Pharmacokinetic Analysis of RO-104 in Rabbit Eye Vitreous

Abstract

Purpose : The objective of this study is to evaluate the vitreal pharmacokinetic (PK) profile of a novel trispecific surrobody, RO-104, designed to inhibit Vascular Endothelial Growth Factor-A and C (VEGF-A, VEGF-C), as well as Angiopoietin-2 (Ang-2).

Methods : Eleven rabbits received bilateral 1 mg intravitreal injections of RO-104 and the resulting concentrations of RO-104 were measured across a 29-day period. To determine the concentration of RO-104 we performed quantitative ELISA analysis utilizing target-based capture of the vitreous humor. Specifically, terminal vitreous analysis was performed on days 1, 3, 8, 15, and 29. The concentration of RO-104 in the left eye of one sacrificed rabbit was measured in target-specific binding ELISA at these time points. Half-life for each target was calculated by using the highest and lowest concentration across the 29-day study. All experiments were performed in accordance with the ARVO statement for Use of Animals in Ophthalmic and Vision research.

Results : For each of the three target-based ELISAs the C_max was observed in day 3 of the vitreal samples. We made our half-life calculations based between day 3 C_max and study end day 29 concentrations. The half-life calculations RO-104 bound to VEGF-A, Ang-2, and VEGF-C were 3.78, 3.91, and 4.07 days, respectively.

Conclusions : In this preclinical pharmacokinetic vitreal animal study, RO-104 showed consistent half-life estimates with each target-based assay. The calculated half-life appears appropriate with consistent. Future testing should be conducted to assess this agent as a treatment option for eye pathologies such as macular degeneration.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Table 1: T_max and C_max of RO-104 bound to VEGF₁₆₅ , Ang-2, and VEGF-C

 

Figure 1: Concentration of RO-104 bound to VEGF₁₆₅, Ang-2, and VEGF-C in vitreous humor across 29-day study