UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE TO

TENDER OFFER STATEMENT UNDER SECTION 14(D)(1) OR 13(E)(1)

OF THE SECURITIES EXCHANGE ACT OF 1934

AKCEA THERAPEUTICS, INC.

(Name of Subject Company (Issuer))

AVALANCHE MERGER SUB, INC.

a wholly owned subsidiary of

IONIS PHARMACEUTICALS, INC.

(Names of Filing Persons (Offeror))

Common Stock, Par Value $0.001 Per Share

(Title of Class of Securities)

00972L 107

(Cusip Number of Class of Securities)

Brett Monia

Chief Executive Officer

Ionis Pharmaceuticals, Inc.

2855 Gazelle Court

Carlsbad, CA 92010

(760) 931-9200

(Name, Address and Telephone Number of Person Authorized to

Receive Notices and Communications on Behalf of Filing Persons)

Copies to:

Graham Robinson

Laura Knoll

Skadden, Arps, Slate, Meagher & Flom LLP

500 Boylston Street

Boston, MA 02116

(617) 573-4850

CALCULATION OF FILING FEE

Check the appropriate boxes below to designate any transactions to which the statement relates:

Check the following box if the filing is a final amendment reporting the results of the tender offer.  ☐

Item 1 through 9, Item 11 and Item 13.

This Tender Offer Statement on Schedule TO (this “Schedule TO”) relates to the offer by Avalanche Merger Sub, Inc., a Delaware corporation (“Purchaser”) and a wholly owned subsidiary of Ionis Pharmaceuticals, Inc., a Delaware corporation (“Parent”), to purchase all outstanding shares of common stock, $0.001 par value per share (“Shares”), of Akcea Therapeutics, Inc., a Delaware corporation (“Akcea”), not owned by Parent at a price of $18.15 per Share, net to the seller in cash, without interest and subject to any withholding of taxes, upon the terms and subject to the conditions described in the Offer to Purchase dated September 14, 2020 (together with any amendments or supplements thereto, the “Offer to Purchase”) and in the accompanying Letter of Transmittal (together with any amendments or supplements thereto and with the Offer to Purchase, the “Offer”).

The information set forth in the Offer to Purchase, including all schedules thereto, is hereby expressly incorporated by reference in response to all of the items of this Schedule TO, including, without limitation, all of the information required by Schedule 13E-3 that is not included in or covered by the items in Schedule TO, and is supplemented by the information specifically provided herein, except as otherwise set forth below.

Item 10. Financial Statements.

Not applicable.

Item 12. Exhibits.

* Filed herewith.

† Certain portions of this exhibit have been redacted and separately filed with the Securities and Exchange Commission pursuant to a request for confidential treatment.

SIGNATURE

After due inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Dated: September 14, 2020

Exhibit (a)(1)(i)

Offer to Purchase

All Outstanding Shares of Common Stock

of

AKCEA THERAPEUTICS, INC.

at

$18.15 Net Per Share in Cash

by

AVALANCHE MERGER SUB, INC.

a wholly owned subsidiary of

IONIS PHARMACEUTICALS, INC.

THE OFFER AND WITHDRAWAL RIGHTS WILL EXPIRE AT ONE MINUTE AFTER

11:59 P.M., EASTERN TIME, ON OCTOBER 9, 2020,

UNLESS THE OFFER IS EXTENDED OR EARLIER TERMINATED.

Avalanche Merger Sub. Inc., a Delaware corporation (“Purchaser”), is offering to purchase (the “Offer”) all outstanding shares of common stock, par value $0.001 per share (“Shares”), of Akcea Therapeutics, Inc., a Delaware corporation (“Akcea”), at a price per Share of $18.15, net to the seller in cash, without interest (the “Offer Price”), and subject to any withholding of taxes, upon the terms and subject to the conditions described in this Offer to Purchase (together with any amendments or supplements hereto, this “Offer to Purchase”) and in the related Letter of Transmittal (together with any amendments or supplements thereto, the “Letter of Transmittal”). Purchaser is a wholly owned subsidiary of Ionis Pharmaceuticals, Inc. (“Parent”), a Delaware corporation. The Offer is being made in connection with the Agreement and Plan of Merger, dated as of August 30, 2020 (together with any amendments or supplements thereto, the “Merger Agreement”), among Akcea, Parent and Purchaser, pursuant to which, after the completion of the Offer and the satisfaction or waiver of certain conditions, Purchaser will be merged with and into Akcea, without a meeting or vote of the Akcea stockholders in accordance with Section 251(h) of the General Corporation Law of the State of Delaware (the “DGCL”), and Akcea will be the surviving corporation and a wholly owned subsidiary of Parent (such corporation, the “Surviving Corporation” and such merger, the “Merger”). At the effective time of the Merger, each Share (other than Shares held by Akcea, Parent, Purchaser, any wholly owned subsidiary of Parent or Purchaser, or by stockholders of Akcea who have perfected their statutory rights of appraisal under DGCL) will be converted into the right to receive an amount in cash equal to the Offer Price, without any interest thereon and subject to any withholding of taxes.

After careful consideration, the Akcea board of directors, acting on the unanimous recommendation of an affiliated transactions committee comprised solely of independent directors, has: (i) determined that the Merger Agreement and the transactions contemplated thereby (the “Transactions”), including the Offer and the Merger, are fair to and in the best interest of Akcea and its stockholders (other than Parent, its affiliates, their respective directors and executive officers and Damien McDevitt, Akcea’s chief executive officer (the “Excluded Holders”)), (ii) declared it advisable to enter into the Merger Agreement, (iii) approved the execution, delivery and performance by Akcea of the Merger Agreement and the consummation of the Transactions, including the Offer and the Merger, (iv) resolved that the Merger shall be effected under Section 251(h) of the DGCL and (v) resolved to recommend that the stockholders of Akcea (other than the Excluded Holders) tender their Shares pursuant to the Offer.

There is no financing condition to the Offer. The Offer is subject to various conditions, including, among others, the non-waivable condition that there shall have been validly tendered and not validly withdrawn Shares that, excluding the Shares beneficially owned by the Excluded Holders, represent at least one more Share than 50% of the Shares not beneficially owned by the Excluded Holders outstanding at the time of the expiration of the Offer. See Section 22—“Conditions of the Offer.” A summary of the principal terms of the Offer appears on pages 1 through 6 of this Offer to Purchase. You should read this entire document carefully before deciding whether to tender your Shares.

September 14, 2020

IMPORTANT

If you desire to tender all or any portion of your Shares to us pursuant to the Offer, you should either (i) if you hold your Shares directly as the registered owner, complete and sign the Letter of Transmittal for the Offer, which is enclosed with this Offer to Purchase, in accordance with the instructions contained in the Letter of Transmittal, mail or deliver the Letter of Transmittal and any other required documents to American Stock Transfer & Trust Company, LLC (the “Depository”), and either deliver the certificates for your Shares to the Depository along with the Letter of Transmittal or tender your Shares by book-entry transfer by following the procedures described in Section 13—“Procedures for Tendering Shares” of this Offer to Purchase, in each case prior to the expiration of the Offer, or (ii) if you hold your Shares in street name, request that your broker, dealer, commercial bank, trust company or other nominee effect the transaction for you. If you hold Shares registered in the name of a broker, dealer, commercial bank, trust company or other nominee you must contact that institution in order to tender your Shares to us pursuant to the Offer.

If you desire to tender your Shares to us pursuant to the Offer and the certificates representing your Shares are not immediately available, or you cannot comply in a timely manner with the procedures for tendering your Shares by book-entry transfer, or you cannot deliver all required documents to the Depository prior to the expiration of the Offer, you may tender your Shares to us pursuant to the Offer by following the procedures for guaranteed delivery described in Section 13—“Procedures for Tendering Shares” of this Offer to Purchase.

*                             *                            *

Questions and requests for assistance may be directed to Alliance Advisors, LLC (the “Information Agent”) at its address and telephone number set forth on the back cover of this Offer to Purchase. Requests for additional copies of this Offer to Purchase, the Letter of Transmittal, the Notice of Guaranteed Delivery and other tender offer materials may be directed to the Information Agent. You may also contact your broker, dealer, commercial bank, trust company or other nominee for assistance.

This Offer to Purchase and the Letter of Transmittal contain important information, and you should read both carefully and in their entirety before making any decision with respect to the Offer.

This transaction has not been approved or disapproved by the U.S. Securities and Exchange Commission (the “SEC”) or any state securities commission nor has the SEC or any state securities commission passed upon the fairness or merits of this transaction or upon the accuracy or adequacy of the information contained in this Offer to Purchase or the Letter of Transmittal. Any representation to the contrary is unlawful.

TABLE OF CONTENTS

i

SUMMARY TERM SHEET

Avalanche Merger Sub, Inc., a recently formed Delaware corporation (“Purchaser”) and a wholly owned subsidiary of Ionis Pharmaceuticals, Inc., a Delaware corporation (“Parent”), is offering to purchase (the “Offer”) all outstanding shares of common stock, par value $0.001 per share (the “Shares”), of Akcea Therapeutics, Inc., a Delaware corporation (“Akcea”), at a price per Share of $18.15, net to the seller in cash, without interest (the “Offer Price”), and subject to any withholding of taxes, upon terms and subject to the conditions set forth in this Offer to Purchase (together with any amendments or supplements hereto, this “Offer to Purchase”) and in the related Letter of Transmittal (together with any amendments or supplements thereto, the “Letter of Transmittal”). The following are some questions you, as a stockholder of Akcea, may have and answers to those questions. This Summary Term Sheet highlights selected information from this Offer to Purchase, and may not contain all of the information that is important to you and is qualified in its entirety by the more detailed descriptions and explanations contained in this Offer to Purchase and the related Letter of Transmittal. To better understand the Offer and for a complete description of the legal terms of the Offer, you should read this Offer to Purchase and the related Letter of Transmittal carefully and in their entirety. Questions or requests for assistance may be directed to Alliance Advisors, LLC (the “Information Agent”) at its address and telephone number, as set forth on the back cover of this Offer to Purchase. Unless otherwise indicated in this Offer to Purchase or the context otherwise requires, all references in this Offer to Purchase to “we,” “our,” or “us” refer to Purchaser or Parent, as the context requires.

WHO IS OFFERING TO BUY MY SECURITIES?

WHAT ARE THE CLASSES AND AMOUNTS OF SECURITIES SOUGHT IN THE OFFER?

HOW MUCH ARE YOU OFFERING TO PAY AND WHAT IS THE FORM OF PAYMENT? WILL I HAVE TO PAY ANY FEES OR COMMISSIONS?

WHY IS PURCHASER MAKING THE OFFER?

WHAT ARE THE MOST SIGNIFICANT CONDITIONS OF THE OFFER?

IS THERE AN AGREEMENT GOVERNING THE OFFER?

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DO YOU HAVE FINANCIAL RESOURCES TO MAKE PAYMENTS IN THE OFFER?

SHOULD PURCHASER’S FINANCIAL CONDITION BE RELEVANT TO MY DECISION TO TENDER IN THE OFFER?

HOW LONG DO I HAVE TO DECIDE WHETHER TO TENDER IN THE OFFER?

CAN THE OFFER BE EXTENDED, AND UNDER WHAT CIRCUMSTANCES?

HOW WILL I BE NOTIFIED IF THE OFFER IS EXTENDED?

3

HOW DO I TENDER MY SHARES?

UNTIL WHAT TIME CAN I WITHDRAW PREVIOUSLY TENDERED SHARES?

HOW DO I WITHDRAW PREVIOUSLY TENDERED SHARES?

WHAT DOES AKCEA’S BOARD OF DIRECTORS THINK OF THE OFFER?

4

WILL THE TENDER OFFER BE FOLLOWED BY A MERGER IF ALL THE SHARES ARE NOT TENDERED?

IF THE OFFER IS COMPLETED, WILL AKCEA CONTINUE AS A PUBLIC COMPANY?

IF I DECIDE NOT TO TENDER, HOW WILL THE OFFER AFFECT MY SHARES?

5

WHAT IS THE MARKET VALUE OF MY SHARES AS OF A RECENT DATE?

IF I ACCEPT THE OFFER, WHEN AND HOW WILL I GET PAID?

IF I AM AN EMPLOYEE OF AKCEA, HOW WILL MY OUTSTANDING EQUITY AWARDS BE TREATED IN THE OFFER AND THE MERGER?

WHAT ARE THE PRINCIPAL U.S. FEDERAL INCOME TAX CONSEQUENCES OF TENDERING MY SHARES IN THE OFFER OR HAVING MY SHARES EXCHANGED FOR CASH PURSUANT TO THE MERGER?

6

WILL I HAVE THE RIGHT TO HAVE MY SHARES APPRAISED?

WITH WHOM MAY I TALK IF I HAVE QUESTIONS ABOUT THE OFFER?

Except as otherwise set forth in this Offer to Purchase, references to “dollars” and “$” shall be to United States dollars.

7

To All Holders of Common Stock of Akcea Therapeutics, Inc.:

INTRODUCTION

Avalanche Merger Sub, Inc., a Delaware corporation (“Purchaser”), is offering to purchase (the “Offer”) all outstanding shares of common stock, par value $0.001 per share (the “Shares”), of Akcea Therapeutics, Inc., a Delaware corporation (“Akcea”), at a price per Share of $18.15, net to the seller in cash, without interest (the “Offer Price”), and subject to any withholding of taxes, upon the terms and subject to the conditions described in this Offer to Purchase (together with any amendments or supplements hereto, this “Offer to Purchase”) and in the related Letter of Transmittal (together with any amendments or supplements thereto, the “Letter of Transmittal”). Purchaser is a wholly owned subsidiary of Ionis Pharmaceuticals, Inc. (“Parent”).

The Offer is being made in connection with the Agreement and Plan of Merger, dated as of August 30, 2020 (together with any amendments or supplements thereto, the “Merger Agreement”), among Akcea, Parent and Purchaser, pursuant to which, after the completion of the Offer and the satisfaction or waiver of certain conditions, Purchaser will be merged with and into Akcea, and Akcea will be the surviving corporation and a wholly owned subsidiary of Parent (such surviving corporation, the “Surviving Corporation” and such merger, the “Merger”).

If your Shares are registered in your name and you tender directly to American Stock Transfer & Trust Company, LLC, the Depository for the Offer (the “Depository”), you will not be obligated to pay brokerage fees or commissions or, except as otherwise provided in Instruction 6 of the Letter of Transmittal, transfer taxes on the purchase of Shares by Purchaser pursuant to the Offer. If you hold your Shares through a broker, dealer, commercial bank, trust company or other nominee you should check with such institution as to whether they charge any service fees or commissions.

In addition, if you do not complete and sign the Internal Revenue Service (“IRS”) Form W-9 that is provided with the Letter of Transmittal, or an IRS Form W-8BEN or other IRS Form W-8, as applicable, or otherwise establish an exemption, you may be subject to U.S. federal backup withholding (at a rate currently equal to 24%) on the gross proceeds payable to you pursuant to the Offer or the Merger. Backup withholding is not an additional tax and any amounts withheld under the backup withholding rules may be refunded or credited against your U.S. federal income tax liability, provided the required information is timely furnished in the appropriate manner to the IRS. All stockholders should review the discussion in Section 13—“Procedures for Tendering Shares” and Section 15—“Certain U.S. Federal Income Tax Consequences of the Offer and the Merger.”

Parent will pay all charges and expenses of the Depository and Alliance Advisors, LLC, the information agent for the Offer (the “Information Agent”).

The Offer is not subject to any financing condition. The Offer is subject to the conditions, among others, that:

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Parent and Purchaser have the right to waive certain of the conditions to the Offer in their sole discretion; provided that (i) Parent and Purchaser may not waive the Minimum Condition and (ii) Parent and Purchaser may not waive the Termination Condition or the Governmental Impediment Condition without the consent of Akcea.

The Offer is subject to other conditions in addition to those set forth above. A more detailed discussion of the conditions to consummation of the Offer is contained in the Introduction, Section 11—“Terms of the Offer” and Section 22—“Conditions of the Offer.”

The Offer will expire at one minute after 11:59 p.m., Eastern Time, on October 9, 2020, unless the Offer is extended. See Section 11—“Terms of the Offer,” Section 22—“Conditions of the Offer” and Section 24—“Certain Legal Matters; Regulatory Approvals.”

After careful consideration, the Akcea board of directors (the “Akcea Board”), acting on the unanimous recommendation of the Affiliate Transactions Committee, comprised solely of independent, disinterested directors of the Akcea Board (the “Affiliate Transactions Committee”), has: (i) determined that the Merger Agreement and the transactions contemplated thereby (the “Transactions”), including the Offer and the Merger, are fair to and in the best interest of Akcea and its stockholders (other than Parent, its affiliates, their respective directors and executive officers and Damien McDevitt, Akcea’s chief executive officer (the “Excluded Holders”)), (ii) declared it advisable to enter into the Merger Agreement, (iii) approved the execution, delivery and performance by Akcea of the Merger Agreement and the consummation of the Transactions, including the Offer and the Merger, (iv) resolved that the Merger shall be effected under Section 251(h) of the DGCL and (v) resolved to recommend that the stockholders of Akcea (other than the Excluded Holders) tender their Shares pursuant to the Offer.

For factors considered by the Akcea Board and the Affiliate Transactions Committee, see Akcea’s Solicitation/Recommendation Statement on Schedule 14D-9 (the “Schedule 14D-9”) filed with the U.S. Securities and Exchange Commission (the “SEC”) in connection with the Offer, a copy of which (without certain exhibits) is being furnished to stockholders concurrently herewith.

The Offer is being made in connection with the Merger Agreement, pursuant to which, after the completion of the Offer and the satisfaction or waiver of certain conditions, the Merger will be effected. The Merger shall become effective when a certificate of merger is filed with the Secretary of State of the State of Delaware (or at such subsequent date and time as may be agreed by Akcea, Parent and Purchaser and specified in the certificate of merger) (the “Effective Time”).

At the Effective Time, each Share (other than Shares held by Akcea, Parent, Purchaser, any wholly owned subsidiary of Parent or Purchaser, or by stockholders of Akcea who have perfected their statutory rights of appraisal under DGCL) will be converted into the right to receive $18.15 in cash, without any interest thereon and subject to any withholding of taxes, upon surrender of the certificate that formerly evidenced such Share or, with respect to uncertificated Shares, upon the receipt by the Depository of an Agent’s Message (as defined below) relating to such Shares.

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The Merger Agreement is more fully described in Section 20—“Summary of the Merger Agreement,” which also contains a discussion of the treatment of Akcea stock options and restricted stock units in the Merger. Section 15—“Certain U.S. Federal Income Tax Consequences of the Offer and the Merger” below describes certain U.S. federal income tax consequences generally applicable to Akcea stockholders whose Shares are tendered and accepted for purchase pursuant to the Offer or whose Shares are converted into the right to receive cash in the Merger.

Because the Merger will be consummated in accordance with Section 251(h) of the DGCL, approval of the Merger will not require a vote of Akcea’s stockholders. Section 251(h) of the DGCL provides that if following consummation of a tender offer for any and all shares of a Delaware corporation whose shares are listed on a national securities exchange or held of record by more than 2,000 holders immediately prior to the execution of the applicable agreement of merger by such corporation, the acquiring entity holds (together with any stock owned by any entity that (i) owns, directly or indirectly, all of the outstanding stock of such acquiring entity or (ii) is a direct or indirect wholly owned subsidiary of such acquiring entity or of any person referred to in the preceding clause (i)) at least the amount of shares of each class of stock of the target corporation that would otherwise be required for the stockholders of the target corporation to adopt a merger agreement with the acquiring entity, and each share of each class or series of stock of the target corporation not irrevocably accepted for purchase in the offer is converted into the right to receive the same consideration as was payable in the tender offer, the target corporation can effect a merger without the vote of the stockholders of the target corporation. Immediately prior to the Offer, Parent owned approximately 76% of all outstanding Shares of Akcea. Therefore, the parties have agreed, and the Merger Agreement requires, that subject to the conditions specified in the Merger Agreement, the Merger will become effective as soon as practicable after the consummation of the Offer, without a vote of Akcea’s stockholders and in accordance with Section 251(h) of the DGCL. As a result of the Merger, Akcea will cease to be a publicly traded company and will become a wholly owned subsidiary of Parent. See Section 20—“Summary of the Merger Agreement.”

