Journey from Aquarium-to-Bedside to Treat Genetic Epilepsies

Emerging from stealth mode with a pipeline of FDA and EMA Orphan Drug Designation candidates, Epygenix Therapeutics Inc. is poised to become the first biopharmaceutical company to commercialize epilepsy drugs discovered in zebrafish. Epygenix Therapeutics’ six lead drug candidates were identified in a high-throughput phenotype-based drug screening system using a unique zebrafish model developed in the laboratory of Professor Scott C. Baraban, PhD at the University of California, San Francisco (UCSF). Founded in 2016, Epygenix Therapeutics has grown to become a clinical stage precision medicine company targeting epilepsies, such as Dravet syndrome, Lennox-Gastaut Syndrome, infantile spasm, and STXBP1-related (Ohtahara) disorders.

Dravet syndrome, a catastrophic childhood epilepsy with an incidence of 1 in 27,000, is the first of several potential indications for which Epygenix Therapeutics (EPX) compounds may be therapeutic.  Preclinical identification of new therapies for Dravet syndrome, as well as other genetic forms of epilepsy, are hampered by a lack of good experimental animal models. In contrast, an innovative phenotype-based drug screening system using a Dravet syndrome zebrafish model (scn1lab mutation) which closely recapitulates the human pathophysiology and pharmacology allowed for rapid identification of efficacious drug candidates with a unique mechanism of action.

While most antiepileptic drugs currently available target GABA receptors or ion channels, EPX compounds selectively target serotonin signaling pathways. “With the zebrafish screening assays identifying both repurposed compounds (EPX-100, -200 and -300) as well as novel chemical entities (EPX-101, -102, -103), Epygenix is well-positioned to develop precision medicine options for many rare genetic epilepsy syndromes,” says Dr. Hahn-Jun Lee, M. Sc., Ph.D., CEO of Epygenix Therapeutics.

Touted as an ‘aquarium-to-bedside’ translational program, EPX-200 (lorcaserin hydrochloride) was the first example of a drug discovered in a Dravet syndrome zebrafish model that went on to show efficacy in multiple Dravet syndrome patients. EPX-100 (clemizole HCl), a drug with a long safety history initially marketed in the 1950s, is the current lead compound in the Epygenix Therapeutics development pipeline. Acting as a serotonin receptor agonist, EPX-100, recently completed a comprehensive series of IND-enabling acute and chronic toxicology, pharmacokinetic, and genotoxicity studies.  “Unlike many current therapies for Dravet syndrome, this clean preclinical safety profile was followed by a highly successful Phase I study confirming safety and tolerability in healthy humans and therefore EPX-100 is now positioned as a potential “best-in-class” drug candidate for Dravet syndrome patients,” says Alex K. Yang, J.D., LL.M., Chair of the Board at Epygenix Therapeutics.

To move EPX drug candidates to the market in a timely manner, Epygenix is now rolling out a multi-national and multi-center clinical trial of EPX-100 as adjunctive therapy in patients with Dravet syndrome, known as the ARGUS trial with clinical sites in the U.S., U.K., and Canada. To participate in the ARGUS trial, pre-specified eligibility criteria should be met. At a minimum, patients are to be 2 to 30 years of age at time of enrollment with clinical and genetic evidence of Dravet syndrome, seizures not adequately controlled by current antiepileptic drugs, and 4 or more convulsive seizures documented during a 4-week Observational baseline period. More information on the ARGUS trial can be found on (NCT04462770).

At Epygenix Therapeutics, our ultimate goal is to develop safe and transformative therapies for those suffering with Dravet Syndrome and other genetic epilepsies.

For more information about the ARGUS trial, please contact Epygenix Therapeutics, Inc. at 201-940-7377. You can also contact via email to Dr. Hahn-Jun Lee or Dr. Dave Luke, Senior Consultant.  

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