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Novel antibiotics against Gram-negative and drug-resistant bacterial pathogens

Dr. Kahne has a pipeline of programs aimed at developing first-in-class antibiotics:

Program I:  Potentiator of polymixin, increasing its therapeutic index for treatment of drug-resistant infections

  • In vitro: Novel agent potentiates activity of polymixin 10-50-fold
  • In vivo: Co-administration at doses ineffective for each agent alone results in a four-log reduction in bacterial colony forming units in a soft tissue infection model
  • Combination is active against ESKAPE pathogens P. aeruginosa, A. baumannii, K. pneumonia, E. cloacae, and E. coli
  • IP: Patent application covering composition of matter filed by Harvard

Program 2:  First-in-class therapeutic for Gram-negative bacteria

  • Novel series of compounds active against a new target class for Gram-negative bacteria
  • Target clinically validated for Gram-positive infections
  • Medicinal chemistry: in vitro activity against Gram-negative strains improved 100-fold
  • IP: Patent application covering composition of matter filed by Harvard

Program 3: Hits from pathway-directed cell-based HTS

  • Validated, pathway-directed HTS has identified novel inhibitors of outer membrane assembly
  • Medicinal chemistry and preclinical testing ongoing for two lead series.

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