Tuberculosis (TB) remains a leading cause of death owing to an infectious disease, claiming around 1.5 million lives each year. Standard TB treatment requires six months combination therapy, and, for drug-resistant TB, this extends to 18 to 24 months. Therefore, there is an urgent need for a shorter, better tolerated antibiotic regimen for the treatment of drug-sensitive TB, as well as a combination therapy that will be more effective in the treatment of drug-resistant TB.
South Africa carries a massive TB burden, and this is exacerbated by co-morbidities including HIV and diabetes. In addition, the country is among the top four globally with the highest prevalence of drug-resistant TB disease (TB-in-South-Africa). Against this backdrop, it is notable but appropriate, that the South African government has invested heavily in research platforms for the discovery and development of new medicines for the treatment of TB.
The H3D centre at the University of Cape Town is one among a limited number of research organizations worldwide with a major investment in anti-tubercular research. The H3D TB programme was initiated in 2011 with funding from the South African government via the South African Tuberculosis Research Innovation Initiative (SATRII, subsequently incorporated in the Strategic Health Innovations Partnership [SHIP] initiative of the South African Medical Research Council), which enabled preliminary screening of the BioFocus compound library for starting chemical material. In 2013, the size and scope of the H3D was expanded further through the kind provision of novel TB hits by the Novartis Institute for Tropical Diseases (NITD).
In a major development in 2013, H3D was awarded funding by the Bill and Melinda Gates Foundation (BMGF) for malaria and TB drug discovery and, subsequently, was elected to the Tuberculosis Drug Accelerator consortium (TBDA). Within the context of the TBDA, further collaborations were initiated with the Infectious Disease Research Institute (IDRI) and Elli Lilly, as well as Celgene Global Health. H3D also partnered with the HIT-TB consortium, taking advantage of powerful collaborations with NIH research groupings as well as leading public and private institutions in exploring advanced research models to identify new medicines to treat TB. More recently H3D initiated collaborative programs with the Broad Institute of MIT and Harvard, Colorado State University and Sapienza University of Rome to progress early leads with high value targets for TB to the preclinical candidate selection stage. H3D has established medium-throughput screening platform for phenotypic as well as target-based screening to identify novels hits to initiate TB lead generation programs. The current H3D TB portfolio comprises few Hit to Lead programs with novel chemical series and a lead optimisation program poised for nominating a preclinical candidate for GLP-toxicological studies. In addition, multiple chemical series identified from phenotypic and target-based screening of pharmaceutical libraries are being evaluated to generate a panel of mechanistically distinct chemical series effective against TB.