Xenon Pharmaceuticals Reports Second Quarter 2022 Financial Results and Provides Corporate Update

Xenon remains on track to initiate the XEN1101 Phase 3 program within second half of this year

Cash runway extended into 2026 following successful completion of equity offering in June

Conference Call at 4:30 pm ET Today

BURNABY, British Columbia, Aug. 09, 2022 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a neurology-focused biopharmaceutical company, today reported financial results for the second quarter ended June 30, 2022 and provided a corporate update.

Mr. Ian Mortimer, Xenon’s President and Chief Executive Officer, stated, “With the benefit of a strong balance sheet, which was further bolstered by a recent equity offering, we are sharply focused on executing our clinical development plans across our pipeline. This past quarter marked several important milestones for our XEN1101 program. Following a positive ‘End-of-Phase 2’ meeting with the FDA, we are excited to advance our XEN1101 Phase 3 program, starting with the initiation of ‘X-TOLE2’ in the second half of this year. Additionally, we have strong scientific rationale supporting the use of XEN1101 to address primary generalized tonic clonic seizures, and we are looking forward to initiating our Phase 3 ‘X-ACKT’ clinical trial in PGTCS. Ultimately, our goal is to deliver a new, differentiated therapeutic option for epilepsy patients.”

Mr. Mortimer continued, “Our team has completed additional sub-analyses of efficacy data from our Phase 2b ‘X-TOLE’ trial, which further support our Phase 3 development plans for XEN1101, including a ‘time course to efficacy’ analysis demonstrating that all doses of XEN1101 rapidly reduced the frequency of focal onset seizures within one week compared to placebo. Additionally, within our analysis of the open label extension (OLE) population, we are seeing seizure frequency continuing to improve after the double-blind period with patients experiencing increased periods of seizure freedom.”

Mr. Mortimer added, “In addition, our Phase 2 ‘X-NOVA’ study is underway examining XEN1101 in major depressive disorder in parallel with an investigator-led Phase 2 MDD study led by our collaborators at Mount Sinai. Our Phase 3 ‘EPIK’ study is also ongoing examining the use of XEN496 in a rare, pediatric epilepsy called KCNQ2-DEE, and is anticipated to be completed in 2023.”

Highlights and Anticipated Milestones

Proprietary Programs

XEN1101 for Epilepsy (Focal Onset Seizures)XEN1101 is a differentiated Kv7 potassium channel opener being developed for the treatment of epilepsy and major depressive disorder (MDD). In October 2021, Xenon announced positive results from its Phase 2b X-TOLE clinical trial, which evaluated the clinical efficacy, safety and tolerability of XEN1101 administered as an adjunctive treatment for adult patients with focal epilepsy. In June 2022, Xenon announced the successful completion of an End-of-Phase 2 (EOP2) meeting with the U.S. Food & Drug Administration (FDA). Based on the EOP2 meeting, Xenon and the FDA aligned on key elements of the Phase 3 program to support a New Drug Application (NDA) submission. Xenon plans to submit an NDA upon completion of the first XEN1101 Phase 3 clinical trial (X-TOLE2), if successful, and use the existing data package from the Phase 2b X-TOLE clinical trial along with additional safety data from other clinical trials to meet regulatory requirements.

Xenon plans to initiate two identical Phase 3 clinical trials called X-TOLE2 and X-TOLE3, which are designed closely after the Phase 2b X-TOLE clinical trial. X-TOLE2 is expected to be initiated in the second half of 2022 followed by the initiation of X-TOLE3 and both studies will run in parallel. These multicenter, randomized, double-blind, placebo-controlled trials will evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in approximately 360 patients per study with focal onset seizures (FOS). The primary efficacy endpoint is the median percent change (MPC) in monthly seizure frequency from baseline through the double blind period (DBP) of XEN1101 compared to placebo. On completion of the DBP in X-TOLE2 and X-TOLE3, eligible patients may enter an open-label extension (OLE) study for up to three years. In addition, the ongoing X-TOLE OLE also continues to generate important long-term data for XEN1101 in FOS.

XEN1101 for Epilepsy (Primary Generalized Tonic Clonic Seizures)Alignment was obtained with the FDA at the EOP2 meeting on key elements of a single Phase 3 clinical trial to pursue an additional epilepsy indication of primary generalized tonic clonic seizures (PGTCS). Following the initiation of X-TOLE2, Xenon plans to initiate a Phase 3 clinical trial, called X-ACKT, to support potential regulatory submissions in PGTCS. This multicenter, randomized, double-blind, placebo-controlled study will evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in approximately 160 patients with PGTCS. The primary efficacy endpoint is the MPC in monthly PGTCS frequency from baseline through the DBP of XEN1101 compared to placebo. On completion of the DBP in X-ACKT, eligible patients may enter an OLE study for up to three years.

XEN1101 for Major Depressive DisorderBased on promising pre-clinical data with XEN1101 and published 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, Xenon is evaluating the clinical efficacy, safety and tolerability of XEN1101 administered as monotherapy in approximately 150 patients with MDD in a Phase 2 clinical trial called X-NOVA. Designed as a randomized, double-blind, placebo-controlled, multicenter clinical study, the primary objective is to assess the efficacy of XEN1101 compared to placebo on improvement of depressive symptoms in subjects diagnosed with moderate to severe MDD, using the Montgomery-Åsberg Depression Rating Scale (MADRS) score change through week six. Topline results from the X-NOVA study are anticipated in 2023.

In addition, Xenon is collaborating with the Icahn School of Medicine at Mount Sinai to support an ongoing investigator-sponsored Phase 2 proof-of-concept, randomized, parallel-arm, placebo-controlled multi-site study of XEN1101 for the treatment of MDD in approximately 60 subjects. The primary objective of the study is to investigate the effect of XEN1101 on the brain reward circuit as measured by the change in bilateral ventral striatum activity as assessed by functional MRI (fMRI). The secondary objectives are to test the effect of XEN1101 compared to placebo on clinical measures of depression and anhedonia using the MADRS and SHAPS scales.

XEN1101 – Additional Supporting DataIn June 2022, Xenon announced new, compelling efficacy data supporting the late-stage, Phase 3 development of XEN1101. A sub-group analysis of Phase 2b X-TOLE data showed that XEN1101 rapidly reduced FOS frequency within one week for all doses compared with placebo. At Week 1, the median percent reduction in monthly focal onset seizure frequency was 55.4% in the 25 mg group (p