Exhibit 99.4

Ionis bpm Update Transcript

Good morning everyone and happy Monday.

I’m reaching out to you this morning to share some very exciting news.

We just announced today that we’ve reached an agreement with Akcea to acquire the outstanding shares of Akcea common stock, the remaining shares that we do not own already, approximately 24%.

This step is yet another step forward in the evolution of Ionis, a step forward that creates a stronger, more efficient organization to the benefit of all stakeholders.

Over the past few years, Ionis and Akcea have grown and evolved significantly. We believe at this time there is significant strategic value in becoming one company – with one vision and one set of strategic priorities, led by one team.

We believe this transaction will greatly enhance the future success of Ionis and accelerate our next phase of growth. By creating an even stronger financial foundation, with the retention of more value from Akcea’s rich pipeline and commercial products, which this transaction will do, Ionis will be ideally positioned to drive forward our vision to lead in the delivery of transformational medicines to the patients that depend on us.

Given how closely we work with Akcea on a day-to-day basis, we expect this to be a seamless transition with minimal disruption.

Until the transaction closes, which we expect to happen in the fourth quarter of this year, Ionis and Akcea will continue to operate as we have, that is to operate business as usual.

I am looking forward to discussing this transaction with you further at an All-Employee Meeting soon, sometime in September. In the meantime, I encourage you to speak with your area Vice President if you have questions.

Thanks, as always, for your hard work, your commitment to Ionis and to the patients we serve. And thanks for listening. More coming soon, but that’s all for now.

Notice to Investors and Security Holders    

The tender offer referred to in this communication has not yet commenced. The description contained in this communication is neither an offer to purchase nor a solicitation of an offer to sell any securities, nor is it a substitute for the tender offer materials that Ionis will file with the Securities and Exchange Commission (the “SEC”). The solicitation and offer to buy shares of Akcea common stock will only be made pursuant to an offer to purchase and related tender offer materials. At the time the tender offer is commenced, Ionis will file a tender offer statement on Schedule TO and thereafter Akcea will file a solicitation/recommendation statement on Schedule 14D-9 with the SEC with respect to the Offer. THE TENDER OFFER MATERIALS (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND CERTAIN OTHER OFFER DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT ON SCHEDULE 14D-9 WILL CONTAIN IMPORTANT INFORMATION. AKCEA SHAREHOLDERS ARE URGED TO READ THESE DOCUMENTS CAREFULLY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION THAT HOLDERS SHOULD CONSIDER BEFORE MAKING ANY DECISION REGARDING TENDERING THEIR SHARES. The offer to purchase, the related letter of transmittal and the solicitation/recommendation statement will be made available free of charge at the SEC’s website at www.sec.gov. Additional copies may be obtained for free by contacting Ionis or Akcea, as applicable. Copies of the documents filed with the SEC by Ionis will be available free of charge on Ionis’ internet website at https://ir.ionispharma.com/financial-information/sec-filings or by contacting Ionis’ investor relations contact at (760) 603-2681. Copies of the documents filed with the SEC by Akcea will be available free of charge on Akcea’s internet website at https://ir.akceatx.com/ or by contacting Akcea’s investor relations contact at (617) 841-9535.

In addition to the offer to purchase, the related letter of transmittal and certain other tender offer documents to be filed by Ionis, as well as the solicitation/recommendation statement to be filed by Akcea, Ionis and Akcea will also file quarterly and current reports with the SEC. Ionis’ and Akcea’s filings with the SEC are available to the public from commercial document-retrieval services and at the website maintained by the SEC at http://www.sec.gov.

Forward-Looking Statements

Ionis Pharmaceuticals, Inc. assumes no obligation to update forward-looking statements contained in this communication as a result of new information or future events or developments except as required by law. This communication includes forward-looking statements regarding the business of Ionis Pharmaceuticals, Inc., including the business of Akcea Therapeutics, Inc., Ionis’ majority owned affiliate, and the proposed acquisition of Akcea that are subject to risks and uncertainties that could cause actual results to differ materially from those expressly or implied by such statements. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Risks and uncertainties also include, among other things, risks related to the satisfaction or waiver of the conditions to closing the proposed acquisition in the anticipated timeframe or at all, including uncertainties as to how many of Akcea’s stockholders will tender their Shares in the tender offer and the possibility that the acquisition does not close; disruption from the transaction making it more difficult to maintain business and operational relationships; risks that anticipated synergies will not be realized or may be delayed; and the magnitude of transaction costs. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. In particular, we caution you that our forward-looking statements are subject to the ongoing and developing circumstances related to the COVID-19 pandemic, which may have a material adverse effect on our business, operations and future financial results. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are described in additional detail in Ionis’ quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the SEC. Copies of these and other documents are available from Ionis.