Aerosol Delivery of CPZEN-45 for Treatment of Nontuberculous Mycobacterial (NTMs) Infections
Technical Report,30 Sep 2018,29 Sep 2019
Infectious Disease Research Institute Seattle United States
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This DOD Therapeutic Development Award is focused on a new antibiotic, CPZEN-45, discovered by our team for treatment of non-tuberculous mycobacterial infections NTM in patients with chronic obstructive pulmonary disease COPD. We have two major objectives Objective 1-To optimize fermentation and scale-up of manufacturing processes for high yield of CPZEN-45, including spray dried CPZEN-45. We have optimized fermentation and scale-up of CPZEN-45 and the processes have been successfully transferred to our manufacturing partner. Objective 2- To further define and characterize in vitro efficacy of CPZEN-45 against additional species of NTMs recently isolated from VA patients with COPD. We have obtained 26 recent NTM isolates from COPD patients VA Aurora, CO, phenotype and titers were determined, and DNA extracted for whole genome sequencing to evaluate phenotypic and genotypic correlation with resistance. Our objective to develop an efficacious regimen for COPD patients has started by screening multiple CPZEN-45 combinations with standard NTM compounds in human THP-1 cells using a checkerboard assay. Synergy measurement by checkerboard analysis will be used to determine the impact on potency of the combination of antibiotics in comparison to their individual activities. The optimized synergistic regimens will then be tested in COPD mouse and guinea pig efficacy models.
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