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 January 2025
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: 01/28/2025
Transforming Patient Outcomes with Superior Vision Gains Investor Event | New York City | January 28, 2025 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. This presentation should be read in conjunction with Opthea's other period corporate reports and continuous disclosure announcements filed with the Australian Securities Exchange, the Australian Securities and Investments Commission and the U.S. Securities and Exchange Commission. 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 potential for Priority Review for the Company’s product candidate, the viability of future opportunities, future market supply and demand, the potential coverage, pricing and labeling for the Company’s product candidate (if approved), the expected timing of top-line data, expected intellectual property and exclusivity protections for the Company’s product candidate, the future cash runway, the financial condition, results of operations and business of Opthea, certain plans, objectives, expectations and strategies of management of Opthea, including with respect to the current and planned clinical trials of its product candidate and the timing thereof, the expected timing for planned regulatory submissions and potential approvals and the market access opportunities and strategies, and the future performance of Opthea, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “opportunity,” “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, the Australian Securities and Investments Commission and the Australian Securities Exchange 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, clinical research organization and labor costs, intellectual property protections, the development, testing, production, marketing and sale of drug treatments, 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.
Featured Speakers Opthea Management Joined by Global Retina Thought Leader Charles C. Wykoff, MD, PhD Chief Investigator for COAST Clinical Advisory Board Member Retina Consultants of Texas, Director of Research Retina Consultants of America, Chairman of Research Blanton Eye Institute, Houston Methodist Hospital, Professor of Clinical Ophthalmology and Deputy Chair of Ophthalmology Fred Guerard, PharmD, MS Chief Executive Officer Graybug Vision, CEO Novartis, Worldwide Head Ophthalmology Alcon, Global Franchise Head Pharmaceuticals Led extension of Novartis ophthalmology piplines: Encore Vision, Lubricin®, Luxturna®, Xiidra® Mike Campbell Chief Commercial Officer Viatris, Sr. VP of Eye Care Novartis, VP, Biologic Commercialization, pre-launch Beovu® Shire, VP Sales & Marketing Xiidra®, divestiture to Novartis Genentech, Head of Sales, Launched Lucentis® for wet AMD, DME, and RVO
Topic Speaker Welcome Fred Guerard, PharmD, MS Wet AMD Unmet Medical Needs Charles C. Wykoff, MD, PhD Sozinibercept Wet AMD Clinical Data Overview Wet AMD U.S. Commercial Market Dynamics Mike Campbell Sozinibercept Customer Insights Strategic Outlook Fred Guerard, PharmD, MS Q&A Session All Focus of Today Is U.S. Sozinibercept Commercial Readiness Preparations
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 Deliver Superior 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 may raise or obtain additional capital in one or more transactions, earlier than 3Q CY 2025. *Potential for Patent Term Extensions & Data and Market Exclusivity (12 Years for Biologic) Proprietary Technology
Anticipated Clinical and Manufacturing Timelines Support BLA Submission in 1H26 and Potential Approval by End of CY2026 FDA Fast Track designation allows rolling submission of completed BLA modules and potential for Priority Review designation at BLA acceptance Drug product PPQ release in early CY25 COAST topline data in early 2Q CY25 ShORe topline data in mid-CY25 BLA submission in 1H CY26 Potential BLA approval as early as end of CY26
