Biota

MRSA dividing normally (left), MRSA ballooning due to inhibition of cell division by a compound (right). The ballooning cell will lyse, killing the bacterium. SEM images, white bar is 0.5µm.

Gram-positive and Gram-negative bacteria are common causes of serious diseases such as pneumonia and complicated skin infections.  The incidence of resistance to currently available antibiotics is increasing and presents an urgent medical need.  For example, it is estimated that more than 70% of cases of bacterial disease in hospitals are now caused by pathogens resistant to at least one antibiotic commonly used in their treatment. Disturbingly, diseases caused by multidrug-resistant (MDR) Gram-positive pathogens are becoming more commonplace turning what were previously manageable diseases into possibly urgent and sometimes unmanageable clinical problems.   

Biota's solution

Biota is actively working to address this need through the discovery of new classes of antibiotics targeting processes which are essential for bacterial growth. The key to our approach is to focus on novel targets and proprietary technology. Our portfolio addresses Gram-positive and Gram-negative bacterial infections by inhibiting targets that include DNA supercoiling (the GYR program), cell division (the CDI program), bacterial coenzyme A biosynthesis (the PPAT program) and others.

The GYR program includes several series of DNA supercoiling inhibitors. This series dual-targets 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 Gram-positive, community-acquired respiratory-tract and sexually-transmitted infections. The market for these therapies is valued in billions of dollars and existing therapies are increasingly compromised by resistance.

The CDI series of cell division inhibitors are targeted at 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 product profile is novel and aimed at multiple segments of the antibacterial market, including hospital-acquired, community-associated and prophylactic therapies for the treatment and carriage of staphylococcal infections.

The PPAT program is focused on optimizing novel inhibitors of bacterial coenzyme A (CoA) biosynthesis. The penultimate step in CoA biosynthesis is catalyzed by PPAT, a ubiquitous enzyme essential for bacterial survival.  As the human equivalent of bacterial PPAT is structurally and functionally distinct from the bacterial enzyme, inhibition of bacterial PPAT is likely to be highly selective.

PPAT inhibitors have the potential to yield a new class of broad spectrum antibiotics active against both Gram-positive and Gram-negative bacteria.