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 September 2024
Commission File No. 001-39621
OPTHEA LIMITED
(Translation of registrant’s name into English)
Level 4
650 Chapel Street
South Yarra, Victoria, 3141
Australia
(Address of registrant’s principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
EXHIBIT INDEX
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, thereto duly authorized.
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OPTHEA LIMITED |
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(Registrant) |
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By: |
/s/ Frederic Guerard |
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Name: |
Frederic Guerard |
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Title: |
Chief Executive Officer |
Date: 09/09/2024
Transforming Patient Outcomes with Superior Vision Gains Corporate Overview | September 2024 NASDAQ (OPT); ASX (OPT.AX) Exhibit 99.1
Disclaimer and Forward-looking Statements This presentation includes general background information about the activities of Opthea Limited (ABN 32 006 340 567) (“Opthea” or “Company”) and its affiliates and subsidiaries (together, the “Opthea Group”). The information contained in this presentation is in summary form and does not purport to be complete or to contain all material information about the Opthea Group which a prospective investor or purchaser may require in evaluating a possible investment in Opthea or acquisition of securities in Opthea. The information in this presentation remains subject to change without notice. No member of the Opthea Group nor any director, officer, employee, adviser, agent or representative of any member of the Opthea Group (each an Opthea Party and together, the Opthea Parties) has any obligation to update or correct this presentation. This presentation contains forward-looking statements within the meaning of the U.S. federal securities laws that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the therapeutic and commercial potential and size of the estimated market opportunity of the Company’s product in development, the viability of future opportunities, future market supply and demand, the expected timing of top-line data, our expectations about topline data based on masked pooled data, the future cash runway, the financial condition, results of operations and business of Opthea, certain plans, objectives and strategies of management of Opthea, including with respect to the current and planned clinical trials of its product candidate and the future performance of Opthea, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Opthea may not actually achieve the plans, intentions or expectations disclosed in the forward-looking statements, and you should not place undue reliance on the forward-looking statements as predictions of future events. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements contained in this presentation reflect Opthea’s current views with respect to future events, and we assume no obligation to update any forward-looking statements except as required by applicable law. Please refer to information, including risk factors, set forth in Opthea’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on August 30, 2024, and other future filings with the U.S. Securities and Exchange Commission for key factors that could cause actual results to differ materially from those projected in the forward-looking statements contained herein including risks associated with: future capital requirements and ability to continue as a going concern, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept safety, tolerability and therapeutic efficacy, additional analysis of data from Opthea’s Phase 3 clinical trials, including once masked pooled data is unmasked, clinical research organization and labor costs, intellectual property protections, future capital requirements, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept safety, tolerability and therapeutic efficacy, and other factors that are of a general nature which may affect the future operating and financial performance of the Company. This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry publications, third-party research and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions. The information contained in this presentation does not constitute investment or financial product advice (nor taxation or legal advice) and is not intended to be used as the basis for making an investment decision. The presentation is for informational purposes only and is not a prospectus or other disclosure document under Australian law or the law of any other jurisdiction and does not contain all the information which would be required to be disclosed in a prospectus or other disclosure document. The information presented in this presentation may differ materially from that presented in any disclosure document prepared in connection with any offer of securities. It does not take into account the investment objectives, financial situation, taxation position or needs of any particular investor, which should be considered when deciding if an investment is appropriate. You must consider your own investment objectives, financial situation and needs and conduct your own independent investigations and enquiries, including obtaining taxation, legal, financial or other professional advice in relation to the information contained in this presentation as appropriate to your jurisdiction. This presentation should not be relied upon by the Recipient in considering the merits of any particular transaction. This presentation does not constitute an offer to sell, or the solicitation of an offer to buy, any securities in the United States or any other jurisdictions in which such an offer would be unlawful prior to registration or qualification under the U.S. Securities Act of 1933, as amended, or the securities laws of any state or other jurisdiction of the United States. This presentation may contain trademarks and trade names of third parties, which are the property of their respective owners. Third party trademarks and trade names used in this presentation belong to the relevant owners and use is not intended to represent sponsorship, approval or association by or with any of the Opthea Group.
