Surrozen (SRZN) H.C. Wainwright 6th Annual Ophthalmology Virtual Conference summary

Scientific rationale and therapeutic targets

• Frizzled-4 (Fzd4) is a key receptor in Wnt signaling, implicated in retinal vascular diseases through genetic studies linking its mutations to vessel dysfunction and leaky vasculature.

• Loss of Wnt signaling in retinal endothelial cells leads to poorly developed vessels and compromised blood-retinal barrier, overlapping with pathologies seen in wet AMD and DME.

• Targeting multiple contributors to retinal disease, including VEGF, Wnt, and IL-6, forms the basis for developing multifunctional antibodies.

• IL-6 is recognized as an additive contributor to retinal inflammation and edema, with evidence supporting its inhibition in diseases like UME and DME.

• The pipeline includes dual and tri-specific antibodies targeting Fzd4, VEGF, and IL-6, aiming to address complex disease mechanisms.

Preclinical data and differentiation

• Preclinical models show synergy between Wnt agonism and VEGF inhibition, with dual-targeting molecules outperforming single-target approaches in reducing avascular areas.

• The combination therapy uniquely addresses retinal non-perfusion, a high unmet need not improved by current VEGF drugs.

• Differentiation for 8141 centers on being a superior drying agent and potentially enabling reperfusion of non-perfused retinal areas.

• Animal models used are validated and predictive for clinical translation, supporting optimism for dual-effect outcomes.

• Achieving both fluid resolution and reperfusion could make 8141 transformative in the field.

Clinical development and strategic positioning

• Regulatory pathways currently focus on treatment-naive DME patients, with registrational studies expected to enroll about 75% naive patients.

• There is significant unmet need among incomplete responders to current therapies, representing a viable future target population.

• The Wnt platform is positioned to address multiple retinal vascular diseases, including DME, wet AMD, UME, and retinal vein occlusion.

• Combined Wnt and VEGF targeting is seen as particularly promising for DME and wet AMD due to their underlying biology.

• Durability and less frequent injections (potentially every 3–9 months) are key goals for clinical differentiation.