# EDGAR Filing Document

**Accession Number:** 0000874015
**File Stem:** 0001140361-25-039650
**Filing Date:** 2025-10
**Character Count:** 34774
**Document Hash:** 4920dc9b0437abd7561d56b0bf9ac51c
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001140361-25-039650.hdr.sgml**: 20251029

**ACCESSION NUMBER**: 0001140361-25-039650

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 14

**CONFORMED PERIOD OF REPORT**: 20251029

**ITEM INFORMATION**: Results of Operations and Financial Condition

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251029

**DATE AS OF CHANGE**: 20251029

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** IONIS PHARMACEUTICALS INC
- **CENTRAL INDEX KEY:** 0000874015
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 330336973
- **STATE OF INCORPORATION:** CA
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 000-19125
- **FILM NUMBER:** 251426794

**BUSINESS ADDRESS:**
- **STREET 1:** 2855 GAZELLE COURT
- **CITY:** CARLSBAD
- **STATE:** CA
- **ZIP:** 92010
- **BUSINESS PHONE:** 7609319200

**MAIL ADDRESS:**
- **STREET 1:** 2855 GAZELLE COURT
- **CITY:** CARLSBAD
- **STATE:** CA
- **ZIP:** 92010

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** ISIS PHARMACEUTICALS INC
- **DATE OF NAME CHANGE:** 19930328

?xml version='1.0' encoding='ASCII'?

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### SECURITIES AND EXCHANGE COMMISSION

#### Washington, D.C. 20549

### FORM 8-K

#### CURRENT REPORT

#### PURSUANT TO SECTION 13 OR 15(d) OF THE

#### SECURITIES EXCHANGE ACT OF 1934
Date of report (Date of earliest event reported): October 29, 2025

## IONIS PHARMACEUTICALS, INC.
(Exact Name of Registrant as Specified in Charter)

#### Delaware
(State or Other Jurisdiction of Incorporation)

---

| | |
|:---|:---|
| **000-19125**<br>| **33-0336973**<br>|
| (Commission File No.) | (IRS Employer Identification No.) |

---

#### 2855 Gazelle Court

#### Carlsbad, CA 92010
(Address of Principal Executive Offices and Zip Code)

Registrant's telephone number, including area code: **(760) 931-9200**

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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

---

| | | |
|:---|:---|:---|
| Title of each class | Trading symbol | Name of each exchange on which registered |
| Common Stock, $.001 Par Value<br>| "IONS" | The Nasdaq Stock Market, LLC<br>|

---

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (Section 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (Section 240.12b-2 of this chapter).

&nbsp;&nbsp;&nbsp;&nbsp;Emerging growth company&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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---

| | |
|:---|:---|
| **Item 2.02** | Results of Operations and Financial Condition. |

---

On October 29, 2025, Ionis Pharmaceuticals, Inc. (the "***Company***") issued a press release announcing the Company's financial results for the quarter ended September 30, 2025. In addition to disclosing results that are determined in accordance with Generally Accepted Accounting Principles ("***GAAP***"), the Company also discloses pro forma or non-GAAP results of operations, which are adjusted from GAAP to exclude non-cash compensation expense related to equity awards and the related tax effects. The Company is presenting pro forma information excluding non-cash compensation expense and the related tax effects because the Company believes it better enables financial statement users to assess and compare its historical performance and project its future operating results and cash flows. A copy of the release is furnished with this report as an exhibit pursuant to "Item 2.02. Results of Operations and Financial Condition" of Form 8-K in accordance with SEC Release Nos. 33-8216 and 34-47583.

The information in this Current Report on Form 8-K and the Exhibit attached hereto shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934 (the "***Exchange Act***") or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, regardless of any general incorporation language in such filing.

---

| | |
|:---|:---|
| **Item 9.01.** | Financial Statements and Exhibits. |

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(d) Exhibits.

