Opthea's COAST Phase 3 Trial: A Setback or a New Path?

The biotech world was abuzz with anticipation as Opthea Limited (ASX/NASDAQ: OPT) announced the topline results from its global Phase 3 clinical trial, COAST, on March 24, 2025. The trial, which evaluated the efficacy and safety of sozinibercept in combination with aflibercept for the treatment of wet age-related macular degeneration (wet AMD), failed to meet its primary endpoint of mean change in best corrected visual acuity (BCVA) from baseline to week 52. This news sent shockwaves through the industry, raising questions about the future of Opthea and its lead product candidate, sozinibercept.



The COAST trial was designed to demonstrate the superiority of sozinibercept combination therapy versus standard of care alone. However, the results showed that participants receiving sozinibercept combination therapy achieved a mean change in BCVA of 13.2 letters from baseline to week 52, compared to 13.8 letters with aflibercept monotherapy. This marginal difference was not statistically significant, leading to the trial's failure to meet its primary endpoint.

The implications of this setback are far-reaching. Opthea's stock price has taken a hit, with a 36.95% decrease over the last four weeks. The company's ability to continue as a going concern is now in question, as it faces potential obligations under its Development Funding Agreement (DFA). If the DFA is terminated, Opthea could be required to pay amounts to the DFA Investors that would have a material adverse impact on its solvency. The potential repayment amounts range from US$0 to US$680.0 million, depending on the termination trigger.



The financial uncertainty and potential repayment obligations under the DFA raise material uncertainty as to Opthea's ability to continue as a going concern. The company is unable to incur further non-equity funding or dispose of its material assets without the prior consent of the DFA Investors, further constraining its financial flexibility.

Despite this setback, Opthea is not ready to throw in the towel. The company is actively discussing possible options with the DFA Investors to explore a pathway that represents the best outcome for the company and its shareholders. Opthea's management and board of directors are exploring all available options, including the possibility of a negotiated settlement that is different from the parties' existing rights under the DFA.

The failure of the COAST trial is a significant setback for Opthea, but it is not the end of the road. The company's lead product candidate, sozinibercept, has the potential to become the first therapy in 20 years to enable patients with wet AMD to live fuller and healthier lives. Opthea's Phase 3 program is designed to support a broad label and, if successful, enable sozinibercept to be approved for use in combination with any anti-VEGF-A therapy in wet AMD patients.

The biotech industry is a high-risk, high-reward game, and Opthea's experience with the COAST trial is a testament to that. The company's ability to navigate this setback and find a new path forward will be crucial to its future success. As Opthea continues to explore its options, investors and industry watchers will be keeping a close eye on the company's next moves.