Suprachoroidal Space Drug Delivery July 24, 2024 Exhibit 99.1
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Agenda 01 02 03 04 05 Versatility of Suprachoroidal Delivery George Lasezkay, PharmD, JD, Clearside President & CEO Real World Use of Suprachoroidal Delivery Glenn Yiu, MD, PhD, Professor of Ophthalmology, University of California, Davis Pipeline Opportunities Victor Chong, MD, MBA, Clearside Chief Medical Officer Large Practice View of Suprachoroidal Delivery David Brown, MD, Director of Research, Retina Consultants Houston Q&A
GEORGE LASEZKAY, PharmD, JD Clearside President & Chief Executive Officer Versatility of Suprachoroidal Delivery 4
Delivering on the Potential of the Suprachoroidal Space Proven Leader in Suprachoroidal Delivery with Thousands of Injections Performed Validated Technology with Approved Product, Multiple Collaborations, and Comprehensive IP Portfolio Differentiated Clinical Program Targeting Multi-Billion Dollar Wet AMD Market with Phase 2b Trial Data Expected in Late Q3 2024 5
Proven Leader in Suprachoroidal Delivery Formulation Expertise Proprietary Microinjector with Significant Clinical Experience ISO Certified Commercial Scale Injector Manufacturing Capability Experience in Navigating the Drug/Device Regulatory Pathway 1st FDA Product Approved for SCS Administration Permanent CPT Code Granted for SCS Injections
Diverse Programs Using Clearside’s Suprachoroidal Injection Platform 1XIPERE® (triamcinolone acetonide injectable suspension), for suprachoroidal use has received U.S. FDA Approval and is being commercialized by Bausch + Lomb. 2In China, Arctic Vision is responsible for clinical development of ARCATUS™ (triamcinolone acetonide injectable suspension), formerly referred to as ARVN001, and known as XIPERE® in the U.S. Clearside Developed Programs THERAPEUTIC TYPE INDICATION IND-ENABLING PHASE 1 PHASE 2 PHASE 3 APPROVAL PARTNER Bel-Sar Viral-like Drug Conjugate Choroidal Melanoma ABBV-RGX-314 AAV Gene Therapy Diabetic Retinopathy (DR) ABBV-RGX-314 AAV Gene Therapy Wet AMD Avoralstat Plasma Kallikrein Inhibitor Diabetic Macular Edema (DME) SCS Microinjector® Partner Clinical Development Programs THERAPEUTIC TYPE INDICATION IND-ENABLING PHASE 1 PHASE 2 PHASE 3 APPROVAL PARTNER CLS-AX (axitinib): Tyrosine Kinase Inhibitor Wet AMD XIPERE® Corticosteroid (Triamcinolone Acetonide) Uveitic Macular Edema1 (U.S. & Canada) XIPERE® / ARCATUS™ Corticosteroid (Triamcinolone Acetonide) Uveitic Macular Edema2 Diabetic Macular Edema2 (Asia Pacific ex-Japan) XIPERE® / ARCATUS™ Corticosteroid (Triamcinolone Acetonide) Phase 2b ALTITUDE AAVIATE UME DME CoMpass
GLENN C. YIU, MD, PhD Professor of Ophthalmology, University of California, Davis Real World Use of Suprachoroidal Delivery 8
Jung et al., Drug Discovery Today, 2019 Naftali & Moisseiev, Pharmaceutics, 2021 Suprachoroidal Drug Delivery Accessing the suprachoroidal space Microneedle Microcatheter orbitsds.com clearsidebio.com 9
Suprachoroidal Drug Delivery OCT shows SCS expansion after SC injection in humans Baseline 1 mo 2 mo 3 mo Suprachoroidal Space * * * 10 Lampen et al. OSLI Retina, 2018 Yiu et al., Am J Ophthalmol, 2018
N = 160 patients with uveitic CME Suprachoroidally injected CLS-TA vs. sham (3:2) at day 0 & week 12 Phase 3 PEACHTREE study Uveitic ME Phase 2 TANZANITE study RVO + CME Phase 1/2 HULK study DME Phase 1/2 OASIS study nAMD Phase 1/2 HULK study DME Phase 2 TANZANITE study RVO + CME Phase 1/2 OASIS study nAMD 11 Yeh et al., Ophthalmology, 2020 Suprachoroidal Drug Delivery Suprachoroidally injected triamcinolone acetonide (CLS-TA) for uveitic ME
Suprachoroidal Drug Delivery IRIS study of real-world durability of suprachoroidally injected triamcinolone acetonide for uveitic ME Dates: Jan 2022 to Jun 2023 Index date: first suprachoroidal triamcinolone acetonide injection Rescue: any injectable, implanted, or topical cortical steroids Follow-up: 24 weeks Age ≥18 years Diagnosis of non-infectious UME Suprachoroidal injection of triamcinolone acetonide IRIS® Registry (Intelligent Research in Sight) linked to Komodo open-source claims data using the Datavant token to identify corticosteroid use Inclusion criteria Study Design 12 Singer, et al. Macula Society 2024. Durability with suprachoroidal injection of triamcinolone acetonide injectable suspension for uveitic macular edema and use of rescue therapy in clinical practice.
