NGP-555

Alzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years.

Using amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques, we investigate the properties of NGP 555, a clinical‐stage γ‐secretase modulator.

NGP 555 shifts amyloid peptide production to the smaller, nonaggregating forms of amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers, pathology, and cognition. NGP 555 has successfully completed chemistry, pharmacology, toxicity, metabolism, and safety studies.

Abundant data support Aβ42 as a target for prophylactic or early‐stage intervention therapies in AD. The γ‐secretase modulator, NGP 555 is being actively developed in human clinical trials for the prevention of Alzheimer's disease with the overall aim to achieve an appropriate balance of potency/efficacy on reducing the toxic forms of amyloid versus safety.

The 240th National Meeting of the American Chemical Society, held in Boston, included topics covering new therapeutic research. This conference report highlights selected presentations on negative allosteric modulators of metabotropic glutamate receptor 5 (mGluR5) for the treatment of Parkinson's disease, BACE1 inhibitors and γ-secretase inhibitors for the prevention or treatment of Alzheimer's disease, opioid modulators for the treatment of reward disorders, SGLT2 inhibitors for the treatment of diabetes, backup compounds to the DPP-4 inhibitor sitagliptin (Januvia) for type 2 diabetes, and MCH R1 inhibitors for the treatment of obesity. Investigational drugs discussed include SCH-1359113 and SCH-1682496 (both Merck & Co), NGP-555 (NeuroGenetic Pharmaceuticals), ALKS-33 (Alkermes), dapagliflozin (Bristol-Myers Squibb/AstraZeneca) and GSK-882380 (GlaxoSmithKline).