Oculis Holding Ag · NASDAQ:OCS
Oculis — Investor Day (July 2023)
76 slides from Oculis's investor day presentation, Jul 12, 2023
Slide 1: Oculis R&D Day: Retina
Oculis R&D Day: Retina July 11, 2023 Rethinking Ophthalmology Nasdaq: OCS Exhibit 99.1
Slide 2: 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 expre
Slide 3: Agenda
Agenda Opening Remarks Riad Sherif, M.D. Chief Executive Officer 5mn OCS-01 Phase 3 DIAMOND Program in Diabetic Macular Edema: Stage 1 Recap and Next Steps Arshad Khanani, M.D., M.A. Sierra Eye Associates, University of Nevada; Co-PI for DIAMOND; Oculis SAB member David Boyer, M.D. Keck School of Me
Slide 4: Our Purpose
To drive innovation to save sight and improve eye care Our Purpose
Slide 5: Oculis is Uniquely Positioned to Build Significant Value
2023 2024 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) Geographic Atrophy (GA). (2) Diabetic Retin
Slide 6: Clinical Retina Programs Addressing Highly Meaningful Unmet Needs
OCS-01 OPTIREACH® enables eye drops treating retinal disease: Two Phase 3 programs: DME, Ocular Surgery and PoC in CME Topical Diabetic Macular Edema and Cystoid Macular Edema treatment candidate based on Optireach technology with consistent positive & significant clinical readouts OCS-05 Promising
Slide 7: OCS-01 delivered consistent positive results in previous DME trials
OCS-01 delivered consistent positive results in previous DME trials DME Exploratory 12 19 pts Tanito Study successfully completed DME Phase 24 144 pts Randomized & double-masked successfully completed DME Exploratory 23 22 pts Ohira Study successfully completed Positive results in exploratory and Ph
Slide 8: Unmet Needs: DME Treatment Algorithm
Unmet Needs DME Treatment Algorithm Patient presents with DME symptoms Diagnosed by OCT(1) Current Treatment Observation Laser Anti-VEGF Steroid implant Laser 1st line 1st line 24% DME recent onset DME with mild visual impairment 43% 33% DME with moderate to severe visual impairment DME Disease Prog
Slide 9: Stage 1 Recap and Next Steps
Stage 1 Recap and Next Steps Arshad M. Khanani, M.D., M.A.
Slide 10: Disclosures - Arshad M. Khanani
Disclosures - Arshad M. Khanani, MD, MA, FASRS Consultant: AbbVie, Adverum, Aerie, Applied Genetics Technologies Corporation, Aldebaran, Allergan, Apellis, Arrowhead, Aviceda Therapeutics, Bausch + Lomb, Broadwing Bio, Clearside, 4D Molecular Therapeutics, Exgenesis, EyePoint, Frontera, Genentech, I
Slide 11: Loading dose regimen & enriched population increase probability of success
Loading dose regimen & enriched population increase probability of success Washout (if needed): 3 - 6 months depending on prior treatment 2:1 Randomization Stage 1: determine dose & sample size for Stage 2 Stage 2: dose regimen and sample size informed by Stage 1 results 2:1 Stage 1 (N = 148) Stage
Slide 12: Loading dose regimen & enriched population increase probability of success
Loading dose regimen & enriched population increase probability of success Washout (if needed): 3 - 6 months depending on prior treatment 2:1 Randomization 6-week loading phase followed by 6-week maintenance phase Assessments at baseline, weeks 2, 4, 6, 8, and 12 2:1 Key Enrollment Criteria Age 18-8
Slide 13: Patient Disposition
AE, adverse event; ITT, intention-to-treat. Data, analysis, and conclusions are preliminary, and subject to change as full analysis is ongoing. Patient Disposition ITT population Screened n = 288 Screen failures n = 140 OCS-01 n = 100 Vehicle n = 48 Completed 12 weeks n = 85 (85.0 %) Completed 12 we
Slide 14: Demographics: Well-balanced Between Arms
Demographics: Well-balanced Between Arms (1) Intraocular pressure. Data, analysis and conclusions are preliminary, and subject to change as full analysis is ongoing. . Parameter OCS-01 (n = 100) Vehicle (n = 48) Age, mean (SD), years 61.9 (9.0) 63.9 (7.3) Male, n (%) 53 (53.0) 26 (54.2) Duration of
