Can you give an overview of AC Immune’s activities and performance in 2021?

2021 was a great year for AC Immune. The company completed its first all stock acquisition of Affiris' alpha-synuclein (a-syn) assets and underlying intellectual property, including a clinically validated a-syn vaccine for the treatment of Parkinson's disease which we will begin the Phase 2 clinical trial for in the second half of 2022. We also completed a private placement transaction with a select group of investors led by Athos Service with additional participation from First Capital Partner and MIG Fonds. The private placement transaction of US$30 million significantly strengthened AC Immune’s cash position.

AC Immune was pleased to announce the first positive cognitive results for a tau-targeting monoclonal antibody in AD in November 2021. The antibody, known as semorinemab, targets a protein called tau that is recognized to play a role in Alzheimer’s (AD). The treatment reduced cognitive decline from baseline by 42.2% compared to placebo in people with mild-to-moderate disease, though it did not meet the other co-primary endpoint and the secondary endpoints. We continue to monitor patients in the study hoping to gain enough data to hopefully begin another study.

We also saw encouraging data from an interim analysis of our phospho-Tau Alzheimer’s vaccine trial ACI-35.30, and there was great antibody generation against the pathological target. This led to the expansion of the trial on the second-highest dose cohort, which will increase the amount of immunogenicity and safety data and potentially facilitate advancement into late-stage development.

Additionally, we are proud to have recently published preclinical data on the optimized formulation of our wholly owned amyloid-beta (Abeta) vaccine program, ACI-24, demonstrating safety, immunogenicity, and target engagement. We plan to advance clinical development to the next stage for both AD and Down syndrome (DS)-related AD in 2022.

With a vast pipeline of 11 therapeutics and 3 diagnostic product candidates, where does AC Immune place priority?

Our pipeline is quite mature around three targets, Abeta, Tau, and a-syn, and our emphasis for 2022 is on delivering on clinical milestones. Out of the 11 therapeutics, we have eight clinical therapeutic products and expect to have seven clinical readouts within 2022. Given their promise, we are currently working to advance our phospho-Tau vaccine ACI-35.030, semorinemab anti-tau antibody, Tau-PET candidate, ACI-24 vaccine, crenezumab Abeta antibody, and our non-invasive diagnostic for alpha-synucleinopathies (e.g. multiple system atrophy). Regarding this latter, we have recently presented at the ADPD congress the first live human brain able to detect pathological alpha-synucleins.  

Can you elaborate on the science behind an antibody approach to misfolded proteins?

The drivers advancing our pipeline are our proprietary SupraAntigen and Morphomer technology platforms which generate highly specific biologics and small molecule drugs. Their agility allows for accelerated discovery and development of candidates targeting novel targets. Using our proprietary SupraAntigen technology, we develop either passive (i.e. monoclonal antibodies) or active (i.e. vaccines) immunization candidates to target neurodegenerative diseases. Drug candidates are selected to distinguish normal from pathological proteins and inhibit key disease pathways both inside and outside of cells. We believe that beyond targeted monotherapies, combination therapy will offer greater efficacy in treating the broad spectrum of pathologies. Leveraging our Morphomer platform, we develop proprietary imaging agents that could become the first in the world to effectively diagnose proteinopathies and improve the timing and accuracy of diagnoses to reshape the treatment and clinical course of neurodegenerative diseases.

At the rate the field is advancing, how far out are we from a reality where neurodegenerative disease prevention is the new normal?

There are different means of prevention, including lifestyle changes such as heightened focus on nutrition. If crenezumab Abeta antibody phase 2 data reads out positively, however, it would be the first time there is a safe drug delaying or preventing AD. This would be a game changer, as people would have a motivation to get screened by a physician, given the possibility of a preventative treatment that comes with the diagnosis. We hope to reach success with our vaccine products soon, given the revolutionary impact of preventing AD through yearly injections.