Xyzagen, Inc. Presented Promising Kv7 Channel Opener Prodrug Research at American Epilepsy Society Annual Meeting
Nashville, TN, December 15, 2022
Xyzagen, Inc., a leading pharmacokinetics consultancy and boutique CRO, presented research on its Kv7 channel opener prodrug program at the American Epilepsy Society (AES) Annual Meeting. The presentation showcased Xyzagen’s work in developing XYG204, a water-soluble prodrug of ezogabine that effectively blocks seizures through both oral and parenteral administration routes.
Presentation Details
“Our presentation at the AES Annual Meeting represents our mission to continue to develop improved therapies for patients with epilepsy and other neurological disorders,”
said Christopher Crean, Founder and CEO of Xyzagen, Inc. “The promising results from our Kv7 research program demonstrate that our prodrug approach can effectively overcome the limitations that led to the market withdrawal of ezogabine, potentially offering patients a more reliable and convenient treatment option.”
Key Research Highlights
- XYG204 demonstrates solubility in water and alcohols at concentrations at least 200 mg/mL at physiological acceptable pH, with stability under acidic conditions against forming ezogabine for more than 11 days at room temperature
- 5 mg/mL 1N HCl at 37C was stable through 11 days while ezogabine essentially fully degraded by Day 4
- The prodrug effectively releases ezogabine (EZG) following administration through multiple routes, including oral (PO), intramuscular (IM), and subcutaneous (SC)
- When administered intramuscularly at 75 mg/kg in rats, XYG-204 provided nearly complete protection (97.6%) in the maximal electroshock (MES) seizure model by 1 hour post-dose and full protection from 2-8 hours
- XYG-204 maintains sustained therapeutic levels of ezogabine for extended periods, with plasma concentrations remaining above 10 μM for 8 hours in rat studies
- The prodrug approach addresses key limitations of ezogabine, including poor solubility and stability to support parenteral administration for acute use neuronal hyperexcitability situations, such as a panic attack associated with anxiety or functional nonepileptic seizures or in instances of more severe status epilepticus.
Background on Ezogabine
Ezogabine (EZG) was a first-in-class Kv7 channel opener approved in June 2011 as adjunctive therapy for partial onset seizures. Despite its efficacy, the drug was removed from the market in June 2017 due to challenges including its three-times-daily dosing regimen and concerns about bluish skin discoloration and potential retinal pigment changes. These pigmentary changes were associated with dimers of ezogabine and its primary metabolite. The XYG204 prodrug approach aims to address these limitations while preserving the therapeutic benefits of Kv7 channel modulation and expanding the routes of administration since EZG is unstable in light and water.
About Xyzagen
Xyzagen augments a client’s pharmacology and pharmacokinetics drug development team. As a leading pharmacokinetics consultancy and contract research organization with wet lab and rodent vivarium facilities, Xyzagen is able to push model informed drug development into its First-in-Rat® and First-in-Mouse® discovery platforms as well as support late-stage clinical noncompartmental PK, PopPK, and Quantitative Medicine.
Our knowledge in pharmacology/pharmacogenomics and in vitro/in vivo pharmacokinetics allows the client to expand their core scientific team during the critical period of candidate selection up to the PreIND meeting and through clinical development and the preNDA meeting. We’re a boutique organization which allows for small clients and CROs to work directly with experts.
