CeNeRx’s HPA (hypothalamic-pituitary-adrenal) axis modulator program includes the novel agent CXB722 and its prodrug Ayrene (CXB724). CXB722 and Ayrene are being developed for the treatment of a variety of CNS disorders including anxiety and depression. In a recent clinical trial, CXB722 showed potential as a novel anxiolytic, demonstrating a significant reduction in the endocrine and cardiovascular biomarkers associated with stress. The following data includes highlights from this study, a Trier Social Stress Test (TSST).
In a Trier Social Stress Test (TSST) study of CXB722 in healthy volunteers who were subjected to stress-inducing situations, subjects who received CXB722 exhibited a significantly lower increase in the hormone ACTH (a stress marker) than subjects who received placebo. Figure 1 shows the change from baseline in the levels of ACTH in the plasma of subjects who received CXB722 compared to the change in levels of ACTH in the plasma of subjects who received placebo.
The graphs in Figure 2 show the change in baseline levels of cortisol (a hormone involved in the response to stress and anxiety) in the plasma (figure on right) and saliva (figure on left) of subjects given CXB722 compared to subjects given placebo, following a stress-inducing event during the TSST study. Subjects who received CXB722 exhibited a more moderate increase in cortisol, particularly as measured in the saliva, than subjects who received placebo during the TSST.
Figure 3 shows the average heart rate of subjects in the CXB722 group during the TSST study compared to the average heart rate of subjects in the placebo group before, during, and after the stress-inducing event. Before the TSST stress-inducing event, the average pulse rate between the groups stays within the same range. During and after the stress-inducing event, the average pulse rate spikes significantly for the placebo group, while it remains more stable for the CXB722 group, indicating CXB722’s potential ability to modulate responses to stress and anxiety.