Topic Speaker Welcome Fred Guerard, PharmD, MS Wet AMD Unmet Medical Needs Charles C. Wykoff, MD, PhD Sozinibercept Wet AMD Clinical Data Overview Wet AMD U.S. Commercial Market Dynamics Mike Campbell Sozinibercept Customer Insights Strategic Outlook Fred Guerard, PharmD, MS Q&A Session All Opthea Investor Day Agenda
Wet AMD Unmet Medical Needs & Sozinibercept Clinical Data Overview Charles C. Wykoff, MD, PhD
Targets VEGF-A, VEGF-B, & PlGF Targets VEGF-A, & Ang-2 2022 2023 Targets all isoforms of VEGF-A 2019 Last Therapy to Improve Visual Outcomes for Wet AMD Patients Was Launched Nearly Two Decades Ago Targets VEGF-A, VEGF-B, & PlGF Targets all isoforms of VEGF-A Targets isoform-specific VEGF-A165 inhibition Improved Efficacy 2004 2006 2011 off-label FDA APPROVAL Legend: Current Wet AMD Treatment Landscape Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
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. Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Effect of Treatment Paradigm Change in nAMD on Outcomes Based on Results From a 12-year Follow-up of 42,161 patients1,2 Group (n) Number of injections (mean ± SD) Number of visits (mean ± SD) Visit/injection ratio (median) 2016–2017 (633) 11.2 ± 6.1 24.2 ± 7.3 2.17 2014–2015 (6,083) 10.4 ± 6.1 22.5 ± 7.9 2.20 2012–2013 (5,432) 7.9 ± 5.1 21.9 ± 8.2 3 2010–2011 (5,017) 9.3 ± 5.6 23.4 ± 9.9 2.6 2008–2009 (2,395) 9.5 ± 5.8 24.4 ± 11.2 2.71 Baseline VA improved over the years—patients identified earlier Final VA improved over the years In a multivariable analysis accounting for baseline VA, which improved over the years, year of treatment initiation was not related to better outcomes Baseline VA remains strongly associated with outcome nAMD – neovascular age-related macular degeneration; VA – visual acuity 1Schwartz R. Ophthalmol Retina. 2021 2Data on file Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Visual Outcomes Are the #1 Factor in Patients’ Anti-VEGF-A Preference Bhagat D, Kirby B, Bhatt H, Jager R, George M, Sheth V. Patient Preferences Associated with Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema. Clin Ophthalmol. 2020 Oct 1;14:2975-2982. doi: 10.2147/OPTH.S273564. PMID: 33061283; PMCID: PMC7534869. Relative Importance of Treatment Attributes for Patients Receiving Anti-VEGF-A Monotherapy n=300 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Improving Vision Now the Largest Unmet Need in Wet AMD for Retina Specialists Which factors are more important to you when selecting an anti-VEGF agent? n=1,021 ASRS PAT Survey 2024 What are the greatest unmet needs in treating wet AMD and DME? n=1,012 ASRS PAT Survey 2023 Ability to improve vision gains and maintain vision gains Improve vision American Society of Retina Specialists (ASRS) annual Preferences and Trends (PAT) survey. AMD, age-related macular degeneration; DME, diabetic macular edema; VEGF, vascular endothelial growth factor; US, United States of America; Intl, international Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Better Durability Better Vision Outcomes Emerging Treatments for Wet AMD: Better Vision Outcomes or Durability Sozinibercept (OPT-302) Sozinibercept is the only late-stage drug in development targeting better vision outcomes OTX-TKI CLS-AX EYP-1901 RGX-314 ADVM-022 4D-150 Tyrosine Kinase Inhibitors Gene Therapy Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Sozinibercept, a First-In-Class VEGF-C/D “Trap” Inhibitor, Has the Potential to Address the Limitations of Anti-VEGF-A Therapies 1 Faricimab also has inhibitory effect on Ang-2. a Bevacizumab is used ’off-label’ for the treatment of neovascular (wet) AMD 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, OPT-302 completely blocks VEGFR-2 and VEGFR-3 signaling. Faricimab (Vabysmo®)1 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
