Benzinga | Feb 22, 2021 04:03PM EST

Xenon Pharmaceuticals To Present XEN1101 Sata At ASENT 2021

Pre-Clinical Data Support the Potential Benefit of XEN1101 to Treat Depression and Anhedonia

XEN1101, in Combination with Other Anti-Seizure Medications, Provides Robust Efficacy in Animal Models

Topline Data from XEN1101 Phase 2b X-TOLE Clinical Trial in Adult Focal Epilepsy on Track for Third Quarter of 2021

BURNABY, British Columbia, Feb. 22, 2021 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (NASDAQ:XENE), a neurology-focused biopharmaceutical company, announced that new pre-clinical data and a clinical overview of its XEN1101 program will be presented at ASENT 2021, the virtual annual meeting of the American Society for Experimental Neurotherapeutics. XEN1101 is a differentiated Kv7 potassium channel modulator being developed for the treatment of epilepsy and potentially other neurological disorders. The X-TOLE Phase 2b clinical trial is currently underway studying the efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in approximately 300 adult patients with focal epilepsy.

Today, Xenon hosted a symposium presentation entitled, "Addressing an Unmet Medical Need in Adult Focal Epilepsy with XEN1101, a Novel Kv7 Modulator," which provided an update on XEN1101's clinical development to date and outlined a number of its unique pharmaceutical properties including:

* Proven anti-seizure Kv mechanism of action

* Efficacious as monotherapy and in combination with other anti-seizure medications (ASMs) in pre-clinical models

* Well-tolerated in Phase 1 clinical studies, and low drop-out and high conversion to open label extension in blinded Phase 2b clinical trial to date

* Once daily (QD) evening dosing, low daily dose and no dose titration in ongoing Phase 2b clinical trial

* No significant drug-drug-interactions (DDI) predicted

Dr. Simon Pimstone, Xenon's Chief Executive Officer, stated, "Our presentations at ASENT 2021 summarize our view that XEN1101 could potentially represent a highly differentiated profile in the focal epilepsy space with important "ease-of use" attributes that we believe are meaningful for physicians and patients combined with a favorable safety/tolerability profile to date. We are looking forward to the read-out of topline results from our ongoing Phase 2b X-TOLE clinical trial, anticipated in the third quarter of this year."

Other presentations at ASENT 2021 include:

* A pipeline presentation entitled "Anticonvulsant Effects of the Differentiated Kv7 Channel Potentiator XEN1101 in Combination with Commonly Used Anti-Seizure Drugs" includes new pre-clinical data showing that combining sub-efficacious doses of XEN1101 and other ASMs provided robust efficacy in animal models, which was not an apparent DDI effect. In addition, the combination dosing was well tolerated in the dose ranges explored. This work suggests that XEN1101 may be well suited for use as a monotherapy or applied in a rational polypharmacy setting to treat seizures. Data were presented combining XEN1101 with commercially approved ASMs, including lacosamide, levetiracetam, cenobamate, phenytoin, and valproic acid.

* A symposium presentation entitled, "Kv7 Modulators in Epilepsy and Depression" outlines the scientific rationale, pre-clinical data, and clinical work to date supporting the use of Kv7 modulators for the treatment of depression and anhedonia. Pre-clinical work demonstrates a regulatory role for the KCNQ-type potassium channels in reversing depressive phenotypes following social defeat stress. Results from clinical studies using the first generation, Kv7 potassium channel modulator, ezogabine, supported the hypothesis that increasing KCNQ channel signaling can be beneficial for patients with depression and anhedonia. Major depression is a common co-morbidity of persons with epilepsy and significantly impacts their quality of life.

* A pipeline presentation entitled "Depression and Anhedonia: Acute Pre-clinical Efficacy for XEN1101, a Differentiated Kv7 Potassium Channel Modulator" included new pre-clinical data from the Forced Swim Test and Progressive Ratio Test animal models, which support a potential benefit of XEN1101 in mood disorders. Of note, the efficacious doses and plasma concentrations from the pre-clinical depression, anhedonia, and seizure studies overlap and occur at plasma levels achieved during a multi-ascending Phase 1 clinical trial suggesting that the current doses being used in the ongoing XEN1101 Phase 2b clinical trial to treat epilepsy may have a beneficial impact on depressed mood.

Mr. Ian Mortimer, Xenon's President and Chief Financial Officer said, "In addition to the ongoing clinical development of our XEN1101 Phase 2b X-TOLE study in adult focal epilepsy, we have been exploring the use of XEN1101 in other non-epilepsy indications. Based on our analysis and these promising pre-clinical data, we expect to initiate a Phase 2 proof-of-concept clinical trial this year examining XEN1101 in major depressive disorder (MDD) and anhedonia in partnership with academic collaborators at the Icahn School of Medicine at Mount Sinai. We look forward to updating you with further details in the coming months."

All of Xenon's presentations at ASENT 2021 will be made available on the Xenon website.