Objective: Immunotherapy against α-synuclein is a promising novel treatment strategy for Parkinson’s disease and related α-synucleinopathies. We have developed exidavnemab (BAN0805), a monoclonal antibody with a high affinity and selectivity for pathological aggregated forms of α-synuclein and a low affinity for physiological monomers. Exidavnemab is in clinical development as a disease-modifying treatment for patients with neuronal synucleinopathies such as Parkinson’s Disease and other synucleinopathy phenotypes.

Background: To increase the confidence of human target engagement in a therapeutic setting, binding of exidavnemab to pathological α-synuclein in post-mortem brains of Parkinson’s disease, Parkinson’s disease dementia, Dementia with Lewy bodies and Multiple system atrophy patients were assessed.

Method: Immunohistochemistry and immunodepletion experiments with brains from Parkinson’s disease, Parkinson’s disease dementia, Dementia with Lewy bodies and Multiple system atrophy patients demonstrate that exidavnemab binds aggregated α-synuclein in all diseases tested. Moreover, exidavnemab almost completely depleted aggregated α-synuclein in brain extracts.

Results: Safety, tolerability, pharmacokinetics, immunogenicity and exploratory biomarkers were assessed in two separate Phase 1 single ascending dose studies, including intravenous or subcutaneous administration of exidavnemab in healthy volunteers. Exidavnemab was generally well tolerated. The pharmacokinetics of exidavnemab was dose linear and the terminal half-life was 30 days.

Conclusion: Taken together, the results from the ex vivo target engagement studies with human tissue and two clinical studies performed support the continued clinical development of exidavnemab in several synucleinopathies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exidavnemab-offers-opportunities-as-a-potential-disease-modifying-therapy-in-several-synucleinopathies/