E2814 / Eisai, University College London - LARVOL DELTA

CLINICAL TRIAL DESIGN FOR CONCURRENT ANTI-AMYLOID AND ANTI-TAU ANTIBODY THERAPY FOR SPORADIC ALZHEIMER'S DISEASE (ADPD 2025) - "Conclusions The Results from this clinical trial will inform clinical dose selection of E2814, when co-administered with lecanemab. This will also provide further evaluation of the safety, as well as biomarker efficacy, over 18 months of E2814 treatment."

Clinical • Alzheimer's Disease • CNS Disorders • Aβ42

Eisai to Present the Latest Research Results, Including Long-Term and Real-Word Data on Lecanemab and Biomarkers for Alzheimer’s Disease at the AD/PD 2025 Annual Meeting (Eisai Press Release) - "Eisai...announced today the company will present the latest findings on lecanemab...at the 2025 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD)....The lecanemab data and additional research findings from Eisai’s AD portfolio will be featured in 16 presentations, including 6 oral presentations....These presentations will include the latest findings from real-world clinical evidence of lecanemab in the United States, efficacy and safety outcomes in apolipoprotein E ε4 (ApoEε4) heterozygous carriers and non carriers in the Phase III Clarity AD clinical study, and a subgroup analysis of Clarity AD open label extension study in the Asian region. In addition to the presentations, the clinical study design of a Phase II study of the anti-MTBR tau antibody E2814 in combination with lecanemab in people living with sporadic early AD...will be presented."

Biomarker • Clinical data • Clinical protocol • Alzheimer's Disease

Effect of anti-MTBR tau antibody E2814 on biomarkers specific to Alzheimer's disease tau pathology (JSNE 2025) - No abstract available

Biomarker • Alzheimer's Disease • CNS Disorders

Cerebellar ARIA in a Patient With an APP Duplication Treated With Lecanemab (AAN 2025) - "This participant was in the symptomatic cohort (CDR=0.5–1) and was to receive open-label lecanemab followed by double-blind E2814...Treatment included high dose IV dexamethasone, and a tapering outpatient course of oral dexamethasone...Cerebellar ARIA from βATAs is uncommon in sporadic AD. This subject's serious cerebellar ARIA-E/H may relate to an APP duplication, and possible evidence of CAA (microhemorrhage). βATA use in patients with similar genotypes or Down's syndrome should be approached carefully."

Clinical • Alzheimer's Disease • CNS Disorders • Hematological Disorders • Ventriculomegaly • APOE

Chimeric Antigen Receptors Discriminate Between Tau and Distinct Amyloid-Beta Species. (PubMed, bioRxiv) - "To investigate this, we engineered CARs based on AD antibodies targeting tau (E2814), Aβ (Lecanemab and Aducanumab), and truncated pyroglutamate form of Aβ (Aβp3-42; Donanemab and Remternetug). Our findings demonstrate that CARs can detect and discriminate between tau preformed fibrils (PFFs), Aβ 1-42 , and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques."

Journal • Alzheimer's Disease • CNS Disorders • Oncology

Developing Topics. (PubMed, Alzheimers Dement) - "Our results reveal the structural details of the key interactions between E2814 and the tau HVPGG motif, which adopts a U-shaped conformation upon binding to E2814. These findings provide atomic insights into the mechanism of E2814-mediated inhibition of tau aggregation and propagation."

Journal • CNS Disorders

A Study of E2814 With Concurrent Lecanemab Treatment in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Eisai Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

EISAI TO PRESENT UPDATED DUAL-ACTING LECANEMAB DATA, RESEARCH ON BLOOD BIOMARKERS FOR PREDICTING PRESENCE OF AMYLOID IN THE BRAIN AND NEW FINDINGS ON THE ANTI-MTBR (MICROTUBULE BINDING REGION) TAU ANTIBODY E2814 AT THE 17TH CLINICAL TRIALS FOR ALZHEIMER'S DISEASE CONFERENCE (CTAD) (PRNewswire) - "Eisai...announced today that the company will present the latest findings on its Alzheimer's disease (AD) pipeline and research, including our dual-acting, anti-amyloid beta (Aβ) protofibril antibody for the treatment of AD, lecanemab (generic name, U.S. brand name: LEQEMBI), at the Clinical Trials for Alzheimer's Disease Conference (CTAD)...Eisai will present data and research in 4 oral and 6 poster presentations at the meeting, and three symposiums on lecanemab will be held, including the importance of continued treatment of AD, a progressive neurodegenerative disease that begins before plaque deposition and continues after plaque removal. Additional findings from Eisai's robust Alzheimer's disease (AD) pipeline will be shared."

Biomarker • Clinical data • Alzheimer's Disease

Anti-tau therapeutic antibody, E2814, reduces early and late tau pathology biomarkers in patients with DIAD (CTAD 2024) - No abstract available

Biomarker • Clinical

Drug-induced cutaneous vasculitis from Alzheimer's disease trial medications: A case series from e2814 and literature review (CTAD 2024) - No abstract available

Clinical • Review • Alzheimer's Disease • CNS Disorders • Vasculitis

A Study of E2814 With Concurrent Lecanemab Treatment in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Eisai Inc.

