Kodiak Reboots Tarcocimab Tedromer Development Program Following Strong Positive Phase 3 DR Results

Three months after deciding to discontinue tarcocimab tedromer due to two failed late-stage trials, Kodiak Sciences announced it is rebooting its clinical program after its phase 3 GLOW superiority study evaluating tarcocimab tedromer 5 mg in moderately severe to severe NPDR met its 1-year primary endpoint.

"This is the first time that 6-month dosing in all patients succeeded in treating diabetic retinopathy which we believe is a meaningful and clinically relevant achievement," Dr. J. Pablo Velazquez-Martin, Senior Vice President of Clinical Sciences at Kodiak Sciences, said in a company news release. "We think that the consistency of the data across all endpoints, where tarcocimab significantly improved the diabetic eye disease status and, importantly, significantly prevented sight-threatening complications, is remarkable. The GLOW data reinforce the durability potential of tarcocimab and the antibody biopolymer conjugate platform (ABC Platform) in the management of retinal vascular diseases."

"We think that durability remains the most clinically relevant unmet patient need," said Dr. Victor Perlroth, CEO of Kodiak. "We now have three successful phase 3 pivotal studies with tarcocimab tedromer across three different retinal vascular and exudative diseases: wet AMD, RVO, and NPDR. In recent discussions with the FDA, which included the GLOW data, we believe we have a clear regulatory pathway requiring one additional positive study to support a single BLA submission for all three indications."

"We have actionable learnings from the tarcocimab clinical program that we used to develop an enhanced commercial formulation of tarcocimab that balances free antibody and conjugated antibody to improve manufacturability and, importantly, to improve usability by reducing injection time from 7-10 seconds to 2-3 seconds. This formulation has already been manufactured at commercial scale and is ready for use in clinical trials. After evaluation of the phase 3 data across the tarcocimab program and based on conversations with members of the retina community, we believe our commercial tarcocimab formulation could be an important future therapeutic option. As a result, we have decided to run another pivotal study with the intent to file a single BLA for RVO, wet AMD and NPDR. This enhancement to the ABC Platform is also being implemented in our first-in-class anti-IL-6 and anti-VEGF bispecific, KSI-501 ABC," Dr. Perlroth said.

Kodiak paused further development of tarcocimab in July after its GLEAM and GLIMMER studies in diabetic macular edema did not meet their primary endpoint, in order to evaluate learnings from its pivotal BEACON study in patients with macular edema due to retinal vein occlusion and from its GLOW study.

The company stated it believes that the 1-year head-to-head BEACON results and primary endpoint and key secondary endpoint GLOW results support the development of three attractive clinical prospects: enhanced tarcocimab ABC, enhanced bispecific KSI-501 ABC, and KSI-501 bispecific free protein (not conjugated) and that Kodiak has on hand sufficient capital to further develop in parallel all three of these prospects.

Dr. Perlroth added, "Kodiak thanks the GLOW investigators and patients whose participation and commitment helped us to generate strong data in GLOW and thus to recognize the continued importance for patients of our ABC Platform and our platform-derived medicines."

About the GLOW Study Results

First time results from GLOW were presented at the American Academy of Ophthalmology retina subspecialty day on November 3, 2023. View original content: https://ir.kodiak.com/static-files/ee94e5bd-da6e-4038-b00c-1956c72e5c72.

The phase 3 GLOW study investigated an every 24-week tarcocimab dosing regimen for all subjects, versus sham, in patients with moderately-severe and severe NPDR without DME.

At 1 year, GLOW met its primary endpoint of the proportion of patients with at least a 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) score, a grading system measuring the degree of retinopathy. Tarcocimab achieved a 29-fold increased response rate ratio, with 41.1% of evaluable patients on tarcocimab demonstrating at least 2-step improvement versus 1.4% of evaluable patients in the sham group (P<0.0001). Visual acuity and retinal anatomy were improved and stable with tarcocimab on its extended-dosing intervals.

GLOW also met all key secondary endpoints, including greater reductions in the proportion of patients developing sight-threatening complications (such as diabetic macular edema and proliferative diabetic retinopathy), versus sham, demonstrating an 89% decreased risk, achieving 21.0% versus 2.3% (P<0.0001). Tarcocimab also showed a 95% risk reduction in the development of DME, versus sham, from 13.7% on sham versus 0.7% on tarcocimab.

After the occurrence of a sight-threatening complication, all subjects were rescued with open-label tarcocimab, where subjects received two loading doses once monthly followed by continued every 12-week dosing. In patients developing sight-threatening complications, the initial visual acuity decrease and retinal anatomy worsening were both rapidly controlled and then stabilized with every 12-week dosing of tarcocimab.

The rates of serious ocular adverse events and intraocular inflammation in patients treated with tarcocimab and sham were similar in both groups.

About the GLOW Study Design

The phase 3 GLOW study is a global, multicenter, randomized pivotal superiority study designed to evaluate the efficacy and safety of tarcocimab tedromer in treatment-naïve patients with moderately severe to severe NPDR. Patients are randomized to receive either tarcocimab every 6 months after initiating doses given at baseline, 8 weeks and 20 weeks into the study, or to receive sham injections. The primary endpoint is at 1 year. Outcomes include changes in diabetic retinopathy severity, measured on a standardized photographic grading scale, and the proportion of tarcocimab treated patients who developed a sight threatening complication due to diabetic retinopathy. Additional information about GLOW (also called Study KS301P106) can be found on www.clinicaltrials.gov under Trial Identifier NCT05066230 (https://clinicaltrials.gov/show/NCT05066230).