NGP 555

NGP 555 is a small molecule γ-secretase modulator developed for the prevention and treatment of Alzheimer's disease. It selectively modulates the activity of the γ-secretase complex to lower levels of amyloid-β peptide Aβ42 while increasing shorter, non-toxic forms such as Aβ37 and Aβ38. This mechanism aims to reduce amyloid plaque formation in the brain—a key pathological feature of Alzheimer's disease—while avoiding side effects associated with γ-secretase inhibitors. Preclinical studies have shown that NGP 555 can prevent amyloid pathology and cognitive decline in animal models without gastrointestinal toxicity. In human clinical trials, oral administration demonstrated good safety, tolerability, brain penetration, target engagement (as measured by favorable shifts in cerebrospinal fluid amyloid biomarkers), and pharmacokinetic properties[1][2][3][4][5][6].