AC Immune Publishes First-in-Class TDP-43 PET Tracer Data in Nature Communications, Advances to Phase 1 Trial
核心洞察
AC Immune SA announced publication in Nature Communications of preclinical data on ACI-19626, a first-in-class brain PET tracer for imaging TDP-43 pathology in neurodegenerative diseases.
The Morphomer-based tracer demonstrates high specificity for pathological TDP-43 aggregates with rapid brain uptake and complete washout, potentially enabling precision diagnosis of ALS, FTD, and LATE.
ACI-19626 has advanced to Phase 1 clinical trials with initial readout expected in Q4 2025, addressing the diagnostic challenge of differentiating TDP-43 proteinopathies.
AC Immune SA announced the publication of preclinical data in Nature Communications for its first-in-class brain positron emission tomography (PET) tracer ACI-19626, designed to image TDP-43 pathology in living patients. The Swiss clinical-stage biopharmaceutical company has advanced the candidate into Phase 1 clinical trials, with initial readout expected in Q4 2025.
Addressing Critical Diagnostic Gap in Neurodegenerative Diseases
TDP-43 serves as the main component in inclusions found in the brains of patients with amyotrophic lateral sclerosis (搜索) (ALS), frontotemporal degeneration (搜索) (FTD), and limbic-predominant age-related TDP-43 encephalopathy (搜索) (LATE). The protein also appears as a co-pathology in Alzheimer's disease (搜索) and Parkinson's disease (搜索). These conditions share many clinical signs and symptoms, making differential diagnosis a difficult and lengthy process in the absence of reliable biomarkers.
"Accurate PET imaging of TDP-43 pathology could significantly improve the diagnosis of multiple neurodegenerative diseases, paving the way to precision prevention with the possibility of intervening before damage occurs," said Dr. Andrea Pfeifer, CEO of AC Immune SA.
Superior Pharmacological Profile Demonstrated
The Nature Communications paper, entitled "Development of [18F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology," reports comprehensive characterization data supporting the tracer's clinical potential. ACI-19626, based on AC Immune's Morphomer technology platform, demonstrated several key advantages:
- High affinity for pathological TDP-43 aggregates while avoiding physiological TDP-43
- Excellent selectivity for TDP-43 over common co-pathologies including amyloid-beta, tau, and alpha-synuclein
- No off-target binding against a panel of more than 100 receptors, enzymes, ion channels, and transporters
- Optimal pharmacokinetic profile in non-human primates with rapid brain uptake, homogeneous distribution across brain regions, and fast, complete washout in absence of the target
Clinical Development and Market Impact
The favorable preclinical profile led to ACI-19626's selection for Phase 1 clinical evaluation, where it will be tested for its ability to detect pathological TDP-43 in patients with TDP-43 proteinopathies compared to healthy volunteers. The diagnostic tool could transform clinical trial design by enabling patient stratification, optimizing therapeutic intervention timing, and facilitating evaluation of target engagement and pharmacodynamic effects.
"PET imaging biomarkers have been proven to be potential game changers in the field of neurodegenerative diseases, as seen with amyloid PET in Alzheimer's disease (搜索)," noted Dr. Francesca Capotosti, VP Research of AC Immune. "We strongly believe that the detection of TDP-43 pathology by PET could not only support earlier and more definitive diagnosis but also accelerate drug development and open new avenues for combination therapies."
Technology Platform and Pipeline
AC Immune's two clinically validated technology platforms, SupraAntigen and Morphomer, fuel its diversified pipeline of therapeutic and diagnostic programs. The company maintains candidates in Phase 2 and Phase 3 development and has secured strategic partnerships with leading pharmaceutical companies, resulting in over $4.5 billion in potential milestone payments plus royalties.
Nature Communications also published an accompanying commentary highlighting the potential of TDP-43 PET ligands for biological diagnosis of TDP-43 proteinopathies, underscoring the scientific community's recognition of this diagnostic approach's significance.