This Offer to Purchase and the related Letter of Transmittal contain important information and both documents should be read carefully and in their entirety before any decision is made with respect to the Offer.

SPECIAL FACTORS

The information set forth below regarding Akcea was provided by Akcea, and none of Parent, Purchaser or any of their affiliates or representatives takes any responsibility for the accuracy or completeness of any information regarding meetings or discussions in which Parent or its affiliates or representatives did not participate. The following contains a description of material contacts between representatives of Parent or Purchaser and representatives of Akcea that resulted in the execution of the Merger Agreement and the agreements related to the Offer. For a review of Akcea’s activities relating to these contacts, please refer to the Schedule 14D-9 that will be filed with the SEC and mailed to all Akcea stockholders with this Offer to Purchase.

In December 2014, Parent formed Akcea as a wholly owned subsidiary. Akcea was created in order to develop and commercialize drugs for the treatment of lipid disorders.

In December 2015, Akcea entered into the Cardiometabolic License Agreement (as defined below) with Parent, pursuant to which Parent granted exclusive rights to Akcea to develop and commercialize certain of Parent’s product candidates for the treatment of lipid disorders. Concurrently with the Cardiometabolic License Agreement, Akcea and Parent entered into a services agreement and an investor rights agreement. For more on these agreements see Section 6—“Related Party Transactions.”

Akcea remained wholly owned by Parent until July 2017. At that time, Akcea completed its initial public offering. Since the completion of Akcea’s initial public offering, Parent has retained a majority ownership

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position in Akcea and Akcea has engaged in various transactions with Parent, which are described further below as well as in Section 6—“Related Party Transactions.” In addition, throughout the life of Akcea certain directors of Parent have served on the Akcea Board. At present, two members of the Akcea Board also serve on Parent’s board of directors (the “Parent Board”): Joseph Klein, III (director of Akcea since September 20, 2019) and B. Lynne Parshall (director of Akcea since its formation and executive chairperson of the Akcea Board since December 16, 2019). Ms. Parshall also serves as a Senior Strategic Advisor to Akcea and a Senior Strategic Advisor to Parent and was Parent’s Chief Operating Officer until January 2018. In addition, Stanley Crooke, who currently serves as executive chairperson of the Parent Board, previously served on the Akcea Board while serving as a member of the Parent Board and as the Chief Executive Officer of Parent. Parent’s current chief executive officer is an Akcea Board observer.

In January 2017, Akcea entered into the Novartis Agreement (as defined below) with Novartis Pharma AG (“Novartis”) for the development and commercialization of certain drugs. Akcea received a $75.0 million upfront payment from Novartis in this transaction, and, pursuant to the terms of its existing agreements with Parent, paid Parent a sublicense fee of $15.0 million.

On March 14, 2018, Akcea entered into the TTR License Agreement (as defined below) with Parent. Under the TTR License Agreement, Akcea licensed additional drug candidates from Parent. In connection with the TTR License Agreement, Parent and Akcea also amended and restated the Services Agreement and the Investor Rights Agreement (both as defined below). In addition, Akcea and Parent entered into the Parent SPA (as defined below), pursuant to which Parent purchased $200.0 million of Akcea’s common stock at approximately $18.75 per Share. The TTR License Agreement, the Parent SPA, and the amended and restated Services Agreement and Investor Rights Agreement, and the consummation of the transactions contemplated thereunder, were all approved by a special transaction committee and a majority of Akcea’s stockholders that were unaffiliated with Parent at a special meeting of Akcea’s stockholders held on April 16, 2018. For further information on these agreements, see Section 6—“Related Party Transactions.”

On October 5, 2018, Parent and Akcea announced the receipt of FDA approval for TEGSEDI for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. As a result of the receipt of FDA approval, on October 17, 2018, Akcea issued 1,671,849 shares to Parent as payment of a $50 million milestone under the TTR License Agreement.

In February 2019, Akcea earned a $150.0 million license fee when Novartis exercised its option to license one of Akcea’s products pursuant to the Novartis Agreement. As a result of this option exercise, on March 26, 2019, Akcea issued 2,837,373 shares to Parent as payment of a $75.0 million sublicense fee under the Cardiometabolic License Agreement.

In October 2019, Akcea entered into the Pfizer Agreement (as defined below) for the development and commercialization of AKCEA-ANGPTL3-LRx. On November 19, 2019, under the terms of the Pfizer Agreement, Akcea received a license fee of $250.0 million and Akcea issued 6,873,344 Shares on December 17, 2019 to Parent as payment of a $125.0 million sublicense fee under the Cardiometabolic License Agreement.

On June 22, 2020, the Parent Board held a telephonic meeting, which included certain members of Parent’s management. Members of Parent management recommended that, as a result of challenges faced by Akcea and the impact of those challenges on Parent, Parent should seek to determine whether a potential acquisition of all Shares of Akcea not held by Parent would be desirable or available to the Parent on desirable terms. The Parent Board authorized the existing finance committee of the Parent Board (the “Finance Committee”), which consisted of Frederick Muto, Peter Reikes, Joseph Wender and B. Lynne Parshall, to (i) work with Parent’s management in the review, evaluation and negotiation to determine whether a transaction involving the acquisition of all shares of Akcea not held by Parent would be desirable or available to Parent on desirable terms and, (ii) if such a transaction were determined to be desirable and available to Parent on desirable terms, make a recommendation to the Parent Board with regard to such a transaction. The Parent Board emphasized that any

11

such transaction would require the review and approval of the Parent Board. The Parent Board did not discuss the terms of any potential transaction involving Akcea. Members of Parent management discussed with the Parent Board that as Parent moved forward with exploring whether a potential acquisition of all shares of Akcea not held by Parent would be desirable or available to Parent on desirable terms, prior to any discussion of the terms of such a transaction with Akcea, a letter would be sent to the Akcea Board undertaking the review and approval conditions set forth in the Initial Letter (as defined below). Mr. Klein and Ms. Parshall were in attendance at this meeting.

In the days following the Parent Board’s meeting on June 22, 2020, a representative of Parent discussed with each of Mr. Klein and Ms. Parshall that given their status as a director of Parent and of Akcea, they would not be involved in or informed with respect to the consideration of any potential transaction with Akcea. As a result, Ms. Parshall did not attend or participate in any meetings of the Finance Committee regarding the transaction, and neither Mr. Klein nor Ms. Parshall attended the August 30, 2020 meeting of the Parent Board with respect to the review and approval of a Potential Transaction (as defined below) (which was the only meeting of the Parent Board with respect to a Potential Transaction).

On July 10, 2020, the Finance Committee held an initial telephonic meeting, which also included members of management and representatives of Skadden, Arps, Slate, Meagher & Flom LLP (“Skadden”), Parent’s legal advisor, Goldman Sachs & Co. LLC (“Goldman Sachs”) and Stifel, Nicolaus & Company, Incorporated (“Stifel”), Parent’s financial advisors. The Finance Committee instructed Parent’s management to send the Initial Letter to the Akcea Board. Members of management discussed with the Finance Committee the upcoming process for reviewing a Potential Transaction with assistance of Parent’s advisors. The Finance Committee made no determination as to whether a Potential Transaction was desirable or whether any proposal to acquire Akcea would in fact be submitted to Akcea.

Also on July 10, 2020, Parent sent a letter to the Akcea Board (the “Initial Letter”) stating that Parent was considering a potential transaction that would result in the acquisition of the outstanding Shares not owned by Parent (with subsequent modifications as described below, the “Potential Transaction”). The Initial Letter stated that, if Parent determined to move forward with a Potential Transaction following internal review, Parent expected to submit a non-binding proposal on a confidential basis to Akcea in the coming weeks. It also indicated that Parent was considering whether to offer Parent stock as consideration in a Potential Transaction. The Initial Letter also stated that Parent would engage in any Potential Transaction only if (i) a fully empowered special committee of independent directors was appointed by the Akcea Board to consider (and had the ability to reject) any proposal by Parent regarding a Potential Transaction with the assistance of its own legal and financial advisors, (ii) such special committee approved a Potential Transaction and (iii), in addition to any other vote required, any Potential Transaction negotiated and approved by the special committee was subject to a non-waivable condition requiring approval of a majority of the Shares not owned by Parent or its affiliates, and such approval were obtained prior to the consummation of the Potential Transaction. The Initial Letter also stated that, in its capacity as a stockholder of Akcea, Parent was only interested in participating in a transaction to acquire Shares that it did not currently own and that Parent had no interest in, and would not expect to vote in favor of, any alternative sale, merger or similar transaction involving Akcea. In addition, the Initial Letter indicated that if the special committee did not approve, or the stockholders of Akcea did not approve, a Potential Transaction, such determination would not adversely affect Parent’s future relationship with Akcea, and Parent’s current intention would be to remain as a long-term stockholder of Akcea in the absence of a Potential Transaction.

On July 10, 2020, after sending the Initial Letter to the Akcea Board, Dr. Brett Monia, CEO of Parent, had separate calls with Ms. Parshall and Damien McDevitt, CEO of Akcea, confirming the Akcea Board’s receipt of the Initial Letter and that the Akcea Board would be meeting to consider the Initial Letter.

On July 11, 2020, representatives of Skadden contacted representatives of Ropes & Gray LLP (“Ropes & Gray”), the legal advisor of the Affiliate Transactions Committee of the Akcea Board (the “Affiliate Transactions

12

Committee”), and informed them Parent wished to seek consent to use information concerning Akcea that Parent had previously received in the course of the parties’ business interactions or contractual relationships, for the purpose of evaluating a Potential Transaction. Representatives of Ropes & Gray indicated that the Affiliate Transactions Committee would consider this request.

On July 13, 2020, a representative of Ropes & Gray communicated to Skadden that the Affiliate Transactions Committee would be amenable to authorizing Parent to use information concerning Akcea that Parent had previously received in the course of the parties’ business interactions or contractual relationships, for the purpose of evaluating a Potential Transaction, but only in the context of a consensually negotiated transaction and pursuant to a confidentiality agreement.

On July 17, 2020, Akcea and Parent entered into the Confidentiality Agreement (as defined below) in connection with the Potential Transaction.

On July 22, 2020, representatives of Cowen and Company, LLC (“Cowen”), the Affiliate Transactions Committee’s financial advisor, spoke with representatives of Goldman Sachs and Stifel, to inform them of the Affiliate Transactions Committee’s determination to engage a third-party consulting firm with respect to aspects of the financial projections to be used by the Affiliate Transactions Committee in valuing Akcea in connection with the Potential Transaction (the “Akcea Projections”) and the associated timing for its review.

On July 29, 2020, Skadden provided Ropes & Gray with Parent’s initial request list for due diligence on Akcea.

On several occasions in late July and early to mid August, in addition to the occasions described above, representatives of Cowen spoke with representatives of Goldman Sachs and Stifel, and representatives of Ropes & Gray spoke with representatives of Skadden. These discussions focused on the process regarding the Potential Transaction. They did not involve any proposal for a Potential Transaction or discussion of valuation of Akcea.

On August 6, 2020, Skadden sent Ropes & Gray an updated request list for due diligence on Akcea.

On August 7, 2020 the Finance Committee held a telephonic meeting, which included members of management and representatives from Goldman Sachs, Stifel and Skadden, during which the Finance Committee reviewed a presentation from Goldman Sachs and Stifel and discussed the possibility of submitting an initial conditional, non-binding proposal within a potential range of $15.00 to $16.00, which proposal would be subject to the Parent Board’s approval, negotiation of a mutually acceptable merger agreement and Parent’s due diligence of Akcea. The timing for such a proposal was also discussed given that Goldman Sachs and Stifel had been informed by Cowen that a third-party consulting firm had been engaged to assist the Affiliate Transactions Committee with respect to the Akcea Projections.

On August 19, 2020, Parent delivered a conditional, non-binding proposal (the “Initial Proposal”) to the Affiliate Transactions Committee. The Initial Proposal proposed a purchase price of $16.00 per Share based on available information, payable in cash, to acquire 100% of Akcea’s outstanding Shares, representing a premium of 42% to Akcea’s August 18, 2020 closing stock price. The Initial Proposal also stated that Parent was prepared to work expeditiously to negotiate a definitive agreement. The Initial Proposal stated that the proposal remained subject to due diligence review based on the requests previously provided to Ropes & Gray and was subject to the approval of the Parent Board. Concurrently with the Initial Proposal, Parent sent a proposed draft Merger Agreement.

On August 21, 2020, Skadden confirmed to Ropes & Gray that Parent was interested in pursuing only an all-cash transaction.

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On August 24, 2020, representatives of Cowen, Goldman Sachs and Stifel discussed the Initial Proposal. Cowen informed Goldman Sachs and Stifel that the Initial Proposal was not sufficient to reflect Akcea’s intrinsic value. Goldman Sachs and Stifel requested through Cowen that the Affiliate Transactions Committee provide Parent with additional insight regarding the financial projections on which it was basing its valuation position (the “Additional Projections Information Request”).

On August 25, 2020, the Finance Committee held a telephonic meeting, with members of management and representatives from Goldman Sachs, Stifel and Skadden. The Finance Committee discussed the timing and strategies of a revised conditional, non-binding proposal in light of Akcea’s response to the Initial Proposal. The Finance Committee noted that any revised proposal submitted to Akcea would continue to be subject to the review and approval of the Parent Board.

Following the Finance Committee meeting on August 25, 2020, Cowen responded to the Additional Projections Information Request by providing additional information to Goldman Sachs and Stifel, which consisted of certain peak product net sales information and high level assumptions that are included in the Akcea Projections disclosed under “–Certain Prospective Financial Information,” in the Schedule 14D-9.

On August 25, 2020, Parent submitted a revised conditional, non-binding proposal of $17.00 per Share, representing a premium of 41% to Akcea’s August 25, 2020 closing stock price, which remained subject to the recommendation of the Finance Committee and the subsequent approval of the full Parent Board.

On August 27, 2020, Parent submitted a revised conditional, non-binding proposal of $17.75, representing a premium of 54% to Akcea’s August 26, 2020 closing stock price, which remained subject to the recommendation of the Finance Committee and the subsequent approval of the full Parent Board (the “Second Revised Proposal”). In connection with the Second Revised Proposal, Parent’s advisors communicated to Cowen that Parent desired to seek to negotiate and finalize a merger agreement in order to execute the transaction over the upcoming weekend and publicly announce it the following Monday morning and that the increase reflected in the Second Revised Proposal was based on that timeline.

On August 28, 2020, at the request of the Affiliate Transactions Committee, Skadden received a markup of the initial draft Merger Agreement and an initial draft of the disclosure schedules.

After discussion between Cowen, Goldman Sachs and Stifel on the evening of August 28, 2020, the Affiliate Transactions Committee agreed to proceed with respect to a Potential Transaction with Parent based on a price of $18.15 per Share.

On August 29, 2020, Parent and its representatives were provided access to Akcea’s virtual data room containing the due diligence information previously requested and which Parent had indicated in its Initial Proposal would be necessary for its review of a Potential Transaction. After being granted access to the data room, Parent and its advisors reviewed the information in the data room over the course of August 29, 2020 and August 30, 2020, for the purpose of confirming whether or not the information contained in the data room affected Parent’s view on whether a transaction would be desirable on the proposed terms.

Over August 29, 2020 and August 30, 2020 Ropes & Gray and Skadden exchanged multiple drafts of the Merger Agreement and engaged in both email correspondence and telephonic conferences on various issues related thereto. Disclosure schedules were also separately negotiated, including the $5 million retention pool for Akcea employees disclosed under “—Arrangements between the Company, Ionis and Certain of its Affiliates” in the Schedule 14D-9.

On August 30, 2020, the Parent Board held a telephonic meeting, which included members of management and representatives from Goldman Sachs, Stifel and Skadden. Mr. Klein and Ms. Parshall did not attend the meeting. The Parent Board discussed the proposed financial terms for the transaction with members of

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management, Goldman Sachs and Stifel and reviewed a presentation from Goldman Sachs and Stifel. Representatives of Skadden reviewed the material terms of the merger agreement with the Parent Board. The Finance Committee recommended that the Parent Board approve the transaction. The Parent Board (other than Mr. Klein and Ms. Parshall), unanimously approved the terms of the transaction and the Merger Agreement, including that the Merger would be effected pursuant to Section 251(h) of the DGCL.

Following the meeting of the Parent Board, on the evening of August 30, 2020, Akcea and Parent executed the Merger Agreement.

On the morning of August 31, 2020, Akcea and Parent issued a joint press release announcing the transaction.

On September 14, 2020, Purchaser commenced the offer and filed the Tender Offer Statement on Schedule TO (the “Schedule TO”).

The rules of the SEC require Parent to express its belief to security holders of Akcea who are unaffiliated with Akcea as to the fairness of the transaction. We believe that the transactions contemplated by the Merger Agreement, including the Offer and the Merger, and the Offer Price to be received by security holders of Akcea who are unaffiliated with Akcea pursuant to the Offer and the Merger, are fair to such security holders.

Parent believes that the price to be paid in the Offer is fair to security holders of Akcea who are unaffiliated with Akcea. Parent bases its belief on the following factors, each of which, in our judgment, supports our view as to the fairness of the transaction:

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In addition, Parent believes that the Offer is procedurally fair to security holders of Akcea who are unaffiliated with Akcea, based on the following factors:

Parent also considered the following factors, each of which Parent considered negative in its considerations concerning the fairness of the terms of the transaction:

Parent did not find it practicable to assign, nor did it assign, relative weights to the individual factors considered in reaching its conclusion as to fairness. Parent’s financial advisors, Goldman Sachs & Co. LLC and Stifel, Nicolaus & Company, Incorporated, were not asked to and have not delivered a fairness opinion to the board of directors of Parent or to any other affiliate of Parent in connection with the Offer.

In reaching its conclusion as to fairness, Parent did not consider the liquidation value or net book value of Akcea. The liquidation value was not considered because Akcea is a viable going concern and Parent has no plans to liquidate Akcea. Therefore, Parent believes that the liquidation value of Akcea is irrelevant to a determination as to whether the Offer is fair to unaffiliated stockholders. Further, Parent did not consider net book value, which is an accounting concept, as a factor because it believes that net book value is not a material indicator of the value of Akcea as a going concern but rather is indicative of historical costs. Except as otherwise disclosed in this Offer to Purchase, and other than the contacts between Akcea and “Party A” as described in the Schedule 14D-9 under the heading “Background of the Offer and the Merger,” Parent is not aware of any firm offers made by a third party to acquire Akcea during the past two years and in any event has no intention of selling the Shares it owns. Parent did not consider third-party offers in reaching its conclusion as to fairness.

The foregoing discussion of the information and factors considered and given weight by Parent is not intended to be exhaustive, but includes the factors considered by Parent that it believes to be material. Parent’s view as to the fairness of the transaction to stockholders of Akcea that are unaffiliated with Parent should not be construed as a recommendation to any stockholder as to whether that stockholder should tender in the Offer.

