnicity, n (%) Hispanic or Latino 33 (19.2) 47 (27.3) Not Hispanic or Latino 139 (8
Slide 63: Ocular Characteristics: Best-Corrected Visual Acuity
Ocular Characteristics: Best-Corrected Visual Acuity Majority of subjects demonstrated ≥10-letter gain prior to baseline and had excellent vision at study entry Screening Visit (Week -8) OTX-TKI 0.45 mg Aflibercept 2 mg Study Eye Characteristics N = 172 N = 172 BCVA, ETDRS letter score, mean (SD) 70
Slide 64: Ocular Characteristics: Central Subfield Thickness
Ocular Characteristics: Central Subfield Thickness Baseline CSFT improved from screening after two aflibercept injections Screening Visit (Week -8) OTX-TKI 0.45 mg Aflibercept 2 mg Study Eye Characteristics N = 172 N = 172 BCVA, ETDRS letter score, mean (SD) 70.9 (11.3) 69.5 (10.8) Snellen Equivalen
Slide 65: Ocular Characteristics at Baseline
Ocular Characteristics at Baseline Well-balanced between treatment arms OTX-TKI 0.45 mg Aflibercept 2 mg Study Eye Characteristics N = 172 N = 172 BCVA, ETDRS letter score >71 letters (~ 20/40)*, n (%) 145 (85.3) 136 (79.1) Presence of Any Fluid (IRF and/or SRF), n (%) 63 (36.6) 72 (41.9) Presence o
Slide 66: Primary Endpoint: Proportion of Subjects Who Maintain Visual Acuity
Primary Endpoint: Proportion of Subjects Who Maintain Visual Acuity* Statistically significant higher proportion of subjects maintained visual acuity* with OTX-TKI vs. aflibercept 2 mg at Week 36 100% P = 0.0006 OTX-TKI Aflibercept Proportion of Subjects, % (0.45 mg) (2 mg) 74.1% n = 170 n = 172 75%
Slide 67: Key Secondary: Proportion of Subjects Who Maintain Visual Acuity
Key Secondary: Proportion of Subjects Who Maintain Visual Acuity* Treatment benefit continued through 52 weeks with high statistical significance 100% P < 0.0001 Proportion of Subjects, % OTX-TKI Aflibercept 75% (0.45 mg) (2 mg) 65.9% n = 170 n = 172 Proportion of Subjects 65.9% 44.2% 50% 44.2% Risk
Slide 68: Key Secondary: Proportion of Subjects Who Maintain Visual Acuity
Key Secondary: Proportion of Subjects Who Maintain Visual Acuity* Key secondary endpoints achieved in accordance with the prespecified hierarchy With <1 Rescue Injection With ≤1 Rescue Injection At Week 52 at Week 52 at Week 36 100% P = 0.0007 100% P < 0.0001 100% P = 0.0036 Proportion of Subjects,
Slide 69: Secondary Endpoint: Improved Anatomic Control
Secondary Endpoint Significantly improved anatomic control with OTX-TKI Proportion of Subjects with CSFT ≤ 350 µm 100% P = 0.0041* P = 0.0001* Proportion of Subjects, % 75% 68.8% 64.7% 52.9% 50% 43.6% 25% 0% Week 36 Week 52 Risk difference vs. aflibercept Risk difference vs. aflibercept 15.0% (95% C
Slide 70: Secondary Endpoint: Decreased Rates of Vision Loss
Secondary Endpoint Significantly decreased rates of vision loss with OTX-TKI Proportion of Subjects Who Lose ≥10 ETDRS Letters 100% P = 0.0029* P = 0.0423* Proportion of Subjects, % 75% 59.3% 50.6% 47.6% 50% 34.1% 25% 0% Week 36 Week 52 Risk difference vs. aflibercept Risk difference vs. aflibercept