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 OPT-302 Aflibercept Aflibercept + OPT 302 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 ^Tammela et al., Nature Cell Biology, 2011; # Zhou et al. BMC Ophthalmology (2020) 20:15; # Cao et al,. Circ Res., 2004; ⍭ Lashkari et al, 2013 ARVO Annual Meeting, 4999-A0128; *Cabral et al,. 2018 Ophthalmology Retina (2018). VEGF-A VEGF-C VEGF-D Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Sozinibercept Is the Only Drug in Development Having Demonstrated Superiority in Combination with Anti-VEGF-A Therapy for Wet AMD 1 Superior vision gains observed for combination therapy over Lucentis® alone Safety profile similar to standard of care observed in over 1,800 injections 2 3 Consistent anatomical improvements further validate novel MOA MOA – Mechanism of Action; SOC – Standard of care Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Sozinibercept 2 mg Combination Therapy Demonstrated Over 30% Improvement in Visual Acuity over Ranibizumab Monotherapy Sham + 0.5 mg ranibizumab (n=119) 2 mg sozinibercept + 0.5 mg ranibizumab (n=121) 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 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Sozinibercept Was Well Tolerated Safety of Combination Therapy Comparable to Standard of Care Monotherapy 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) 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%) Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Similar Rate of Intraocular Inflammation Between Standard Of Care and Sozinibercept in Combination Therapy 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 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 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Global Pivotal Program Involves 33 Countries and ~400 Sites Combination with Aflibercept Enrolled (N=998) Aflibercept 2 mg Q8W + Sham Aflibercept 2 mg Q8W + Sozinibercept 2 mg Q4W Aflibercept 2 mg Q8W + Sozinibercept 2 mg Q8W Randomized (1:1:1) CNV – choroidal neovascularization; BCVA – Best Corrected Visual Acuity; RAP – retinal angiomatous proliferation Ranibizumab 0.5 mg Q4W + Sham Ranibizumab 0.5 mg Q4W + Sozinibercept 2 mg Q4W Ranibizumab 0.5 mg Q4W + Sozinibercept 2 mg Q8W Combination with Ranibizumab Enrolled (N=986) Randomized (1:1:1) Multi-center, sham controlled, double-masked trials in treatment naïve wet AMD patients Key Exclusion Criteria Subfoveal fibrosis or >25% of total lesion Hemorrhage >50% total lesion Other clinically significant ocular disease RAP lesions Key Inclusion Criteria Active CNV >50% lesion: classic, minimally classic, occult BCVA ≥ 25 and ≤ 60 letters Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Pivotal Trial Design Supports Potential Broad Label for Use With Any Anti-VEGF-A Therapy 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. Proportion of participants gaining ≥15 letters Proportion of participants gaining ≥10 letters Change in CNV area Proportion of participants with absence of both SRF and IR cysts Wet AMD Tx-Naïve Patients N=998 Wet AMD Tx-Naïve Patients N=986 1:1:1 1:1:1 Loading Doses Maintenance Dosing Primary Endpoint Mean change in BCVA from baseline to week 52 Key Secondary Endpoints (Baseline to Week 52) Topline Data COAST anticipated in early 2Q CY 25 ShORe anticipated in mid-CY25 Aflibercept q8w + Sozinibercept q4w Aflibercept q8w + Sham q4w Aflibercept q8w + Sozinibercept q8w Aflibercept + Sozinibercept q4w Aflibercept + Sozinibercept q4w Aflibercept + Sham q4w Safety Follow-up Week 100 Ranibizumab q4w + Sozinibercept q4w Ranibizumab q4w + Sham q4w Ranibizumab q4w + Sozinibercept q8w Ranibizumab + Sozinibercept q4w Ranibizumab + Sozinibercept q4w Ranibizumab + Sham q4w Safety Follow-up Week 100 Primary Efficacy Endpoint Week 52 Primary Efficacy Endpoint Week 52 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
