51: Kv7 Potentiation - a Novel Non-Opioid Strategy for Modulating Hyperexcitability Across Pain Pathways

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Pharmacological interventions, Drug development

Background and Aims: Kv7 potassium channels are widely expressed across nociceptive pathways and can regulate neuronal excitability by suppressing repetitive action potential firing. Dysregulation or reduced Kv7 activity has been associated with pathological pain states, highlighting a key role for Kv7 in pain signaling. Xenon is developing selective Kv7 opener, such as XEN1120, as a novel non-opioid approach to potentially treat acute and chronic pain.

Methods: Electrophysiology, cellular assays in human and rodent systems, and rodent pain models were used to assess Kv7 expression, function, and pharmacologic modulation. A Phase 1 double-blind, placebo-controlled, randomized study was conducted to evaluate the safety, tolerability, and pharmacokinetics, of single and multiple ascending oral doses of XEN1120 in healthy volunteers.

Results: Kv7 channels are enriched in small-diameter dorsal root ganglion (DRG) nociceptors and Kv7 potentiation can reduce excitability across multiple points of the pain pathway, including DRG and spinal dorsal horn neurons. In the formalin mouse model, XEN1120 and other exemplar Kv7 potentiators, reduced both Phase 1 (acute) and Phase 2 (inflammatory) pain responses. Results from the Phase 1 study will be presented.

Conclusions: Kv7 channels are highly expressed and play a major role in regulating the activity of pain pathways, making them a compelling non-opioid target for the treatment of pain. Preclinical studies with exemplary Kv7 potentiators show they can reduce neuronal hyperexcitability and deliver robust efficacy in both phases of the formalin mouse model, a high bar where most non-opioid drugs are ineffective.

References: N/A

Presenting Author: JP Gilbert
Submitting Author: Alison Cutts

Senior Author: Chris Kenney

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• JP Gilbert: PhD - Xenon Pharmaceuticals
• Richard Dean: PhD - Xenon Pharmaceuticals
• JP Johson: PhD - Xenon PHarmaceuticals
• Noam Butterfield: PhD - Xenon Pharmaceuticals
• Jeff Bechard: MSc - Xenon Pharmaceuticals
• Emily Casavant: BSc - Xenon Pharmaceuticals
• Rostam Namdari: PhD - Xenon Pharmaceuticals
• Christoph Dehnhardt: PhD - Xenon Pharmaceuticals
• Michael Clark: PhD - Xenon Pharmaceuticals
• Charles Bernard: PhD - Xenon Pharmaceuticals
• Dejan Pavlovic: MD PhD - Xenon Pharmaceuticals
• Ariel Le Huquet: MSc - Ariel Le Huquet
• Alison Cutts: PhD - Ariel Le Huquet
• Girish Bankar: MSc - Xenon Pharmaceuticals
• Luis Bettio: PhD - Xenon Pharmaceuticals
• Nina Weishaupt: PhD - Xenon Pharmaceuticals
• Joe McIntosh: MD - Xenon Pharmaceuticals
• James Empfield: PhD - Xenon Pharmaceuticals
• Matt Ronsheim: PhD - Xenon Pharmaceuticals
• Chris Kenney: MD - Xenon Pharmaceuticals