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AC Immune Provides Update on Alzheimer’s Disease Vaccine Candidates Targeting Pathological Amyloid-Beta
Optimized vaccine candidate generates enhanced polyclonal antibody response against pyroglutamate Abeta in non-human primates Phase 2 interim analysis of
About this update from Ac Immune Sa
[{"type":"text","content":"Optimized vaccine candidate generates enhanced polyclonal antibody response against pyroglutamate Abeta in non-human primates Phase 2 interim analysis of ACI-24 confirms good safety and tolerability profile in people with mild Alzheimer’s disease LAUSANNE, Switzerland, June 02, 2021 (GLOBE NEWSWIRE) -- AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, today provided key clinical and preclinical updates for its SupraAntigen®-derived liposomal vaccine candidates, which are designed to convey active, long-lasting immunization against pathological forms of amyloid-beta (Abeta). AC Immune is completing a Phase 2 study of its first clinical candidate, ACI-24, in people with mild Alzheimer’s disease (AD), and is also advancing an optimized ACI-24 formulation, which demonstrates enhanced and sustained immunogenicity in non-human primate studies, particularly against key pathological forms of Abeta such as oligomeric and pyroglutamate Abeta. Pyroglutamate Abeta (pyroGlu-Abeta) is a highly neurotoxic form of Abeta that is N-terminally truncated and post-translationally modified to form pyroglutamate. Extracellular pyroGlu-Abeta is an important target for immunotherapy, as the peptide’s altered biochemical properties make it more prone to aggregate compared to full-length Abeta, and it is a major component of Abeta plaques. Passive immunization with a monoclonal antibody specific for pyroglutamate Abeta demonstrated encouraging clinical results in a recently published Phase 2 clinical study. In non-human primates, vaccination with the optimized ACI-24 vaccine generated a strong, conformation-specific antibody response against oligomeric and pyroGlu-Abeta. A robust boosting effect was also observed, the magnitude of which was substantially greater against pyroGlu-Abeta compared to full-length Abeta (approx. 8-fold vs 4-fold increase, respectively, between the 3rd and 5th injections). Epitope mapping studies using sera from immunized cynomolgus monkeys showed the strongest signals for sites binding to peptides covering N-terminal regions of Abeta located just beyond where cleavage occurs to form pyroGlu-Abeta (amino acids 3-10, 4-11, 5-12). This further supports the strong response observed against this key pathological variant. Prof. Andrea Pfeifer, CEO of A...