Alzheon, Inc. announced the initiation of a Phase 2 study evaluating biomarker effects of ALZ-801, an oral treatment blocking formation of neurotoxic soluble amyloid oligomers, in Early AD patients carrying one or two copies of the e4 allele of the apolipoprotein E (APOE4) gene. AD patients with this genetic profile have a higher risk of rapid disease progression and are responsive to drug agents targeting pathogenic amyloid oligomers. The primary objective of Phase 2 biomarker study is to assess the effects of 265 mg oral tablet of ALZ-801, administered twice daily for two years, on fluid and imaging biomarkers shown to be sensitive early markers of AD progression. The biomarkers selected for this study have been shown to correlate with clinical benefit in AD patients in trials with amyloid-targeted antibody therapies. This Phase 2 study is the first AD biomarker trial to prospectively evaluate APOE4 carriers using cerebrospinal fluid (CSF) and plasma biomarkers, as well as volumetric magnetic resonance imaging (MRI) evaluating brain atrophy. Study evaluations will include a battery of biomarkers that reflect amyloid pathology (beta amyloid 42 and 40), tau pathology (phosphorylated tau protein, or p-tau) and neuronal injury (neurofilament light chain protein, or NfL). A Biomarker Steering Committee comprised of AD experts advised on the design of the trial and will oversee its conduct. Committee members include: Kaj Blennow, MD, PhD, Professor and Head of Research on Neurochemical Pathogenesis and Diagnostics at the University of Gothenburg in Sweden; Eric Reiman, MD, PhD, Executive Director of the Banner Alzheimer’s Institute and Clinical Director of the Neurogenomics Division at the Translational Genomics Research Institute in Phoenix, Arizona; and Philip Scheltens, MD, Professor of Cognitive Neurology and Director of the Alzheimer Center at Amsterdam University Medical Centers in Netherlands. Phase 2 Biomarker Study Expands NIA-Backed ALZ-801 Pivotal Phase 3 Program: Recently, Alzheon was awarded a $47 million grant from the National Institute on Aging (NIA) to advance the Phase 3 study of ALZ-801 in high risk APOE4/4 homozygous AD patients, starting in first quarter 2021. The addition of this Phase 2 biomarker trial will provide first-ever insights into the biomarker profile of a broader population of APOE4 carriers who receive ALZ-801 treatment, and thereby expand the potential indications for ALZ-801 to approximately two thirds of all Alzheimer’s patients. The Phase 2 biomarker trial is designed to accelerate development of ALZ-801 for prevention of AD in asymptomatic individuals with risk factors, based on their genetic and biomarker profile. ALZ-801 is an oral small molecule, with a favorable safety and tolerability profile more suitable for long-term use in AD treatment and prevention than amyloid-targeted antibodies that require burdensome 1-3 hour bi-weekly or monthly intravenous infusions or subcutaneous injections, as well as MRI safety monitoring for serious adverse events such as brain edema and microbleeds. The Phase 2 biomarker trial will initially enroll 40 Early AD patients with one or two copies of the APOE4 gene, at leading clinical research sites in the Czech Republic and the Netherlands. All patients will receive ALZ-801 in 265 mg oral tablets twice daily for two years. Frequent fluid biomarker assessments, volumetric MRI imaging, and cognitive tests will be performed throughout the duration of the trial.