Developing strategies for preserving
quality of life

AC Immune is advancing one of the broadest product portfolios focused on pioneering precision medicine for neurodegenerative diseases. Leveraging our proprietary technology platforms, Morphomer® and SupraAntigen®, we are pursuing multiple therapeutic modalities in parallel by advancing diagnostics, antibodies, small molecules and active immunotherapies targeting carefully selected therapeutic targets: amyloid beta (Abeta), Tau, alpha-synuclein (a-syn), TDP-43 and (NOD)-like receptor protein 3 (NLRP3).

We believe adaptive biomarker-based trial designs provide the necessary flexibility in an increasingly dynamic regulatory environment and shorten the time from bench to bedside for our diagnostics and therapeutic candidates.

If you are interested in participating in one of our clinical trials or would like more information, we recommend you first discuss it with your medical doctor to provide guidance related to your specific situation.

anti-Abeta active immunotherapy in Alzheimer's disease and Alzheimer's disease in Down Syndrome

AC Immune is pursuing clinical development with ACI-24.060, an optimized formulation of ACI-24, which is intended to prime, boost and maintain a strong antibody response against key pathological Abeta species (including oligomeric and pyroglutamate Abeta; Vukicevic M. et al., Brain Communications, 2022).

This Phase 1b/2 study, ABATE, will evaluate the active immunotherapy candidate in early Alzheimer’s disease and the target population will consist of both patients with Alzheimer’s disease and people living with Down syndrome, with evidence of presence of brain amyloid pathology.

ABATE is a multicenter adaptive, double-blind, placebo-controlled study that will assess the safety, tolerability, immunogenicity and pharmacodynamic effects of ACI-24.060.

Key outcome measures for the study will include assessments of safety, immunogenicity, pharmacodynamics, Abeta-PET imaging, and target engagement.

http://www.clinicaltrials.gov/study/NCT05462106

View our Expanded Access Policy for ACI-24.060

AC Immune Technology Platforms Anti-ptau vaccine | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-Abeta vaccine
Indication Prodromal Alzheimer’s disease and Alzheimer's disease in Down Syndrome (AD in DS)
Clinical stage Phase 1b/2
Current status ongoing

anti-pTau active immunotherapy in Alzheimer's disease

In collaboration with Janssen Pharmaceuticals Inc., AC Immune is advancing the anti-phospho-Tau active immunotherapy candidate in subjects with early Alzheimer’s disease. It targets phosphorylated Tau proteins, a key component of the Alzheimer’s pathology that is found in Tau tangles, its aggregated form.

Interim results showed that immunization with ACI-35.030 generates a potent antigen-specific antibody response against phospho-Tau (Streffer J. et al., CTAD 2021).

The Phase 1b/2a study is a randomized, multicenter, double-blind, placebo-controlled clinical study with a primary objective to assess the safety, tolerability and immunogenicity of different doses of ACI-35.030 in patients with early Alzheimer’s disease. Secondary objectives assess additional immunogenicity parameters. Other endpoints assess clinical and cognitive parameters as well as additional immunogenicity and safety parameters.

http://www.clinicaltrials.gov/ct2/show/NCT04445831

AC Immune Technology Platforms Anti-ptau vaccine | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-phospho-Tau vaccine
Indication early Alzheimer's disease, i.e. mild cognitive impairment (MCI) due to Alzheimer's disease and mild Alzheimer's disease
Clinical stage Phase 1b/2a
Current status completed

anti-a-synuclein active immunotherapy in Parkinson's disease

Our wholly owned candidate ACI-7104.056 is an optimized formulation designed to induce a-syn-specific antibodies recognizing aggregated a-syn species that are toxic to neurons.

Building on the strong Phase 1 data of the predecessor active immunotherapy (Volc D. et al., Lancet Neurol., 2020), ACI-7104.056 has advanced into an adaptive, biomarker-based Phase 2 study in early Parkinson’s disease.

This Phase 2 study has two parts: in the first part, we utilize biomarker-based interim analyses to tailor the dosing regimen and monitor the disease-specific biomarkers.

In part two, the goal is to generate clinical proof-of-concept in early Parkinson’s disease and to monitor the progression of motor and non-motor symptoms, as well as digital, imaging, and fluid biomarkers.

