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20-F
AC IMMUNE SA filed this Form 20-F on 03/21/2019
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ACI-24 in Down syndrome

 

Individuals with Down syndrome (DS) have an extra copy of chromosome 21 where the gene for APP resides. These individuals have a rate of AD that is three to five times that of the general population and develop the disease at a much younger age. At autopsy, AD has been reported in 80% of people with DS over age 40 and 100% over age 60. Alzheimer’s-like characteristics develop in more than 98% of people with DS over the age of 40 with up to 80% developing associated dementia over the age of 60. It is estimated that there are 6 million people with DS worldwide, with 250,000 in the United States. Pre-clinical results published by AC Immune in collaboration with Dr. Mobley of the University of California, San Diego in March 2016, shows, in a DS mouse model (Ts65Dn), a significant 20% memory improvement and a 27% reduction of Abeta in the brain following vaccination with ACI-DS-01, the mouse equivalent of ACI-24.

 

A Phase 1b clinical trial (called the 3 Star study) is ongoing and evaluates the safety and tolerability of ACI-24, effect on induction of antibodies against Abeta, biomarkers for Abeta brain and CSF load in adult participants with DS. The study is being partially funded through a grant from the US National Institute on Ageing, a part of the US National Institutes of Health (NIH) with an additional grant from the LuMind Research Down Syndrome Foundation. The dose escalation study includes up to 24 participants across all cohorts, aged 25 to 45 and treated for 12 months, with a 12-month safety follow-up. The recruitment of adults with DS for the low dose cohort was completed in the third quarter of 2017 and for the high dose cohort in the third quarter of 2018. A favorable safety and tolerability profile has emerged as, to date, there are neither serious adverse events nor any early withdrawals from the study. Importantly, preliminary assessment of the low dose cohort for immunogenicity at over the 12 months demonstrates a specific anti-Abeta IgG response induced in actively treated DS subjects.

 

Tau Programs

 

Targeting both intracellular seeds and extracellular spreading by combination therapy of Morphomers and Immunotherapy could enable the full control of the Tau pathology progression. High selective Tau imaging diagnostic enables more precise patient characterization and potentially more precise prediction of AD progression.

 

Figure 20: AC Immune targets pathological Tau at key points in the disease pathway

 

 

Anti-Tau Therapeutic Antibody Candidate

 

Our anti-Tau monoclonal antibody program generated humanized antibodies for use as passive immunotherapies that are highly specific for pathological forms of Tau found in AD brains and other Tauopathies. Results from pre-clinical studies demonstrated a significant reduction in pathological Tau with reduced effector function, meaning decreased ability to affect the function of Tau, as well as improvement of long-term spatial memory. The anti-Tau antibody program was out-licensed to Genentech in 2012. The anti-Tau monoclonal antibody, known as RG6100, was discovered and humanized as part of AC Immune’s collaboration with Genentech. It is an IgG4 isotype and in clinical development for the treatment of AD and other neurodegenerative diseases. It shows a high specificity for pathological Tau and is designed to intercept the cell-to-cell spread of pathological Tau in the extracellular space of the brain.

 

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