1st Primary Analysis Population in Phase 3 2nd Primary Analysis Population in Phase 3 Phase 2b Superiority Data Informed Enrichment of Phase 3 *Unadjusted p-values 1Olsen, Timothy W et al. Fluorescein angiographic lesion type frequency in neovascular Age-Related macular degeneration. Ophthalmology, 111(2), 250 – 255. 2Daniel, E. et al. Outcomes in eyes with retinal angiomatous proliferation in the comparison of age-related macular degeneration treatments trials (CATT). Ophthalmology, 123(3), 609–616. 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 ) 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) Mean Change in BCVA (SEM) (Letters) Total Patient Population (RAP Absent) Represents ~75%1 of wet AMD patients Represents ~90%2 of wet AMD patients Δ = +4.4 p = 0.0025* +10.6 +15.0 Sham + 0.5 mg ranibizumab (n=102) 2 mg sozinibercept + 0.5 mg ranibizumab (n=103) Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Phase 2b Phase 3 Demographic/Baseline Disease Characteristic Sham + ranibizumab n=121 2 mg sozinibercept + ranibizumab n=123 COAST N=997* ShORe N=985* Mean Age – years ± SD 76.1 ± 9.48 77.8 ± 8.82 74.8 ± 8.02 75.4 ± 8.47 Sex – n (%) Male 48 (39.7%) 45 (36.6%) 442 (44.3%) 456 (46.2%) Female 73 (60.3%) 78 (63.4%) 556 (55.7%) 530 (53.8%) Race – n (%) Caucasian 117 (99.2%) 117 (97.5%) 859 (86.1%) 825 (83.7%) Asian 0 (0.0%) 0 (0.0%) 85 (8.5%) 134 (13.6%) Mean Visual Acuity (BCVA) – letters ± SD 50.7 ± 10.21 49.5 ± 10.26 52.5 ± 9.43 52.2 ± 9.12 Mean Total Lesion Area - mm2 ± SD 6.08 ± 3.21 6.62 ± 3.39 6.38 ± 3.20 6.37 ± 3.09 Lesion Occult - n (%) 53 (43.8%) 54 (43.9%) 555 (55.7%) 568 (57.6%) Minimally classic – n (%) 53 (43.8%) 53 (43.1%) 340 (34.1%) 334 (33.9%) Predominantly classic – n (%) 15 (12.4%) 16 (13.0%) 102 (10.2%) 84 (8.5%) PCV detected1 – n (%) 20 (16.5%) 22 (17.9%) 261 (26.2%) 236 (23.9%) RAP detected2 – n (%) 15 (12.7%) 14 (11.8%) — — Mean central subfield thickness (CST) - mm ±SD 412.10 ± 110.62 414.12 ± 123.25 446.5 ± 139.7 451.7 ± 137.8 Sub-retinal fluid (SRF) present – % participants 89.3% 87.8% 95.8% 94.3% Intra-retinal cysts present – % participants 57.9% 56.1% 78.6% 83.7% Phase 3 Enrolled a Higher Proportion of Patients With Best Responding Lesion Types Compared to Phase 2b SD – standard deviation; BCVA – Best Corrected Visual Acuity *Intent-to-Treat (ITT) population; 1 patient in each of COAST and ShORe was randomized but not treated 1PCV - polypoidal choroidal vasculopathy, detected by SD-OCT, FA and fundus photography. 2RAP - retinal angiomatous proliferation, detected by SD-OCT, FA and fundus photography. Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Higher Proportion of Patients With Best Responding Lesion Types Sham + 0.5 mg ranibizumab (n=20) 2 mg sozinibercept + 0.5 mg ranibizumab (n=22) Δ +6.7 p = 0.0253* PCV Lesion Types Sham + 0.5 mg ranibizumab (n=47) 2 mg sozinibercept + 0.5 mg ranibizumab (n=49) Δ +6.5 p = 0.0005* Occult (RAP Absent) Lesion Types Proportion of Population at Baseline Phase 2b 43.9% COAST 55.7% ShORe 57.6% Phase 2b 17.2% COAST 26.2% ShORe 24.0% *Unadjusted p-value PCV – Polypoidal Choroidal Vasculopathy Proportion of Population at Baseline Phase 2b Phase 2b Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Design supports potential broad label for combination with any anti-VEGF-A therapy and provides data on sozinibercept dosing flexibility Superior vision is the #1 unmet need in wet AMD for patients and physicians Large, global pivotal program optimized for success with primary analysis on high responding patient population Sozinibercept Has the Potential to Transform Wet AMD Clinical Practice 1 2 3 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Wet AMD U.S. Commercial Market Dynamics & Sozinibercept Customer Insights Mike Campbell
Superior Vision Is the #1 Unmet Need in Wet AMD Across Patients, Retina Specialists, and Payers Sozinibercept integrates seamlessly into a highly attractive U.S. wet AMD market Substantial Market Opportunity Established and Concentrated Market Favorable Market Access Environment ~$7B potential addressable U.S. market1 and >1.2M treated eyes annually2 Sozinibercept developed for broad combination potential and superior vision Buy-and-bill business model supports second injection Scalable market with ~1,400 physicians driving 80% of U.S. injection volume3 The top 5 product attributes in wet AMD are related to visual acuity4 >90% of the U.S. wet AMD patient population are covered by Medicare5 1 2 3 1Assumes U.S. represents 59% of wet AMD market (2024 GlobalData). 