Slide 71: Proportion of Rescue Free Subjects
Proportion of Rescue Free Subjects Significant reduction in need for rescue treatment through week 52 100% P = 0.0856* P = 0.0006* P = 0.0001* 80.6% Proportion of Subjects, % 74.7% 75% 72.1% 68.8% 56.4% 50% 47.7% 25% 0% Week 24 Week 36 Week 52 OTX-TKI 0.45 mg (n=170) Aflibercept 2 mg (n=172) Rescue-
Slide 72: Secondary Endpoint: Time to First Rescue Treatment
Secondary Endpoint: Time to First Rescue Treatment OTX-TKI meaningfully extended durability, significantly delaying first rescue injection 1.0 0.9 Probability of Not Having Rescue Injection P = 0.0005* 0.8 0.7 0.6 0.5 0.4 0.3 0.2 ~24 24 weeks weeks 0.1 0.0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 6
Slide 73: Mean Change in BCVA and CSFT Over Time
Mean Change in BCVA and CSFT Over Time 75% of OTX-TKI subjects were rescue-free with maintenance of visual acuity and anatomy at Week 36 0 Mean (±SE) Change from Baseline, ETDRS Letters -5 -10 Weeks -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Mean (±SE) Change from 74.7% 75 Rescue free Baseline, µm
Slide 74: Mean Change in BCVA and CSFT Over Time
Mean Change in BCVA and CSFT Over Time 75% of OTX-TKI subjects were rescue-free with maintenance of visual acuity and anatomy at Week 36 0 Mean (±SE) Change from Baseline, ETDRS Letters -5 -10 Weeks -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Mean (±SE) Change from 74.7% 56.4% 75 Rescue free Rescue
Slide 75: Mean Change in BCVA and CSFT Over Time
Mean Change in BCVA and CSFT Over Time 75% of OTX-TKI subjects were rescue-free with maintenance of visual acuity and anatomy 0 OTX_TKI Bioresorption OTX-TKI Bioresorption Mean (±SE) Change from Baseline, ETDRS Letters -5 -10 Weeks -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Mean (±SE) Change from
Slide 76: Mean Change in BCVA and CSFT Over Time
Mean Change in BCVA and CSFT Over Time 75% of OTX-TKI subjects were rescue-free with maintenance of visual acuity and anatomy 0 OTX_TKI Bioresorption OTX-TKI Bioresorption Mean (±SE) Change from Baseline, ETDRS Letters -5 -10 Weeks -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Mean (±SE) Change from
Slide 77: Mean Change in BCVA and CSFT Over Time
Mean Change in BCVA and CSFT Over Time 75% of OTX-TKI subjects were rescue-free with maintenance of visual acuity and anatomy 0 OTX_TKI Bioresorption OTX-TKI Bioresorption Mean (±SE) Change from Baseline, ETDRS Letters -5 -10 Weeks -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Mean (±SE) Change from
Slide 78: Mean Change in Intra-Retinal and Sub-Retinal Total Fluid Volume
Mean Change in Intra-Retinal and Sub-Retinal Total Fluid Volume OTX-TKI delivered robust, durable IRF and SRF control 70 +54 60 Mean (±SE) Change, nL 50 40 30 20 +30 10 0 0 4 8 12 16 20 24 28 32 36 Weeks OTX-TKI 0.45 mg (n=170) Aflibercept 2 mg (n=172) Pre-specified exploratory analysis SE, standard
