Xenon Pharmaceuticals (XENE) investor relations material

Corporate and Pipeline Overview

• Focus on neuroscience and ion channel drug discovery, with expertise in potassium (Kv7) and sodium (Nav1.7) channels for pain and neurological disorders.

• Lead molecule azetukalner is in phase III for epilepsy and depression, with over 700 patient years of data.

• Lead pain compounds XEN1120 (Kv7 opener) and XEN1701 (Nav1.7 inhibitor) are both in phase I clinical studies.

• Early-stage pipeline includes Kv7 openers and Nav1.7 inhibitors for pain, both in phase I, with strong patent protection to at least 2040.

• Additional programs target Nav1.1 for Dravet Syndrome and collaborations on Nav1.6/1.2 inhibitors for epilepsy.

Scientific Rationale and Discovery

• Human genetics underpin the selection of ion channel targets, with Nav1.7 loss-of-function mutations causing congenital insensitivity to pain.

• Kv7 and Nav1.7 channels are critical in pain transduction, transmission, and relay, making them compelling non-opioid pain targets.

• Preclinical models show Kv7 openers and Nav1.7 inhibitors reduce pain signaling at multiple pathway points.

• Advanced in-house capabilities include electrophysiology, computational chemistry, and AI-driven drug design.

• Pain signals travel from peripheral tissues through DRG neurons to the spinal cord and brain.

Kv7 Pain Program Highlights

• Kv7 channels suppress repetitive firing; dysfunction is linked to pain states.

• Kv7 openers decrease excitability in DRG and spinal cord, blocking pain signaling.

• XEN1120 shows efficacy in preclinical models, including acute sensory pain where most non-opioids are ineffective.

• Phase 1 study of XEN1120 is underway, with additional Kv7 compounds advancing toward IND-enabling studies.