Slide 15: Primary Endpoint Achieved with Robust Statistical Significance
Primary Endpoint Achieved with Robust Statistical Significance Rapid improvement in vision with OCS-01 treatment, as assessed by BCVA Strong Improvement in Vision with OCS-01 at Week 6 (95% CI, 1.1-7.0) OCS-01 Vehicle P = 0.007 Loading Phase (week 6), ITT Population BCVA, best corrected visual acuit
Slide 16: Improvement in Vision with OCS-01 Sustained to Week 12
Loading Phase (6x/day) Maintenance Phase (3x/day) Improvement in Vision with OCS-01 Sustained to Week 12 Rapid improvement in BCVA with loading dose regimen sustained with maintenance regimen BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; ITT, intention-to-tre
Slide 17: 25% of OCS-01 Patients Achieve ≥3-Line Improvement in BCVA at Week 6
25% of OCS-01 Patients Achieve ≥ 3 Line Improvement in BCVA at Week 6 Vision Gainers Analysis at Week 6 3-line (15 letter) improvement in BCVA deemed highly clinically relevant ≥ 15-Letter Gain P = 0.015 ETDRS, Early Treatment Diabetic Retinopathy Study; ITT, intention-to-treat. Data, analysis and c
Slide 18: 27% of OCS-01 Patients with ≥3-Line Improvement in BCVA at Week 12
27% of OCS-01 Patients with ≥ 3-Line Improvement in BCVA at Week 12 Vision Gainers Analysis at Week 12 3-line (15 letter) improvement in BCVA deemed highly clinically relevant ≥ 15-Letter Gain OCS-01 Vehicle P = 0.009 ETDRS, Early Treatment Diabetic Retinopathy Study; ITT, intention-to-treat. Data,
Slide 19: 63.6 μm Reduction in CST Achieved with OCS-01 at Week 6
63.6 μm Reduction in CST Achieved with OCS-01 at Week 6 CST as Assessed by Optical Coherence Tomography (OCT) Central subfield thickness (CST) is a key metric used by physicians to manage DME patients (95% CI, -97.7, -40.5) P < 0.0001 OCS-01 Vehicle CI, confidence interval; CST, central subfield thi
Slide 20: Reduction in CST Achieved with OCS-01 Sustained to Week 12
Maintenance Phase (3x/day) Loading Phase (6x/day) Reduction in CST Achieved with OCS-01 Sustained to Week 12 CST as Assessed by Optical Coherence Tomography (OCT) Rapid improvements in CST with loading dose regimen sustained with maintenance regimen (95% CI, -76.8, -14.4) P = 0.004 (95% CI, -97.7, -
Slide 21: No Unexpected Safety Findings
No Unexpected Safety Findings Treatment Emergent Adverse Events OCS-01 (N = 100) n (%) Vehicle (N = 48) n (%) Any TEAE 70 (70.0) 30 (62.5) Diabetic retinal edema 10 (10.0) 9 (18.8) Intraocular pressure increased 14 (14.0) 1 (2.1) Hypertension 10 (10.0) 1 (2.1) Ocular hypertension 8 (8.0) 0 Macular e
Slide 22: IOP Increase Consistent with Literature
IOP Increase Consistent with Literature OCS-01 n=100 n (%) Vehicle n=48 n (%) Any IOP related AE 22/100 (22.0) 1/48 (2.1) 10 mmHg IOP change from baseline at any visit 16/97 (16.5) 0/47 (0) Greater or equal to 25 mmHg IOP at any visit 19/97 (19.6) 1/47 (2.1) Greater or equal to 35 mmHg IOP at any vi
Slide 23: Minimal Mean IOP Increase is Similar Across Loading and Maintenance
Minimal Mean IOP Increase is Similar Across Loading and Maintenance Loading Phase (6x/day) Maintenance Phase (3x/day) IOP, intraocular pressure. Mean (SD) baseline IOP: OCS-01, 15.3 (3.1) mm Hg; vehicle, 14.7 (3.0) mm Hg. Data, analysis and conclusions are preliminary, and subject to change as full
Slide 24: Overall Conclusion
Overall Conclusion BCVA, best corrected visual acuity. Data, analysis, and conclusions are preliminary, and subject to change as full analysis is ongoing. Study met its pre-specified objective i.e. to enable the selection of a dosing regimen for stage 2 No unexpected safety findings were observed Si
Slide 25: OCS-01 in DME Phase 3 DIAMOND-1 and DIAMOND-2 Next Steps
OCS-01 in DME Phase 3 DIAMOND-1 and DIAMOND-2 Next Steps David S. Boyer, MD
Slide 26: Disclosures - David S. Boyer
