ScheduleA-1 NaV1.6

Exhibit 10.1

May 13, 2015

Genentech, Inc.

1 DNA Way

South San Francisco

California, USA 94080

Attention:Kate Skrable, Alliance Management

Dear Kate,

Further to our recent discussions and in accordance with Section 16.14 of the Agreement, and in consideration of the premises and mutual covenants contained herein, Xenon and Genentech agree as follows:

1.This amendment to the Agreement shall hereinafter be referred to as the “Letter Amendment #4.”  Except as specifically defined below, capitalized terms used in this Letter Amendment #4 shall have the same meaning as ascribed to such terms in the Agreement.

“Field” means treating the following diseases by modulating NaV1.6: epilepsy, including Dravet Syndrome.

“NaV1.6” means the voltage gated sodium channel polypeptide of the SCN8A gene, having the sequence described in Schedule A-1 hereto and mutant and splice variants thereof, provided in any case, NaV1.6 shall exclude NaV1.7.

“NaV1.6 Modulator(s)” means a [†].

“NaV1.6 IP” means Intellectual Property conceived, identified, or first made by Xenon (either alone, jointly with any Third Parties and/or by any Third Parties on behalf of Xenon) as a result of conducting any research activities under the NaV1.6 Research Program.  For clarity, Xenon Collaboration IP and Post-Research Term IP exclude NaV1.6 IP. NaV1.6 IP does not include Intellectual Property that was owned or controlled by a Third Party prior to the date of a Change of Control Event involving such Third Party and Xenon, provided that such Third Party Intellectual Property was conceived, identified, or first made independently from Xenon.

[†] DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION“NaV1.6 Research Program” means those research and discovery activities conducted by Xenon (either alone, jointly with any Third Parties and/or by any Third Parties on behalf of

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Xenon) outside the Research Program that are directed toward the identification, design, synthesis, discovery and optimization of NaV1.6 Modulators.

“Other Compound” means a Compound that Xenon conceived, identified or first made (either alone, jointly with any Third Parties and/or by any Third Parties on behalf or Xenon) (i) during the course of conducting a NaV1.6 Research Program, and (ii) through the exercise of the license granted in paragraph 6(a) below, (iii) that is not otherwise a Collaboration Compound and (iv) was not conceived, identified or first made by Genentech prior to the date Xenon conceived, identified or first made such Compound.

“Xenon Research Data” means the data, results and information that are specifically set forth under paragraph 4(a) below, if and to the extent that the foregoing is generated by Xenon (either alone, jointly with any Third Parties and/or by any Third Parties on behalf of Xenon) in the course of conducting the NaV1.6 Research Program from [†] until the date that the [†] expires under the Agreement.

3.XENON NAV1.6 RESEARCH PROGRAM.  Further to the discussions of the JRC in its meeting of [†] regarding Xenon’s interest to conduct a NaV1.6 Research Program in the Field outside of the Research Program and outside the Agreement and GNE’s support of Xenon’s interest to conduct such a NaV1.6 Research Program, and notwithstanding anything to the contrary in the Agreement including without limitation the Exclusivity provision set forth under Section 3.8 of the Agreement, for good and valuation consideration the sufficiency and receipt thereof which is specifically acknowledged by each Party hereto, the Parties have agreed to enter into this Letter Amendment #4, and specifically agree to the terms set out herein.

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Effective as of [†], Genentech hereby:

a royalty-free, non-exclusive, fully paid, revocable, perpetual, world-wide license under such Licensed IP and/or Genentech Collaboration IP that is necessary or useful to make and use (but not to sell, or offer for sale) NaV1.6 Modulators under the NaV1.6 Research Program in the Field.

The license granted in this paragraph 6(a) is and shall be revocable at Genentech’s sole discretion, upon delivery of ninety (90) days prior written notice to Xenon at any time after the third (3rd) year anniversary of the date of this Letter Agreement #4.  In the event of uncured material breach (pursuant to Section 12.4) of Xenon’s obligations or duties under the Letter Amendment #4, Genentech may terminate the license granted in this paragraph 6(a) at any time following the date set forth on page 1 of Letter Amendment #4.  Nothing in the foregoing shall waive or otherwise alter Genentech’s right to terminate the Agreement pursuant to Section 12.3(a)(i).

[†] DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSIONFor clarity, the terms “make and use” referenced in this paragraph 6(a) include, without limitation, “research, identify, design, synthesize, discover, import and export.” The

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rights granted by this paragraph 6(a) may be exercised by Third Parties conducting research, identification, design, synthesis or discovery activities with or on behalf of Xenon under the NaV1.6 Research Program (hereinafter referred to as “Xenon CROs”).