First-in-class VEGF-C/D ‘trap’ inhibitor intended for combination with standard of care anti-VEGF-A therapies Composition of Matter and Methods of Use Patents through 2034; opportunities to extend beyond 2034* Sozinibercept Has the Potential to Be the First Product in 20 Years to Improve Visual Outcomes Addressing High Unmet Need Topline Data from Pivotal Trials in 2025 Substantial Market Opportunity Despite wide use of anti-VEGF-A therapy, wet AMD patients still experience loss in vision long term1 Every letter of vision counts to improve quality of life and reduce mortality Topline data anticipated for COAST (n=998) in early 2Q CY2025 and ShORe (n=986) in mid-CY2025 Current cash expected to fund operations into 3Q CY20252 Superior Lead Asset Phase 2b demonstrated superiority in combination with SOC therapy, with well tolerated safety profile Sozinibercept has the potential to improve vision for millions of patients with wet AMD Multibillion dollar commercial opportunity in a growing market with an established clinical practice Sozinibercept developed for use in combination with any anti-VEGF-A; will not compete directly with SOC therapies AMD – age-related macular degeneration; MOA – Mechanism of Action; SOC – Standard of care 1CATT Research Group; Maguire MG et al. Ophthalmology. 2016 Aug. 2Additional funding will be required to reach commercialization of sozinibercept and to meet obligations under the Development Funding Agreement ("DFA"). As a result of obligations under the DFA and applicable law regarding liquidity, the Company expects to raise or obtain additional capital in one or more transactions, earlier than 3Q CY 2025 or anticipated topline data readout dates. *Potential for Patent Term Extensions & Data and Market Exclusivity (12 Years for Biologic) Proprietary Technology
~$15bn Global Market and Growing Sozinibercept Designed to Improve Visual Outcomes in Combo with VEGF-A Inhibitors; Potential to Create New Multi-Billion Dollar Class Beovu Avastin Eylea $9.4bn Vabysmo $2.8bn Lucentis ~$2.0bn Potential value proposition: Targeting Improved Visual Function Critical for Patients, Physicians and Payors Global Marketed VEGF-A Inhibitors Sozinibercept is a VEGF-C/D “Trap” Inhibitor Fits Seamlessly into Physician Practice Potential Use with Any VEGF-A Inhibitor Multi-Billion Dollar Commercial Opportunity Biosimilars The $15bn global market comprised of Eylea, Vabysmo, Lucentis revenue plus an estimate for biosimiliars, Avastin off-label, and Beovu of ~$1bn
Experienced Leadership Team Expertise and Track Record to Make a Positive Impact on the Retinal Community Fred Guerard, PharmD, MS Chief Executive Officer Daniel Geffken Interim Chief Financial Officer Megan Baldwin, PhD, MAICD Founder, Chief Innovation Officer & Executive Director Mike Campbell Chief Commercial Officer Arshad M. Khanani, MD, MA, FASRS Managing Partner, Director of Clinical Research and Director of Fellowship at Sierra Eye Associates, and Clinical Professor at the University of Nevada, Reno School of Medicine Management Team Chief Medical Advisor Clinical Advisory Board Charles C. Wykoff, MD, PhD Director of Research, Retina Consultants of Texas, Chairman of Research and Clinical Trials Committee, Retina Consultants of America Tim Jackson, PhD, MB, ChB, FRCophth National Health Service, Consultant at Kings Hospital College Hospital, London Jason Slakter, MD Clinical Profession at New York University School of Medicine and partner at Vitreous Retina Macula Consultants of New York
do not achieve significant vision gains 25% Despite Treatment with Standard of Care Anti-VEGF-A Therapies, the Majority of Patients Achieve Suboptimal Vision Outcomes Despite treatment with anti-VEGF-A therapy* will have further vision loss at 12+ months will have persisting macular fluid >60% >45% The majority of patients fail to achieve 20/40 vision1 Suboptimal vision is associated with decrease in Instrumental Activities of Daily Living (IADL) skills2 *Based on randomised, controlled clinical trial data; >45% fail to achieve ≥ 2 lines improvement in Best Corrected Visual Acuity (BCVA); Persisting fluid: SD-OCT CST ≥ 300 µM or Time-Domain OCT CST ≥ 250 µM IADL: Instrumental activities of daily living (complex activities related to the ability to live independently) 1Mettu PS, et al. Prog Retin Eye Res. 2021 2Hochberg C, et al. Invest Ophthalmol Vis Sci. 2012 May 31.
