HELP - Collaboration for innovation: Establishment of a pan-nematode drug development platform

To target helminth elimination, a drug research and development (R&D) pipeline is needed to provide new chemotherapeutics that effectively eliminate or sterilize adult worms, thus bringing about the paradigm shift necessary to reach the 2030 SDG goals on health.

Our consortium proposes to establish a R&D pipeline for anthelminthics targeting nematodes. The focus will be on soil-transmitted helminthiasis and onchocerciasis, since these infections are among the leading neglected tropical diseases. Ground breaking characteristics of the drugs developed within our project are that they will have a unique mechanism of action that, at best, will target multiple nematodes (pan-nematode) with an excellent safety profile, including no efficacy against non-targeted co-endemic species.

We will benefit from collaborations with our industrial partners Bayer and Celgene providing preselected compounds to populate the early preclinical stages of the R&D pipleline. Compounds with the best profile will be progressed through preclinical studies. Corrallopyronin A, a compound with proven efficacy against essential Wolbachia endosymbionts in filariae that has superiority to the gold standard doxycycline, excellent bioavailability and promising exploratory safety data will undergo state-of-the-art toxicity profiling to advance towards phase 1 trials. We will also evaluate oxfendazol and oxantel pamoate in clinical trials. They have already proven efficacious in animals or humans and will only require clinical trials accoridng to current regulatory guidelines to be implemented.

With this strategy, the consortium will ensure that a pipeline of drug candidates is available for treating onchocerciasis, especially should current candidates fail in upcoming clinical trials. Moreover, we will establish a much-needed drug R&D pipeline to treat soil-transmitted helminth infections for which there is currently neither a drug with good efficacy against all species nor any prospects on the horizon.

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