Multidrug resistant bacteria
Gram-positive and Gram-negative bacteria are common causes of serious diseases such as pneumonia and complicated skin infections. Resistance to currently available antibiotics is increasing and presents a vital medical need. For example, more than 70% of cases of bacterial disease in hospitals are now believed to be caused by pathogens resistant to at least one antibiotic commonly used in their treatment. Disturbingly, diseases caused by multidrug-resistant (MDR) Gram-positive pathogens such as MRSA (methicillin-resistant staphylococcus aureus) are becoming more commonplace, turning what were previously manageable infections into urgent, potentially life-threatening clinical problems.
Biota is actively addressing this need through the discovery of new classes of antibiotics targeting processes that are essential for bacterial growth. The key to our approach is to focus our proprietary technology on novel targets with potential to yield entirely new classes of antibacterials with activity against emerging drug resistant bacteraia. Our portfolio addresses Gram-positive and Gram-negative bacterial infections.
The GYR program focuses on DNA supercoiling inhibitors, which target the ATPase of the enzymes DNA gyrase and DNA topoisomerase IV. Both enzymes are essential for bacterial survival and are simultaneously inhibited by compounds from this series. Dual-targeting inhibitors are attractive because they reduce the development of target-based resistance. The program is aimed at treating serious skin infections, bacterial pneumonia and sexually-transmitted infections in the first instance. The market for these therapies is valued in billions of dollars and existing therapies are increasingly compromised by resistance. Biota's GYR inhibitors have demonstrated class-leading efficacy through oral and intravenous routes in established models of skin infections and pneumonia.
One of Biota's cell division inhibitor programs (CDI) targets staphylococcal infections, including MRSA and MRSE. This series inhibits FtsZ, an essential bacterial cell division protein. As a targeted agent, this offers new clinical opportunities to treat staphylococcal infections selectively without disrupting the native bacterial flora. The novel product profile aims at multiple segments of the antibacterial market, including hospital-acquired, community-associated and prophylactic therapies for the treatment and carriage of staphylococcal infections. Our compounds have demonstrated both intravenous and oral efficacy in animal models as single agents, and their specificity enables them to be used in combination with other antibiotics that may have developed independent resistance.
The DIF program, funded by a grant from the National Institutes of Health, targets digestive tract disease caused by Clostridium difficile. C. difficile can infect and flourish in the colon of patients following eradication of the normal gut bacteria by a course of broad spectrum antibiotics. This can lead to severe inflammation of the colon which can prove life threatening, particularly in the elderly. Authorities are also increasingly concerned about the potential emergence of an epidemic strain with increased virulence and/or antibiotic resistance. Biota is developing DIF inhibitors which are targeted to the gut and are not absorbed into the bloodstream. This approach circumvents several obstacles normally associated with drug discovery and development, such as oral absorption, and provides a localized delivery to the site of infection. Moreover, our antibacterials are highly selective and spare beneficial gut flora, distinguishing DIF program inhibitors from existing therapies that disrupt the normal functioning of the digestive system.