Alzheon, Inc. announced that it will be presenting two scientific posters at the 14th Annual Clinical Trials on Alzheimer?s Disease (CTAD) conference to be held on November 9-12, 2021 in Boston, MA, USA. At the CTAD conference, Alzheon will provide the first presentation of baseline data from the ongoing Phase 2 biomarker study of oral drug candidate ALZ-801 in Early AD patients, who carry either one or two copies of the e4 allele of apolipoprotein E gene (APOE3/4 heterozygotes and APOE4/4 homozygotes, respectively). APOE4 genotype, the most important risk factor for Alzheimer?s after aging, is associated with a several-fold higher brain burden of amyloid oligomers. ALZ-801 is an oral agent being evaluated in Alzheon?s APOLLOE4 Phase 3 trial as a disease-modifying treatment for AD. In mechanism of action studies, ALZ-801 has been shown to fully inhibit the formation of neurotoxic soluble amyloid oligomers at the Phase 3 clinical dose. The Phase 2 study completed enrollment earlier this year and is evaluating the effects of 265 mg twice-daily oral dose of ALZ-801 on fluid biomarkers, imaging, and clinical outcomes over two years of treatment. The study objective is to confirm the disease-modifying potential of oral tablet ALZ-801 in APOE4/4 and APOE3/4 patients with Early AD, by assessing its effects on cerebrospinal fluid (CSF) and plasma biomarkers of beta amyloid (A?), phosphorylated tau (p-tau), neuronal injury and neuroinflammation. The study also evaluates drug effects on brain hippocampal volume using magnetic resonance imaging (MRI), and on cognitive and functional outcomes. Alzheon?s scientists analyzed baseline CSF, MRI, and clinical data from 131 screened subjects enrolled in the Phase 2 biomarker study evaluating ALZ-801 oral tablet, of which 108 provided baseline CSF samples and 110 provided baseline MRI data included in this analysis. Analysis of 108 Early AD subjects with one or two copies of the APOE4 gene enrolled in Phase 2 study showed significant baseline differences in CSF biomarker profiles between APOE4/4 homozygotes and APOE3/4 heterozygotes. Almost all homozygotes (>97%) had abnormal p-tau/A?42 levels, thereby validating the selection of this patient population for the ALZ-801 APOLLOE4 Phase 3 study focused on the subjects with APOE4/4 genotype. In contrast, one third of APOE3/4 heterozygotes had negative CSF biomarkers, indicating the necessity for PET imaging or fluid biomarkers to identify subjects with AD. These data support the selection of a genetically defined APOE4/4 AD population enriched in A? pathology for the pivotal APOLLOE4 Phase 3 trial of ALZ-801 in Alzheimer?s disease. In cross-sectional analyses of baseline MRI data in 110 Early AD patients, a comparison of APOE4/4 homozygotes versus APOE3/4 heterozygotes showed distinct profiles of hippocampal atrophy and cortical thinning with advanced disease and age. In APOE3/4 heterozygotes, both volumetric measures showed significant and strong correlations with clinical measure Mini-Mental Status Examination, while in APOE4/4 homozygotes this correlation was significant but modest. In addition, in APOE3/4 heterozygotes, cortical thinning appears to be more prominent with advanced disease.