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Purpose of the Offer. The purpose of the Offer and the Merger is for Parent, through Purchaser, to acquire the entire equity interest in Akcea. Pursuant to the Merger, Parent will acquire all of the stock of Akcea not purchased pursuant to the Offer or otherwise. Stockholders of Akcea who sell their Shares in the Offer will cease to have any equity interest in Akcea or any right to participate in its earnings and future growth.

Parent believes that a number of benefits would follow from Akcea becoming a wholly owned subsidiary of Parent at this time, including the benefits of aligning the strategic priorities of Parent and Akcea under a single leadership team; enabling Parent to generate additional value from Akcea’s pipeline and commercial products in order to facilitate future investments and support Parent’s long-term capital allocation strategy; and realizing potential cost synergies associated with the acquisition.

Parent and Purchaser did not consider any alternative structures for the proposed transaction. Parent and Purchaser believe that the tender offer and second step merger structure was preferable to a one-step merger because they believe that this structure can provide a faster and more efficient process for completing the transaction than structures which require calling a special meeting of Parent’s stockholders.

Effects of the Offer. If the Offer is consummated, the interest of Parent in Akcea’s net book value and net earnings would increase in proportion to the number of Shares acquired in the Offer. If a merger is consummated, Parent’s indirect interest in such items would increase to 100%, and Parent would be entitled to all benefits resulting from that interest, including all income generated by Akcea’s operations and any future increase in Akcea’s value. Former stockholders would thereafter have no opportunity to participate in the earnings and growth of Akcea and would not have any right to vote on corporate matters. Similarly, after any such merger, Parent would also bear the entire risk of losses generated by Akcea’s operations and any decrease in the value of Akcea, and former stockholders would not face the risk of losses generated by Akcea’s operations or decline in the value of Akcea.

According to Akcea’s Annual Report on Form 10-K for the fiscal year ending December 31, 2019 (the “Akcea 10-K”), as of December 31, 2019, Akcea had federal and state tax net operating loss carry forwards on a separate basis of $99.5 million and $1.4 million, respectively. Such net operating losses may be available to offset taxable income (if any) generated by Akcea or Parent’s U.S. consolidated tax group (which may include Akcea after the closing), and thereby reduce the amount of taxes owed by Parent and its subsidiaries. The timing and amount of the tax savings will depend on a number of factors, including the overall amount of Akcea’s net operating losses through the closing (which has yet to be calculated), whether Akcea or Parent generates U.S. federal taxable income after the closing (and when and in what amount) and the tax rates in effect at the time net operating losses are utilized.

Merger Without a Stockholder Vote. If the Offer is consummated, we do not anticipate seeking the approval of Akcea’s remaining public stockholders before effecting the Merger. Section 251(h) of the DGCL provides that following consummation of a successful tender offer for a public corporation, and subject to certain statutory provisions, if the acquiring corporation owns at least the amount of shares of each class of stock of the target corporation that would otherwise be required to adopt a merger agreement for the target corporation, and the other stockholders receive the same consideration for their stock in the merger as was payable in the tender offer, the acquiring corporation can effect a merger without the action of the other stockholders of the target corporation. Accordingly, if we consummate the Offer, we intend to effect the closing of the Merger (the “Closing”) without a vote of the stockholders of Akcea in accordance with Section 251(h) of the DGCL, upon the terms and subject to the satisfaction or waiver of the conditions to the Merger, as soon as practicable after the consummation of the Offer. Accordingly, we do not expect there to be a significant period of time between the consummation of the Offer and the consummation of the Merger.

Plans for Akcea. At the Effective Time, the certificate of incorporation of Akcea will be amended and restated in its entirety pursuant to the terms of the Merger Agreement. As of the Effective Time, the bylaws of

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the Surviving Corporation will be amended and restated to conform to the bylaws of Purchaser as in effect immediately prior to the Effective Time, except that references to the name of Purchaser will be replaced by references to the name of the Surviving Corporation. Purchaser’s directors and officers immediately prior to the Effective Time will be the initial directors and officers of the Surviving Corporation until their respective successors are duly elected and qualified, or their earlier death, resignation or removal. See Section 20— “Summary of the Merger Agreement—Board of Directors and Officers.”

Parent is conducting a detailed review of Akcea and its assets, corporate structure, capitalization, operations, properties, policies, management and personnel, and will consider which changes would be desirable in light of the circumstances that exist upon completion of the Offer and the Merger. Parent will continue to evaluate the business and operations of Akcea during the pendency of the Offer and after the consummation of the Offer and the Merger and will take such actions as they deem appropriate under the circumstances then existing. Thereafter, Parent intends to review such information as part of a comprehensive review of Akcea’s business, operations, capitalization and management with a view to optimizing development of Akcea’s potential in conjunction with Akcea’s or Parent’s existing businesses. Possible changes could include changes in Akcea’s business, corporate structure, certificate of incorporation, bylaws, capitalization, board of directors and management. Plans may change based on further analysis and Parent, Purchaser and, after completion of the Offer and the Merger, the reconstituted Akcea Board reserves the right to change their plans and intentions at any time, as deemed appropriate.

Except as disclosed in this Offer to Purchase, Parent and Purchaser do not have any present plan or proposal that would result in the acquisition by any person of additional securities of Akcea, the disposition of securities of Akcea, an extraordinary corporate transaction, such as a merger, reorganization or liquidation, involving Akcea or the sale or transfer of a material amount of assets of Akcea.

Financial Interests. The financial interests of Parent with regard to the Offer Price are generally adverse to the financial interests of the stockholders being asked to tender their Shares because Parent has an interest in acquiring the Shares as inexpensively as possible and the stockholders being asked to tender their Shares have an interest in selling their Shares for the highest possible price.

Executive Officers and Directors of Akcea. The stockholders being asked to tender their Shares should be aware that the executive officers and certain directors of Akcea have interests in connection with the Offer and the Merger that present them with actual or potential conflicts of interest. A description of these interests, including the information required to be disclosed pursuant to Item 402(t) of Regulation S-K, is included in the Schedule 14D-9 under the heading “Arrangements with the Company’s Directors and Executive Officers,” which description and information is incorporated herein by reference.

Conflicts of Interest. In considering the fairness of the consideration to be received in the Offer, stockholders should be aware that Parent has certain current actual or potential conflicts of interest in connection with the Offer and the Merger. As a result of Parent’s current ownership of approximately 76% of the outstanding Shares, Parent may be deemed to control Akcea. In addition, certain of Parent’s directors are also directors of Akcea, and one of Parent’s directors is party to a strategic advisory services agreement with Akcea under which she is entitled to receive compensation, in each case as described in the Schedule 14D-9 under the heading “Arrangements with the Company’s Directors and Executive Officers.” We note that the Akcea Board, based on the unanimous recommendation of the Affiliate Transactions Committee, comprised solely of independent, disinterested directors who are unaffiliated with Parent, approved the Merger Agreement and determined that the Offer is fair to, and in the best interests of, Akcea and its stockholders (other than Parent, its affiliates, their respective directors and executive officers and Damien McDevitt, Akcea’s chief executive officer).

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Except as set forth elsewhere in this Offer to Purchase or Schedule A to this Offer to Purchase: (i) none of Purchaser, Parent or, to Purchaser’s and Parent’s knowledge, the persons listed in Schedule A to this Offer to Purchase or any associate or majority owned subsidiary of Parent, Purchaser or of any of the persons so listed, beneficially owns or has a right to acquire any Shares or any other equity securities of Akcea; (ii) none of Purchaser, Parent or, to Purchaser’s and Parent’s knowledge, the persons or entities referred to in clause (i) above has effected any transaction in the Shares or any other equity securities of Akcea during the past 60 days; (iii) none of Purchaser, Parent or, to Purchaser’s, and Parent’s knowledge, the persons listed in Schedule A to this Offer to Purchase, has any contract, arrangement, understanding or relationship with any other person with respect to any securities of Akcea (including, but not limited to, any contract, arrangement, understanding or relationship concerning the transfer or the voting of any such securities, joint ventures, loan or option arrangements, puts or calls, guaranties of loans, guaranties against loss or the giving or withholding of proxies, consents or authorizations); (iv) during the two years before the date of this Offer to Purchase, there have been no transactions between Purchaser, Parent, their respective subsidiaries or, to Purchaser’s and Parent’s knowledge, any of the persons listed in Schedule A to this Offer to Purchase, on the one hand, and Akcea or any of its executive officers, directors or affiliates, on the other hand, that would require reporting under SEC rules and regulations; (v) during the two years before the date of this Offer to Purchase, there have been no contacts, negotiations or transactions between Purchaser, Parent, their respective subsidiaries or, to Purchaser’s and Parent’s knowledge, any of the persons listed in Schedule A to this Offer to Purchase, on the one hand, and Akcea or any of its subsidiaries or affiliates, on the other hand, concerning a merger, consolidation or acquisition, a tender offer or other acquisition of securities, an election of directors or a sale or other transfer of a material amount of assets; (vi) none of Purchaser, Parent or, to Purchaser’s and Parent’s knowledge, the persons listed in Schedule A to this Offer to Purchase, has been convicted in a criminal proceeding during the past five years (excluding traffic violations or similar misdemeanors); (vii) none of the persons listed on Schedule A of this Offer to Purchase has made a recommendation either in support of or opposed to the Offer or the Merger and (viii) none of Purchaser, Parent or, to Purchaser’s and Parent’s knowledge, the persons listed in Schedule A to this Offer to Purchase, has been a party to any judicial or administrative proceeding during the past five years that resulted in a judgment, decree or final order enjoining that person from future violations of, or prohibiting activities subject to, federal or state securities laws or a finding of any violation of federal or state securities laws.

Akcea has informed Parent that, to the knowledge of Akcea, each executive officer, director and affiliate (excluding Parent) of Akcea currently intends to tender all Shares held of record or beneficially owned by such person or entity in the Offer. However, there are no agreements requiring them to do so.

Merger Agreement. The Merger Agreement governs the contractual rights among Akcea, Parent and Purchaser in relation to the Transactions. For additional detail regarding the Merger Agreement, see Section 20—“Summary of the Merger Agreement.”

Non-Disclosure Agreement. Parent and Akcea are party to a letter agreement, effective as of July 17, 2020, regarding certain confidentiality obligations between Akcea and Parent (the “Confidentiality Agreement”). Under the terms of the Confidentiality Agreement, Akcea and Parent agreed not to (i) use any confidential information of the other party except for and solely to the extent necessary to evaluate, negotiate and consummate the transaction between the parties or (ii) disclose any such confidential information to third parties, in each case subject to certain exceptions. For additional detail regarding the Confidentiality Agreement, see Section 20—“Summary of the Merger Agreement.”

Prior Investments. Upon the closing of Akcea’s initial public offering on July 19, 2017 (the “IPO”), Parent received (i) 28,884,540 Shares upon the conversion of Series A preferred stock of Akcea acquired by Parent prior to the IPO and (ii) 13,438,339 Shares in satisfaction of Akcea’s obligations to Parent pursuant to a Senior

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Unsecured Line of Credit Agreement, dated as of January 18, 2017, by and between Akcea and Parent. Parent also purchased 3,125,000 Shares in the IPO at a purchase price of $8.00 per Share.

On April 17, 2018, Parent (i) received 8,000,000 Shares in satisfaction of Akcea’s obligations to Parent pursuant to that certain Development, Commercialization, Collaboration, and License Agreement, dated March 14, 2018, between Akcea and Parent (the “TTR License Agreement”) and (ii) purchased 10,666,666 Shares pursuant to that certain Stock Purchase Agreement, dated March 14, 2018, between Akcea and Parent (the “Parent SPA”) at a purchase price of $18.75 per Share. For additional detail regarding these transactions, see “—License Agreements.”

On August 3, 2018 and October 17, 2018, Parent received 1,597,571 Shares and 1,671,849 Shares, respectively, in satisfaction of certain of Akcea’s obligations to Parent pursuant to the TTR License Agreement. For additional detail regarding these transactions, see “—License Agreements”.

On March 29, 2019 and December 17, 2019, Parent received 2,837,373 Shares and 6,873,344 Shares, respectively, in satisfaction of certain of Akcea’s obligations to Parent pursuant to that certain Development, Commercialization and License Agreement, dated December 18, 2015, between Akcea and Parent (the “Cardiometabolic License Agreement”). For additional detail regarding these transactions, see “—License Agreements”. Immediately following Parent’s receipt of the Shares on December 17, 2019, Parent and its affiliates collectively beneficially owned approximately 76% of the outstanding Shares.

As of September 8, 2020, Parent and its affiliates collectively beneficially owned 77,094,682 Shares representing approximately 76% of the outstanding Shares.

License Agreements. In December 2015, Parent and Akcea entered into the Cardiometabolic License Agreement related to its cardiometabolic franchise and a services agreement. In March 2018, Parent and Akcea entered into the TTR License Agreement related to its TTR franchise. Akcea also has strategic collaborations with Novartis, Pfizer Inc. (“Pfizer”) and PTC Therapeutics International Limited (“PTC Therapeutics”) pursuant to which Akcea sublicenses certain products licensed to it by Parent. Milestone payments and royalties that Akcea earns on these strategic collaborations are shared with Parent. The following sections summarize these related party agreements with Parent.

Cardiometabolic Development, Commercialization and License Agreement. The Cardiometabolic License Agreement granted exclusive rights to Akcea to develop and commercialize WAYLIVRA, AKCEA-APO(a)-LRx, AKCEA-APOCIII-LRx, and AKCEA-ANGPTL3-LRx (collectively, the “Lipid Drugs”). Parent granted Akcea an exclusive license to certain patents and know-how to develop and commercialize products containing the Lipid Drugs. Parent also granted Akcea a non-exclusive license to the Parent antisense platform technology for Akcea to develop and commercialize products containing the Lipid Drugs. Parent also granted Akcea non-exclusive rights to manufacture the Lipid Drugs in Akcea’s own facility or at a contract manufacturer. As part of the Cardiometabolic License Agreement, both companies agreed not to work with any other parties to develop or commercialize other RNA-targeting medicines that are designed to inhibit any of the Lipid Drug targets so long as Akcea is developing or commercializing the Lipid Drugs.

Akcea and Parent share development responsibilities for the Lipid Drugs, other than the medicines licensed to Novartis pursuant to the Novartis Agreement (as defined below), and AKCEA-ANGPTL3-LRx, which is licensed to Pfizer pursuant to the Pfizer Agreement (as defined below) (such excluded Lipid Drugs, collectively, the “Excluded Lipid Drugs”). Akcea pays Parent for the research and development expenses it incurs on Akcea’s behalf, which include both external and internal expenses. A Joint Steering Committee (“JSC”) comprising two senior members from each company sets the development strategy for the Lipid Drugs by mutual agreement. A regulatory subcommittee, established by the JSC and having equal membership from each company, sets the regulatory strategy for each of the Lipid Drugs by mutual agreement. If the regulatory sub-committee cannot agree on an issue related to the regulatory strategy for any one of the Lipid Drugs, the disputed issues are

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submitted to a mutually agreed-upon regulatory expert, with the costs of the expert shared between the companies and the expert’s decision being binding. At the time of the Cardiometabolic License Agreement, Akcea agreed to the initial membership of a cardiometabolic advisory board that advises the JSC on matters related to the development of the Lipid Drugs. Akcea must notify Parent of all meetings of this advisory board and Parent personnel have the ability to attend these meetings.

As Akcea commercializes each of the Lipid Drugs other than the Excluded Lipid Drugs, it pays Parent royalties from the mid-teens to the mid-twenty percent range on sales related to the Lipid Drugs that it sells. If Akcea sells a Lipid Drug for a Rare Disease Indication (defined in the Cardiometabolic License Agreement as less than 500,000 patients worldwide or an indication that required a Phase 3 program of less than 1,000 patients and less than two years of treatment), it pays a higher royalty rate to Parent than if it sells a Lipid Drug for a Broad Disease Patient Population (defined in the agreement as more than 500,000 patients worldwide or an indication that required a Phase 3 program of 1,000 or more patients and two or more years of treatment). Other than with respect to the Excluded Lipid Drugs, if Akcea’s annual sales reach milestones of $500 million, $1 billion and $2 billion, it is obligated to pay Parent in the amount of $50 million for each sales milestone reached by each Lipid Drug. If and when triggered, Akcea pays Parent each of these sales milestones over the subsequent 12 quarters in equal payments. Akcea shares 50% of payments it receives from Novartis and Pfizer with Parent.

To sublicense one or more Lipid Drugs licensed to it under the Cardiometabolic License Agreement, Akcea needs to mutually agree with Parent on the terms of the sublicense. If Akcea sublicenses any one of the Lipid Drugs to a commercial partner, it is required to share 50% of any revenue from the commercial partner with Parent, excluding (1) money received from its partner specifically designated to fund future research and development costs and (2) money it is obligated to spend in support of commercialization of a Lipid Drug in a co-commercialization arrangement.

Either party may terminate the Cardiometabolic License Agreement if the other party is in material breach of the agreement. In such a circumstance, the party that is in breach has an opportunity to cure the breach prior to the other party terminating the agreement.

In April 2017, Parent granted Akcea a right of first negotiation with respect to Parent development candidates that are designed to treat a rare cardiometabolic disease or a rare inherited metabolic disease, where Akcea has the capability and financial and other resources to develop and commercialize the development candidate and Parent does not have an agreement with a third party that would preclude granting Akcea this right. If Akcea exercises its right of first negotiation for an eligible development candidate, Akcea and Parent are to negotiate in good faith the terms of an exclusive license for Akcea to develop and commercialize the development candidate. If Akcea and Parent cannot agree to the terms of such a license, Parent may grant a license to a third party on terms no more favorable than Parent last offered to Akcea. This right of first negotiation expires in April 2024.

TTR Development, Commercialization, Collaboration, and License Agreement. In March 2018, Parent and Akcea entered into the TTR License Agreement and the Parent SPA, which were both approved by a majority of Akcea’s stockholders other than Parent and its affiliates at a special meeting of stockholders held on April 16, 2018, and which both closed on April 17, 2018 (such transaction, the “Inotersen Transaction”). In addition, in connection with the Inotersen Transaction, Akcea entered into an amended and restated services agreement and an amended and restated investor rights agreement with Parent. For additional detail regarding the amended and restated services agreement, see “—Services Agreement”. For additional detail regarding the amended and restated investor rights agreement, see “—Investor Rights Agreement”.

In accordance with the terms and provisions of the TTR License Agreement, Akcea received the rights: (a) to commercialize inotersen and perform certain other non-commercial activities with respect to inotersen, in each case, in accordance with a global strategic plan; (b) to assist in the development, through the completion of

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all pivotal studies, of a follow-on medicine to inotersen, AKCEA-TTR-LRx, and to perform other non-commercial activities with respect to AKCEA-TTR-LRx; (c) to commercialize AKCEA-TTR-LRx, following receipt of regulatory approval in accordance with a global strategic plan; (d) to share in profits of sales of, and losses incurred with respect to, inotersen and AKCEA-TTR-LRx; and (e) to manufacture (including through a third party) each product following receipt of regulatory approval for such product.

Pursuant to the TTR License Agreement, Parent granted to Akcea (i) an exclusive, worldwide license under Parent’s patents and know-how (other than manufacturing patents and know-how) to develop and sell inotersen and AKCEA-TTR-LRx and (ii) a non-exclusive, worldwide license under the Parent manufacturing patents and know-how. Akcea may grant sublicenses under the rights granted to it with Parent’s prior written consent, not to be unreasonably withheld and with certain exceptions. In addition, the parties agreed to certain exclusivity covenants that prevent (A) each company from clinically developing or commercializing products that use the same mechanism of action as the products under the TTR License Agreement and (B) Akcea from clinically developing or commercializing products that are reasonably expected to decrease the market share for a product under the TTR License Agreement and that treats or is intended to treat transthyretin amyloidosis or any other indication for which a product under the TTR License Agreement is being developed or commercialized, in each case ((A) or (B)) without the other party’s consent.

