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PubMed · 42693483

A third-generation, high-affinity biparatopic anti-tau antibody inhibits intracellular tau aggregation seeded by Alzheimer's brain extracts.

Eric Hatterer·Lucile Broyer·Sara Pecoraro·Fabien Cusin·Naz Simsek·John J Breve·Mathieu Clavel·Kevin L Batenburg·Bart Klein·Thuur Zuidweg·Kristin Piché·Jeremie Bourguignon·Margot Bonnet-Gamard·Pauline Malinge·Franck Gueneau·Valery Moine·Nadia Anceriz·Krzysztof Masternak·Nicolas Fischer·Torleif Tollefsrud Gjølberg·Jenny Skjermo Telstad·Gaia Calamera·Simone Mester·Wiep Scheper·Wilma D J Van de Berg·Jean-Philippe Courade
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Abstract

BACKGROUND: Tau immunotherapy has recently shown clinical promise but required high dosing. We developed NIDB-3101, a novel third-generation, high-affinity anti-tau biparatopic antibody designed for superior tau binding, aggregation inhibition, and extended half-life. METHODS: NIDB-3101 binds tau's microtubule-binding region and C-terminal domains. Various binding and cellular functional assays using recombinants, but more importantly human AD extracts were used to assess NIDB-3101 benefits. Half-life mutations impact was assessed via FcRn binding and cellular assays recycling. RESULTS: NIDB-3101 exhibited sub-nanomolar affinity, binding a broad spectrum of pathological tau species in AD homogenates, inhibited AD extracts-induced cellular effect compared to benchmark antibodies. Mutations enhanced hFcRn-mediated cellular recycling. CONCLUSIONS: NIDB-3101 captures a broad spectrum of pathological tau species leading to strong cellular efficacy using human AD extracts, supporting further clinical development as a potential disease-modifying therapy for AD and related tauopathies.

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tau ProteinsHumansAlzheimer DiseaseBrainAnimalsProtein Aggregation, PathologicalAlzheimer’s diseaseBiparatopic antibodyBispecific antibodyFcRnHalf-life extensionImmunotherapySeeded aggregationTauJournal Article

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Eric Hatterer, Lucile Broyer, Sara Pecoraro, Fabien Cusin, Naz Simsek, John J Breve, Mathieu Clavel, Kevin L Batenburg, Bart Klein, Thuur Zuidweg, Kristin Piché, Jeremie Bourguignon, Margot Bonnet-Gamard, Pauline Malinge, Franck Gueneau, Valery Moine, Nadia Anceriz, Krzysztof Masternak, Nicolas Fischer, Torleif Tollefsrud Gjølberg, Jenny Skjermo Telstad, Gaia Calamera, Simone Mester, Wiep Scheper, Wilma D J Van de Berg, Jean-Philippe Courade. 2026-08-22. A third-generation, high-affinity biparatopic anti-tau antibody inhibits intracellular tau aggregation seeded by Alzheimer's brain extracts.. https://doi.org/10.1186/s13195-026-02155-9

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