Tetraphase Pharmaceuticals presents preclinical data of TP-434 antibacterial drug

Tetraphase Pharmaceuticals, Inc., today presented encouraging preclinical data for its lead drug candidate, TP-434, which showed the potent antibacterial activity of TP-434 against a very broad spectrum of susceptible and multidrug-resistant pathogens. The data supported the utility of TP-434 as a once-daily monotherapy for serious infections. Data on TP-434, as well as data for another drug candidate, TP-271, from Tetraphase's antibiotics product portfolio, were presented in 10 poster presentations at the 2010 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) annual meeting in Boston, MA, being held September 12 -15. Tetraphase Pharmaceuticals is a clinical-stage biopharmaceutical company utilizing breakthrough synthetic chemistry technology to discover and develop next-generation antibiotics.

“We are highly encouraged by the comprehensive data for TP-434, which suggests a highly advantageous product profile for a single antibiotic to treat gram-negatives as well as a broad spectrum of other difficult-to-treat resistant pathogens, thereby fitting the needs of a first-line antibiotic for serious infections”

"We are highly encouraged by the comprehensive data for TP-434, which suggests a highly advantageous product profile for a single antibiotic to treat gram-negatives as well as a broad spectrum of other difficult-to-treat resistant pathogens, thereby fitting the needs of a first-line antibiotic for serious infections," said Guy Macdonald, President and Chief Executive Officer of Tetraphase. "We are continuing to expand the profile for TP-434 with additional development plans for a Phase 2 study to assess the treatment of community-acquired complicated intra-abdominal infections and to do further studies on an oral formulation of TP-434. In addition, we have a pipeline of other novel antibiotics to address unmet needs for complicated urinary tract infections, including those caused by gram-negative bacteria expressing extended-spectrum β-lactamases and/or carbapenemases, and a monotherapy for community-acquired bacterial pneumonia."

The preclinical data for TP-434 showed the unique features of this antibiotic drug candidate, including:

  • TP-434 is a novel, totally synthetic fluorocycline (C7 position is fluorine) that inhibits protein synthesis.
  • TP-434 was protective against both tetracycline-specific efflux and ribosomal protection mechanisms and not impacted by resistance to other antibiotic classes (e.g., methicillin, fluoroquinolones, extended-spectrum β-lactams and third-generation cephalosporins, carbapenems, daptomycin, and linezolid).
  • TP-434 was shown to treat the broadest reported range of serious pathogens, including multidrug-resistant gram-negative, gram-positive, anaerobic, and atypical bacteria.
  • TP-434 is expected to be used as monotherapy against all ESKAPE pathogens (except Pseudomonas), including ESBL-producing and carbapenem-resistant Enterobacteriaceae.
  • TP-434 was 3-5 times more active than conventional therapy in a mouse model of MRSA infection.
  • Phase 1 human clinical studies of TP-434 showed that high exposures could be reached and tolerated.

The wide range of preclinical and clinical data on TP-434 presented in poster sessions at ICAAC supports the ongoing clinical development of TP-434 and the exciting prospect of a companion oral formulation to provide a much needed IV-oral step down therapy.

Source:

: Tetraphase Pharmaceuticals

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