Novartis Institute for Tropical Diseases (NITD)

Partnership objectives

  1. To discover and develop novel treatments and prevention methods for major tropical diseases up to proof-of-concept in man.
  2. To provide students and scientists in developing countries with teaching and training opportunities for drug discovery and development.

NITD is contributing to the effort to build the capabilities essential to enabling the discovery and development of new medicines. NITD is contributing to the effort to build the capabilities essential to enabling the discovery and development of new medicines. Copyright Novartis

What are the health needs and challenges?

One of the challenges of discovering drugs for diseases of the developing world is the lack of basic research into the underlying causes of these diseases – an example of this is dengue fever. Dengue fever is caused by any one of -the four serotypes of dengue viruses transmitted by mosquitoes. The challenge in dengue drug discovery is the limited knowledge about virus infection cycle and the lack of understanding of the relationship between viremia and severe disease progression. Novartis is one of the few large pharmaceutical companies working on research for dengue fever at NITD.

About 2.5 billion people, or 40 percent of the world’s population, lives in areas where there is a risk of dengue transmission and a certain small percentage of the infected patients develop into -life-threatening hemorrhagic fever and shock syndrome that can lead to death. Over the past four decades, dengue disease has become recognized as the world's most important mosquito-borne viral disease.

Malaria kills an estimated 429,000 people each year, mostly among African children.  In South East Asia, the first signs of drug resistance against the malaria parasite have been reported and new drugs different from the current arsenal of antimalarials are needed to fight the resistant parasites.

Screening for drugs effective in infectious diseases is challenging because of the often limited understanding of the pathophysiology of the disease and the death of validated drug targets. The best way to screen is thus to use the whole organism and look for compounds that cause cell death – Human African trypanosomiasis is one example. An estimated 70 million people, in sub-Saharan Africa are at risk of contracting Human African trypanosomiasis or sleeping sickness, a parasitic disease caused by the protozoan Trypanosoma brucei, which is transmitted by the bite of the tsetse fly. 7,197 new cases were reported in 2012, however it is acknowledged that cases are under-reported and that WHO estimates the number of actual cases to be 30,000. Current treatments have complicated administration regimes and have serious adverse side-effects.

Description of partnership activities and how they address needs and challenges

The Novartis Institute for Tropical Diseases is a part of the Novartis Institutes for BioMedical Research that, in partnership with other organizations, is dedicated to drug discovery research on neglected diseases for the developing world. As a small-molecule drug discovery research institute, it combines the drug-discovery expertise and cutting-edge technologies of Novartis to fight infectious tropical diseases, including Dengue fever, Human African Trypanosomiasis and Malaria. The NITD international team of scientists is engaged in neglected disease research efforts, from target discovery and screening development to compound optimization and preparation for clinical testing.

The NITD dengue team has worked with many of Singapore local and international collaborators to establish novel research tools and approaches, characterizing NS4B target to enable -drug discovery, establishing -Dengue animal models for antiviral testing, defining structure and function of Dengue viral proteins, and developing screening assays which have been used to identify several candidate compounds in the fight against dengue.

In the area of malaria, Novartis is currently initiating clinical studies of two anti-malaria treatments developed at NITD, including a promising new candidate against drug-resistant malaria which is active on both vivax and falciparum malaria. This new class of antimalarial compound, termed spiroindolones, was discovered and developed from a chemical hit out of the Novartis Compound Library. An extensive medicinal chemical optimization campaign which focused on improving the activity and the physicochemical or drug-like properties of the molecule lead to the development of KAE609. KAE609 is the first new class of antimalarial with a different mode of action to the current drugs to enter clinical trials in over 20 years. In addition, a clinical Proof-of-Concept study in malaria with KAF156, an imidazolepiperazine, achieved a positive outcome (parasite clearance of plasmodium vivax and falciparum) and this compound is now moving forward in partnership with a new formulation of the antimalarial lumefantrine into Phase 2B studies. Novartis will lead the development of antimalarial compound KAF156 with scientific and financial support from Medicines for Malaria Venture in collaboration with the Bill & Melinda Gates Foundation. Novartis has also identified PI4K as a new drug target with potential to prevent, block and treat malaria.

NITD is contributing to the effort to build the capabilities that are essential to enable the discovery and development of new medicines for the people in the environment where they will be used. NITD has provided training for drug discovery to PhD students and hosts Postdoctoral fellows since 2003, with the majority of the individuals coming from disease endemic countries.                    

Realizing the importance of fostering long-term training opportunities for drug discovery scientists in developing countries, NITD linked up with the Biozentrum of the University of Basel and the Swiss Tropical and Public Health Institute to create a Master of Science program in infectious diseases, vaccinology and drug discovery. Launched in early 2005, this provides a high-quality MSc-level research-based training in novel approaches to tackle major communicable and emerging disease problems.

Summary of impact and forward looking information

Phase II clinical studies with KAE609 demonstrated rapid parasite clearance for both types of malaria (vivax and falciparum); long-half-life of the drug supports a once-daily oral dosing regimen.

Clinical Proof-of-Concept study with KAF156 achieved a positive outcome (parasite clearance of plasmodium vivax and falciparum).

New malaria target identified with potential to treat multiple stages of the malaria life cycle, including liver-stage infections of plasmodium vivax.  

Partnership information

Company(ies) Novartis

Partner(s) Agency for Science, Technology and Research (A*STAR), Bill and Melinda Gates Foundation, Biomedical Primate Research Centre, Global Alliance for TB Drug Development (TB Alliance), Medicines for Malaria Venture (MMV), Singapore Economic Development Board, Swiss Tropical and Public Health Institute (Swiss TPH), University of Basel, Switzerland, Wellcome Trust

Type of Partner(s) Academia / Hospitals, Government, NGOs, PDPs

Therapeutic Focus Neglected Tropical Diseases, Infectious Diseases

Disease(s) Buruli Ulcer, Chagas Disease, Cysticercosis, Dengue, Dracunculiasis (Guinea Worm), Echinococcosis, Endemic Treponematoses (Yaws), Fascioliasis, Human African Trypanosomiasis (Sleeping Sickness), Leishmaniasis, Leprosy, Lymphatic Filariasis, Malaria, Onchocerciasis (River Blindness), Podoconiosis, Schistosomiasis, Soil-Transmitted Helminthiasis, Trachoma

Program Type(s) Availability of Treatment - Technology Transfer - Scientific Collaboration and Knowledge Sharing, Health System Infrastructure - Training, Prevention Programs - Vaccines, Research & Development - Development of Treatments, Research & Development - Operations Research, Research & Development - Pediatric R&D

Targeted Population(s) Marginalised / Indigenous People, People with low income

Region(s) East Asia & Pacific, Europe & Central Asia, South Asia, Sub-Saharan Africa

Number of Countries 7

Country(ies) India, Indonesia, Malaysia, Russia, Tanzania, Thailand, Vietnam

Start Date 2002

More information Novartis Institute for Tropical Diseases

Anticipated completion date Ongoing