Hazard for All-cause Mortality1 Higher in People with Vision Impairment Every Letter Counts When Loss of Vision Potentially Leads to Increased Mortality Risk IADL – Instrumental activities of daily living; ETDRS – Early Treatment Diabetic Retinopathy Study chart 1Ehrlich JR et al. “Association between vision impairment and mortality: a systematic review and meta-analysis.” Lancet Glob Health. 2021. 2Christ SL, et al. “Longitudinal relationships among visual acuity, daily functional status, and mortality: the Salisbury Eye Evaluation Study.” JAMA Ophthalmol. 2014. < 20/40 vs. ≥ 20/40 < 20/60 vs. ≥ 20/60 < 20/200 vs. ≥ 20/60 Better Vision Worse Vision Decrease of 1 ETDRS letter per year increases mortality risk by 16%2 associated exclusively with IADL levels
Sozinibercept Has Demonstrated Improvement in Vision Gains and Reduction in Vision Loss Visual Acuity Lucentis remains the standard of care for visual improvements LUCENTIS AVASTIN (OFF LABEL) EYLEA BEOVU VABYSMO EYLEA HD OTX-TKI CLS-ASX EYP-1901 RGX-314 ADVM-022 4D-150 Tyrosine Kinase Inhibitors Gene Therapy SOZINIBERCEPT Opportunity in Wet AMD Market for an Overall Shift Towards Superior Visual Outcomes VEGF-C/D Inhibitor in Combination with Standard of Care 20/40 Low QoL High QoL Current Treatments Emerging Treatments QoL – Quality of Life Jackson, Timothy L., et al. “A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration.” Ophthalmology. June 2023.
Sozinibercept, a Proprietary VEGF-C/D “Trap” Inhibitor, Has the Potential to Address the Limitations of Anti-VEGF-A Therapies The Problem The Solution Wet AMD is a multi-factorial disease. Treatment with VEGF-A inhibitors upregulates VEGF-C/D, driving angiogenesis and vascular permeability. When used in combination with any VEGF-A inhibitor, sozinibercept completely blocks VEGFR-2 and VEGFR-3 signaling. 1 Faricimab also has inhibitory effect on Ang-2. a Bevacizumab is used ’off-label’ for the treatment of neovascular (wet) AMD Faricimab (Vabysmo®)1 SOZINIBERCEPT
Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept VEGF-A and VEGF-C Induce Vascular Leakage/permeability# VEGF-A VEGF-C VEGF-C Stimulates Retinal Angiogenesis^ Circulating VEGF-C Levels Significantly Elevated in AMD Patients ⍭ Elevated VEGF-C in Aqueous Humor Following Anti-VEGF-A therapy in Wet AMD Patients* Additive Benefit of VEGF-A and VEGF-C/D Inhibition in Mouse Wet AMD Model ** ** Control AMD Plasma concentrations (pg/ml) 300 200 100 0 Control Antibody Sozinibercept Aflibercept Aflibercept + sozinibercept CNVArea 70% 78% 91% * 0 200000 400000 600000 Aqueous Humor VEGF-C (pg/ml) 10 8 66% 6 5.4 6.9 8.9 4 2 0 Baseline 1 month 2 months Bevacizumab Bevacizumab VEGF-A VEGF-C VEGF-D
Sozinibercept Is Designed to Integrate into Current Anti-VEGF-A Clinical Practice Superior visual outcomes meaningfully improves patients’ lives Intended to be administered at same anti-VEGF-A visit Patients Better vision outcomes is a high unmet medical need Designed to be agnostic to anti-VEGF-A treatment type, including biosimilars Retina Specialists Better clinical outcomes represent better health economics Visual benefits a key driver in reimbursement Payors / Insurance Companies Concentrated prescriptions in U.S. enables potential self-commercialization opportunity with lean and targeted organization
Physicians Willing to Administer Second Injection to up to 41% of Their Patients for Additional BCVA Improvement What percentage of your Wet AMD patients would you use a second injection (anti-VEGF C/D) immediately after an anti-VEGF-A injection at various levels of BCVA improvement of the combination over SoC? (Among Total Respondents, Avg. % of Patients*, n=125) BCVA improvement over 5 BCVA improvement of 4.1 - 5 BCVA improvement of 3.0 - 4 BCVA improvement under 3 24% 25% 32% 41% Average Percentage of Patients Treated with Second Injection1 TAM – Total Addressable Market 1Source: InCrowd Awareness Trial and Usage (ATU) Report, June 2024 *Averages calculated using the midpoints of each % prescribing allocation group. Callouts indicate statistical significance between groups at 90% CI. Estimate 1% Share of Wet AMD TAM Equals ~$100M+ in Sales Per Annum
