Fig. 8: SAR’336 reduces inflammation in a mouse DTH model.
From: A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism
Groups of C57BL6 mice (n = 10) were sensitized with 250 µg KLH with CFA/IFA on Day 1 and dosed on day 0 & 3 with SAR’336 at 0.03, 0.1 & 0.3 mg/kg. Ear pinnae were challenged with 10 µg KLH on day 7 and ear thickness readings were measured on days 7-10. a Treg cells were measured in blood on days 0, 3, 7 & 10, showing dose-dependent induction. Overall ear thickness from days 7-10 was significantly lower in 0.1 & 0.3 mg/kg dose groups (t test, p < 0.002, 0.0001) compared to vehicle. b Ear pathology was assessed by scoring inflammatory infiltrates, hyperkeratosis, epidermal hyperplasia, and corneal pustules, which were compiled into an overall score, showing that the 0.3 mg/kg group improved vs vehicle (1-way ANOVA p < 0.05). Representative images show reduced inflammatory infiltrates with SAR’336 treatment. ANOVA analysis of variance, AUC area under the curve, CFA complete Freund’s adjuvant, D day, IFA incomplete Freund’s adjuvant, KLH keyhole limpet hemocyanin, SC subcutaneous.