AC Immune Technology Platforms Anti-ptau vaccine | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-a-synuclein vaccine
Indication Early idiopathic Parkinson’s disease
Clinical stage Phase 2
Current status ongoing

Tau-PET tracer in Alzheimer's and NeuroOrphan diseases

With our partner, Life Molecular Imaging (LMI), we are advancing PI-2620 as a best-in-class Tau diagnostic for Alzheimer’s disease as well as other disorders caused by misfolding Tau protein, so-called tauopathies. These include progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).

PI-2620 demonstrated excellent characteristics potentially allowing for differentiation between 3/4R- and 4R-tauopathies and might serve as a supportive readout in the diagnostic workup of neurodegenerative disorders.

The ADvance Phase 3 trial is an open-label, multi-center, non-randomized pivotal study to assess the efficacy and safety of PET imaging with [18F]PI-2620 for detection of Tau deposition in subjects with Alzheimer’s disease (AD) during lifetime when compared to histopathology obtained after death and completion of brain autopsy.  Two test-retest studies in PSP (Phase 1) are currently ongoing.

http://www.clinicaltrials.gov/ct2/show/NCT05641688

AC Immune Technology Platforms Pi-2620 | Pioneering Precision Medicine for neurodegenerative diseases
Modality Tau-PET imaging agent
Indication Alzheimer's and NeuroOrphan diseases
Clinical stage Phase 3 & Phase 1
Current status ongoing

anti-Tau antibody in Alzheimer's disease

Our anti-Tau monoclonal antibody, semorinemab, is designed to slow the spreading of Tau pathology, which correlates with clinical symptoms and disease progression in Alzheimer’s disease.

A Phase 2 trial (TAURIEL) demonstrated safety, tolerability and target engagement but a lack of clinical effect in prodromal-to-mild Alzheimer’s disease (Teng E. et al., CTAD 2020).

LAURIET, a Phase 2 study, was evaluating semorinemab in mild-to-moderate Alzheimer’s disease. Top-line data showed a statistically significant reduction on one of two co-primary endpoints, ADAS-Cog11, providing the first positive cognitive results for an anti-Tau antibody therapy in Alzheimer’s disease. The second co-primary endpoint, ADCS-ADL, and secondary endpoints were not met. Semorinemab was well tolerated with no unanticipated safety signals.

The primary completion was accomplished in 2021 and further analyses are ongoing.

The Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was evaluating the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in 260 patients with mild-to-moderate Alzheimer’s disease. The primary objectives were to assess cognitive function and functional capacities.

http://www.clinicaltrials.gov/ct2/show/NCT03828747

AC Immune Technology Platforms Semorinemab | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-Tau antibody
Indication Mild-to-moderate Alzheimer’s disease
Clinical stage Phase 2
Current status Completed – open-label extension results awaited

anti-Abeta antibody in Alzheimer's disease prevention

The API-ADAD (Alzheimer’s Prevention Initiative – Autosomal-Dominant Alzheimer’s disease) study was a landmark prevention trial providing the unique opportunity to evaluate crenezumab, our anti-Abeta antibody, as a preventative therapy.

This was a collaboration between the National Institutes of Health (NIH), the Banner Alzheimer’s Institute and Genentech, a member of the Roche group.

The Phase 2 Alzheimer’s Prevention Initiative trial in Colombia was evaluating crenezumab in cognitively healthy individuals with an autosomal dominant PSEN1 E280A mutation, which puts them at high risk of developing familial Alzheimer’s disease.

This study was to determine whether treating people carrying this mutation with crenezumab prior to the onset of Alzheimer’s symptoms, could slow or prevent the decline of cognitive and functional abilities.

http://www.clinicaltrials.gov/ct2/show/NCT01998841

AC Immune Technology Platforms Semorinemab | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-Abeta antibody
Indication Alzheimer's disease prevention
Clinical stage Phase 2
Current status Completed

Morphomer® Tau small molecule aggregation inhibitors in Alzheimer's and NeuroOrphan diseases

In collaboration with our partner, Eli Lilly & Co., we are researching and developing small molecule Tau aggregation inhibitors with plans to evaluate candidates in Alzheimer’s disease and NeuroOrphan indications.

In 2020, a Phase 1 clinical study in healthy volunteers was completed. It showed a dose-dependent exposure and brain penetration, achieving the desired levels of ACI-3024 in the CSF.

