Oculis Holding AG 6-K, filed Apr 14, 2023
Oculis Holding AG (OCS)
About this 6-K
Oculis Holding AG filed this 6-K on April 14, 2023.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
OF THE SECURITIES EXCHANGE ACT OF 1934
For the Month of April 2023
(Commission File No. 001-41636)
Oculis Holding AG
(Translation of registrant’s name into English)
Bahnhofstrasse 7
CH-6300
Zug, Switzerland
(Address of registrant’s principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
Enclosed hereto is a copy of an investor presentation published by Oculis Holding AG on April 13, 2023.
The information contained in this Form 6-K, including Exhibit 99.1, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.
EXHIBIT INDEX
| Exhibit | Description | |
| 99.1 | Investor Presentation dated April 13, 2023 | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| OCULIS HOLDING AG | ||||||
| Date: April 13, 2023 |
By: |
/s/ Sylvia Cheung | ||||
| Sylvia Cheung Chief Financial Officer | ||||||
Exhibit 99.1 Rethinking Ophthalmology INVESTOR WEBCAST April 13, 2023 1
Safe Harbor Statements Cautionary Note on Forward-looking Statements These slides and the accompanying oral presentation contain forward-looking statements and information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward-looking statements. For example, all statements we make regarding the initiation, timing, progress and results of our preclinical studies, our clinical studies, our research and development programs, our regulatory strategy, our future development plans, our ability to advance product candidates into, and successfully complete, and the timing or likelihood of regulatory filings and approvals and statements regarding the potential therapeutic benefits of our product candidates are forward looking. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: the possibility that Oculis may be adversely affected by economic, business, and/or competitive factors; Oculis' estimates of expenses and profitability; Oculis' ability to develop, manufacture and commercialize the product candidates in its pipeline; actions of regulatory authorities, which may affect the initiation, timing and progress of clinical studies or future regulatory approvals or marketing authorizations; the ability of Oculis or its partners to enroll and retain patients in clinical studies; the ability of Oculis or its partners to gain approval from regulators for planned clinical studies, study plans or sites; Oculis' ability to obtain and maintain regulatory approval or authorizations of its products, including the timing or likelihood of expansion into additional markets or geographies; the success of Oculis' current and future collaborations, joint ventures, partnerships or licensing arrangements; the ongoing and evolving COVID-19 pandemic on Oculis' business, financial position, strategy and anticipated milestones; and other risks and uncertainties set forth in the sections entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in documents that Oculis may from time to time file or furnish with the SEC. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to update or revise any forward- looking statement, whether as a result of new information, future events or otherwise, except as required by law. Copyright of this presentation is owned by Oculis. No part of this presentation may be reproduced in any manner without the permission of Oculis. 22
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 5
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 Market Report. 66
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). 88
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 TNFα 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 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 Angiogenesis Foundation, Inc., All Rights Reserved. www.scienceofdme.org 1 Diabetic Macular Edema (DME) 1 1 1
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 data 12 12
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-Naïve 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-Naïve 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 (μm) Mean Change in BCVA From Baseline Mean Change in CMT From Baseline (μm)
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 μm ▪ 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 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 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-TNFα 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 TNFα � 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-TNFα 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 to TNF pathway and Sjogren’s syndrome ▪ Among the gene variants tested, one variant 25 out of 4 showed significant effect on the High responders: VAS change from baseline >20 15 response to OCS-02. 5 -5 ▪ Patients with this gene variant tended to have -15 larger improvement vs other p < 0.0001 -25 -35 # subj. (%) VAS >20 ▪ Oculis is planning to further validate OCS-02 -45 biomarker in the upcoming Phase 2b study -55 OCS-02 12 (18%) -65 Successful Phase 2b will support advancement -75 Vehicle 3 (5%) -85 to Phase 3 while evaluating the potential for a *P=0.018 -95 precision medicine for DED Full analysis set -105 Presented at ARVO 2021 by KOL (Perez V.) 23 23 Change from Baseline
