Alzheon, Inc. announced that it will be presenting baseline imaging characteristics from ongoing APOLLOE4 Phase 3 clinical trial and 12-month results from the Phase 2 biomarker study evaluating ALZ-801 oral tablet at the upcoming American Academy of Neurology (AAN) Conference to be held from April 22 to April 27, 2023 in Boston, Massachusetts. ALZ-801 (valiltramiprosate) is an investigational oral disease-modifying therapy in Phase 3 development for the treatment of early AD. In mechanism-of-action studies, ALZ-801 fully blocked the formation of neurotoxic soluble beta amyloid (Aß) oligomers at the Phase 3 clinical dose.

ALZ-801 has shown potential for robust clinical efficacy in the highest-risk Alzheimer's population – patients with two copies of the apolipoprotein e4 allele (APOE4/4 homozygotes), and favorable safety with no increased risk of brain vasogenic edema. This population is the focus of Alzheon's pivotal Phase 3 APOLLOE4 trial, which is now fully enrolled and will be completed in mid-2024. Imaging findings of subjects enrolled in pivotal APOLLOE4 Phase 3 trial showed that this patient population exhibits a high rate of cerebral amyloid angiopathy (CAA)-related lesions at baseline, making them more susceptible to treatment-induced amyloid related imaging abnormalities (ARIA) lesions that represent brain edema and microhemorrhage.

32% of subjects presented with at least one lobar microhemorrhage (MH), including 9% with greater than four MH and 9% with superficial siderosis. Occipital and frontal lobes were the most common locations of CAA-related lesions. ALZ-801 is currently being evaluated in two clinical trials in early AD subjects: an 84-patient Phase 2 biomarker study comprising APOE4 carriers, including 31 APOE4/4 homozygotes, and a 325-patient pivotal Phase 3 study comprising APOE4/4 homozygotes.

The Phase 2 biomarker trial will be completed in mid-2023, and the APOLLOE4 trial will read out in mid-2024 with a planned NDA filing the same year and expected commercial launch in 2025. The modified intent to treat (mITT) population of Phase 2 trial included 84 subjects, with 75 completing 12 months of treatment. The mean age of the subjects was 69 years, with 51% female, having a mean MMSE of 26.0. Approximately 70% of patients were in MCI stage and 30% were in Mild AD stage.

Significant plasma p-tau181 reduction started at 13 weeks of treatment and reached -41% at 52 weeks (p=0.016), with significant reduction in plasma Aß42 and Aß40 at 52 weeks (-5%, p=0.002, p=0.005 respectively). Hippocampal atrophy was reduced by approximately 20% following 12 months of treatment compared to matched Alzheimer's Disease Neuroimaging Initiative (ADNI) external controls. Composite cognitive Z-score improved significantly at 13 and 26 weeks remaining above baseline at 52 weeks.

Common adverse events were mild nausea and COVID infection, with no drug-related serious events or ARIA-E.