New conjugate biopolymer safe anti-VEGF antibody, effective in first phase 1b results

Pravin U. Dugel

CHICAGO – Several intravitreal administrations of KSI-301, a novel biopolymer conjugate of anti-VEGF antibodies, have improved the improved corrected visual acuity and retinal anatomy in patients with macular degeneration related to age, diabetic macular edema and retinal occlusion, a speaker being said here.

"Biopolymer antibody conjugates, or ABCs, are a new scientific approach and a new design platform for intravitreal drugs. The Kodiak Sciences KSI-301 has achieved its first developmental goals: to demonstrate high efficiency and excellent safety in major vascular retinal diseases ", Pravin U. Dugel, MD, said at the meeting of the American Society of Retina Specialists.

Phase 1b of the open-label study will include 90 patients randomized to 1: 3 receiving 2.5 mg KSI-301 or 5 mg. Patients receive three initial injections of KSI-301 at 4-week intervals and the need to administer additional doses of KSI-301 every 4 weeks starting from week 16 will be badessed. Are underway, said Dugel.

Dugel shared the current data from the 12-week study. Seventeen patients with wet AMD presented an improvement of 8 letters ETDRS and a reduction of 96 central subzone thickness (CST) from beginning to week 12. Eight patients with macular edema and diabetic retinopathy showed a 9.5-letter improvement and a 197-m reduction in CST compared to baseline. Finally, 10 patients with retinal vein occlusion had an improvement of 26.5 letters and a CST reduction of 209 m compared to departure, he said. Antibody-polymer (ABC) conjugates are designed for increased durability and efficiency. The ABC platform consists of an antibody and a biopolymer covalently linked via a specific binding at a single site. The KSI-301 molecule has a higher molecular weight of 950 kDa compared to 26 kDa for brolucizumab, 48 kDa for ranibizumab and 115 kDa for aflibercept.

"This is a big molecule … and most importantly, the equivalent ocular concentration of three months is one million times that of ranibizumab," he said.

"Multi-dose exposure to KSI-301 is well tolerated, with no intraocular inflammation at 181 doses," said Dugel. – by Robert Linnehan