Disclosures - David S. Boyer, MD Consultant: 4DMT, Achillion Pharma, Acucela, Adverum Biotechnologies, Aerie, AiViva Biopharma, Alcon, Aldeyra Therapeutics, Alimera Sciences, Alkahest, Allegro, Allergan, Allgenesis, Alzheon, Amgen, Amydis, Annexon Biosciences, Apellis, AGTC, AsclepiX, Ashvattha, Avi
Slide 27: Purpose and Design
Purpose and Design Purpose To evaluate the efficacy and safety of OCS-01 in the treatment of patients with Diabetic Macular Edema (DME) The studies will provide the required clinical data for a New Drug Application (NDA) to the US FDA Design Two randomized, multi center, masked, vehicle-controlled p
Slide 28: The DIAMOND Program in DME at a Glance
OCS-01 | The DIAMOND Program in DME at a Glance Washout (if needed): 3 - 6 months depending on prior treatment 6-week loading phase followed by 46-week maintenance phase 1:1 Key Enrollment Criteria Age 18-85 years No participation in Stage 1 Confirmed diagnosis of DME Diabetes mellitus 1 and 2 ETDRS
Slide 29: Eligibility Criteria and Number of Patients
Population Approximately 700 - 800 patients with DME (across both studies), aged 18-85 years with best corrected vision (BCVA) of 24-65 letters, and central retinal thickness (CST) ≥ 310 µm will be enrolled. Eligibility criteria defining DME were selected to be similar: to criteria used in previous
Slide 30: Methods and Main Outcome Measures
Methods and Main Outcome Measures Patients will be randomized 1:1 to study treatment with OCS-01 or matching vehicle and will be followed for 52 weeks. Study treatment will be administered as an eye drop 6 times a day (loading phase) for 6 weeks followed by 3 times a day (maintenance phase) for the
Slide 31: Operational Organization and Timelines
Operational Organization and Timelines The studies will be conducted globally in selected sites based on expertise and experience. Centers in the US and ex-US will be included in each study. A best-in-class CRO was selected for the global conduct of the study. A Steering Committee, composed of exper
Slide 32: Global DIAMOND Program Steering Committee Members
Global DIAMOND Programm Steering Committee Members July 2023 SC member Affiliation David S. Boyer, MD Retina -Vitreous Associates Medical Group, Los Angeles, CA, USA Bastian Dehmel, MD Oculis Head of Development, Lausanne, Switzerland Arshad M. Khanani, MD Retina- Sierra Eye Associates, Reno, NV, US
Slide 33: OCS-01 PoC LEOPARD Trial in CME
OCS-01 PoC LEOPARD Trial in CME Quan Dong Nguyen, MD, MSc, FARVO, FASRS
Slide 34: LEOPARD Study Overview
LEOPARD Study Overview Efficacy and Safety Of Dexamethasone OphthaLmic Suspension Eye DrOps In Uveitic and Post Surgical MAculaR EDema – The LEOPARD Study Research and Development Retina Day with Oculis July 11, 2023 – New York City Quan Dong Nguyen, MD, MSc, FAAO, FARVO, FASRS Byers Eye Institute S
Slide 35: Disclosure
Disclosure Stanford University, the employer of Dr. Nguyen, has received research funding from Boehringer-Ingelheim, Genentech, Novartis, Oculis, Regeneron, Santen, and Belite Bio among others Dr. Nguyen serves on the Scientific Advisory Boards for Belite Bio, Boehringer-Ingelheim, Genentech, Kriya,
Slide 36: Introduction and Study Rationale
Introduction and Study Rationale
Slide 37: Uveitic Macular Edema
Uveitic Macular Edema Uveitic macular edema (UME) is a common complication of uveitis ~ 33%(1) Even after control of active inflammation, uveitic macular edema may persist(2) Intravitreal steroid results in complete resolution of 50-60% of uveitic macular edema(3) Lardenoye et al. Impact of Macular
Slide 38: Post-Surgical Macular Edema
Post-Surgical Macular Edema Cataract extraction is the most prevalent surgical procedure of all medical specialties with an estimated 3.7 million cases per year in the USA, 7 million in Europe and 20 million worldwide(1) Clinically significant CME occurs in up to 5.8% of cataract surgeries(2) repres
