The development of a therapeutic peptide for mitochondrial protection ‐ from bench to bedside

In addition to their pivotal role in providing cellular energy, mitochondria are also the major producer of intracellular reactive oxygen species (ROS), and serve as central regulators of life and death. Defects in oxidative phosphorylation, oxidative stress, and mitochondrial permeability transition (MPT) play a major role in diverse diseases including ischemic‐reperfusion (IR) injury, metabolic syndrome, heart failure, and Alzheimer's Disease. Here we present the development of Bendavia™, a novel therapeutic specifically designed for mitochondria protection. Bendavia™ belongs to the family of Szeto‐Schiller (SS) peptides that are the only compounds known to selectively target the inner mitochondrial membrane. The SS peptides are multi‐functional agents, they promote electron flux, increase ATP synthesis, reduce ROS generation, inhibit MPT, prevent apoptosis and necrosis, and protect against exaggerated immune response. Bendavia™ has demonstrated superior efficacy in animal models of IR injury, neurodegenerative diseases, insulin resistance, cardiac failure, and muscle weakness. Phase 1 clinical trial showed excellent pharmacokinetic properties and patient tolerability in healthy individuals. Bendavia represents a first‐in‐class mitochondrial therapy with the potential of treating complex diseases with unmet needs. Funded by DA08924, DK073595 , NS48295, Stealth Peptides Inc