A platform for the rapid development of protein binders

Abstract The purpose of this Phase 1 pre-commercialization SBIR grant proposal is to establish a pipeline for developing therapeutically-viable protein scaffolds that bind targets of interest for early stage lead discovery. Proteins that selectively bind to specific targets are essential for research, diagnostics, and therapeutics, yet current methods for discovering these binders are slow, costly, and prone to high failure rates, especially with challenging targets such as disordered proteins. PeptiForge seeks to address this critical bottleneck by establishing a platform that is at least 50-times faster, 50-times less expensive, and significantly more accurate than existing immunization, display, or computational methods. The platform leverages proprietary technologies which enable the screening of high-diversity protein libraries against hundreds of targets simultaneously without secondary screening. In preliminary data, we show our technology has the ability to rapidly identify binders for diverse protein targets, using model protein scaffold libraries. These breakthroughs have the potential to enable rapid and cost-effective binder discovery while expanding the scope of targetable proteins, including previously intractable targets. Here, we propose to synthesize testbed libraries of therapeutic scaffolds, using a variety of known clinically viable scaffolds to assess the feasibility of the platform for developing therapeutic leads (Aim 1). Next, we will run test scale selections of scaffold libraries against high-value human therapeutic targets (Aim 2). This research proposal will test if PeptiForge’s platform can accelerate therapeutic development, allowing for quicker discovery of probes for conventional therapeutic targets and facilitating new opportunities for tackling challenging diseases. The innovation also provides a scalable resource for academic and commercial users seeking to advance drug discovery efforts, opening up future product development opportunities. By enabling faster, cheaper, and more reliable development of protein binders, PeptiForge is aimed at revolutionizing the biotechnology landscape and fueling advancements in drug discovery.