Kodiak Sciences Inc. announced that the primary endpoints were met for both zenkuda (tarcocimab tedromer) and tabirafusp-ted (KSI-501) in the phase 3 DAYBREAK study in patients with wet age-related macular degeneration (AMD).
Give me a refresher on Kodiak Sciences.
The pre-commercial, retina-focused biotechnology company currently has three candidates in development for retinal vascular diseases:
- Zenkuda (tarcocimab tedromer)
- proposed ndications: diabetic retinopathy (DR), wet AMD, and retinal vein occlusion (RVO)
- KSI-501 (tabirafusp alfa tedromer [tabirafusp-ted])
- proposed indications: wet AMD and diabetic macular edema (DME)
- KSI-101 (tabirafusp-ted 100 mg/mL [high strength formula])
- proposed indication: macular edema secondary to inflammation (MESI)
And what scientific approach are these assets built on?
That would be the antibody biopolymer conjugate (ABC) platform, designed to enable multi-mechanism therapies with durability and to block all vascular endothelial growth factor (VEGF)-A isoforms.
- What it does: combines a targeting antibody (which binds VEGF in the eye) to a large, water-soluble biopolymer (attached to that antibody) to create a single, long-lasting therapeutic.
See here for a step-by-step (and 3-D) look at this process.
Now, didn’t we recently hear from Kodiak?
Indeed. In August the company reported that the first patients were enrolled in the global phase 3 ALTO trial (NCT07734844).
- That trial is designed to explore the superiority of bispecific KSI-501 (anti-VEGF, anti-IL-6) versus monospecific aflibercept (anti-VEGF) in DME patients.
Click here to review our previous coverage of the ALTO trial, which is actively enrolling patients.
Let’s zero in on Zenkuda.
Zenkuda has a mean ocular half-life in humans of 20 days, approximately three times longer than approved anti-VEGF therapies and is designed to maintain potent and effective drug levels in ocular tissues for longer.
The goal: providing a flexible 1- through 6-month label for all patients with retinal vascular disease (ex: treatment-naïve, treatment-experienced, mild, and severe patients).
And its clinical journey, to date?
The investigational therapy has completed five successful phase 3 pivotal studies across three indications:
- Wet AMD: DAYBREAK (NCT06556368) and DAYLIGHT (NCT04964089)
- DR: GLOW1 (NCT05066230) and GLOW2 (NCT06270836)
- RVO: BEACON (NCT04592419)
How did Zenkuda perform in the trials for DR and RVO?
In the GLOW1 and GLOW2 studies, Zenkuda successfully treated DR patients and prevented disease progression with 100% of patients on extended 6-month dosing at Year 1.
For RVO: During the first 6 months of the BEACON study, Zenkuda-treated patients were dosed at an 8-week interval (compared to 4-week intervals for aflibercept).
- In the second 6 months:
- Identical retreatment criteria were used for the Zenkuda and aflibercept arms
- Nearly half of Zenkuda patients did not require any treatment while achieving similar vision and anatomical outcomes as the aflibercept group at 1 year.
Noted. Moving on to KSI-501 …
The investigational, first-in-class bispecific therapy is designed to potently inhibit two complementary pathways implicated in retinal vascular disease:
- Interleukin-6 (IL-6)-mediated inflammation
- VEGF-mediated vascular permeability and neovascularization
Its prior trial performance: In preclinical models, KSI-501 was shown to be a potent inhibitor of both VEGF and IL-6 and to normalize the blood-retinal barrier—opening the possibility for it to be a disease-modifying therapy for retinal vascular diseases.
Next up: the DAYBREAK study.
This phase 3 non-inferiority trial is evaluating parallel investigational arms of Zenkuda and KSI-501 against the active comparator aflibercept.4
The primary endpoint is non-inferiority in change in best-corrected visual acuity (BCVA) from baseline to the average of Week 40, 44 and 48.
The dosing regimen for each arm is as follows:
- Zenkuda: Individualized dosing every 4 to 24 weeks on an as-needed basis following four monthly loading doses and those randomized to
- KSI-501: Fixed every-8-week dosing with additional individualized dosing (up to monthly dosing) on an as-needed basis after four monthly loading doses.
- DAYBREAK utilized KSI-501's enhanced 50 mg/mL formulation containing both conjugated and unconjugated antibodies that is intended to balance immediacy and durability.
- Aflibercept 2 mg: dosed per label.
The individualized dosing of Zenkuda was determined by a treat-to-dryness proactive approach using the presence of retinal fluid as a disease activity marker, which resembles retina specialists' practice and optimizes each patient's treatment, instead of using a combination of central subfield thickness and vision loss.
What were Kodiak’s goals for DAYBREAK?
DAYBREAK was designed to showcase the potential for Zenkuda to be a mainstay biologic for VEGF-driven retinal vascular diseases with both a strong efficacy/immediacy (driven by its enhanced formulation) and a strong durability (driven by its ABC design and science of durability).
Conversely: The objective for KSI-501 in DAYBREAK was to explore the efficacy potential of bispecific IL-6 and VEGF inhibition in a broad treatment-naïve wet AMD population.
Let’s get to those findings.
In the DAYBREAK study, Zenkuda met the primary endpoint (p=0.0007) demonstrating meaningful vision gains as well as rapid and sustained retinal drying with the majority of patients (54%) on 6-month dosing, establishing a first-line benchmark in wet AMD.
Plus: Zenkuda demonstrated strong immediacy of clinical effect, matching and/or exceeding that of the aflibercept comparator through the loading phase.
Regarding its safety profile: The candidate demonstrated favorable safety and was well tolerated in the study with a
- 0% intraocular inflammation (IOI) rate
- 0.5% cataract adverse event rate (vs. 0.9% with aflibercept comparator)
Regarding KSI-501’s performance …
The candidate met the vision primary endpoint (p=0.0036) and anatomical key secondary endpoint (p<0.0001).
KSI-501 also demonstrated favorable safety and was well tolerated in the study with a 0.4% IOI rate and a 0% cataract adverse event rate (vs. 0.9% with aflibercept).
- In addition: Post-hoc analyses to identify which treatment-naïve wet AMD patient subgroups can benefit from IL-6 inhibition are planned.
Any comments from the company on this news?
"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, DR, and RVO" noted Victor Perlroth, MD, CEO of Kodiak Sciences.
He added: "The results generated in DAYBREAK with [KSI-501] are also highly encouraging, and we are enthusiastic to explore the potential for tabirafusp-ted to demonstrate superiority in patients with DME in the ongoing phase 3 ALTO pivotal program.”
And on that BLA application?
Kodiak plans to submit a three-indication Biologics License Application (BLA) for Zenkuda to regulatory authorities in Q4 2026 based on data from the five positive phase 3 studies (i.e.,
- DAYBREAK and DAYLIGHT in wAMD
- GLOW1 and GLOW2 in DR
- BEACON in macular edema following RVO
Anything else to keep on my radar?
The company also reported that it remains on track to announce topline data in December 2026 for KSI-101 in the phase 3 PEAK study (NCT06990399) in patients with MESI, in which KSI-101 is being evaluated for superiority against sham-treated patients.
- Kodiak plans to file a BLA for KSI-101 in Q2 2027.