Akcea granted to Parent a fully-paid, royalty-free, irrevocable, worldwide, non-exclusive, sublicensable license under any collaboration technology Akcea develops under the TTR License Agreement to develop, manufacture and commercialize products that include an oligonucleotide as an active pharmaceutical ingredient (other than competing products during the term of the TTR License Agreement).

The TTR License Agreement remains in effect until the expiration of all included payment obligations, unless earlier terminated. The TTR License Agreement may be terminated under certain circumstances, including: (i) by mutual written consent of the parties; (iii) by either party if any applicable law makes the transaction documents illegal or otherwise restrains transaction consummation; (iv) by either party, for the other’s uncured material breach under the TTR License Agreement; (v) by Akcea for convenience with written notice to Parent; or (vi) by Parent if Akcea disputes the validity of any Parent patent right licensed to Akcea under the TTR License Agreement. Upon termination, all rights received under the TTR License Agreement will terminate.

Akcea agreed to share inotersen and AKCEA-TTR-LRx profits and losses with Parent as follows: for inotersen, beginning on January 1, 2019, Akcea shares profits and losses from the development and commercialization of inotersen with Parent (A) on a 60/40 basis (60% to Parent and 40% to Akcea) through the end of the quarter in which the first commercial sale of AKCEA-TTR-LRx occurs, and (B) on a 50/50 basis commencing on the first day of the first quarter thereafter; and for AKCEA-TTR-LRx, beginning January 1, 2018, Akcea shares all profits and losses from the development and commercialization of AKCEA-TTR-LRx on a 50/50 basis with Parent.

As consideration for the grant of rights under the TTR License Agreement, Akcea paid an upfront licensing fee of $150 million, which was paid through the issuance of 8,000,000 Shares under the Parent SPA, priced by reference to a trading average at the time of execution of the Parent SPA. In addition, Akcea is obligated to make milestone payments to Parent in connection with the achievement of certain development, regulatory and commercialization events. Akcea may elect to pay each milestone payment in cash or Shares and Parent may require payment in Shares. Once Akcea has achieved the milestone event for aggregate worldwide annual net sales of $750 million for products under the TTR License Agreement, all subsequent milestone payments must be paid in cash.

On April 17, 2018, to support the commercialization of TEGSEDI and AKCEA-TTR-LRx, Parent purchased 10,666,666 Shares for $200 million under the Parent SPA.

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On July 11, 2018, Akcea received regulatory approval in the E.U. for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (“hATTR amyloidosis”). As a result of the regulatory approval in the E.U., on August 3, 2018, Akcea issued 1,597,571 Shares to Parent as payment of the $40 million regulatory approval milestone for TEGSEDI.

On October 5, 2018, Akcea received regulatory approval for TEGSEDI from the FDA for the treatment of polyneuropathy of hATTR amyloidosis in adults in the U.S. As a result of the regulatory approval in the U.S., on October 17, 2018, Akcea issued 1,671,849 Shares to Parent as payment of the $50 million regulatory approval milestone for TEGSEDI.

Novartis Agreement. On January 5, 2017, Parent, Akcea and Novartis entered into a Stock Purchase Agreement (the “Novartis SPA”) in connection with the Strategic Collaboration, Option and License Agreement entered into between Akcea and Novartis (as amended, the “Novartis Agreement”) for the development and commercialization of AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx. Under the Novartis SPA, in July 2017, Novartis purchased 6,250,000 Shares in a private placement concurrent with the completion of Akcea’s IPO at a price per Share equal to the IPO price.

On January 18, 2017, Parent and Akcea entered into a Letter Agreement regarding the Cardiometabolic License Agreement to reflect the agreed upon payment terms with respect to the upfront option payment that Akcea received from Novartis and to allocate the premium that Novartis paid for Parent’s common stock in connection with Akcea’s strategic collaboration with Novartis.

Under the Novartis Agreement, Akcea received $75 million in an upfront option payment in February 2017, of which it retained $60 million and paid Parent a $15 million sublicense fee, and Novartis purchased $100 million of Parent’s common stock at a premium. Akcea also received a $150 million license fee when Novartis exercised its option to license AKCEA-APO(a)-LRx in February 2019, for which Akcea issued 2,837,373 Shares to Parent in March 2019 as payment of a $75 million sublicense fee.

In addition, Akcea is obligated to share any milestone payments and royalties equally with Parent. Under the Novartis Agreement, Akcea is eligible to receive up to $675 million in milestone payments from Novartis for AKCEA-APO(a)-LRx, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $360 million for the achievement of commercialization milestones. Akcea is also eligible to receive tiered, double-digit royalties in the mid-teens to low twenty percent range on net sales of AKCEA-APO(a)-LRx; these royalties would be reduced upon the expiration of certain patents or if a generic competitor negatively impacts the product in a specific country.

The Novartis Agreement is described more fully in the Schedule 14D-9 under the heading “License Agreements—Strategic Collaboration With Novartis.”

Pfizer Agreement. On October 4, 2019, Akcea entered into a License Agreement with Pfizer (the “Pfizer Agreement”), which has a potential aggregate transaction value of up to $1.6 billion, plus royalties, which Akcea would generally be required to share equally with Parent. Under the Pfizer Agreement, Akcea received a license fee of $250 million from Pfizer on November 19, 2019, for which Akcea issued 6,873,344 Shares on December 17, 2019, to Parent as payment of a $125 million sublicense fee.

In addition, Akcea is obligated to share any milestone payments and royalties equally with Parent. Under the Pfizer Agreement, Akcea is eligible to receive up to $1.3 billion in milestone payments, including up to $205 million for the achievement of development milestones, up to $250 million for the achievement of regulatory milestones and up to $850 million for the achievement of commercialization milestones. Akcea is also eligible to receive tiered, double-digit royalties in the mid-teens to low twenty percent range on net sales of AKCEA-ANGPTL3-LRx; these royalties would be reduced upon the expiration of certain patents or if a generic competitor negatively impacts the product in a specific country.

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The Pfizer Agreement is described more fully in the Schedule 14D-9 under the heading “License Agreements—Strategic Collaboration With Pfizer.”

PTC Agreement. On August 1, 2018, Akcea entered into a Collaboration and License Agreement (the “PTC Agreement”) with PTC Therapeutics to commercialize TEGSEDI, WAYLIVRA and products containing those compounds (collectively, the “PTC Products”) in Latin America and certain Caribbean countries (the “PTC Territory”). In addition, Akcea has granted to PTC Therapeutics a right of first negotiation to commercialize AKCEA-TTR-LRx, a follow-on product candidate to inotersen, on an exclusive basis in the PTC Territory. Parent is entitled to receive certain percentage of license fees, royalties and milestone payments Akcea receives under the PTC Agreement.

Akcea is entitled to receive royalty payments in the mid-twenty percent range of net sales on a country-by-country and product-by-product basis, commencing on the earlier to occur of (1) 12 months after the first commercial sale of such PTC Product in Brazil or (2) the date when PTC Therapeutics, its affiliates or sublicensees have recognized revenue of $10 million or more in cumulative net sales for such PTC Product in the PTC Territory. The royalty payments are subject to reduction in certain circumstances as set forth in the PTC Agreement.

In May 2019, Akcea received $6.0 million from PTC Therapeutics as a result of regulatory approval of WAYLIVRA in Europe, of which Akcea paid Parent $3.0 million as a sublicense fee under the Cardiometabolic License Agreement. In October 2019, Akcea received $4.0 million from PTC Therapeutics as a result of regulatory approval of TEGSEDI in Brazil, of which Akcea paid Parent $2.4 million as a sublicense fee under the TTR License Agreement.

PTC Therapeutics’ obligation to pay royalties to Akcea begins on the earlier of 12 months after the first commercial sale of a product in Brazil or the date that PTC Therapeutics recognizes revenue of at least $10.0 million in the PTC Territory; these royalties will be reduced upon the expiration of certain patents or if a generic competitor negatively impacts the market share of the product in the PTC Territory. Milestone payments and royalties that Akcea is eligible to receive from PTC Therapeutics for TEGSEDI are split 60% to Parent and 40% to Akcea in accordance with the TTR License Agreement. All WAYLIVRA milestone payments and royalties that Akcea is eligible to receive from PTC Therapeutics are split equally with Parent in accordance with the Cardiometabolic License Agreement. PTC Therapeutics is solely responsible for the commercialization of the products in the PTC Territory at its sole cost and expense, including the pursuit and maintenance of applicable regulatory approvals. Unless earlier terminated, the PTC Agreement will continue in effect until the date on which the royalty term and all payment obligations with respect to all products in all countries in the PTC Territory have expired.

The PTC Agreement is described more fully in the Schedule 14D-9 under the heading “License Agreements—Strategic Collaboration with PTC Therapeutics.”

Services Agreement. Parent and Akcea originally entered into a Services Agreement on December 18, 2015, in conjunction with the Cardiometabolic License Agreement. Parent and Akcea entered into an Amended and Restated Services Agreement on March 14, 2018 (the “Services Agreement”) in connection with the Inotersen Transaction. The primary purpose of the Services Agreement is to allow for the expansion of general and administrative services provided by Parent to Akcea to cover the TEGSEDI and AKCEA-TTR-LRx products under terms substantially similar to the prior 2015 services agreement.

Under the Services Agreement, Parent provides Akcea with certain services, including, without limitation, general and administrative support services and development support services. Parent has allocated a certain percentage of personnel to perform the services that it provides to Akcea based on its good faith estimate of the required services. Akcea pays Parent for these allocated costs, which reflect the Parent full-time equivalent (“FTE”) rate for the applicable personnel, plus out-of-pocket expenses, such as occupancy costs, associated with

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the FTEs allocated to providing Akcea with these services. Akcea does not pay a mark-up or profit on the external or internal expenses Parent bills to it. Parent invoices Akcea quarterly for all amounts due under the services agreement and payments are due within 30 days of the receipt of an invoice.

In addition, as long as Parent continues to consolidate Akcea’s financials, Akcea is obligated to comply with Parent’s policies and procedures and internal controls. As long as Akcea is consolidated into Parent’s financial statements under U.S. Generally Accepted Accounting Practices (“GAAP”), Akcea may continue to access the following services from Parent:

The Services Agreement provides that, if Akcea desires to provide the foregoing services internally, and doing so would not negatively impact Parent’s internal controls and procedures for financial reporting, Akcea has the right to negotiate in good faith with Parent for a reduced scope of services related to the aforementioned services. When Parent determines it should no longer consolidate Akcea’s financials, Akcea may mutually agree with Parent in writing to extend the term of this arrangement in six-month increments.

The Services Agreement permits Akcea to establish its own benefits programs or continue to use Parent’s benefits programs, in which case, Akcea must provide Parent a minimum advance notice to opt-out of using Parent’s benefits programs.

Investor Rights Agreement. Akcea originally entered into an Investor Rights Agreement with Parent on December 18, 2015, in conjunction with the Cardiometabolic License Agreement. Akcea entered into an Amended and Restated Investor Rights Agreement with Parent in April 2018 (the “Investor Rights Agreement”) in connection with the Inotersen Transaction.

Under the Investor Rights Agreement, as long as Parent owns at least 50% of Akcea’s stock, (i) Akcea needs to obtain Parent’s approval to issue equity or debt securities in Akcea in a financing valued at over $10 million, (ii) Akcea needs to obtain Parent’s approval to in-license a product, acquire a product or acquire another company and, (iii) subject to certain exceptions, equity issuances by Akcea, including the issuance of common stock, are subject to a right of first refusal by Parent. In addition, for so long as greater than 50% of Akcea’s revenue is derived from products licensed from Parent, and subject to the execution of confidentiality agreements, Parent may appoint one non-voting observer to Akcea’s audit and compensation committees.

Real Property Sublease. On November 12, 2018, Akcea entered into an operating lease agreement with Parent to sublease 4,723 square feet of office space located in Carlsbad, California. The commencement date was March 2018 and the term of the lease is 64 months with a four-month free rent period. There is no extension option for this lease.

Transactions with Certain Akcea Directors and Officers. In addition to serving on the Akcea Board, both B. Lynne Parshall and Joseph Klein, III serve on the Parent Board. Ms. Parshall also serves as a Senior Strategic Advisor to Parent. Both Ms. Parshall and Mr. Klein receive cash compensation, stock awards, and option awards

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in respect of their roles. Ms. Parshall’s total compensation in respect of her roles as a director of Parent and a Senior Strategic Advisor to Parent totaled approximately $1,552,000 year-to-date in fiscal year 2020, $2,428,000 in fiscal year 2019 and $1,845,000 in fiscal year 2018. Mr. Klein’s total compensation in respect of his role as a director of Parent totaled approximately $760,000 year-to-date in fiscal year 2020, $1,166,000 in fiscal year 2019 and $635,000 in fiscal year 2018. The foregoing amounts reflect certain assumptions regarding each individual’s equity compensation. For a description of the compensation earned by Parent’s non-employee directors, reference is made to the subsection “Director Compensation” beginning on page 66 of Parent’s Proxy Statement pursuant to Section 14(a) of the Exchange Act, filed April 24, 2020, which is incorporated herein by reference, and qualifies the foregoing in its entirety.

Prior to joining Akcea in September 2019, Damien McDevitt served as Chief Business Officer at Parent. Dr. McDevitt’s compensation from Parent totaled approximately $2,150,000 in fiscal year 2019 and approximately $2,515,000 in fiscal year 2018. Pursuant to the terms of that certain Offer Letter, dated September 19, 2019, between Dr. McDevitt and Akcea, Dr. McDevitt’s outstanding options to purchase shares of Parent common stock and Parent restricted stock units continue to vest while Dr. McDevitt is employed by Akcea.

Parent currently owns approximately 76% of all the outstanding Shares. Because Purchaser is an affiliate of Akcea, the transactions contemplated by the Merger Agreement constitute a “going private” transaction under Rule 13e-3 under the Securities Exchange Act of 1934, as amended (the “Exchange Act”). Rule 13e-3 requires, among other things, that certain financial information concerning Akcea and certain information relating to the fairness of the Offer, any subsequent merger that may be effected following the consummation of the Offer and the consideration offered to minority stockholders be filed with the SEC and disclosed to minority stockholders prior to consummation of the Offer and such merger. Parent has provided such information in this Offer to Purchase and a Tender Offer Statement on Schedule TO and the exhibits thereto filed with the SEC pursuant to Rule 14d-3 under the Exchange Act. If the purchase of Shares pursuant to the Offer results in fewer than 300 holders of record of Shares, Parent intends to file a Form 15 to evidence the termination of Akcea’s duty to file reports pursuant to Section 15(d) of the Exchange Act as soon after the consummation of the Offer as the requirements for deregistration are met.

For a description of certain contacts between Akcea and Purchaser and its affiliates that were related to the Offer, please see Section 1—“Background of the Offer; Contacts with Akcea.” Further, please see Section 3—“Purpose of the Offer and Plans for Akcea,” Section 20—“Summary of the Merger Agreement” and Section 24—“Certain Legal Matters; Regulatory Approvals” for a description of (i) the purpose the Offer, (ii) our plans for Akcea, (iii) why Parent does not anticipate seeking the approval of Akcea’s stockholders who are unaffiliated with Parent and its affiliates and (iv) the availability of appraisal rights in connection with the Offer and the Merger.

If the Offer is not consummated, we will re-evaluate our options with respect to Akcea. In particular, we may, among other things:

If we were to pursue any of these alternatives, it might take considerably longer for the public stockholders of Akcea to receive any consideration for their Shares (other than through sales in the open market) than if they had tendered their Shares in the Offer. No assurance can be given that any of such alternatives will be pursued or as to the price per Share that may be paid in any such future acquisition of Shares or the effect any such actions could have on trading price of Akcea’s common stock.

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The Akcea Board has established an Affiliate Transactions Committee, comprised solely of independent, disinterested directors who are unaffiliated with Parent and are not officers or employees of Akcea, and delegated to it authority to review, evaluate, negotiate, recommend or not recommend the proposal by Parent with respect to a business combination transaction with Parent.

Akcea has represented to us that, prior to the execution of the Merger Agreement:

B. Lynne Parshall, Joseph Klein, III and Damien McDevitt recused themselves from related meetings and deliberations of the Akcea board, and Sandford D. Smith and Elaine Hochberg abstained from voting at related meetings of the Akcea board, in each case due to actual or potential conflicts as further explained in Section 1—“Background of the Offer; Contacts with Akcea” of the Schedule TO and the section entitled “Background of the Offer and the Merger” of the Schedule 14D-9.

Akcea has agreed to file a Solicitation/Recommendation Statement on Schedule 14D-9 with the SEC indicating the Affiliate Transactions Committee’s recommendation to the Akcea Board, and the Akcea Board’s approval of the Transactions and its recommendation that Akcea’s stockholders tender their Shares in the Offer.

Parent engaged Goldman Sachs and Stifel as Parent’s co-financial advisors in connection with its consideration of the acquisition by Parent of the outstanding Shares that were not owned by Parent. Goldman Sachs and Stifel were not requested to provide, and they did not provide, to Parent, Akcea, the holders of common stock of Parent or Akcea, or any other person, any opinion as to the fairness, from a financial point of view or otherwise, of the Transactions or the Offer Price or the Merger Consideration (as defined below) to Parent, Akcea, the holders of common stock of Parent or Akcea, or any other person. Nor did Goldman Sachs or Stifel opine on any other consideration received in connection with the Transactions by the holders of any class of securities, creditors, or other constituencies of Parent or Akcea; or the amount or nature of any compensation to be paid or payable to any of the officers, directors or employees of Parent or Akcea or any class of such persons in connection with the Transactions, whether relative to the Offer Price, the Merger Consideration or otherwise.

Goldman Sachs and Stifel, as co-financial advisors to Parent, made presentations of financial analyses to the Parent Board and to the Finance Committee relating to the acquisition by Parent of the outstanding shares of Akcea common stock that were not owned by Parent (the “Goldman Sachs and Stifel Presentations”). The

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Goldman Sachs and Stifel Presentations were provided for the benefit of the Parent Board or the Finance Committee, as applicable, for their information and assistance in connection with their consideration of the Transactions.

Copies of the Goldman Sachs and Stifel Presentations, which are summarized below, have been filed as exhibits to the Schedule TO and are incorporated herein by reference, and will be made available for inspection and copying at Parent’s principal executive offices during its regular business hours by any interested Akcea equity holder or its representative who has been so designated in writing. The Schedule TO, including the Goldman Sachs and Stifel Presentations, may be examined at, and copies may be obtained from, the SEC in the manner described in Section 18—“Certain Information Concerning Akcea” under “Available Information.” The information in the Goldman Sachs and Stifel Presentations is subject to the assumptions, limitations, qualifications and other conditions contained therein and is necessarily based on economic, monetary, market and other conditions as of, and the information made available to Goldman Sachs or Stifel, as the case may be, in advance of the date of, each such presentation. The Goldman Sachs and Stifel Presentations do not constitute a recommendation to Parent, Akcea or any holder of common stock of Parent or Akcea with respect to the Transactions, or any other matter. The Goldman Sachs and Stifel Presentations do not constitute, and are not intended to represent, any view or opinion as to the fairness, from a financial point of view or otherwise, of the Transactions, or any aspect, term or implication of the Offer Price or the Merger Consideration, to Parent, Akcea, the holders of common stock of Parent or Akcea or any other person.

