NewAmsterdam Pharma Announces Initial Data from Phase 2a Clinical Trial Evaluating Obicetrapib in Patients with Early Alzheimer’s Disease Who Carry an ApoE4 Mutation

-- Observed reductions of 11% and 12% in 24- and 27-hydroxycholesterol in cerebrospinal fluid (“CSF”), respectively, indicating potential improvement of cholesterol metabolism in the brain --
-- Observed 8% increase in Aβ42/40 ratio, a key biomarker of AD risk, suggesting improvement in disease pathology --

NAARDEN, The Netherlands and MIAMI, Sept. 21, 2023 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or “NewAmsterdam” or the “Company”), a clinical-stage biopharmaceutical company developing oral, non-statin medicines for patients at high risk of cardiovascular disease with residual elevation of low-density lipoprotein cholesterol (“LDL-C”), for whom existing therapies are not sufficiently effective or well-tolerated, today announced initial data from its Phase 2a clinical trial evaluating obicetrapib in patients with early Alzheimer’s disease (“AD”) and at least one copy of the apolipoprotein E4 mutation (“ApoE4”).

This Phase 2a trial was designed to explore the effects of obicetrapib on lipid metabolism in the brains of early AD patients who are ApoE4 carriers. Two key biomarkers measured in the trial include 24- and 27-hydroxycholesterol; increases in these oxysterols over time have been observed to lead to a rise in cognitive and related functional impairment. As such, NewAmsterdam believes reductions of 24- and 27-hydroxycholesterol in the CSF may indicate improved cholesterol metabolism in the brain and may lead to improved cognitive function. In addition, the Phase 2a trial assessed the Aβ42/40 ratio and plasma pTau181, also believed to be biomarkers of AD, with lower levels of Aβ42/40 and increased levels of pTau181 having been associated with a greater risk of AD.

This trial builds on observations from NewAmsterdam’s preclinical studies and third-party genetic studies that inhibiting cholesteryl ester transfer protein (“CETP”) may protect against ApoE4-associated AD risk by preventing the accumulation of amyloid plaque in the brain through improved cholesterol metabolism and, as a result, potentially slow disease progression.

“These data represent an important first step in determining the role of lipid metabolism in the brain,” said Jeffrey Cummings, M.D., Director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas. “Approximately two thirds of patients with Alzheimer’s dementia carry at least one copy of the ApoE4 gene and CETP loss-of-function mutations have been shown to protect against ApoE4-associated AD risk. These data warrant further study of CETP inhibition as a potential mechanism to ameliorate ApoE4-associated AD risk.”