sozinibercept (OPT-302) / Opthea, Ligand - LARVOL DELTA

A Dose Ranging Study of OPT-302 With Aflibercept for Persistent Diabetic Macular Edema (clinicaltrials.gov) - P1/2 | N=153 | Completed | Sponsor: Opthea Limited | Phase classification: P1b/2a ➔ P1/2

Phase classification • Diabetic Macular Edema • Ophthalmology

ShORe: OPT-302 With Ranibizumab in Neovascular Age-related Macular Degeneration (nAMD) (clinicaltrials.gov) - P3 | N=986 | Terminated | Sponsor: Opthea Limited | Trial completion date: Jul 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Mar 2025; The primary endpoint was not achieved in the study.

Trial completion date • Trial primary completion date • Trial termination • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

COAST: OPT-302 With Aflibercept in Neovascular Age-related Macular Degeneration (nAMD) (clinicaltrials.gov) - P3 | N=998 | Terminated | Sponsor: Opthea Limited | Trial completion date: Jul 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Mar 2025; The primary endpoint was not achieved in the study.

Trial completion date • Trial primary completion date • Trial termination • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Opthea Announces Decision to Discontinue Wet AMD Trials (GlobeNewswire) - P3 | N=990 | ShORe (NCT04757610) | Sponsor: Opthea Limited | "Opthea Limited...today announced updates on its Phase 3 clinical program, including the termination of COAST (Combination of OPT-302 with Aflibercept Study) and accelerated topline results from its second Phase 3 trial ShORe (Study of OPT-302 in combination with Ranibizumab) in patients with wet AMD....The global ShORe Phase 3 trial evaluated the efficacy and safety of intravitreally administered 2 mg sozinibercept every four or eight weeks in combination with 0.5 mg ranibizumab every four weeks, as per label, versus 0.5 mg ranibizumab monotherapy. The trial did not meet its primary endpoint of mean change in best corrected visual acuity (BCVA) from baseline to week 52....'We are disappointed that COAST and ShORe did not demonstrate the improvements in vision with sozinibercept combination therapy compared to standard of care that we had hoped for,'..."

P3 data: top line • Trial termination • Wet Age-related Macular Degeneration

Opthea Announces COAST Phase 3 Trial Topline Results (Opthea Press Release) - P3 | N=990 | COAST (NCT04757636) | Sponsor: Opthea Limited | " The trial did not meet its primary endpoint of mean change in best corrected visual acuity (BCVA) from baseline to week 52. In wet AMD patients with minimally classic and occult lesions, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=296) or every eight weeks (n=297) achieved a mean change in BCVA of 13.2 or 13.2 letters from baseline to week 52, respectively, versus 13.8 letters with aflibercept monotherapy (n=299, p-values of 0.59 and 0.62 respectively). In the overall population, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=333) or every eight weeks (n=330) achieved a mean change in BCVA of 13.5 and 12.8 letters from baseline to week 52, respectively, versus 13.7 letters with aflibercept monotherapy (n=330, p-values of 0.86 and 0.42 respectively)."

P3 data: top line • Wet Age-related Macular Degeneration

Opthea Announces Phase 2b Wet AMD Publication (GlobeNewswire) - P2b | N=366 | NCT03345082 | Sponsor: Opthea Limited | "Opthea Limited...today announced the publication of sozinibercept Phase 2b data in the peer-reviewed journal Ophthalmic Surgery, Lasers and Imaging (OSLI) Retina...The Phase 2b pre-specified analyses of subgroups showed that in patients with occult and minimally classic lesions excluding RAP, which represented 73% of the Phase 2b total patient population, sozinibercept combination therapy demonstrated a statistically significant additional 5.7 letter mean gain in best corrected visual acuity (BCVA) compared to ranibizumab alone. A greater proportion of patients in this subgroup also gained ≥15 letters and had improved anatomy of better drying of the retina with reduced CNV area at week 24 compared to ranibizumab alone."

P2b data • Age-related Macular Degeneration

Opthea Reports Half Year Results and Business Updates (GlobeNewswire) - "Anticipated Milestones: Phase 3 topline results from COAST, expected in early Q2 CY2025; Phase 3 topline results from ShORe, expected in mid-CY2025; BLA submission in 1H CY2026..."

FDA filing • P3 data: top line • Age-related Macular Degeneration

Opthea Completes Drug Product PPQ Campaign (Opthea Press Release) - "Opthea Limited...announced the completion of its drug product Process Performance Qualification (PPQ) campaign for sozinibercept....The PPQ campaign consisted of the successful production of three consecutive commercial-scale drug product batches required to further validate Opthea’s manufacturing process....'The successful completion of the drug product PPQ campaign is a critical step in support of a potential BLA filing of sozinibercept in wet AMD in the first half of CY2026'."

Commercial • FDA filing • Wet Age-related Macular Degeneration

Opthea Completes COAST Final Week 52 Patient Visit (GlobeNewswire) - "Opthea Limited...today announced that it has completed the final week 52 patient visit in COAST, the first of two Phase 3 pivotal trials investigating the superiority and safety of sozinibercept in combination with aflibercept (COAST) or ranibizumab (ShORe), compared to standard of care alone for the treatment of wet AMD. The topline results from both trials are anticipated in early Q2 CY25 (COAST) and mid-CY25 (ShORe)."

