Figure 10.

(Left) 5/6 nephrectomy in C57BL/6 mice does not dramatically impact the TMDD serum PK profile of M616. Shown are overlaid results from two separate PK studies where either male or female mice were given 4 mg/kg IV dose of M616 highlighting a lack of gender influence on IL-36 R-mediated TMDD in serum. Also shown (red) is a 5 mg/kg IV arm to illustrate that partial kidney ablation has only a minor impact on TMDD. (Right) 5/6 nephrectomy has no impact on M616 TMDD at 0.5 mg/kg IV dose and does not alter the impact of IL-36 R saturation as observed by a cassette dosing strategy. Additionally, cassette dosing of anti-TNP, rat IgG2a does not change the pharmacokinetics of M616, suggesting fast CL at low dose (0.5 mg/kg) is predominantly driven by target binding.