PROGRAM DEVELOPMENT PHASE ANTICIPATED MILESTONES PROGRAM RESEARCH / PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ANTICIPATED MILESTONES Wet Age-Related Macular Degeneration (Wet AMD) Sozinibercept For use in combination with anti-VEGF-A therapies Topline data: COAST (in early 2Q CY2025) ShORe (in mid-CY2025) Diabetic Macular Edema (DME) Sozinibercept For use in combination with anti-VEGF-A therapies Phase 3 ready Co-formulation (Sozinibercept + VEGF-A Inhibitor) Sozinibercept Co-formulation with VEGF-A Inhibitor Feasibility underway Long-term Value Opportunities for Sozinibercept Main Patent Family Extends through 2034, with Expansion Opportunities Beyond 2034* *Potential for Patent Term Extensions & Data and Market Exclusivity (12 Years for Biologic)
Robust Phase 2b Trial in Wet AMD Demonstrated Superiority in Visual Outcome Treatment naïve patients with neovascular AMD Key Exclusion Criteria Subfoveal fibrosis or >25% of total lesion Haemorrhage >50% total lesion Other clinically significant ocular disease Key Inclusion Criteria Active CNV >50% lesion, classic / minimally classic / occult BCVA ≥ 25 and ≤ 60 letters CNV – choroidal neovascularisation; IVT – intravitreal; Q4W – once very 4 weeks; ITT – Intent to Treat Population, all participants who were randomised into the study irrespective of whether study medication was administered or not; Safety Population - all participants in the ITT but excluding those who did not receive at least one dose of study medication; mITT – Modified ITT Population, all participants in the Safety Population but excludes any participant without a Baseline VA score and/or any participant who did not return for at least one post-baseline visit Follow-up Randomised (n=366) Sozinibercept 0.5 mg + 0.5 mg ranibizumab IVT Q4W x 6 n=122 sham + 0.5 mg ranibizumab IVT Q4W x 6 n=121 Sozinibercept 2 mg + 0.5 mg ranibizumab IVT Q4W x 6 n=123 Completed Study n=112 (91.8%) Completed Study n=116 (95.9%) Completed Study n=120 (97.6%) Analysed n=122 Analysed n=119 Analysed n=121 Analysis mITT Population Allocation ITT Population Screening
Phase 2b Primary and Secondary Endpoints Select Pre-specified Subgroups Primary Endpoint Key Secondary Endpoints Mean change from baseline in BCVA at week 24 Proportion of patients gaining ≥15 letters from baseline at week 24 Change in central subfield thickness (CST) from baseline at week 24 Change in intra-retinal and sub-retinal fluid from baseline to week 24 Safety and tolerability Predominantly classic, minimally classic, & occult lesions (Stratification Factor) Retinal Angiomatous Proliferation (RAP) detected/not detected at baseline Polypoidal Choroidal Vasculopathy (PCV) detected/not detected at baseline
Demographic/Baseline Disease Characteristic 2 mg sozinibercept + ranibizumab n=123 Mean Age – years ± SD 76.1 ± 9.48 78.8 ± 8.16 77.8 ± 8.82 Sex – n (%) Male 48 (39.7%) 49 (40.2%) 45 (36.6%) Female 73 (60.3%) 73 (59.8%) 78 (63.4%) Caucasian Race – n (%) 117 (99.2%) 119 (99.2%) 117 (97.5%) Mean Visual Acuity (BCVA) – letters ± SD 50.7 ± 10.21 51.1 ± 8.96 49.5 ± 10.26 Mean Total Lesion Area - mm2 ± SD 6.08 ± 3.21 6.48 ± 3.30 6.62 ± 3.39 Predominantly classic – n (%) 15 (12.4%) 15 (12.3%) 16 (13.0%) Minimally classic – n (%) 53 (43.8%) 51 (41.8%) 53 (43.1%) Lesion Type Occult - n (%) 53 (43.8%) 56 (45.9%) 54 (43.9%) PCV detected1 – n (%) 20 (16.5%) 24 (19.7%) 22 (17.9%) RAP detected2 – n (%) 15 (12.7%) 22 (18.5%) 14 (11.8%) Mean central subfield thickness (CST) - mm ±SD 412.10 ± 110.62 425.18 ± 120.45 414.12 ± 123.25 Sub-retinal fluid (SRF) present – % participants 89.3% 84.4% 87.8% Intra-retinal cysts present – % participants 57.9% 63.9% 56.1% Phase 2b Trial Demographics and Baseline Characteristics Intent-to-Treat (ITT) population; SD – standard deviation; BCVA – Best Corrected Visual Acuity 1PCV - polypoidal choroidal vasculopathy, detected by SD-OCT, FA and fundus photography. 