tarcocimab tedromer (KSI 301) / Kodiak Sciences - LARVOL DELTA

Based on the strong safety, efficacy and durability data demonstrated in the GLOW2 study, Zenkuda now has a multi-indication Biologics License Application (BLA)-ready profile, and Kodiak intends to accelerate the BLA submission timeline. (PRNewswire) - "'Leaning into FDA's new single-pivotal-trial default option for approval, we are also anticipating a potential BLA submission for KSI-501 in wet AMD after the DAYBREAK study primary endpoint readout (expected 3Q2026, if successful) and for KSI-101 in Macular Edema Secondary to Inflammation (MESI) after the PEAK study pivotal analysis 1 readout (expected 4Q2026, if successful).'...'four different Phase 3 studies with three readouts expected in 2026...'"

Clinical data • FDA filing • Diabetic Retinopathy • Macular Edema • Ocular Inflammation • Wet Age-related Macular Degeneration

Kodiak Sciences Announces Positive Topline Results in GLOW2, the Second Phase 3 Study in Diabetic Retinopathy, Demonstrating Superiority of Zenkuda (tarcocimab tedromer) Over Sham (PRNewswire) - "A total of 62.5% of patients treated with Zenkuda achieved a ≥2-step improvement in DRSS score at Week 48, compared with 3.3% in the sham group, meeting the primary endpoint of superiority to sham with high statistical significance (p<0.0001)...Zenkuda demonstrated superiority in the key secondary endpoint of reducing the risk of developing prespecified sight-threatening complications, including new or worsening proliferative DR or center-involving DME, by 85% compared to sham through Week 48 (2.4% with Zenkuda versus 15.8% with sham, p=0.0001)....The full end-of-study results will be presented at an upcoming congress by Dr. Charles Wykoff."

P3 data: top line • Diabetic Retinopathy

Tarcocimab – Phase 3 topline data expected in 1Q 2026 (6 months) and 3Q 2026 (12 months) (PRNewswire) - "Phase 3 GLOW2 diabetic retinopathy study...Phase 3 DAYBREAK wet AMD study....Completed the manufacturing and release of BLA-facing commercial-scale batches in Kodiak's URSUS facility."

P3 data: top line • Diabetic Retinopathy • Wet Age-related Macular Degeneration

A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK (clinicaltrials.gov) - P3 | N=675 | Active, not recruiting | Sponsor: Kodiak Sciences Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2027 ➔ Aug 2027 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Enrollment closed • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Beyond the injection: delivery systems reshaping retinal disease management. (PubMed, Expert Opin Pharmacother) - "Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone)...Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies."

Journal • Review • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders

GLOW2: A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer Compared With Sham Treatment in Participants With Diabetic Retinopathy (DR) (clinicaltrials.gov) - P3 | N=255 | Active, not recruiting | Sponsor: Kodiak Sciences Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetic Retinopathy • Retinal Disorders

DAYBREAK Phase 3 study (PRNewswire) - "We remain focused on completing enrollment in our ongoing DAYBREAK Phase 3 study to broaden the efficacy profile for tarcocimab in wet age-related macular degeneration ('wet AMD'), and it is our plan to wait for DAYBREAK topline data expected in 2Q 2026 in order to file a single BLA for tarcocimab in wet AMD..."

P3 data: top line • Trial status • Wet Age-related Macular Degeneration

Kodiak Sciences Completes Enrollment in Second Registrational Trial of Tarcocimab in Patients with Diabetic Retinopathy (PRNewswire) - "Kodiak Sciences...announced that it has completed enrollment in its GLOW2 Phase 3 clinical trial of tarcocimab tedromer in patients with diabetic retinopathy ('DR')....'We randomized more than 250 patients into our GLOW2 Phase 3 study, exceeding our enrollment target', said Victor Perlroth, M.D., Chief Executive Officer of Kodiak. 'With its 48-week duration of treatment, all patients are expected to complete their primary endpoint visits by the end of January 2026, and we expect to announce topline clinical data in 1Q 2026'."

P3 data: top line • Trial status • Diabetic Retinopathy

A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants with Neovascular (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK (clinicaltrials.gov) - P3 | N=675 | Recruiting | Sponsor: Kodiak Sciences Inc | Trial completion date: Jan 2026 ➔ Apr 2027 | Trial primary completion date: Jan 2026 ➔ Apr 2026

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Kodiak Sciences Announces Recent Business Highlights and Third Quarter 2024 Financial Results (PRNewswire) - "'It is our objective to complete enrollment for the Phase 3 GLOW2 and DAYBREAK studies of tarcocimab and KSI-501 in the first half of 2025, so we and all Kodiak stakeholders can have a clear line of sight to our 48-week topline data readouts....The decrease in R&D expenses for the third quarter of 2024, as compared to the same period in 2023, was primarily driven by reduced manufacturing activities, decreased clinical activities for completed trials, partially offset by costs from active clinical trials for the tarcocimab development program as well as expanding clinical activities for KSI-501 and KSI-101."

