Characterizing a Novel Bispecific Platform (Surrobody) for use in Back of the Eye Disease

Abstract

Purpose : Several back of the eye diseases are mediated through multiple complex pathways with cross-talk. Having the ability to bind multiple targets with a single molecule may prove especially beneficial, bringing gains in efficacy of treatment. The purpose of this study is to characterize a novel bispecific platform (surrobody) for use in back of the eye disease. This study describes the structure of the novel platform and characterizes its Chemistry, Manufacturing, and Controls(CMC) characteristics through use of Size Exclusion Chromatography (SEC), its pharmacokinetic half-life (PK) in cynomolgus monkeys, and its thermostability after 12 months of storage at various temperatures.

Methods : All experiments were performed in accordance with the ARVO statement for Use of Animals in Ophthalmic and Vision Research. Three cynomolgus monkeys were administered an intravenous dose of Bispecific surrobody (10 mg/kg). Serum was tested over a 28 day period, with PK values then calculated. SEC was used to characterize the product after HEK293F transfection which showed high expression. Thermostability was assessed by holding Bispecific Surrobodies at room temperature, -80°C , and 4°C for 12 months and then assessing half maximal effective concentration via Enzyme Linked Immunosorbent Assay (ELISA).

Results : PK in cynomolgus monkeys was found to be 6.04 days for the Bispecific Surrobody as compared to 10.88 days for the control antibody using ELISA. SEC revealed single peaks indicating high levels of heterodimeric bispecific product formation. ELISA testing revealed no loss of activity of the Bispecific Surrobody with storage between -80°C and room temperature for 12 months.

Conclusions : This novel bispecific platform has several desirable characteristics for a potential therapeutic agent. Its CMC characteristics show single peaks on SEC indicating high levels of heterodimeric bispecific product. Its full length constant fragment (Fc) affords long half-life as demonstrated in serum of cynomolgus monkeys on par with typical antibody half-life. Additionally, its thermostability at room temperature and ability to withstand a freeze-thaw cycle without losing efficacy points to its durability and potential to do away with cold chain logistics required for current generation therapeutics. Further study of the platform is warranted as the potential to develop into a next generation therapeutic exists.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.