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Rethinking Ophthalmology INVESTOR WEBCAST April 13, 2023 3
Inventor webcast agenda Opening remarks Sylvia Cheung, CFO Company
presentation Dr. Riad Sherif, CEO Sylvia Cheung, CFO Discussions with KoL's Dr. Pravin Dugel Dr. Arshad Khanani Dr. Eric Donnenfeld Q&A Pall Johannesson, CSO Closing remarks Riad Sherif, CEO 44
Our Purpose To drive innovation to save sight and improve eye care
Unmet needs and substantial rise in visual impairments Underpinning
demand for ophthalmic innovations Driven by three key areas: A growing At least 2.2 billion people Retina $22+bn have a vision impairment, and (1) of these, at least 1 billion Market ~196m (1) people have a vision with age-related ~146m impairment
that could have macular with diabetic Rising sharply due to degeneration been prevented or is yet to be retinopathy addressed. changes in: Glaucoma Aging Population Dry Eye (1) Diabetes Epidemic ~80m Dr Tedros Adhanom Ghebreyesus and
10% leading (2) Lifestyle Changes to blindness ~1.4BN Director-General WHO WHO Vision report, 2019 Living with dry eye (1) WHO: https://apps.who.int/iris/rest/bitstreams/1257940/retrieve. (2) Source: Market Scope: 2020 Dry Eye Products
Building a world leader in ophthalmology Possible Effects of DME Normal
Vision Poised to Breakthrough Key unmet deliver innovations medical needs Ophthalmology experienced A leading and Strategic presence in key markets and with a solid differentiated portfolio of maximizing success track record of success life-changing
therapies OCS-01 in Diabetic Macular Breakthrough innovations Edema (DME) developed specifically to create a step shift in the treatment of ocular disease Neuro Ophtha. Retina and vision loss. DED 1 77
Uniquely positioned to build significant value st OCS-01: 1
Retina eye-drop for Diabetic Macular Edema (DME) in Ph3 Targeting critical unmet needs in 3 major st OCS-02: 1 Biologic eye-drop for Dry Eye Disease (DED) in Ph2b ophthalmology segments (upside potential from biomarker-driven precision
medicine approach) st OCS-05: 1 Neuroprotective agent for neuro-retina treatments in PoC 2023 2024 Near-term value inflection points expected OCS-01 DME Phase 3 (Stage 1) readout OCS-01 Ocular Surgery NDA (1) OCS-01
Ocular Surgery Phase 3 readout OCS-01 CME PoC readout OCS-02 DED Phase 2b readout OCS-02 Uveitis Phase 2b readout (2) OCS-05 AON PoC readout (1) Cystoid Macular Edema (CME). (2) Acute Optic Neuritis (AON).
Innovative, diversified and late-stage pipeline Next Catalysts Product
Investigational Pre-clinical Phase 1 Phase 2 Phase 3 2023 2024 Candidate(s) Indication(s) Ph3 Stage 1 readout DIABETIC MACULAR EDEMA OCS-01 Ph3 readout NDA Optireach INFLAMMATION AND PAIN FOLLOWING OCULAR SURGERY technology CYSTOID MACULAR
EDEMA PoC readout Ph2b readout DRY EYE DISEASE OCS-02 Anti TNF Ph2b readout UVEITIS PoC readout ACUTE OPTIC NEURITIS GLAUCOMA OCS-05 GEOGRAPHIC ATROPHY SGK2 Activator DIABETIC RETINOPATHY NEUROTROPHIC KERATITIS CORNEAL NV, PTERYGIUM OCS-03 CORNEAL
TRANSPLANT OCS-04 (1) (2) (3) Wet-AMD , RVO , DR (Undisclosed) OCS-01 is based on the OPTIREACH technology, OCS-02 is a single chain antibody fragment (ScFv) against TNF and OCS-05 is a SGK-2 activator peptidomimetic small molecule with
novel MoA targeting the activation of the trophic factor pathways. (1) Age-related macular degeneration (AMD). (2) Retinal Vein Occlusion (RVO). 99 (3) Diabetic Retinopathy (DR).
