Skip To Main Content

Trontinemab (RG6102)

Modality: Brainshuttle™ bispecific 2+1 amyloid-beta targeting monoclonal antibody

Disease State: Alzheimer's Disease (AD)

Summary

Trontinemab is a bispecific 2+1 Brainshuttle™ amyloid-beta (Aβ)-targeting immunoglobulin G1 (IgG1) monoclonal antibody (mAb) engineered for transferrin receptor 1 (TfR1)-mediated transport across the blood–brain barrier (BBB).

Clinical Trials

Alzheimer's Disease (AD)
Phase	Enrollment Status	Title
Phase III	Recruiting	A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (TRONTIER 1)	View Details
Phase III	Recruiting	A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (TRONTIER 2)	View Details
Non-interventional	Recruiting	Screening Study to Determine Individuals With Potential Trial Eligibility for Alzheimer's Disease Studies (TRAVELLER)	View Details

Proposed Mechanism of Action

Trontinemab’s proposed mode of action for the treatment of Alzheimer’s disease:

Trontinemab is a bispecific 2+1 Brainshuttle™ Aβ-targeting IgG1 mAb engineered for TfR1-mediated transport across the BBB.^1-4

Trontinemab is a Novel Bispecific 2+1 Brainshuttle™ Aβ-Targeting mAb that Crosses the BBB Via TfR1-Mediated Transcytosis

Preclinical data with a murine surrogate of trontinemab.
Image not to scale.

Brainshuttle™ MoA video
Discover Brainshuttle™, an innovative technology to achieve rapid and deep amyloid clearance which may unlock the full potential of disease modification in AD.^5-8

Proposed MOA of Trontinemab

Kulic L, Alcaraz F, Klein G, et al. Latest interim results from the Brainshuttle™ AD study, a phase Ib/IIa study of trontinemab in people with Alzheimer’s disease. Paper presented at: Clinical Trials on Alzheimer's Disease (CTAD) conference; October 30, 2024; Madrid, Spain
Hultqvist G, Syvänen S, Fang XT, et al. Bivalent brain shuttle increases antibody uptake by monovalent binding to the transferrin receptor. Theranostics. 2017;7(2):308-318. doi:10.7150/thno.17155
Kulic L, Alcaraz F, Klein G,et al. Trontinemab — from early preclinical groundwork to the clinical validation of the Brainshuttle™ platform. Paper presented at: AD/PD 2025: International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders; April 3, 2025; Vienna, Austria.
Grimm HP, Schumacher V, Schäfer M, et al. Delivery of the Brainshuttle™ amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans. MAbs. 2023;15(1):2261509. doi:10.1080/19420862.2023.2261509
Jeffries WA, Brandon MR, Hunt SV, Williams AF, Gatter KC, Mason DY. Transferrin receptor on endothelium of brain capillaries. Nature. 1984;312(5990):162-163. doi:10.1038/312162a0
Niewoehner J, Bohrmann B, Collin L, et al. Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron. 2014;81(1):49-60. doi:10.1016/j.neuron.2013.10.061
Sade H, Baumgartner C, Hugenmatter A, Moessner E, Freskgård PO, Niewoehner J. A human blood-brain barrier transcytosis assay reveals antibody transcytosis influenced by pH-dependent receptor binding. PLoS One. 2014;9(4):e96340. doi:10.1371/journal.pone.0096340
Weber F, Bohrmann B, Niewoehner J, et al. Brain shuttle antibody for Alzheimer's disease with attenuated peripheral effector function due to an inverted binding mode. Cell Rep. 2018;22(1):149-162. doi:10.1016/j.celrep.2017.12.019

Looking for more information?

Reach out to a Genentech Medical Science Liaison near you, or connect with the contact center.

Connect with an MSL

Submit a Request

Call the Trial Information Support Team: 1-888-662-6728 Hours: Monday-Friday, 5am-5pm PT

Aβ
Amyloid-beta
AD
Alzheimer’s disease
BBB
Blood–brain barrier
Fc domain
Fragment crystallizable domain
IgG1
Immunoglobulin G1
TfR1
Transferrin receptor 1