SEMINAR: Prof. Eric Andrew Appel

Speaker: Prof. Eric Andrew Appel

Title: Biomimetic Polymer Technologies for Improving Biologic Formulation and Delivery

Abstract: Protein aggregation is a critical challenge impacting biologic drug product manufacturing, accessible therapeutic concentrations, and stability of biologic formulations. Extensive efforts have been devoted to developing excipients to stabilize proteins in formulation. Yet, while some “gold-standard” materials such as polysorbates and pluronics have arisen for these purposes, these additives exhibit critical limitations on account of their propensity to form particles, poor stability, toxicity limits, low glass transition temperatures, and variable efficacy under different formulation conditions. To address these shortcomings, we leveraged a high-throughput combinatorial synthesis and screening approach to develop polyacrylamide-based copolymer excipients comprising water-soluble “carrier” monomers and functional “dopant” monomers. These efforts generated a lead candidate copolymer composed of acryloylmorpholine and n-isopropylacrylamide, which we call MoNi, that acts as simple “drop-in” excipient to prevent protein aggregation in formulation. Indeed, with commercial insulin drugs, we show that MoNi maintains protein formulation integrity, bioactivity, pharmacokinetics, and pharmacodynamics over 6 months of severe stressed aging conditions that cause commercial formulations to fail in under 2 weeks. Using various techniques, we have shown that MoNi efficacy is agnostic to the protein in formulation, enabling broad utility across many therapeutic modalities including hormones, cytokines, vaccines, protein conjugates, and antibodies. In one use case, MoNi enabled the development of an ultra-fast-acting insulin formulation exhibiting unprecedented potential to improve glucose control and reduce burden for patients with diabetes. In a second use case, MoNi has enabled the generation of ultra-high concentration biologic formulations (greater than 500 mg/mL protein) with exceptional stability. Particularly for monoclonal antibody formulations, accessing ultra-high formulation concentrations in a format that can be administered with standard autoinjectors fitted with high-gauge needles is highly distinguishing for reducing burden of treatment. Overall, we will discuss the development of novel polyacrylamide-based copolymer excipients capable of addressing critical, complex challenges facing biologic formulation and delivery, thereby affording unique opportunities in biomedicine.