IND-Enabling Studies of Encephlavir, a Pre-Clinical Candidate for Treatment of Neurotropic Alphaviruses

This is a proposed contract action in response to approved concept and solicitation HHS-NIH-NIAID-BAA2025-1 to fund proposal entitled - IND-Enabling Studies of Encephlavir, a Pre-Clinical Candidate for Treatment of Neurotropic Alphaviruses. The proposal fulfills a gap to develop a therapeutic for a mosquito-borne, lethal, encephalitic virus unique to the US. This proposal aims to develop an oral therapeutic, to treat New World alphaviruses that cause encephalitis, including Eastern (EEEV), Western (WEEV), and Venezuelan (VEEV), equine encephalitis viruses. These viruses are carried by mosquitoes. EEEV is unique to the United States and causes a severe encephalitis with 30-75% mortality. Survivors often die after initial recovery or have long-term disabilities. Currently there are no drugs for these viruses, and the mortality rate for EEEV infection is 30-75% across age groups, and nearly all survivors experience debilitating long-term neurological damage. Ideally, since this virus is very similar to two other encephalitic alphaviruses, this candidate therapeutic is likely to be a broad-spectrum drug that benefits a larger population of people in both the Northern and Southern hemispheres, as well as the US military that has identified these viruses as a potentially significant threat for warfighters. An immediate return-to-duty after infection from any one of these viruses is unlikely, unless a beneficial therapeutic such as this promising candidate, is available. The final decision on a cost-plus-fixed-fee contract will be made based on the availability of funds and the outcome of contract negotiations with the University of Tennessee Health Science Center but should be lower when UTHSC applies a CAP in calculating their G&A rate on subcontracts per 2 CFR 200.1 - Modified Total Direct Cost Definition - Calculating Indirect Costs which applies to academic institutions.