Amendment No. 1 to the Strategic Collaboration, Option and License Agreement between the Registrant and Novartis Pharma AG dated February 22, 2019

CONFIDENTIAL

CONFIDENTIAL TREATMENT REQUESTED

UNDER 17 C.F.R.§§ 200.80(B)4, AND 240.24B-2

Exhibit 10.1

AMENDMENT No. 1

to the Strategic Collaboration, Option and License Agreement

between Novartis Pharma AG and Akcea Therapeutics, Inc.

This Amendment No. 1 (“Amendment”) is entered into as of February 22, 2019 (“Amendment Effective Date”) by and between Novartis Pharma AG, a Swiss corporation having its principal place of business at Lichtstrasse 35, CH-4056 Basel, Switzerland (“Novartis”), and Akcea Therapeutics, Inc., a Delaware corporation having its principal place of business at 22 Boston Wharf Road, 9th Floor, Boston, MA 02210, USA (“Akcea”). Novartis and Akcea are each referred to individually as a “Party” and together as the “Parties”.

WHEREAS, Novartis and Akcea are parties to a Strategic Collaboration, Option and License Agreement dated as of January 5^th, 2017 (the “Agreement”) with respect to the Development and Commercialization of the Product in the Territory;

WHEREAS, the Parties mutually desire to amend, modify and restate certain terms and conditions of the Agreement;

NOW THEREFORE, in consideration of the mutual promises contained herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, and intending to be legally bound, the Parties hereto agree as follows:

Unless otherwise defined herein, capitalized words in this Amendment shall have the meanings attributed to them in the Agreement.

The Parties agree that, as of the Amendment Effective Date, the Agreement is amended as set forth in this Section 2.

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CONFIDENTIAL

“6.5(A) Akcea’s Right to Co-Commercialize AKCEA-APO(a)-L_Rx

On or before the [***] calendar day after [***] or [***] for AKCEA-APO(a)-L_Rx, whichever is earlier, Novartis shall deliver written notice to Akcea indicating its election, in Novartis’ sole discretion, to either:

(i)Increase the sales milestones in relation to AKCEA-APO(a)-L_Rx to the amounts stated below, whereupon Table 3 in Section 7.5 of the Agreement shall be deleted in its entirety and replaced with the following:

For the avoidance of doubt, if Novartis exercises this option (i), Akcea shall have no right, interest or claim in or to the Co-Commercialization of AKCEA-APO(a)-L_Rx and Novartis shall have no obligation to negotiate any such rights with Akcea; or

(ii)Enter into good faith negotiations with Akcea on the terms and conditions upon which Akcea will Co-Commercialize AKCEA-APO(a)-L_Rx, whereby the scope of such good faith negotiations would be within the following framework:

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6.5 (B) Akcea’s Right to Co-Commercialize AKCEA-APOCIII-L_Rx.

Akcea has the right to Co-Commercialize AKCEA-APOCIII-L_Rx with Novartis in selected markets with the terms and conditions of such Co-Commercialization to be mutually agreed between Akcea and Novartis.  If, on or before the [***] calendar day after [***] or [***] for AKCEA-APOCIII-L_Rx, Akcea delivers written notice to Novartis indicating that Akcea intends to Co-Commercialize AKCEA-APOCIII-L_Rx, then the Parties shall negotiate in good faith on the terms and conditions upon which Akcea will Co-Commercialize AKCEA-APOCIII-L_Rx.

As specifically amended hereunder, all terms and conditions of the Agreement remain and shall remain in full force and effect. This Amendment shall hereafter be incorporated into and deemed part of the Agreement and any future reference to the Agreement shall include the terms and conditions of this Amendment.

This Amendment shall be governed by, and construed in accordance with, the laws which govern the Agreement, and the Parties submit to the jurisdiction and dispute resolution provisions as set forth in the Agreement.

This Amendment may be executed in counterparts with the same effect as if both Parties had signed the same document. All such counterparts shall be deemed an original, shall be construed together and shall constitute one and the same instrument. Signature pages of this Amendment may be exchanged by facsimile or other electronic means without affecting the validity thereof.

[Remainder of Page Intentionally Left Blank – Signature Page to Follow]

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CONFIDENTIAL

IN WITNESS WHEREOF, the Parties intending to be bound have caused this Amendment to be executed by their duly authorized representatives.

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