Novel tetracyclines with improved potency, efficacy against contemporary P. aeruginosa isolates

Tetraphase Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on next-generation antibiotics, announced today that it is presenting new results from studies that demonstrate the improved potency and pharmacokinetics of several of its newest discovery-stage tetracycline analogs. These data, which focus on significant gram-negative pathogens - including Pseudomonas aeruginosa, and troublesome gram-positive respiratory pathogens - were described in seven poster presentations at the 22nd European Congress of Clinical Microbiology and Infectious Disease (ECCMID) in London, UK.

“These are the first reports of novel tetracyclines with improved potency and efficacy against contemporary P. aeruginosa isolates”

"These are the first reports of novel tetracyclines with improved potency and efficacy against contemporary P. aeruginosa isolates," said Guy Macdonald, President and Chief Executive Officer. "These compounds retain activity against other major gram-negative pathogens, as well, and merit additional research to advance them into later-stage development. Even as we move our clinical-stage compounds forward, we continue to search for new candidates with the potential to treat the most virulent infections, including those caused by multi-drug resistant bacterial strains."

Presentation Summary:

• "Mouse pharmacokinetics, dose fractionation and efficacy of TP-559, a novel tetracycline with anti-Pseudomonas activity, in murine infection models challenged with Pseudomonas aeruginosa." J. Sutcliffe, X. Xiao, R. Clark, T. Grossman. (Poster #1425).
• "The intravenous pharmacokinetics and efficacy of a novel tetracycline TP-433 in murine infection models challenged with Pseudomonas aeruginosa." Y. Deng, T. Grossman, R. Clark, X. Xiao, J. Sutcliffe. (Poster #1426).
• "TP-834, a novel IV and oral isoindoline-containing pentacycline, is highly efficacious in rodent models of pneumonia." J. Sutcliffe, P. Hogan, C. Katz, W. Zhang, Z. Zhu, T. Grossman. (Poster #1427).
• "TP-834, an isoindoline-containing pentacycline antibiotic, is orally bioavailable, metabolically stable and has low potential for drug-drug interactions." T. Grossman, M. Ronn, N. Dunwoody, J. Sutcliffe. (Poster #1428).
• "In vitro potency of novel tetracyclines against Pseudomonas aeruginosa and other major Gram-negative pathogens." W. O'Brien, C. Fyfe, T. Grossman, C. Chen, R. Clark, Y. Deng, M. He, D. Hunt, C. Sun, X. Xiao, J. Sutcliffe. (Poster #1448).
• "Synthesis and antibacterial activity of isoindoline-containing pentacyclines: a novel class of tetracycline analogs with oral bioavailability." R. Clark, D. Hunt, M. He, C. Fyfe, W. O'Brien, T. Grossman, J. Sutcliffe, X. Xiao. (Poster #1451).
• "The novel isoindoline-containing pentacycline TP-834 is active against community and biothreat respiratory pathogens, and problematic Gram-positive pathogens." T. Grossman, W. O'Brien, C. Fyfe, J. Sutcliffe. (Poster #1452).