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Forward-Looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words "may," "will," "could," "would," "should," "expec

Key Takeaway: Corporate Presentation | June 2021 Forward-Looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words "may," "will," "could," "would," "should," "expect," "plan," "anticipat

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Corporate Presentation | June 2021
Forward-Looking Statements This
presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words "may," "will," "could," "would," "should,"
"expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue,"
"target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Clearside Biomedical, Inc.'s views as of the date of this
presentation about future events and are subject to risks, uncertainties, assumptions, and changes in circumstances that may cause Clearside's actual results, performance, or achievements to differ significantly from those expressed or implied
in any forward-looking statement. Although Clearside believes that the expectations reflected in the forward-looking statements are reasonable, Clearside cannot guarantee future events, results, performance, or achievements. Some of the key factors
that could cause actual results to differ from Clearside's expectations include its plans to develop and potentially commercialize its product candidates; Clearside's planned clinical trials and preclinical studies for its product
candidates; the timing of and Clearside's ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Clearside's product candidates; the clinical utility and
market acceptance of Clearside's product candidates; Clearside's commercialization, marketing and manufacturing capabilities and strategy; Clearside's intellectual property position; and Clearside's ability to identify
additional product candidates with significant commercial potential that are consistent with its commercial objectives. For further information regarding these risks, uncertainties and other factors you should read the "Risk Factors"
section of Clearside's Annual Report on Form 10-K for the year ended December 31, 2020, filed with the SEC on March 15, 2021, and Clearside's other Periodic Reports filed with the SEC. Clearside expressly disclaims any obligation to
update or revise the information herein, including the forward-looking statements, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by Clearside relating to market size
and growth and other data about its industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of Clearside's
future performance and the future performance of the markets in which Clearside operates are necessarily subject to a high degree of uncertainty and risk.
Versatile Therapeutic Platform SCS
Microinjector with proprietary drug formulations target the Suprachoroidal Space Proprietary Access to the Suprachoroidal Space (SCS ) Utilization Across Small Molecules and Gene Therapy Ability to Target Multiple Ocular Diseases Internal
Research & Development Pipeline External Collaborations for Pipeline Expansion Developing and Delivering Treatments that Restore and Preserve Vision for People with Serious Back of the Eye Diseases
Core Advantages of Treating Via the
Suprachoroidal Space Sources: Rai UDJ, Young SA, Thrimawithana TR, et al. The suprachoroidal pathway: a new drug delivery route to the back of the eye. Drug Discov Today. 2015;20(4):491-495. | Moisseiev E, Loewenstein A, Yiu G. The suprachoroidal
space: from potential space to a space with potential. Clin Ophthalmol. 2016;10:173-178. | Chiang B, Jung JH, Prausnitz MR. The suprachoroidal space as a route of administration to the posterior segment of the eye. Adv Drug Deliv Rev.
2018;126:58-66. TARGETED The back of the eye is the location of many irreversible and debilitating visual impairments BIOAVAILABLE & PROLONGED DRUG LEVELS Fluid spreads circumferentially and posteriorly when injected within the suprachoroidal
space, bathing the choroid and adjacent areas with drug COMPARTMENTALIZED Drug is compartmentalized in the suprachoroidal space, which helps keep it away from non-diseased tissues and entirely behind the visual field for efficacy for safety for
Administration of any drug to the
suprachoroidal space by microinjection Administration of any drug to the eye by inserting a microinjector into the sclera SCS Microinjector features Methods of using SCS Microinjector for drug delivery Device using an adjustable needle Pioneers in
the Suprachoroidal Space (SCS ) with Patented Technology DEVICE PATENTS DRUG PATENTS Methods of treating posterior ocular disorders by SCS administration DISEASE PATENTS Key Intellectual Property Components Comprehensive IP portfolio that
includes protection of: SCS delivery technology, proprietary SCS Microinjector, treatment of various conditions with SCS administration of therapeutic products 24 U.S. and >50 European and International issued patents with multiple pending patent