Suprachoroidal Drug Delivery Study demographics & comorbidities Abbreviations: DR, diabetic retinopathy; DME, diabetic macular edema; ME, macular edema; CRVO, central retinal vein occlusion; BRVO, branch retinal vein occlusion Abbreviations: SD, standard deviation * This was only evaluated in the 786 patients whose data could be linked to claims 41.8% of patients had glaucoma or ocular hypertension prior to suprachoroidal injection of triamcinolone acetonide 13
Suprachoroidal Drug Delivery Time to rescue with injectable / implantable corticosteroid 100% 80% 60% 40% 20% 0% Weeks IRIS data In PEACHTREE 86.5% did not require rescue therapy by week 24 *In PEACHTREE, all subjects had a second injection at week 12 * PEACHTREE trial Kaplan Meier Estimate 87.7% of eyes did not require an injected or implanted corticosteroid by week 24 14
Suprachoroidal Drug Delivery Types of injected / implanted rescue therapy Fluocinolone acetonide intravitreal implant (0.18mg), 0.8% Fluocinolone acetonide intravitreal implant (0.59mg), 0.8% Subtenon triamcinolone acetonide, 9.8% Dexamethasone intravitreal implant, 21.3% 15
Suprachoroidal Drug Delivery Time to rescue with any corticosteroid (including topical) 100% 80% 60% 40% 20% 0% Weeks Kaplan Meier estimate from IRIS data 75.4% of eyes did not require any corticosteroid by week 24 16
Suprachoroidal Drug Delivery Patient considerations for suprachoroidal injections High myopia or axial length Known scleral thinning History of glaucoma or hypotony History of ocular surgery (esp. trabeculectomy or glaucoma shunt) Patient Selection Sensation of “pressure wave” Longer duration of procedure Possible change in needle or injection site Patient Expectations Patient in supine position with head support Topical or subconjunctival anesthetic Povidone-iodine antiseptic Lid speculum recommended Patient Preparation 17 Wykoff CC, Avery RL, Barakat MR, Boyer DS, Brown DM, Brucker AJ, Cunningham ET, Heier JS, Holekamp NM, Kaiser PK, Khanani AM, Kim JE, Demirci H, Regillo CD, Yiu G, Ciulla TA. Suprachoroidal Space Injection Technique: Expert Panel Guidance. Retina | Image courtesy of Bausch & Lomb
Suprachoroidal Drug Delivery Needle lengths & injection locations Two needle lengths: 900 mm & 1,100 mm Preferred locations: Superotemporal or Inferotemporal 18 Image courtesy of Bausch & Lomb
Suprachoroidal Drug Delivery Suprachoroidal injection technique Hold the microinjector perpendicular to the ocular surface Ensure firm contact with sclera by maintaining a dimple throughout injection Inject slowly over 5 – 10 seconds Perpendicular Dimple Slow 19 Images courtesy of Bausch & Lomb
Suprachoroidal Drug Delivery Gene Therapy Drug Development for Geographic Atrophy To date, intravitreal biologics have failed in geographic atrophy (GA) Biofactory gene therapy uses retinal cells to produce biologics Intravitreal delivery: gene therapy mostly transfects transfects inner retina and non retinal cells, so would be similar to intravitreal biologics Subretinal delivery: even for wet AMD, it has been difficult for patient acceptance; therefore, may be even more difficult for GA without foveal involvement and good vision Suprachoroidal delivery: could be the preferred way to go 20
Conclusion Key Takeaways SCS Microinjector® enables targeted in-office delivery to the suprachoroidal space Clearside is the leader with FDA-approved product, XIPERE® (triamcinolone acetonide injectable suspension), for suprachoroidal use to treat uveitic macular edema Durability of suprachoroidally injected triamcinolone acetonide in the real-world is comparable to Phase 3 trial results, with only ~12% needing subsequent corticosteroid within 24 weeks Suprachoroidal delivery represents a new and innovative technique that has many potential applications beyond delivering steroids, including angiogenesis inhibitors and gene therapies 21 Singer, et al. Macula Society 2024. Durability with suprachoroidal injection of triamcinolone acetonide injectable suspension for uveitic macular edema and use of rescue therapy in clinical practice.
