Data from Phase 1b/2 Study 103 (NCT04971733) presented at AAIC 2026 in London show that etalanetug reduced plasma eMTBR-tau243 by more than 90% at nine months in DIAD patients, with plasma levels closely tracking CSF changes, supporting its potential as a less invasive tool for monitoring tau pathology in future trials.
Written By: Anamika Koshti, Pharm D
Reviewed By: Pharmacally Editorial Team
On July 14, 2026, Eisai presented new findings on etalanetug (E2814) at the Alzheimer’s Association International Conference (AAIC) 2026 in London. Data from the Phase Ib/II Study 103 (NCT04971733) showed that the investigational anti-MTBR tau antibody reduced plasma eMTBR-tau243, a biomarker of tau tangle pathology in Alzheimer’s disease (AD), by more than 90% after nine months in patients with dominantly inherited Alzheimer’s disease (DIAD). The results were presented during the Featured Research Session, Mechanisms Beyond Amyloid: Etalanetug Reduces Tau Tangle-Specific Plasma Biomarker eMTBR-tau243 in Dominantly Inherited Alzheimer’s Disease.
What Is eMTBR-tau243?
eMTBR-tau243 is a novel fluid biomarker composed of tau protein fragments containing the microtubule-binding region (MTBR) and amino acid residue 243, with endogenous cleavage at residue 256. It is generated during the formation of neurofibrillary tangles, a hallmark of AD, and closely correlates with tau PET imaging in both plasma and cerebrospinal fluid (CSF).
Unlike plasma phosphorylated tau biomarkers such as p-tau217, p-tau181, and p-tau231, which may include tau originating from peripheral tissues, plasma eMTBR-tau243 appears to specifically reflect brain-derived tau pathology. The biomarker was largely absent in healthy adults and detected only in patients with DIAD, supporting its disease specificity.
Why a Plasma Biomarker Matters
Monitoring tau pathology currently relies on CSF sampling or tau PET imaging, both of which are invasive or resource-intensive. A blood-based biomarker that accurately reflects brain tau pathology could provide a more accessible method for monitoring disease progression and treatment response. The eMTBR-tau243 assay was developed with this objective and may offer a practical alternative to CSF testing during clinical development.
Key Findings from Study 103
Following etalanetug treatment:
- CSF eMTBR-tau243 decreased by 62% at three months and 89% at nine months.
- Plasma eMTBR-tau243 decreased by 78% at three months and more than 90% at nine months, closely mirroring CSF reductions.
- Plasma eMTBR-tau243 remained largely absent in healthy adults, confirming its specificity for disease-related brain tau pathology.
- Plasma p-tau217, p-tau181, p-tau231, and total tau (t-tau) increased after treatment, an effect attributed to peripheral non-CNS tau binding to etalanetug, which slows its degradation rather than reflecting disease progression.
- Etalanetug reduced multiple CSF phosphorylated tau biomarkers and p-tau205, a marker of late-stage tau pathology (T2 biomarker), representing the first reported reduction of CSF p-tau205 by an anti-tau therapy in DIAD.
Together, these findings indicate that etalanetug is acting on its intended biological target by modifying tau pathology in the brain.
Etalanetug’s Development Programme
Etalanetug was discovered through a collaboration between Eisai and University College London and is designed to bind the MTBR of tau, inhibiting the seeding and propagation of tau pathology. The therapy received FDA Fast Track Designation in September 2025 and is being evaluated in two ongoing studies: the Tau NexGen Phase II/III trial (NCT05269394), assessing etalanetug plus lecanemab (LEQEMBI) in DIAD under the DIAN-TU, and the global Phase II Study 202 (NCT06602258) in early sporadic AD.
What This Means for Future Development?
The ability to monitor etalanetug’s biological activity through a blood draw, rather than CSF sampling or tau PET imaging, could reduce participant burden and make it more practical to assess tau pathology in larger clinical trials. The close correspondence between plasma and CSF eMTBR-tau243 reductions suggests that plasma eMTBR-tau243 could serve as a less invasive biomarker for monitoring disease-related brain tau pathology during treatment.
Together, the close correspondence between plasma and CSF changes, combined with the biomarker’s specificity for brain-derived tau pathology, supports the potential of plasma eMTBR-tau243 as a practical biomarker for monitoring disease progression and treatment response in ongoing and future clinical studies.
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About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.