applications Granted patents provide exclusivity for our delivery technology and product candidates to mid-2030s with pending applications potentially extending exclusivity beyond 2040
Clearside's SCS Microinjector :
The Only Clinically Tested Injection Device for Suprachoroidal Drug Delivery Clinically tested in >1200 suprachoroidal Injections 8 clinical trials completed Injections performed across multiple retinal disorders Safety profile comparable to
intravitreal injections1 No Serious Adverse Events (SAEs) involving lens injury, suprachoroidal hemorrhage, or endophthalmitis have been observed 4 clinical trials ongoing including partner programs SUPRACHOROIDAL SPACE INJECTION Novel SCS
Microinjector allows for precise delivery into the suprachoroidal space Sources: Clearside data on file | 1Kurup, et. al, Macula Society 2021 Safety of the Suprachoroidal Injection Procedure Utilizing SCS Microinjector across Three
Exclusive Access to the Back of the Eye
Using Clearside's Proprietary SCS Microinjector
CLS-AX Delivered with SCS
Microinjector for Wet AMD
Suprachoroidal Space (SCS )
Injection Platform PARTNER THERAPEUTC ENTITY INDICATION IND-Enabling PHASE 2 PHASE 3 NDA REGENXBIO AAV-based Gene Therapy Wet AMD (AAVIATE) REGENXBIO AAV-based Gene Therapy Diabetic Retinopathy (ALTITUDE) AURA BIOSCIENCES Viral-like Drug Conjugate
Ocular Oncology/Choroidal Melanoma XIPERE (triamcinolone acetonide suprachoroidal injectable suspension) is an investigational product SCS Microinjector Partner Programs XIPERE Commercial Partners PARTNER THERAPEUTC ENTITY
TERRITORY PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 NDA BAUSCH HEALTH Small Molecule U.S. & Canada; options ex-North America ARCTIC VISION Small Molecule Greater China & South Korea PROGRAM THERAPEUTC ENTITY INDICATION RESEARCH PRECLINICAL PHASE
1/2 PHASE 3 CLS-AX (axitinib injectable suspension) Small Molecule Wet AMD Integrin Inhibitor (Injectable suspension) Small Molecule Diabetic Macular Edema (DME) Gene Therapy Non-Viral Vectors "Therapeutic Biofactory" / Inherited Retinal
Disease Internal Development Pipeline PDUFA 10/30/21
Macular edema is the leading cause
of vision loss in patients with non-infectious uveitis NDA was resubmitted and accepted for review with PDUFA goal date of October 30, 2021 Commercialization and development partnerships to enhance value and expand patient access XIPERE :
Potential Suprachoroidal Approach to Treating Uveitic Macular Edema XIPERE is an investigational product If approved, XIPERE would represent the FIRST therapy for macular edema associated with uveitis FIRST uveitis trial using visual acuity
change as a primary endpoint (Phase 3 PEACHTREE) FIRST approved therapeutic delivered into the suprachoroidal space FIRST commercial product for Clearside
Sources for in-vitro IC50 range:
Stellato et al. J Allergy Clin Immol. 1999 volume 104, number 3, part 1 | Yuan et al. Haematologica 2017 Mar, 102(3) 466-475 | Inlyta, EMA 2012 May; CHMP assessment report | 2014 R13 HAE conference, Che, Wilson, Babu, Preclinical Characterization of
BCX4161, an oral plasma kallikrein inhibitor, for the treatment of Hereditary Angioedema. Preclinical Data Supports Durability Potential of Small Molecule Suspensions Delivered into the Suprachoroidal Space
CLS-AX (axitinib injectable
suspension) for Suprachoroidal Injection
AMD causes a progressive loss of
central vision and is the most common cause of blindness in individuals over age 55 Neovascular or Wet AMD accounts for the majority of blindness U.S. prevalence expected to increase to 22 million by the year 2050 Global prevalence expected to
increase to 288 million by the year 2040 Current treatments require frequent injections causing reduced compliance Under-treatment contributes to limited outcomes Age-Related Macular Degeneration (AMD) A large and growing market opportunity Sources:
Medscape: F Ryan Prall, MD, et al Assistant Professor of Ophthalmology, Indiana University School of Medicine | Pennington, Katie L and DeAngelis, Margaret M Eye and Vision, Epidemiology of age-related macular degeneration (AMD): associations with
cardiovascular disease phenotypes and lipid factors , Dec 22, 2016. 170 million patients worldwide 10-20% patients wet AMD 11 million U.S. Patients
Ceiling of efficacy Treatment burden
Limited outcomes with current regimens CURRENT THERAPY On-label dosing involves fixed frequent injections With on-label anti-VEGF dosing, at 1 year1-3: ~1/5 of patients lose BCVA ~1/2 do not achieve 20/40 ~2/3 do not gain 3 lines
BCVA In clinical trials, more intensive anti-VEGF regimens or dosage yield no additional BCVA benefit1,6,7 In clinical practice, patients cannot maintain intensive on-label dosing and are undertreated, improving by only 1-3 letters at 1 year4,5
Undertreatment and limited real-world outcomes Current Wet AMD Therapies Lead to Under-Treatment and Limited "Real-World" Clinical Outcomes Sources: 1. Heier JS et al. Ophthalmology. 2012;119:2537-2548. | 2. Brown DM et al.