In connection with the Goldman Sachs and Stifel Presentations, Goldman Sachs and Stifel reviewed, among other things, certain publicly available business and financial information concerning Parent and Akcea; certain internal financial analyses and forecasts for Akcea prepared by its management; and the Projections as described more fully in Section 18—“Certain Information Concerning Akcea—Certain Prospective Financial Information,” which are referred to in this Section 10 as the “Forecasts.” Additionally, Parent management provided Goldman Sachs and Stifel with, and Parent approved the use by Goldman Sachs and Stifel of, certain projections for cost savings, operating synergies and other assumptions following completion of the Transactions, referred to as the “Synergies.” Goldman Sachs and Stifel also held discussions with certain members of the management of Parent regarding their assessment of the strategic and financial rationale for, and the potential benefits of, the Transactions and the past and current business operations, financial condition and future prospects of Parent and Akcea, and each of Goldman Sachs and Stifel considered such other factors, in connection with the preparation of the Goldman Sachs and Stifel Presentations, as it deemed appropriate.

For purposes of the Goldman Sachs and Stifel Presentations, each of Goldman Sachs and Stifel, with Parent’s consent, relied upon and assumed the accuracy and completeness of all of the financial, legal, regulatory, tax, accounting and other information provided to, discussed with or reviewed by, it, without assuming any responsibility for independent verification thereof. In that regard, each of Goldman Sachs and Stifel assumed with Parent’s consent that the Forecasts, including the Synergies, were reasonably prepared on a basis reflecting the best currently available estimates and judgments of the management of Parent. Neither Goldman Sachs nor Stifel made an independent evaluation or appraisal of the assets and liabilities (including any contingent, derivative or other off-balance-sheet assets and liabilities) of Parent or Akcea or any of their respective subsidiaries and neither Goldman Sachs nor Stifel was furnished with any such evaluation or appraisal. Each of Goldman Sachs and Stifel assumed that all governmental, regulatory or other consents and approvals necessary for the consummation of the Transactions would be obtained without any adverse effect on Parent or Akcea or on the expected benefits of the Transactions in any way meaningful to its analyses included in the Goldman Sachs and Stifel Presentations. Goldman Sachs and Stifel had also assumed that the Transactions would be consummated on the terms set forth in the Merger Agreement, without the waiver or modification of any term or condition the effect of which would be in any way meaningful to their analyses included in the Goldman Sachs and Stifel Presentations.

Neither Goldman Sachs nor Stifel addressed the underlying business decision of Parent to engage in the Transactions or the relative merits of such transactions as compared to any strategic alternatives that may be

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available to Parent; nor did either Goldman Sachs or Stifel address any legal, regulatory, tax or accounting matters. The Goldman Sachs and Stifel Presentations were necessarily based on economic, monetary market and other conditions as of, and the information made available to Goldman Sachs or Stifel, as the case may be, in advance of, the relevant presentation. Goldman Sachs and Stifel assumed no responsibility for updating, revising or reaffirming the analyses in any of the Goldman Sachs and Stifel Presentations based on circumstances, developments or events occurring after the date thereof. In addition, Goldman Sachs and Stifel did not express any opinion as to the prices at which shares of Parent or Akcea common stock would trade at any time, as to the potential effects of volatility in the credit, financial and stock markets on Parent or Akcea or the Transactions, or as to the impact of the Transactions on the solvency or viability of Parent or Akcea or the ability of Parent or Akcea to pay their respective obligations when they come due.

The following is a summary of the material financial analyses contained in the Goldman Sachs and Stifel Presentations. The following summary, however, does not purport to be a complete description of the financial analyses performed by Goldman Sachs or Stifel, nor does the order of analyses described represent relative importance or weight given to those analyses by Goldman Sachs or Stifel. Except as otherwise noted, the following quantitative information, to the extent that it is based on market data, is based on market data as it existed on or before August 28, 2020 (in the case of the August 30, 2020 Presentation) or on or before August 6, 2020 (in the case of the August 7, 2020 Presentation) and in all cases is not necessarily indicative of current market conditions.

The August 30 Presentation. On August 30, 2020, Goldman Sachs and Stifel presented the following analyses to the Parent Board.

Historical Trading Analysis and Analyst Price Targets. Goldman Sachs and Stifel reviewed the historical trading prices and volumes for the Shares for the one-year period ended August 28, 2020. In addition, Goldman Sachs and Stifel analyzed the $18.15 in cash consideration to be paid to holders of Shares pursuant to the Merger Agreement in relation to the closing price on August 28, 2020, in relation to the volume weighted average price (VWAP) per share at which shares of Akcea common stock traded over the 30, 60, 90 and 180 days ending on August 28, 2020, and in relation to the price per Share in the IPO.

This analysis indicated that the price per share to be paid to Akcea stockholders pursuant to the Merger Agreement represented:

In addition, Goldman Sachs and Stifel noted, for reference purposes, that publicly available research analyst target prices per Share ranged from $16.00 to $41.00 and that the 52-week trading range for Akcea common stock was $10.84 to $22.47 per Share.

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Premia Analysis. Goldman Sachs and Stifel reviewed and analyzed, using publicly available information, the acquisition premia for selected transactions announced during the time period from January 2008 through August 2020 across all sectors, excluding banks and utilities, where a majority stockholder of a public company in the United States acquired all of the shares of such target company that such majority stockholder did not

already own and where the aggregate consideration exceeded $200,000,000. These were the transactions that were analyzed:

For the entire period, using publicly available information, Goldman Sachs and Stifel calculated premia of the final prices paid in the transactions relative to the target’s last undisturbed closing stock price prior to announcement of the transaction. This analysis indicated a low premium of 15.2% and a high premium of 100.8% across the period. Using this analysis, Goldman Sachs and Stifel applied a reference range of illustrative premiums of 15.2% to 100.8% to the closing price per Share of $11.38 as of August 28, 2020 and calculated a range of implied equity values per Share of $13.11 to $22.85.

Additional Financial Analyses by Goldman Sachs.

Discounted Cash Flow Sum of the Parts—Akcea Standalone. Using the Forecasts for Akcea on a stand-alone basis, Goldman Sachs performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 8% to 10%, reflecting estimates of the weighted average cost of capital of Akcea on a stand-alone basis, Goldman Sachs discounted to present value as of June 30, 2020 estimates of unlevered free cash flow for Akcea on a stand-alone basis through 2040 as reflected in the Forecasts. Goldman Sachs derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate and a beta for the company, as well as certain financial metrics for the United States financial markets generally. Goldman Sachs derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Goldman Sachs then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided by the management of Parent, to derive a range of illustrative equity values for Akcea on a stand-alone basis. Goldman Sachs then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea (which includes outstanding restricted stock units and stock options on a treasury stock method basis), as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $14.44 to $17.89.

Discounted Cash Flow Sum of the Parts—Akcea Under Parent Control. Using the Forecasts for Akcea under Parent control and, at the direction of Parent, using a limited set of upside and downside sensitivities

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reflected in these Forecasts for Akcea under Parent control, Goldman Sachs performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 8% to 10%, reflecting estimates of the weighted average cost of capital of Akcea under Parent control, Goldman Sachs discounted to present value as of June 30, 2020 estimates of unlevered free cash flow for Akcea under Parent control through 2040 as reflected in the Forecasts. Goldman Sachs derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate and a beta for the company, as well as certain financial metrics for the United States financial markets generally. Goldman Sachs derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Goldman Sachs then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided by the management of Parent, to derive a range of illustrative equity values for Akcea under Parent control. Goldman Sachs then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea (which includes outstanding restricted stock units and stock options on a treasury stock method basis), as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $19.32 to $23.87.

Additional Financial Analyses by Stifel.

Discounted Cash Flow Sum of the Parts—Akcea Standalone. Using the Forecasts for Akcea on a stand-alone basis, Stifel performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 9% to 12%, reflecting estimates of the weighted average cost of capital of Akcea on a stand-alone basis, Stifel discounted to present value as of October 31, 2020 estimates of unlevered free cash flow for Akcea on a stand-alone basis through 2040 as reflected in the Forecasts. Stifel derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate, a beta and size premium for the company, as well as certain financial metrics for the United States financial markets generally. To derive beta, Stifel analyzed the two-year weekly betas of selected publicly traded biotechnology companies. Stifel derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Stifel then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided in the Forecasts, to derive a range of illustrative equity values for Akcea on a stand-alone basis. Stifel then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea, which includes outstanding restricted stock units and stock options, valuing them on a treasury stock method basis, as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $11.59 to $15.78.

Discounted Cash Flow Sum of the Parts—Akcea Under Parent Control. Using the Forecasts for Akcea under Parent control, Stifel performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 7.5% to 9.5%, reflecting estimates of the weighted average cost of capital of Akcea under Parent control, Stifel discounted to present value as of October 31, 2020 estimates of unlevered free cash flow for Akcea under Parent control through 2040 as reflected in the Forecasts, including the net cumulative effect of selected Synergies provided by the management of Parent at the time of analysis. Stifel derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate, a beta and size premium for the company, as well as certain financial metrics for the United States financial markets generally. To derive beta, Stifel analyzed the two-year weekly betas of selected publicly traded biotechnology companies. Stifel derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Stifel then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided in the Forecasts, to derive a range of illustrative equity values for Akcea under Parent control. Stifel then divided the range of illustrative equity values it derived by the number of fully diluted

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outstanding shares of Akcea, which includes outstanding restricted stock units and stock options, valuing them on a treasury stock method basis, as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $21.16 to $26.00.

The August 7, 2020 Presentation. On August 7, 2020, Goldman Sachs and Stifel presented the following analyses to the Finance Committee.

Historical Trading Analysis and Analyst Price Targets. Goldman Sachs and Stifel reviewed the historical trading prices and volumes for the Shares for the period from January 1, 2020 through August 6, 2020. In addition, Goldman Sachs and Stifel analyzed an illustrative range of consideration to be paid to holders of Akcea common stock in relation to the closing price on August 6, 2020, in relation to the VWAP per share at which Shares traded over the 30, 60, 90 and 180 days and year ending on August 6, 2020, in relation to the high and low trading prices for the 52 weeks ending on August 6, 2020, in relation to the median target price published by Wall Street research analysts, and in relation to the price per Share in the IPO.

A summary of this analysis is presented in the table below:

In addition, Goldman Sachs and Stifel noted, for reference purposes, that publicly available Wall Street research analyst target prices per Share ranged from $16.00 to $41.00.

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Premia Analysis. Goldman Sachs and Stifel reviewed and analyzed, using publicly available information, the acquisition premia for selected transactions announced during the time period from January 2008 through August 2020 across all sectors, excluding banks and utilities, where a majority stockholder of a public company in the United States acquired all of the shares of such target company that such majority stockholder did not already own and where the aggregate consideration exceeded $200,000,000. These were the transactions that were analyzed:

For the entire period, using publicly available information, Goldman Sachs and Stifel calculated premia of the final prices paid in the transactions relative to the target’s last undisturbed closing stock price prior to announcement of the transaction. This analysis indicated a low premium of 15.2% and a high premium of 100.8% across the period. Using this analysis, Goldman Sachs and Stifel applied a reference range of illustrative premia of 28.6% (representing the 25^th percentile premium over the target’s last undisturbed closing stock price prior to announcement of the transaction) and 46.7% (representing the 75^th percentile premium over the target’s last undisturbed closing stock price prior to announcement of the transaction) to the closing price per Share of $11.47 as of August 6, 2020 and calculated a range of implied equity values per Share of $14.75 to $16.83. In addition, Goldman Sachs and Stifel calculated premia of the final prices paid in the transactions relative to the target’s high closing stock price for the 52-week period ending with the target’s last undisturbed trading day prior to announcement of the transaction. Using this analysis, Goldman Sachs and Stifel applied a reference range of illustrative premia of (4.8)% (representing the 25^th percentile premium over the target’s high closing stock price for the 52-week period ending with the target’s last undisturbed trading day prior to announcement of the transaction) and 17.2% (representing the 75^th percentile premium over the target’s high closing stock price for the 52-week period ending with the target’s last undisturbed trading day prior to announcement of the transaction) to $22.47, representing Akcea common stock’s high closing price for the 52-week period ending August 6, 2020, and calculated a range of implied equity values per Share of $21.39 to $26.33.

Additional Financial Analyses by Goldman Sachs.

Discounted Cash Flow Sum of the Parts—Akcea Standalone. Using the Forecasts for Akcea on a stand-alone basis, Goldman Sachs performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 8% to 10%, reflecting estimates of the weighted average cost of capital of Akcea on a stand-alone basis, Goldman Sachs discounted to present value as of June 30, 2020 estimates of unlevered free cash flow for Akcea on a stand-alone basis through 2040 as reflected in the Forecasts. Goldman Sachs derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt,

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after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate and a beta for the company, as well as certain financial metrics for the United States financial markets generally. Goldman Sachs derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Goldman Sachs then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided by the management of Parent, to derive a range of illustrative equity values for Akcea on a stand-alone basis. Goldman Sachs then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea (which includes outstanding restricted stock units and stock options on a treasury stock method basis), as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $14.46 to $17.95.

Discounted Cash Flow Sum of the Parts—Akcea Under Parent Control. Using the Forecasts for Akcea under Parent control and, at the direction of Parent, using select upside sensitivities reflected in these Forecasts for Akcea under Parent control, Goldman Sachs performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 8% to 10%, reflecting estimates of the weighted average cost of capital of Akcea under Parent control, Goldman Sachs discounted to present value as of June 30, 2020 estimates of unlevered free cash flow for Akcea under Parent control through 2040 as reflected in the Forecasts. Goldman Sachs derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate and a beta for the company, as well as certain financial metrics for the United States financial markets generally. Goldman Sachs derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Goldman Sachs then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided by the management of Parent, to derive a range of illustrative equity values for Akcea under Parent control. Goldman Sachs then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea (which includes outstanding restricted stock units and stock options on a treasury stock method basis), as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $29.73 to $36.72.

Additional Financial Analyses by Stifel.

Discounted Cash Flow Sum of the Parts—Akcea Standalone. Using the Forecasts for Akcea on a stand-alone basis, Stifel performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 9% to 12%, reflecting estimates of the weighted average cost of capital of Akcea on a stand-alone basis, Stifel discounted to present value as of October 31, 2020 estimates of unlevered free cash flow for Akcea on a stand-alone basis through 2040 as reflected in the Forecasts. Stifel derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate, a beta and size premium for the company, as well as certain financial metrics for the United States financial markets generally. To derive beta, Stifel analyzed the two-year weekly betas of selected publicly traded biotechnology companies. Stifel derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Stifel then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided in Forecasts, to derive a range of illustrative equity values for Akcea on a stand-alone basis. Stifel then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea, which includes outstanding restricted stock units and stock options, valuing them on a treasury stock method basis, as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $11.59 to $15.79.

Discounted Cash Flow Sum of the Parts—Akcea Under Parent Control. Using the Forecasts for Akcea under Parent control, Stifel performed an illustrative discounted cash flow analysis on each of the parts of Akcea. Using discount rates ranging from 7% to 9%, reflecting estimates of the weighted average cost of capital of Akcea under Parent control, Stifel discounted to present value as of October 31, 2020 estimates of unlevered free

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cash flow for Akcea under Parent control through 2040, including the net cumulative effect of selected Synergies provided by the management of Parent at the time of analysis, as reflected in the Forecasts. Stifel derived such discount rates by application of the Capital Asset Pricing Model, which requires certain company-specific inputs, including the company’s target capital structure weightings, the cost of long-term debt, after-tax yield on permanent excess cash, if any, future applicable marginal cash tax rate, a beta and size premium for the company, as well as certain financial metrics for the United States financial markets generally. To derive beta, Stifel analyzed the two-year weekly betas of selected publicly traded biotechnology companies. Stifel derived a range of illustrative enterprise values for Akcea by adding the ranges of present values it derived above for each of the parts. Stifel then added to the range of illustrative enterprise values it derived for Akcea an estimate of net cash for Akcea, as provided in the Forecasts, to derive a range of illustrative equity values for Akcea under Parent control. Stifel then divided the range of illustrative equity values it derived by the number of fully diluted outstanding shares of Akcea, which includes outstanding restricted stock units and stock options, valuing them on a treasury stock method basis, as provided by the management of Parent, to derive a range of illustrative present values per Share ranging from $24.53 to $29.92.

General.

Selecting portions of the analyses or of the summary set forth above, without considering the analyses as a whole, could create an incomplete view of the processes underlying the Goldman and Stifel Presentations. In connection with these presentations, each of Goldman Sachs and Stifel considered the results of all of its analyses and did not attribute any particular weight to any factor or analysis considered by it. No company or transaction used in the above analyses as a comparison is directly comparable to Parent or Akcea or the Transactions.

Each of Goldman Sachs and Stifel prepared these analyses for purposes of their presentations to the Parent Board or to the Finance Committee, as applicable. These analyses do not purport to be appraisals, nor do they necessarily reflect the prices at which businesses or securities actually may be sold. Analyses based upon forecasts of future results are not necessarily indicative of actual future results, which may be significantly more or less favorable than suggested by these analyses. Because these analyses are inherently subject to uncertainty, being based upon numerous factors or events beyond the control of the parties or their respective advisors, none of Parent, Akcea, Goldman Sachs, Stifel or any other person assumes responsibility if future results are materially different from those forecasted.

The Offer Price and Merger Consideration were determined through arm’s-length negotiations between Parent and the Affiliate Transactions Committee and were approved by each party’s board of directors. Goldman Sachs and Stifel provided advice to Parent during these negotiations. Goldman Sachs and Stifel did not, however, recommend any specific amount of consideration to Parent or its board of directors or that any specific amount of consideration constituted the only appropriate consideration for the merger.

The Goldman Sachs and Stifel Presentations were among many factors taken into consideration by the Parent Board in making its determination to approve the Merger Agreement. The foregoing summary does not purport to be a complete description of the analyses performed by Goldman Sachs and Stifel in connection with the Goldman Sachs and Stifel Presentations and is qualified in its entirety by reference to the Goldman Sachs and Stifel Presentations included as exhibits to the Schedule TO.

Goldman Sachs and its affiliates are engaged in advisory, underwriting and financing, principal investing, sales and trading, research, investment management and other financial and non-financial activities and services for various persons and entities. Goldman Sachs and its affiliates and employees, and funds or other entities they manage or in which they invest or have other economic interests or with which they co-invest, may at any time purchase, sell, hold or vote long or short positions and investments in securities, derivatives, loans, commodities, currencies, credit default swaps and other financial instruments of Parent, Akcea, any of their respective affiliates and third parties, or any currency or commodity that may be involved in the transaction contemplated by the merger agreement. Goldman Sachs acted as financial advisor to Parent in connection with, and participated in certain of the negotiations leading to, the Transactions. Goldman Sachs has provided certain financial advisory

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and/or underwriting services to Parent and/or its affiliates (other than Akcea and its subsidiaries) from time to time for which the Investment Banking Division of Goldman Sachs has received, and may receive, compensation. During the two-year period ended August 30, 2020, Goldman Sachs has recognized compensation for financial advisory and/or underwriting services provided by its Investment Banking Division to Parent and/or its affiliates (other than Akcea and its subsidiaries) of approximately $525,000. During the two-year period ended August 30, 2020, the Investment Banking Division of Goldman Sachs has not been engaged by Akcea or its subsidiaries to provide financial advisory or underwriting services for which Goldman Sachs has recognized compensation. We further note that concurrent with the issuance of the Ionis 0.125% Convertible Senior Notes due 2024 (aggregate principal amount of $548,826,000) (the “Convertible Notes”) in December 2019, Ionis entered into convertible note hedge and related warrant transactions with respect to the Convertible Notes with several call spread counterparties, including Goldman Sachs & Co. LLC, each acting as principal for its own account. The convertible note hedge transactions collectively and warrant transactions collectively each cover approximately 6.59 million shares of Ionis common stock, the aggregate number of shares initially underlying the Convertible Notes, and the convertible note hedge and related warrant transactions could be subject to potential adjustment in certain circumstances in connection with the Transactions. Goldman Sachs may also in the future provide financial advisory and/or underwriting services to Parent, Akcea and their respective affiliates for which the Investment Banking Division of Goldman Sachs may receive compensation. In addition, Joseph Wender, an advisory director at Goldman Sachs, serves on the Parent Board.

