IN VIVO STUDY

Determination of the dose effect of compound TAV64 administered as a bolus intravenously in a model of sepsis in rats

Randomization of animals into 5 groups of 8 Wistar rats according to body weight on D1.

Induction of sepsis by intraperitoneal injection of a solution of lipopolysaccharides at a dose of 5.5 mg/kg.

Administration of TAV64 every 6 hours for 24 hours in order to “mimic” a continuous infusion.

3 daily doses of TAV64 tested, based on the targeted human daily dose and converted to the dose to be administered to the rat based on the publication “A simple practice guide for dose conversion between animals and human” (Nair and Jacob; Journal of Basic and Clinical Pharmacy Vol.7-Issue 2-March-May 2016)

TAV64015 < TAV64040 < TAV64065 = potential target daily doses

IN VIVO STUDY

Efficacy study of compound TAR64 in Chronic Inflammatory Bowel Disease (IBD) in mice

Dextran Sulfate Sodium (DSS), an acute colitis inducer, is administered for 7 days followed by 5 days of withdrawal (no DSS). The DSS is administered (at 4%) in the drinking water available ad libitum for the animals, and renewed every two days, according to the SOPs of the TCS for the induction of IBD.
All treatments start on D1 (the same day of DSS induction) and are administered until the end of the study (D12). The mice are randomized into the following 4 treatment groups: vehicle, TAR64100, TAR64200 and TAR64400.
Study endpoints:
• Assessment of animal health and body weight
• Overall clinical score for daily IBD: diarrhea or stool consistency, bleeding, loss of body weight, mortality.
•  Endoscopy quotation D8 and D12
• Blood leukocytes D7 and D14
• Assays of plasma cytokines:IL1-β, IL-6, IL-10, IL-17A,TNF-α, IFN-γ and IL-12p70 and IL-23p19/p40
• Assay of blood biomarkers: Myeloperoxidase (MPO)
• Colon weight and lenght
• Histopathological assessment of the colon.

The study is on-going.