Ophthalmology. 2009;116:57-65.e5. | 3. Rosenfeld PJ et al. N Engl J Med. 2006;355:1419-1431. | 4. Ciulla TA et al. Ophthalmology Retina. 2019 May 25. pii: S2468-6530(19)30280-5. | 5. Rao P, Lum F, Wood K, et al. Ophthalmology. 2018;125:522e528. | 6.
Busbee BG et al. Ophthalmology. 2013;120:1046-1056. | 7. Schmidt-Erfurth U et al. Ophthalmology. 2014;121:193-201.
CLS-AX (axitinib injectable
suspension) for Suprachoroidal Injection in wet AMD Proprietary CLS-AX suspension formulation Potential to improve the treatment landscape for wet AMD patients Longer lasting treatment may reduce patient burden from monthly injections Targeted high
levels to affected choriod-retina for potential efficacy benefits Protecting the vitreous and anterior chamber may eliminate symptomatic floaters and other side effects Given experience with >1200 injections, may be easily adopted in current
clinical practice Axitinib is a tyrosine kinase inhibitor (TKI) Delivery via proprietary SCS Microinjector High potency and pan-VEGF attributes of TKI axitinib
Axitinib: a Highly Potent, pan-VEGF
TKI to Treat Wet AMD Axitinib's intrinsic pan-VEGF inhibition through receptor blockade Approved treatments are focused VEGF-A inhibitors Inhibits VEGFR-1, VEGFR-2, VEGFR-3 receptors More effective than anti-VEGF-A in in-vitro angiogenesis
model1-2 Highly potent tyrosine kinase inhibitor (TKI) >10x more potent than other TKIs in preclinical studies Better ocular cell biocompatibility than other TKIs3 More effective than other TKIs for experimental corneal neovascularization in
preclinical models Preclinical data showed axitinib inhibition and regression of angiogenesis Sources: 1. Cabral T et al. Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol
Retina. 2018 January ; 2(1): 31-37. doi:10.1016/j.oret.2017.04.004. | 2. Lieu et al. The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer. PLoS ONE 8(10): e77117. | 3. Theile et
al. Multikinase Inhibitors as a New Approach in Neovascular Age-Related Macular Degeneration (AMD) Treatment: In Vitro Safety Evaluations of Axitinib, Pazopanib and Sorafenib for Intraocular Use. Klin Monatsbl Augenheilkd 2013; 230: 247-254. | Image
by Mikael H ggstr m, used with permission. H ggstr m, Mikael (2014). "Medical gallery of Mikael H ggstr m 2014". WikiJournal of
Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.
Suprachoroidal Injection of CLS-AX
Provides Targeted Delivery Relative to Intravitreal Injection at Same Dose 11x SCS vs IVT Retina / RPE-choroid-sclera 0.003X SCS vs IVT Vitreous humor Aqueous Humor SCS CLS-AX at or below level of detection Rabbit Model Values: area under the curve
ratios, SCS / IVT SCS : 1 mg/eye, 100 L. | IVT: 1 mg/eye, 25 L Single bilateral injection, 1-wk rabbit PK studies Plasma SCS CLS-AX at or below level of detection Source: Based on Clearside Biomedical preclinical data Abbreviations: SCS:
Suprachoroidal Space | IVT: Intravitreal Injection | PK: Pharmacokinetic | LLOQ: lower limit of quantification, 0.15 mg/mL | RPE: Retinal pigment epithelium Concentration (nM) High Retina Levels: Sufficient to block VEGF pathway Low Plasma Levels:
<1 ng/mL Time (days) CLS-AX: High, Sustained Drug Levels in the Retina after SCS Administration
CLS-AX has Potential for Meaningful
Durability Therapeutic Levels > IC50 for 6 months after 1.05 mg/eye SC Injection in Rabbits Rabbit toxicology study with single bilateral suprachoroidal injection of axitinib, 1.05 mg/eye (n=4 eyes/ timepoint) On day 182, mean axitinib levels in
the RPE-choroid-sclera (199 g/gm) and in the retina (1.1 g/gm) were 3-5 log orders higher than the in-vitro IC50 value (0.2 ng/mL, VEGFR2 autophosphorylation inhibition assay). Based on this IC50 value, therapeutic levels were achieved
in the RPE-choroid-sclera and retina for 6 months after a single suprachoroidal injection of axitinib in rabbits. Source: Translational Vision Science & Technology, 2021, in press.