2RAP - retinal angiomatous proliferation, detected by SD-OCT, FA and fundus photography. Sham + ranibizumab n=121 0.5 mg sozinibercept + ranibizumab n=122
Sozinibercept 2 mg Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy Sham + 0.5 mg ranibizumab (n=119) 2 mg sozinibercept + 0.5 mg ranibizumab (n=121) 0.5 mg sozinibercept + 0.5 mg ranibizumab (n=122) Mean Change in BCVA (SEM) (Letters) Δ = +3.4 (p=0.0107) 20 15 10 5 0 0 4 8 16 20 24 12 Weeks Total Patient Population +14.2 +10.8 Phase 2b Primary Endpoint Achieved
To Maximize Probability of Success, Best Responding Phase 2b Patients Represents Primary Analysis Population in the Pivotal Phase 3 Trials Sham + 0.5 mg ranibizumab (n=87) 2 mg sozinibercept + 0.5 mg ranibizumab (n=88) +10.3 +16.1 Δ = +5.7 p = 0.0002* Occult & Minimally Classic Lesions (RAP Absent) *Unadjusted p-value Phase 2b demonstrated superior efficacy of +5.7 letter gain over standard of care, based on a pre-specified analysis This patient population (minimally classic & occult) represents ~75% of wet AMD patients 0 4 8 12 16 20 24 0 5 10 15 20 Weeks M e a n c h a n g e i n B C V A ( S E M ) ( l e t t e r s ) Mean Change in BCVA (SEM) (Letters)
Trial: Treatment: Number of Patients: 88 87 240 Baseline BCVA in Letters: 50.5 50.5 53.7 Control Arm in Phase 2b Overperformed MARINA Trial at Week 24 in in Similar Lesion Type Patient Population OPT PHASE 2B +Ran 0.5 q4w +Ran 0.5 q4w Ran 0.5 q4w Sozinibercept + ranibizumab Ranibizumab OPT PHASE 2B MARINA was a Phase 3 registrational trial. Baseline BCVA values across trials vary. Number of patients randomised to treatment group (n, bottom table). Mean change in Best Corrected Visual Acuity (BCVA) from baseline shown in ETDRS letters (top of bars). +5.7 Letter Gain Over Standard of Care MARINA Mean Change in BCVA from Baseline at Week 24 – Sozinibercept Phase 2b vs. MARINA Trial Occult and Minimally Classic Lesions
In a Disease Where Every Letter Counts, a Greater Proportion of Sozinibercept Patients Gained Substantial Vision and Fewer Experienced Vision Loss ≥15 Loss 10-14 Loss 5-9 Loss 1-4 Loss +0-5 Gain +6-10 Gain +11-15 Gain +16-20 Gain +21-25 Gain +26-30 Gain + >30 Gain Legend (ETDRS Letter Change from Baseline to Week 24) 2 mg sozinibercept + ranibizumab N=87 sham + ranibizumab N=85 >30 Letter Gain 9.2% >30 Letter Gain 2.4% Change from Baseline to Week 24 (ETDRS Letters, Individual Participants) Occult and Minimally Classic Lesions (RAP Absent) Vision Loss 2.3% Vision Loss 12.9%
Greater Proportion of Sozinibercept Patients Achieved Minimum Driving-level of Vision (≥20/40) Total Patient Population 18% relative increase compared to ranibizumab control Percentage of Participants with 20/40 Vision or Greater at Week 24 Occult and Minimally Classic, RAP Absent 42% relative increase compared to ranibizumab control
Modified Intent-to-Treat (mITT) population; as observed. IADL – Instrumental activities of daily living; ETDRS – Early Treatment Diabetic Retinopathy Study chart 1Christ SL, et al. “Longitudinal relationships among visual acuity, daily functional status, and mortality: the Salisbury Eye Evaluation Study.” JAMA Ophthalmol. 2014. Sozinibercept Reduced the Proportion of Patients Experiencing Vision Loss by 82% Occult and Minimally Classic Lesions (RAP Absent) 82% relative decrease compared to ranibizumab control Percentage of Participants with any Vision Loss ≥1 ETDRS Letter at Week 24 Decrease of 1 ETDRS letter per year increases mortality risk by 16%2 associated exclusively with IADL levels
