clemizole (EPX-100) / Paragon Biosci - LARVOL DELTA

ARGUS: A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Epygenix | Phase classification: P2 ➔ P3 | N=100 ➔ 150 | Trial completion date: May 2026 ➔ May 2029

Enrollment change • Phase classification • Trial completion date • CNS Disorders • Epilepsy

An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P3 | N=260 | Recruiting | Sponsor: Epygenix | Not yet recruiting ➔ Recruiting | Phase classification: P2 ➔ P3 | N=24 ➔ 260 | Trial completion date: Feb 2025 ➔ Nov 2029 | Trial primary completion date: Feb 2025 ➔ Nov 2026

Enrollment change • Enrollment open • Phase classification • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

A 20-Week Multicenter, Randomized, Double-Blind (DB), Placebo-Controlled, Phase 3 Trial (EPX 100-003) of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in patients with Lennox-Gastaut Syndrome (LGS) (AAN 2025) - "This is an upcoming Phase 3 study to determine effectiveness and safety of EPX-100 in patients with LGS."

Clinical • P3 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Harmony Biosciences Reports Strong 2024 Financial Results and Reiterates 2025 Net Revenue Guidance; Highlights 2025 Catalysts in Sleep/Wake and Fragile X Syndrome Development Programs (Businesswire) - "Topline data readout from Phase 3 registrational trial of ZYN002 in FXS (RECONNECT study) in Q3 2025 with potential PDUFA date in 2026; Phase 3 registrational trial in 22q11.2 deletion syndrome (22q) to initiate in 2025...EPX-100 (clemizole hydrochloride}....Topline data readout from Phase 3 registrational trial in Dravet syndrome (ARGUS Study) anticipated in 2026; Topline data for Phase 3 registrational trial in patients with Lennox-Gastaut syndrome (LIGHTHOUSE study) anticipated in 2026."

New P3 trial • P3 data: top line • Epilepsy • Fragile X Syndrome

ARGUS: A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Epygenix | Trial completion date: Dec 2024 ➔ May 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children With Lennox Gastaut Syndrome (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Epygenix | Trial completion date: Jul 2023 ➔ Feb 2025 | Trial primary completion date: Jul 2023 ➔ Feb 2025

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

ARGUS: EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Epygenix | Completed ➔ Recruiting | Trial completion date: Oct 2023 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Dec 2024

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

ARGUS: EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome (clinicaltrials.gov) - P2 | N=100 | Completed | Sponsor: Epygenix | Trial completion date: Dec 2024 ➔ Oct 2023 | Trial primary completion date: Dec 2024 ➔ Oct 2023 | Recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

EPX-100 as an Adjunctive Therapy in Dravet Syndrome: Phase 1 and Phase 2 Randomized, Double-blind, Placebo-controlled Trials (AES 2022) - "EPX-100 was well-tolerated with all adverse events being mild or moderate, with drowsiness being the most common finding in Phase 1 trials. EPX-100 has the potential to be a safe and effective treatment option for patients with DS."

Clinical • P1 data • P2 data • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation

ARGUS: EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Epygenix | Trial completion date: Sep 2023 ➔ Dec 2024 | Trial primary completion date: Sep 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

ARGUS: EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Epygenix | N=60 ➔ 100

Enrollment change • CNS Disorders • Epilepsy

Epygenix Therapeutics Receives FDA Orphan Drug Designation for EPX-100 For Treatment of Ohtahara Syndrome (EIN Presswire) - "Epygenix Therapeutics...announces that the U.S. Food & Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to EPX-100 to treat Ohtahara syndrome. EPX-100 was previously granted Rare Pediatric Disease (RPD) designation by the FDA for Ohtahara and has also received FDA ODD and RPD designations for Dravet syndrome and Lennox-Gastaut syndrome (LGS)."

Orphan drug • CNS Disorders • Epilepsy

Epygenix Therapeutics to Provide Update at the Dravet Syndrome Foundation (DSF) 2022 Conference (EIN News) - "Epygenix Therapeutics...will present at the Dravet Syndrome Foundation’s 5th Biennial Conference on June 23-25, 2022 in Fort Worth, Texas....'We look forward to sharing a presentation updating our progress with EPX-100, our lead therapeutic compound, and the ongoing ARGUS trial for Dravet syndrome patients.'"

Clinical • CNS Disorders • Epilepsy

First Canadian Participant Dosed in ARGUS Trial, A Phase 2 Potentially Pivotal Study of EPX-100 Treatment of Dravet Syndrome (GlobeNewswire) - "Epygenix Therapeutics...announces the dosing of the first Canadian study participant in the Phase 2 potentially pivotal ARGUS trial....The primary goal of the ARGUS trial is to determine the efficacy of EPX-100 (clemizole hydrochloride) towards decreasing the number of countable convulsive seizure frequency in children and adults with Dravet syndrome who are 2 years and older."

