Trontinemab (RG6102) is a brain-penetrant, anti-amyloid, bispecific and humanizedized IgG1-κ antibody, targeting to Aβ plaques and transferrin receptor 1 (TFR1). Trontinemab binds to fibrillar Aβ as well as Aβ plaques triggering plaque clearance by engaging immune cells on Alzheimer disease (AD) brain sections. Trontinemab also shows specific affinity to cynomolgus and human TFR1.
Trontinemab (0-5 μg/mL, 45 min)-decorated Aβ plaques by Fc receptor-mediated phagocytosis is a major mechanism of Aβ plaque clearance in primary human macrophages[3].
Trontinemab (20 µg/mL) binding to TFR induces first infusion reaction (FIRs) and stimulation of cytokine release via Fc-mediated effector functions in FcgR-humanized mice[3].
References:
[1]. Neațu M, et al. Monoclonal Antibody Therapy in Alzheimer's Disease. Pharmaceutics. 2023 Dec 29;16(1):60.
[2]. Trontinemab. IMGT/mAb-DB. [3]. Weber F, et al. Brain Shuttle Antibody for Alzheimer's Disease with Attenuated Peripheral Effector Function due to an Inverted Binding Mode. Cell Rep. 2018 Jan 2;22(1):149-162.
[4]. Roche H L. Brainshuttle AD: A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Participants with Prodromal or Mild to Moderate Alzheimer’s Disease[J]. ClinicalTrialsgov Identifier: NCT04639050, 2021, 2024.