In vitro and in vivo characterization of Bisphosphocin Nu-3—a novel broad-spectrum antimicrobial compound with high potency against resistant pathogens

Abstract

Lakewood-Amedex Biotherapeutics Inc. has developed a new class of antimicrobials called the Bisphosphocin class, with Nu-3 as a leading candidate, which is currently in clinical development for treating mildly infected diabetic foot ulcers (iDFUs). Nu-3 acts through a novel mechanism of action that destabilizes bacterial membranes within minutes, which significantly reduces the potential for resistance development. It demonstrates broad-spectrum activity against Gram-positive, Gram-negative, and multidrug-resistant bacteria, including recent clinical isolates from infected wounds. Nu-3 is especially effective in acidic environments and can be formulated for topical application at high concentrations and low pH, that has been shown to be beneficial for wound healing, making it well-suited for treating infections in diabetic foot ulcers. Its rapid, bactericidal action has been confirmed against pathogens, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Propionibacterium acnes, Proteus mirabilis, Acinetobacter baumannii, and Staphylococcus saprophyticus, with complete bacterial eradication occurring within minutes. Resistance testing over 21 days showed a very low probability of resistance development. In vivo testing in murine dermal methicillin-resistant Staphylococcus aureus (MRSA) infection models demonstrated robust efficacy for Nu-3 given as a solution- or gel-formulation in both single and multidose protocols. Given its efficacy, broad-spectrum activity, and topical formulation, Nu-3 has the potential to be an important therapeutic intervention for the treatment of mild infections in diabetic foot ulcers—a serious complication of diabetes associated with high amputation risk.