trontinemab (RG6102) / Roche, Royalty - LARVOL DELTA

NEXT-GENERATION NEURODEGENERATIVE DISEASES THERAPEUTICS WITH STRONG BINDING FOR AMYLOID-BETA/TAU/ALPHA-SYNUCLEIN AGGREGATES, REDUCED RISK OF ARIA, AND IMPROVED BRAIN DELIVERY. (ADPD 2026) - "Benchmark comparisons were made with Lecanemab, Trontinemab and other mAbs. Fusion to a new Fc domain activated phagocytosis of Aβ fibrils to levels comparable to Lecanemab while reducing TNF-α release by 50%. These results pave the way for the development of a next-generation therapeutic solution for mixed NDD pathologies like AD/PD."

Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • TNFA

DATA-DRIVEN APPROACHES TO REPRESENTATIVE US ENROLMENT PLANNING IN THE TRONTIER STUDIES OF TRONTINEMAB IN EARLY SYMPTOMATIC ALZHEIMER'S DISEASE (ADPD 2026) - "Characterizing AD trial sites and modelling the screening funnel with real-world data provided valuable tools for data-driven US site landscaping and representative enrollment planning in the TRONTIER studies."

Alzheimer's Disease • CNS Disorders

ADVANCING IMMUNOTHERAPY WITH BISPECIFIC ANTIBODIES THAT CROSS THE BLOOD-BRAIN BARRIER (ADPD 2026) - "1A) were engineered based on either the anti-amyloid-beta antibody Bapineuzumab or Lecanemab, combined with TfR-binding domains...Preclinical and clinical data indicated that, at therapeutic dosing, monovalent TfR-binding (as in Trontinemab) or moderate rather than high TfR affinity favoured efficient delivery. Bispecific antibodies offer a promising approach to AD therapy by improving brain penetration and treatment efficacy. Their distinct route of brain entry also reduces vascular antibody accumulation, a likely contributor to adverse effects such as amyloid-related imaging abnormalities (ARIA), that are commonly observed with conventional amyloid-beta antibodies."

Bispecific • Alzheimer's Disease • CNS Disorders

TRAVELLER MASTER PRE-SCREENER STUDY UPDATE: BROADENING RECRUITMENT INTO TRONTIER 1 AND 2, PHASE III STUDIES IN EARLY SYMPTOMATIC ALZHEIMER'S DISEASE (ADPD 2026) - " TRAVELLER is a global, multicentre, master pre-screening study designed to assess potential eligibility for Roche AD trials, including Phase III TRONTIER 1 and 2 studies evaluating trontinemab in early symptomatic AD... Initiatives such as the TRAVELLER study have the potential to streamline pre-screening, reduce participant burden by early exclusion of ineligible participants, and facilitate inclusive enrollment in AD clinical trials compared to traditional single-study screening approaches."

P3 data • Alzheimer's Disease • CNS Disorders • Dementia

DETERMINING AN ECONOMICALLY JUSTIFIABLE PRICE FOR TRONTINEMAB IN EARLY ALZHEIMER'S DISEASE (ISPOR 2026) - "Patients treated with Trontinemab received increases in QALYs, however at considerable cost increases. Ultimately, despite increased reported efficacy compared to existing anti-amyloid options, trontinemab's cost effectiveness is subject to substantial uncertainty as results are based on a select report from very early clinical testing."

