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

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

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

New P1 trial

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2; N=420; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial completion date: Mar 2025 ➔ Nov 2025

Clinical • Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • MRI • Tau PET

Development of immunoprecipitation - two-dimensional liquid chromatography - mass spectrometry methodology as biomarker read-out to quantify phosphorylated tau in cerebrospinal fluid from Alzheimer disease patients. (PubMed, J Chromatogr A) - P1 | "This enabled the quantification of total p217+tau in CSF leading to the confirmation that in addition to reductions in free p217+tau levels total p217+tau levels were also reduced following administration of the tau mAb JNJ-63733657, correlating with the previous measurement with the PT3 x PT82 Simoa assay. An orthogonal sample clean-up using offline TiO/ZrO combined with 1DLC-TQMS was developed to confirm the presence of mono-ptau (pT217) tryptic peptides in CSF."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • CSF P-tau

Autonomy: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2; N=420; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • MRI • Tau PET

[VIRTUAL] A MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF THE ANTI-PHOSPHO-TAU ANTIBODY JNJ-63733657 (CTAD 2020) - "JNJ-63733657 to date shows a favorable clinical profile and biomarker response following multiple dose administration. A phase 2 study of JNJ-63733657 in subjects with early AD is planned."

Clinical • 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=420; Not yet recruiting; Sponsor: Janssen Research & Development, LLC

Clinical • New P2 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • MRI • Tau PET

A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease (clinicaltrials.gov) - P1; N=72; Completed; Sponsor: Janssen Research & Development, LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease (clinicaltrials.gov) - P1; N=72; Active, not recruiting; Sponsor: Janssen Research & Development, LLC; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of JNJ-63733657 in Healthy Japanese Participants (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Janssen Pharmaceutical K.K.; Recruiting ➔ Completed

Clinical • Trial completion

A Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Anti-Phospho-Tau Antibody JNJ-63733657 in Healthy Subjects (AAIC 2019) - "JNJ-63733657 exhibits clearance of toxic tau species in preclinical models and to date shows a favorable clinical profile and biomarker response following single dose administration."

Clinical • PK/PD data