An Anti-tau Therapeutic Antibody Etalanetug (E2814)
Sumit Rawal, Kristin R. Wildsmith, Jagadeesh Aluri, Takuya Yagi, Min‐Kun Chang, Hongmei Niu, Jin Zhou, Kanta Horie, Eri Takahashi, Peter D. W. Boyd, Larisa Reyderman
Abstract
BACKGROUND: Etalanetug (E2814), an anti-tau monoclonal antibody (mAb), is intended to inhibit spreading of pathologic tau species by binding to the microtubule binding region (MTBR). It is being developed as a potential disease-modifying therapy for Alzheimer disease. METHODS: This randomized, placebo-controlled study comprised of 2 parts: single ascending doses evaluating 5 etalanetug doses and multiple ascending doses evaluating 4 fixed doses in each cohort, 8 healthy subjects were randomized (3:1) to single etalanetug dose or placebo. Safety, pharmacokinetics (PK), antidrug antibodies (ADA), and target engagement (TE) were assessed. RESULTS: Etalanetug was safe and well-tolerated following single and multiple infusions. After single-dose and multiple-dose administration, serum exposure of etalanetug increased in a dose-related manner. Serum-to-cerebrospinal fluid (CSF) concentration ratio at week 12 was ∼0.1% to 0.3% and ∼1% following single and multiple dosing, respectively. Mean t ½ was ∼19 to 25 days independent of dose and time. etalanetug immunogenicity was minimal, with low titers and no impact on PK. TE was demonstrated; CSF concentrations of etalanetug between 100 and 200 ng/mL saturated binding of MTBR-tau299 at 82.1% and binding of MTBR-tau354 at 64.9%. CONCLUSION: Etalanetug presented an adequate safety and immunogenicity profile in healthy adults. PK was comparable to other mAbs. Etalanetug demonstrated target engagement by binding to MTBR tau species.