VICTOR CHONG, MD, MBA Clearside Chief Medical Officer Pipeline Opportunities 22
Benefits for Patients and Physicians Using SCS Microinjector® Delivery Enhanced Safety Much lower risk of endophthalmitis as direct contact to immune system vs intravitreal injection Injectate Flows to Back of the Eye Reduced risk of floaters, snow globe effect, or other visual disturbances No Implants or Devices in the Vitreous Can be easily re-dosed for potentially longer durability Injection Similar to Intravitreal Advanced technology requires only a few seconds longer for each injection
Competitive Advantage in Needle Gage Diameter 22G 25G 30G Outer Diameter of the Needle Relative to the Ocular Tissue Inner Diameter of the Needle Drug Product Passage 30G needle results in less damage to the ocular tissue wound size to the ocular tissue is >4x greater with 22G Needle >2x greater with 25G Needle Clearside SCS Microinjector® Gustavo Barreto Melo, et al. Progress in Retinal and Eye Research. “Critical analysis of techniques and materials used in devices, syringes, and needles used for intravitreal injections”. https://doi.org/10.1016/j.preteyeres.2020.100862
CLS-AX: Wet AMD Clinical Development Program
Leveraging a Highly Potent Pan-VEGF Inhibitor with Suprachoroidal Delivery Axitinib High potency TKI with pan-VEGF inhibition Proprietary CLS-AX Suspension Formulation Clearside formulation expertise Delivery via SCS Microinjector® Compartmentalization may eliminate treatment related floaters, haze, and anterior segment side effects Utilizes the same device as FDA-approved product XIPERE® 01 02 03 CLS-AX
Key CLS-AX Program Features Differentiated Approach to Targeting Wet AMD Utilizes the same SCS Microinjector device as FDA-approved product XIPERE Competitors’ delivery devices differ from their approved products Objective is to maintain efficacy and reduce the number of injections and required visits Reduced treatment burden benefits patients, caregivers and payors with improved outcomes Opportunity for treatments that may have longer duration of action in multi-billion-dollar market 2 - 3x/year maintenance dosing compared to approved drugs*: Re-dosing incorporated in Phase 2b design to provide insight for Phase 3 program Allowing re-dosing comparable to VABYSMO® and EYLEA HD® in real-world setting Potential CLS-AX Competitive Advantages LUCENTIS®: 12x/year | VABYSMO®: 3 - 6x/year EYLEA®: 6x/year | EYLEA HD®: 3 - 4x/year *Dosing regimens are per respective product labels | EYLEA® and EYLEA HD® are registered trademarks of Regeneron Pharmaceuticals| LUCENTIS® and VABYSMO® are registered trademarks of Genentech/Roche CLS-AX target profile: maintain visual acuity without need for retreatment for potentially up to 6 months
* Disease Activity Assessments (DAA): Conducted at Week 12 through 32 to determine need for supplemental treatment. # In CLS-AX arm, following 3 loading doses of aflibercept and initial dose of CLS-AX at Baseline, participants will receive CLS-AX at least every 24 weeks unless more frequently required based on DAA; if disease is active and participant is <12 weeks since last CLS-AX injection, participant receives dose of aflibercept; if disease is active and participant is >12 weeks since last CLS-AX injection, participant receives dose of CLS-AX. ^ In aflibercept arm, following 3 loading doses of aflibercept, participants will receive aflibercept on fixed dosing regimen every 8 weeks unless more frequently required based on DAA; if disease is active, participant receives dose of aflibercept. CLS-AX 1.0 mg Flexible dosing N=40 Aflibercept 2 mg Fixed dosing every 8 weeks N=20 VISIT 1 2 3 4 5 6 7 8 9 10 11 WEEK -6 -4 Day 1 4 12 16 20 24 28 32 36 + + Primary Outcome Disease Activity Assessments* Baseline 2:1 Randomization Sham Procedure CLS-AX 1.0 mg Suprachoroidal Injection (SCS) Aflibercept 2 mg Intravitreal Injection (IVT) Screening visit Required aflibercept dose every 8 weeks^ Multiple Dosing Requirement To Help Inform Phase 3 Development Program Required CLS-AX dose (if not given prior) #Participants can be re-dosed with CLS-AX up to every 12 weeks Participants can be re-dosed with CLS-AX at Weeks 12, 16, 20, if needed, based on DAA# Participants can be re-dosed with aflibercept at Weeks 16, 24, 32, if needed, based on DAA
ODYSSEY Phase 2b Key Differences Every patient in the CLS-AX group will be re-dosed at least once Re-dosing with CLS-AX 36 Week Treatment Duration Anticipated primary endpoint duration of Phase 3 wet AMD study based on FDA draft guidance Other longer duration therapies (other TKIs, gene therapy) need rescue with anti-VEGF Harder to implement in clinical practice as patients do not want to come in for a scan every 4 weeks as in clinical trials
