Positive Data Reported for ACI-12589, First-in-class Parkinson’s Diagnostic Agent

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by Forest Ray PhD |

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AC Immune anticipates advancing ACI-12589, its novel alpha-synuclein positron emission tomography (PET) tracer for Parkinson’s disease diagnosis, to clinical development in the last quarter of this year.

Based on positive new data, the company made the announcement during an oral presentation at the virtual Alzheimer’s Association International Conference (AAIC).

ACI-12589 is a non-invasive diagnostic tool meant to distinguish disorders that are due to alpha-synuclein abnormalities — alpha-synucleinopathies — from other pathological or conditions.

Tools of this nature are needed to make accurate clinical diagnoses, monitor disease progression and determine the benefits of therapeutic interventions.

In the presentation “Developing a novel alpha-synuclein positron emission tomography (PET) tracer for the diagnosis of a-synucleinopathies,” the company reported that preclinical results for ACI-12589 showed enhanced contrast and alpha-synuclein target specificity.

This, the company said in a press release, positioned its PET tracer to become a first-in-class precision diagnostic tool for Parkinson’s. The neurodegenerative condition currently lacks effective diagnostic agents, representing a substantial unmet clinical need.

PET is a non-invasive imaging technique that allows researchers and clinicians to observe metabolic processes inside the body. A PET tracer specific to alpha-synuclein would allow scientists to study how these toxic clumps change both form and location as the disease progresses.

Clumps of misfolded alpha-synuclein are a key component of Lewy bodies, a hallmark feature of Parkinson’s and related conditions such as multiple system atrophy and Lewy body dementia.

“I am highly encouraged by these results, as they demonstrate AC Immune’s industry-leading expertise in the development of alpha-synuclein-targeting agents. There is increasing recognition of the importance of targeting the right disease pathology at the right time in neurodegenerative diseases, and AC Immune continues to lead the way towards facilitating such an approach through the parallel development of therapeutic and diagnostic agents for important targets such as alpha-synuclein, as well as more well established targets like Tau and Abeta,” said Andrea Pfeifer, CEO of AC Immune. “The data presented at AAIC are a prime example of the power of our Morphomer platform to facilitate the rapid optimization of our PET tracers.”

The Morphomer platform is a proprietary method for screening collections of small molecules for those that are important to a given research goal. Molecules identified through this platform are used to design other small molecules called morphomers, which specifically bind to target misfolded proteins. These morphomers then break up neurotoxic clusters to prevent their aggregation (clumping).

AC Immune also announced that it had advanced its alpha-synuclein antibody candidate from discovery phase into preclinical development.

The decision to move forward followed proof-of-concept data that AC Immune presented at the AAT-AD/PD conference earlier this year.

The presentation also included mention of ACI-3847, another alpha-synuclein PET tracer. This tracer efficiently entered the brain and showed very low non-specific activity in a first-in-human study among both idiopathic Parkinson’s patients and healthy volunteers.

This data, the company says, support testing ACI-3847 in alpha-synucleinopathies with greater amounts­ of accumulated alpha-synuclein.