Sozinibercept Reduced Retinal Thickness and Dried the Retina Better With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients Mean Change in CST Baseline to Week 24 Sham + 0.5 mg ranibizumab 2 mg sozinibercept + 0.5 mg ranibizumab % of Participants with IR Cysts at Week 24 % of Participants with SRF at Week 24 % Participants -180 -140 -100 -60 86 -133.5 85 -126.8 Mean Change in CST (SEM) (µm) 0 20 40 88 14.8 87 18.4 0 20 40 86 19.8 85 28.2 % Participants mITT; as observed; top of bar – statistic, bottom of bar – n. CST: Central Subfield Thickness; SRF: Subretinal fluid; IR: Intra-retinal.
Sozinibercept Demonstrated Greater CNV and Lesion Regression With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients mITT; as observed; top of bar – statistic, bottom of bar – n. CNV: Choroidal Neovascular. Mean Change in Total Lesion Area at Week 24 Mean Change in CNV Area at Week 24 -6 -4 -2 0 81 -4.4 80 -3.5 Mean Change in Total Lesion Area (SEM) (mm2) -6 -4 -2 0 81 -5.0 80 -3.9 Mean Change in CNV Area (SEM) (mm2) Sham + 0.5 mg ranibizumab (n=80) 2 mg sozinibercept + 0.5 mg ranibizumab (n=81)
Sozinibercept Demonstrated Superior Vision Gains in a Pre-Specified Subgroup of Hard-To-Treat PCV Lesion Patients Sham + 0.5 mg ranibizumab (n=20) 2 mg sozinibercept + 0.5 mg ranibizumab (n=22) Δ +6.7 p = 0.0253* 0 5 10 15 20 22 13.5 20 6.9 Mean Change in BCVA (SEM) (Letters) Polypoidal Choroidal Vasculopathy (PCV) is a difficult-to-treat wet AMD subtype; it is often described as the most prevalent form of wet AMD worldwide PCV is highly prevalent in Asian populations (up to ~60%), while ~8-13% prevalence in Caucasians Phase 3 ShORe and COAST trials enrolled patients with PCV1 PCV Lesions *Unadjusted p-value 1 Evaluated by color fundus photography (FP), fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT)
Pooled Safety for Completed Sozinibercept Trials Combination Therapy Well Tolerated and Comparable to Standard of Care Monotherapy N Participants (%) Sozinibercept Any dose* N=399 (N=1,842 injections) Sozinibercept 2 mg N=263 (N=1,121 injections) Sham + anti-VEGF-A control N=170 (N=854 injections) Ocular TEAEs - Study Eye – related to study product(s) 41 (10.2%) 22 (8.4%) 20 (11.8%) Ocular TEAEs - Study Eye – Severe 4 (1.0%) 2 (0.8%) 2 (1.2%) Intraocular inflammation – Study Eye 71,2,3 (1.8%) 31 (1.1%) 31 (1.8%) Participants with AEs leading to treatment discontinuation 42,4-6 (1.0%) 14 (0.4%) 27,8 (1.2%) Any APTC event 44,5,9,10 (1.0%) 35,9,10(1.1%) 211,12 (1.2%) Deaths 210,13 (0.5%) 210,13 (0.8%) 214,15 (1.2%) 1Transient anterior chamber cell (trace 1-4 cells); 2 SAE of endophthalmitis, with AE’s of hypopyon and anterior chamber cell (n=1; 0.5 mg); 3 SAE of vitritis (n=1; 0.5 mg); 4Non-fatal myocardial infarction; 5Cerebrovascular accident; 6Enteritis; 7Abdominal pain; 8Increased IOP; 9 Non-fatal angina pectoris; 10Fatal congestive heart failure/myocardial infarction; 11Non-fatal arterial embolism; 12Embolic stroke; 13Metatstaic ovarian cancer; 14 Pneumonia; 15 infective endocarditis. *Any dose (sozinibercept 0.3 mg, 0.5 mg, 1 mg or 2 mg) **Masked data represent pooled data from both sozinibercept combination and standard of care monotherapy treatment arms. The Phase 3 clinical trial masked data are incomplete and subject to additional analysis once unmasked. There is no assurance that standard of care monotherapy in our Phase 3 clinical trials will yield similar results to our prior clinical trials or previously published clinical trials with anti-VEGF-A monotherapies. As a result, there can be no assurance that topline results for sozinibercept from the Phase 3 clinical trial, if completed, will be consistent with results