Slide 79: Mean Change in Intra-Retinal and Sub-Retinal Total Fluid Volume
Mean Change in Intra-Retinal and Sub-Retinal Total Fluid Volume OTX-TKI delivered robust, durable IRF and SRF control 70 +54 Total Fluid Volume: 60 nL 60 Mean (±SE) Change, nL 50 40 30 Total Fluid Volume: 30 nL 20 +30 10 0 0 4 8 12 16 20 24 28 32 36 Weeks OTX-TKI 0.45 mg (n=170) Aflibercept 2 mg (n=
Slide 80: Proportion of Subjects with ≤30 µm Increase in CSFT vs Baseline
Proportion of Subjects with ≤30 µm Increase in CSFT vs Baseline Superior fluid control in OTX-TKI arm 75% P = 0.0403* P = 0.0013* P = 0.1094* Proportion of Subjects, % 55.9% 51.8% 50% 44.1% 40.1% 37.8% 34.9% 25% 0% Week 24 Week 36 Week 52 Risk difference vs. aflibercept Risk difference vs. afliberce
Slide 81: Effect of Baseline Fluid Status and Maintaining Vision at Week 36
Effect of Baseline Fluid Status and Maintaining Vision* at Week 36 Subjects who were dry at baseline, maintained vision* with OTK-TKI Favors Aflibercept 2 mg Favors OTX-TKI 0.45 mg OTX-TKI Aflibercept Risk Difference (95% CI) Overall 74.1% 55.8% 17.5 (7.7, 27.4) IRF/SRF Absent 80.4% 56.0% 23.5 (11.1
Slide 82: Visual Outcomes in Rescue-free Subjects through Week 36
Visual Outcomes in Rescue-free Subjects through Week 36 75% of OTX-TKI subjects were rescue-free vs 56% of aflibercept subjects 10 Mean (±SE) Change, ETDRS Letters 5 0 -8 -4 0 4 8 12 16 20 24 28 32 36 Mean BCVA, ETDRS Letters Weeks OTX-TKI 71.8 76.0 81.2 78.8 78.0 Aflibercept 71.2 75.0 79.8 77.0 77.
Slide 83: OCT Outcomes in Rescue-free Subjects through Week 36
OCT Outcomes in Rescue-free Subjects through Week 36 Better disease control demonstrated in a greater proportion of OTX-TKI subjects Weeks -8 -4 0 4 8 12 16 20 24 28 32 36 Weeks 0 -10 -20 Mean (±SE) Change, µm -30 -40 -50 -60 -70 -80 -90 Mean CSFT, µm OTX-TKI 297.7 227.1 218.9 241.5 238.3 Aflibercep
Slide 84: SOL-1: Key Efficacy Outcomes
SOL-1: Key Efficacy Outcomes Superior Superior Superior Visual Outcomes Anatomic Control Rescue-Free Rates 74% of OTX-TKI subjects 56% of OTX-TKI subjects had 75% of OTX-TKI subjects maintained vision* to Week 36 ≤30 µm increase in fluid to Week 36 rescue-free to Week 36 Robust intraretinal and Redu
Slide 85: Safety Results
Safety Results Treatment Tolerability through Week 52 Patricio G. Schlottmann, MD 85
Slide 86: Safety Summary: Non-Ocular Events
Safety Summary: Non-Ocular Events No treatment or procedure related SAEs Subjects with Non-Ocular AEs Through OTX-TKI 0.45 mg Aflibercept 2 mg Week 52, n (%) n = 170 n = 172 Non-ocular AEs ≥ 1 AE 84 (49.4) 73 (42.4) ≥ 1 SAE 19 (11.2) 21 (12.2) ≥ 1 treatment-related AE 0 0 ≥ 1 treatment-related SAE 0
Slide 87: Safety Summary: Ocular Events in the Study Eye