CLS-AX Has the Potential to Improve
Current Wet AMD Treatment SCS Delivery May Synergistically Enhance Pan-VEGF Effect SAFETY EFFICACY TREATMENT BURDEN Well characterized small molecule Potential for less immune response & inflammation vs biological products Better compatibility
with retinal pigment epithelial cells vs other TKIs AXITINIB SUPRACHOROIDAL DELIVERY Compartmentalized SCS drug delivery potentially results in few anterior AEs Favorable tolerability profile of SCS Microinjector in >1200 patient injections Use
of SCS Microinjector is well accepted by physician-investigators Shows pan-VEGF inhibition Pan-VEGF inhibition shows greater effect preclinically & clinically Regresses neovascularization preclinically >10x the in-vitro potency vs. other TKIs
Current anti-VEGF agents only target VEGF-A Targets drug to the diseased chorioretinal tissue in wAMD Shows up to 11x higher drug levels vs intravitreal administration Shown prolonged duration in preclinical studies Potential to have less frequent
dosing compared to current anti-VEGF products which may: Limit undertreatment by facilitating better compliance Further enhance clinical outcomes Sources: Clearside Biomedical preclinical and clinical studies | Cabral T et al. Bevacizumab Injection
in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol Retina. 2018 January ; 2(1): 31-37. doi:10.1016/j.oret.2017.04.004. | Lieu et al. The Association of Alternate VEGF Ligands with
Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer. PLoS ONE 8(10): e77117. | Theile et al. Multikinase Inhibitors as a New Approach in Neovascular Age-Related Macular Degeneration (AMD) Treatment: In Vitro Safety Evaluations of
Axitinib, Pazopanib and Sorafenib for Intraocular Use. Klin Monatsbl Augenheilkd 2013; 230: 247-254.
CLS-AX Phase 1/2a Clinical Trial in
Wet AMD 2 mg aflibercept dosed at screening CLS-AX dosed at baseline (30 days post screening) Cohort Enrollment and Treatment Open-label study to evaluate safety and tolerability of escalating single doses of CLS-AX administered through
suprachoroidal injection following IVT aflibercept 3 Cohorts of 5 patients each: n=15 Dose-escalation of CLS-AX (in mg): Cohort 1 at 0.03; Cohort 2 at 0.10; Cohort 3 currently planned at 0.30 Evaluate visual function, ocular anatomy, and need for
additional treatment Assessment for additional therapy: loss from best measurement of >10 letters in BCVA with exudation; increase in CST >75 microns; a vision-threatening hemorrhage Trial Design and Objectives Note: aflibercept is dosed via
intravitreal injection (IVT); CLS-AX is dosed via suprachoroidal injection | clinicaltrials.gov NCT# 04626128 Assessment for additional therapy Assessment for additional therapy Assessment for additional therapy Screening Baseline Week 4 Week 8 Week
Cohort 1 Objective: To establish a
floor of safety in this first-in-human trial with low dose CLS-AX (0.03 mg dose) Patients: Highly treatment-experienced Total number prior anti-VEGF treatments: mean = 25.8, median = 28.0 Total number prior anti-VEGF treatments within the last 12
months: mean = 9.0, median = 11.0 Conclusion Cohort 1 supports progression to Cohort 2 Cohort 1: Encouraging Results Support Progression to Cohort 2 Source: Clearside data on file.
Last updated: Jun 15, 2021