Oculis leadership team with successful track record Committed to build
an industry leader in ophthalmic innovation Highly experienced leadership team Expertise in drug development leading to Joanne Chang M.D. Bastian Dehmel M.D. Sylvia Cheung Pall Johannesson Riad Sherif M.D. approvals and launches
with Head of Development Head of medical Affairs Chief Financial Officer Chief Strategy Officer Chief Executive Officer > 40 approved drugs globally Expertise in public company management and launching new classes of therapeutics 10
Possible Effects of DME Normal Vision Possible Effects of DME Normal
Vision Possible Effects of DME Normal Vision OCS-01 in OCS-01 in Diabetic Macular Diabetic Macular Edema (DME) Edema (DME) Possible Effects of DME Normal Vision Possible Effects of DME Normal Vision OCS-01 in OCS-01 in Diabetic Macular Normal
Diabetic Macular Edema (DME) Vision Edema (DME) Possible Effects of DME Normal Vision OCS-01 in 1 OCS-01 in Diabetic Macular Diabetic Macular Effects Edema (DME) Edema (DME) of DME 1 OCS-01 in Image: Source and Copyright: 2022 by The
DME is a large and growing market with critical unmet needs Growing DME
patient Only invasive Late start (1) population size treatments approved of treatment Global DME Patients DME - Treatment rate and (2) (7% of diabetics ) market size in G7 countries (4) (US, EU5 and JP) 2045 53m+ Undiagnosed 2021 $8bn (46%)
37m High burden of treatment Untreated (58%) Diagnosed Not appropriate for early (54%) $6bn Treated (42%) intervention $3bn A leading cause of new cases of 2019 2029 (3) blindness in US adults (1) International Diabetes Federation -
diabetesatlas.org Estimated diabetes around the world in 2021: 537m, reaching 783m in 2045 (2) Yau et al. Global Prevalence and Major Risk Factors of Diabetic Retinopathy, Diabetes Care 2012 Mar; 35(3): 556-564. (3)
https://preventblindness.org/diabetic-macular-edema-dme/ (4) DRG Diabetic Macular Edema / Diabetic Retinopathy Disease Landscape & Forecast 2020 12 (5) Gonzalez 2016 Early and Long-term Responses to VEGF Therapy in DME: Analysis of protocol I
OCS-01 | Current DME treatment paradigm leaves two patient segments
undertreated and losing vision Patient presents with DME with DME DME with moderate to severe DME symptoms 43% 33% 24% mild visual recent onset visual impairment (1) Diagnosed by OCT impairment (2) (2) (2) DME Disease Progression and Treatment
Landscape st st 1 line Laser 1 line Current Observation Laser Anti-VEGF Treatment Steroid implant 3 1 2 60% 1 X Lack of pre-invasive treatment X 40% Inadequate Adequate response response Low anti-VEGF ~ 19% of patients with
good vision (5) response rate Unmet Needs experience deterioration by 5 letters (3) Combination to drive over 2 years efficacy and or durability (4)(6) Addressable US patient population: 1.2 million (1) Optical coherence tomography
(OCT) imaging. (2) Baseline Demographics and Clinical Characteristics of Treatment-Na ve Patients with Diabetic Macular Edema Listed in the IRIS Registry (4) Gonzalez 2016 Early and Long-term Responses to VEGF Therapy in DME: Analysis of
protocol I data (Table S1) www.aao.org (5) Kiss 2014 ; Berenger and Kiss, Feb. 2016, Real-world Utilization of VEGF agents (DME section), Review of Ophthalmology (3) Baker, Carl W., et al. Effect of initial management with aflibercept vs laser
photocoagulation vs observation on vision loss among patients with https://www.reviewofophthalmology.com/article/realworld-utilization-of-antivegf-agents 13 13 diabetic macular edema involving the center of the macula and good visual acuity: a
randomized clinical trial. Jama 321.19 (2019): 1880-1894. (6) Decision Resources Group: DME - DR Landscape Forecast - Disease Landscape Forecast 2020
OCS-01 | First eye drop for DME Positive results in exploratory Phase 3
program initiated after Unique product candidate and Phase 2 studies in DME positive Phase 2 results and EoP2 meeting OCS-01 is a unique high-concentration (3) Patient Case (Phase 2 DX211 ) nanoparticle formulation of OCS-01 showed biological effect
in Dexamethasone (15mg/ml) DME Exploratory 1 (1) (2) CMT reduction and BCVA improvement 19 pts Tanito Study successfully completed Age 55 OPTIREACH Treatment Group OCS-01 Formulation Technology DME Exploratory 2 DME Dur. 4 m 22 pts Ohira Study
Prior DME Tx No Baseline successfully completed (1) Baseline CMT 765 (1) Week 12 CMT 328 DME Phase 2 144 pts (2) Baseline BCVA 40 Randomized & double-masked (2) Week 12 W12 BCVA 56 successfully completed Exploratory 1: Investigator-initiated,
open-label, single-center study. Tanito M, et al. Invest Ophthalmol Vis Sci. 2011;52:7944-7948 Exploratory 2: Ohira A, et al. Acta Ophthalmologica. 2015;93:610-615. Ohira A, et al. Acta Ophthalmologica. 2015;93:610-615. DME Phase 2: Note: Data
presented at Angiogenesis, Exudation and Degeneration, 2020 by KOL (Dugel P.) (1) Central macular thickness (CMT) (2) Best-corrected visual acuity (BCVA) 14 14 (3) Dugel PU. The Oculis OCS-01 phase 1/2 study: an effective topical therapeutic for
DME. Presented at: Angiogenesis, Exudation, and Degeneration 2020; Feb. 8, 2020; Miami.