OCS-02 | Phase 2b study in Dry Eye Disease A multi-center, randomized, double-masked, vehicle-controlled study evaluating the safety and efficacy of OCS-02 for the treatment of signs and symptoms of DED Phase 2b study design: Objectives: Key enrollment criteria: ▪ Randomized, masked, vehicle-▪ Subjects with history of DED for 6 mos. ▪ The objective of this study is to controlled study evaluate the safety and efficacy of ▪ Schirmer’s test at baseline < 10 mm ▪ Multi-center, 10-week, approx. OCS-02 for the treatment of signs ▪ Corneal fluorescein stain > 2 in at least 1 120 subjects and symptoms of dry eye disease region (inferior, superior) ▪ Stratification based on genotype (CC SNP) 30 Patients 2 week run in, all subjects (6+2) weeks TBD OCS-02 3x/day (TID) Follow-up Screening Artificial tears TID Patients who respond to artificial tears Vehicle (TID) Follow-up will not be randomized Randomization 24 24
OCS-02 | Recap – first Anti-TNFα eye drop for DED and Uveitis INNOVATIVE Next gen. ophthalmic anti-TNFα to directly address core inflammation in THERAPY both, DED and Uveitis Total addressable US patient population for DED: ~10M LARGE MARKET Ready to advance Phase 2b with three clinical Phase 2a studies for DED and Uveitis: IN PHASE 2b Statistically significant efficacy and safety in both indications in prior studies Phase 2b in DED: readout expected in 2H 2024 MILESTONES Phase 2b in Uveitis: readout expected in 2H 2024 (1) Multiple Sclerosis. (2) Acute Optic Neuritis. 25 25
OCS-05 in Neuro-Ophthalmology: Acute Optic Neuritis Normal vision Early glaucoma Advanced glaucoma
OCS-05 | Candidate overview SGK-2 activator peptidomimetic small molecule with a unique MoA for neuro-ophthalmology Unique & Differentiated MOA Disease modifying drug to protect and OCS-05 targets SGK as part of the neurotrophic factor repair neurons signalling pathways triggering multiple beneficial effects on ▪ Activates neurotrophic signalling pathways apoptosis, anti-oxidation and anti-inflammation supporting neuronal survival and repair SGK promotes neuronal Foxo3 Survival survival and Multiple potential applications: Apoptosis SGK GSK3B differentiation trough X Foxo3 and GSK3B ▪ Glaucoma Neuron ▪ Dry AMD / Geographic Atrophy ▪ Diabetic Retinopathy NDRG1 OCS-05 SGK ▪ Acute Optic Neuritis Oligodendrocyte SGK induces the cell protective phenotype of microglia NDRG1 activation by SGK ▪ Neurotrophic Keratitis (e.g., CNTF production) induces Oligodendrocyte Precursors differentiation and myelination CNTF Cell protective Microglia (M2) 27 27
OCS-05 | New neuro-ophthalmology candidate Compelling data showing prevention of RGC’s damage in Glaucoma and AON models (3) OCS-05, IVT and topical, shown to prevent RGCs AON model: Short term study (5-day OCS-05 shown to promote improvement of damage (the key element in Glaucoma vision loss) treatment, assessment at day 6) clinical function (disability) in experimental autoimmune encephalomyelitis ( EAE) model Visual of RGC Protection (4) (3) (5) OCS – 05 | H&E for RGC density at week 6 (5) OCS – 05 | Model of autoimmune AON and MS Sham control Clinical assessment (score) RGC 5 Severe disabilities 4 Placebo Placebo Treatment initiation 3 Loss OCS-05 50 mpk of RGC 2 OCS-05 100 mpk 1 OCS-05 70 mg/kg 0 Normal High-pressure Glaucoma rat model of neurodegeneration More RGC without inflammation Experimental Autoimmune Encephalomyelitis model in mice remain (1) Primary Open-Angle Glaucoma (POAG). (2) Experimental autoimmune encephalomyelitis (EAE). (3) Retinal ganglion cell (RGC). (4) Hematoxylin and eosin (H&E) staining. 28 28 (5) Villoslada P. et al. Neurotherapeutics, published online: 27 February 2019. Intravitreal Eyedrops D1 D3 D5 D7 D9 D11 D13 D15 D17 D19 D21 D23 D25 D27 D29 D31 D33 D35 D37 D39 D41 D43 D45 D47
OCS-05 | Development status Paving the way to multiple indications 1 Oculis New Sponsor Q3 2022 2 Previous and ongoing studies in Europe Acute Optic Neuritis (AON) Phase 1: No drug-related side effects Glaucoma ▪ Randomized, double-blind, placebo-controlled, single and multiple Oculis is considering to study several ascending dose study of the safety, tolerability and PK in adult healthy Geographic Atrophy neuro-Ophtha volunteers (UK, MHRA) indications Diabetic Retinopathy ▪ Recruitment of 48 healthy volunteers (36 OCS-05, 12 placebo) Cornea: Neurotrophic Keratitis Phase 2a: First-in-patients trial in AON ▪ Objective to evaluate safety and explore efficacy of OCS-05 compared to CNS: Multiple Sclerosis (MS) placebo in patients diagnosed with a first unilateral AON of a demyelinating origin ▪ Randomized double-blind placebo-controlled, multicentre trial in France (1) 3 Oculis is working with FDA on pursuing the Dev in the U.S. (1) U.S. Clinical hold in 2016 under prior sponsor. 29 29
