Authors :
Presenting Author: Alexandra Zanin-Zhorov, PhD – Equilibre Pharmaceuticals
Wei Chen, Ph.D. – Equilibre Biopharmaceuticals; Julien Moretti, Ph.D. – Equilibre Biopharmaceuticals; Melanie Nyuydzefe, Miss – Equilibre Biopharmaceuticals; Firas Fahoum, M.D. – Tel Aviv Sourasky Medical Center, Israel; Pavel Klein, M.D. – Mid-Atlantic Epilepsy and Sleep Center, Maryland; Asfi Rafiuddin, D.O. – Northeastern Regional Epilepsy Group; Claude Steriade, M.D. – NYU Langone Health, New York; Robert Wechsler, M.D., Ph.D., FAES, FAAN – Consultants in Epilepsy and Neurology PLLC, Idaho; Michael Sperling, M.D. – Farber Institute for Neuroscience (Thomas Jefferson University Hospitals), Philadelphia; Felix Benninger, M.D. – Rabin Medical Center; Nathan Fountain, M.D. – UVA Health (University of Virginia Medical Center), Virginia; Dana Ekstein, M.D., Ph.D. – Hadassah Medical Organization; Nicola Maggio, M.D., Ph.D. – Chaim Sheba Medical Center; Amy Melsaether, M.D. – Equilibre Biopharmaceuticals; Ya-El Mandel-Portnoy, Ph.D. – Equilibre Biopharmaceuticals; Samuel Waksal, Ph.D. – Equilibre Biopharmaceuticals Graviton Bioscience Corporation
Rationale:
EQU-001 is a novel anti-inflammatory candidate for adjunctive therapy to treat seizures in patients with epilepsy. The findings from a placebo-controlled, double-blind, randomized trial conducted to evaluate safety and tolerability of EQU-001 (NCT05063877) demonstrated favorable safety profile and 60 mg daily dose of EQU-001 reduced seizure frequency after twelve weeks of treatment (Fahoum et al. Abstract # 1562257). The exploratory outcome of the study was to evaluate the levels of pro-inflammatory cytokines including IL-17, IL-1b, TNF-a, IL-6, IL-23, IL-12p70, IL-10 and IFN-g in peripheral blood samples over the course of the treatment with EQU-001.Methods:
Peripheral blood samples from clinical trial subjects (eight treated and two placebo subjects per cohort) were collected in heparin tubes at Day 0 before dosing begins (pre-dose) and after two, four, eight, and twelve weeks of treatment with 10 mg, 20 mg, 40 mg, or 60 mg of EQU-001. After centrifugation, plasma samples were transferred into cryovials and stored at -80oC. The levels of cytokines were determined by using Meso Scale Discovery (MSD) platform-based multi-plex ELISA. % Change was calculated as (after-dosing value/pre-dosing -1) X 100. Statistical analysis was performed by using Two-way ANOVA, Fisher’s LSD test.Results:
The measured cytokines such as IL-17, IL-1b, IL-6, TNF-a, IL-12p70, IL-10, IFN-g, and IL-23 were detected in majority of the samples collected from clinical trial subjects. Oral administration of EQU-001 (60 mg) significantly (p < 0.01) reduced the plasma levels of IL-17 and IL-1