Slide 39: The Unmet Needs to Be Addressed by LEOPARD
The Unmet Needs to Be Addressed by LEOPARD There is no optimal treatment for uveitic and post-surgical macular edema OCS-01 has demonstrated excellent safety and efficacy profiles in diabetic macular edema in clinical trials to-date Previous study (Shulman et al, 2015) has shown that topical dexamet
Slide 40: Dexamethasone Ophthalmic Suspension (OCS-01)
Dexamethasone Ophthalmic Suspension (OCS-01) A high-concentration OPTIREACH formulation of dexamethasone (15 mg/ml) conjugate forming nano- and microparticles Cyclodextrins are hydrophilic carriers that can: Enhance the permeation of relatively lipophilic molecules (e.g., dexamethasone) through bio-
Slide 41: LEOPARD Study Design
LEOPARD STUDY DESIGN ~~
Slide 42: Study Objectives
Study Objectives To evaluate the effects of OCS-01 Ophthalmic Suspension on visual acuity and central subfield thickness (CST) in subjects with UME and PSME To monitor the safety of OCS-01
Slide 43: Study Overview
Study Overview Prospective, multi-center, single masked, randomized, controlled study Subjects and BCVA examiner will be masked 24 eligible subjects 12 with UME 12 with PSME Study Duration: 24 weeks for each subject Four Phases Screening Phase Loading Phase: All subjects will receive 1 drop of OCS-0
Slide 44: Primary Outcomes
Primary Outcomes Mean change in central subfield thickness (CST) on optical coherence tomography (OCT) at week 12 compared to baseline Mean change in ETDRS BCVA letter score at Week 12
Slide 45: Secondary Outcomes
Secondary Outcomes Mean change in ETDRS BCVA letters at weeks 2, 4, 6, 8, 16, 20, and 24 compared to baseline The percentage of subjects who gain ≥10 or ≥15 ETDRS letters at week 12 and 24 compared to baseline Mean change in central subfield thickness (CST) at weeks 2, 4, 6, 8, 16, 20, and 24 compar
Slide 46: Safety Endpoints
Safety Endpoints Adverse Events (AEs) at 8, 12, and 24 weeks Slit Lamp Examination Parameters indicating ocular toxicity to the investigational drug at 8, 12, and 24 weeks Intraocular Pressure at 8, 12, and 24 weeks Percentage of subjects who lose ≥15 ETDRS letters or more at weeks 8, 12, and 24 com
Slide 47: Retreatment Criteria
Retreatment Criteria Subjects who continue to have ME on OCT from week 12 onwards, will be treated according to the following criteria: Subjects randomized to High-Dose group (6 drops OCS-01 daily) will continue to receive 6 drops OCS-01 daily. Subjects randomized to Low-Dose group (receive 3 drops
Slide 48: LEOPARD Eligibility Criteria
LEOPARD ELIGIBILITY CRITERIA 48
Slide 49: Inclusion Criteria
Inclusion Criteria Age 18 years or older A diagnosis of UME or PSME Can provide written informed consent prior to any study procedure being performed, able and willing to follow all instructions, and attend all study visits An ETDRS BCVA letter score ≤ 70 (Snellen 20/40) and ≥ 35 (Snellen 20/200) in
Slide 50: Study Timelines
Study Timelines Activation of Sites (completed) May – June 2023 LPLV Q3 2024 Topline Results Q4 2024/Q1 2025 Enrollment June 2023 to January 2024
Slide 51: Clinical Sites
Clinical Sites Byers Eye Institute at Stanford, Palo Alto, CA Texas Retina Associates, Dallas, TX Valley Retina Institute, McAllen, TX Stein Eye Institute at UCLA, Los Angeles, CA Retina Vitreous Associates Medical Group, Beverly Hills, CA
Slide 52: Summary
Summary OCS-01, a high-concentration OPTIREACH formulation of dexamethasone (15 mg/ml), is being evaluated as therapeutic option for uveitic macular edema (UME) and post-surgical macular edema (PSME), aiming to address important unmet needs, in addition to diabetic macular edema (DME) Strong safety
Slide 53: Thank You
THANK YOU LEOPARD STUDY LEOPARD
Slide 54: OCS-05 PoC ACUITY Trial in AON
OCS-05 PoC ACUITY Trial in AON Sophie Bonnin, M.D.
