XEN1101, A Differentiated KV7 Potassium Channel Modulator for the Treatment of Epilepsy

We are developing XEN1101, a differentiated Kv7 potassium channel modulator, for the treatment of epilepsy, major depressive disorder (MDD), and potentially other neurological disorders.

The Kv7 potassium channel mechanism has been clinically validated with ezogabine, an earlier generation Kv7 modulator that was approved by the FDA as an adjunctive treatment for adults with focal seizures with or without secondary generalization. XEN1101’s unique composition is chemically designed to improve upon potency, selectivity and pharmacokinetics, or PK, of ezogabine, and is not expected to have ezogabine’s composition-specific tissue pigmentation effects.

Phase 2b X-TOLE Clinical Trial

On October 4, 2021, Xenon reported positive topline results from the Phase 2b X-TOLE clinical trial, which evaluated the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in adult patients with focal epilepsy.

The trial met its primary efficacy endpoint with XEN1101 demonstrating a statistically significant and dose-dependent reduction from baseline in monthly (defined as 28 days) focal seizure frequency when compared to placebo (monotonic dose response; p<0.001). Additional primary and secondary measures included a pairwise comparison of each active dose to placebo and a responder analysis with the proportion of patients who achieved a 50% or greater reduction in monthly focal seizure frequency from baseline.

Read the full news release with topline data here: Xenon Pharmaceuticals Announces Positive Topline Results from Phase 2b ‘X-TOLE’ Clinical Trial of XEN1101 for the Treatment of Focal Epilepsy

Listen to replay of Management Call discussing X-TOLE topline results here: Webcast – October 4, 2021

View the accompanying slides here: Presentation slide deck

About Focal Seizures

A focal seizure is localized within the brain and can either stay localized or spread to the entire brain, which is typically categorized as a secondary generalized seizure. Focal seizures are the most common type of seizure experienced by people with epilepsy. The treatment of an individual patient with focal seizures is currently focused on reduction of seizure frequency, with seizure freedom as the ultimate goal. Focal seizures (simple, complex and secondary generalized tonic-clonic) account for approximately 60% of seizures (GlobalData Report 2017) of which approximately 33% are considered resistant to current treatments (Epilepsy Foundation). It is estimated that the addressable population in the United States could include approximately 460,000 adults and 70,000 pediatric patients with focal epilepsy.

Potential Non-Epilepsy Indications - Major Depressive Disorder (MDD)

Pre-clinical data were presented at ASENT 2021 that support the potential benefit of XEN1101 to treat depression and anhedonia.

Xenon is collaborating with the Icahn School of Medicine at Mount Sinai to facilitate an investigator-sponsored Phase 2 proof-of-concept, randomized, parallel-arm, placebo-controlled clinical trial of XEN1101 for the treatment of major depressive disorder (MDD) and anhedonia, which is expected start enrollment in October 2021.

In parallel, Xenon is planning a company-sponsored clinical study in MDD, which is supported by promising pre-clinical data with XEN1101 and clinical data generated from both an open-label study and a randomized, placebo-controlled clinical trial that explored the targeting of KCNQ channels as a treatment for MDD using ezogabine.