etalanetug (E2814) / Eisai, University College London - LARVOL DELTA

FROM CLINICAL TRIALS TO THE DISH: IPSC-DERIVED NEURONAL MODELS FOR PRECISION DRUG SCREENING IN AD, PD, AND TAUOPATHIES (ADPD 2026) - "The LumiSTAR tri-culture platform can also serve as a Tau aggregate clearance model for therapeutic validation, as demonstrated using clinical candidates such as MAPTRx (Tau antisense oligonucleotide) and E2814 (Tau monoclonal antibody)... LumiSTAR establishes a robust high-throughput discovery platform with automated signal detection, high-content imaging, and robotic handling that dramatically reduces manual variability — and has already validated with multiple FDA-approved antibody therapeutics for AD/PD. This system provides a translational and scalable preclinical platform that enables precision drug validation, repurposing, and de novo therapeutic discovery for neurodegenerative disease."

Clinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2

CROSSING MOLECULAR BOUNDARIES: AN IMMUNOTHERAPEUTIC SIMULTANEOUSLY TARGETING AMYLOID-Β, TAU, AND Α-SYNUCLEIN AMYLOID AGGREGATES (ADPD 2026) - "Lecanemab, Etalanetug, and Prasinezumab biosimilars served as benchmarks. Amyl-2 has nanomolar affinity for amyloid aggregates, inhibits aggregation across Aβ, Tau, and α-synuclein, and promotes robust phagocytic clearance of amyloid aggregates. Amyl-2 presents a strong potential to act as a disease-modifying therapeutic across amyloid-driven neurodegenerative diseases. Ongoing optimization to enhance binding affinities, improve brain permeability and mitigate amyloid-related imaging abnormalities (ARIA) strengthens the translational promise of this platform technology for AD, PD, and other amyloid-mediated diseases."

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=438 | Active, not recruiting | Sponsor: Washington University School of Medicine | N=210 ➔ 438 | Trial primary completion date: Sep 2019 ➔ Sep 2023

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=210 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2016 ➔ Mar 2017

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=438 | Recruiting | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Recruiting

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jul 2022 ➔ Oct 2027 | Trial primary completion date: Jul 2022 ➔ Oct 2027

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Recruiting | Sponsor: Washington University School of Medicine | Completed ➔ Recruiting | N=194 ➔ 490 | Trial completion date: Mar 2020 ➔ Jul 2022 | Trial primary completion date: Nov 2019 ➔ Jul 2022

Biomarker • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Oct 2027 ➔ Jul 2028 | Trial primary completion date: Oct 2027 ➔ Apr 2028

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=194 | Completed | Sponsor: Washington University School of Medicine | Recruiting ➔ Completed | N=490 ➔ 194 | Trial completion date: Mar 2021 ➔ Mar 2020 | Trial primary completion date: Dec 2020 ➔ Nov 2019

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=210 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=210 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Recruiting | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Recruiting

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=438 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=210 | Recruiting | Sponsor: Washington University School of Medicine | Trial primary completion date: Jan 2017 ➔ Sep 2019

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=210 | Recruiting | Sponsor: Washington University School of Medicine

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=490 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2023 ➔ Mar 2021 | Trial primary completion date: Sep 2023 ➔ Dec 2020

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (clinicaltrials.gov) - P2/3 | N=210 | Recruiting | Sponsor: Washington University School of Medicine | Trial primary completion date: Jul 2014 ➔ Jan 2017

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

A Study of E2814 With Concurrent Lecanemab Treatment in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=105 | Active, not recruiting | Sponsor: Eisai Inc. | Trial completion date: Feb 2027 ➔ Aug 2027

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

Drug Development. (PubMed, Alzheimers Dement) - P2/3 | "This trial will investigate potential benefits of anti-tau etalanetug with lecanemab, given as background therapy."

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

Drug Development. (PubMed, Alzheimers Dement) - "The baseline characteristics for DIAN-TU-001 Tau NexGen trial were consistent with clinical features of asymptomatic and symptomatic DIAD. These characteristics were also generally consistent between Cohort 1 and Cohort 2 with the exception of clinical, and cognitive scores."

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

Drug Development. (PubMed, Alzheimers Dement) - "The baseline imaging characteristics of the DIAN-TU-001 trial population reveal significant spatial differences in tau PET and vMRI between symptomatic and asymptomatic DIAD subjects. Baseline amyloid levels were consistent with the stage of disease in DIAD. Symptomatic DIAD subjects exhibit higher tau SUVR values and greater atrophy, particularly in the parietal cortex, compared to asymptomatic DIAD subjects. These tau PET findings corroborate the distinctly different pattern of tau deposition in DIAD vs. sporadic AD, as previously reported. Future analysis will elucidate the therapeutic effects of E2814 and lecanemab on this pathological tau spread."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Drug Development. (PubMed, Alzheimers Dement) - "Lecanemab was generally well-tolerated. The most common adverse events of lecanemab in the DIAD population were ARIA-H, headache, ARIA-E, and infusion-related reactions. DIAD population may have a higher rate of cerebral amyloid angiopathy with ARIA rates between heterozygotes and homozygotes in sporadic AD."

Clinical • Journal • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Pain

Drug Development. (PubMed, Alzheimers Dement) - P2/3 | "Lecanemab reduced amyloid PET in symptomatic participants with DIAD at Week 24. The reduction in amyloid PET was in line with predictions based on PK/PD modeling developed from sporadic AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Drug Development. (PubMed, Alzheimers Dement) - "Our results suggest that E2814 may slow down pathological spread of tau by directly preventing tau uptake into neurons and accelerating the removal of MTBR-tau via microglial clearance pathway."

Journal • Alzheimer's Disease • CNS Disorders