Slide 55: ACUITY study: towards neuroprotection
ACUITY study: towards neuroprotection Sophie Bonnin, MD
Slide 56: Why neuroprotection is an unmet medical need?
Glaucoma: blurred or no peripheral vision Macular Degeneration: blurred or no vision in the center of visual field Diabetic Retinopathy: spots or dark strings floating in vision In all these diseases, the loss of neurons, i.e. ganglion cells, is responsible for the loss of vision. Neuroprotection ai
Slide 57: Unmet medical need in glaucoma
Unmet medical need in glaucoma Cumulative incidences of blindness(2) “Currently available therapies for [glaucoma] only attempt to reduce intraocular pressure, the major risk factor, without addressing the associated optic neuropathy and retinopathy. “Development of glaucoma neuroprotective treatmen
Slide 58: OCS-05: SGK-2 activator with unique mode of action
SGK-2 activator peptidomimetic small molecule with a unique mode of action for neuro-ophthalmology OCS-05 targets SGK as part of the neurotrophic factor signalling pathways triggering multiple beneficial effects on apoptosis, anti-oxidation and anti-inflammation Disease modifying drug to protect and
Slide 59: OCS-05: Glaucoma neuroprotection model results
OCS-05: Glaucoma neuroprotection model results OCS-05 promotes neuroprotection in glaucoma by preventing damage to the retinal ganglion cells RGL IGL OGL Sham control NGF OCS-05 Sham control Glaucoma OCS-05 Glaucoma OCS-05 intravitreal | H&E for RGC density % of Efficacy 82.1 81.7 77.1 *p < 0.0001 c
Slide 60: OCS-05: Prevention of retinal ganglion cell loss in optic neuritis
OCS-05: Prevention of retinal ganglion cell loss in optic neuritis **p < 0.01 ; ***p < 0.001 compared to placebo Prevention of Retinal Ganglion Cell (RGC) loss Sham control Loss of RGC Placebo OCS-05 70 mg/kg % of Efficacy 35.9 64.0 Lysolecithin induced demyelinating model in rat (model of acute opt
Slide 61: OCS-05: Safety and pharmacokinetic in healthy subjects
OCS-05: Safety and pharmacokinetic in healthy subjects Phase I study included 48 healthy subjects: 36 were treated by OCS-05. No serious adverse events were reported in the OCS‐05 group. Villoslada, P., Masso, M., Paris, S., Hutchings, S., & Koch, A. (2023). A Phase 1 randomized study on the safety
Slide 62: Towards the assessment of efficacy of OCS-05: Phase 2 ACUITY Trial
Preziosa, P., Comi, G., & Filippi, M. (2016). Optic neuritis in multiple sclerosis: Looking from a patient’s eyes. Neurology, 87(3), 338–339. Towards the assessment of the efficacy of OCS-05 in patients: Phase 2 ACUITY Trial in acute optic neuritis Acute optic neuritis : Rare disease with acute infl
Slide 63: Acute optic neuritis and multiple sclerosis
Acute optic neuritis and multiple sclerosis Acute optic neuritis: occurring in adults between the age 20 and 40 years Aetiology: multiple sclerosis, idiopathic, neuromyelitis optica, … Multiple sclerosis is affecting more than 2.8 million persons worldwide(1) Mean age at diagnosis: 32 years and with
Slide 64: Acute optic neuritis: towards neuroprotection
Acute optic neuritis: towards neuroprotection Ongoing multiple sclerosis treatment : anti-inflammatory drugs Neuroprotective therapies are required for multiple sclerosis and acute optic neuritis. The retinal changes can be non-invasively and accurately measured by optical coherence tomography. “Acu
Slide 65: OCS-05 in acute optic neuritis: Phase 2 ACUITY Trial