2Based on prevalence, treatment and diagnosis rate, and bilateral disease factor. See slide 31. 3,5Komodo Health 2024 4U.S. Payer Research (N=16), Fingerpaint 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Opthea Commercial Leadership Team Has Strong Track Record and Experience Launching New Retina Therapies Opthea Commercial Leadership Team Has Over Half Century of Retina Launch Expertise Anand Sundaram VP, Marketing 10+ years in retina Launched Lucentis® PFS, Beovu®, and Izervay™ Marketing and market access leadership Mike Campbell Chief Commercial Officer 26+ years in ophthalmology & retina Launched Lucentis® for wet AMD, DME, RVO, pre-launch Beovu® Field, marketing, market access, and operations leadership Anthony Bonifazio VP, Market Access 15+ years in retina Launched Lucentis® PFS, Beovu®, and Izervay™ Field and market access leadership Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Branded VEGF-A Inhibitors Sozinibercept Designed to Tap into the Entire Anti-VEGF-A Market With a Broad Combination Indication and No Direct Competitors Potential Total Addressable Wet AMD Market Sozinibercept *potential market size assuming branded pricing ~30%2 of patients receive biosimilars and off-label AVASTIN® Global wAMD Revenues of Anti-VEGF-A Inhibitors1 ~$12B Branded VEGF-A Inhibitors Biosimilars & Off-label Biosimilars & Off-label 1GlobalData 2024 2Komodo Health 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook ~$8.2B ~$3.5B*
U.S. Wet AMD Market Is Well-Established with High Diagnosis and Treatment Rates Estimate >1.2M eyes treated annually in U.S. with anti-VEGF-A therapy ~1.5M U.S. Wet AMD Prevalence1 Diagnosis Rate2 80% 1.2M Diagnosed Patients Treatment Rate3 75% 0.9M Treated Patients Bilateral Disease3 35% 1David B. Rein, et al. JAMA Ophthalmol. 2022 2Retina Specialist Quantitative Survey (N=125), ClearView 2022 3Komodo Health 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
High Concentration of Injection Volume in U.S. Wet AMD Market Enables a Lean Commercial Footprint ~1,400 HCPs represent 80% of injection volume ~500 HCPs represent 50% of injection volume 4 private equity firms represent ~25% of injection volume U.S. Wet AMD HCP Concentration Curve1 HCP – Healthcare Professional 1Komodo Health 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
U.S. Physicians in the Wet AMD Market Continue to Use Branded Therapies, Despite Increasing Availability of Lower-Cost Options Vabysmo Launch Biosimilars Launch % of Wet AMD Patients on An Anti-VEGF-A Therapy Claim, by Product1 OFF-LABEL & BIOSIMILARS BRANDED ANTI-VEGF-A Sozinibercept designed to be used in combination with any anti-VEGF-A therapy Providers continue to choose novel branded agents to treat their wet AMD patients Eylea HD Launch 1Komodo Health 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Practices directly "buy" the product Practices receive reimbursement with 4.3% product margin Practices store and inject product in their offices Practices directly "bill" payers Buy-and-Bill Business Model Supports Combination Therapy for Retina Practices Buy-and-Bill Model Injectable products are critical for the financial health of a retina practice Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Practice Administrators consulted in National Retina Advisory Boards Medical Directors engaged in payer research covering ~204M lives Robust U.S. Market Research Informs Commercial Launch Strategy 350 Retina Specialists surveyed in three rounds of market research 16 19 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
