Fig. 4: Clinical pharmacodynamic activity of AG-270/S095033.

a Reductions in plasma SAM concentration at steady state (C1D15) in patients. Average reductions in plasma SAM concentration are within the range associated with maximum tumor growth inhibition in preclinical models (60–80%). b Increase in plasma methionine concentration at steady state (C1D15) in patients. In (a, b), box denotes 25th to 75th percentiles, horizontal bar the mean, and dotted bar the median, with whiskers extending to the minimum and maximum values. n indicates the number of patients evaluated in each cohort for each biomarker (SAM or methionine). c, d SDMA assessment by IHC in paired tumor biopsies collected before treatment and upon treatment of patients at C1D28. In c, H-scores found in 9 patients treated with AG-270/S095033 at the indicated doses, are shown (p-value = 0.055, two sided Wilcoxon matched-pairs test). In d, an example of SDMA staining is shown for a NSCLC patient with 39% SDMA reduction after 1 cycle of treatment with AG-270/S095033 at 50 mg QD.