Research & Development at NITD

Novartis Research and Development (R&D)

Drug discovery and development process
Novartis Institutes for BioMedical Research (NIBR)
Pharmaceutical Development
Novartis Biologics
Corporate Research
Research and Development locations

Research & Development at NITD

The Dengue unit at NITD focuses on finding new small molecular antiviral treatments.

The goal of the NITD Dengue unit is to:

Discover medicines that reduce the viral load in people with dengue;
Reduce dengue-related morbidity and mortality;
Curtail transmission of the virus.

Prevalence of dengue
The global burden of dengue has grown dramatically in recent decades. It is classified as a re-emerging infectious disease. Dengue and dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) occur in more than 100 countries, with more than 2.5 billion people at risk and an estimated 50 to 100 million infections per year. The major disease burden is found in Southeast Asia and the Western Pacific, with increased reporting of dengue in the Americas.

Financial burden of dengue
There is currently no treatment for dengue, only supportive care. DHF/DSS is a leading cause of hospital admissions and death among children in most Asian countries. The strain put on countries’ healthcare systems during a dengue epidemic can be staggering, both financially and with respect to resources, especially in developing countries. Dengue epidemics are often well publicized. They have the attention of governments and ministries of health because of the burden on the health resources and the economy.

Virology of dengue
The increasing number of dengue epidemics in endemic countries within the tropical/subtropical regions of the world may be due to new virulent strains or higher rate of secondary dengue infections. Both situations can lead to increased viremia and this has been directly correlated with severe dengue diseases (DHF and DSS). By comparison, patients suffering from classical dengue appear to have a lower viral load (Libraty et al., Journal of Infectious Diseases, 2002, 185:1213-21).

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Read about the Dengue unit drug discovery portfolio and collaborators
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Tuberculosis unit

The NITD Tuberculosis unit is working to identify new treatments for drug-resistant TB and approaches to shorten TB treatment time.

The goal of the Tuberculosis (TB) unit is to deliver preclinical development compounds that are eventually brought to Proof-of-Concept studies in patients.

TB drug development
The objectives for TB drug development are:

To identify new drugs with new mechanisms of action to improve multidrug-resistant (MDR) and extensive drug-resistant (XDR) TB treatment;
To drastically reduce the time required to treat the disease.

New drugs need to be easy to administer, well tolerated, cheap and stable for use in resource-limited areas. Furthermore, new drugs should be free from significant drug-drug interaction liabilities for use in TB combination therapy and against HIV.

TB drug-discovery collaboration
The discovery of new anti-mycobacterials is carried out in close interaction with the Chemistry and Pharmacology units at NITD, as well as the company’s screening and bioinformatics labs. Key to the discovery process is a close collaboration with the Novartis Institutes for BioMedical Research and the Genomics Institute of the Novartis Research Foundation. Activities include:

High-throughput screening (HTS);
Structure determination;
Compound archive;
Compound profiling;
Databases;
Joint drug-discovery projects;

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Malaria unit

NITD intends to discover new antimalarial drugs, including a potential single-dose cure for falciparum malaria.

Malaria treatment
Today, artemisinin is the last defense against drug-resistant malaria. Recent reports suggest that decades of continuous use of these potent antimalarials as monotherapies may have fostered artemisinin drug resistance in Plasmodium. Unfortunately there are few ongoing efforts to discover and develop novel and effective antimalarial drugs.

NITD research consortium
To address this unmet global health need, NITD has led the formation of a research consortium that brings together cutting-edge drug discovery at Novartis with world-class malaria biology expertise. Armed with a grant from the Wellcome Trust, the Medicines for Malaria Venture and the Singapore Economic Development Board, the consortium has the ambitious goals of identifying:

New drugs with a potential for a single-dose cure for P. falciparum malaria;
A curative modality for P. vivax malaria.

These two goals were set to address two weaknesses with the current antimalarials: poor patient compliance and the inability to rapidly and safely eradicate the parasite liver stages following a P. vivax infection.

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Chemistry unit

The Chemistry unit contains some of the core drug discovery skills that are necessary to identify drug candidates for development.

The Chemistry unit generates drug candidates based on research leads. The team is made up of seven principle scientists and 14 research associates. In close collaboration with biologists, pharmacologists and scientists from the molecular informatics team, our chemists design, synthesize and purify compounds to identify new dengue or TB drugs. Several state-of-the-art technologies are used for this purpose:

Microwave synthesis;
Solid phase and multi-parallel solution synthesis;
Mass directed high-throughput preparative high performance liquid chromatography (HPLC);
Parallel column purification.

The compounds are then analyzed using nuclear magnetic resonance (NMR), HPLC and mass spectrometry to make sure that the correct structure has been assigned. These methods also determine the amount of impurities in the compound.

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Pharmacology unit

The Pharmacology unit is coordinating in-house and outside efforts to study drug candidates, using in vitro profiling assays and in vivo studies in rodents.

Information about the NITD Pharmacology

The Pharmacology unit collaborates closely with the Chemistry group during the hit-to-lead and lead optimization phases. This ensures acceptable pharmacokinetic (PK) properties of the selected molecules that are designed, synthesized and purified by the medicinal chemists. This is initially accomplished using a battery of in vitro assays, followed by in vivo PK assessment of the compounds in rodents to evaluate oral bioavailability and overall systemic exposure. We support the PK evaluation of novel compounds for the dengue, tuberculosis and malaria drug-discovery programs.

In parallel, we have launched several research projects aimed at addressing some of the most crucial gaps in TB drug discovery. In collaboration with the Pasteur Institute and the Public Health Research Institute, NITD is developing a novel rat model of TB infection. We are doing this to answer the lack of a rapid, convenient and cost-effective animal model in a species that is widely adopted for PK and toxicology evaluation in the pharmaceutical industry. In collaboration with the National University of Singapore and with the Experimental Therapeutic Center in Singapore, our group works to identify biomarkers of disease stage and drug response in the rat model of TB infection.

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