Accelerating pre-clinical drug discovery for schistosomiasis

Schistosomiasis is a neglected tropical disease (NTD) affecting more than 140 million people in 78 countries. Mass drug administration with a single agent, praziquantel (PZQ), is the primary strategy for disease control, with an estimated 260 million people receiving periodic treatment. However, the sustainability of this strategy is at risk due to PZQ’s inactivity against juvenile worms and the potential for PZQ resistance to emerge in endemic communities. To achieve morbidity control and elimination, new effective treatment options are required. Over the last 3 years, our team has assembled a unique toolkit of approaches to support schistosomiasis drug discovery. We are now in an excellent position to leverage this toolkit to deliver lead compounds with activity against all human-residing life-cycle stages for the treatment of schistosomiasis. We will combine phenotypic and target-based approaches to accelerate the drug discovery process. These two strategies will be bridged through comprehensive drug target deconvolution studies to identify the molecular target(s) of phenotypically active compounds. We will be guided by Compound Progression Criteria based on the Target Product Profile for new anti-schistosomal treatments. Our overarching aim is to deliver a pre-clinical drug candidate with activity against adult and juvenile worms and schistosomula within 5 years.