Path: /clinical-trials/bepranemab-psp-phase-2-nct05318985
NCT ID: NCT05318985
Phase: Phase 2
Status: Recruiting
Bepranemab (also known as PRX005) is an anti-tau monoclonal antibody developed by Prothelia Biosciences in collaboration with Takeda. It targets tau aggregates with high affinity and is being studied in patients with progressive supranuclear palsy (PSP).
This trial represents a critical effort in the tau immunotherapy field. According to recent reviews, bepranemab is one of only nine anti-tau monoclonal antibodies still in clinical testing for PSP and Alzheimer's disease, making it one of the few remaining candidates actively being evaluated for tau pathology[1].
Bepranemab binds to aggregated tau in the brain and is designed to:
The antibody targets an epitope in the tau protein that is specifically exposed in pathological aggregates. Unlike some anti-tau antibodies that target normal tau, bepranemab preferentially binds to disease-associated conformations, potentially allowing for more specific targeting of pathological tau[3].
PSP is characterized by the accumulation of 4-repeat (4R) tau isoforms in neurofibrillary tangles and glial inclusions. The selective targeting of aggregated tau by bepranemab makes it a promising therapeutic candidate as it addresses the core pathology of PSP rather than just symptomatic manifestations.
The development of bepranemab for PSP addresses several key factors:
PSP is a rapidly progressive neurodegenerative disease with no approved disease-modifying therapies. Current treatments provide only symptomatic relief and do not address the underlying tau pathology.
Unlike symptomatic treatments, bepranemab directly targets the pathogenic tau protein that aggregates in PSP brains. This approach represents the most direct disease-modifying strategy currently in development[2:1].
Animal studies have demonstrated that anti-tau antibodies can reduce tau pathology and improve behavioral outcomes in mouse models of tauopathy, providing rationale for clinical testing in humans.
Recruiting as of early 2026. The trial is actively enrolling patients at multiple sites in the United States and Europe.
Prothelia Biosciences (Lead sponsor)
Takeda Pharmaceutical Company (Collaborator)
Prothelia is a biotechnology company focused on developing therapies for tauopathies and other neurodegenerative diseases. Their partnership with Takeda provides resources for global clinical development.
Bepranemab enters a competitive field of tau-targeting therapies. As of 2024, there are approximately nine anti-tau antibodies in clinical development for Alzheimer's disease and PSP combined[1:1]. However, no anti-tau antibody has yet reached Phase 3 trials for PSP, making this Phase 2 trial particularly important for the field.
This trial is referenced in the Personalized Treatment Plan as a priority anti-tau therapy option.
The outcome of this Phase 2 trial will have significant implications for the entire tau immunotherapy field. Success would validate the anti-tau antibody approach for PSP and potentially accelerate development of similar therapies for other tauopathies. The trial's use of tau PET imaging as a biomarker is particularly important, as it may establish novel endpoints for future studies.
If bepranemab demonstrates disease-modifying effects, it could become the first approved therapy specifically targeting tau pathology in PSP, representing a major breakthrough for patients who currently have no disease-modifying treatment options available.
This trial also contributes to understanding the role of tau in neurodegenerative diseases more broadly. The biomarker data collected—including CSF tau species, tau PET signals, and clinical measures—will provide valuable insights into tau biology and how anti-tau therapies affect pathological processes.
Maloney JA, et al. Anti-tau antibodies in clinical development for Alzheimer's disease and progressive supranuclear palsy. Expert Opinion on Investigational Drugs. 2023. ↩︎ ↩︎
Sigurdsson EM. Tau immunotherapy for neurodegenerative diseases: Progress and challenges. Nature Reviews Neurology. 2024. ↩︎ ↩︎
Courtroom J, et al. Tau-targeted immunotherapy for progressive supranuclear palsy. Lancet Neurology. 2024. ↩︎