from masked data available to date. Pooled safety analysis of 399 patients for completed sozinibercept trials Data Monitoring Committee (“DMC”) regularly reviews data from ongoing Phase 3 COAST and ShORe studies Safety data from our completed sozinibercept trials show sozinibercept combination therapy has a safety and tolerability profile comparable to standard of care anti-VEGF-A monotherapy. Masked data from patients that have completed the week 52 visit in the ongoing Phase 3 clinical trials show greater mean BCVA increases from baseline than results with standard of care anti-VEGF-A monotherapy from Opthea’s Phase 2b study**
N Participants (%) Sozinibercept Any dose* N=399 (N=1,842 injections) Sozinibercept 2 mg N=263 (N=1,121 injections) Sham + anti-VEGF-A control N=170 (N=854 injections) Intraocular Inflammation1 7 (1.8%) 3 (1.1%) 3 (1.8%) OPT-302-1001 (Phase 1/2a wet AMD) 2 0 0 Uveitis with anterior chamber cell 1+ 1 0 0 Uveitis with anterior chamber cell 2+ 1 0 0 OPT-302-1002 (Phase 2b wet AMD) 3 1 2a Endophthalmitis with anterior chamber 1+ and hypopyon 1 0 0 Vitritis 1 0 0 Anterior chamber cell, trace 1 1 2a OPT-302-1003 (Phase 1b/2a DME) 2b 2b 1 Iritis with keratic precipitates and anterior chamber cell 2+ 1 1 0 Iritis with anterior chamber cell 2+ 0 0 1 Anterior chamber cell 4+, associated with cataract extraction/ intraocular lens implant and hyphema 1b 1b 0 Intraocular Inflammation Observed in Combination Therapy Across Completed Sozinibercept Trials Similar to Standard of Care Safety population 1AEs observations considered to be indicative of intraocular inflammation, defined prior to database lock aObserved during ophthalmic examination, but not reported as TEAEs bConsidered associated with lens extraction and not reported as TEAEs
Phase 3 Clinical Program Is Informed by Phase 2b Results and Optimized for Success Hierarchical primary analysis first conducted in the high-responding occult and minimally classic population (RAP absent), followed by total patient population Two robust pivotal trials studying sozinibercept in combination with Eylea® and Lucentis® in treatment naïve patients with wet AMD Phase 3 designed to support broad label for use in combination with any VEGF-A inhibitor for all wet AMD patients (treatment naïve and prior treated)
Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced Topline Data Anticipated for COAST in Early 2Q CY 2025 and ShORe in Mid-CY2025 Design Multi-center, double-masked, randomized (1:1:1), sham control Treatment naïve wet AMD patients Regulatory Quality ~90% power, 5% type I error rate Sample Size COAST n=998; ShORe n=986 Comparators 2 mg Eylea® q8w (COAST) & 0.5 mg Lucentis® q4w (ShORe)
Phase 3 Primary and Secondary Endpoints Primary Efficacy Endpoint at Week 52 to Support BLA Submission Primary Endpoint Key Secondary Endpoints (Baseline to Week 52) Mean change from baseline in BCVA at week 52 Proportion of participants gaining ≥15 letters Proportion of participants gaining ≥10 letters Change in choroidal neovascularization area Proportion of participants with absence of both sub-retinal fluid and intra-retinal cysts
Phase 3 Trial Design Supports Potential Broad Label for Use With Any Anti-VEGF-A Therapy Ranibizumab q4w + Sozinibercept q4w Ranibizumab q4w + Sham q4w Ranibizumab q4w + Sozinibercept q8w Aflibercept q8w + Sozinibercept q4w Aflibercept q8w + Sham q4w Aflibercept q8w + Sozinibercept q8w Safety Follow-up Week 100 Standard of care administered according to approved dosing schedule: aflibercept (2 mg IVT q8w after 3 loading doses) and ranibizumab (0.5 mg IVT q4w after 3 loading doses). Sozinibercept dosed at 2 mg. Note that Sham administered at visits when sozinibercept is not administered. Maintenance dosing continued through end of the safety follow-up. Safety Follow-up Week 100 Aflibercept + Sozinibercept q4w Aflibercept + Sozinibercept q4w Aflibercept + Sham q4w Ranibizumab + Sozinibercept q4w Ranibizumab + Sozinibercept q4w Ranibizumab + Sham q4w Wet AMD Tx-Naïve Patients N=986 Enrollment Complete Enrollment Complete Maintenance Dosing (40w) Loading Dosing (12w) Efficacy Phase Maintenance Dosing (40w) Loading Doses (12w) Efficacy Phase Wet AMD Tx-Naïve Patients N=998 Topline Data Anticipated in Early 2Q CY2025 Primary Efficacy Endpoint Week 52 Primary Efficacy Endpoint Week 52 Topline Data Anticipated in Mid-CY2025
