posdinemab (JNJ-63733657) / J&J - LARVOL DELTA

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2032 ➔ Mar 2026

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

RESULTS FROM THE PHASE 2B AUTONOMY TRIAL OF ANTI-P-TAU MONOCLONAL ANTIBODY POSDINEMAB FOR EARLY ALZHEIMER'S DISEASE (ADPD 2026) - P2 | "Auτonomy trial results will provide valuable data to evaluate the hypothesis that interfering with tau spreading by targeting mid-domain tau can slow clinical decline in early AD."

P2b data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Drug Development. (PubMed, Alzheimers Dement) - P2 | "This analysis showed numerically higher overall SF rates amongst Black/African American population compared with other races evaluated. The Black/African American population had a higher proportion of SF due to the early AD clinical inclusion criterion compared with the White population; however, comparison is limited by the low number of Black/African American participants screened. Analysis of SF data from existing AD trials may help inform on recruiting a diverse study population by furthering understanding of any racial differences in underlying AD pathophysiology levels or co-morbidities contributing to cognitive impairment."

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

Biomarkers. (PubMed, Alzheimers Dement) - P2 | "In participants with intermediate tau and early AD, randomized in the Auτonomy trial, we map using a spatially unbiased analysis of tau PET, which cognitive domains are relatively most impacted by tau pathology across the brain. The ensuing maps reflect established brain functional organization. These findings demonstrate close association between presence/location of tangles and cognitive profile."

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

Alzheimer's Imaging Consortium. (PubMed, Alzheimers Dement) - P2 | "In participants with intermediate tau and early AD, randomized in the Auτonomy trial, we map using a spatially unbiased analysis of tau PET, which cognitive domains are relatively most impacted by tau pathology across the brain. The ensuing maps reflect established brain functional organization. These findings demonstrate close association between presence/location of tangles and cognitive profile."

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

Mechanistic Population Pharmacokinetic-Pharmacodynamic Model of the Tau-Targeted Antibody Posdinemab in Healthy Participants and Participants with Alzheimer's Disease. (PubMed, Clin Pharmacol Ther) - P1, P2 | "The PK-PD model-based simulations for fixed intravenous doses of 1,000 mg and 3,000 mg every 4 weeks predicted >90% reduction in tau seeds in ISF by Day 391 and Day 154, respectively, following treatment initiation. This model provides a physiologically relevant simulation-framework to investigate the impact of various posdinemab dose levels on PK-PD profiles, thereby supporting the clinical trial design of the Auτonomy study (NCT04619420)."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Feb 2026 ➔ Oct 2025

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

J&J discontinues Alzheimer’s study of tau-targeting antibody (Firstwordpharma Press Release) - "J&J plans to share a full evaluation of the results, which it said 'underscore the deep complexity of the disease,' with the scientific community' in due course."

Trial termination • Alzheimer's Disease

A Phase 1 Study of the Pharmacokinetics, Safety, and Tolerability of Posdinemab (JNJ-63733657) in Healthy Chinese Adults. (PubMed, J Clin Pharmacol) - P1 | "There were no new safety concerns. These results support further global development of posdinemab in AD."

Journal • P1 data • PK/PD data • Alzheimer's Disease • Back Pain • CNS Disorders • Musculoskeletal Pain • Pain

Johnson & Johnson showcases latest advancements in Alzheimer’s research at AAIC 2025 (J&J Press Release) - "Early data from robust Autonomy Phase 2b posdinemab trial demonstrate Company’s leadership in multimodal biomarkers and early detection...Johnson & Johnson...announced promising new data from its Alzheimer’s disease (AD) research program will be presented at the Alzheimer’s Association International Conference (AAIC), taking place July 27–31 in Toronto, Canada. Across 12 abstracts, the Company will share insight into how tau impacts brain function in early AD and reinforce the predictive strength of plasma biomarker pTau217 for tracking cognitive decline in at-risk individuals. The Company will also introduce findings from the Global Neurodegeneration Proteomics Consortium (GNPC), a public-private partnership co-founded by Johnson & Johnson and Gates Ventures, the private office of Bill Gates."

Clinical data • Alzheimer's Disease • Tauopathies And Synucleinopathies

NOVEL SCREENING METHODS USING COGNITIVE MEASURES IN AU ΤONOMY, A MULTICENTER PHASE 2 TRIAL OF ANTI -PHOSPHORYLATED TAU ANTIBODY POSDINEMAB IN EARLY ALZHEIMER'S DISEASE (ADPD 2025) - P2 | "Novel screening methods using cognitive measures in the Au τonomy study can inform future study designs. One practice test prior to baseline was sufficient to minimize learning effects. Flexibility with RBANS DMI allowed enrollment of less impaired particip ants without impacting overall population characteristics."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Developing Topics. (PubMed, Alzheimers Dement) - "The assay was initially created for CSF in 2017 and used as a pharmacodynamic marker in the Ph1 posdinemab trials, demonstrating substantial dose dependent reduction in CSF p217+tau...This test, marketed as Lucent AD p217, was evaluated in two large cohorts (n = 352 and 521, MCI/AD) against amyloid status (PET or CSF). The assay captured 100% of samples in the linear range and employs a 2-cutoff approach for identifying subjects with low/intermediate/high risk of amyloid positivity (ala Brum 2023), with observed 90.3% sensitivity, 91.3% specificity for identifying low and high-risk groups To accelerate clinical trials the assay is currently being used as a prescreening tool in multiple Janssen-sponsored Ph2 trials."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders

Johnson & Johnson's Posdinemab and Tau Active Immunotherapy Receive U.S. FDA Fast Track Designations for the Treatment of Alzheimer's Disease (PRNewswire) - "Johnson & Johnson...announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to posdinemab...The internally discovered mAb has shown the potential in targeting disease-associated phosphorylated tau in cerebrospinal fluid (CSF) from treated AD patients, and in blocking the development and spread of tau aggregates in non-clinical models of disease."

Fast track • Alzheimer's Disease

Phase 1 Studies of the Anti-Tau Monoclonal Antibody JNJ-63733657 in Healthy Participants and Participants with Alzheimer's Disease. (PubMed, J Prev Alzheimers Dis) - "In these Phase 1 trials, no safety or tolerability concerns were identified, and dose dependent reductions in p217+tau in the cerebrospinal fluid were demonstrated following administration of JNJ-63733657. The safety and biomarker profiles support the continued investigation of this compound for the slowing of disease progression in Alzheimer's disease."

Clinical • Journal • P1 data • Alzheimer's Disease • CNS Disorders

Study Design and Screening Experience from the Phase 2 AUΤONOMY Trial of Anti-P-tau Monocloncal Antibody Posdinemab for Early Alzheimer's Disease (CTAD 2024) - No abstract available

P2 data • Alzheimer's Disease • CNS Disorders

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Nov 2025 ➔ Feb 2026

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

Development, Validation, and Clinical Utility of the Janssen plasma p-tau 217+tau Simoa assay (AAIC 2024) - "The assay was initially created for CSF in 2017 and used as a pharmacodynamic marker in the Ph1 posdinemab trials, demonstrating substantial dose dependent reduction in CSF p217+tau... To accelerate clinical trials the assay is currently being used as a prescreening tool in multiple Janssen-sponsored Ph2 trials."

Clinical • Alzheimer's Disease • CNS Disorders

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Mar 2025 ➔ Nov 2025

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

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2025 ➔ Dec 2032

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

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Novel therapies for Alzheimer's disease (ECNP 2023) - "This year alone in the United States, there were at least 2 drugs that have been early approved by the FDA: Lecanemab, and Donanemab [5]...Current clinical trials testing anti-tau drugs include Janssen JNJ-63733657, a humanized IgG1 monoclonal antibody that binds to aggregated phosphorylated tau [1]...Also in development are anti-inflammatory drugs, such as that of Cassava Sciences, simufilam, which binds to an altered conformation of filamin A, which is related to elevated levels of beta amyloid [3] . The altered filamin A prevents various toxic signaling cascades as seen in the AD brain."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry

Passive tau-based immunotherapy for tauopathies. (PubMed, Handb Clin Neurol) - "At present, 12 anti-tau antibodies have entered clinical trials, and 7 of them are still in clinical testing for primary tauopathies and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, PNT00, and APNmAb005). Two other anti-tau monoclonal antibodies have been discontinued for the treatment of primary tauopathies, i.e., gosuranemab and tilavonemab. Further evidence will come from ongoing Phase I/II trials on passive immunotherapeutics for treating primary and secondary tauopathies."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

Clinical Development of Passive Tau-Based Immunotherapeutics for Treating Primary and Secondary Tauopathies. (PubMed, Expert Opin Investig Drugs) - "At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

A Study of JNJ-63733657 in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Completed | Trial primary completion date: Nov 2022 ➔ Aug 2022

Trial completion • Trial primary completion date

A Study of JNJ-63733657 in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open