In addition to Alzheimer’s disease, the program is planned to be expanded to NeuroOrphan indications and candidates will be further evaluated for efficacy in models of rare Tauopathies.

Continued candidate characterization across the research program has also identified new and highly differentiated candidates with excellent cerebrospinal fluid exposure and selectivity for pathological aggregated Tau. These will be assessed for their further development in Tau-dependent neurodegenerative diseases.

AC Immune Technology Platforms Morphomer-tau | Pioneering Precision Medicine for neurodegenerative diseases
Modality Tau small molecule aggregation inhibitor
Indication Alzheimer's and NeuroOrphan diseases
Clinical stage Phase 1
Current status completed

a-synuclein-PET tracer in Parkinson's and NeuroOrphan diseases

Our next-generation PET tracer has shown significant potential to reliably detect and map deposits of the pathological form of a-synuclein protein in the brain and was advanced into clinical development in 2021.

Supported by the Michael J. Fox Foundation for Parkinson’s Research, a First-in-Human study and an investigator-initiated study were begun in 2021 and evaluate the imaging tracer’s characteristics as a diagnostic tool in patients with Parkinson’s disease, multiple system atrophy (MSA) and other a-synucleinopathies.

AC Immune Technology Platforms Pi-2620 | Pioneering Precision Medicine for neurodegenerative diseases
Modality a-syn-PET imaging agent
Indication Parkinson's and NeuroOrphan diseases
Clinical stage First-in-Human study
Current status ongoing

anti-Abeta active immunotherapy in Down Syndrome

Our anti-Abeta active immunotherapy candidate ACI-24 is designed to stimulate the immune system to produce antibodies that specifically target misfolded Abeta, prevent accumulation and enhance the clearance of amyloid plaques.

This Phase 1b clinical study of ACI-24 in people living with Down syndrome was a prospective multicenter, placebo-controlled, double-blind, randomized study to assess the effect of one dose of ACI-24 versus placebo over a 74-week treatment period and 26-week safety follow-up period.

It assessed safety, tolerability and immunogenicity.

The results were presented at the 2021 AAIC conference and demonstrated a favorable safety and tolerability profile of ACI-24 supporting the advancement of this program with an optimized formulation of ACI-24 (Rafii M. et al., AAIC, 2021).

http://www.clinicaltrials.gov/ct2/show/NCT02738450

AC Immune Technology Platforms Anti-ptau vaccine | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-Abeta vaccine
Indication Down syndrome
Clinical stage Phase 1b
Current status completed

anti-Abeta active immunotherapy in Alzheimer's disease

This Phase 2 trial analyzed the effects of the anti-Abeta active immunotherapy candidate ACI-24 on brain amyloid levels assessed by PET imaging in patients with mild Alzheimer’s disease.

This double-blind, randomized, placebo-controlled adaptive design study assessed the safety, tolerability, immunogenicity and target engagement of ACI-24 in mild Alzheimer’s disease.

It was completed in 2021 and confirmed that ACI-24 was safe and well tolerated while triggering an immune response. There was evidence of a pharmacodynamic effect suggesting target engagement.

The full study results were presented at CTAD 2021 (Sol O. et al., CTAD, 2021).

http://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-000445-39

AC Immune Technology Platforms Anti-ptau vaccine | Pioneering Precision Medicine for neurodegenerative diseases
Modality anti-Abeta vaccine
Indication Mild Alzheimer’s disease
Clinical stage Phase 2
Current status completed
Addressing Alzheimer’s, Parkinson’s and other neurodegenerative diseases

BROAD AND DIVERSIFIED PIPELINE FOCUSED ON NEURODEGENERATIVE DISEASES

Our clinical stage pipeline uniquely integrates diagnostic and therapeutic candidates as well as different treatment modalities (such as antibodies, active immunotherapies and small molecule drugs) against the most promising validated therapeutic targets.

Therapeutic Focus

Alzheimer’s disease is the most prevalent neurodegenerative disease leading to dementia and a major focus of AC Immune. In recent years, as our pipeline has grown, we have diversified to develop product candidates targeting Parkinson’s disease and other NeuroOrphan diseases.

AC Immune Therapeutic Focus | Pioneering Precision Medicine for neurodegenerative diseases