Biomarker • New P2 trial • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - P1, P1/2, P2/3 | "E2814 demonstrated promising safety, PK and CSF target engagement profile in DIAD participants, and showed evidence of downstream effects on tangle-specific biomarker MTBR-tau243. Data supports further evaluation in the ongoing Ph2/3 DIAN-TU Tau NexGen Platform Study in DIAD (NCT05269394) and future exploration in sporadic AD."

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

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

A Study to Assess Safety and Target Engagement of E2814 in Participants With Mild to Moderate Cognitive Impairment Due to Dominantly Inherited Alzheimer's Disease (clinicaltrials.gov) - P1/2 | N=8 | Completed | Sponsor: Eisai Inc. | Recruiting ➔ Completed | N=13 ➔ 8 | Trial completion date: Jul 2025 ➔ May 2024 | Trial primary completion date: Jul 2025 ➔ May 2024

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

Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation (DIAN-TU) (clinicaltrials.gov) - P2/3 | N=197 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2027 ➔ Jul 2028 | Trial primary completion date: Jul 2027 ➔ Apr 2028

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

Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics. (PubMed, PCN Rep) - "The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments...The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients."

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

Crystal structure of E2814 bound to Tau (AAIC 2024) - "Our results reveal the structural details of the key interactions between E2814 and the tau HVPGG motif, which adopts a U-shaped conformation upon binding to E2814. These findings provide atomic insights into the mechanism of E2814-mediated inhibition of tau aggregation and propagation."

CNS Disorders

A Study to Assess Safety and Target Engagement of E2814 in Participants With Mild to Moderate Cognitive Impairment Due to Dominantly Inherited Alzheimer's Disease (clinicaltrials.gov) - P1/2 | N=13 | Recruiting | Sponsor: Eisai Inc. | Phase classification: P1b/2 ➔ P1/2

Phase classification • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APP

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

Efficacy of the murine version of E2814 in a validated AD brain seed-injection model in hTau mice (AAIC 2023) - "AD seed-injection in hTau mice has been further validated and can be used in therapeutic intervention studies. The murine version of E2814, 7G6-IgG2a, reduced pathological tau seeding and spreading in this model. The nonclinical data obtained here further supports E2814 being tested in clinical trials."

Preclinical • Alzheimer's Disease • CNS Disorders

Safety, Pharmacokinetics and Immunogenicity of Single and Multiple Ascending Doses of the Anti-Tau Therapeutic Antibody E2814: A Phase 1, First-In-Human (FIH) Study in Healthy Subjects (AAIC 2023) - "E2814 presented an adequate safety and immunogenicity profile in healthy adults. E2814 PK was comparable to that with other mAbs. These results support further development of E2814 as a potential disease-modifying therapy for AD."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

Safety, Pharmacokinetics and Immunogenicity of Single and Multiple Ascending Doses of the Anti-Tau Therapeutic Antibody E2814: A Phase 1, First-In-Human (FIH) Study in Healthy Subjects (AAIC 2023) - "E2814 presented an adequate safety and immunogenicity profile in healthy adults. E2814 PK was comparable to that with other mAbs. These results support further development of E2814 as a potential disease-modifying therapy for AD."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

Safety, Pharmacokinetics and Immunogenicity of Single and Multiple Ascending Doses of the Anti-Tau Therapeutic Antibody E2814: A Phase 1, First-In-Human (FIH) Study in Healthy Subjects (AAIC 2023) - "E2814 presented an adequate safety and immunogenicity profile in healthy adults. E2814 PK was comparable to that with other mAbs. These results support further development of E2814 as a potential disease-modifying therapy for AD."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

Safety, Pharmacokinetics and Immunogenicity of Single and Multiple Ascending Doses of the Anti-Tau Therapeutic Antibody E2814: A Phase 1, First-In-Human (FIH) Study in Healthy Subjects (AAIC 2023) - "E2814 presented an adequate safety and immunogenicity profile in healthy adults. E2814 PK was comparable to that with other mAbs. These results support further development of E2814 as a potential disease-modifying therapy for AD."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

E2814: an anti-tau therapy engages its CNS target and affects the downstream tangle-specific biomarker MTBR-tau243 in Dominantly Inherited Alzheimer’s Disease (AAIC 2023) - P1, P1b/2, P2/3 | "E2814 demonstrated promising safety, PK and CSF target engagement profile in DIAD participants, and showed evidence of downstream effects on tangle-specific biomarker MTBR-tau243. Data supports further evaluation in the ongoing Ph2/3 DIAN-TU Tau NexGen Platform Study in DIAD (NCT05269394) and future exploration in sporadic AD."

Biomarker • Alzheimer's Disease • CNS Disorders • Cognitive Disorders