P3 data: top line • Trial status • Age-related Macular Degeneration • Wet Age-related Macular Degeneration

Opthea Wet AMD Data Featured at Macula Society Meeting (GlobeNewswire) - "Opthea Limited...today announced that sozinibercept will be highlighted during an oral presentation at the Macula Society 48th Annual Meeting being held February 12-15, 2025 in Charlotte Harbor, Florida. The Macula Society is a forum for new research in retinal vascular and macular diseases."

P2b data • Age-related Macular Degeneration

Opthea Announces Publication in Diabetic Macular Edema (GlobeNewswire) - P1b/2a | N=153 | "Opthea Limited...announced the publication of its Phase 1b trial of sozinibercept combination therapy in diabetic macular edema (DME) in the peer-reviewed journal Translational Vision Science & Technology (TVST), issued on December 19, 2024....Sozinibercept combination therapy was well tolerated with no dose-limiting toxicities. The trial also demonstrated a dose-response relationship of increased gains in BCVA for ascending doses of sozinibercept, with the 2 mg sozinibercept combination arm demonstrating the highest BCVA gain. All sozinibercept doses demonstrated a meaningful CST reduction....DME program to be advanced after wet AMD topline data readout anticipated for COAST in early CY Q2 2025 and ShORe in mid-2025."

P1 data • P3 data: top line • Age-related Macular Degeneration • Diabetic Macular Edema

Opthea’s Wet AMD Program Featured at Ophthalmology Events (GlobeNewswire) - "Opthea Limited...announced that Opthea and sozinibercept will be highlighted during two upcoming Ophthalmology conferences....will present data from a predefined subgroup of the sozinibercept Phase 2b wet AMD trial related to patients with polypoidal choroidal vasculopathy (PCV), measured at 24 weeks. Data from this subgroup show that patients treated with a combination of sozinibercept and ranibizumab experienced significantly better visual and anatomic outcomes compared to ranibizumab alone."

P2b data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues. (PubMed, Eye (Lond)) - "Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC • VEGFD

Opthea Appoints Chief Medical Officer and Chief Financial Officer as Company Prepares for Phase 3 Topline Data Readouts in 2025 (GlobeNewswire) - "Opthea Limited...announced three senior hires as the Company continues to prepare for the sozinibercept Phase 3 topline data readouts of COAST anticipated in early Q2 calendar year 2025 and ShORe in mid calendar year 2025."

P3 data: top line • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

EURETINA 2024: New therapeutics for wet AMD address the broader VEGF family (Ophthalmology Times) - "In this video, he speaks about VEGF-A/C/D inhibition with sozinibercept and ranibizumab, providing subgroup analysis of a phase 2b study to assess the angiographic predictors of response....We see good results on the phase 2b studies; it was a randomised, double-masked, sham control trial. What it showed was that superior visual versus just a ranibizumab monotherapy control. That's relatively exciting. Most of the treatments we've got at the minute are about fewer injections and non-inferiority of terms of acuity, but there's nothing else I'm aware of, at least that's setting the bar high enough to actually aim for superior visual acuity output....but we've now got a massive phase 3 trial underway. It's almost 2,000 patients in the COAST and SHORE studies."

P2 data • Trial status • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

Opthea Announces Completion of Drug Substance PPQ Campaign Validating Manufacturing Process of Sozinibercept (GlobeNewswire) - "Opthea Limited...announced the completion of its drug substance Process Performance Qualification (PPQ) campaign for sozinibercept. The PPQ campaign consisted of the production of three successful consecutive commercial-scale drug substance batches required for the validation of Opthea’s manufacturing process. The batches have been produced following an extensive manufacturing process development program....'We expect to share a progress update of our drug product PPQ campaign in early 2025.'"

Clinical • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Macular Edema • Ophthalmology • Wet Age-related Macular Degeneration

Sozinibercept combination therapy shows durability in patients with DME, neovascular AMD (Healio) - P1 | N=51 | NCT02543229 | Sponsor: Opthea Limited | "After three initial loading doses, from week 8 through week 24 the mean number of injections was 0.4 for the prior-treated DME group, 1.4 for the treatment-naive neovascular AMD group and 1.9 for the prior-treated neovascular AMD group. Time to first supplemental injection for each group was 79.6 days, 60.4 days and 50.7 days, respectively, showing an overall reduction of treatment burden."

P1 data • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Edema • Ophthalmology • Wet Age-related Macular Degeneration

ShORe: OPT-302 With Ranibizumab in Neovascular Age-related Macular Degeneration (nAMD) (clinicaltrials.gov) - P3 | N=990 | Active, not recruiting | Sponsor: Opthea Limited | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ASRS 2024: Combination therapy of sozinibercept with ranibizumab in nAMD or aflibercept in DME (Ophthalmology Times) - "Specifically, so far we've looked at aflibercept and ranibizumab. Well, going forward now we have 2 very large global trials, the SHORE trial and the COAST trial. Each of them are 1,000 patients looking at neovascular AMD. The COAST trial looked at combination sozinibercept and aflibercept, and the SHORE trial looked at combination sozinibercept and ranibizumab. Two different doses of sozinibercept: you have 4- or 8-week dosing in combination with on-label therapy for aflibercept in COAST or ranibizumab. in SHORE. What we're looking at is the 1-year primary endpoint, which will come out early- to mid-2025. So exciting things. Both these 1,000 patient trials, which are huge trials, are fully enrolled and ongoing now. We'll know the results again early- to mid-2025."