Trial status • CNS Disorders • Epilepsy

EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children With Lennox Gastaut Syndrome (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Epygenix | N=36 ➔ 24 | Initiation date: Feb 2022 ➔ Oct 2022

Enrollment change • Trial initiation date • CNS Disorders • Epilepsy

Health Canada Issues No Objection Letter to Initiate the ELEGANSE Trial With EPX-100 to Treat Lennox-Gastaut Syndrome (Yahoo Finance) - "Epygenix Therapeutics, Inc...announced today that Health Canada issued a No Objection Letter (NOL) to proceed with the ELEGANSE trial for the treatment of Lennox-Gastaut Syndrome (LGS) with EPX-100 (Clemizole HCl). This ELEGANSE trial will evaluate the efficacy and safety of EPX-100 with patients suffering from LGS."

New trial • CNS Disorders • Epilepsy

LGS: EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children With Lennox Gastaut Syndrome. (clinicaltrials.gov) - P2; N=36; Not yet recruiting; Sponsor: Epygenix

Clinical • New P2 trial • CNS Disorders

ARGUS: EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Epygenix; Trial completion date: Oct 2022 ➔ Sep 2023

Clinical • Trial completion date • CNS Disorders • Epilepsy • MRI

Epygenix Therapeutics Announces FDA Acceptance of IND to Initiate a Clinical Trial of EPX-100 to Treat Lennox-Gastaut Syndrome (PRNewswire) - "Epygenix Therapeutics, Inc...announced today that the U.S. Food and Drug Administration ('FDA') has accepted the Company's Investigational New Drug ('IND') application to initiate A 20-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Patients with Lennox-Gastaut Syndrome."

New trial • CNS Disorders • Epilepsy

Health Canada Grants No Objection Letter to Epygenix Therapeutics to Proceed With ARGUS Trial for the Treatment of Dravet Syndrome (PRNewswire) - "Epygenix Therapeutics, Inc...pleased to announce that the company's ARGUS trial with EPX-100 (Clemizole Hydrochloride) in patients with Dravet syndrome (DS) has been approved by Health Canada. The No Objection Letter (NOL) from Health Canada is equivalent to a 'May You Proceed' letter from the FDA. It provides the acknowledgement of EPX-100's drug candidacy and the authority to proceed with a 20-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of EPX-100 as Adjunctive Therapy."

New P2 trial • CNS Disorders • Epilepsy

A Trial of EPX-100 (Clemizole Hydrochloride) as an Add-on Therapy in Children With Dravet Syndrome (clinicaltrials.gov) - P2; N=56; Recruiting; Sponsor: Epygenix; N=24 ➔ 56; Trial primary completion date: Oct 2021 ➔ Oct 2022

Clinical • Enrollment change • Trial primary completion date

Structural basis for human TRPC5 channel inhibition by two distinct inhibitors. (PubMed, Elife) - "These structures suggest that both clemizole and HC-070 exert the inhibitory functions by stabilizing the ion channel in a non-conductive closed state. These results pave the way for further design and optimization of inhibitors targeting human TRPC5."

Journal • CNS Disorders • Depression • Mood Disorders • Nephrology • Psychiatry • Renal Disease

Synthesis and therapeutic potential of imidazole containing compounds. (PubMed, BMC Chem) - "The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their..."

Journal • Review • Immunology • Inflammatory Arthritis • Oncology • Pain • Rheumatoid Arthritis • Rheumatology

Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome. (PubMed, Expert Opin Drug Discov) - "Experimental data and results from initial clinical studies have brought attention to several drugs with various mechanisms of action including: ataluren (a suppressant of premature stop codons; under clinical evaluation), EPX-100, EPX-200, fenfluramine (serotonin modulators), soticlestat (an 24-hydroxylase cholesterol enzyme inhibitor), SPN-817 (an inhibitor of acetylcholinesterase), verapamil (a voltage-dependent calcium channel inhibitor) and STK-001 (an antisense oligonucleotide). The latter is scheduled for clinical evaluation."

Journal • CNS Disorders • Epilepsy

Therapeutic advances in Dravet syndrome: a targeted literature review. (PubMed, Expert Rev Neurother) - "Stiripentol was associated with responder rates (greater than 50% reduction in convulsive seizure frequency) of 67%-71%, when added to valproic acid and clobazam; cannabidiol was associated with responder rates of 43%-49% (48%-63% in conjunction with clobazam), and fenfluramine of 54%-68% across studies. Therapies in development include soticlestat, ataluren, verapamil, and clemizole, with strategies to treat the underlying cause of DS, including gene therapy and antisense oligonucleotides beginning to emerge from preclinical studies. Despite the challenges of drug development in rare diseases, this is an exciting time for the treatment of DS, with the promise of new efficacious and well-tolerated therapies, which may pave the way for treatment advances in other DEEs."

Journal • CNS Disorders • Epilepsy • Gene Therapies • Rare Diseases