Safety Summary: Ocular Events in the Study Eye No treatment or procedure related SAEs Subjects with Ocular AEs Through OTX-TKI 0.45 mg Aflibercept 2 mg Week 52, n (%) n = 170 n = 172 Ocular AEs in the study eye ≥ 1 AE 90 (52.9) 58 (33.7) ≥ 1 SAE* 1 (0.6) 0 ≥ 1 treatment-related AE 15 (8.8) 1 (0.6) ≥
Slide 88: Ocular Adverse Events in the Study Eye
Ocular Adverse Events in the Study Eye OTX-TKI was generally well tolerated Subjects with Ocular AEs (> 2%) Through OTX-TKI 0.45 mg Aflibercept 2 mg Week 52, n (%) n = 170 n = 172 Vitreous floaters 21 (12.4) 2 (1.2) Cataract 12 (7.1) 5 (2.9) Conjunctival hemorrhage 11 (6.5) 5 (2.9) Retinal hemorrhag
Slide 89: Safety Across nAMD Trials
Safety Across nAMD Trials OTX-TKI relative to other therapeutic agents SOL-1 DAVIO21 Prescribing Information OTX-TKI Aflibercept EYP-1901 Aflibercept 2 Aflibercept 3 Ranibizumab 4 Faricimab 5 (0.45 mg) (2 mg) (3 mg) (2 mg) (8 mg) (0.5 mg) (6 mg) n=170 n=172 n=52 Vitreous 12.4% 1.2% 11.5% 6% 4% 19% 3
Slide 90: Evaluation of Vitreous Floaters
Evaluation of Vitreous Floaters Appearance of floaters likely corresponds to hydrogel dissolution and drug elution Time to Onset OTX-TKI Aflibercept 0.45 mg 2 mg n = 23* n=2 Time to onset, days Mean (SD) 187.9 (64.0) 164.5 (164.8) Median 207.0 164.5 BCVA change from prior visit before onset of float
Slide 91: Evaluation of Intraocular Inflammation (IOI)
Evaluation of Intraocular Inflammation (IOI) Cases were mild/moderate in severity and resolved with topical treatment • Nine events observed in 7 subjects in the MedDRA AE Event Number of Subjects Classified as* OTX-TKI arm AC inflammation 1 • All cases mild or moderate in severity: Eye inflammation
Slide 92: SOL-1: Safety Summary
SOL-1: Safety Summary OTX-TKI was generally well tolerated through Week 52 Vitreous Intraocular Floaters Inflammation Timing likely corresponds with Mild or moderate in severity hydrogel dissolution and drug elution per investigator No visual acuity impact All resolved with topical treatment or obse
Slide 93: Clinical Evidence: Representative Cases
Clinical Evidence Representative Cases Mark R. Barakat, MD 93
Slide 94: Aflibercept Case
Aflibercept Case 1 BCVA 90 20/16 20/25 80 ETDRS Letters 70 (15 letter loss) 60 20/63 50 -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time (Weeks) -8 Weeks BCVA: 74 Ltrs CSFT: 227 µm Screening Study Aflibercept Aflibercept (2 mg) (2mg) Case study of one subject; individual results may vary BCVA, best
Slide 95: Aflibercept Case
Aflibercept Case 1 Baseline BCVA: 88 Ltrs Snellen: 20/16 CSFT: 210 µm BCVA 90 20/16 Week 4 20/25 BCVA (Δ): 84 (-4) Ltrs CSFT (Δ): 213 (+3) µm 80 ETDRS Letters 70 Week 12 (15 letter loss) BCVA (Δ): 79 (-9) Ltrs 60 CSFT (Δ): 208 (-2) µm 20/63 50 Week 24 -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 BCV
Slide 96: Aflibercept Case
Aflibercept Case 2 -8 Weeks BCVA BCVA: 78 Ltrs CSFT: 389 µm 90 20/20 ETDRS Letters 80 Baseline BCVA: 84 Ltrs 20/40 Snellen: 20/20 70 CSFT: 273 µm (15 letter loss) 60 20/50 Week 4 BCVA (Δ): 83 (-1) Ltrs 50 CSFT (Δ): 282 (+9) µm -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time (Weeks) CSFT Week 8 BCV
