Discovered in 1959, pleuromutilins have the potential to be developed as a new class of antibiotics for systemic use in humans. Although in 2007 retapamulin became the first pleuromutilin approved for topical use in humans, it was not until 2011 that a pleuromutilin antibiotic, lefamulin (BC‑3781), was tested successfully in a Phase 2 clinical trial for systemic use in patients.
Nabriva's world class medicinal chemistry
In recent years, bacterial infections resistant to most forms of current antibiotics have appeared throughout the world and are currently the third leading cause of death in the US and Western Europe. Pleuromutilins represent a new class of antibiotics, inhibiting bacterial protein synthesis by binding to unique sites on the 50S subunit of the ribosome. These new antibiotics have two distinct advantages: they have a very low potential for cross-resistance with other established antibacterial classes and display a very low potential for resistance development.
Nabriva Therapeutics' pleuromutilins are unique antimicrobial compounds that interfere with bacterial protein synthesis via a specific interaction with the 23S rRNA of the 50S bacterial ribosome subunit. These antibacterials have a distinct anti-bacterial profile. Their unique mechanism of action implies a very low probability of cross resistance with other antibacterials. In an industry first, Nabriva's world class medicinal chemistry expertise achieved the development of intravenous and orally available pleuromutilins clearing the way for i.v. and oral therapy with this antibiotic class. This achievement constitutes a significant milestone in providing appropriate medication for the treatment of life-threatening bacterial infections offering a distinctly different class of antibiotics for the treatment of bacterial diseases.
- New class of antibiotics on the human market
- High target specificity plus a unique mode of action ensures differentiation from existing antibiotic classes and compounds in development
- Very low propensity for resistance development
- Accessibility to both Gram-positive & Gram-negative ribosomes translates into broad spectrum activity against a wide range of infections
- Excellent safety profile
- Oral, intraveneous and topical delivery
Nabriva is the first company with proof of concept achieved for the systemic use of pleuromutilins in patients. Two new pleuromutilins, lefamulin and BC‑7013, from Nabriva have shown excellent results in clinical studies. Lefamulin is about to enter Phase 3. Since Nabriva´s pleuromutilin antibiotics have an ideal anti-bacterial spectrum for both skin and respiratory infections and are available as both oral and i.v. formulations, they address a significant medical need and constitute an excellent commercial opportunity.