ODYSSEY Update All participants in the study have completed 6 months of treatment Participants in the CLS-AX arm have received two doses of CLS-AX per protocol In July 2024 meeting, the ODYSSEY Safety Review Committee (SRC) reviewed masked safety data and recommended that the trial continue as planned without modifying the protocol or unmasking of the participants SRC noted that there have been no drug-related Serious Adverse Events (SAEs) in masked study treatments observed to date, including no endophthalmitis or retinal vasculitis On-track to release top-line data in late Q3 2024
Our Target Success Measures for ODYSSEY No drug related ocular Severe Adverse Events Majority of participants reach Week 24 without re-treatment BCVA changes from baseline similar at all visits in particular at Week 24 and Week 36 CST changes from baseline similar at all visits in particular at Week 24 and Week 36
Pipeline Expansion Opportunity in Geographic Atrophy
Pathology of Age-Related Macular Degeneration (AMD) Wong JHC et al., Front Neurosci 16: 1009599
Choroidal Hypoxia Theory and Choriocapillaris are Damaged First Geographic Atrophy is a Choroidal Disease Choriocapillaris endothelial cells damage with ghost vessels before any significant RPE changes Choriocapillaris (CC) vascular density is significantly lower in GA donor No meaningful differences in vascular lumen area / stroma area 1 VEGF level increased with low vascular density support the choroidal hypoxia theory 2 3 RPE = Retinal Pigment Epithelium Images modified from Sohn EH et al., Am J Path 2019: 189: 1473-80
Larger molecules cannot get through Bruch’s membrane So, if given intravitreally, it can only treat the RPE side Aging intensifies disease actions and even peptides might not be able to get through Small Molecule Can Access the Diseased Area of the RPE and Choroid Images modified from Hammadi et al JCM 2023, 12 (8), 2870 Bruch’s membrane
Suprachoroidal Administration Could Be Preferred Delivery Method Setting Distribution Deliver large molecules Deliver small molecules Gene therapy Suprachoroidal Office Posterior segment Not used Suspension RPE and Choroid Intravitreal Office Widespread in eye Standard Implant Mostly ganglion cells Subretinal Operating room Localized to treatment bleb Not used Not used Photoreceptor and RPE Systemic Home Whole body Need injection Oral Liver Images modified from Kasetty VM et al. Retinal Physician Aug 1, 2022, 19-23
Potential Target Product Profile (TPP) Aligns with SCS Suspension or SCS Gene Therapy Potential Advantages of Suprachoroidal Delivery in Geographic Atrophy Less invasive, in-office procedure Systemic therapy may be effective, but potential infection risks in this elderly population Local ocular therapy may have fewer adverse events Small molecules may have better efficacy than current therapies Potential to treat complement activation in both RPE and choroid Suprachoroidal suspension/gene therapy may have longer duration (3 to 6 months) Intravitreal gene therapy may not achieve efficacy Subretinal has additional risks Targeted delivery compartmentalized to the posterior segment Potentially fewer adverse events Able to reach the choroid first Fluid spreads circumferentially and posteriorly when injected within the suprachoroidal space, bathing the choroid, RPE, retina and adjacent areas with drug
Traditional Target Pathways for Geographic Atrophy Holz FG et al. Ophthalmology 2014, 1079-91 Choroidal perfusion Complement Genetic risk HTRA1 Mast cell microglia, macrophage Neuro protection Lipids oxidation Lipo fuscin
DAVID M. BROWN, MD Director of Research, Retina Consultants Houston Large Practice View of Suprachoroidal Delivery 39
Suprachoroidal (SCS) Timeline Intravitreal (IVT) Timeline Patient Travel: 45min round trip Exam: 15min Imaging: 15min Set-Up Anesthesia Sterile Prep (2min) Post Injection (0.5min) Injection as Percentage of Total Time: 0.57%* 5min 5min Injection (0.5 min) Injection (1.0 min) 30 sec increase in doctor’s time performing procedure Injection as Percentage of Total Time: 1.1%# IVT vs SCS Procedure Time Comparison in Optimized High-Volume Practice Patient Travel: 45min round trip Exam: 15min Imaging: 15min 5min 5min *IVT Injection as % of Total Time: 0.5 min / (45 + 15 + 15 + 5 + 5 + 2 + 0.5 + 0.5) min = 0.57% #SCS Injection as % of Total Time: 1.0 min / (45 + 15 + 15 + 5 + 5 + 2 + 1.0 + 0.5) min = 1.1%
Understanding wet AMD patients have variable dosing frequency requirements Aflibercept 8mg and Faricimab extension criteria are not typically used in clinical practice However, physicians are using them as a replacement of other anti-VEGF in Treat and Extend Ideal Phase 3 design for longer duration wet AMD therapy Re-treatment extension criteria closer to clinical practice Treatment naïve patients: to allow more direct comparison to established therapy Learning from Phase 3 Designs of Aflibercept 8mg and Faricimab
Discussion with Dr. Brown 42
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