Federal Project Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $501,137 Project Grant to Scripps Research Institute for the period June 15, 2026 through May 31, 2028 under the Allergy and Infectious Diseases Research program (CFDA 93.855). The award supports the development of broadly cross-reactive monobodies (MBs) engineered to neutralize botulinum neurotoxins (BONTs) after intracellular internalization into neuronal cells. The primary deliverables include the identification and optimization of monobodies capable of broadly neutralizing multiple clinically relevant subtypes of BONT/A and BONT/B through high-throughput discovery, deep mutational scanning, and multistate affinity maturation workflows. The optimized monobody candidates will be engineered specifically for robust cytoplasmic stability and enhanced biophysical properties including increased solubility, reduced aggregation propensity, and favorable pharmacokinetic profiles.

The project deliverables further encompass integration of optimized monobody therapeutic components into an established "Trojan Horse" delivery platform and comprehensive preclinical evaluation of therapeutic efficacy, safety, pharmacokinetics, and manufacturability. Evaluation activities include in vitro analyses and in vivo studies in rodent and low-dose non-human primate models, with assessment of critical drug development parameters such as immunogenicity, off-target interactions, and stability. These research activities are intended to advance the development of post-internalization therapeutics addressing the urgent medical need for botulinum intoxication treatment.