Stifel and its affiliates are engaged in advisory, underwriting and financing, principal investing, sales and trading, research, investment management and other financial and non-financial activities and services for various persons and entities. Stifel and its affiliates and employees, and funds or other entities they manage or in which they invest or have other economic interests or with which they co-invest, may at any time purchase, sell, hold or vote long or short positions and investments in securities, derivatives, loans, commodities, currencies, credit default swaps and other financial instruments of Parent, Akcea, any of their respective affiliates and third parties, or any currency or commodity that may be involved in the transaction contemplated by the merger agreement. Stifel acted as financial advisor to Parent in connection with, and participated in certain of the negotiations leading to, the transaction contemplated by the Merger Agreement. Stifel has provided certain financial advisory and/or underwriting services to Parent and its affiliates from time to time for which Stifel has received, and may receive, compensation, including having acted as a financial advisor to Parent for the issuance of the Ionis 0.125% Convertible Senior Notes due 2024 (aggregate principal amount of $548,826,000) (the “Convertible Notes”) in December 2019 and a broker to Parent for a 10b5-1 share repurchase plan that was completed in the first quarter of 2020. During the two-year period ended August 30, 2020, Stifel has recognized compensation for financial advisory and/or underwriting services provided by its Investment Banking Division to Parent of approximately $1,300,000 in the aggregate. During the two-year period ended August 30, 2020, the Investment Banking Division of Stifel has not been engaged by Akcea or its subsidiaries to provide financial advisory or underwriting services for which Stifel has recognized compensation. Stifel may also in the future provide financial advisory and/or underwriting services to Parent, Akcea and their respective affiliates for which the Investment Banking Division of Stifel may receive compensation. In addition, Peter Reikes, Vice Chairman at Stifel, serves on the Parent Board.

Parent selected each of Goldman Sachs and Stifel as its financial advisor because each is an internationally recognized investment banking firm that has substantial experience in transactions similar to the Transactions as well as familiarity with Parent and its business.

Pursuant to a letter agreement dated August 29, 2020, Parent engaged Goldman Sachs to act as its financial advisor in connection with the contemplated transaction. The engagement letter between Parent and Goldman Sachs provides for a transaction fee that is estimated, based on the information available as of the date of announcement, at approximately $10,000,000, all of which is contingent upon consummation of the Transactions. In addition, Parent has agreed to reimburse Goldman Sachs for certain of its expenses, including attorneys’ fees and disbursements, and to indemnify Goldman Sachs and related persons against various liabilities, including certain liabilities under the federal securities laws.

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Pursuant to a letter agreement dated August 28, 2020, Parent engaged Stifel to act as its financial advisor in connection with the contemplated transaction. The engagement letter between Parent and Stifel provides for a transaction fee of $10,000,000, all of which is contingent upon consummation of the Transactions. In addition, Parent has agreed to reimburse Stifel for certain of its expenses, including attorneys’ fees and disbursements, and to indemnify Stifel and related persons against various liabilities, including certain liabilities under the federal securities laws.

THE TENDER OFFER

Upon the terms and subject to the prior satisfaction or waiver of the conditions of the Offer (including, if the Offer is extended or amended, the terms and conditions of any extension or amendment), Parent will accept for payment, purchase and pay for all Shares at a purchase price of $18.15 per Share, net to the seller of such Shares in cash, without interest and subject to any withholding taxes, validly tendered prior to the expiration of the Offer, and not properly withdrawn in accordance with the procedures set forth in Section 14—“Withdrawal Rights.” The Offer will expire at one minute after 11:59 p.m. Eastern Time on Friday, October 9, 2020 (the “Expiration Date”), unless Purchaser has extended the Offer in accordance with the terms of the Merger Agreement, in which event the term “Expiration Date” will mean the date to which the initial expiration date of the Offer is so extended.

The Offer is conditioned upon the satisfaction of the Minimum Condition and the other conditions described in Section 22—“Conditions of the Offer.” Purchaser may terminate the Offer without purchasing any Shares if certain events described in Section 20—“Summary of the Merger Agreement—Termination” occur.

Purchaser expressly reserves the right to (i) increase the Offer Price, (ii) waive any Offer Condition (as defined below) and (iii) make any other changes in the terms and conditions of the Offer that are consistent with the terms of the Merger Agreement, except that Akcea’s prior written approval is required for Parent or Purchaser to:

None of Parent, Purchaser and Akcea may amend, modify or waive the Minimum Condition.

Upon the terms and subject to the satisfaction or waiver of the conditions of the Offer and the Merger Agreement, Purchaser will (i) immediately after the Expiration Date irrevocably accept for payment all Shares

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tendered (and not validly withdrawn) pursuant to the Offer and (ii) promptly thereafter pay for all such Shares. The time at which Purchaser accepts for payment Shares tendered in the Offer is referred to as the “Offer Acceptance Time.”

If, on or before the Expiration Date, Purchaser increases the consideration being paid for Shares accepted for payment in the Offer, such increased consideration will be paid to all stockholders whose Shares are purchased in the Offer, whether or not such Shares were tendered before the announcement of the increase in consideration. Purchaser also expressly reserves the right to modify the terms of the Offer, subject to compliance with the Exchange Act, the Merger Agreement and the restrictions identified above.

The Merger Agreement provides that, if, as of the then-scheduled Expiration Date, any of the conditions to the Offer is not satisfied and has not been waived by Parent or Purchaser, Parent and Purchaser may in their sole discretion extend the Offer, or are required to extend the Offer if requested by Akcea, on one or more occasions, for an additional period of up to 10 business days per extension, to permit such condition to the Offer to be satisfied. In addition, Purchaser has agreed to extend the Offer for any period required by any law, rule, regulation, interpretation or position of the SEC or the Nasdaq Stock Market (“Nasdaq”) applicable to the Offer. However, Parent and Purchaser are not required to extend the Offer if the Minimum Condition is the only condition to the Offer that is not satisfied or waived as of then-scheduled Expiration Date (other than conditions which by their nature are to be satisfied at the expiration of the Offer) and none of the Schedule TO, Schedule 14D-9 and Parent’s and Akcea’s Schedule 13E-3 is still being reviewed or commented on by the SEC. In no event will Parent and Purchaser be required to extend the Offer beyond the earlier to occur of the valid termination of the Merger Agreement or December 30, 2020. See Section 20—“Summary of the Merger Agreement.”

Except as set forth above, there can be no assurance that we will be required under the Merger Agreement to extend the Offer. During any extension of the initial offering period pursuant to the paragraphs above, all Shares previously tendered and not withdrawn will remain subject to the Offer and subject to withdrawal rights. See Section 14—“Withdrawal Rights.”

Without Akcea’s consent, there will not be a subsequent offering period for the Offer.

If, subject to the terms of the Merger Agreement, we make a material change in the terms of the Offer or the information concerning the Offer, or if we waive a material condition of the Offer, we will disseminate additional tender offer materials and extend the Offer if and to the extent required by Rules 14d-3(b)(1), 14d-4(d), 14d-6(c) and l4e-1 under the Exchange Act or otherwise. The minimum period during which a tender offer must remain open following material changes in the terms of the tender offer or the information concerning the tender offer, other than a change in the consideration offered or a change in the percentage of securities sought, will depend upon the facts and circumstances, including the relative materiality of the terms or information changes. With respect to a change in the consideration offered or a change in the percentage of securities sought, a tender offer generally must remain open for a minimum of 10 business days following such change to allow for adequate disclosure to stockholders.

We expressly reserve the right, in our sole discretion, subject to the terms and upon the conditions of the Merger Agreement and the applicable rules and regulations of the SEC, to not accept for payment any Shares if, at the expiration of the Offer, any of the conditions to the Offer set forth in Section 22—“Conditions of the Offer” have not been satisfied. Under certain circumstances, Parent and Purchaser may terminate the Merger Agreement and the Offer.

Any extension, waiver or amendment of the Offer or termination of the Offer will be followed, as promptly as practicable, by public announcement thereof, such announcement in the case of an extension to be issued not later than 9:00 a.m., Eastern Time, on the next business day after the then-scheduled Expiration Date in accordance with the public announcement requirements of Rules 14d-3(b)(1), 14d-4(d), 14d-6(c) and l4e-1(d)

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under the Exchange Act. Without limiting our obligation under such rule or the manner in which we may choose to make any public announcement, we currently intend to make announcements by issuing a press release to the PR Newswire (or such other national media outlet or outlets we deem prudent) and making any appropriate filing with the SEC.

Promptly following the purchase of Shares in the Offer, we expect to complete the Merger without a vote of Akcea’s stockholders pursuant to Section 251(h) of the DGCL.

Akcea has provided us with its list of stockholders and security position listings for the purpose of disseminating the Offer to holders of Shares. This Offer to Purchase and the related Letter of Transmittal will be mailed to record holders of Shares whose names appear on Akcea’s stockholder list and will be furnished to brokers, dealers, commercial banks, trust companies and similar persons whose names, or the names of whose nominees, appear on the stockholder list or, if applicable, who are listed as participants in a clearing agency’s security position listing, for subsequent transmittal to beneficial owners of Shares.

Subject to the satisfaction or waiver of all the conditions to the Offer set forth in Section 22—“Conditions of the Offer,” we will, immediately after the expiration of the Offer, irrevocably accept for payment all Shares tendered (and not validly withdrawn) pursuant to the Offer and, promptly after the Offer Acceptance Time, pay for such Shares.

In all cases, payment for Shares tendered and accepted for payment pursuant to the Offer will be made only after timely receipt by the Depository of (i) certificates representing such Shares or confirmation of the book-entry transfer of such Shares into the Depository’s account at The Depository Trust Company (“DTC”) pursuant to the procedures set forth in Section 13—“Procedures for Tendering Shares,” (ii) a Letter of Transmittal, properly completed and duly executed, with any required signature guarantees (or, in the case of a book-entry transfer, an Agent’s Message (as defined below) in lieu of the Letter of Transmittal), and (iii) any other documents required by the Letter of Transmittal or any other customary documents required by Depository. See Section 13—“Procedures for Tendering Shares.”

For purposes of the Offer, if and when Purchaser gives oral or written notice to the Depository of its acceptance for payment of such Shares pursuant to the Offer, then Purchaser has accepted for payment and purchased Shares validly tendered and not validly withdrawn pursuant to the Offer. Upon the terms and subject to the conditions of the Offer, payment for Shares accepted for payment pursuant to the Offer will be made by deposit of the aggregate Offer Price with the Depository, which will act as agent for the tendering stockholders for purposes of receiving payments from us and transmitting such payments to the tendering stockholders. Under no circumstances will interest be paid on the Offer Price for Shares, regardless of any extension of the Offer or any delay in payment for Shares.

If any tendered Shares are not accepted for payment pursuant to the terms and conditions of the Offer for any reason, or if certificates are submitted for more Shares than are tendered, certificates for such unpurchased Shares will be returned (or new certificates for the Shares not tendered will be sent), without expense to the tendering stockholder (or, in the case of Shares tendered by book-entry transfer into the Depository’s account at DTC pursuant to the procedures set forth in Section 13—“Procedures for Tendering Shares,” such Shares will be credited to an account maintained with DTC) promptly following expiration or termination of the Offer.

Valid Tender of Shares. Except as set forth below, to validly tender Shares pursuant to the Offer, (i) a properly completed and duly executed Letter of Transmittal in accordance with the instructions of the Letter of Transmittal, with any required signature guarantees, or an Agent’s Message (as defined below) in connection

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with a book-entry delivery of Shares, and any other documents required by the Letter of Transmittal and any other customary documents required by the Depository, must be received by the Depository at one of its addresses set forth on the back cover of this Offer to Purchase prior to the expiration of the Offer and either (a) certificates representing Shares tendered must be delivered to the Depository or (b) such Shares must be properly delivered pursuant to the procedures for book-entry transfer described below and a confirmation of such delivery received by the Depository (which confirmation must include an Agent’s Message (as defined below) if the tendering stockholder has not delivered a Letter of Transmittal), in each case, prior to the Expiration Date or (ii) the tendering stockholder must comply with the guaranteed delivery procedures set forth below. The term “Agent’s Message” means a message, transmitted by DTC to, and received by, the Depository and forming a part of a Book-Entry Confirmation (as defined below), which states that DTC has received an express acknowledgment from the participant in DTC tendering the Shares which are the subject of such Book-Entry Confirmation (as defined below) that such participant has received and agrees to be bound by the terms of the Letter of Transmittal and that Purchaser may enforce such agreement against the participant.

Book-Entry Transfer. The Depository will take steps to establish and maintain an account with respect to the Shares at DTC for purposes of the Offer. Any financial institution that is a participant in DTC’s systems may make a book-entry transfer of Shares by causing DTC to transfer such Shares into the Depository’s account in accordance with DTC’s procedures for such transfer. However, although delivery of Shares may be effected through book-entry transfer, either the Letter of Transmittal, properly completed and duly executed, together with any required signature guarantees, or an Agent’s Message in lieu of the Letter of Transmittal, and any other required documents, must, in any case, be transmitted to and received by the Depository at one of its addresses set forth on the back cover of this Offer to Purchase prior to the Expiration Date or the tendering stockholder must comply with the guaranteed delivery procedures described below. The confirmation of a book-entry transfer of Shares into the Depository’s account at DTC as described above is referred to herein as a “Book-Entry Confirmation.”

Delivery of documents to DTC in accordance with DTC’s procedures does not constitute delivery to the Depository.

Signature Guarantees and Stock Powers. Except as otherwise provided below, all signatures on a Letter of Transmittal must be guaranteed by a financial institution (including most commercial banks, savings and loan associations and brokerage houses) that is a member in good standing of a recognized Medallion Program approved by the Securities Transfer Association, Inc., including the Security Transfer Agents Medallion Program, the New York Stock Exchange Medallion Signature Program and the Stock Exchanges Medallion Program (each, an “Eligible Institution”). Signatures on a Letter of Transmittal need not be guaranteed (i) if the Letter of Transmittal is signed by the registered owner(s) (which term, for purposes of this section, includes any participant in any of DTC’s systems whose name appears on a security position listing as the owner of the Shares) of Shares tendered therewith and such registered owner has not completed the box entitled “Special Payment Instructions” or the box entitled “Special Delivery Instructions” on the Letter of Transmittal or (ii) if such Shares are tendered for the account of an Eligible Institution. See Instructions 1 and 5 of the Letter of Transmittal. If the certificates for Shares are registered in the name of a person other than the signer of the Letter of Transmittal, or if payment is to be made or certificates for Shares not tendered or not accepted for payment are to be returned to a person other than the registered owner of the certificates surrendered, then the tendered certificates must be registered or accompanied by appropriate stock powers, in either case, signed exactly as the name or names of the registered owner(s) or holder(s) appear on the certificates, with the signatures on the certificates or stock powers guaranteed as described above. See Instructions 1 and 5 of the Letter of Transmittal.

If certificates representing Shares are forwarded separately to the Depository, a properly completed and duly executed Letter of Transmittal must accompany each delivery of certificates.

Guaranteed Delivery. A stockholder who desires to tender Shares pursuant to the Offer and whose certificates for Shares are not immediately available and cannot be delivered to the Depository prior to the

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expiration of the Offer, or who cannot complete the procedure for book-entry transfer prior to the expiration of the Offer, or who cannot deliver all required documents to the Depository prior to the expiration of the Offer, may tender such Shares by satisfying all of the requirements set forth below:

The Notice of Guaranteed Delivery may be delivered by overnight courier to the Depository or mailed to the Depository and must include a guarantee by an Eligible Institution in the form set forth in such Notice of Guaranteed Delivery. Shares tendered by a Notice of Guaranteed Delivery will not be deemed validly tendered for purposes of satisfying the Minimum Condition unless and until Shares underlying such Notice of Guaranteed Delivery are delivered to the Depository prior to the expiration of the Offer.

THE METHOD OF DELIVERY OF SHARES, THE LETTER OF TRANSMITTAL AND ALL OTHER REQUIRED DOCUMENTS, INCLUDING DELIVERY THROUGH DTC, IS AT THE ELECTION AND RISK OF THE TENDERING STOCKHOLDER. DELIVERY OF ALL SUCH DOCUMENTS WILL BE DEEMED MADE ONLY WHEN ACTUALLY RECEIVED BY THE DEPOSITORY (INCLUDING, IN THE CASE OF A BOOK-ENTRY TRANSFER, BY BOOK-ENTRY CONFIRMATION). IF SUCH DELIVERY IS BY MAIL, IT IS RECOMMENDED THAT ALL SUCH DOCUMENTS BE SENT BY PROPERLY INSURED REGISTERED MAIL WITH RETURN RECEIPT REQUESTED. IN ALL CASES, SUFFICIENT TIME SHOULD BE ALLOWED TO ENSURE TIMELY DELIVERY.

Other Requirements. Notwithstanding any provision of the Merger Agreement, Purchaser will pay for Shares tendered (and not validly withdrawn) pursuant to the Offer only after timely receipt by the Depository of (i) certificates for (or a timely Book-Entry Confirmation with respect to) such Shares, (ii) a Letter of Transmittal, properly completed and duly executed, with any required signature guarantees (or, in the case of a book-entry transfer, an Agent’s Message in lieu of the Letter of Transmittal), and (iii) any other documents required by the Letter of Transmittal or any other customary documents required by the Depository. Accordingly, tendering stockholders may be paid at different times depending upon when certificates for Shares or Book-Entry Confirmations with respect to Shares are actually received by the Depository. Under no circumstances will Purchaser pay interest on the purchase price of Shares, regardless of any extension of the Offer or any delay in making such payment. If your Shares are held in street name (i.e., through a broker, dealer, commercial bank, trust company or other nominee), your Shares can be tendered by your nominee by book-entry transfer through the Depository. If you are unable to deliver any required document or instrument to the Depository by the expiration of the Offer, you may gain some extra time by having a broker, a bank or other fiduciary that is an eligible guarantor institution guarantee that the missing items will be received by the Depository by using the enclosed Notice of Guaranteed Delivery. For the tender to be valid, however, the Depository must receive the missing items together with the Shares within 2 Nasdaq trading days after the date of execution of the Notice of Guaranteed Delivery.

Binding Agreement. Our acceptance for payment of Shares tendered pursuant to one of the procedures described above will constitute a binding agreement between the tendering stockholder and us upon the terms and subject to the conditions of the Offer.

