Xenon and Genentech Publish in Science the 3-D Crystal Structure of a Novel Nav1.7 Compound Binding Site Enabling the Development of Potent Selective Inhibitors to Treat Pain

December 17, 2015 – Xenon Pharmaceuticals Inc.

BURNABY, British Columbia, Dec. 17, 2015 (GLOBE NEWSWIRE) — Xenon Pharmaceuticals Inc. (NASDAQ:XENE), a clinical-stage biopharmaceutical company, today announced publication of a key article in Science by researchers at Xenon and Genentech describing for the first time the X-ray crystal structure of a pharmacological binding site on the Nav1.7 sodium channel allowing for the rational drug design of highly selective inhibitors. Nav1.7 is a member of the voltage-gated ion channel super-family and is a genetically validated target for treating inflammatory and neuropathic pain. These channels open ion-selective pores in response to sensed changes in membrane voltage and stimulate the generation of a response in nerve cells.

Using its Extreme Genetics™ platform, Xenon identified Nav1.7 as a drug target for pain after discovering that the Nav1.7 protein is deficient in the rare genetic disorder congenital indifference to pain, in which people are unable to feel pain. Nav1.7 appears to be essential for pain signaling and based on the significant human validation was selected by Xenon as a key target for the development of novel analgesics.

Since 2011, Xenon and Genentech have been collaborating to discover and develop innovative selective oral inhibitors of Nav1.7 for the treatment of pain.  The Science publication, titled “Structural Basis of Nav1.7 Inhibition by a Selective Small Molecule Antagonist,” by Ahuja et al. describes for the first time the use of X-ray crystallography and protein engineering to describe at the molecular level a new receptor site within a Nav1.7 voltage sensor potentially enabling the development of highly selective small molecule inhibitors. The authors believe that this discovery establishes a structural blueprint for designing other selective Nav channel inhibitors for treating pain and other diseases.

Morgan Sheng, M.B.B.S., Ph.D., Vice President, Neuroscience at Genentech, said, “This important discovery reported in Science has the potential to accelerate the development of potentially breakthrough treatments for pain. We believe that our studies characterize the mechanism of an important new class of compounds that possess both functional and molecular selectivity, which is previously unknown among small molecule ligands of the Nav channel family.”

Dr. Simon Pimstone, Xenon’s President and Chief Executive Officer, said, “We believe that this publication provides additional validation for Xenon’s Extreme Genetics discovery platform, which enables us to leverage unique insights into human genetics to identify single genes associated with rare phenotypes that can represent important new targets for intractable diseases. We are excited by the progress we are making in our pain-focused strategic alliances with Genentech. Furthermore, we believe that the elucidation of the X-ray structure and novel binding site on Nav1.7 could also enhance Xenon’s ability to discover novel molecules targeting other voltage gated ion channel programs.”

Genentech is developing two novel Nav1.7 small-molecule inhibitors for pain, GDC-0276 and GDC-0310, which are both currently in Phase I clinical trials.  These compounds are both highly potent and selective inhibitors of Nav1.7.

About Xenon Pharmaceuticals Inc
Xenon is a clinical-stage biopharmaceutical company discovering and developing a pipeline of differentiated therapeutics for orphan indications that it intends to commercialize on its own and for larger market indications that the company intends to partner with global pharmaceutical companies. Xenon has built a core enabling discovery platform, referred to as Extreme Genetics®, for the discovery of validated drug targets by studying rare human diseases with extreme traits, including diseases caused by mutations in ion channels, known as channelopathies. Xenon’s Extreme Genetics® platform has yielded the first approved gene therapy product in the European Union and a broad development pipeline and multiple pharmaceutical partnerships, including with Teva and Genentech. For more information, please visit www.xenon-pharma.com.

Safe Harbor Statement
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995 and Canadian securities laws. These forward-looking statements are not based on historical fact, and include statements regarding the potential discovery and design of selective sodium channel inhibitors and other novel molecules for the treatment of pain and other diseases, the results of research and development efforts, the progress and potential of ongoing development programs, including those in pain and epilepsy, and the plans of our collaboration partners. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; our Extreme Genetics® discovery platform or ongoing collaborations may not yield additional product candidates; any of our or our collaborators’ product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones pursuant to our collaboration agreements; the impact of competition; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in our filings with the Securities and Exchange Commission and the securities commissions in British Columbia, Alberta and Ontario. These forward-looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

Ian Mortimer, Chief Financial Officer and Chief Operating Officer
Xenon Pharmaceuticals Inc.
Phone: 604.484.3300

Email: investors@xenon-pharma.com