Abstract
Purpose :
We proposed to test retention of vascular leakage-inhibiting function in a novel anti VEGF/anti IL17a antibody, BIOP 653.1 (Biophtha, Suwanee, GA), versus Aflibercept (Regeneron Tarrytown, NY) in a chronic DL-a-Aminoadipic acid (AAA)-induced vascular leakage model.
Methods :
Dutch Belted rabbits were injected intravitreally (IVT) with 1.0 mg of AAA (Sigma) in left (OS) eyes two weeks prior to 50 mL IVT administration of Aflibercept (2 mg; Group 1) or BIOP 653.1 (2.5 mg; Group 2). Right eyes (OD) remained non-AAA-treated in Group 1 and Group 2. Group 2 OD received BIOP 653.1 to assess test article safety. Evaluations at day -2 prior to dose at day 0 confirmed leakage induction and animals were stratified across groups according to leakage severity. Slit lamp biomicroscopy was used to evaluate ocular inflammatory scores (Hackett-McDonald [HM]) alongside monitoring of intraocular pressure (IOP) on days -2, 1, 3, 7, 14 and 28. Fluorescein angiography and fundoscopy were performed on days -2, 7, 14, 21 and 28. Background-normalized total leakage signal was determined by image analysis to quantify changes in leakage signal over time.
Results :
AAA-induced vascular leakage occurred in 10/10 rabbits by day -2. Resolution of leakage was comparable between Aflibercept and BIOP 653.1, suggesting that BIOP 653.1 retained leakage-inhibiting anti VEGF function. By day 14 HM scores were elevated in OS eyes treated with BIOP 653.1 compared to Aflibercept-injected OS eyes, and HM scores remained elevated thereafter. Results from IOP measurements and ocular exams were documented.
Conclusions :
BIOP 653.1 is a novel multifunctional antibody with anti VEGF and anti IL17a components. Biophtha partnered with Powered Research to determine if anti VEGF activity is retained through BIOP 653.1 engineering and manufacture using an established rabbit model. Here we demonstrate inhibition of vascular leakage by BIOP 653.1 with efficacy comparable to that of Aflibercept. BIOP 653.1 is early in development and a likely candidate for studies to determine half-life and durability of effect. We did not expect effects from the BIOP 653.1 IL17a component due to low sequence conservation between human and rabbit IL17a epitopes. Testing in primates will be needed to assess activity of the BIOP 653.1 anti IL17a component.
This is a 2021 ARVO Annual Meeting abstract.