All Customers Highlight Vision as the #1 Unmet Need in Wet AMD Sozinibercept Value Proposition Highly Aligns with Customer Needs Patients Retina Specialists Payers Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Combination Therapy Delivering Superior Vision Would Meet Patients’ Highest-Ranking Attribute When Selecting Wet AMD Therapy Vision is the #1 unmet need for patients Visual outcomes are the #1 objective in patients’ anti-VEGF-A preference The majority of patients fail to achieve >20/40 in spite of sufficient anti-VEGF-A treatment2 1Ozdemir S, et al. PLoS One. 2022 2Mettu PS, et al. Prog Retin Eye Res. 2021 n=180 Vision Relative Attribute Importance in Anti-VEGF-A Patient Preference1 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Which factors are more important to you when selecting an anti-VEGF agent? Improving Vision Is the Largest Unmet Need in Wet AMD for Retina Specialists ASRS PAT Survey 2024 (n=1,021) Ability to improve vision gains and maintain vision gains American Society of Retina Specialists (ASRS) annual Preferences and Trends (PAT) survey. AMD, age-related macular degeneration; DME, diabetic macular edema; VEGF, vascular endothelial growth factor; US, United States of America; Intl, international Vision is the #1 unmet need for retina specialists Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
U.S. Retina Specialists Are Willing to Administer Second Injection to at Least 24% 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 BCVA – Best Corrected Visual Acuity TAM – Total Addressable Market 1Source: Awareness Trial and Usage (ATU) Report, InCrowd 2024 *Averages calculated using the midpoints of each % prescribing allocation group. Estimate 1% Share of Wet AMD TAM Equals ~$100M+ in Sales Per Annum Vision is the #1 unmet need for retina specialists Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Additional injections in the established buy-and-bill business model supports practice economics Sozinibercept Has the Potential to Serve Both Clinical and Non-Clinical Needs for Retina Specialists Vision is the #1 unmet need for retina specialists Clinical Clinical Non-clinical Vision improvement over anti-VEGF-A monotherapy is a straightforward conversation for retina specialists to have with patients Physicians willing to administer 2nd injection to ≥1/4 of their patients for additional vision improvement Early positive clinical experience in harder-to-treat patients unlocks utilization across the category Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
RANK: Product Attributes Ranked by Importance in Plan’s Coverage Decision-Making U.S. Payer’s Top 5 Product Attributes Are Related to Vision Vision is the #1 unmet need for payers HIGH LOW Mean improvement in vision (BCVA) Proportion of patients achieving 20/40 vision or better Proportion of patients gaining vision Maintenance of vision Time to improvement in vision Source: U.S. Payer Research (N=16), Fingerpaint 2024 Avg. Score (N=16) 1.9 3.1 3.5 3.9 6.1 6.8 7.2 7.6 8.1 8.4 8.5 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
3% 5% 49% 43% Medicare Advantage Commercial Payer Mix Supports a Favorable Access Environment for Sozinibercept Other Vision is the #1 unmet need for payers Medicare Fee-for-Service U.S. Wet AMD Payer Mix1 >90% Medicare Sozinibercept clinical profile achieved desired threshold to potentially support broad coverage similar to anti-VEGF-A Anticipate streamlined access for sozinibercept combination therapy similar to anti-VEGF-A 1Komodo Health 2024 Managed Medicare with broad coverage profiles for branded anti-VEGF-A Unmanaged Medicare with minimal access restrictions for branded anti-VEGF-A Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Payers view a minimum of 20% improvement in vision over anti-VEGF-A monotherapy as clinically meaningful to potentially support broad coverage1 Sozinibercept's Clinical Profile Demonstrated in Phase 2b Met the Desired Threshold to Potentially Support Broad Coverage in the U.S. Vision is the #1 unmet need for payers Sozinibercept Phase 2b Relative Vision Improvement Polypoidal Choroidal Vasculopathy +6.7L Minimally Classic & Occult (-RAP) Total Patient Population (-RAP) +5.7L +4.4L 42% 56% 96% 1U.S. Payer Research (N=16), Fingerpaint 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