---

| | |
|:---|:---|
| **<u>Exhibit No.</u>** | **<u>Description</u>** |
| [99.1](ef20057869_ex99-1.htm) | Press Release dated October 29, 2025. |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |

---

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#### SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

---

| | | |
|:---|:---|:---|
|  | **Ionis Pharmaceuticals, Inc.** | **Ionis Pharmaceuticals, Inc.** |
| Dated: October 29, 2025 | By: | <u>/s/ Patrick R. O'Neil</u> |
|  |  | **Patrick R. O'Neil** |
|  |  | Executive Vice President, Chief Legal Officer and General Counsel |

---

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## Exhibit 99.1

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**Exhibit 99.1**<br>

![](image0.jpg)

#### Ionis reports third quarter 2025 financial results and highlights progress on key programs

*- TRYNGOLZA*<sup>®</sup> *generated $32 million in net product sales in the third quarter 2025 -*

*- DAWNZERA™ (donidalorsen) launch off to encouraging start -*

*- Olezarsen significantly reduced triglycerides and acute pancreatitis events in severe hypertriglyceridemia (sHTG) in landmark Phase 3 studies; sNDA submission on track by year-end –*

*- Positive pivotal zilganersen results in Alexander disease position Ionis for first independent neurology launch in 2026 -*

*- Increasing 2025 financial guidance driven by continued strength across the business –*

**CARLSBAD, Calif., October 29, 2025** – Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company") today reported financial results and provided key updates for the third quarter ended September 30, 2025.

"The third quarter was a watershed moment for Ionis, as we made important progress advancing our Ionis-owned medicines. With two independent launches now underway, and two more anticipated in 2026, we are delivering on our goal to bring a steady cadence of new medicines to people in need," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "Last month, we announced groundbreaking, positive topline Phase 3 results for olezarsen in severe hypertriglyceridemia and for zilganersen in Alexander disease, with regulatory filings planned in the coming months. Our approved and late-stage portfolio continues to deliver — positioning Ionis for substantial growth while, most importantly, offering the opportunity to profoundly improve the lives of people with serious diseases."

#### Third Quarter 2025 Summary Financial Results<sup>(1)</sup>:

---

| | | | | |
|:---|:---|:---|:---|:---|
|  | Three months ended | Three months ended | Nine months ended | Nine months ended |
|  | September 30, | September 30, | September 30, | September 30, |
|  | 2025 | 2024 | 2025 | 2024 |
|  | (amounts in millions) | (amounts in millions) | (amounts in millions) | (amounts in millions) |
| Total revenue | $157 | $134 | $740 | $479 |
| Operating expenses | $317 | $282 | $907 | $843 |
| Operating expenses on a non-GAAP basis | $286 | $250 | $816 | $749 |
| Loss from operations | $(160) | $(148) | $(167) | $(364) |
| Loss from operations on a non-GAAP basis | $(129) | $(116) | $(76) | $(270) |

---

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(1) Reconciliation of GAAP to non-GAAP basis contained later in this release.

------

#### Recent Financial Highlights
&nbsp;&nbsp;&nbsp;&nbsp;• Revenue increased 17% in the third quarter of 2025 and increased 55% in the nine months ended September 30, 2025, compared to the same periods last year, driven by the continued successful launch
 of TRYNGOLZA and increased royalty revenues. Contributing to the year-to-date increase, Ionis earned a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025

&nbsp;&nbsp;&nbsp;&nbsp;• Operating expenses increased 14% in the third quarter of 2025 and increased 9% in the nine months ended September 30, 2025, compared to the same periods last year, primarily due to investments
 related to commercialization efforts for TRYNGOLZA, DAWNZERA and WAINUA

&nbsp;&nbsp;&nbsp;&nbsp;• Increasing 2025 financial guidance reflects strong overall revenue performance experienced year-to-date and fourth quarter outlook, including strong momentum seen with TRYNGOLZA revenues:

---

| | | |
|:---|:---|:---|
| <br> Full Year 2025 Guidance | Previous<br> Guidance | New<br> Guidance |
| Total Revenue | $825-850 million | $875-900 million |
| TRYNGOLZA product sales, net | $75-80 million | $85-95 million |
| Operating loss on a non-GAAP basis | $300-325 million | $275-300 million |
| Cash, cash equivalents and short-term investments | ~$2.0 billion | >$2.1 billion |

---

#### Third Quarter 2025 Financial Results
"In the third quarter of 2025, we delivered strong revenue performance, highlighted by TRYNGOLZA's nearly 70% increase over the prior quarter. As a result of this strength and our fourth quarter outlook, we are increasing our financial guidance again for 2025," said Elizabeth L. Hougen, chief financial officer of Ionis. "Looking ahead, we expect the 2026 independent launches of olezarsen in severe hypertriglyceridemia and zilganersen in Alexander disease to further strengthen our commercial portfolio. We anticipate that growth in our product revenues coupled with additional partner revenues will position Ionis to achieve cash flow breakeven in 2028 and generate substantial and sustainable positive cash flow for years to come."

#### Recent Highlights - Wholly Owned Medicines

&nbsp;&nbsp;&nbsp;&nbsp;• TRYNGOLZA<sup>®</sup> (olezarsen), the first and only FDA approved treatment for adults living with familial chylomicronemia syndrome (FCS) as an
 adjunct to diet

---

| | |
|:---|:---|
| &nbsp;&nbsp;&nbsp;&nbsp;o | Generated net product sales of $32 million in the third quarter of 2025, its third full quarter on the market, a nearly 70% increase over the prior quarter, and $57 million in the nine months ended September 30, 2025 |

---

<br> o Approved in the European Union (EU) as an adjunct to diet in adult patients for the treatment of genetically confirmed FCS; Sobi anticipates launching in the fourth quarter 2025

&nbsp;&nbsp;&nbsp;&nbsp;• Olezarsen demonstrated positive topline results in the pivotal Phase 3 CORE and CORE2 studies in sHTG

---

| | |
|:---|:---|
| &nbsp;&nbsp;&nbsp;&nbsp;o | Olezarsen demonstrated a highly statistically significant placebo-adjusted mean reduction in fasting triglycerides of up to 72% and a highly statistically significant reduction in acute pancreatitis events of 85% with favorable safety and tolerability |

---

------

<br> o sNDA submission on track for the end of 2025 with approval anticipated in the fourth quarter of 2026

<br> o Detailed data to be presented at the American Heart Association Conference on November 8, 2025, in a late-breaking session

&nbsp;&nbsp;&nbsp;&nbsp;• DAWNZERA™ (donidalorsen) was approved on August 21, 2025, by the FDA for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older

<br> o First and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector every four or eight weeks

<br> o U.S. launch underway and off to an encouraging start

<br> o Currently under regulatory review in the EU

&nbsp;&nbsp;&nbsp;&nbsp;• Zilganersen demonstrated positive results in the pivotal study in children and adults with Alexander disease (AxD), a rare, progressive, and often fatal neurological disorder with no approved
 disease-modifying treatments

---

| | |
|:---|:---|
| &nbsp;&nbsp;&nbsp;&nbsp;o | Zilganersen 50 mg demonstrated statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at week 61 (mean difference 33.3%) with favorable safety and tolerability |

---

<br> o Additional data from the pivotal study in children and adults living with Alexander disease were presented at the Child Neurology Society Annual Meeting in October 2025

<br> o NDA submission planned for the first quarter of 2026 with approval anticipated next year

&nbsp;&nbsp;&nbsp;&nbsp;• ION582 granted Breakthrough Therapy designation from FDA for the treatment of Angelman syndrome

<br> o Phase 3 REVEAL study expected to be fully enrolled in 2026

<br> o Phase 2 HALOS study showed continued improvement across multiple functional measures versus natural history through 18 months including expressive communication

#### Recent Highlights – Partnered Medicines
&nbsp;&nbsp;&nbsp;&nbsp;• WAINUA<sup>®</sup> (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of
 hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $59 million and $143 million resulting in royalty revenue of $13 million and $33 million in the third quarter and the nine months ended September 30, 2025,
 respectively

<br> o Launches underway in numerous regions, including the EU; additional submissions in progress to expand WAINUA access globally

&nbsp;&nbsp;&nbsp;&nbsp;• SPINRAZA<sup>®</sup> (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $374 million and $1.2 billion
 resulting in royalty revenue of $56 million and $158 million in the third quarter and the nine months ended September 30, 2025, respectively

------

#### Revenue
Ionis' revenue was comprised of the following:

---

| | | | | |
|:---|:---|:---|:---|:---|
|  | Three months ended | Three months ended | Nine months ended | Nine months ended |
|  | September 30, | September 30, | September 30, | September 30, |
|  | 2025 | 2024 | 2025 | 2024 |
|  Revenue: | (amounts in millions) | (amounts in millions) | (amounts in millions) | (amounts in millions) |
| &nbsp;&nbsp;&nbsp; Commercial revenue: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Product sales, net: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; TRYNGOLZA sales, net | $32 | $- | $57 | $- |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total product sales, net | 32 | - | 57 | - |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Royalty revenue: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; SPINRAZA royalties | 56 | 57 | 158 | 152 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; WAINUA royalties | 13 | 5 | 33 | 10 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Other royalties | 7 | 5 | 19 | 17 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total royalty revenue | 76 | 67 | 210 | 179 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Other commercial revenue | 8 | 9 | 27 | 28 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; **Total commercial revenue** | **116** | **76** | **294** | **207** |
| &nbsp;&nbsp;&nbsp; Research and development revenue: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Collaborative agreement revenue | 31 | 45 | 414 | 237 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; WAINUA joint development revenue | 10 | 13 | 32 | 35 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; **Total research and development revenue** | **41** | **58** | **446** | **272** |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; **Total revenue** | $**157** | $**134** | $**740** | $**479** |

---

Commercial revenue for the third quarter and the nine months ended September 30, 2025, increased 53% and 42%, respectively, compared to the same periods in 2024. This increase was primarily driven by TRYNGOLZA product sales. Higher royalty revenue also contributed to the year over year increase.

The remainder of the Company's revenue came from programs under its R&D collaborations, including a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025, reflecting the value that Ionis' pipeline and technology continues to generate.

#### Operating Expenses
SG&A expenses increased as anticipated for the third quarter and the nine months ended September 30, 2025, compared to the same periods in 2024, primarily due to the launches of TRYNGOLZA, DAWNZERA and WAINUA. This increase was partially offset by a decrease in R&D expenses as several late-stage studies ended. Overall, this led to a modest year-over-year increase in total operating expenses, which was in line with expectations.

#### Balance Sheet
As of September 30, 2025, Ionis' cash, cash equivalents and short-term investments were $2.2 billion, compared to $2.3 billion on December 31, 2024. Ionis' working capital decreased over the same period primarily due to the reclassification of the Company's 0% convertible notes as a current liability.

------

#### Webcast and Other Updates

Management will host a conference call and webcast to discuss Ionis' third quarter 2025 results at 11:30 a.m. Eastern time on Wednesday, October 29, 2025. Interested parties may access the webcast <u>here</u>. A webcast replay will be available for a limited time at the same address. To access the Company's third quarter 2025 earnings slides click <u>here</u>.

#### Ionis' Marketed Medicines

#### INDICATION for TRYNGOLZA<sup>®</sup><sup></sup>(olezarsen)
TRYNGOLZA<sup>®</sup> (olezarsen) was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS).

#### IMPORTANT SAFETY INFORMATION

#### CONTRAINDICATIONS
TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring medical treatment have occurred.

#### WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions

Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills and myalgias) have been reported in patients treated with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur.

#### ADVERSE REACTIONS
The most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count and arthralgia.

Please see full <u>Prescribing Information</u> for TRYNGOLZA.

#### INDICATION for DAWNZERA<sup>TM</sup> (donidalorsen)

DAWNZERA™ (donidalorsen) was approved by the U.S. Food and Drug Administration for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.

#### IMPORTANT SAFETY INFORMATION

#### CONTRAINDICATIONS

DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA.

#### WARNINGS AND PRECAUTIONS

#### Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with DAWNZERA. If signs and symptoms of serious hypersensitivity reactions occur, discontinue DAWNZERA and institute appropriate therapy.

------

#### ADVERSE REACTIONS
Most common adverse reactions (incidence ≥ 5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort.

Please see full <u>Prescribing Information</u> for DAWNZERA.

#### INDICATION for WAINUA<sup>®</sup> (eplontersen)
WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

**IMPORTANT SAFETY INFORMATION for WAINUA**<sup>®</sup> **(eplontersen)**

#### WARNINGS AND PRECAUTIONS
**Reduced Serum Vitamin A Levels and Recommended Supplementation** WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur.

