Alzheon, Inc. announced that it has entered into a collaboration and license agreement with the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB) to develop the first clinical assay to measure neurotoxic beta amyloid (amyloid, Aß) oligomers in human cerebrospinal fluid (CSF). Under the collaboration agreement, IOCB will apply Alzheon’s technology for detecting oligomers into a customized clinical assay in human CSF, to be developed by the IOCB and commercialized by Alzheon. This initiative builds on successfully completed feasibility studies performed over the past year by the two organizations. The assay developed by the Alzheon-IOCB collaboration will be sensitive to the full spectrum of soluble oligomer species in CSF and will be able to quantify the amyloid oligomer burden in the brain. The new diagnostic is designed to address the limitations of current assays used to detect amyloid oligomers, such as enzyme-linked immunosorbent assays, that can be sensitive to oligomer levels, but are non-specific, as they do not distinguish individual species of Aß oligomers. The collaboration between Alzheon and IOCB will leverage Alzheon’s discoveries and scientific expertise in AD, particularly the insights into the role of Aß oligomers in disease biology. Alzheon will provide biospecimens from AD patients including samples from patients treated with ALZ-801. The IOCB will be primarily responsible for the development and validation of an assay to detect amyloid oligomers and to measure the change in amyloid levels in biological samples following treatment with Alzheon’s anti-oligomer agents, such as ALZ-801. Recent findings from AD studies and clinical trials provide strong evidence that soluble amyloid oligomers are directly neurotoxic upstream drivers of AD pathology, leading to progressive increase in phosphorylated tau protein and markers of neuronal injury in CSF and plasma of AD patients. Amyloid oligomers are a key target of several promising Phase 3 antibodies for Early AD including aducanumab, lecanemab/BAN2401 and donanemab, as well as Alzheon’s lead clinical candidate, ALZ-801, an oral treatment that fully blocks formation of neurotoxic oligomers in the brain at clinical dose. About ALZ-801: An oral anti-amyloid drug, ALZ-801 is an optimized prodrug of tramiprosate that has shown promising results in analyses of Phase 3 clinical data,6,8 and has a novel anti-amyloid oligomer mechanism of action.4,7 ALZ-801 received Fast Track designation from the U.S. Food and Drug Administration in 2017. The clinical data for ALZ-801 and its active agent, tramiprosate, indicate long-term clinical efficacy in AD patients with the APOE4 genotype and a favorable safety profile.4,6,8 ALZ-801 acts through a novel enveloping molecular mechanism of action to fully block formation of neurotoxic soluble amyloid oligomers6 associated with the onset of cognitive symptoms and progression of AD.2,3 The cognitive improvements observed in the tramiprosate Phase 3 studies may also be attributed in part to the therapeutic effects of 3-sulfopropanoic acid (3-SPA), an endogenous anti-oligomer substance in the human brain discovered by Alzheon scientists that, like tramiprosate, inhibits formation of toxic amyloid oligomers.4 3-SPA is the primary metabolite of ALZ-801 and its discovery helps explain the beneficial pharmaceutical attributes of ALZ-801, including favorable safety profile, high selectivity for amyloid, and excellent brain penetration. ALZ-801 treatment increases levels of 3-SPA in the brain and augments the body’s natural mechanism to inhibit formation of toxic amyloid oligomers.4,5 The initial Phase 3 program for ALZ-801 will focus on Early AD patients with the APOE4/4 genotype, with future expansion to investigate ALZ-801 for prevention of Alzheimer’s onset and in patients carrying only one copy of the APOE4 gene.