Anti-Tau Antibody Etalanetug Reduces Novel Tau Biomarker in Phase Ib/II Study

New data presented at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference showed that the anti-tau antibody etalanetug (E2814) reduced levels of a novel cerebrospinal fluid (CSF) and plasma biomarker of tau pathology in individuals with dominantly inherited Alzheimer’s disease (DIAD). Etalanetug is designed to bind to the microtubule-binding region (MTBR) of tau and inhibit its seeding and propagation.

Largest Reductions Observed at 9 Months

The Phase Ib/II study (E2814-103) included 7 participants with DIAD, 3 of whom underwent tau PET imaging. Investigators reported previously that tau PET signals in these individuals were stabilized or trended toward decrease after treatment, suggesting inhibition of tau propagation.

In the new analysis, researchers evaluated eMTBR-tau243, a fluid biomarker consisting of tau fragments that include amino acid residue 243 and the MTBR region. The biomarker correlates strongly with tau PET and reflects the formation of neurofibrillary tangles.

Etalanetug reduced CSF eMTBR-tau243 by 62% at 3 months and by 89% at 9 months. Plasma eMTBR-tau243 decreased by 78% at 3 months and more than 90% at 9 months. According to the press release, these findings support the agent’s proposed mechanism of inhibiting tau seeding and spread.

Biomarker May Enable Blood-Based Assessment of Tau Pathology

Investigators noted that development of eMTBR-tau243 allows tau pathology to be monitored using a blood test. The biomarker has demonstrated strong correlation with tau PET in both plasma and CSF and may facilitate measurement of disease activity in clinical trials.

Ongoing Trials Evaluating Etalanetug

Etalanetug is currently being studied in two clinical programs:

• Tau NexGen Phase II/III Trial in DIAD, conducted by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) and evaluating etalanetug added to standard-of-care lecanemab.
• Phase II Study 202, a global randomized trial in early sporadic Alzheimer’s disease, also evaluating etalanetug in combination with lecanemab.

The agent received Fast Track designation from the US Food and Drug Administration in September 2025.