Kodiak Sciences (KOD) Study result summary

Study background and design

• DAYBREAK Phase III trial evaluated Zenkuda (tarcocimab) and tabirafusp-ted in treatment-naïve wet AMD patients, using aflibercept as the control arm.

• The trial featured independent pivotal analyses for each investigational therapy against aflibercept, with AI-based fluidics analysis and real-world retreatment criteria.

• The primary endpoint was mean change in best-corrected visual acuity at one year, with baseline visual acuity around 20/60 and CST about 350–355 microns.

• The study aimed to address the need for durable anti-VEGF therapies in wAMD without sacrificing efficacy or immediacy.

• The design and fluid-based retreatment criteria closely mirror real-world retina specialist practice.

Efficacy and durability results

• Both Zenkuda and tabirafusp-ted met primary endpoints, demonstrating non-inferior visual gains and anatomic outcomes compared to aflibercept at one year.

• Zenkuda achieved rapid and sustained retinal drying, with 54% of patients reaching 6-month dosing intervals using treat-to-dryness criteria; 62% achieved 5–6 month durability.

• Tabirafusp-ted also met vision and anatomical endpoints, with ongoing post hoc analyses to identify subgroups benefiting from IL-6 inhibition.

• Both drugs maintained overlapping visual acuity and CST curves with aflibercept throughout the study.

• AI-driven retreatment allowed individualized dosing, closely mirroring real-world clinical practice.

Safety and clinical implications

• Both therapies demonstrated safety profiles consistent with aflibercept, with low rates of intraocular inflammation, cataract, and serious ocular adverse events.

• No cases of intraocular inflammation, occlusive retinal vasculitis, or endophthalmitis were observed with Zenkuda; one intraocular inflammatory event occurred with tabirafusp-ted.

• The trial's retreatment algorithm is considered the closest to real-world practice among pivotal wet AMD trials.

• Zenkuda’s conjugated/unconjugated protein formulation provides rapid disease control and extended durability, with a mean ocular half-life of 20 days, three times longer than faricimab.

• The majority of patients could extend dosing intervals, potentially reducing treatment burden.