07.29.19

Kodiak Sciences Announces Positive Interim Data from Phase 1b Study of KSI-301, a Novel Anti-VEGF Antibody Biopolymer Conjugate for Treatment of Retinal Diseases

Source: Kodiak Sciences

Kodiak Sciences announced positive interim results from the ongoing phase 1b study of KSI-301, its investigational intravitreal anti-VEGF antibody biopolymer conjugate in patients with anti-VEGF treatment-naïve wet age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema due to retinal vein occlusion (RVO). 

The results were presented by Pravin U. Dugel, MD, an investigator in the study, as an oral presentation at the American Society of Retina Specialists (ASRS) 2019 Annual Meeting. Dr. Dugel is Managing Partner, Retinal Consultants of Arizona and Retinal Research Institute, Phoenix, and Clinical Professor, Roski Eye Institute, USC Keck School of Medicine, Los Angeles. The detailed study findings presented by Dr. Dugel can be found on the Kodiak Investor Relations website at http://ir.kodiak.com.

Summary of Efficacy Outcomes through Week 12

Across all three diseases under study, strong improvements in vision and retinal anatomy were observed over 12 weeks. Vision is measured as change in Best Corrected Visual Acuity (BCVA) on a standardized eye chart, and retinal anatomy is measured as change in retinal central subfield thickness (CST) using optical coherence tomography (OCT) imaging. The efficacy data presented at ASRS include outcomes from 35 patients in the study who had reached the week 12 visit. In the study, patients are being treated with three monthly doses of either 2.5 mg or 5 mg KSI-301 and followed for 7 months thereafter, with additional treatments according to protocol-specified retreatment criteria.

The following results were observed at Week 12*:

Disease (number

of patients)

Median

Baseline

BCVA, letters

Median Baseline

OCT CST,

microns

Change in Median

BCVA at Week 12,

letters

Change in Median

OCT CST at Week 12,

microns

Wet AMD (n=17)

66

380

+8

-96

DME (n=8)

69.5

491

+9.5

-197

RVO (n=10)

52.5

513

+26.5

-209

*Includes patients who reached Week 12 visit by July 24, 2019 data cutoff date; 2.5 & 5 mg doses pooled.

“We are pleased with KSI-301’s promising efficacy and safety data to date,” Jason Ehrlich, MD, PhD, Kodiak’s Chief Medical Officer and Chief Development Officer, said in a company news release. “In addition to vision and anatomic improvements, we have observed encouraging signs of disease modification. In the individual case studies presented at ASRS, using OCT angiography we observed normalization of retinal vascular flow in an RVO patient seen as early as one week after the first dose and reduction in choroidal neovascularization size and vascular flow rate in a wet AMD patient. In a DME patient with proliferative retinopathy, we observed conversion to non-proliferative retinopathy and a two-step improvement in diabetic retinopathy severity score at the 12-week assessment. These findings increase our conviction in the promise of KSI-301 and the further potential of our ABC Platform. We look forward to presenting emerging durability data from the Phase 1b study at the American Academy of Ophthalmology Retina Subspecialty Day on October 11, 2019.”

Summary of Safety Outcomes

A total of 200 injections with KSI-301 have been given to date across the phase 1a and phase 1b program with no intraocular inflammation or ocular serious adverse events reported.

As of the July 24, 2019 ASRS presentation’s data cut-off date, a total of 77 patients were enrolled in the phase 1b study. Multiple-dose exposure to KSI-301 has been well tolerated. A total of 77 patients have received one injection, 60 patients have received two injections and 44 patients have received three injections. No drug-related adverse events or serious adverse events have been reported. Most of the adverse events reported have been assessed as mild (70%) and are consistent with the profile of intravitreally-injected anti-VEGF agents. Eight nonocular serious adverse events have been reported in four patients, none being assessed as drug-related.

Twelve leading retinal research centers in the United States are participating in the phase 1b study. For additional details about the study, please see https://clinicaltrials.gov/ct2/show/NCT03790852.

Phase 1b Trial Expansion

The phase 1b study of KSI-301 is nearing completion of enrollment of the planned cohorts. Based on the positive data observed to date, Kodiak is planning for supplemental cohorts to explore additional scientific questions relevant to KSI-301 and its use for the treatment of retinal diseases.

Status of Phase 2 ‘DAZZLE’ Study in Wet AMD

Recruitment in a phase 2 head-to-head trial of KSI-301 versus aflibercept in treatment-naïve wet AMD patients is expected to begin in the third quarter of 2019. In this study, called DAZZLE, approximately 364 patients are planned to be enrolled worldwide. Patients will be randomized to receive either KSI-301 on a dosing regimen as infrequently as every 20 weeks or standard-care aflibercept on its every 8-week dosing regimen. All patients randomized to KSI-301 will be on an every 12-week or longer regimen after 3 monthly loading doses.

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