Fig. 1. Preclinical data in SJSA-1 tumour-bearing mice treated with CGM097.
a NanoString analysis with selected known p53-regulated genes performed in SJSA-1 tumours from animals treated with a single 50 mg/kg dose of CGM097. b For PK/PD experiment, mice were randomised into groups of n = 3 and sacrificed/sampled over a 48 h period of time. Unbound plasma exposure was calculated on the basis of a free fraction of 0.193% in the mouse. The black dotted lines represent the biochemical IC90. c For efficacy experiment, mice were randomised into groups of n = 6 and CGM097 was administered at several doses according to respective dosing regimen for 14 days. Differences between the means of TVol were assessed on the endpoint using a one-way ANOVA with Dunnett’s tests post hoc (*P < 0.05 considered as significant). d One-compartment PK model (WinNonlin/Phoenix 6.3) of the mouse was used to estimate PK parameters (average plasma concentrations at steady-state [Cave-ss] and maximum plasma concentrations at steady-state [Cmax-ss]) for the four dosing regimens and correlate with the observed regression. a Gene expression analyses by NanoString of p53 target genes in vivo. b In vivo PK/PD relationship. c In vivo efficacy. d In vivo PK modelling.