The fluorocycline TP-271 is efficacious in models of aerosolized Bacillus anthracis infection in BALB/c mice and cynomolgus macaques [PublishAheadOfPrint]

The fluorocycline TP-271 was evaluated in mouse and non-human (NHP) primate models of inhalational anthrax. BALB/c mice were exposed by nose-only aerosol to 18 - 88 LD₅₀Bacillus anthracis Ames spores. When 21 days of once-daily dosing was initiated at 24 hours post-challenge (post-exposure prophylaxis, PEP), survival for the 3, 6, 12 and 18 mg/kg TP-271 groups was 90%, 95%, 95%, and 84%, respectively. When 21 days of dosing was initiated at 48 hours post-challenge (treatment, Tx) survival for the 6, 12 and 18 mg/kg TP-271 groups was 100%, 91%, and 81%, respectively. No deaths of TP-271-treated mice occurred during the 39-day post-treatment observation period. In the NHP model, cynomolgus macaques received an average dose of 197 LD₅₀B. anthracis Ames spore equivalents using a head-only inhalation exposure chamber and once daily treatment of 1mg/kg TP-271, lasting for 14 or 21 days, was initiated within 3 hours of detection of protective antigen (PA) in the blood. No animals (0/8) survived in the vehicle control group, whereas all 8 infected macaques treated for 21 days, and 4 of 6 in the 14-day treatment group, survived to the end of study (56 days post-challenge). All survivors developed toxin-neutralizing antibody and anti-PA IgG titers, indicating an immunologic response. Based on results in mouse and NHP models, TP-271 shows promise as a countermeasure for the treatment of inhalational anthrax.

http://ift.tt/2vepO2i