Xenon Pharmaceuticals Investor Presentation — August 2018

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A First- in-Human Phase I Study to Assess the Pharmacodynamic

Profile of a Novel Potassium Channel Opener (XEN 1101 ) on

Human Cortical Excitability with TMS -EEG and TMS -EMG

Presented by: Isabella Premoli, PhD | 13th European Congress on Epileptology | August 29, 2018

Institute of Psychiatry, Psychology and Neuroscience

Disclosure Declaration

•Xenon Pharmaceuticals Inc. provided financial support for the study of

the new antiepileptic drug XEN1101.

Please note: comparisons of XEN1101 and ezogabine are based on results in published literature, not based

on data resulting from head -to-head trials, and are not direct comparisons of safety or efficacy. Different

protocol designs, trial designs, patient selection and populations, number of patients, trial endpoints, trial

objectives and other parameters that are not the same between the relevant trials may cause any

comparisons of results from different trials to be unreliable.

2 Transcranial Magnetic Stimulation (TMS)

•TMS is a non -invasive tool to study human cortical excitability

•Multiple approved AEDs show effects on TMS at efficacious plasma levels

•Stimulation responses can be measured with:

Resting Motor Threshold ( RMT% )

reflects cortico -spinal excitability

TMS -evoked EEG potentials ( TEPs ) allow direct evaluation

of cortical excitability in a time -resolved fashion manner

XEN1101: Potential Best- in-Class KCNQ2 Modulator

•Same mechanism of action as retigabine/ezogabine, but with substantial

▪More potent in vitro and in vivo

▪Once daily dosing plus modest selectivity predicts better tolerability

▪No pigmented dimers and no predicted discoloration liability

•Safe and well tolerated in ongoing Phase 1 study

▪5 SAD cohorts, a food effect cohort, and 3 MAD cohorts of 66 healthy subjects to

▪TMS Phase 1a pilot study in 8 subjects

▪TMS Phase 1b double -blind, placebo -controlled crossover study in 20 subjects

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