Francesca Capotosti (Switzerland)
AC Immune SA
Research
Dr. Francesca Capotosti is the Group Leader for in vivo pharmacology and non-clinical safety at AC Immune, where she is responsible for leading in vivo pharmacology, ADME, DMPK, and toxicology activities for the Company’s small molecule, vaccine, and monoclonal antibody candidates. She also serves as Global Project Leader for the alpha-synuclein PET program. Previously, she served as Research Scientist and then Team Leader, working primarily on small molecules targeting Tau as therapeutic and diagnostic agents. Before joining AC Immune in 2013, Dr Capotosti worked as postdoctoral fellow in the Bioengineer Department of the École Polytechnique Fédérale de Lausanne (EPFL), focusing on new therapeutic approaches for immuno-oncology. Dr Capotosti holds a PhD in life science from the University of Lausanne, work for which she obtained the Young Investigator Award, and a Master Degree in pharmaceutical chemistry from the University of Pisa, Italy.

Moderator of 1 Session

 Conference Calendar
SYMPOSIUM

ALPHA-SYNUCLEIN- DISEASE MECHANISMS, DETECTION & THERAPEUTIC RELEVANCE

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 114
Chair(s)

Presenter of 1 Presentation

 Conference Calendar

DISCOVERY OF [18F]ACI-12589, A NOVEL AND PROMISING PET-TRACER FOR ALPHA-SYNUCLEIN

Session Name
1080 - ALPHA-SYNUCLEIN- DISEASE MECHANISMS, DETECTION & THERAPEUTIC RELEVANCE (ID 53)
Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 114
Lecture Time
09:55 AM - 10:10 AM
Presenter

Abstract

Aims

Background: Synucleinopathies are characterized by progressive accumulation of a-synuclein (a-syn) inclusions in specific brain regions, correlating with clinical manifestations and disease severity. Due to co-pathologies and low density of a-syn pathology, a reliable a-syn PET tracer must display strong selectivity, high binding affinity and minimal non-specific binding.

Methods

Methods: Using our proprietary Morphomer® library in conjunction with iterative medicinal chemistry, optimized compounds have been identified with appropriate on-target affinity and target occupancy as well as selectivity for potential co-pathologies. Autoradiography and radiobinding techniques were employed to discover initial leads and generate optimized compounds. The most advanced compounds were 18F radiolabeled and their pharmacokinetic (PK) profiles assessed in non-human primates (NHPs). The clinical candidate, [18F]ACI-12589, was advanced in preclinical activities prior to evaluation in patients with different synucleinopathies.

Results

Results: Several highly promising chemical scaffolds have been identified with the ability to bind brain-derived a-syn. From one series, ACI-12589 has demonstrated superior target occupancy on tissues from different synucleinopathies with a binding pattern matching well the distribution of pathological a-syn. Moreover, ACI-12589 demonstrates selectivity towards a-syn versus potential co-pathologies. Studying [18F]ACI-12589 in NHPs revealed good brain uptake, homogenous distribution and fast washout. Initial results from the recent clinical trials confirm these favorable parameters in patients including suitable brain uptake and rapid signal equilibration.

Conclusions

Conclusions: [18F]ACI-12589 displays the preclinical and clinical characteristics deemed necessary to become a reliable and accurate PET radiotracer for synucleinopathies. Particularly its extensive preclinical characterization on different synucleinopathy tissues seems to match with the promising clinical data that will be presented at this conference.


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