MICA: Pre-Clinical Development of a Small Molecule anti-Wolbachia Candidate Macrofilaricide Drug

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Lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness) are two important neglected tropical diseases that cause severe disability and affect more than 157 million people globally. Control efforts are hindered by the lack of a safe macrofilaricidal (adult parasite killing) drug. Targeting the Wolbachia bacterial endosymbionts in these parasites with doxycycline leads to a macrofilaricidal outcome, but protracted treatment regimens and contraindications restrict its widespread implementation. As part of an ongoing macrofilaricide drug discovery project we have successfully completed a lead optimisation programme to deliver a pre-clinical candidate anti-Wolbachia based macrofilaricide. The candidate AWZ1066S shows superior efficacy compared to doxycycline in a range of validated animal infection models, meets all current Target Candidate Profile characteristics (including extensive non-GLP safety/pharmacology and DMPK evaluation) and is positioned for onward development. We now request funding to support the critical formal pre-clinical development programme in order to progress AWZ1066S to the first into man transition.