Opthea Limited, a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD), 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.
ShORe topline results
Following the negative results of the COAST phase 3 trial announced on March 24, 2025, Opthea determined that the most appropriate course of action for wet AMD patients, shareholders, and other stakeholders was to accelerate the ShORe trial topline data readout, including in consultation with its Development Funding Agreement investors (“DFA Investors”).
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.
In wet AMD patients with minimally classic and occult lesions, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=301) or every eight weeks (n=301) achieved a mean change in BCVA of 13.3 or 12.9 letters from baseline to week 52, respectively, versus 14.2 letters with ranibizumab monotherapy (n=299, p-values of 0.35 and 0.19 respectively). In the overall population, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=328) or every eight weeks (n=326) achieved a mean change in BCVA of 13.3 and 12.6 letters from baseline to week 52, respectively, versus 14.3 letters with ranibizumab monotherapy (n=331 p-values of 0.32 and 0.09 respectively).
Sozinibercept combination therapy was well tolerated.
“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,” said Frederic Guerard, PharmD, CEO of Opthea. “We are grateful to all patients, clinical investigators and their staff around the world who participated in the sozinibercept phase 3 clinical program, and for their contributions in investigating new treatments for wet AMD.”
“As previously disclosed, the company has certain obligations under the DFA. In light of the phase 3 clinical trial results, the Company and the DFA Investors will continue to discuss this matter in good faith, and we will provide updates on this matter in the future,” Dr. Guerard concluded.
Corporate Updates
Following the negative results of the COAST and ShORe trials, Opthea and the DFA Investors agreed to discontinue the development of sozinibercept in wet AMD with immediate effect, and that this decision did not constitute a termination event under the DFA resulting in any amount payable by Opthea.
It remains possible that under the DFA, in certain circumstances upon or following termination of the DFA, Opthea could become required to pay a multiple of the amount funded by the DFA Investors that would have a material adverse impact on the solvency of the Company. As previously disclosed, termination can be triggered by a range of events, including, among other things, Opthea’s insolvency, in which case Opthea will be obligated to pay a multiple of the amounts funded by the DFA Investors.
Opthea continues active discussions with the DFA Investors, pursuant to and as required under the DFA, to explore possible options to deliver the best outcome for the Company and its shareholders.
A copy of the DFA is included as Exhibit 4.19 to Opthea’s Annual Report on Form 20-F filed with the US Securities and Exchange Commission on August 30, 2024.
Opthea estimates it will have unaudited cash and cash equivalents of US$100M at the end of March 2025.
In light of these matters, there remains material uncertainty as to Opthea's ability to continue as a going concern.1 As noted above, discussions with the DFA Investors are ongoing and Opthea cannot be certain as to the outcome of those discussions or when that outcome may become known.
Opthea is currently relying on the "safe harbour" provisions in section 588GA of the Corporations Act 2001 (Cth).
Trading in Opthea’s listed securities will be suspended by ASX under ASX Listing Rule 17.3 until Opthea is in a position to provide an announcement to the market providing more clarity on these issues and the impact on Opthea’s financial position.
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