Federal Project Grant Award Summary

The National Center for Advancing Translational Sciences (NCATS) awarded Columbia University in the City of New York a Project Grant totaling $451,136 (Award Date: May 1, 2026; Ultimate Completion Date: April 30, 2028) to advance RF-409, a first-in-class synthetic insulin receptor (IR) agonist designed to treat severe insulin resistance syndromes, including Donohue and Rabson-Mendenhall syndromes. The project delivers preclinical and translational research services to evaluate RF-409's pharmacokinetic and pharmacodynamic profiles in disease-relevant mouse models, including a validated knock-in model (IR-D707A) carrying a patient-derived insulin-binding-defective mutation that mirrors human severe insulin resistance phenotypes. Through rigorous in vivo efficacy testing and time-resolved liquid chromatography-mass spectrometry analysis, Columbia will characterize systemic exposure, tissue distribution, and therapeutic activation of mutant IR variants unresponsive to conventional insulin therapy.

This award supports NCATS' mission to accelerate the translational research pipeline by removing bottlenecks in drug development and delivering new therapeutics to patients faster. The project addresses an urgent unmet clinical need in rare disease therapeutics, as no FDA-approved treatments currently target the underlying insulin receptor defect in these life-threatening conditions. Preclinical data demonstrate that RF-409 achieves superior glucose-lowering efficacy and longer duration compared to insulin in multiple disease models, establishing a robust scientific foundation for potential clinical translation and advancement toward patient benefit.