Commercial • Enrollment status • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Edema • Ophthalmology • Wet Age-related Macular Degeneration

Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues. (PubMed, Eye (Lond)) - "Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC • VEGFD

Intraocular drugs: pharmacokinetic strategies and the influence on efficacy and durability. (PubMed, Expert Opin Drug Metab Toxicol) - "Durability strategies include inhibiting additional pathways (faricimab), increasing molar dose (abicipar, brolucizumab, faricimab, and aflibercept 8 mg), and prolonging the intravitreal half-life (abicipar and KSI-301). Recent phase 3 trials demonstrated modest improvements in durability, but failures that might be attributed to these strategies (conjugation and manufacturing processes) have occurred. Future drug development focuses on extending duration of action with implantable reservoirs (ranibizumab port delivery system), sustained release devices (tyrosine kinase inhibitors), and gene therapy."

Journal • PK/PD data • Review • Gene Therapies

Kodiak Sciences Announces Recent Business Highlights and Second Quarter 2024 Financial Results (PRNewswire) - "Following submission of the study protocol to the FDA in the first quarter of 2024, we began to operationalize the study including site selection in the second quarter of this year. The DAYBREAK Phase 3 study is now actively enrolling patients....Research and development (R&D) expenses were $32.5 million for the second quarter of 2024, as compared to $67.0 million for the second quarter of 2023. The R&D expenses for the second quarter of 2024 included non-cash stock-based compensation of $8.9 million, as compared to $14.7 million for the second quarter of 2023. The decrease in R&D expenses for the second quarter of 2024, as compared to the same period in 2023, was primarily driven by reduced manufacturing and clinical activities for tarcocimab."

Commercial • Enrollment status • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Wet Age-related Macular Degeneration

A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK (clinicaltrials.gov) - P3 | N=675 | Recruiting | Sponsor: Kodiak Sciences Inc

New P3 trial • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

DAZZLE: A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration. (clinicaltrials.gov) - P2/3 | N=559 | Terminated | Sponsor: Kodiak Sciences Inc | Phase classification: P2b ➔ P2/3

Phase classification • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Kodiak Sciences Announces Treatment of First Patients in Phase 3 GLOW2 Study of Tarcocimab Tedromer in Diabetic Retinopathy (PRNewswire) - "Kodiak Sciences...announced today that the first patients with diabetic retinopathy (DR) have been treated in the randomized double masked Phase 3 GLOW2 study of tarcocimab tedromer. GLOW2 is the second Phase 3 study of tarcocimab in diabetic retinopathy in which all patients on investigational therapy will receive tarcocimab on extended dosing intervals, including 6-month dosing for all patients."

Trial status • Diabetic Retinopathy

Perspectives on the currently available pharmacotherapy for wet macular degeneration. (PubMed, Expert Opin Pharmacother) - "Promising developments include extending treatment intervals with newer anti-VEGF agents like brolucizumab and faricimab, biosimilars offering cost-effective options, and exploring innovative drug delivery methods such as subretinal gene therapy. Combination therapies, gene therapies, and novel agents like KSI-301 and OPT-302 show potential for improving treatment outcomes and reducing treatment burden. While current treatments for w-AMD have significantly advanced with the advent of anti-VEGF therapies, their limitations in terms of treatment burden and incomplete responses have spurred research into diverse alternative approaches. These innovative strategies offer hope for improving patient outcomes and reducing healthcare burdens, suggesting a promising future for w-AMD management."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Kodiak Sciences Data at ARVO 2024 Highlight Depth of Early and Late-Phase Retina Pipeline including Advancements with High Drug-Antibody-Ratio Therapeutics Built on Kodiak's Antibody Biopolymer Conjugate (ABC) Platform (PRNewswire) - P3 | N=253 | GLOW (NCT05066230) | Sponsor: Kodiak Sciences Inc | "Kodiak Sciences Inc...announced today that nine scientific presentations on its clinical and research pipeline programs will be made at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting, being held from May 5 – 9 in Seattle, Washington....Kodiak's GLOW1 study with tarcocimab showed for the first time that a therapeutic agent dosed in all patients on an every 6-month interval can successfully treat and prevent disease worsening in DR patients. Tarcocimab offers the hope of an achievable prevention and treatment strategy in real-world clinical practice for DR patients at risk of vision loss. Currently, the Phase 3 GLOW2 study is enrolling patients with DR, with the goal to enable tarcocimab's marketing authorization application."