OCS-01 | Data support OCS-01 to address large DME patient pool A
potential effective and versatile option to treat all DME patients Patient presents with DME with DME DME with moderate to severe DME symptoms 24% 43% 33% mild visual recent onset visual impairment Diagnosed by OCT impairment (1) (1) (1) OCS-01
Topical Treatment Covers Entire Continuum of DME Care Expands patient and Early intervention Standalone/Combination prescriber base treatment (2) Change in OCT & BCVA among patients with baseline BCVA 65 Change in OCT
among patients with baseline BCVA > 65 6 OCS-01 (n = 45) 0 Vehicle (n = 14) Physicians 5 -20 -10.6 3.8 4 -23.1 -40 General Retina -40 3 Ophthalmologist Specialists -41.9 -60 2 0.9 -80 OCS-01 (n = 47) 1 -77.4 -90 Vehicle (n = 28) 0 -100 (1)
Baseline Demographics and Clinical Characteristics of Treatment-Na ve Patients with Diabetic Macular Edema Listed in the IRIS Registry (Table S1) www.aao.org 15 15 (2) Dugel PU. The Oculis OCS-01 phase 1/2 study: an effective topical
therapeutic for DME. Presented at: Angiogenesis, Exudation, and Degeneration 2020; Feb. 8, 2020; Miami. Mean ( SD) Change in CMT From Baseline ( m) Mean Change in BCVA From Baseline Mean Change in CMT From Baseline ( m)
OCS-01 | Phase 3 DME study post positive EoP2 FDA meeting Protocol with
loading dose & enriched population to drive probability of success Successful EoP2 meeting with FDA supporting Phase 3 program Primary Endpoints (EoP2 meeting w/FDA): Key Enrollment Criteria: Phase 3 study design: Mean change in BCVA vs
baseline at 52 weeks Diabetes mellitus 1 and 2 Multicenter, randomized, double- masked, vehicle-controlled ETDRS BCVA letter score Key Secondary Endpoints: between 65 and 24 Stage 1: selection of dose regimen
Mean change in central retinal thickness with better efficacy, 130 patients assessed by SD-OCT Macular thickness (CST) of 310 m Stage 2: two global Phase 3 with % of patients with +15 ETDRS letters vs baseline
~350-450 pts each Stage 2 Stage 1 6 weeks 6weeks 52 weeks Dose and sample size Selected dose regimen 6x/day 3x/day Screening selection 6x/day 3x/day Matching vehicle Randomization End of treatment End of trial 2:1 Stage 1 OCS-01 Vehicle 16
OCS-01 | Recap - first retina eye-drop for DME First Eye drop
in DME expected to address broad DME population TRANSFORMATIVE (1)(2) Total addressable US patient population for DME ~1.2M THERAPY Phase 2 in DME: CMT & BCVA endpoints reached with statistical significance, 144 pts IN PHASE 3
Phase 2 in Ocular Surgery: Pain and inflammation endpoints reached, 150 patients On-going Phase 3 programs in both indications Milestone: Phase 3 Stage 1 readout expected in Q2 2023 UPCOMING DME Regulatory success
case: statistical significance in mean BCVA change READOUT Next steps: commencement of Phase 3 Stage 2 studies in 2H 2023 Phase 3 in Ocular Surgery: Readout expected in Q3 2023 FURTHER OCS-01 PoC in CME: Readout expected in
2H 2024 MILESTONES Ocular Surgery NDA application: Application in late 2024 (1) ARVO Annual Meeting Abstract, June 2021, Hennings et al. Prognostic determinants of postoperative pseudophakic macular oedema in a tertiary hospital setting. (2)
Data on file, Skyggn phase 2 study. 17 17
OCS-02 in Dry Eye Disease 18
OCS-02 | DED a large, underpenetrated and growing market USD 4bn Market
- 13% of patients experience lasting relief after 12 months of treatment Dry Eye Rx drug market Significant market opportunity (1) G7 countries, 2019 Corticosteroids (ophthalmic), (1) Large and growing market forecasted to reach $7.3bn
in 2029 3% Secretagogues, 5% Aqueous Underpenetrated - only 9% of diagnosed patients in the US supplements, (1) receiving treatment 0% LFA-1 Despite current options an under-addressed patient Antagonists, Mucolytics, 0% (2) 20%
