THE BIOVERSYS APPROACH AGAINST TB
For the development of its tuberculosis program, BioVersys is relying strongly on grants, foundations and external partnerships. Tuberculosis is a neglected disease, mostly of the third world, with the indication classified as "orphan". Orphan indications receive special support from regulatory authorities due to their high unmet medical need and lack of treatments.
BioVersys has started a strong collaboration with some of the leading scientists in the tuberculosis field. Together with the Institut Pasteur de Lille, INSERM, CNRS and University of Lille 2, BioVersys has signed a co-development and license agreement to develop in a collaborative effort compounds that are able to boost the efficacy of the established TB drug ethionamide (ETH). ETH has been in use for over 40 years as a second-line drug. ETH is a crucial pillar of TB treatment, especially in therapies fighting MDR (multiple drug resistant) and XDR (extensively drug resistant) strains (see Miglori et al.in The European Respiratory Journal 2012). ETH is a prodrug and requires bioactivation by the bacterial mono-oxygenase EthA to become bactericidal. This activation pathway is negatively controlled by the transcriptional repressor EthR.
BioVersys, together with its partners, develops small molecule drugs that target EthR to boost the bioactivation of ETH. The team has shown that this novel approach is able to dramatically increase the sensitivity of wild-typeM. Tuberculosis to ETH in vitro and in vivo using drug-like EthR inhibitors (see Villemagne et al in J Med Chem 2014, Flipo et al J Med Chem 2011 and 2012, and Willand et al in Nature 2009). Our team is now working on the development of boosters that are able to counteract ETH resistance.