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

Drug-drug Interaction Study of Clemizole (EPX-100) in Healthy Participants (clinicaltrials.gov) - P1 | N=54 | Completed | Sponsor: Epygenix

New P1 trial

Progress report on new epilepsy treatments: A summary of the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII). II. Treatments in more advanced clinical development. (PubMed, Epilepsia) - "The treatments reviewed include bexicaserin, a selective 5-hydroxytryptamine (5-HT, serotonin) type 2C (5-HT2C) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB-101, a selective 5-HT2C receptor agonist investigated for the treatment of absence seizures and DEEs; elsunersen, an antisense oligonucleotide designed for the treatment of early-onset SCN2A-DEE; EPX-100 (clemizole hydrochloride), an antihistamine endowed with agonist activity at 5-HT2A and 5-HT2B receptors, repurposed as a treatment for DEEs; ES-481, an antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors containing the transmembrane AMPA receptor regulatory protein γ8 (TARP-γ8), under investigation for the treatment of drug-resistant epilepsy; ETX-101, a gene therapy in development for the treatment of SCN1A-positive Dravet syndrome; PrevEp-006 (intranasal seletracetam), a synaptic vesicle glycoprotein 2A..."

Journal • Absence Seizure Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Psychiatry • GRIN2B • NAV1 • SCN8A

ARGUS: A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Epygenix | Trial primary completion date: Apr 2026 ➔ Apr 2027

Trial primary completion date • CNS Disorders • Epilepsy

Harmony Biosciences Reports Q1 Financial Results and Confirms 2026 Net Revenue Guidance of Over $1 Billion; Reinforces 2026 Strategic Priorities (PharmiWeb) - "Pitolisant GR (gastro-resistant)...NDA submission on track for Q2 2026; anticipated PDUFA date in Q1 2027...Phase 3 registrational clinical trials ongoing in narcolepsy (ONSTRIDE 1) and idiopathic hypersomnia (IH) (ONSTRIDE 2)...anticipated PDUFA date in 2028...EPX-100 (clemizole hydrochloride)....potential PDUFA date in 2028."

FDA filing • PDUFA • Epilepsy • Narcolepsy

EPX-100-003: An Efficacy and Safety Study of Clemizole HCl in Patients with Lennox-Gastaut Syndrome (clinicaltrialsregister.eu) - P2/3 | N=62 | Not yet recruiting | Sponsor: Epygenix Therapeutics Inc.

New P2/3 trial • CNS Disorders • Epilepsy

ARGUS: A Study of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Participants with Dravet Syndrome (DS): Preliminary Results from the Open-label Extension Phase (AAN 2026) - "Preliminary effectiveness data demonstrates that participants who had at least 6-month OLE exposure to EPX-100 experienced, from DB Baseline to the first 6 months of the OLE, a CMS-28 mean reduction of −40.8% (SD: 44.9%) and median reduction of −49.2%. Conclusions The preliminary safety, tolerability and effectiveness data for EPX-100 as adjunctive therapy in participants with DS are encouraging."

Clinical • CNS Disorders • Epilepsy • Infectious Disease • Respiratory Diseases

EPX-100 as Adjunctive Therapy in Patients With Dravet Syndrome: Preliminary Results From the Open-Label Extension Phase of the ARGUS Study (AES 2025) - "The preliminary safety, tolerability and effectiveness data for EPX-100 as adjunctive therapy in patients with DS are encouraging. Updated safety and effectiveness data from the OLE phase will be presented."

Clinical • CNS Disorders • Epilepsy • Infectious Disease • Respiratory Diseases

A Drug-Drug Interaction Study of EPX-100 (Clemizole Hydrochloride) With Clinical Probe Substrates for Selected CYP Enzymes (AES 2025) - P3 | "Each part was designed as a 2-period fixed sequence, with Parts 1 and 2 involving administration of a single oral 80-mg dose of EPX-100 on Day 1 (Period 1), followed in Period 2 by either 200-mg oral itraconazole twice daily for 1 day followed by 200-mg oral itraconazole once daily for 4 days (Part 1), or 100-mg oral phenytoin 3 times daily for 14 days (Part 2)...During Period 2, 80-mg twice-daily doses of EPX-100 were administered for 18 days with a single oral dose of 40-mg omeprazole, 2-mg midazolam, or 100-mg bupropion on Days 12, 14, and 15, respectively... The drug-drug interaction profile with EPX-100 has been evaluated, and final results will be presented. EPX-100 was generally safe and well tolerated in this study of healthy participants. Findings from this study will inform other studies of EPX‑100, including the currently enrolling ARGUS study for DS (NCT04462770) and the LIGHTHOUSE study for LGS (NCT05066217)."

Clinical • CNS Disorders • Epilepsy • CYP2C19 • CYP3A4

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