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.