tuberculosis

Tuberculosis (TB) is caused by infection with the bacterium Mycobacteria tuberculosis (Mtb) and is the leading cause of mortality in the world for a single infectious agent. As efforts to treat TB expand, the prevalence of multidrug-resistant TB (MDR-TB), which are resistant to the frontline standard of care antibiotics rifampicin and isoniazid, is increasing. Despite the dire need for new treatments against drug resistant TB, only one new class of antibiotics has made it into the clinic for treatment of MDR-TB in the past 40 years. Therefore, new classes of drugs that target Mtb in ways that synergize with existing drug sensitive TB and MDR-TB standard of care therapies are desperately needed.

The Opportunity: Targeting the Mtb Respiratory Chain Protein QcrB

Fimbrion has in-licensed the intellectual property for a series of heterocyclic compounds with inhibitory and bactericidal activity against Mtb in vitro. This technology originated at Washington University in Saint Louis and Saint Louis University, and the most potent members of these series have inhibitory activity at concentrations in the low nanomolar range. The target of this compound series is the QcrB protein, a component of the respiratory electron transport chain in Mtb, suggesting that these compounds inhibit Mtb growth and survival through disrupting respiration. QcrB has recently been identified as a viable drug target for treating TB, but our compound series has a unique structure and potentially superior resistance profile compared to the one QcrB inhibitor, Q203, that is currently in clinical trials. This preclinical development of this technology is supported by Phase I/II SBIR funding from NIH/NIAID.