This weekend results from novel therapeutics to treat chronic, high-prevalence retinal diseases, were presented during the European Society of Retina Specialists’ 19th EURETINA Congress, held September 5 – 8, 2019 in the Palais des Congrés de Paris, in Paris, France.

Among the presentations were positive interim results from the ongoing phase 1b study of KSI-301, an investigational intravitreal anti-VEGF antibody biopolymer conjugate in patients with anti-VEGF treatment-naïve wet age-related macular degeneration (AMD; n=17), diabetic macular edema (DME; n=8), and macular edema due to retinal vein occlusion (RVO; n=10). The drug is being developed by Kodiak Sciences.

KSI-301 is an investigational agent based on the company’s Antibody-Biopolymer Conjugate (ABC-) Platform, and has achieved its early development goals of demonstrating strong efficacy and excellent safety in the major retinal vascular diseases. The illustration shows the individual elements of Kodiak Sciences’ proprietary ABC Platform.

KSI-301 is an investigational therapy built using Kodiak Sciences’ proprietary Antibody Biopolymer Conjugate (ABC-) Platform, a new scientific approach and design platform for intravitreal drugs which includes a novel monospecific and bispecific antibody protein engineered for site-specific conjugation to a phosphorylcholine-based biopolymer.

The agent is designed to maintain potent and effective drug levels in ocular tissues for longer than existing agents and treatment options.  The novel anti-VEGF biologic with an extended ocular half-life may block the ocular effects of high blood sugar levels, potentially preventing or slowing the progression of diabetic eye disease.

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The company plans to use KSI-301, to improve real-world outcomes for patients with retinal vascular diseases and to enable earlier treatment and prevention of vision loss for patients with diabetic eye disease.

Trial results
During the EURETINA Congress the latest interim results results were presented by Pravin U. Dugel, MD,  Clinical Professor, Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California and Managing Partner, Retinal Consultants of Arizona, Retinal Research Institute, Phoenix, AZ.

Dugel showed that across the 3 diseases, strong improvements in best-corrected visual acuity (BCVA) and central subfield thickness were observed over 12 weeks. This was particularly the case in retinal vein occlusion (RVO). The efficacy data presented include outcomes from 35 participating patients who had reached the week-12 visit.

In this Phase 1b open-label study patients are were being treated with 3 monthly doses of either 2.5 mg (50 μL) or 5 mg (100 μL) KSI-301 and followed for 7 months, with additional treatments according to protocol-specified retreatment criteria.

In the second study, researchers evaluated the efficacy, safety, durability, and pharmacokinetics of KSI-301 administered at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).

“In addition to vision and anatomic improvements, our team observed encouraging signs of disease modification,” explained Jason Ehrlich, MD, Ph.D, Kodiak’s chief medical officer and chief development officer.

“Using Optical Coherence Tomography (OCT) angiography we noticed normalization of retinal vascular flow in a patient with retinal vein occlusion who was seen as early as 1 week after the first dose and reduction in choroidal neovascularization size and vascular flow rate in a patient diagnosed with wet age-related macular degeneration,” Ehrlich said.

“In [one patient with diabetic macular edema] with proliferative retinopathy, we observed conversion to nonproliferative retinopathy and a 2-step improvement in diabetic retinopathy severity score at the 12-week assessment,” Ehrlich concluded.

“We continue to be pleased with the promising efficacy and safety data of KSI-301,” noted Victor Perlroth, MD, Chief Executive Officer of Kodiak Sciences.

“At EURETINA, we reported outcomes with over 100 patients dosed and a growing safety database with over 250 injections of KSI-301. The data being presented continue to demonstrate the potential for KSI-301 to be a first-line intravitreal anti-VEGF therapy,” Perlroth said.

“The early Phase Ib results presented during the EURETINA meeting warrant further evaluation in randomized pivotal studies,” Dugel concluded.

In addition to KSI-301 Kodiak Sciences has used its ABC Platform to build a pipeline of product candidates, including KSI-501, a bispecific anti-IL-6/VEGF biopolymer conjugate for the treatment of inflammatory neovascular retinal diseases.

Clinical trials
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. (DAZZLE) – NCT04049266

Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO – NCT03790852

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