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Priming the pipeline: Antimalarial drugs

The chemical structure of the spiroindolone, NITD609, a preclinical candidate for malaria
A promising antimalarial is on course to enter the Medicines for Malaria Venture drug development pipeline.

With resistance to artemisinin-based drugs a growing concern, there remains a need to pursue new pharmacological leads in the battle against malaria. With Technology Transfer funding, the Novartis Institute for Tropical Diseases in Singapore is testing a range of possible new compounds, with a view to passing on the most promising to the Medicines for Malaria Venture (MMV) - a public-private partnership based in Switzerland that has also received funding from the Wellcome Trust. Encouragingly, the first compound is due to make the transition to the MMV pipeline.

The Novartis Institute for Tropical Diseases (NITD), a public-private partnership between Novartis and the Singapore Economic Development Board, was set up in 2002. Its aim is to develop small-molecule therapeutics for infectious diseases of low-income countries, principally dengue, tuberculosis and malaria. It works on compounds originating within Novartis as well as others identified in academic research.

The NITD concentrates on early stages of drug discovery, identifying and chemically refining potential new agents, and carrying out preclinical studies to test for efficacy and toxicity in animal models.

Its most promising antimalarial compound emerged from a screen of a large library of natural products held by the Novartis parent company. The compound was lethal to cultured parasites, and in vivo tests after chemical optimisation have confirmed its potency. Three doses rapidly and completely eliminated malaria parasites in infected mice - far exceeding the 'gold standard' for efficacy at this stage of development.

The next step is to file for 'investigational new drug' status late in 2010, which would enable the compound to be registered for clinical trials. MMV and NITD will jointly manage the clinical development, and phase I clinical trials could start in the first half of 2011.

Image: The chemical structure of the spiroindolone, NITD609, a preclinical candidate for malaria. Credit: Ida Ma, Novartis Institute Tropical Diseases.

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