Acute Optic Neuritis (AON) Optic Neuritis trials allows to validate OCS-05 in neuro-ophthalmology 130k patients a year (US/EU) Preventing axonal damage at the Retinal thickness (pRNFL and GCIPL) as optic nerve and RGC loss will preserve surrogate of permanent visual impairment AON mean annual prevalence of acute: 7.9 cases per visual function 100,000 person-year and AON mean annual 1 Promising Imaging techniques incidence rate is 5.4 cases per 100,000 person-years …is clinically relevant which could be surrogate markers 7 letters (1.5 lines) 5 um Change in GCIP thickness predicts 2 a meaningful change of a loss of 7 letters in 2.5% LCVA clinical relevance. GCIP layer • Not approved therapy for AON OCS-05 • SoC is intravenous methylprednisolone, that 2.5% Sloan Letter Chart for LCVA. OCT of the human retina captures 1 µm resolution. is not reducing permanent disability 1. Martínez-Lapiscina et al. J Neurol. 2014 Apr;261(4):759-67; 2. Gabilondo et al. Ann Neurol. 2015 Mar;77(3):517-28; 3. 3Beck RW, et al. N Engl J Med. 1992 Feb 27;326(9):581-8 2. LCVA: Low Contrast Visual Acuity . 30 30 GCIP thickness
OCS-05 | Recap - first SGK neuroprotective candidate in ophthalmology • Disease modifying drug with neuroprotective activities in neuro ophthalmology TRANSFORMATIVE • Potential paradigm shift in treating major blinding diseases, acting directly on retinal neurons THERAPY • No treatment to-date • Potential application for multiple indications in ophthalmology: Glaucoma, Geographic LARGE Atrophy, Diabetic Retinopathy, and corneal indications such as Neurotrophic Keratitis MARKET • Preclinical data: Neuroprotection by preventing retinal ganglion cell death and PROMISING improvement of function in MS and AON models PRECLINICAL DATA • Phase 1 study: Well-tolerated in 48 healthy volunteers • 2H 2024: Proof-of-concept data readout in AON expected MILESTONE 31 31
Summary 32
Proven track record of efficient capital deployment Building a world leader in ophthalmology Clinical readouts: OCS-01 Optireach® clinical validation in OCS-01 ➢ OCS-01 DME Ph3 Stage 1 DME/retina and Oc Sx➢ OCS-02 DED Ph2b Building a ➢ OCS-01 Oc Sx Ph3 Positive EoP2 with FDA for DME and ➢ OCS-02 Uveitis Ph2b OCS-05 world leader in Optireach® animal & Ocular Sx commenced Phase 3 studies ➢ OCS-05 AON PoC Neuroprotective ophthalmology human POC ➢ OCS-01 CME PoC disease modifying OCS-02 ➢ OCS-01 Oc Sx NDA technology in-licensing Biologic eye drop: Novartis in-licensing Technical development advancement < 2016 - 2017 2018 - 2022 2023 and beyond • Successful Merger with EBAC and listing on : • > USD 110 m private funding from leading international life March 3, 2023 sciences investors • Raised total proceeds of $104 m; Adequately capitalized with • Successful clinical validation of Optireach® / OCS-01 cash runway to beginning of 2025 • Strong and balanced portfolio: OCS-01, OCS-02 and OCS-05 • Track record of success and well funded to deliver key business • Efficient deployment of of capital transforming Oculis into milestones in 2023 and 2024: multiple assets with late-stage candidates • 6 clinical readouts • 1 NDA application 33 33 Financial Business highlights Milestones
Uniquely positioned to build significant value st ▪ OCS-01: 1 Retina eye-drop for Diabetic Macular Edema (DME) in Ph3 st Advanced and Innovative product portfolio ▪ OCS-02: 1 Biologic eye-drop for Dry Eye Disease (DED) in Ph2b (upside potential from biomarker-driven precision medicine approach) st ▪ OCS-05: 1 Neuroprotective agent for neuro-retina treatments in PoC Strong management team ready to ▪ Targeting critical unmet needs in 3 major ophthalmology segments materialize significant commercial potential 2023 2024 ▪ OCS-01 DME Phase 3 (Stage 1) readout▪ OCS-01 Ocular Surgery NDA (1) Near-term value inflection points expected ▪ 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). 34 34
Investor Webcast – Discussion with KoL’s 35
Key Opinion Leaders Dr. Eric Donnenfeld Dr. Donnenfeld, who is a trustee of Dartmouth Medical School and clinical professor of ophthalmology at New York University. He is a past president of The American Society of Cataract and Refractive Surgery, President of the International Intraocular Implant Society, a Fellow of the American Academy of Ophthalmology and editor-in-chief of EyeWorld. Dr. Pravin Dugel Dr. Dugel is an Oculis Board member and is internationally recognized as a major clinical researcher and has served as a visiting professor at universities worldwide – contributions that earned him the prestigious Senior Honor Award from the American Academy of Ophthalmology. He has previously served as a member of the Board of Directors of the American Society of Retina Specialists (ASRS), and Europe’s retina society, EURETINA. He is also President of the biopharmaceutical company, Iveric Bio. Dr. Arshad Khanani Dr. Khanani has been a principal investigator for more than 100 clinical trials and a top enroller in the United States for multiple Phase 1-3 trials. He is a Clinical Associate Professor at the University of Nevada, Reno School of Medicine, an elected member of the Retina Society, Macula Society and has received numerous awards of distinction including the Senior Honor Award from the American Society of Retina Specialists. Dr. Khanani founded the clinical research section at Sierra Eye Associates and currently serves as its Managing Partner, Director of Clinical Research, and Director of Fellowship. 36 36
Investor Webcast – Q&A 37
THANK YOU 38
Our Purpose To drive innovation to save sight and improve eye care 39 39