population with only 13% of patients achieving lasting relief ~$4bn Vast majority of treated patients are receiving anti- (1) in 2019 inflammatory drugs (1) Next generation anti-inflammatory drug with novel MoA Calcineurin remains
key unmet medical need inhibitors (Ophthalmic), 72% (1) DRG Dry Eye Disease Landscape and Forecast 2020 (2) Mukamal, R. Why is Dry Eye So Difficult to Treat? 2021 https://www.aao.org/eye-health/tips-prevention/fix-dry-eye-treatment-eyedrops 19
OCS-02 | First topical treatment candidate for DED Clinically proven
MoA with potential transformative impact in Ocular Inflammatory Diseases Topical Biologic Candidate Innovative Antibody Fragment Technology Illustration of fragment technology scFv* IgG Fab OCS-02 is an anti-TNF antibody fragment formulation
(OCS-02) with potential to become the first approved topical Regions that bind to Regions that bind to biologic for DED neutralize TNF neutralize TNF Clinically proven MoA Anti-inflammation and anti-necrosis MoA approved as
systemic treatment for ocular disease and with transformative impact in other areas Enhanced ocular penetration Lower molecular weight, enhanced ocular Framework for OCS-02 penetration and higher concentration optimized for stability
Standard and other drug-like antibody properties frameworks Proprietary genetic biomarker 149 kDa 48 kDa 26 kDa Associated with OCS-02 response highlighting opportunity for a precision treatment in DED 20 20
OCS-02 | Anti-TNF biologic Eye Drop Advancing into Phase 2b for
DED & Uveitis Positive Phase 2 / PoC Advancing into Significant in DED and Uveitis Phase 2b for both indications market opportunity Potential to become the OCS-02 in Phase 2b to DED#1 FIRST precision medicine in Dry Eye evaluate signs in DED 85
pts Phase 2 POC successfully completed Disease - de-risks clinical trial and creates (with secondary endpoint in symptoms) potential market pricing upside DED#2 Stratification to validate genetic A unique benefit in DED given its
multifactorial 131 pts Phase 2 POC successfully completed nature and heterogenous patient population biomarker in severe DED population (1) ~10m patients Addressable US patient segment for DED Advance OCS-02 in Phase 2b as Uveitis steroid-sparing
alternative for chronic and 32 pts Phase 2 POC successfully completed recurring Non-Infectious Anterior Uveitis (1) DED Disease and Landscape - DRG Report, Dec. 2020 21 21
OCS-02 | Phase 2a positive results in DED Proof-of-Concept Phase 2
trial evaluating symptoms demonstrated statistically (1) significant reduction in symptoms and well-tolerated profile Full study population High responders P=0.02 % Points 20 0 Vehicle OCS-02 18% (12/67 pts) Safety: -4 No meaningful safety
findings 10 Well tolerated -8 P=0.04 5% (3/64 pts) OCS-02 Vehicle 0 -12 N 67 64 Vehicle OCS-02 (2) Consistent results in a previous study with fast onset at day 14 reaching and maintaining statistical significance Statistical significance
reached in both all-comers and biomarker / high responders (1) Predecessor of OCS-02 (LME636); Note: Presented at ARVO 2021 by KOL (Perez V.) (2) Phase 2a study in acute anterior uveitis; data presented at ARVO, 2021 by KOL (Galor A.) 22 22
Reduction in global ocular discomfort score % Pts with > 20 points improvement
OCS-02 | Biomarker identified for high responders - potential for
precision medicine approach Genetic biomarker for OCS-02 response Association between gene variants and global ocular discomfort score at treatment day 29 was Pre-specified exploratory pharmacogenetic analysis focused on tested: the genes relevant