Alzheon, Inc. announced that the U.S. National Institute on Aging (NIA) of the National Institutes of Health has awarded the company a grant (NIA grant number R01AG065253) expected to total $47 million over 5 years to support a Phase 3 clinical study with ALZ-801 – an oral agent that blocks the formation of neurotoxic soluble amyloid oligomers. The study will enroll Early AD patients, who have two copies of the apolipoprotein e4 allele (APOE4/4), as a cutting-edge precision medicine approach to Alzheimer’s disease. AD patients with this genetic profile have been shown to have a higher risk of rapid disease progression and to be responsive to agents targeting pathogenic amyloid oligomers. The award of this NIA grant is recognition of ALZ-801’s compelling clinical rationale and pioneering Phase 3 trial design in the field of Alzheimer’s treatment: a precision medicine focus on APOE4/4 patients to increase the probability of success, and a therapeutic mechanism selectively targeting neurotoxic soluble amyloid oligomers. Independent research has shown that APOE4/4 patients have several-fold higher brain levels of toxic beta amyloid oligomers than APOE4 non-carriers, and are expected to benefit from an anti-oligomer agent like ALZ-801. In published research, Alzheon scientists demonstrated that ALZ-801 fully blocks the formation of soluble neurotoxic amyloid oligomers in the brain at the target clinical dose, and with a favorable long term safety profile. Furthermore, Alzheon scientists uncovered the mechanism by which ALZ-801 augments the body’s natural defenses to inhibit formation of toxic amyloid oligomers. The Phase 3 study is designed to evaluate ALZ-801 in 300 patients with Early AD and the APOE4/4 genotype. Subjects will be randomized to receive 265 mg tablets of ALZ-801 or a matching placebo twice daily for 18 months. The study will evaluate the cognitive endpoint, Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog), as the primary clinical outcome, and other functional, behavioral, and global clinical endpoints. Biomarker assessments will include plasma and cerebrospinal fluid (CSF) measures of core AD pathologies (amyloid and phosphorylated tau protein) and of neurodegeneration (neurofilament light chain protein, tau protein, and neurogranin), and neuroinflammatory markers. Imaging biomarkers will include measurements of hippocampal volume and cortical thickness. The independent co-chairs of the Steering Committee for the Phase 3 trial are Dr. Anton Porsteinsson and Dr. Marwan Sabbagh, Director of theCleveland Clinic Lou Ruvo Center for Brain Health. Alzheon plans to initiate the Phase 3 trial in first quarter of 2021.