AC Immune announces publication of preclinical data on ACI-19626

AC Immune (ACIU) announced the publication in Nature Communications of preclinical data on its first-in-class brain positron emission tomography tracers for imaging TDP-43 pathology. The selected candidate, ACI-19626, potentially enables a precision medicine approach to multiple neurodegenerative diseases that are currently difficult to diagnose and differentiate from each other. TDP-43 is the main component in inclusions found in the brains of people with amyotrophic lateral sclerosis, frontotemporal degeneration and limbic-predominant age-related TDP-43 encephalopathy, as well as a co-pathology in Alzheimer’s disease and Parkinson’s disease. These conditions share many of the same clinical signs and symptoms, making differential diagnosis a difficult and lengthy process in the absence of reliable biomarkers. PET imaging of aggregated TDP-43 offers a new era for the development of disease-modifying therapies for TDP-43 proteinopathies, potentially revolutionizing both diagnosis and treatment. The data showed that ACI-19626, a Morphomer-based TDP-43 PET tracer, demonstrates high specificity and selectivity for the target, with rapid brain uptake and fast and complete washout, supporting the potential to detect TDP-43 pathology by PET in the brains of living patients. Nature Communications also published an accompanying commentary on the potential of TDP-43 PET ligands for biological diagnosis of TDP-43 proteinopathies. Specifically, data on ACI-19626 in the paper showed: High affinity for pathological TDP-43 aggregates, but not physiological TDP-43 Excellent selectivity for TDP-43 over common co-pathologies including Abeta, Tau and alpha-synuclein No off-target binding against a panel of more than 100 receptors, enzymes, ion channels and transporters A pharmacokinetic profile in non-human primates suitable for human brain PET imaging, with rapid brain uptake, homogenous distribution across different brain regions. and fast and complete washout in absence of the target, suggesting minimal background in healthy controls Based on these data, ACI-19626 was selected for further evaluation and is now in an ongoing Phase 1 clinical trial for its promising potential to detect pathological TDP-43 in the brains of patients with TDP-43 proteinopathies compared to healthy volunteers.