Kodiak Sciences announced that Zenkuda (tarcocimab tedromer) and tabirafusp alfa tedromer (tabirafusp-ted/KSI-501) both met their primary endpoints in the pivotal Phase 3 DAYBREAK study evaluating patients with wet age-related macular degeneration (wAMD). Both investigational therapies were noninferior to aflibercept in vision gains at one year.
The results were particularly notable for Zenkuda, which demonstrated rapid clinical activity during the loading phase and sustained effects that allowed 54% of patients to reach a six-month, or 24-week, dosing interval at year one under strict treat-to-dryness retreatment criteria. Kodiak said the approach was designed to resemble real-world retinal specialist practice by using retinal fluid as the marker for retreatment.
Zenkuda met its primary endpoint with a p-value of 0.0007, demonstrating meaningful vision gains along with rapid and sustained retinal drying. The company said the combination of immediate disease control and extended durability could establish a new first-line benchmark for treating wet AMD.
The treatment also demonstrated a favorable safety profile. No intraocular inflammation was reported among Zenkuda-treated patients, while the cataract adverse-event rate was 0.5%, compared with 0.9% for aflibercept.
Zenkuda is an investigational anti-VEGF biopharmaceutical built using Kodiak’s proprietary antibody biopolymer conjugate (ABC) platform. The company says it has a mean ocular half-life of about 20 days, roughly three times longer than approved anti-VEGF therapies. Kodiak ultimately aims for a flexible dosing label ranging from one month to six months across retinal vascular diseases.
The DAYBREAK results add to Zenkuda’s broader late-stage clinical program. The drug has now completed five successful Phase 3 pivotal studies, including DAYBREAK and DAYLIGHT in wet AMD, GLOW1 and GLOW2 in diabetic retinopathy, and BEACON in retinal vein occlusion.
Kodiak plans to submit a three-indication biologics license application (BLA) for Zenkuda in the fourth quarter of 2026, incorporating data from the five Phase 3 studies across wet AMD, diabetic retinopathy, and macular edema following retinal vein occlusion.
Tabirafusp-ted also produced positive results in DAYBREAK. The bispecific therapy, which targets both VEGF and IL-6, met its vision primary endpoint with a p-value of 0.0036 and its anatomical key secondary endpoint with a p-value below 0.0001. Kodiak plans post-hoc analyses to determine which treatment-naïve wet AMD patient subgroups could particularly benefit from IL-6 inhibition.
Tabirafusp-ted was also well tolerated, with a 0.4% intraocular inflammation rate and no reported cataract adverse events, compared with a 0.9% cataract rate for aflibercept.
Kodiak is simultaneously advancing tabirafusp-ted in the Phase 3 ALTO study for diabetic macular edema. The approximately 910-patient global study is evaluating whether the bispecific treatment can demonstrate superiority over aflibercept and includes regimens allowing individualized dosing intervals of up to 24 weeks.
Kodiak also expects a Phase 3 topline readout for KSI-101 in December 2026 in patients with macular edema secondary to inflammation. The company said its late-stage portfolio could potentially result in marketing authorization for both Zenkuda and KSI-101 by the end of 2027 or early 2028.
KEY QUOTES:
“The strength of these DAYBREAK data positions us for the next stage of Kodiak’s evolution, as we prepare for the planned commercialization of Zenkuda as a potential best-in-class therapy for patients with wet AMD, diabetic retinopathy and retinal vein occlusion.”
Victor Perlroth, M.D., Chief Executive Officer of Kodiak Sciences
“Four years and seven months after our first Phase 3 readout, Zenkuda’s profile has come fully into focus through rigorous science, disciplined learning and thoughtful execution. DAYBREAK demonstrated the attributes we designed Zenkuda to achieve: rapid disease control in wet AMD and the potential for six-month durability under stringent treat-to-dryness retreatment criteria.”
J. Pablo Velazquez-Martin, M.D., Chief Medical Officer of Kodiak Sciences
“More than half of patients reached a 24-week dosing interval using strict treat-to-dry retreatment criteria. This combination of immediacy, flexibility and true durability is unique and differentiated.”
Charles Wykoff, M.D., Ph.D., Chairman of Research at Retina Consultants of Texas, Professor of Clinical Ophthalmology and Deputy Chair of Ophthalmology at Houston Methodist Hospital
“These Zenkuda data bring us closer to the best possible outcomes with fewer injections. I look forward to offering Zenkuda to my patients, if approved.”
David M. Brown, M.D., Chief Medical Officer of Retina Consultants of America
