Eisai EU Limited
Clinical Pharmacology & Translational Medicine
Pharmacist by training, and with previous work experience in diverse aspects of the Pharmacy practice –including Community, Clinical and Production Pharmacy– Pau focused his professional career path in the field of Clinical Pharmacology (CP) and PK/PD Modelling & Simulation since 2006. Pau Aceves holds a Master’s Degree in PK/PD Modelling & Simulation from the University of Manchester in the UK. His MSc project was on an "Exploratory Quantitaitve Systems Pharmacology Model (QSP) of the Squalene Synthase Inhibitor Lapaquistat Acetate". Pau has a total of 15 years of QCP experience in the design, analysis and reporting of clinical studies in a wide range of therapeutic areas across all phases of drug development. Currently, at Eisai, he is focused in the area of Neurology and more specifically Alzheimer's Disease. In addition to having worked on CP-type studies (i.e. food effect, bioavailability, DDIs), Pau also has a wide range of experience in other modalities, including: First-in-Human (SAD/MAD), Proof-of-Mechanism (PoM), Proof-of-Concept (PoC), Positron Emission Tomography (PET), and complex combination (or umbrella-type) studies; as well as experience interacting with regulatory agencies (FDA, EMEA) at various stages of drug development. Pau always enjoys devising innovative strategies to streamline and maximize the value of clinical development programmes by combining efficient clinical strategies with fit-for-purpose PK/PD analysis methodologies (e.g. Population PK/PD, Physiologically Based Pharmacokinetic modelling, and Quantitative Systems Pharmacology approaches).

Presenter of 1 Presentation

SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SINGLE AND MULTIPLE ASCENDING DOSES OF THE NOVEL ANTI-TAU THERAPEUTIC ANTIBODY E2814: A PHASE 1, FIRST-IN-HUMAN STUDY IN HEALTHY VOLUNTEERS

Session Type
SYMPOSIUM
Date
Sun, 20.03.2022
Session Time
09:05 AM - 11:05 AM
Room
ONSITE: 113
Lecture Time
10:35 AM - 10:50 AM

Abstract

Aims

E2814 is a novel anti-tau therapeutic monoclonal antibody (mAb) that inhibits the propagation of pathological tau species by binding to the microtubule binding region (MTBR). This study evaluated safety, pharmacokinetics (PK), immunogenicity and target engagement (TE) of single and multiple doses of E2814.

Methods

This randomized, placebo-controlled, Phase 1 study evaluated 3 single ascending doses (SAD) and 2 multiple ascending doses (MAD) in healthy adults. Subjects (n=8/cohort) received single or multiple (every 4 weeks) 1-hour IV infusions of E2814 (or placebo). PK was characterized in blood and CSF samples. TE was evaluated in CSF by measuring E2814-bound and free MTBR-tau proxy peptide concentrations (MTBR-tau354 and MTBR-tau299 containing epitopes in R4 and R2, respectively).

Results

E2814 has an adequate single and multiple dose safety profile. No dose limiting events were observed. E2814 exposures (Cmax, AUC) increased in a dose-related manner. E2814 acumulation index on multiple dosing (Rac=1.5) was consistent with its elimination half-life (22 days). The serum-to-CSF ratio was 0.2%. TE was dose related and sustained over time with maximum TE levels of 45% and 76% in the SAD and 47% and 62% in the MAD for MTBR-tau354 and MTBR-tau299, respectively. In the SAD, 2 out of 24 subjects had transient low level anti-drug antibody (ADA) titers by the last study day; no post dose ADA were detected in the MAD.

Conclusions

E2814 presented an adequate safety, PK and immunogenicity profile in healthy adults. Increase in TE was dose-related and sustained. These results support further development of E2814 as a disease-modifying therapy for AD.

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