Slide 97: Aflibercept Case
Aflibercept Case 2 -8 Weeks BCVA BCVA: 78 Ltrs CSFT: 389 µm 90 20/20 ETDRS Letters 80 Baseline BCVA: 84 Ltrs 20/40 Snellen: 20/20 70 CSFT: 273 µm (15 letter loss) 60 20/50 Week 4 BCVA (Δ): 83 (-1) Ltrs 50 CSFT (Δ): 282 (+9) µm -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time (Weeks) CSFT Week 8 BCV
Slide 98: Aflibercept Case
Aflibercept Case 2 Screening Aflibercept Study Aflibercept (2 mg) Per-Protocol Rescue Aflibercept (2mg) Investigator Discretion Rescue (2mg) -8 Weeks Week 24 BCVA: 78 Ltrs BCVA (Δ): 74 (-10) Ltrs CSFT: 389 µm CSFT (Δ): 335 (+62) µm Baseline Week 28 BCVA: 84 Ltrs BCVA (Δ): 74 (-10) Ltrs Snellen: 20/2
Slide 99: Aflibercept Case
Aflibercept Case 3 -8 Weeks BCVA: 80 Ltrs CSFT: 394 µm BCVA 20/16 Baseline BCVA: 89 Ltrs 90 Snellen: 20/16 20/25 20/25 80 CSFT: 328 µm ETDRS Letters 70 (15 letter loss) Week 4 60 BCVA (Δ): 78 (-11) Ltrs CSFT (Δ): 349 (+21) µm 50 40 Week 16 30 BCVA (Δ): 83 (-6) Ltrs -8 -4 0 4 8 12 16 20 24 28 32 36 4
Slide 100: Aflibercept Case
Aflibercept Case 3 Study Screening Aflibercept Per-Protocol Rescue Investigator Aflibercept (2 mg) (2mg) injection Aflibercept (2mg) Discretion Rescue administration -8 Weeks BCVA: 80 Ltrs CSFT: 394 µm Week 28 Baseline BCVA: 89 Ltrs BCVA (Δ): 82 (-7) Ltrs Snellen: 20/16 CSFT (Δ): 421 (+93) µm CSFT:
Slide 101: OTX-TKI Case
OTX-TKI Case 1 -8 Weeks BCVA: 74 Ltrs (-10) CSFT: 467 µm BCVA Baseline 95 BCVA: 84 Ltrs Snellen: 20/20 90 20/20 20/20 CSFT: 285 µm ETDRS Letters 85 80 20/32 Week 4 BCVA (Δ): 83 (-1) Ltrs 75 CSFT (Δ): 320 (+35) µm 70 Week 12 65 BCVA (Δ): 82 (-2) Ltrs -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 CSFT
Slide 102: OTX-TKI Case
OTX-TKI Case 2 -8 Weeks BCVA: 75 Ltrs CSFT: 344 µm BCVA Baseline BCVA: 86 Ltrs 95 Snellen: 20/20 New hemorrhage CSFT: 247 µm 90 20/20 ETDRS Letters 85 20/25 20/25 Week 4 80 BCVA (Δ): 84 (-2) Ltrs CSFT (Δ): 254 (+7) µm 75 70 Week 12 65 BCVA (Δ): 85 (-1) Ltrs -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48
Slide 103: OTX-TKI Case
OTX-TKI Case 3 -8 Weeks BCVA BCVA: 74 Ltrs 95 CSFT: 448 µm 90 20/20 ETDRS Letters Baseline 85 BCVA: 85 Ltrs Snellen: 20/20 80 CSFT: 261 µm 20/25 75 20/25 Week 4 70 BCVA (Δ): 85 (0) Ltrs 65 CSFT (Δ): 257 (-4) µm -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time (Weeks) Week 12 CSFT BCVA (Δ): 84 (-1)
Slide 104: OTX-TKI Case
OTX-TKI Case 4 -8 Weeks BCVA: 64 Ltrs CSFT: 363 µm BCVA 95 Baseline BCVA: 85 Ltrs 90 20/20 20/16 Snellen: 20/20 85 CSFT: 273 µm ETDRS Letters 80 Week 4 75 20/25 BCVA (Δ): 82 (-3) Ltrs 70 CSFT (Δ): 274 (+1) µm 65 60 Week 16 -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 BCVA (Δ): 83 (-2) Ltrs Time (Wee
Slide 105: Key Insights: Interpreting the Data
Key Insights Interpreting the Data Adnan Tufail, MBBS, MD 105
Slide 106: What is the Rationale for the SOL-1 Trial Design?