ACUITY (Acute optiC neUrITis with a demYelinating origin) Aim: To assess the safety and to explore the efficacy of OCS-05, compared to placebo, in patients with acute optic neuritis receiving the standard of care Design: 2 arms randomized double-blind placebo-controlled study (1 OCS-05: 1 placebo) D
Slide 66: ACUITY primary and exploratory endpoints
ACUITY (Acute optiC neUrITis with a demYelinating origin) Primary endpoints: safety & tolerability Exploratory endpoints: efficacy Gold Standard vision-related outcome measures consider structure and function of the visual pathway including routine non-invasive optical coherence tomography and low-c
Slide 67: OCS-05: this neuroprotective treatment offers hope for our patients
OCS-05: this neuroprotective treatment offers hope for our patients Multiple sclerosis : several neuroprotective drugs in development but no validated drug. Optic neuropathies and retinal diseases : the focus is on anti-inflammatory treatment or anti-VEGF treatment but not on neuroprotection even th
Slide 68: OCS-05 summary: First SGK neuroprotective candidate in ophthalmology
OCS-05 summary: First SGK neuroprotective candidate in ophthalmology ACUITY First-in-patient study ongoing Data supporting MoA and safety First SGK neuroprotective ophthalmic candidate Disease modifying drug which protects and repairs neurons Potential paradigm shift in treating major blinding disea
Slide 69: Thank you for your attention
Ww Université Paris Cité | AP-HP. Nord 9g Université Paris Cité yy HOPITAL FONDATION ; d Adolphe de ROTHSCHILD 7aS\S 2 X Thank you for your attention
Slide 70: Q&A Session and Closing Remarks
Q&A Session and Closing Remarks Dr. Riad Sherif Chief Executive Officer
Slide 71: Results validated loading and maintenance regimen to optimize OCS-01
Results validated loading and maintenance regimen to optimize OCS-01 efficacy potential in DME with robust statistical significance OCS-01 met all functional and clinical benefit endpoints in a robust, statistically superior manner (in 3-month trial): Improvement of visual acuity (Functional Endpoin
Slide 72: Benefits highlighted in third-party market research
Benefits highlighted in third-party market research performed independently with payers & physicians(1,2) Ophthalmologists DME Patients Payors Potential lower total cost with an efficacious and safe alternative Early intervention could result in reducing cost burden for payor system and improving lo
Slide 73: OCS-01: Multi Programs Asset Covering Front and Back of the Eye
OCS-01 | Multi Programs Asset Covering Front and Back of the Eye (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. (3) Cystoid Macular Edema (CME).
Slide 74: OCS-05 Recap: First SGK Neuroprotective Candidate in Ophthalmology
(1) Multiple Sclerosis. OCS-05 | Recap: First SGK Neuroprotective Candidate in Ophthalmology First SGK Neuroprotective Ophthalmic Candidate Disease modifying drug which protects and repairs neurons Potential application in ophthalmology including Glaucoma, Geographic Atrophy, Diabetic Retinopathy, a
Slide 75: Oculis is Uniquely Positioned to Build Significant Value
Oculis is Uniquely Positioned to Build Significant Value Targeting critical unmet needs in 3 major ophthalmology segments Near-term value inflection points expected (1) Cystoid Macular Edema (CME). (2) Acute Optic Neuritis (AON). OCS-01: 1st Eye drop for Diabetic Macular Edema (DME) in Ph 3 OCS-02:
Slide 76: Our Purpose
To drive innovation to save sight and improve eye care Our Purpose