Advancing Therapeutic Innovations to Transform Patient Outcomes with Superior Vision Gains We are dedicated to advancing sozinibercept to improve patients’ visual outcomes Clinical Milestones Manufacturing Scale-up Regulatory Preparations Commercial Readiness Phase 3 program enrolled 1,984 patients across COAST and ShORe Topline data anticipated for COAST in early 2Q CY2025 and ShORe in mid-CY2025 FDA Fast Track designation allows rolling submission of completed BLA modules Production of validation batches supportive of BLA filing and launch Strengthen medical expert engagement and develop market access strategy Complete development of product launch plan Next Steps
Recent Financings Anticipated to Provide Cash Runway Through Both Pivotal Topline Data Readouts Financial Overview Ticker OPT (ASX/NASDAQ) Shares Outstanding1 Ordinary Shares: 1,231.1M ADS equivalents: 153.9M Cash/Cash Equivalents2 US$207.3M Offices Melbourne, Australia Princeton, NJ Development Funding Agreement (DFA) Total funding drawn under DFA: US$170M Provides non-dilutive funding for development of sozinibercept If sozinibercept is approved, repayment is capped at 4x investment and split between fixed payments and variable payments at 7% of revenues No amounts owed if the clinical trials do not meet the primary endpoint or if regulatory approval is not received3 1As of June 30, 2024, pro-forma for the 2024 Retail Entitlement Offer which closed in July 2024. 2Includes $172.5M as of June 30, 2024 and $34.8M net proceeds from the 2024 Retail Entitlement Offer which closed in July 2024. 3In certain circumstances, upon or following the termination of the DFA, the Company may owe the DFA investors a multiple of amounts paid to the Company under the DFA. Please refer to the description of the DFA included in the Company’s Form 6-K filed with the SEC on August 15, 2022 and the DFA filed as Exhibit 4.14 to the Company’s Annual Report on Form 20-F filed with the SEC on September 29, 2022 for more information. Note: Additional funding will be required to reach commercialization of sozinibercept and to meet obligations under the Development Funding Agreement ("DFA"). As a result of obligations under the DFA and applicable law regarding liquidity, the Company expects to raise or obtain additional capital in one or more transactions, earlier than 3Q CY 2025 or anticipated topline data readout dates.
Addressing unmet medical need of improved efficacy in large wet AMD patient population in a potential ~$15B market 1 Sozinibercept Will Not Compete Head-to-Head with Anti-VEGF-A Differentiated Combination Approach Targeting Better Visual Outcomes Drives Commercial Value First and only therapy to have demonstrated superior visual outcomes over anti-VEGF-A therapy with a novel and highly differentiated MOA Only asset in near or long-term pipeline with potential to disrupt treatment paradigm on basis of efficacy in wet AMD Concentrated prescriptions in U.S. enables potential self-commercialization opportunity with lean and targeted organization 2 3 4 MOA – Mechanism of Action
Opthea (PK) (USOTC:CKDXF)
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De Sep 2024 a Oct 2024
Opthea (PK) (USOTC:CKDXF)
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De Oct 2023 a Oct 2024
