Opthea (OPT) UBS Virtual Ophthalmology Day Conference summary

Mechanism and clinical rationale

• Sozinibercept targets VEGF-C and VEGF-D, complementing standard anti-VEGF-A therapies for wet AMD.

• Combination therapy demonstrated superior visual outcomes in phase II-B trials compared to standard of care alone.

• Upregulation of VEGF-C and VEGF-D occurs after anti-VEGF-A treatment, supporting the need for broader pathway inhibition.

• Animal models and clinical data show VEGF-C/D drive abnormal blood vessel growth and fluid accumulation in the retina.

• Blocking the full VEGF pathway is expected to improve disease control and patient outcomes.

Competitive landscape and differentiation

• Current treatments for wet AMD are all anti-VEGF-A biologics, with no proven superior efficacy over Lucentis.

• New technologies, including small molecules and gene therapies, are emerging but are mostly aiming for non-inferiority.

• Sozinibercept is the only program seeking to demonstrate additional efficacy on vision outcomes.

• Biosimilars are entering the market, increasing competition among standard of care options.

Phase II-B trial design and results

• Over 360 patients were randomized into three arms: sham, low-dose, and high-dose sozinibercept, all with standard of care.

• Inclusion criteria focused on patients with lower baseline vision to better demonstrate efficacy.

• High-dose sozinibercept showed clear superiority in visual acuity over Lucentis alone; low-dose improved anatomy but not vision.

• Hard-to-treat subgroups, such as PCV patients, saw greater vision gains with combination therapy.

• Safety profile was similar across all arms, with no significant differences in inflammation rates.