AC Immune Announces New Clinical Results in Down Syndrome, Plans for Future Development of Anti-Amyloid-Beta Vaccine

AC Immune SA recently announced plans to advance its novel anti-amyloid-beta (Abeta) vaccine into mid-stage clinical testing to treat and prevent the progression of Down syndrome (DS)-related Alzheimer’s disease (AD). Topline results reported today by AC Immune’s Chief Scientific Officer, Dr. Marie Kosco-Vilbois, at a global DS symposium co-sponsored by AC Immune, showed that ACI-24 demonstrated encouraging immunogenicity and safety in Phase 1b clinical testing in people with DS. The company also disclosed new non-human primate data for an optimized formulation of the vaccine, which shows broad potential for the treatment and prevention of Abeta-driven diseases based on its superior efficacy in non-human primates.

Dr. Kosco-Vilbois, said “As World Down Syndrome Day approaches, which is held each year on March 21 to raise awareness for the DS community, we are proud to be leading the way towards addressing a key health challenge facing those living with DS, the early development of AD symptoms. Specifically, we are advancing our anti-Abeta vaccine, which demonstrated encouraging results in a first-of-its-kind Phase 1b study in people with DS. Importantly, the successful completion of this study demonstrates the feasibility of safely testing our Abeta vaccine in individuals with DS. The trial resulted in a very high retention rate with no early withdrawals, at any dose, during the treatment period. We look forward to continuing clinical development in order to potentially offer an effective vaccine strategy to treat, and perhaps ultimately prevent, the development of AD in individuals with DS.”

Highlights from the Phase 1b study in DS-related AD

• Vaccination of adults with DS with ACI-24 resulted in encouraging immunogenicity (generation of anti-Abeta antibodies)
• A positive pharmacodynamic response was observed, as measured by an increase in plasma Abeta
• ACI-24 was safe and well tolerated with no serious adverse events (SAEs) reported
• There was no evidence of central nervous system (CNS) inflammation, meningoencephalitis, or ARIA (amyloid-related imaging abnormalities), including ARIA-E (-edema) and ARIA-H (-hemorrhage)
• AC Immune plans to present the full Phase 1b study results at the upcoming Alzheimer’s Association International Conference (AAIC)

Due to the high vulnerability of people with DS to severe Covid-19 sequelae, initiation of the next clinical trial will be delayed to ensure the safety of study participants. In the interim, AC Immune is taking advantage of this time to accelerate development of its optimized anti-Abeta vaccine formulation, which demonstrated encouraging safety and superior immunogenicity results in mouse and non-human primate (NHP) studies. Dr. Kosco-Vilbois presented some of these key findings during her presentation:

Key preclinical results for the optimized anti-Abeta vaccine formulation in NHPs

•  The optimized vaccine formulation primes, boosts, and maintains strong anti-Abeta antibody responses in two NHP species
• The optimized vaccine formulation generates conformation-specific antibodies targeting key pathological Abeta species, including oligomeric and pyroglutamate Abeta
• The antibodies elicited by the optimized vaccine formulation in NHPs showed clear target engagement by binding to human Abeta plaques on AD patient-derived brain tissue

ACI-24 is also currently being tested in a Phase 2 clinical trial in patients with mild AD. In this study, there have been no safety concerns nor evidence for CNS inflammation or ARIA related to ACI-24 in any subject. The Phase 2 study is progressing toward an 18-month interim analysis, which is planned for Q2 2021.

Prof. Andrea Pfeifer, CEO of AC Immune SA, said “There is broad potential for our optimized Abeta vaccine formulation across Abeta-driven diseases, including DS-related, genetic, and sporadic AD. We plan to complete the current Phase 2 study in mild AD and, in line with our proven business strategy, seek a strategic partner for further development for AD in the general population. This allows us to focus our in-house efforts on advancing our vaccine into later-stage clinical development to address genetically defined AD in people with DS. We look forward to initiating a follow-on clinical trial in DS as soon as the threat to this vulnerable patient population from Covid-19 subsides. In the interim, we are in discussions with the FDA on a potentially accelerated development pathway for the optimized vaccine formulation and expect to file an investigational new drug application for the new formulation in Q4 2021. In parallel, we are encouraged by the recent data from Abeta therapeutic antibodies in AD and expect our optimized vaccine formulation data showing strong responses against pathological oligomeric and pyroglutamate Abeta to further support ongoing clinical development in large and NeuroOrphan indications.”

AC Immune SA is a Nasdaq-listed clinical-stage biopharmaceutical company, which aims to become a global leader in precision medicine for neurodegenerative diseases. The Company utilizes two proprietary platforms, SupraAntigenTM and MorphomerTM, to design, discover and develop small molecule and biological therapeutics as well as diagnostic products intended to diagnose, prevent and modify neurodegenerative diseases caused by misfolding proteins. The Company’s pipeline features nine therapeutic and three diagnostic product candidates, with six currently in clinical trials. It has collaborations with major pharmaceutical companies including Genentech, a member of the Roche Group, Eli Lilly and Company, and Janssen Pharmaceuticals Inc.