The Parties further agree that notwithstanding s 3.8(a)(ii) of the Agreement:

Xenon may exercise the foregoing right by providing written notice to Genentech at any time within [†] from the date of this Letter Agreement #4.  Following receipt by Genentech of such written notice, the Parties shall enter into good faith negotiations for the NaV1.6 Commercialization License.  Such NaV1.6 Commercialization License shall be on terms that are [†] under the circumstances.  The total compensation for such license shall not exceed [†].  In the event that:

i.the Parties do not reach mutual agreement on a definitive NaV1.6 Commercialization License within [†] following the receipt of the notice by Genentech:

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ii.The Right of First Negotiation set forth in this paragraph 6(b) shall expire [†] from the date of this Letter Agreement, or until such time that Xenon gives notice to Genentech that Xenon is not interested in pursuing a NaV1.6 Commercialization License, whichever comes first.

i.under NaV1.6 IP, an exclusive, world-wide license to make, use, sell, offer for sale and import Other Compounds and Licensed Products containing Other Compounds, for all uses other than for uses in the Field; and

ii.under the NaV1.6 IP, a royalty-free, exclusive, fully paid, perpetual, world-wide license to make, use, sell, offer for sale and import Compounds (excluding Other Compounds) and Licensed Products containing Compounds (excluding Other Compounds), for all uses; and

iii.the right to grant sublicenses to Third Parties of its licensed rights under subparagraph 6(c)(i) and 6(c)(ii) above [†], such sublicense rights to be subject to the same terms and conditions, mutatis mutandis, as are set forth in Sections 9.3 and 9.4 of the Agreement.

7.RIGHT OF FIRST NEGOTIATION FOR DEVELOPING AND COMMERCIALIZING XENON’S NAV 1.6 MODULATORS.

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All NaV1.6 IP (including without limitation Xenon Research Data and Other Compounds) is owned solely by Xenon.

[†] DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSIONNaV1.6 Research Program.  Should Xenon wish to file a patent application for NaV1.6 IP (“NaV1.6 Patent Filing”) Xenon shall inform in writing to an individual designated in writing by Genentech (e.g., Genentech’s outside counsel) of its intention to file such application and in confidence shall specify with particularity the subject matter of the application, including for composition of matter applications directed to new small molecule compounds [†] disclosed in the application.  Genentech shall have [†] from the receipt of such notification by such an individual designated by Genentech to inform Xenon’s Alliance Manager in writing as to whether Genentech wishes to coordinate with Xenon on the filing of the NaV1.6 Patent Filing with a filing of a patent application related to Compounds.  Upon such notification by Genentech, the Parties shall coordinate

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and cooperate in good faith to ensure the disclosure and timing of any such NaV1.6 Patent Filing would not adversely affect the validity of claims in (i) any Patent Rights covering Compounds that are being Prosecuted by Genentech and/or (ii) any Patent Rights covering Compounds that Genentech reasonably anticipates Prosecuting following such notification by Genentech (each (i) and (ii) hereinafter referred to as “Genentech Compound Patents”), provided that, such process of coordination and cooperation shall not delay the filing of Xenon’s NaV1.6 Patent Filing for a timeframe greater than [†] following receipt of Genentech’s notification that it wishes to coordinate with Xenon on such filing.  Thereafter, during the further Prosecution of NaV1.6 Patent Filings, Xenon shall not and shall not permit any Third Party on its behalf to cite or characterize (i) Xenon Background Patent Rights, (ii) Genentech Background Patent Rights, (iii) Patent Rights comprised in Collaboration IP, or (iv) Patent Rights covering Compounds developed independently by Genentech, in such Prosecution of NaV1.6 IP Patent Filings without Genentech’s prior review, comment, and written permission, provided that such comments by Genentech shall be promptly delivered to Xenon’s Alliance Manager, and further provided that such written permission by Genentech will not be withheld or delayed except in circumstances where such citation or characterization would adversely affect the validity of claims of Genentech Compound Patents, in which case the Parties will enter into good faith discussions respecting the NaV1.6 IP Patent Filing(s) at issue, and will devote [†] efforts to finding a [†] compromise that would allow Xenon to continue its Prosecution of such NaV1.6 Patent Filing(s).

[†] DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION

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By the signatures below, the Parties have caused this Letter Amendment #4 to be executed by their respective duly authorized officers to be effective as of [†].

Sincerely,

XENON PHARMACEUTICALS INC.

By:/s/ Simon Pimstone

Simon Pimstone

President & CEO

GENETECH, INC

By: /s/ James Sabry

Name: James Sabry

Title: SVP

F. HOFFMAN-LA ROCHE LTD

By: /s/ Stefan Arnold/s/ Dr. Melanie Frey Wick

Name: Stefan ArnoldDr. Melanie Frey Wick

Title: Head Legal PharmaAuthorized Signatory

[†] DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION

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Schedule A-1

NaV1.6

NCBI LOCUSAAD157891980 aa

DEFINITION voltage-gated sodium channel alpha subunit [Homo sapiens].

NCBI ACCESSIONAAD15789

VERSIONAAD15789.1GI ###-###-####

Nav1.6 SCN8A AMINO ACID SEQ

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