S.C. delivery of ultra-high concentration (up to 500 mg/mL) protein microparticle suspensions: pharmacokinetics, efficacy, biodistribution, and immunogenicity.

A shift towards the subcutaneous (S.C.) delivery of protein therapeutics is enabling patient-centric at-home self-administration. To circumvent the volume constraints of the S.C. route of delivery, protein therapeutics are required to achieve ever higher concentrations to administer doses beyond 1 g. Aqueous technologies rarely concentrate above 175 mg/mL and endure syringability and stability complications. Elektrofi's novel non-aqueous microparticle suspensions enable such ultra-high concentration delivery of protein therapeutics subcutaneously. In this work, we demonstrate the bioequivalence of high-concentration suspensions compared to their aqueous counterparts in a rodent model. The 500 mg/mL concentration iteration of the injection was injectable in 20 s with forces below 20 N. We also demonstrate comparable subcutaneous clearance of the suspension test articles to the aqueous comparator. To the best of our knowledge, this work is the first to report comparable efficacy and immunogenicity of microparticle suspensions to the aqueous comparator formulation. The model commercially available reagents serve as a glimpse into the performance of the Elektrofi technology which is in the process of advancing into the clinic with a multitude of biopharma partnerships.