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.

Grant Number: 1R43GM161157-01
NIH Institute/Center: NIH
Principal Investigator: Christopher Basile