Amendment No. 1 to the Neurology III Agreement between the Registrant and Biogen MA Inc., dated August 16, 2019 (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed)

The Parties, through the Neurology JRC, may add up to [***] gene targets to the High Interest Target List, beyond the [***]-target limit set forth in Section 1.2.3(a), under this Section 1.2.3(g) (each, an “Expanded High Interest Target”).

Before adding an Expanded High Interest Target to the High Interest Target List, the Parties must mutually agree upon and submit to the Neurology JRC for approval a research plan that meets the requirements of either Section 1.2.3(g)(ii)(A) or Section 1.2.3(g)(ii)(B) (each, an “Expanded High Interest Target Plan”) for each such proposed Expanded High Interest Target.

An Expanded High Interest Target Plan may consist of an initial plan to conduct limited research by the Parties that clearly defines the scope of work to be performed by each Party.  Ionis and Biogen will use Commercially Reasonable Efforts to conduct their respective activities under the Expanded High Interest Target Plan.

An Expanded High Interest Target Plan may consist of a Target Sanction Plan.

The Neurology JRC will review and, in its discretion, approve the addition of a proposed Expanded High Interest Target to the High Interest Target List along with the Expanded High Interest Target Plan corresponding to such proposed Expanded High Interest Target.

With respect to each proposed Expanded High Interest Target, if the Neurology JRC, in good faith, does not unanimously agree to (1) add such proposed Expanded High Interest Target to the High Interest Target List and (2) adopt the Expanded High Interest Target Plan corresponding to such proposed Expanded High Interest Target, then the proposed Expanded High Interest Target will not be added to the High Interest Target List under this Section 1.2.3(g).  Such gene target may be added to the High Interest Target List in accordance with Section 1.2.3(b) or may be pursued independently by the Parties in accordance with Section 1.2.3(f).

With respect to any Expanded High Interest Target Plan under Section 1.2.3(g)(ii)(A), once the Parties complete all work under such plan and present the results of such research to the Neurology JRC or [***] days following approval of such Expanded High Interest Target Plan by the Neurology JRC, whichever is earlier, the Neurology JRC will have [***] days within which to unanimously agree upon a Target Sanction Plan for such Expanded High Interest Target.  If the Neurology JRC does not unanimously agree upon a Target Sanction Plan for such Expanded High Interest Target within such [***]-day period, then the Expanded High Interest Target will be removed from the High Interest Target List.  Such gene target may be added to the High Interest Target List in accordance with Section 1.2.3(b) or may be pursued independently by the Parties in accordance with Section 1.2.3(f).

An Expanded High Interest Target that is approved by the Neurology JRC to add to the High Interest Target List will not be subject to the terms of Section 1.2.3(a), Section 1.2.3(b), or Section 1.2.3(d)(i) of this Agreement.

Once approved by the Neurology JRC, an Expanded High Interest Target will become a High Interest Target for all purposes under this Agreement except as expressly set forth in this Section 1.2.3(g), and the Expanded High Interest Target Plan approved by the Neurology JRC for such Expanded High Interest Target will become part of the Neurological Disease Research Plan.

If, on or after the [***] anniversary of the date an Expanded High Interest Target was added to the High Interest Target List, such target remains or becomes an Inactive Target, then, unless the Parties mutually agree through the Neurology JRC that such Expanded High Interest Target may remain on the High Interest Target List, such Expanded High Interest Target will automatically be removed from the High Interest Target List and will no longer be an Expanded High Interest Target.  However, during the remainder of the Research Term, such target will remain a Neurology Target and the Parties may add such target to the High Interest Target List in accordance with Section 1.2.3(b) or again add such target to the High Interest Target List in accordance with this Section 1.2.3(g).

The maximum number of Expanded High Interest Targets set forth in Section 1.2.3(g)(i) may be increased or decreased by the Neurology JRC, and any such change will be reflected in the minutes of the meeting of the Neurology JRC where such increase or decrease occurred and subsequently formalized in a letter between the Parties.

review and approve amendments to the Core Research Plan and the Neurological Disease Research Plan, as described in Section 1.2.2 and 1.2.3(d)(iv), and review and approve Expanded High Interest Targets to add to the High Interest Target List, as well as the Expanded High Interest Target Plans corresponding to such Expanded High Interest Targets, as described in Section 1.2.3(g);