Project Summary This 3-year Phase II SBIR Application focuses on advancing the lead “ultra-broad-spectrum” carbapenem (USBC) VNRX-4099, possessing an unprecedented antibacterial spectrum of activity including MRSA, Enterobacteriaceae and Pseudomonas aeruginosa, to IND filing status. The UBSC VNRX-4099 will be paired with a proprietary in-house β-lactamase inhibitor VNRX-5133 (BLI) to protect against resistance by Ambler Class A, B and D carbapenemase-producing Gram negatives. In parallel, a discovery effort will be executed to identify a fast follower and/or chemically-diverse back-up UBSC that could be advanced into IND-enabling studies if required. Ultimately, it is envisioned that this new combination product will provide a unique clinical option for empiric therapy of multi-drug resistant polymicrobial infections in the hospital general ward and ICU, and as a second line therapy for susceptible organisms.