GT-055 / Geom Therap - LARVOL DELTA

In vitro and in vivo activity of GT-1, a novel siderophore cephalosporin, and GT-055, a broad-spectrum β-lactamase inhibitor, against biothreat and ESKAPE pathogens. (PubMed, J Antibiot (Tokyo)) - "Here, we demonstrated sub-4 µg ml efficacy against a number of pathogens in vitro. We further determined that in mice infected via aerosol route with Yersinia pestis, efficacy of GT-1/GT-055 treatment is at least equivalent to the comparator antibiotic, ciprofloxacin."

Journal • Preclinical • Infectious Disease

Pharmacokinetics-pharmacodynamics of the novel beta-lactamase inhibitor GT-055 in combination with the siderophore cephalosporin GT-1 (ECCMID 2019) - "When GT-055 is paired with the novel siderophore cephalosporin, GT-1 (formerly LCB10-0200), the BLI has been shown to improve the in vitro activity up to 8-fold against a variety of Gram-negative organisms including Enterobacteriaceae. Results of GT-1 + GT-055 in vitro studies provided insight about the activity of the inhibitor when utilized in combination with GT-1 and will serve to guide future studies."

Combination therapy • PK/PD data

Penicillin-binding protein activity of beta-lactamase inhibitor GT-055 (ECCMID 2019) - "Other antibiotics (ceftriaxone and mecillinam) and BLIs (avibactam and OP0595) were used as controls. BLI GT-055 was found to bind PBP2, but not other PBPs in E. coli and K. pneumoniae. GT-055 bound to PBP2 with slightly higher affinity than the other diazabicyclooctane-class BLIs, avibactam and OP0595. Therefore, these results suggest that BLI GT-055 bind to and inhibit PBP2."

Infectious Disease • Pneumonia • Respiratory Diseases

In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains. (PubMed, Antibiotics (Basel)) - "This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems...Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1-resistant strains."

Journal • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases