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Preclinical and clinical testing of a repurposed drug for use as an early oral therapeutic for tropical snakebite: a model to leverage western markets for LMIC access
Investigator(s): Professor Nicholas Casewell
Amount Awarded: 101,939

Snakebite is a life-threatening neglected tropical disease that causes more than 130,000 deaths annually. Current treatment is restricted to intravenous antivenom, which has to be delivered in a clinical environment, resulting in delays and poor patient outcomes. Our previous work demonstrates that the orally available, licensed, heavy metal poisoning drug Dimaval® shows preclinical efficacy against African/Asian snake venoms rich in metalloproteinase toxins, and that early oral delivery followed by later antivenom administration confers increases in efficacy in mouse models over antivenom alone. Thus, Dimaval® may prove to be a valuable early therapeutic intervention, via oral delivery in a community setting soon after a bite, against certain snakebites. In this project, we seek to transition the repurposing of Dimaval® for snakebite indication from TRL4 to TRL6 via two specific activities. First, we propose to perform pharmacokinetic analyses to define drug levels collected from healthy volunteer patient cohorts receiving escalating oral doses to define optimal human dosing  regimens. This will enable the transition of Dimaval® for snakebite from TRL4 laboratory-scale validation, through TRL5 via small scale safety testing, ready for entry into a Phase II clinical trial (i.e. larger-scale testing in relevant environment, TRL6), thus overcoming a major clinical and regulatory milestone. Simultaneously, we will conduct in vitro and in vivo preclinical research, backfilling the TRL4 space, to investigate the efficacy of Dimaval® against other snake venoms. This enabling strategy will allow the commercial partner leverage of additional markets, where a tangible return on investment exists, to facilitate clinical and regulatory progression while simultaneously prioritising an LMIC access plan.