Enrollment status • P3 data • Diabetic Retinopathy • Ophthalmology

Kodiak Sciences Data at ARVO 2024 Highlight Depth of Early and Late-Phase Retina Pipeline including Advancements with High Drug-Antibody-Ratio Therapeutics Built on Kodiak's Antibody Biopolymer Conjugate (ABC) Platform (PRNewswire) - P3 | N=253 | GLOW (NCT05066230) | Sponsor: Kodiak Sciences Inc | "The prespecified analysis of the GLOW1 study demonstrated that both the tarcocimab treatment arm and sham arm had negligible change in systemic metabolic control as measured by HbA1c levels, and both arms showed similar distribution of change in HbA1c from baseline to primary endpoint at Week 48. These results suggest that subjects in the tarcocimab arm achieved superiority in ≥2-step improvement in DRSS over sham injections irrespective of baseline and systemic metabolic control, as evidenced by HbA1c levels, and any potential presumed knowledge by the patient about treatment assignment due to the use of sham as a comparator did not systematically influence their glycemic control."

P3 data • Diabetic Retinopathy • Ophthalmology

Tarcocimab tedromer (KSI-301) 5mg: outcomes of the Phase 3 GLOW Study in patients with non-proliferative diabetic retinopathy. (ARVO 2024) - "The adoption of approved anti-VEGF therapies for DR is constrained partly by the high treatment burden. The results from the GLOW Study demonstrate that treatment with tarcocimab in a reduced dosing regimen is superior to sham for treatment of NPDR. With a total of 4 doses in the first year and 6-month dosing, tarcocimab could represent a clinically meaningful alternative for this patient population."

Clinical • P3 data • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

Metabolic control in patients with non-proliferative diabetic retinopathy (NPDR) treated with anti-VEGF active injections or sham injections. Prespecified results from the Phase 3 GLOW Study in patients treated with tarcocimab tedromer. (ARVO 2024) - "Results demonstrate that subjects in the tarcocimab arm achieved superiority over sham irrespective of the baseline and change in systemic metabolic control, as evidenced by HbA1c.In the GLOW Study, the use of sham as a comparator resulted in an adequate and well controlled study. Results demonstrate that any presumed knowledge from treatment assignment by the patient did not systematically influence their glycemic control."

Clinical • P3 data • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

GLOW2: A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer Compared With Sham Treatment in Participants With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Kodiak Sciences Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetic Retinopathy • Retinal Disorders

Kodiak Sciences Announces Recent Business Highlights and Fourth Quarter and Full Year 2023 Financial Results (PRNewswire) - "New Phase 3 GLOW2 study of tarcocimab in diabetic retinopathy actively recruiting...We are discussing the study design of DAYBREAK with the FDA and plan to initiate the study as soon as regulatory alignment is completed, which we hope is mid-2024....Tarcocimab commercial scale manufacturing: Our custom-built commercial scale manufacturing facility, Ursus, was commissioned as a cGMP facility in January 2023....In October 2023, we made a final payment of $26.8 million to Lonza for final activation of Ursus. Separately, tarcocimab drug product based on our go-to-market formulation was released in March 2024 and is ready for use in GLOW2 and DAYBREAK Phase 3 studies."

Commercial • New P3 trial • Trial status • Age-related Macular Degeneration • Diabetic Retinopathy • Ophthalmology • Wet Age-related Macular Degeneration

GLOW2: A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer Compared With Sham Treatment in Participants With Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR) (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Kodiak Sciences Inc

New P3 trial • Diabetic Retinopathy • Retinal Disorders

Kodiak Sciences Announces Third Quarter 2023 Financial Results and Recent Business Highlights (PRNewswire) - "KSI-501 clinical program: Our Phase 1 study of KSI-501 ABC has completed its enrollment and dosing phases, and patient data are continuing to be collected. Clinical data are expected to be presented in the first quarter of 2024 at an upcoming scientific meeting....Research and development (R&D) expenses were $36.2 million for the third quarter of 2023, as compared to $61.7 million for the third quarter of 2022....The decrease in R&D expenses for the third quarter of 2023 was primarily driven by reduction in expense during the pause of tarcocimab development and equity award forfeitures related to the 2021 Long-Term Performance Incentive Plan."

Commercial • P1 data • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Vein Occlusion • Wet Age-related Macular Degeneration