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Appointment as Proxy. By executing and delivering a Letter of Transmittal as set forth above (or, in the case of a book-entry transfer, by delivery of an Agent’s Message in lieu of a Letter of Transmittal), the tendering stockholder irrevocably appoints Purchaser’s designees as such stockholder’s proxies, each with full power of substitution, to the full extent of such stockholder’s rights with respect to the Shares tendered by such stockholder and accepted for payment by us and with respect to any and all other Shares or other securities issued or issuable in respect of such Shares on or after the date of the Merger Agreement. All such proxies and powers of attorney will be considered coupled with an interest in the tendered Shares. Such appointment is effective when, and only to the extent that, we accept for payment Shares tendered by such stockholder as provided herein. Upon the effectiveness of such appointment, all prior powers of attorney, proxies and consents given by such stockholder will be revoked, and no subsequent powers of attorney, proxies and consents may be given (and, if given, will not be deemed effective). Our designees will, with respect to the Shares or other securities and rights for which the appointment is effective, be empowered to exercise all voting and other rights of such stockholder as they, in their sole discretion, may deem proper at any annual, special, adjourned or postponed meeting of the stockholders of Akcea, by written consent in lieu of any such meeting or otherwise. We reserve the right to require that, in order for Shares to be deemed validly tendered, immediately upon our payment for such Shares we must be able to exercise full voting, consent and other rights to the extent permitted under applicable law with respect to such Shares and other securities, including voting at any meeting of stockholders or executing a written consent concerning any matter.

Determination of Validity. All questions as to the validity, form, eligibility (including time of receipt) and acceptance of any tender of Shares will be determined by us in our sole and absolute discretion, which determination will be final and binding, subject to the rights of the tendering holders of Shares to challenge our determination in a court of competent jurisdiction. Purchaser reserves the absolute right to reject any and all tenders determined by us not to be in proper form or the acceptance for payment of or payment for which may, in our opinion, be unlawful. Purchaser also reserves the absolute right to waive any defect or irregularity in the tender of any Shares of any particular stockholder whether or not similar defects or irregularities are waived in the case of any other stockholder. No tender of Shares will be deemed to have been validly made until all defects and irregularities relating thereto have been cured or waived. None of Parent, Purchaser or any of their respective affiliates or assigns, the Depository, the Information Agent, or any other person will be under any duty to give notification of any defects or irregularities in tenders or incur any liability for failure to give any such notification. Purchaser’s interpretation of the terms and conditions of the Offer (including the Letter of Transmittal and the instructions thereto and any other documents related to the Offer) will be final and binding, subject to the rights of the tendering holders of Shares to challenge our determination in a court of competent jurisdiction.

Certification Regarding Tax Treatment and Withholding. Tendering stockholders will be asked to certify whether cash received pursuant to the Offer or the Merger should be treated for U.S. federal income tax purposes as a payment in exchange for the stockholder’s shares or as a distribution to which Section 301 of the Code (as defined in Section 15—“Certain U.S. Federal Income Tax Consequences of the Offer and the Merger”) applies. Stockholders who provide the latter certification or who fail to certify will be treated as having received a distribution to which Section 301 of the Code applies. Dividends paid to Non-U.S. Holders (as defined below) generally are subject to withholding tax at a rate of 30% (or such lower rate as may be provided under an applicable income tax treaty).

In order to avoid “backup withholding” of U.S. federal income tax on payments of cash pursuant to the Offer or the Merger, a stockholder that is a “U.S. person” (as defined in the instructions to the IRS Form W-9 provided with the Letter of Transmittal) who surrenders Shares for cash pursuant to the Offer or the Merger must, unless an exemption applies, provide the Depository with such stockholder’s correct taxpayer identification number (“TIN”) on an IRS Form W-9, certify under penalties of perjury that such TIN is correct and provide certain other certifications. If a stockholder does not provide such stockholder’s correct TIN or fails to provide the required certifications, the IRS may impose penalties on such stockholder, and the gross proceeds payable to such stockholder pursuant to the Offer or the Merger may be subject to backup withholding at a rate currently

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equal to 24%. All stockholders that are U.S. persons surrendering Shares pursuant to the Offer or the Merger should complete and sign the IRS Form W-9 included as part of the Letter of Transmittal to provide the information and certifications required to avoid backup withholding (unless an applicable exemption exists and is established in a manner satisfactory to the Depository).

Certain stockholders (including, among others, all corporations and certain foreign individuals and entities) are not subject to backup withholding. Exempt stockholders that are “U.S. persons” should complete and sign an IRS Form W-9 indicating their exempt status in order to avoid backup withholding. Stockholders that are not “U.S. persons” should complete and sign an IRS Form W-8BEN, IRS Form W-8BEN-E, or other appropriate IRS Form W-8 (instead of an IRS Form W-9) in order to avoid backup withholding. An appropriate IRS Form W-8 may be obtained from the Depository or at the IRS website (www.irs.gov). See Instruction 9 to the Letter of Transmittal.

Backup withholding is not an additional tax and any amounts withheld under the backup withholding rules may be refunded or credited against your U.S. federal income tax liability, provided the required information is timely furnished in the appropriate manner to the IRS.

Information reporting to the IRS may also apply to the receipt of cash pursuant to the Offer or the Merger.

Except as otherwise provided in this Section 14, tenders of Shares pursuant to the Offer are irrevocable. However, a stockholder has withdrawal rights that are exercisable until the expiration of the Offer (i.e., at any time prior to one minute after 11:59 p.m., Eastern Time on October 9, 2020), or in the event the Offer is extended, on such date and time to which the Offer is extended. In addition, Shares may be withdrawn at any time after November 13, 2020, which is the 60th day after the date of the commencement of the Offer, unless prior to that date Purchaser has accepted for payment the Shares validly tendered in the Offer.

For a withdrawal of Shares to be effective, a written or facsimile transmission notice of withdrawal must be timely received by the Depository at its address set forth on the back cover of this Offer to Purchase. Any notice of withdrawal must specify the name of the person having tendered the Shares to be withdrawn, the number of Shares to be withdrawn and the name of the record holder of the Shares to be withdrawn, if different from that of the person who tendered such Shares. The signature(s) on the notice of withdrawal must be guaranteed by an Eligible Institution, unless such Shares have been tendered for the account of any Eligible Institution. If Shares have been tendered pursuant to the procedures for book-entry transfer as set forth in Section 13—“Procedures for Tendering Shares,” any notice of withdrawal must specify the name and number of the account at DTC to be credited with the withdrawn Shares. If certificates representing the Shares to be withdrawn have been delivered or otherwise identified to the Depository, the name of the registered holder and the serial numbers shown on such certificates must also be furnished to the Depository prior to the physical release of such certificates.

All questions as to the form and validity (including time of receipt) of any notice of withdrawal will be determined by us, in our sole discretion, which determination will be final and binding, subject to the rights of the tendering holders of Shares to challenge our determination in a court of competent jurisdiction. No withdrawal of tendered Shares will be deemed to have been properly made until all defects and irregularities have been cured or waived. None of Parent, Purchaser or any of their respective affiliates or assigns, the Depository, the Information Agent, or any other person will be under any duty to give notification of any defects or irregularities in any notice of withdrawal or incur any liability for failure to give such notification. Withdrawals of tendered Shares may not be rescinded, and any Shares properly withdrawn will be deemed not to have been validly tendered for purposes of the Offer. However, withdrawn Shares may be retendered by following one of the procedures for tendering Shares described in Section 13—“Procedures for Tendering Shares” at any time prior to the expiration of the Offer.

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If Purchaser extends the Offer, delays its acceptance for payment of Shares, or is unable to accept for payment Shares pursuant to the Offer, for any reason, then, without prejudice to Purchaser’s rights under the Offer, the Depository may nevertheless, on Purchaser’s behalf, retain tendered Shares, and such Shares may not be withdrawn except to the extent that tendering stockholders exercise withdrawal rights as described in this Section 14.

The following discussion summarizes certain U.S. federal income tax considerations generally applicable to Holders (as defined below) of Shares who exchange their Shares for the Offer Price or the Merger Consideration pursuant to the Offer or the Merger, respectively. This discussion is for general information only and does not purport to consider all aspects of U.S. federal income taxation that might be relevant to stockholders of Akcea. This discussion is based on the Internal Revenue Code of 1986, as amended (the “Code”), Treasury Regulations promulgated thereunder, court decisions, published positions of the U.S. Internal Revenue Service (the “IRS”) and other applicable authorities, each as currently in effect as of the date hereof and all of which are subject to change or differing interpretations (possibly with retroactive effect). No ruling has been requested or will be obtained from the IRS regarding the U.S. federal income tax consequences of the Offer or the Merger or any other matter; thus, there can be no assurance that the IRS will not challenge the U.S. federal income tax treatment described below or that, if challenged, such treatment will be sustained by a court. This summary is not binding on the IRS, and the IRS is not precluded from taking a position that is different from, and contrary to, the positions taken in this summary. In addition, because the authorities on which this summary is based are subject to various interpretations, the IRS and the courts could disagree with one or more of the positions taken in this summary.

This discussion applies only to Holders that hold their Shares as “capital assets” within the meaning of Section 1221 of the Code (generally, assets held for investment). For purposes of this discussion, a “U.S. Holder” is a beneficial owner of Shares that is one of the following:

As used in this summary, the term “Non-U.S. Holder” means a beneficial owner of Shares that is neither a U.S. Holder nor a partnership for U.S. federal income tax purposes, and the term “Holder” means a U.S. Holder or a Non-U.S. Holder.

This discussion does not address all of the U.S. federal income tax considerations that may be relevant to a particular Holder in light of such Holder’s particular circumstances, or to Holders that are subject to special treatment under U.S. federal income tax laws, such as: financial institutions; brokers or dealers in securities or commodities; mutual funds; insurance companies; tax-exempt organizations (including private foundations); certain former citizens or long-term residents of the United States; Holders who acquired their Shares pursuant to the exercise of employee stock options or otherwise in connection with the performance of services; partnerships (including limited liability companies or other arrangements, in each case that are treated as partnerships for U.S. federal income tax purposes), S corporations, or pass-through entities (and investors and partners in such entities); Holders who hold their Shares as part of a “straddle,” “hedge,” “conversion transaction” or other integrated transaction; Holders who have a functional currency other than the U.S. dollar; Holders who are

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subject to the alternative minimum tax; regulated investment companies and real estate investment trusts; traders in securities who elect the mark-to-market method of accounting for their securities; controlled foreign corporations; and passive foreign investment companies.

This discussion does not address any U.S. state or local or non-U.S. tax considerations, other U.S. federal tax considerations (e.g., estate or gift tax), the Medicare contribution tax on net investment income, or the alternative minimum tax considerations of exchanging Shares in the Offer or the Merger.

If an entity or arrangement treated as a partnership for U.S. federal income tax purposes holds Shares, the U.S. federal income tax treatment of a partner in such partnership will generally depend upon the status of the partner and the activities of the partnership. Partnerships (including entities or arrangements treated as partnerships for U.S. federal income tax purposes) holding Shares and the partners therein should consult their tax advisors with respect to tax considerations of the Offer or the Merger applicable to them.

Because this discussion is intended to be a general summary only and individual circumstances may differ, each Holder should consult its tax advisor to determine the applicability of the rules discussed below and the particular tax effects of the Offer or the Merger on a beneficial holder of Shares, including the application and effect of the alternative minimum tax and any state, local and non-U.S. tax laws and of changes in such laws.

Certain Tax Considerations for U.S. Holders. The receipt of cash for Shares pursuant to the Offer or the Merger will be a taxable transaction for U.S. federal income tax purposes to a U.S. Holder of Shares. Subject to the discussion below relating to the application of Section 304 of the Code under “—Special Consequences of the Offer and the Merger to U.S. Holders of Shares that Actually or Constructively Own Parent Common Stock,” a U.S. Holder of Shares will generally recognize taxable gain or loss equal to the difference between (i) the stockholder’s adjusted tax basis in the Shares surrendered in the exchange, and (ii) the amount of cash received by such Holder in the Offer and/or the Merger.

If a U.S. Holder acquired Shares by purchase, the U.S. Holder’s adjusted tax basis in its Shares will generally equal the amount the U.S. Holder paid for the relevant Shares, less any returns of capital that the U.S. Holder might have received with regard to the relevant Shares. Such gain or loss will generally be long term capital gain or loss if, as of the date of the exchange, a U.S. Holder’s holding period in the Shares exchanged is more than one year. Long term capital gain recognized by certain noncorporate U.S. Holders, including individuals, is currently subject to tax at a reduced rate. The deductibility of capital losses is subject to limitations under the Code. If a U.S. Holder acquired different blocks of Shares at different times or at different prices, such U.S. Holder generally must determine its adjusted tax basis and holding period separately with respect to each such block of Shares.

Special Consequences of the Offer and the Merger to U.S. Holders of Shares that Actually or Constructively Own Parent Common Stock. Section 304 of the Code affects the tax treatment of certain transactions where there is overlapping ownership between the acquired and acquiring corporations, and is expected to apply to the Offer and the Merger because Parent currently owns more than 50% of the Shares. By virtue of the application of Section 304 of the Code, some Holders who exchange their Shares for the Offer Price or the Merger Consideration pursuant to the Offer or the Merger will be treated in the same manner as if they sold their Shares in a taxable transaction (i.e., as described above) (“sale treatment”), while others will instead be treated as having received a distribution with respect to such Holders’ stock to which Section 301 of the Code applies (“dividend treatment”). As more fully described below, the application of sale or dividend treatment may depend on the extent of the stockholder’s actual and constructive ownership of stock of Akcea prior to the Effective Time and of Parent after the Effective Time.

As described above, a U.S. Holder of Shares to whom sale treatment applies will recognize capital gain or loss in an amount equal to the difference, if any, between the amount of cash received and such U.S. Holder’s adjusted tax basis in the Shares exchanged.

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As noted above, a U.S. Holder of Shares to whom dividend treatment applies will treat the proceeds of the Offer or Merger as a distribution on Parent common stock to which Section 301 of the Code applies, and the adjusted tax basis in the Shares exchanged generally will be added to any shares of Parent common stock retained by the U.S. Holder. Such a distribution will be treated as a dividend to the extent of Parent’s and Akcea’s current and accumulated earnings and profits, as determined under U.S. federal income tax principles. To the extent that the amount of the deemed distribution exceeds Parent’s and Akcea’s current and accumulated earnings and profits, the excess first will be treated as a non-taxable return of capital that will reduce the U.S. Holder’s adjusted tax basis in its Parent common stock, and any remaining portion will be taxable to a U.S. Holder as capital gain. Such gain will generally be long term capital gain if, as of the date of the deemed redemption, the U.S. Holder’s holding period in the Parent common stock deemed redeemed is more than one year. Long term capital gain recognized by certain noncorporate U.S. Holders, including individuals, is currently subject to tax at a reduced rate. Parent’s and Akcea’s current and accumulated earnings and profits may not be readily determinable or made available.

Sale treatment applies to those holders of Shares who do not actually or constructively own any shares of Parent common stock immediately before, during, or immediately after the Offer or the Merger. Sale treatment also applies to U.S. Holders of Shares who actually or constructively own shares of Parent common stock immediately before, during, or immediately after the Effective Time, if they meet certain tests under Section 302 of the Code.

Under Sections 302 and 304 of the Code, sale treatment applies if the deemed redemption is “substantially disproportionate” or is “not essentially equivalent to a dividend.” The deemed redemption generally will be “substantially disproportionate” with respect to a U.S. Holder if the percentage of the outstanding Parent stock that the U.S. Holder actually and constructively owns immediately after the Effective Time is less than 80% of the percentage of the outstanding Shares that the U.S. Holder actually and constructively owned immediately before the Effective Time. The deemed redemption will be “not essentially equivalent to a dividend” if it results in a “meaningful reduction” in the U.S. Holder’s percentage of stock ownership of Parent immediately after the Effective Time as compared to such U.S. Holder’s percentage of stock ownership in Akcea immediately before the Effective Time, in each case applying constructive ownership rules. The IRS has ruled that a minority stockholder in a publicly traded corporation whose relative stock interest is minimal and who exercises no control with respect to corporate affairs is considered to have experienced a “meaningful reduction” if the stockholder has even a small reduction in such stockholder’s percentage of stock ownership under the above analysis. In applying the “substantially disproportionate” and “not essentially equivalent to a dividend” tests to a Holder, sales or purchases of Parent common stock made by such Holder (or by persons whose shares are attributed to such Holder) in connection with the Offer or the Merger will be taken into account. In addition, in applying these tests, a Holder that owns Parent stock immediately before the Effective Time is treated as owning a proportionate share of the Shares that are owned by Parent at such time.

Holders of Shares who own or acquire Parent stock and who do not meet the criteria for sale treatment will be subject to dividend treatment, as described above.

Because the application of Sections 302 and 304 of the Code may depend on a U.S. Holder’s particular circumstances, and because whether a deemed distribution under Sections 302 and 304 of the Code constitutes the distribution of a dividend depends on Parent’s and Akcea’s then-current and accumulated earnings and profits, a withholding agent may not be able to determine the amount of cash paid pursuant to the Offer or Merger that is a dividend for U.S. federal income tax purposes, if any. Withholding agents may report, on an applicable Form 1099, some or all of the cash received pursuant to the Offer or Merger as dividend income unless the withholding agent has established special procedures allowing U.S. Holders to certify that the cash they receive pursuant to the Offer or Merger is not treated as a distribution to which Section 301 of the Code applies under the Section 302 tests described above. However, there can be no assurances that such withholding agent will establish such special certification procedures. A withholding agent’s treatment of amounts received pursuant to the Offer or Merger as a dividend for U.S. federal income tax purposes is not dispositive, and is not binding on the IRS or such U.S. Holder.

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Because the possibility of dividend treatment may depend upon each Holder’s particular circumstances, including the application of constructive ownership rules, U.S. Holders of Shares should consult their own tax advisors regarding the application of the foregoing rules to their particular circumstances, and any actions that may be taken to mitigate the potential application of such rules (such as the desirability of selling their shares of Parent common stock or Shares prior to the Effective Time, and the considerations relating to the timing of any such sales).

Certain Tax Considerations for Non-U.S. Holders. The U.S. federal income tax consequences of the Offer and the Merger to Non-U.S. Holders will be the same as those described above for U.S. Holders of Shares, except that, subject to the discussion below regarding potential dividend treatment, a Non-U.S. Holder generally will not be subject to U.S. federal income tax or withholding tax on any gain realized in connection with the Offer or the Merger unless:

Gain described in the first bullet point above will be subject to U.S. federal income tax on a net income basis at the regular graduated U.S. federal income tax rates in the same manner as if such Non-U.S. Holder were a U.S. person. A Non-U.S. Holder that is a corporation also may be subject to an additional branch profits tax at a rate of 30% (or such lower rate as may be specified by an applicable income tax treaty) on its “effectively connected earnings and profits” for the taxable year, subject to certain adjustments.

Gain described in the second bullet point above will be subject to U.S. federal income tax at a 30% rate (or such lower rate as may be specified by an applicable income tax treaty), but may be offset by U.S.-source capital losses, if any, of the Non-U.S. Holder.

If the third bullet point above applies to a Non-U.S. Holder, gain recognized by such Non-U.S. Holder on the exchange of Shares for the Offer Price or the Merger Consideration pursuant to the Offer or the Merger, as applicable, will be subject to tax at generally applicable U.S. federal income tax rates. In addition, Parent may be required to withhold U.S. income tax at a rate of 15% of the Offer Price or the Merger Consideration, as applicable. Akcea will be classified as a United States real property holding corporation if the fair market value of its “United States real property interests” equals or exceeds 50% of the sum of the fair market value of its worldwide real property interests plus its other assets used or held for use in a trade or business, as determined for U.S. federal income tax purposes. We do not believe Akcea currently is or has previously been a United States real property holding corporation, and we anticipate receiving a certification from Akcea in that regard. Non-U.S. Holders are urged to consult their tax advisors regarding the application of these rules.

