• Opthea to focus on Lymphangioleiomyomatosis (LAM), a rare and devastating lung disease affecting women
• Leveraging existing assets, expertise and safety data to develop OPT-302 for LAM treatment
• Staged, data-driven development plan to mitigate risks and preserve optionality

Following a strategic review, Opthea has decided to pivot its focus to the development of OPT-302 for the treatment of Lymphangioleiomyomatosis (LAM), a rare and progressive lung disease that predominantly affects women of reproductive age. LAM is characterized by the gradual onset of breathlessness, cough, and fatigue, and can ultimately lead to the need for lung transplantation. The company believes that OPT-302, which is designed to trap VEGF-C and VEGF-D and block VEGFR-3 activation, has the potential to address the lymphatic dysfunction that is central to LAM pathology. This mechanism complements existing mTOR inhibitor treatments and offers a potentially more comprehensive therapeutic approach. Opthea has developed a rigorous, staged-gated plan to mitigate key uncertainties, including evaluating optimal delivery routes, exposure in lung and lymphatic tissues, chronic dosing tolerability, and demonstration of clinical benefit in well-defined LAM patient populations. The LAM development program is fully funded from existing cash reserves, with no near-term equity raise anticipated. Opthea will work closely with the global LAM ecosystem, including specialist clinics and patient foundations, to support study feasibility, endpoint development, patient engagement, and broader community alignment. This strategic shift away from the company's historical ophthalmology focus is grounded in scientific rationale, disciplined capital management, and the potential to deliver meaningful value for shareholders and patients.

Over the next 12 months, Opthea's key objectives are to: engage extensively with the LAM community, demonstrate the feasibility of delivering OPT-302 into the lungs in preclinical studies, conduct the nonclinical safety studies required to support clinical trials, and seek shareholder approval for a name change to reflect the company's new strategic direction.