NVB333

Infections from antibiotic-resistant Gram-positive bacteria such as MRSA (methicillin-resistant Staphylococcus aureus), and VRE (vancomycin-resistant Enterococcus spp.) remain a major problem in hospitals worldwide. The CDC lists MRSA and VRE as Serious threats with approx. 100,000 cases per annum leading to more than 12,000 deaths.

Despite some recent additions to the armamentarium there is still a very limited diversity of specialised antibiotics which can address these drug-resistant Gram-positive infections and there is a strong need for new classes lacking cross-resistance to existing agents.

NVB333 is a semi-synthetic derivative of the lantibiotic deoxyactagardine B, a class known to act by inhibition of cell wall biosynthesis. Rather than acting on a protein target which could mutate to avoid resistance, NVB333 binds to the cell wall biosynthetic intermediate lipid II. This is a validated antibiotic target being shared by the most prominent class of anti-MRSA antibiotics, the glycopeptides (eg vancomycin). However, the binding site for NVB333 is distinct to that for the glycopeptides and there is no cross-resistance. Indeed spontaneous resistance to NVB333 cannot be detected.

NVB333 is a drug candidate which has strong activity in both murine thigh and lung efficacy models as well as a promising profile in preliminary toxicology.