As discussed above under the section entitled “—Certain Tax Considerations for U.S. Holders”, in certain circumstances, dividend treatment may apply to the Offer Price or the Merger Consideration received pursuant to the Offer or the Merger, as applicable, in which case a Non-U.S. Holder may be treated as receiving a dividend up to the amount of the cash received. Any amount so treated generally would be subject to U.S. withholding tax at a rate of 30%, or such lower rate as may be specified by an applicable income tax treaty, unless such dividend is effectively connected with the Non-U.S. Holder’s conduct of a trade or business within the United States (and, if required by an applicable income tax treaty, is attributable to a permanent establishment of such Non-U.S. Holder in the United States).

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Because the application of Sections 302 and 304 of the Code may depend on a Non-U.S. Holder’s particular circumstances, and because whether a deemed distribution under Sections 302 and 304 of the Code constitutes the distribution of a dividend depends on Parent’s and Akcea’s then-current and accumulated earnings and profits, a withholding agent may not be able to determine the amount subject to such withholding with respect to a Non-U.S. Holder. Accordingly, withholding agents may withhold tax at a rate of 30% (or such lower rate as may be specified by an applicable income tax treaty) on the entire amount of the cash consideration payable to such Non-U.S. Holder pursuant to the Offer or the Merger, as applicable, unless (i) the withholding agent has established special procedures allowing Non-U.S. Holders to certify that they are exempt from such withholding tax, and (ii) such Non-U.S. Holder is able to certify that it meets the requirements of such exemption (e.g., because such Non-U.S. Holder is eligible for sale rather than dividend treatment under the tests described above). However, there can be no assurance that such withholding agent will establish such special certification procedures. If a withholding agent withholds amounts from the cash consideration payable to a Non-U.S. Holder in excess of the tax actually owing (e.g., because the “Non-U.S. Holder” is eligible for sale treatment or because the “Non-U.S. Holder” is entitled to a lower rate of withholding on dividends under a treaty), such Non-U.S. Holder may obtain a refund of any such excess amounts by timely filing an appropriate claim with the IRS.

Non-U.S. Holders should consult their own tax advisors regarding the application of the foregoing rules in light of their particular facts and circumstances, the procedures for claiming treaty benefits or otherwise establishing an exemption from U.S. withholding tax with respect to any portion of the cash consideration payable to them pursuant to the Offer or the Merger, as applicable, and the possible desirability of selling their Shares or Parent common stock (and considerations relating to the timing of any such sales).

Information Reporting and Backup Withholding. Payments to Holders may be subject to information reporting and backup withholding. A U.S. Holder may avoid such backup withholding if such U.S. Holder furnishes its correct TIN on an IRS Form W-9 (or substitute or successor form or, if appropriate, another withholding form) or provides proof of an applicable exemption, and otherwise complies with all applicable requirements of the backup withholding rules. If a U.S. Holder fails to provide the correct TIN or certification or otherwise fails to comply with the applicable backup withholding rules, payments received pursuant to the Offer or the Merger may be subject to backup withholding. The backup withholding rate is currently 24%. Certain Holders (including corporations and Non-U.S. Holders) generally are exempt backup withholding. Exempt Holders may be required to comply with certification requirements and identification procedures in order to establish an exemption from information reporting and backup withholding.

Backup withholding is not an additional tax. Rather, any amounts withheld under the backup withholding rules generally will be allowed as a refund of, or credit against, the U.S. federal income tax liability of persons subject to backup withholding, provided that the required information is timely furnished to the IRS.

Foreign Account Tax Compliance Act. Sections 1471 through 1474 of the Code and the Treasury Regulations and administrative guidance promulgated thereunder (commonly referred as the “Foreign Account Tax Compliance Act” or “FATCA”) generally impose withholding at a rate of 30% in certain circumstances on dividends in respect of our securities which are held by or through certain foreign financial institutions (including investment funds), unless any such institution (1) enters into, and complies with, an agreement with the IRS to report, on an annual basis, information with respect to interests in, and accounts maintained by, the institution that are owned by certain U.S. persons and by certain non-U.S. entities that are wholly or partially owned by U.S. persons and to withhold on certain payments, or (2) if required under an intergovernmental agreement between the United States and an applicable foreign country, reports such information to its local tax authority, which will exchange such information with the U.S. authorities. An intergovernmental agreement between the United States and an applicable foreign country may modify these requirements. Accordingly, the entity through which our securities are held will affect the determination of whether such withholding is required. Similarly, dividends in respect of our securities held by an investor that is a non-financial non-U.S. entity that does not qualify under

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certain exceptions will generally be subject to withholding at a rate of 30%, unless such entity either (1) certifies to Parent or the applicable withholding agent that such entity does not have any “substantial United States owners” or (2) provides certain information regarding the entity’s “substantial United States owners,” which will in turn be provided to the U.S. Department of Treasury. Holders should consult their tax advisors regarding the possible implications of FATCA on the Offer or the Merger.

The U.S. federal income tax considerations described above are not intended to constitute a complete description of all tax considerations applicable to the Offer or the Merger. Because individual circumstances may differ, each Holder of Shares should consult such Holder’s tax advisor regarding the applicability of the rules discussed above to the Holder and the particular tax effects to the Holder of the Offer or the Merger in light of such Holder’s particular circumstances and the application of state, local and non-U.S. tax laws.

The Shares are traded on Nasdaq under the symbol “AKCA.” Akcea has advised Parent that, as of the close of business on September 8, 2020, 101,759,772 Shares were outstanding. The following table sets forth, for the fiscal quarters indicated, the high and low sales prices per Share on Nasdaq with respect to the fiscal years ended December 31, 2018 and December 31, 2019 and, with respect to the fiscal year ended December 31, 2020, through September 11, 2020, using Share data reported by Nasdaq.

Akcea has never paid dividends on its common stock. In Akcea’s Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2020 (the “Akcea 10-Q”), Akcea had indicated that it would continue to retain its future earnings to maintain and expand its operations. Additionally, under the terms of the Merger Agreement, Akcea is not permitted to declare or pay any dividends on or make other distributions in respect of any of its capital stock. See Section 23—“Dividends and Distributions.”

On August 28, 2020, the trading day before the public announcement of the execution of the Merger Agreement, the reported closing sales price of the Shares on Nasdaq was $11.38. On September 11, 2020, the last full trading day prior to the commencement of the Offer, the reported closing sales price per Share on Nasdaq during normal trading hours was $18.14 per Share. Stockholders are urged to obtain a current market quotation for the Shares.

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Possible Effects of the Offer on the Market for the Shares. The purchase of Shares pursuant to the Offer will reduce the number of Shares that might otherwise trade publicly and could adversely affect the liquidity and market value of the remaining Shares held by the public. The purchase of Shares pursuant to the Offer can also be expected to reduce the number of holders of Shares. We cannot predict whether the reduction in the number of Shares that might otherwise trade publicly would have an adverse or beneficial effect on the market price or marketability of the Shares or whether it would cause future market prices to be greater or less than the Offer Price.

Nasdaq Listing. Depending upon the number of Shares purchased pursuant to the Offer, the Shares may no longer meet the requirements for continued listing on the Nasdaq. According to the published guidelines of The Nasdaq Stock Market, LLC, Nasdaq would consider disqualifying the Shares for listing on Nasdaq if, among other possible grounds, (i) the total number of holders of record and holders of beneficial interest, taken together, in the Shares falls below 400, (ii) the bid price for a Share over a 30 consecutive business day period is less than $1.00, or (iii)(a) Akcea has stockholders’ equity of less than $10 million, the number of publicly held Shares falls below 750,000, the market value of publicly held Shares over a 30 consecutive business day period is less than $5 million or there are fewer than two active and registered market makers in the Shares over a 10 consecutive business day period, (b) the number of publicly held Shares falls below 1,100,000, the market value of publicly held Shares over a 30 consecutive business day period is less than $15 million, there are fewer than four active and registered market makers in the Shares over a 10 consecutive business day period, or the market value of Akcea’s listed securities is less than $50 million over a 10 consecutive business day period or (c) the number of publicly held shares falls below 1,100,000, the market value of publicly held Shares over a 30 consecutive business day period is less than $15 million, there are fewer than four active and registered market makers in the Shares over a 10 consecutive business day period, or Akcea’s total assets and total revenue is less than $50 million each for the most recently completed fiscal year (or in two of the last three fiscal years). Shares held by officers or directors of Akcea, or by any beneficial owner of more than 10 percent of the Shares, will not be considered as being publicly held for this purpose. According to Akcea, there were, as of September 8, 2020, approximately 101,759,772 Shares issued and outstanding. If, as a result of the purchase of Shares pursuant to the Offer or otherwise, the Shares are delisted from Nasdaq, the market for Shares will be adversely affected.

If Nasdaq were to delist the Shares, it is possible that the Shares would continue to trade on other securities exchanges or in the over-the-counter market and that price or other quotations for the Shares would be reported by other sources. The extent of the public market for such Shares and the availability of such quotations would depend, however, upon such factors as the number of stockholders and the aggregate market value of such securities remaining at such time, the interest in maintaining a market in the Shares on the part of securities firms, the possible termination of registration under the Exchange Act as described below, and other factors. We cannot predict whether the reduction in the number of Shares that might otherwise trade publicly would have an adverse or beneficial effect on the market price for or marketability of the Shares or whether it would cause future market prices to be greater or less than the Offer Price.

Trading in the Shares will cease upon consummation of the Merger if trading has not ceased earlier as discussed above.

Exchange Act Registration. The Shares currently are registered under the Exchange Act. The purchase of the Shares pursuant to the Offer may result in the Shares becoming eligible for deregistration under the Exchange Act. Registration of the Shares may be terminated by Akcea upon application to the SEC if the outstanding Shares are not listed on a “national securities exchange” and if there are fewer than 300 holders of record of Shares.

We intend to seek to cause Akcea to apply for termination of registration of the Shares as soon as possible after consummation of the Offer if the requirements for termination of registration are met. Termination of registration of the Shares under the Exchange Act would reduce the information required to be furnished by

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Akcea to its stockholders and to the SEC and would make certain provisions of the Exchange Act (such as the short-swing profit recovery provisions of Section 16(b), the requirement of furnishing a proxy statement or information statement in connection with stockholders’ meetings or actions in lieu of a stockholders’ meeting pursuant to Sections 14(a) and 14(c) under the Exchange Act and the related requirement of furnishing an annual report to stockholders) no longer applicable with respect to the Shares. In addition, if the Shares are no longer registered under the Exchange Act, the requirements of Rule 13e-3 under the Exchange Act with respect to “going private” transactions would no longer be applicable to Akcea. Furthermore, the ability of “affiliates” of Akcea and persons holding “restricted securities” of Akcea to dispose of such securities pursuant to Rule 144 under the Securities Act of 1933, as amended, may be impaired or eliminated. If registration of the Shares under the Exchange Act were terminated, the Shares would no longer be eligible for continued inclusion on the list of “margin securities” of the Board of Governors of the Federal Reserve System (the “Federal Reserve Board”) or be eligible for stock exchange listing.

If registration of the Shares is not terminated prior to the Merger, then the registration of the Shares under the Exchange Act will be terminated following completion of the Merger.

Margin Regulations. The Shares are currently “margin securities” under the regulations of the Federal Reserve Board, which has the effect, among other things, of allowing brokers to extend credit using such Shares as collateral. Depending upon factors similar to those described above regarding listing and market quotations, following the Offer, the Shares may no longer constitute “margin securities” for the purposes of the margin regulations of the Federal Reserve Board, in which event the Shares would be ineligible as collateral for margin loans made by brokers.

The following description of Akcea and its business was taken from the Akcea 10-K, and is qualified in its entirety by reference to such annual report.

Akcea is a commercial stage biopharmaceutical company developing and commercializing transformative medicines to treat patients with serious and rare diseases. Akcea’s large and advancing pipeline of medicines in late-stage development and medicines on the market allow it to capitalize on its strengths in supporting patients, healthcare professionals and caregivers in treating rare and serious diseases. Akcea is highly focused on commercializing its approved therapies, TEGSEDI and WAYLIVRA. Akcea also has a robust portfolio of antisense medicines in development covering multiple targets and diseases that it has licensed from Parent. Akcea’s strong relationship with Parent allows it to continue to expand its pipeline.

Akcea is a Delaware corporation incorporated in December 2014. Akcea’s corporate headquarters are located at 22 Boston Wharf Road, 9th Floor, Boston, MA 02210. Akcea’s telephone number at such corporate headquarters is (617) 207-0202.

Historical Selected Financial Information. The following tables sets forth summary historical consolidated financial data for Akcea as of and for each of the years ended December 31, 2018 and 2019 and as of and for each of the six months ended June 30, 2019 and 2020. The selected financial data and the per Share data set forth below are extracted from, and should be read in conjunction with, the consolidated financial statements and other financial information contained in the Akcea 10-Q and the Akcea 10-K. More comprehensive financial information is included in such reports (including management’s discussion and analysis of financial condition and results of operation) and other documents filed by Akcea with the SEC, and the following summary is qualified in its entirety by reference to such reports and other documents and all of the financial information and notes contained therein. The financial statements included as Item 8 of the Akcea 10-K and Item 1 of Part I in the Akcea 10-Q are hereby incorporated by reference in this Offer to Purchase. The reports may be examined, and copies may be obtained from the SEC in the manner described under “Available Information” below. Historical results are not necessarily indicative of results to be expected in any future

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period. Set forth below are Akcea’s selected consolidated financial data (in thousands, except share and per share amounts):

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Book Value Per Share. Akcea’s net book value per share as of June 30, 2020 was $4.71 (calculated based on 101,598,619 Shares outstanding as of July 29, 2020).

Certain Prospective Financial Information. Neither Parent nor Akcea, as a matter of course, publicly discloses forecasts or projections as to future performance, earnings or other results due in part to the inherent unpredictability of the underlying assumptions, estimates and projections and the likelihood that the underlying assumptions, estimates and projections may not be realized.

The financial projections contained in this Offer to Purchase (the “Projections”), while presented with numerical specificity, necessarily were based on numerous variables and assumptions that are inherently

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uncertain and many of which are beyond Parent’s, Purchaser’s and Akcea’s control. Because the Projections cover multiple years, by its nature, this information becomes subject to greater uncertainty with each successive year. The assumptions upon which the Projections were based necessarily involve judgments with respect to, among other things, development timelines, likelihood of clinical success, product pricing, market uptake, reimbursement and potential competition, all of which are difficult or impossible to predict accurately and many of which are beyond Parent’s, Purchaser’s and Akcea’s control. The Projections also reflect assumptions as to certain business decisions and transactions that are subject to change and may not occur, at all or on the terms assumed. Important factors that may affect actual results and result in the Projections not being achieved include, but are not limited to: (1) the availability and level of third-party reimbursement for Akcea’s products and services; (2) market acceptance of such products and services; (3) the introduction of new Akcea products and services; (4) access to sufficient capital; (5) the impact of competition; (6) the effect of regulatory actions; (7) the effect of global economic conditions; (8) changes in applicable laws, rules and regulations; and (9) other risk factors described in Parent’s and Akcea’s Annual Reports on Form 10-K for the fiscal year ended December 31, 2019, and their subsequent respective Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. In addition, the Projections may be affected by the ability of Parent, Purchaser or Akcea to achieve strategic goals, objectives and targets over the applicable period.

Accordingly, the Projections may not be realized, and actual results may vary materially from those contained in the Projections. The inclusion of the Projections in this Offer to Purchase should not be regarded as an indication that Parent or any of its affiliates (including Akcea), advisors or representatives considered or consider the Projections to be predictive of actual future events, and the Projections should not be relied upon as such. None of Parent or any of its affiliates (including Akcea), advisors, officers, directors or representatives can give any assurance that actual results will not differ materially from the Projections, and none of them undertakes any obligation to update or otherwise revise or reconcile the Projections to reflect circumstances existing after the dates on which the Projections were prepared or to reflect the occurrence of future events even in the event that any or all of the assumptions underlying the Projections are shown to be in error. Parent does not intend to make publicly available any update or other revision to the Projections, and the Projections have not been updated since the date of preparation to reflect subsequent developments or events that could impact Akcea or its future financial performance, and should not be treated as guidance with respect to projected results for any fiscal year or other period. None of Parent or any of its affiliates (including Akcea), advisors, officers, directors or representatives has made or makes any representation to any Parent or Akcea stockholder or other person regarding the ultimate performance of Akcea compared to the information contained in the Projections or that the Projections will be achieved or that any intervening event, development, change or result since the date of preparation of the Projections has not rendered the Projections unreliable or no longer current.

The Projections were developed under the assumption of Akcea’s continued standalone operation and did not give effect to any changes or expenses as a result of the Transactions or reflect any effects of the Transactions or the effect of the failure of the Transactions to be consummated. The Projections were not prepared with a view toward public disclosure; and, accordingly, do not necessarily comply with published guidelines of the SEC, the guidelines established by the American Institute of Certified Public Accountants for preparation and presentation of financial forecasts, or GAAP. Certain of the Projections may be considered non-GAAP financial measures. Non-GAAP financial measures should not be considered in isolation from, or as a substitute for, financial information presented in compliance with GAAP, and non-GAAP financial measures as used by Parent or Akcea may not be comparable to similarly titled amounts used by other companies. Such non-GAAP financial measures should not be considered as an alternative to operating income or net income as measures of operating performance, or as an alternative to cash flows, as a measure of liquidity. Neither Parent’s nor Akcea’s independent registered public accounting firm, nor any other independent accountant, has audited, reviewed, compiled or performed any procedures with respect to the Projections or expressed any opinion or any other form of assurance related thereto.

The Projections are not intended to influence or induce any Akcea stockholder to tender Shares in the Offer. Instead, the Projections are included solely because the Projections were made available to Goldman Sachs and

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Stifel, who, at the instruction of Parent, used such projections in connection with rendering their respective presentations to Parent’s Finance Committee and Board of Directors and performing their related financial analyses, as described above in Section 10—“Materials Prepared by Parent’s Financial Advisors.”

In light of the foregoing factors and the uncertainties inherent in the financial projections included in this Offer to Purchase, stockholders are cautioned not to place undue, if any, reliance on the projected financial information included below.

As described in the Schedule 14D-9 under the heading “Certain Prospective Financial Information,” in connection with Parent’s regular long-term business planning process, Parent receives certain nonpublic financial, operating and other forward-looking information from Akcea in the ordinary course of business.

In advance of a meeting of the Akcea Board held on May 28, 2020, Akcea management presented certain financial projections for Akcea for the fiscal years 2020-2029 (the “May Projections”), which are summarized in the Schedule 14D-9 under the heading “Certain Prospective Financial Information.” The May Projections were prepared at the request of the Akcea Board in order to inform its review of Akcea’s strategic plans and anticipated financing needs. Consistent with past practice, Akcea’s management developed the May Projections with the assistance of members of the Parent Board and management of Parent. The May Projections were provided to Parent in the ordinary course of business at or around the time of the May 28, 2020 meeting of the Akcea Board.

In connection with Parent’s consideration of a potential acquisition of the Shares during July and August 2020, Parent used the May Projections to develop projections (with additional assumptions, adjustments and extrapolations by Parent) covering the period from the fiscal year ending December 31, 2020, through the fiscal year ending December 31, 2041, or the Projections. Parent provided the Projections to Goldman Sachs and Stifel for use in connection with rendering their respective presentations to Parent’s Finance Committee and Board of Directors on August 7, 2020 and August 30, 2020 and performing their related financial analyses, as described more fully in Section 10—“Materials Prepared by Parent’s Financial Advisors.” The Projections were not made available to Akcea or its representatives.

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The following table presents the Projections: