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

Spatial Determinants of Posdinemab's Effect on Tau PET (CTAD 2026) - No abstract available

Tau PET

SYMPOSIUM 2: When Target Engagement Is Not Enough: Lessons from Posdinemab on Bridging Tau Biology to Clinical Outcomes (CTAD 2026) - No abstract available

Clinical • Clinical data

Rethinking tau-targeted therapy in Alzheimer's disease: Toward a dual biomarker strategy. (PubMed, Alzheimers Dement) - "Conversely, marked p-tau217 lowering with posdinemab was not accompanied by clinical benefit...This framework applies across antibodies, antisense oligonucleotides, and other biologic tau-directed strategies. Future trials should test joint biomarker-clinical response functions rather than importing thresholds from anti-amyloid therapy, and should prespecify adequately powered analyses of sex, population background, disease stage, and other potential modifiers."

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

Safety And Tolerability Of Posdinemab In Early Alzheimer's Disease: Results From The Phase 2 Autonomy Trial (AAIC 2026) - No abstract available

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

Consistent Cognitive And Functional Outcomes Across Prespecified Subgroups In The Autonomy Trial Evaluating Posdinemab In Early AD (AAIC 2026) - No abstract available

Tau PET Results From The Phase 2b Autonomy Trial Evaluating Posdinemab In Early Alzheimer's Disease (AAIC 2026) - No abstract available

P2b data • Tau PET • Alzheimer's Disease • CNS Disorders

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=523 | Terminated | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Terminated; Posdinemab did not achieve statistical significance in slowing clinical decline

Trial termination • 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 | "Posdinemab was not superior to placebo in slowing clinical decline in early AD. Study results will provide valuable insights regarding tau targeting in AD."

P2b data • 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 2032 ➔ Mar 2026

Trial completion date • 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