Rationally-designed, D-conformation Antimicrobial Peptides as Novel Antibacterial Drug Candidates for the Treatment of Multi-drug-resistant Bacterial

The goal of this Navy Phase II STTR project is to identify and develop a D-conformation antimicrobial peptide as a novel, effective, and safe antibacterial drug candidate capable of entering human clinical trials. From a set of 4 uniquely designed analogs that exhibit superior in vitro biologic activity/safety data against clinical and drug-resistant gram-negative A. baumannii bacterial isolates, a lead compound will be identified and rapidly advanced into pilot and IND-enabling pharmacokinetic, pharmacologic and toxicokinetic research. The research plan is scheduled for up to 36 months and is expected to provide data necessary to initiate human clinical trials and, ultimately, provide the Navy, the DoD, and the civilian healthcare community with a novel and field-compatible solution to the problem of bacterial resistance to conventional antibiotics. More specifically, the sequential objectives of the plan are to 1) Quantify the lead compound; 2) Determine the tolerable in vivo dose to move into efficacy testing; 3) Confirm a stable formulation; 4) Identify the effective single and repeat doses; 5) Produce the GLP IND data in two species; 6) Transfer manufacturing technology to a GMP facility; and 7) Submit an approvable IND and identify a Phase 1 human clinical trial center (military).