Alzheimer's Disease • CNS Disorders • Dementia

WN45447: A Efficacy and Safety Study of Trontinemab in Participants With Early Symptomatic Alzheimers Disease (MCI to Mild Dementia Due to AD) (clinicaltrialsregister.eu) - P2/3 | N=247 | Recruiting | Sponsor: F. Hoffmann-La Roche AG

New P2/3 trial • Alzheimer's Disease • CNS Disorders • Dementia

Drug Development. (PubMed, Alzheimers Dement) - P1/2 | "Results from the completed Cohorts 1-4 in Part 1 of the Brainshuttle™ AD study suggest that early and pronounced effects on several key markers of AD pathophysiology can be achieved with trontinemab treatment with very limited incidence of ARIA."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Drug Development. (PubMed, Alzheimers Dement) - P1/2 | "Utilizing active transport mechanisms, such as the Brainshuttle™ technology, to achieve rapid and efficient amyloid clearance may unlock the full potential of disease modification with Aβ-targeting monoclonal antibodies in AD. Active transport mechanisms could also be used in other large molecule delivery systems to improve distribution of drugs as well as efficacy and safety profiles."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Drug Development. (PubMed, Alzheimers Dement) - P1/2 | "The recent Phase Ib/IIa interim results suggest that rapid and robust amyloid plaque clearance and fluid biomarker changes may be achieved with low ARIA incidence. The overall favorable safety and interim biomarker results to date support the rationale for moving into the pivotal Phase III studies TRONTIER 1 and TRONTIER 2. These studies will provide the opportunity to assess whether treatment with trontinemab slows disease progression in people living with early symptomatic AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia

Drug Development. (PubMed, Alzheimers Dement) - P1/2 | "Preliminary results from the ongoing Brainshuttle™ AD study suggest that rapid and deep amyloid reduction can be achieved in most participants at 1.8 and 3.6 mg/kg doses within ≤28 weeks. New biomarker data will be presented to further evaluate trontinemab's continued development as a potential AD treatment."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Brainshuttle™ AD: New interim results of a randomized, placebo-controlled Phase Ib/IIa proof-of-concept study with trontinemab, a novel anti-amyloid monoclonal bispecific antibody for the treatment of Alzheimer's disease (CTAD 2025) - No abstract available

Clinical • P1/2 data • Alzheimer's Disease • CNS Disorders

TRONTIER 1 and 2: Rationale and design of two identical Phase III trials to assess the efficacy and safety of trontinemab in early symptomatic Alzheimer's disease (CTAD 2025) - No abstract available

Clinical • P3 data • Alzheimer's Disease • CNS Disorders

SYMPOSIUM 1: Trontinemab's path to Phase III – From proof-of-concept in the ongoing Brainshuttle™ AD study to the pivotal studies TRONTIER 1 and TRONTIER 2 in people with early-stage symptomatic Alzheimer's disease (CTAD 2025) - No abstract available

P3 data • Alzheimer's Disease • CNS Disorders

Modeling Brain Exposure and Efficacy of Next-Generation Brainshuttle Antibodies (CTAD 2025) - "Developing a quantitative systems pharmacology model to predict brain exposure and efficacy of receptor-mediated transcytosis antibodies such as trontinemab, offering insights into amyloid clearance mechanisms."

Clinical

Trontinemab Shows Promise for Treatment of Alzheimer Disease in New Data at CTAD (Psychiatric Times) - "The Brainshuttle AD study has so far demonstrated a reduction in amyloid levels below 24-centiloid for 92% of patients treated, passing a key disease threshold to determine presence of amyloid plaques in the brain. Biomarker analysis also indicated potential for trontinemab to affect tau accumulation...Less than 5% of patients in the Brainshuttle study have shown amyloid-related imaging abnormalities that indicate swelling or bleeding in the brain...Results presented at CTAD focused on cohorts of participants in the phase 1b/2a study receiving trontinemab 1.8 mg/kg or 3.6 mg/kg every 4 weeks for 28 weeks. At the higher dose, participants showed especially rapid and robust amyloid lowering....The current Brainshuttle AD study is still ongoing, with a planned primary completion date of June 2030."

