Trial Information.Q C1: What is the current status of...

Trial Information
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Q C1: What is the current status of Sozinibercept (OPT-302)?

A: Sozinibercept (OPT-302) is in pivotal Phase 3 trials, specifically the COAST and SHORE studies, which are designed to evaluate its efficacy and safety in treating wet AMD. The COAST trial completed enrollment in February 2024 with 998 patients, while the SHORE trial completed enrollment in May 2024 with 986 patients. Top-line data (TLD) for the 52-week safety and efficacy results are anticipated in early Q2 2025 for COAST and mid-2025 for SHORE. Both trials focus on patient sub-groups representing approximately 75% of the wet AMD population, where Sozinibercept previously demonstrated a significant benefit of +5.7 letters in BCVA at 24 weeks during Phase 2b trials.
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Q C2: What is COAST?

A: COAST is a Phase 3 clinical trial evaluating Sozinibercept (OPT-302) in combination with aflibercept (Eylea) for the treatment of wet AMD. The name COAST stands for "Combination therapy with OPT-302, Aflibercept (Eylea), and Standard Treatment." The trial successfully completed enrollment in February 2024 with 998 patients. Top-line data is expected in early Q2 2025. The primary endpoint of the trial will focus on a specific sub-group of patients who showed the highest benefit in visual acuity (BCVA) during earlier trials, aiming to maximize the likelihood of Phase 3 success.
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Q C3: What is SHORE?

A: SHORE is another Phase 3 clinical trial for Sozinibercept (OPT-302), similar in design to COAST, and also focuses on patients with wet AMD. The name SHORE stands for "Standard therapy with High-dose OPT-302 Optimized for Retinal Evaluation." SHORE completed enrollment in May 2024 with 986 patients. Top-line data is expected in mid-2025. Like the COAST trial, SHORE emphasizes the same patient sub-group identified in earlier trials to increase the probability of successful outcomes in Phase 3.

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Q C4: What were the results of the Phase 2b trial of Sozinibercept (OPT-302)?

A: The Phase 2b trial of Sozinibercept (OPT-302) involved 366 participants and was conducted over 6 months. In this trial, Sozinibercept was co-administered with ranibizumab (Lucentis). The trial demonstrated a statistically significant improvement in visual acuity, with a P-value of 0.0107, confirming the efficacy of Sozinibercept when combined with Lucentis. It is important to note that this trial did not test Sozinibercept in combination with Eylea (aflibercept). The Phase 2b trial also highlighted a +5.7 letter improvement in BCVA at 24 weeks for a sub-group representing approximately 75% of wet AMD patients, which is now the focus of the ongoing Phase 3 trials.
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Q C5: What is the significance of Fast Track Designation for Sozinibercept?

A: Sozinibercept (OPT-302) has been granted Fast Track Designation by the U.S. FDA, which is designed to expedite the review process for drugs that address unmet medical needs. With positive top-line data from the COAST trial expected in early Q2 2025, Opthea could initiate a rolling Biologics License Application (BLA) submission as early as Q3 2025. The rolling submission process allows Opthea to submit completed sections of the BLA as they become available, potentially speeding up the overall review process. The BLA submission could be completed by early 2026, with FDA approval possibly following by mid to late 2026. If approved, Sozinibercept could enter the U.S. market shortly thereafter. This accelerated timeline is contingent on successful outcomes from the COAST trial and favorable FDA review.
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Q C6: What are the key endpoints being measured in the Phase 3 trials of Sozinibercept?

A: The key endpoints in the Phase 3 trials (COAST and SHORE) for Sozinibercept (OPT-302) include Best Corrected Visual Acuity (BCVA), measured by the number of letters gained on the ETDRS eye chart at 52 weeks. Secondary endpoints include the proportion of patients who gain 15 or more letters, central retinal thickness, and the safety profile of Sozinibercept in combination with Eylea. The trials also measure patient-reported outcomes to assess the impact of the treatment on quality of life.
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Q C7: What are the risks associated with the Phase 3 trials of Sozinibercept?

A: The primary risks associated with the Phase 3 trials of Sozinibercept include the possibility of not meeting the primary or secondary endpoints, which could delay or derail the approval process. Additionally, any unexpected safety concerns that arise during the trials could negatively impact the drug's prospects. There is also the risk that the patient sub-groups identified as likely to benefit most from Sozinibercept may not show the same level of efficacy in a larger, more diverse population, which could affect the overall trial outcomes.
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Q C8: How does Sozinibercept compare to other treatments in development for wet AMD?

A: Sozinibercept (OPT-302) differentiates itself by targeting VEGF-C and VEGF-D in addition to VEGF-A, potentially offering broader inhibition of the angiogenic pathways involved in wet AMD. This could provide an advantage over treatments that only target VEGF-A. However, several other treatments are also in late-stage development, such as faricimab, which targets both VEGF-A and Angiopoietin-2 (Ang-2). The relative success of Sozinibercept will depend on its performance in Phase 3 trials compared to these emerging therapies.
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