University of Bristol, Liverpool School of Tropical Medicine, Liége Université, Aix Marseille Université

ADDovenom

Novel Snakebite Therapy Platform of Unparalleled Efficacy, Safety and Affordability

ADDovenom initiates a major multidisciplinary effort to achieve a timely step-change in snakebite therapy, by creating an innovative platform with transformative potential for antivenom generation to save countless lives.

ADDovenom exploits a disruptive new, protein-based nanoscaffold we developed, the ADDomer – a megadalton sized, thermostable synthetic virus-like particle that offers 60 high-affinity binding sites to rapidly eliminate venom toxins from the blood stream. Further, we will for the first time deploy ADDobody, a small, stable protein motif with randomized flexible loops that will be utilized as a naïve library to select and evolve high-affinity binders in vitro by Ribosome Display. Of note, the ADDobody and ADDomer ‘superbinder’ formats are interconvertible.

The ADDovenom project brings to bear cutting-edge proteomics, transcriptomics and bioinformatics to inventorise the toxin repertoire of eight snakes that inflict the most clinically-challenging envenoming syndromes in sub-Saharan Africa: haemorrhage, coagulopathy, paralysis and tissue necrosis.

We will implement rational design and high-throughput expression to produce antigens for our selections, based on the major toxin groups we target. We will design consensus-toxins and epitope strings combining conserved sequences, to achieve maximal intergeneric efficacy of our ADDobody binders, boosting neutralizing efficacy for entire toxin families simultaneously. We will develop state-of-the-art bioprocessing to manufacture ADDomer-based antivenoms at pharma scale, preparing for future clinical trials.

To achieve these ambitious goals, ADDovenom synergistically combines unique expertise across a range of techniques and scientific disciplines, towards the objective to develop easy to produce, first-in-class neutralizing superbinders for snakebite therapy, to protect with unprecedented efficacy against the most prevalent snakebites – a strategy that can be adapted to all snakes in any geographic region.

 

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899670.