Letter Amendment #7, dated July 25, 2018, to the Collaborative Research and License Agreement, dated December 22, 2011, by and among the Company, Genentech, Inc. and F. Hoffmann-La Roche Ltd, as amended

Collaborative Research and License Agreement between Xenon Pharmaceuticals Inc. (“Xenon”) and Genentech, Inc. (“GNE”) together with F. Hoffmann-La Roche Ltd (“Roche”) (GNE and Roche, collectively, “Genentech”), made as of December 22, 2011, as amended (prior to this Amendment) (the “Agreement”)

Letter Amendment #7

DEFINITIONS

“Amendment Date” means July 25, 2018.

“Final Patent Review” means the patent review of the NaV1.6 IP (excluding the patents covering the patent applications listed in Exhibit A, which have already been subject to review) following the process set out in the Letter Agreement of May 8, 2017, which review has been completed prior to the Amendment Date.

“ [†] Assay” means the assay described in Exhibit B to this Letter Amendment #7.

“[†] Model” means the [†].

“NaV1.6 Compound(s)” means [†].

“NaV1.6 IP” has the meaning set out in Letter Amendment #4 up to the NaV1.6 Research Program End Date, including the subject matter of the patent applications listed in Exhibit A and any other patent applications that claim priority to one or more of the patent applications listed in Exhibit A, and any other Intellectual Property Controlled by Xenon arising from the NaV1.6 Research Program identified in the Final Patent Review.

“NaV1.6 Licensee” means a Third Party licensed by Xenon to make, use, sell, offer for sale, or import products containing NaV1.6 Compounds above the NaV1.7 Threshold. A “NaV1.6 Licensee” does not include [†].

“NaV1.6 Research Program End Date” means [†].

“NaV1.7 Threshold” means [†] as measured using the [†] Assay.

“Pain Field” means treating the following diseases by modulating NaV1.7: pain indications and pain associated with other diseases or conditions.

Wind-down of the NaV1.6 Research Program

As of the NaV1.6 Research Program End Date, the NaV1.6 Research Program shall terminate. Thereafter, Xenon may conduct its own independent NaV1.6 research program.

As of the Amendment Date, Xenon’s obligations to disclose Xenon Research Data under Section 4 of Letter Amendment #4 shall cease; and Section 4.2 of Letter Amendment #4 is hereby amended and restated as follows:

As of the Amendment Date, the Parties shall cease their patent cooperation under Section 9 of Letter Amendment #4, and Section 9 of Letter Amendment #4 is hereby terminated.

Royalties

For products containing NaV1.6 Compounds above the NaV1.7 Threshold (except for Excluded Collaboration Compounds), Xenon shall pay Genentech a royalty on Net Sales of such products on a product by product basis and on a country by country basis, at the percentage rate set out below.  The royalties shall be paid for a period of ten (10) years commencing on the date of First Commercial Sale of such product(s) in such country.

The calculation, reporting, payment and audit rights respecting such royalty shall be as if sales by Xenon or a licensee of products containing NaV1.6 Compounds above the NaV1.7 Threshold were sales of a Licensed Product by Genentech or a licensee, and Sections 8.11, Royalty Reports; Payments; 8.12, Audits; 8.13, Tax Matters; 8.14, Currency Exchange; 8.15, Late Payments; 8.16, Mode of Payment; 8.17, No Set Off; and 8.20, Sublicensees; shall apply to such royalties, mutatis mutandis.

LICENSES

Xenon’s License

Section 6(a) of Letter Amendment #4 is hereby amended and restated as follows:

NaV1.6 Compound(s) above the NaV1.7 Threshold (whether or not Collaboration Compounds) and products containing NaV1.6 Compounds above the NaV1.7 Threshold (except for Excluded Collaboration Compounds) are not subject to the restrictions in Section 3.8 of the Agreement.

Section 6(b) and Section 7 of Letter Amendment #4 are hereby deleted.

Genentech’s Licenses in NaV1.6 IP and [†] Model

The licenses under Section 6(c)(i), (ii) and (iii) of Letter Amendment #4 are hereby amended and restated as follows:

under NaV1.6 IP, a royalty-free, non-exclusive, world-wide license to make, use, sell, offer for sale and import Compounds at or under the NaV1.7 Threshold and products containing Compounds at or under the NaV1.7 Threshold, for all uses and indications except epilepsy; and

the right to grant sublicenses to Third Parties of its licensed rights under subparagraph 6(c)(i) above without the prior consent of Xenon, 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.”

Xenon hereby grants Genentech the irrevocable, non-exclusive license to use the NaV1.6 IP and the [†] Model for any internal research purposes.

Certain Prohibitions

Although Xenon Controls NaV1.6 IP (except as licensed to Genentech pursuant to Section 5.2 above), Xenon agrees that it shall, and shall cause its NaV1.6 Licensees to not, directly or indirectly, develop, seek approval for, market or promote:

NaV1.6 Compounds at or under the NaV1.7 Threshold for epilepsy;

NaV1.6 Compound(s) for the Pain Field; and

Excluded Collaboration Compounds in any field.

OWNERSHIP OF INTELLECTUAL PROPERTY

GENERAL

As of the Amendment Date, except as set out above, Letter Amendment #6 is terminated and Xenon shall return all Collaboration Compounds in Xenon’s possession (if any) to Genentech within [†] ([†]) days.

In the event of a conflict between the terms of this Letter Amendment #7 and the terms of the Agreement, the terms of this Letter Amendment #7 shall prevail.

Except as specifically provided above in this Letter Amendment #7, the Agreement remains in full force and effect, unamended.

Any rights and obligations of the Parties set out in this Letter Amendment #7 which, from the context hereof, are intended to survive any termination or expiration of the Agreement, including those rights and obligations set out in Sections 4, 5, 7 and 8 above, shall survive any such termination or expiration. Sections 5.2(a) and 6 shall terminate on termination or expiry of the Agreement.