Material Event Form 8 K

On September 9, 2024, Ionis Pharmaceuticals, Inc. ("Ionis") entered into an underwriting agreement (the "Underwriting Agreement") with Morgan Stanley & Co. LLC and Goldman Sachs & Co. LLC as representatives of the several underwriters named therein (collectively, the "Underwriters"), relating to the public offering, issuance and sale (the "Offering") of 11,500,000 shares of its common stock, par value $0.001 per share ("Common Stock"), at a price to the public of $43.50 per share. Pursuant to the Underwriting Agreement, the Underwriters purchased the shares of Common Stock from Ionis at a price of $42.6020 per share. Ionis also granted the Underwriters a 30-dayoption to purchase up to an additional 1,725,000 shares of Common Stock from Ionis at the public offering price, less the underwriting discounts and commissions.

The gross proceeds to Ionis from the Offering were approximately $500.3 million, before deducting underwriting discounts and commissions and other estimated offering expenses payable by Ionis. The closing of the Offering occurred on September 11, 2024.

The Offering is being made pursuant to Ionis' effective registration statement on Form S-3(Registration Statement No. 333-275741),as previously filed with the Securities and Exchange Commission, and a related prospectus and prospectus supplement.

The Underwriting Agreement contains customary representations, warranties and covenants by Ionis, customary conditions to closing, indemnification obligations of Ionis and the Underwriters, including for liabilities under the Securities Act of 1933, as amended, other obligations of the parties and termination provisions. The representations, warranties and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to such agreement and may be subject to limitations agreed upon by such parties.

The Underwriting Agreement is filed as Exhibit 1.1 hereto. The foregoing description of the terms of the Underwriting Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit hereto. A copy of the opinion of Cooley LLP relating to the legality of the issuance and sale of the securities in the Offering is attached as Exhibit 5.1 hereto.