P3 data • Age-related Macular Degeneration • Diabetic Macular Edema • Ophthalmology • Wet Age-related Macular Degeneration

Opthea Announces Placement and Partially Underwritten Entitlement Offer to Raise up to Approximately A$227.3 million (US$150.0 million) (Opthea Press Release) - "Opthea Limited...announced that the Company is seeking to raise up to approximately A$227.3 million (US$150.0 million) via an approximately A$10.0 million (US$6.6 million) placement ('Placement') and an approximately A$217.3 million (US$143.4 million) Accelerated Non-Renounceable Entitlement Offer ('ANREO' or 'Entitlement Offer'). The Company expects the net proceeds from the Placement and Entitlement Offer, together with cash on hand, to fund the Company, through the anticipated Phase 3 topline data readouts for COAST (Combination OPT-302 with Aflibercept Study), and ShORe (Study of OPT-302 in combination with Ranibizumab). Based on the completion of enrollment in COAST in February 2024 and ShORe in May 2024, as well as Opthea’s internal expansion of its clinical development team, the topline data readout of COAST is now accelerated to early in the second calendar quarter of 2025, and the topline data readout for ShORe is anticipated in mid-calendar year 2025."

Financing • P3 data: top line • Age-related Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

Opthea To Present at Clinical Trials at the Summit Meeting (GlobeNewswire) - "Opthea Limited...announced that the Company will make several presentations at the Clinical Trials at the Summit (CTS) Meeting being held in Park City, Utah on June 8, 2024. Frederic Guerard, PharmD, Chief Executive Officer of Opthea, will participate in a panel, there will be two scientific presentations related to the sozinibercept (OPT-302) clinical trial program and a sponsor talk."

Clinical • Age-related Macular Degeneration • Diabetic Macular Edema • Ophthalmology • Wet Age-related Macular Degeneration

Opthea Completes Enrollment in Pivotal Phase 3 Clinical Program with Sozinibercept in Wet AMD (GlobeNewswire) - "Opthea Limited...announced that it has now completed enrollment in both the COAST and ShORe trials constituting its pivotal Phase 3 clinical program. This program is designed to assess the safety and superior efficacy of sozinibercept in combination with standard-of-care anti-VEGF-A therapies compared to standard of care alone for the treatment of patients with wet AMD....'We are excited about the potential of sozinibercept to transform the current treatment paradigm, with pivotal 52-week topline data expected in mid-CY2025 to support a potential BLA submission.'"

P3 data • Age-related Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

RWC 2024: Rationale for the design of the phase 3 superiority clinical trials of sozinibercept combination therapy (Modern Retina) - "Hi I'm David Eichenbaum, director of research at Retina Vitreous Associates of Florida, and I'm very excited to present the rationale for the design of the sozinibercept anti-VEGF-C, and anti-VEGF-D combination treatment with anti-VEGF-A for wet macular degeneration....The phase 3 studies COAST, combining sozinibercept with aflibercept, and is SHORE, combining sozinibercept with ranibizumab, are designed similarly to the phase 2 study, which showed this increased efficacy eliminating patients with a rap and there's a pre-specified hierarchical analysis looking first at patients who are optimal responders minimally classic and occult patients who make up the majority of our real-world with AMD patients. 990 patients per study, and we're putting this to the test."

Clinical protocol • Age-related Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

Perspectives on the currently available pharmacotherapy for wet macular degeneration. (PubMed, Expert Opin Pharmacother) - "Promising developments include extending treatment intervals with newer anti-VEGF agents like brolucizumab and faricimab, biosimilars offering cost-effective options, and exploring innovative drug delivery methods such as subretinal gene therapy. Combination therapies, gene therapies, and novel agents like KSI-301 and OPT-302 show potential for improving treatment outcomes and reducing treatment burden. While current treatments for w-AMD have significantly advanced with the advent of anti-VEGF therapies, their limitations in terms of treatment burden and incomplete responses have spurred research into diverse alternative approaches. These innovative strategies offer hope for improving patient outcomes and reducing healthcare burdens, suggesting a promising future for w-AMD management."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Opthea Announces Upcoming Presentations at the Retina World Congress 2024 (GlobeNewswire) - "Opthea Limited...announced that two scientific presentations on the sozinibercept (OPT-302) Phase 2 clinical trial results and ongoing Phase 3 clinical trial program will be made at the Retina World Congress (RWC), being held from May 9-12, 2024 in Fort Lauderdale, Florida. Frederic Guerard, PharmD, Chief Executive Officer (CEO) of Opthea, will participate in the Retina Unplugged panel discussion."

Clinical protocol • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration