Alzheon, Inc. announced the dosing of the first patient in its APOLLOE4 Phase 3 study evaluating the efficacy and safety of ALZ-801 in Early AD patients carrying two copies of the e4 allele of the apolipoprotein E gene (APOE4/4 homozygotes). AD patients with this genetic profile present with an early onset and rapid progression of the disease and are responsive to drug agents that remove or inhibit pathogenic amyloid oligomers. ALZ-801 is an oral treatment that has been shown in preclinical mechanistic studies to fully inhibit the formation of neurotoxic soluble beta amyloid oligomers at the Phase 3 clinical dose. APOLLOE4 is the only Phase 3 trial evaluating an oral anti-amyloid treatment and applying a precision medicine approach to disease-modification in AD. The APOLLOE4 study is supported by a $47 milliongrant from the National Institute on Aging (NIA). The primary objective of the APOLLOE4 study is to measure the impact of ALZ-801 on cognition using the Alzheimer's Disease Assessment Scale – cognitive subscale (ADAS-cog). Secondary endpoints include assessments of function, ability to perform daily activities, and neuropsychiatric symptoms. The study will also evaluate ALZ-801’s effects on fluid and imaging biomarkers shown to be sensitive early markers of AD progression and neuroinflammation. The APOLLOE4 randomized, double-blind, placebo-controlled trial will enroll 300 APOE4/4 homozygotes with Early AD at approximately 85 sites in the United States, Canada, and Europe. Recent findings from clinical trials with anti-amyloid agents provide strong evidence that soluble amyloid oligomers are neurotoxic upstream drivers of AD pathology, leading to progressive worsening in tau pathology and neuronal injury markers in cerebrospinal fluid (CSF) of AD patients. AD patients with the APOE4/4 genotype will be enrolled in the APOLLOE4 Phase 3 trial into either placebo or active treatment arms, each including 150 patients. Patients will receive 265 mg of ALZ-801 or matching placebo tablets twice daily for 78 weeks. Frequent cognitive tests, functional assessments, and volumetric magnetic resonance imaging will be performed, and all patients will have plasma biomarker assessments. A subgroup of patients will also provide CSF samples for biomarker testing at three timepoints during the trial. Correlation of clinical efficacy to biomarker effects may allow the use of these biomarkers as surrogate outcomes in future studies in other AD populations, and in prevention studies in pre-symptomatic patients.