VEGF-A Inhibitors Mechanism of Action Combination Coverage (N=16) VEGF-A inhibitor VEGF-A inhibitor VEGF-A + VEGF-B + PIGF inhibitor VEGF-A + VEGF-B + PIGF inhibitor VEGF-A inhibitor VEGF-A + Ang-2 inhibitor VEGF-A inhibitor VEGF-A inhibitor Anti-VEGF-A Appropriate for Sozinibercept Combination1 Payers Confirmed Coverage for Potential Broad Sozinibercept Label in Combination with Any Anti-VEGF-A Assuming Positive Phase 3 Phase 3 design in combination with Eylea and Lucentis enables potential broad sozinibercept combination with any anti-VEGF-A Vision is the #1 unmet need for payers Phase 3 design and target indication statement reviewed with FDA at end of Phase 2 1U.S. Payer Research (N=16), Fingerpaint 2024 Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Payers Indicated Sozinibercept Combination Therapy with Any Anti-VEGF-A Could Be Priced Comparably to Branded Anti-VEGF-A Therapies $1,850 $1,950 $2,190 $2,625 Potential price range for sequential injection based on launch U.S. WAC of branded anti-VEGF-A Vision is the #1 unmet need for payers WAC – Wholesale Acquisition Cost Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Soziniberept Designed to Deliver on Highly Aligned Customer Priorities Superior Vision Is the #1 Unmet Need in Wet AMD Patients Retina Specialists Payers Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Vision Is the Most Important Attribute for Patients When Choosing Their Wet AMD Therapy Planning strategies to activate patients on superior vision through traditional, digital, and social media executions. Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Physicians Indicate They Would Treat a Minimum of 24% of Their Patients with Sozinibercept for Any Additional Vision Improvement Sozinibercept is differentiated with superior vision outcomes and a nonclinical profile supportive of practice logistics and economics. Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Payers View a 20% Relative Improvement on Vision as Meaningful to Potentially Support Broad Sozinibercept Coverage in Wet AMD Engaging payers early in support of potential broad coverage and a smooth reimbursement process. Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Superior Vision Is the #1 Unmet Need in Wet AMD Across Retina Specialists, Patients, and Payers Opthea Commercial Leadership Team Has Over Half Century of Retina Launch Expertise Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook Sozinibercept integrates seamlessly into a highly attractive U.S. wet AMD market Substantial Market Opportunity Established and Concentrated Market Favorable Market Access Environment ~$7B potential addressable U.S. market1 and >1.2M treated eyes annually2 Sozinibercept developed for broad combination potential and superior vision Buy-and-bill business model supports second injection Scalable market with ~1,400 physicians driving 80% of U.S. injection volume3 The top 5 product attributes in wet AMD are related to visual acuity4 >90% of the U.S. wet AMD patient population are covered by Medicare5 1 2 3 1Assumes U.S. represents 59% of wet AMD market (2024 GlobalData). 2Based on prevalence, treatment and diagnosis rate, and bilateral disease factor. See slide 31. 3,5Komodo Health 2024 4U.S. Payer Research (N=16), Fingerpaint 2024
Fred Guerard, PharmD Strategic Outlook
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 Potential BLA filing as early as CY2026 DS PPQ campaign completed Sep-2024; update on DP PPQ in early CY2025 PPQ validation batches supportive of BLA filing and launch Hired seasoned retina commercial launch leaders and conducted robust research Complete development of product launch plan Progress & Next Steps DS: Drug Substance; DP: Drug Product Investor Day Tracker: Wet AMD Unmet Need & Sozinibercept Clinical Data Commercial Market Dynamics & Sozinibercept Customer Insights Strategic Outlook
Question & Answer Session Fred Guerard, PharmD, MS Chief Executive Officer Charles C. Wykoff, MD, PhD Chief Investigator for COAST Clinical Advisory Board Member Mike Campbell Chief Commercial Officer Anthony Bonifazio VP, Market Access Anand Sundaram VP, Marketing
Opthea (PK) (USOTC:CKDXF)
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