DAYBREAK Topline Readout: Wet AMD Bar Is High, Results Unknown, Mechanism Unconfirmed

Kodiak Sciences to Present DAYBREAK Phase 3 Topline Results

Kodiak Sciences Inc. announced it will present topline results from its pivotal Phase 3 DAYBREAK study on Monday, September 28, 2026. The study evaluates Zenkuda (tarcocimab tedromer) and KSI-501 (tabirafusp alfa tedromer) for the treatment of patients with wet age-related macular degeneration. The company will host a webcast at 8:30 AM Eastern Time to discuss these results, which can be accessed via a dedicated link or Kodiak's investor relations website.

• The DAYBREAK study is a pivotal Phase 3 trial investigating two of Kodiak Sciences' therapeutic candidates, Zenkuda (tarcocimab tedromer) and KSI-501 (tabirafusp alfa tedromer), for the treatment of wet age-related macular degeneration. The upcoming presentation of topline results is a significant milestone for these programs, aiming to address a leading cause of blindness.
• Kodiak Sciences will host a webcast on September 28, 2026, at 8:30 AM Eastern Time to present and discuss the DAYBREAK study's topline results. Interested parties can access the live webcast via a dedicated link or through the Events and Presentations page on the company's investor relations website, with an archived replay available for a limited time.
• Kodiak Sciences is a pre-commercial retina-focused biotechnology company with a portfolio of late-stage clinical programs. Zenkuda also has a BLA-ready profile in diabetic retinopathy and retinal vein occlusion, while KSI-501 is also being evaluated in diabetic macular edema. These drugs target the substantial $15 billion anti-VEGF market, alongside KSI-101, a bispecific protein in Phase 3 for Macular Edema Secondary to Inflammation (MESI).

Navigating Current Challenges in Wet AMD Treatment

Despite the transformative impact of anti-VEGF therapies on neovascular AMD outcomes, real-world evidence reveals persistent gaps between clinical trial results and long-term patient outcomes. Treatment burden, suboptimal response rates, and disease progression over time remain central concerns for clinical and strategic teams.

• Declining visual acuity over time despite ongoing treatment. In a large real-world cohort of 98,821 eyes, VA changes from baseline (ETDRS letters) followed a deteriorating trajectory: +1.1 in year 1, −1.3 in year 2, −3.1 in year 3, and −5.2 in year 4, indicating that gains achieved early in treatment are not sustained over a 4-year horizon.

• Reducing injection frequency over time, potentially contributing to vision loss. Mean injection counts declined from 7.5 ± 1.9 in year 1 to 6.4 ± 2.3 by year 4, and the proportion of eyes treated at intervals more frequent than the recommended ≥8-week schedule increased 40% from year 1 (32.4%) to year 4 (45.3%), suggesting intensification driven by year-on-year VA loss and disease progression.

• Risk of losing driving vision, with outcomes strongly tied to injection frequency. The probability of maintaining driving vision over 4 years was 56% for nAMD patients overall; among those receiving 1–5, 6–7, and ≥8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (P<0.001), underscoring the clinical consequences of under-treatment.

• Resistance, variable response, and adverse effects of broad VEGF blockade. Anti-VEGF therapies face limitations from resistance, variable patient response, the burden of frequent injections, and adverse effects associated with broad VEGF blockade — driving exploration of alternative targets including PDGF, angiopoietin-2 (Ang-2), Tie2, and integrin inhibitors, as well as long-acting biologics, gene therapy, and nanocarrier platforms.

• Older age and worse baseline VA as independent risk factors for driving vision loss. Beyond injection frequency, baseline factors associated with driving vision loss in nAMD included older age, worse index VA, and the presence of geographic atrophy, highlighting that patient-level characteristics compound the limitations of current treatment paradigms.

DAYBREAK: Design and Endpoints for Wet AMD

Several trials and real-world studies have evaluated anti-VEGF agents, novel biologics, radiation modalities, and surgical interventions for neovascular AMD, spanning treatment-naïve and previously treated populations across a range of dosing regimens. The table below summarizes key design parameters and endpoints across these studies.

Kodiak's DAYBREAK Data: A New Horizon for Wet AMD?

The upcoming topline results from Kodiak Sciences' Phase 3 DAYBREAK study for Zenkuda and KSI-501 represent a pivotal moment for the future of wet age-related macular degeneration (w-AMD) management. W-AMD remains a leading cause of severe vision loss, and while the advent of anti-VEGF therapies has been revolutionary, the current treatment paradigm is characterized by a significant burden of frequent intravitreal injections. This high treatment frequency often leads to suboptimal real-world outcomes due to patient adherence challenges and healthcare system strain.

Zenkuda (tarcocimab tedromer) and KSI-501 (tabirafusp alfa tedromer) are pipeline therapies designed to offer extended treatment intervals, potentially alleviating this burden. If the DAYBREAK study demonstrates strong efficacy and safety alongside significantly reduced injection frequency, it could mark a substantial strategic advantage for Kodiak. Such an outcome would not only validate their innovative 'tedromer' platform but also position these agents to potentially redefine the standard of care, offering a more patient-friendly and efficient treatment option.

However, the path to market leadership in w-AMD is fraught with challenges. The competitive landscape is robust, featuring established anti-VEGFs like ranibizumab and aflibercept, a growing array of biosimilars, and other novel approaches including bispecific antibodies, long-lasting drug delivery systems, and gene therapies. Furthermore, new entrants face a high bar: while reducing injection frequency is a clear benefit, maintaining or improving best-corrected visual acuity (BCVA) is paramount. As seen with other novel agents, anatomical improvements do not always translate to superior visual outcomes in nAMD. Therefore, the DAYBREAK results will be scrutinized not just for durability, but for their comprehensive impact on functional vision and overall patient experience, including patient-reported outcomes, which are increasingly recognized as critical measures of treatment success.