Trius' GyrB/ParE preclinical program is fully funded by our NIAID contract. We are focused on identifying and developing antibacterial agents targeting bacterial enzymes DNA gyrase, consisting of GyrA and GyrB, and Topoisomerase IV, consisting of ParC and ParE, required for the replication of bacterial cells. GyrA and ParC are the targets of the fluoroquinolone class of antibacterial agents, such as ciprofloxacin. GyrB is the target of the natural product novobiocin. However, there are no antibacterial therapeutics in clinical use today that inhibit both GyrB and ParE.
As our lead compounds are dual-targeting, inhibiting both GyrB and ParE, we expect that they will be active against fluoroquinolone-resistant strains of bacteria. We believe that the key advantages of inhibiting both targets include an expected low rate of emergence of bacterial resistance and increased potency. Moreover, the compounds that we have identified in our GyrB/ParE program have broad antibacterial spectrum.
In our research funded by NIAID, we are focused on developing agents directed to the gram-negative spectrum that include bacteria important for biodefense purposes. Antibiotics active against these biodefense targets often have cross activity against clinically important gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli. Consequently, compounds developed under our NIAID contract should also have significant utility in treating infections caused by these clinically important bacteria, such as respiratory tract, urinary tract and intra-abdominal infections. With resistance to current drug classes (including carbapenems and fluoroquinolones) growing rapidly among gram-negative bacteria, we believe treatment for these infections is a significant unmet medical need. Our NIAID contract supports the GyrB/ParE program for biodefense purposes through Phase 1 clinical trials, subject to the achievement of program milestones.