What is the Rationale for the SOL-1 Trial Design? Clinical trials aimed to get regulatory approval Evidence gap: translating from RCT to real world clinical management Limitation of recent clinical trial designs • Suggest extended interval in subgroups • Investigational drug subgroup extended but no
Slide 107: Disruptive Trial Design – Demonstrates Superiority
Disruptive Trial Design – Demonstrates Superiority Only way to show superiority of duration in a meaningful time frame and be compliant with FDA guidance • Proportion of 15-letter events • Both arms treated identically • Efficient trial design aligned with FDA with a Special Protocol Agreement (SPA)
Slide 108: Why was 15-Letter Change Chosen as the Endpoint?
Why was 15-Letter Change Chosen as the Endpoint? Threshold Letters Lines Clinical Meaning Regulatory Context Minimum Borderline real change; FDA non-inferiority margin detectable 5 1 triggers closer follow-up (4.5) in some trials (good vision) Primary Endpoint: Proportion of Subjects Who Maintain Vi
Slide 109: SOL-1: Treatment Arms Had Excellent Mean Vision at Baseline
SOL-1: Treatment Arms Had Excellent Mean Vision at Baseline (~70 letters at Screening; – ~80 letters at Baseline) Anti-VEGF trials to date associated with mean VA improvement but low baseline vision (~53-60 letters) Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration VIE
Slide 110: SOL-1: Treatment Arms Had Excellent Mean Vision at Baseline
SOL-1: Treatment Arms Had Excellent Mean Vision at Baseline (~70 letters at Screening; – ~80 letters at Baseline) Anti-VEGF trials to date associated with mean VA improvement but low baseline vision (~53-60 letters) Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration VIE
Slide 111: Eyes with Excellent Baseline Acuity Decline on Average in RWE Studies
Eyes with Excellent Baseline Acuity Decline on Average in RWE Studies Writing Committee for the UK Age-Related Macular Degeneration EMR Users Group. The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity. Ophthalmology.
Slide 112: Visual Acuity State and NOT Change is what is Most Meaningful to Patients
Visual Acuity State and NOT Change is what is Most Meaningful to Patients Writing Committee for the UK Age-Related Macular Degeneration EMR Users Group. The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity. Ophthalmolo
Slide 113: Does Reduced Potential for Visual Acuity Gain Occur in Pivotal Trials?
Does Reduced Potential for Visual Acuity Gain Occur in Pivotal Trials? Sub-Analysis of ANCHOR and MARINA In Good VA group (72), 4 letter loss from peak m6 Tufail A, et al.. Br J Ophthalmol. 2020;104(5):672-677. 113
Slide 114: Does Reduced Potential for Visual Acuity Gain Occur in Pivotal Trials?
Does Reduced Potential for Visual Acuity Gain Occur in Pivotal Trials? Sub-Analysis of ANCHOR and MARINA M2 M6 Tufail A, et al.. Br J Ophthalmol. 2020;104(5):672-677. 114
Slide 115: Clin Transl Sci. 2021;14:1166–1175
Clin Transl Sci. 2021;14:1166–1175. 115
Slide 116: What does a real-world SOL-1 eligible emulated population look like?
