Preclinical program targeting antibiotic-resistant Gram-positive infections

  • MRSA skin infections
  • MRSA & PRSP pneumonia
  • Group A strep
  • VRE bacteremia
  • Anthrax
  • Listeria food poisoning

We are developing a novel class of small molecule antibiotics targeting PolC, the replicative DNA polymerase in Gram-positive bacteria. By inhibiting a novel bacterial target, these compounds circumvent existing mechanisms of antibiotic resistance. These agents exhibit broad spectrum activity against all clinically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), Streptococcus pyogenes (Group A strep), vancomycin-resistant Enterococci (VRE), Bacillus anthracis (anthrax), Listeria monocytogenes.

  • Novel mechanism of action based on inhibition of PolC, an essential DNA polymerase
  • Oral bioavailability, facilitating outpatient treatment
  • Bactericidal activity
  • Low spontaneous resistance rates
  • In vivo efficacy in preclinical models of infection
  • Low propensity for toxicity observed in vitro and in vivo

 

DNA
PolC DNA polymerase (white) bound to DNA (blue) and nucleotide (red)