The objectives for TB drug development are to identify new drugs (new mechanism of action) to improve MDR/XDR TB treatment and drastically reduce the time required to cure the disease. New drugs need to be orally bioavailable, well-tolerated, cheap and stable for use in resource limited countries. Furthermore, new drugs should be free from significant drug-drug interaction liabilities for use in TB combination therapy and against HIV/TB.
The objective of the TB unit is to deliver preclinical development compounds that are then - in collaboration with NITD's preclinical and clinical development managers, and with the support of Novartis Development - brought to Proof of Concept studies in man.
The discovery of new anti-mycobacterials is carried out in close interaction with NITD's Chemistry and Pharmacology Units, Screening and Bioinformatics labs. Key to the discovery process is furthermore a close collaboration with the Novartis Institute of Biomedical Research in Basel and Cambridge, Massachusetts and the Genomics Institute of the Novartis Research Foundation in San Diego (e.g. HTS, structure determination, compound archive, compound profiling, databases, joint drug discovery projects).
To drive TB drug discovery from the biology side, the TB unit has established all required assay capabilities, from protein tool production, various M. tuberculosis cell and macrophage-infection assays to mouse/rat models. The approaches taken to identify new targets involve genetics as well as chemical genetics. Lead compounds are identified employing target-based as well as cell-based/pathway screens.
The unit established strategic global partnerships in TB drug discovery with the Clif Barry lab (NIH), and the Douglas Young 'Grand Challenges in Global Health TB consortium' (Imperial College, funded by the Bill and Melinda Gates Foundation, Welcome Trust). In clinical research / development interactions are established with the TB Alliance, Korea's International TB Research Center / National Masan TB Hospital / Yonsei University, and Indonesia's Hasanuddin University / Eijkman Institute. Local collaborations are with the National University and the Genome Institute of Singapore.
Members of the NITD TB unit: 6 Principal Scientists (Vasan Sambandamurthy, Sabai Phyu, Luis Camacho, Srinivasa Rao, Manjunatha Ujjini and Kevin Pethe), 12 Research Associates, 3 Postdocs and Unit Head (Thomas Dick).
Novartis Institute for Biomedical Research
