SBIR/STTR Award attributes
The treatment of snakebite envenoming is an urgent, global unmet medical need and clear occupational hazard with a pervasive psychological burden to U.S. and allied military personnel. Our soldiers, non-combat service members and their canine companions face the occupational hazard of snakebite while working in remote areas, potentially unable to evacuate because of combat or inclement conditions. It is estimated that worldwide more than 5 million snakebite envenomings occur annually with approximately 400,000 permanent deformities or amputations and over 135,000 deaths every year1,2. Approximately 5.8 billion people live in regions that place them at risk for being bitten by a venomous snake2 and it is estimated that > 75% of deaths from snakebite occur outside the hospital setting before victims can reach medical care. While not all snakebites result in envenoming and morbidity and mortality, often by the time patients receive the appropriate medical care in a hospital setting it is far too late and the toxicities of snakebite envenoming have substantially progressed and no longer amenable to effective treatment by antivenom therapy3,4. Even when the standard of care (SOC) antivenom therapies are available, their use is associated with a number of challenges and limitations, many of which could be overcome with a small-molecule therapeutic5, summarized in Table 1. To underscore the urgency of the global public health crisis posed by snakebite envenoming, the World Health Organization (WHO) recently classified snakebite envenoming as a neglected tropical disease2. Furthermore, the WHO’s Snakebite Envenoming Working Group stated that the accelerated development of promising prehospital treatments, such as Varespladib, the phospholipase A2 (PLA2) inhibitor being developed by Ophirex, may lead to improvements in prehospital survival6. "This proposal includes data that shall not be disclosed outside the Government and shall not be duplicated, used, or disclosed-in whole or in part-for any purpose other than to evaluate this proposal. If, however, a contract is awarded to this offeror as a result of – or in connection with – the submission of this data, the Government shall have the right to duplicate, use, or disclose the data to the extent provided in the resulting contract. This restriction does not limit the Government's right to use information contained in this data if it is obtained from another source without restriction. The data subject to this restriction are contained in page 2-5" 2 Snake venom PLA2 is involved in virtually every critical venom effect and exists as a major weapon in virtually all venomous snakes around the world7-12. Phase II enhancement funds will be used to develop a low dose oral formulation of Varespladib to broaden applicability to a greater variability of patient weights and allow oral dosage in a patients with difficulty swallowing. Eventually, the Varespladib low dose capsule will be used as a first step towards development of a combination prinomastat and Varespladib drug to provide full efficacy against snakebite envenoming. Ultimately, treatments with Varespladib, in its IV and oral formulations, will support significantly better patient outcomes over current antivenom capabilities. The eventual addition of a metalloprotease inhibitor, such as prinomastat will provide complete coverage for snakebite and minimize the burden of snakebite envenoming globally where the burden is greatest and the need desperate for attention to this long-neglected scourge.