P1/2 data • Alzheimer's Disease

TRONTIER 2: A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2028 ➔ Jun 2028

Trial completion date • Alzheimer's Disease • CNS Disorders • Dementia

BP42155: 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 (clinicaltrials.gov) - P1/2 | N=285 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Mar 2028 ➔ Jun 2030 | Trial primary completion date: Mar 2028 ➔ Jun 2030

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • APOE

TRONTIER 1: A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2028 ➔ Jun 2028

Trial completion date • Alzheimer's Disease • CNS Disorders • Dementia

TRONTIER 2: A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Dementia

TRONTIER 2: A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Alzheimer's Disease • CNS Disorders • Dementia

TRONTIER 1: A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Alzheimer's Disease • CNS Disorders • Dementia

Roche presents new insights in Alzheimer’s disease research across its diagnostics and pharmaceutical portfolios at AAIC (Roche Press Release) - P1b/2a | N=285 | Brainshuttle AD (NCT04639050) | Sponsor: Hoffmann-La Roche | "New data on the latest results for trontinemab from the completed dose-expansion part of the 1.8 mg/kg and 3.6 mg/kg cohorts from the ongoing Phase Ib/IIa Brainshuttle AD study continued to show rapid and robust reduction of amyloid plaques in the brain as measured by amyloid positron emission tomography (PET). In the 3.6 mg/kg cohort, trontinemab reduced amyloid levels below the 24 centiloid positivity threshold in 91% of participants (n=49/54) after 28 weeks of treatment; 72% (n=39/54) achieved deep clearance below 11 centiloids....Trontinemab continues to show a favourable safety and tolerability profile. Amyloid-related imaging abnormalities-edema/effusion (ARIA-E) continued to be observed in <5% of participants (blinded data; N=4/149 across 1.8 and 3.6mg/kg dose cohorts)."

P1/2 data • Alzheimer's Disease

Design of the Phase III TRONTIER 1 and 2 studies of trontinemab in early symptomatic Alzheimer’s disease featured, with initiation planned in 2025 (Roche Press Release) - "In a 90-minute Featured Research session, designs were shared for the Phase III studies, TRONTIER 1 and 2, which will initiate later this year, investigating the efficacy and safety of investigational trontinemab in people with early Alzheimer’s disease. The primary endpoint will measure the change in cognition and function based on the Clinical Dementia Rating – Sum of Boxes scale after 18 months of treatment. Secondary endpoints will include assessments of cognition, function, behavioural symptoms, and quality of life. A pre-screening study, TRAVELLER, based on a brief clinical assessment and a plasma biomarker, which will be identified using the Elecsys pTau217 test, has also been initiated, to enable broader community outreach and extend access to these trials to more diverse populations representative of Alzheimer’s disease."

Clinical protocol • Alzheimer's Disease • CNS Disorders

Translational minimal physiologically based pharmacokinetic model for transferrin receptor-mediated brain delivery of antibodies. (PubMed, MAbs) - "Clinical validation using human PK data from plasma and CSF for the monovalent anti-TfR bsAb trontinemab demonstrated good predictive performance without major model recalibration. The availability of the TfR mPBPK model is envisaged to provide better understanding of the relationship between TfR binding affinity, dose, and brain exposure, which would lead to more robust selection of lead candidates and efficacious dosing regimens."

Journal • PK/PD data

IXICO assists FDA clearance of new Alzheimer’s blood-based diagnostic (Vox) - "Today, the company announced that its 'gold standard' analysis of PET scans had helped one of its clients, Fujirebio, obtain FDA approval for its breakthrough new blood test for AD - thus further extending IXICO 's neuroimaging biomarker capabilities beyond clinical trials to the analysis and validation of diagnostic biomarkers...later this year, two potentially blockbuster new Alzheimer's treatments are hopefully moving into Phase 3 clinical trials - namely Bristol Myers Squibb’s Cobenfy and Roche’s trontinemab. Here, advanced digital imaging is also the quickest, cheapest, safest and most effective way to understand, monitor and treat brain disorders, alongside playing a vital role in obtaining FDA approval and conducting post-marketing surveillance."

Diagnostic • FDA approval • New P3 trial • Alzheimer's Disease