What does a real-world SOL-1 ‘eligible’ emulated anti-VEGF-treated population with good baseline VA look like (IRIS Registry)? Patients Patients Step Criteria (N) (%) 1 A first anti-VEGF injection (Injection 1, Week -8) in index period (no prior injection) 866,981 100.00% First injection between Jan
Slide 117: Baseline Characteristics
Baseline Characteristics SOL-1 OTX-TKI RWE SOL-1 Emulated N = 172 N = 6178 Age, years, mean (SD) 75.7 (8.3) 76.6 (7.8) Sex, female, n (%) 103 (59.9) 3755 (60.8) VA, ETDRS letters, mean (SD) Screening 70.9 (11.3) 68.4 (10.1) Baseline 80.8 (7.6) 79.0 (6.1) CSFT, µm, mean (SD) Screening 303.6 (72.5) 31
Slide 118: SOL-1 Eligible Emulated RWE Population
SOL-1 ‘Eligible’ Emulated RWE Population Mean Visual Acuity Change From Screening with Standard of Care Dosing 16 16 Change from baseline 70 Screening, EDTRS Letters 14 14 -3.2 -3.7 -3.9 Mean BCVA Change from 60 Mean VA Change from Screening, Mean Number of Anti-VEGF 12 12 50 10.5 EDTRS Letters 10 1
Slide 119: How Does this Align with Previous Studies?
How Does this Align with Previous Studies? SOL-1 IRIS Registry – SOL-1 Emulated Data on File, Ocular Therapeutix 119
Slide 120: SOL: OTX-TKI Phase 3 Clinical Program in nAMD
SOL: OTX-TKI Phase 3 Clinical Program in nAMD Evaluating the efficacy, durability and safety of OTX-TKI in nAMD Registrational Trials Extension Study SOL-1 SOL-R SOL-X Phase 3 Phase 3 Superiority Trial Non-Inferiority Trial Open-Label Extension Durability of a single Repeat dosing Long-term safety a
Slide 121: SOL-R: Phase 3 nAMD Study Design
SOL-R: Phase 3 nAMD Study Design Primary Safety Endpoint follow-up* Week -24 -20 -16 -12 -8 -4 R 2:2:1 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 … 72 … Evaluation OTX-TKI Visits (0.45 mg) SOL-R Aflibercept Q8W Q8W End of (2 mg) year 2 Loading Aflibercept (8 mg) Randomization Monthly Visits (Day 1) S
Slide 122: Further Insights Utilizing SOL-R Rescue Criteria to the SOL Program
Further Insights Utilizing SOL-R Rescue Criteria to the SOL Program SOL-R Rescue Treatment Criteria BCVA loss >5 ETDRS letters from best recorded BCVA AND ≥75 µm increase in CSFT from lowest measure OR New macular hemorrhage that would likely lead to irreversible vision loss if left untreated in the
Slide 123: Key Insights
Key Insights OTX-TKI SHOWS SUPERIOR Durability Vision Outcomes Anatomic Control (rescue-free rates) Future studies should consider superiority trial design 123
Slide 124: Defined Regulatory Strategy
Defined Regulatory Strategy Jeffrey S. Heier, MD 124
Slide 125: Next Steps: 505(b)(2)
Next Steps: 505(b)(2) 505(b)(2) Pathway • New drug application for approval of drugs that are similar to, but not identical, to previously approved drugs • Allows reliance on established safety and efficacy • Accelerates approval for new formulations, dosages, route of administration or indications
Slide 126: One Pivotal Trial for NDA: The New Default
One Pivotal Trial for NDA: The New Default Factors that contribute to strength of submission • Statistical significance • Mechanistic science • Blinding/masking • Alignment with the FDA • Supporting secondary data Prasad V, Makary MA, N Engl J Med. 2026;394(8):815-817 126
Slide 127: Panel Discussion
Retina experience THERAPEUTIX redefined OCULAR
Slide 128: Faculty
Faculty Mark R. Barakat, MD Dilsher S. Dhoot, MD Jeffrey S. Heier, MD Peter K. Kaiser, MD Founder and Director of Clinical Vitreoretinal Specialist, Chief Scientific Officer, Chief Development Officer, Research, Retina Macula Institute California Retina Consultants, Ocular Therapeutix, Inc. Ocular T
Slide 129: Redefining the Management of Neovascular AMD
Redefining the Management of Neovascular AMD February 27, 2026 49th Annual Macula Society Meeting | Coronado, CA
Ocular Therapeutix — 49th Annual Macula Society Meeting 2026 on 6ix