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
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.
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.