Extended Data Fig. 1: PK/PD data observed in phase 1 is consistent with population-based model and predicts neutralization of free GDF-15 in the tumour.
From: Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours
(a) Observed concentrations of total visugromab and total GDF-15 (free and drug-bound GDF-15) determined in serum of phase 1 participants across all tested dose levels within 8 weeks of treatment and at end of treatment. Mean and individual data points. (b) A population PK/PD model was derived from NHP studies and updated with clinical phase 1 data to describe GDF-15 neutralization in tumour micro-vasculature. Free GDF-15 is predicted for serum GDF-15 baseline levels of 0.5 ng/mL (left panel), 2 ng/mL (middle panel) and 10 ng/mL (right panel) and dosing schemes (upper panel = q2wk, middle panel = q3wk, lower panel = q4wk) as well as different concentrations (red, solid line = 3 mg/kg, green dashed line = 10 mg/kg and blue dashed line = 20 mg/kg) of visugromab. The threshold indicates the average physiological serum GDF-15 level (0.5 ng/mL).