#### ADVERSE REACTIONS
Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%).

Please see link to <u>U.S. Full Prescribing Information</u> for WAINUA.

For more information about SPINRAZA and QALSODY, visit <u>https://www.spinraza.com/</u> and <u>https://www.qalsody.com/</u>, respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s).

#### About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit <u>Ionis.com</u> and follow us on <u>X (Twitter)</u>, <u>LinkedIn</u> and <u>Instagram</u>.

#### Ionis' Forward-looking Statement
This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development, technologies and our expectations regarding development and regulatory milestones. 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 including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. 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. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. 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' annual report on Form 10-K for the year ended December 31, 2024, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.

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In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries.

IONIS<sup>®</sup> is a registered trademark of Ionis Pharmaceuticals, Inc. TRYNGOLZA<sup>®</sup> is a registered trademark of Ionis Pharmaceuticals, Inc. DAWNZERA<sup>TM</sup> is a trademark of Ionis Pharmaceuticals, Inc. AKCEA<sup>TM</sup> is a trademark of Akcea Therapeutics, Inc. TEGSEDI<sup>TM</sup> is a trademark of Akcea Therapeutics, Inc. WAYLIVRA<sup>TM</sup> is a trademark of Akcea Therapeutics, Inc. SPINRAZA<sup>®</sup> and QALSODY<sup>®</sup> are registered trademarks of Biogen. WAINUA<sup>®</sup> is a registered trademark of the AstraZeneca group of companies.

#### Ionis Investor Contact:
D. Wade Walke, Ph.D.

<u>IR@ionis.com</u>

760-603-2331

#### Ionis Media Contact:
Hayley Soffer

<u>media@ionis.com</u>

760-603-4679

------

#### IONIS PHARMACEUTICALS, INC.

#### SELECTED FINANCIAL INFORMATION

#### Condensed Consolidated Statements of Operations

#### (In Millions, Except Per Share Data)

#### <br>

---

| | | | | |
|:---|:---|:---|:---|:---|
|  | Three months ended | Three months ended | Nine months ended | Nine months ended |
|  | September 30, | September 30, | September 30, | September 30, |
|  | 2025 | 2024 | 2025 | 2024 |
|  | (unaudited) | (unaudited) | (unaudited) | (unaudited) |
| Revenue: |  |  |  |  |
| &nbsp;&nbsp;&nbsp; Commercial revenue: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Product sales, net | $32 | $- | $57 | $- |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Royalty revenue | 76 | 67 | 210 | 179 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Other commercial revenue | 8 | 9 | 27 | 28 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total commercial revenue | 116 | 76 | 294 | 207 |
| &nbsp;&nbsp;&nbsp; Research and development revenue: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Collaborative agreement revenue | 31 | 45 | 414 | 237 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; WAINUA joint development revenue | 10 | 13 | 32 | 35 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total research and development revenue | 41 | 58 | 446 | 272 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total revenue | 157 | 134 | 740 | 479 |
| &nbsp;&nbsp;&nbsp; Expenses: |  |  |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Cost of sales | 2 | 1 | 8 | 7 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Research, development and patent | 218 | 220 | 636 | 656 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Selling, general and administrative | 97 | 61 | 263 | 180 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total operating expenses | 317 | 282 | 907 | 843 |
| Loss from operations | (160) | (148) | (167) | (364) |
| Other income (expense): |  |  |  |  |
| &nbsp;&nbsp;&nbsp; Interest expense related to the sale of future royalties | (18) | (19) | (55) | (55) |
| &nbsp;&nbsp;&nbsp; Other income, net | 49 | 23 | 70 | 66 |
| Loss before income tax benefit | (129) | (144) | (152) | (353) |
| Income tax benefit | - | 4 | - | 3 |
| Net loss | $(129) | $(140) | $(152) | $(350) |
| Basic and diluted net loss per share | $(0.80) | $(0.95) | $(0.95) | $(2.38) |
| Shares used in computing basic and diluted net loss per share | 160 | 149 | 159 | 147 |

---

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#### IONIS PHARMACEUTICALS, INC.

#### Reconciliation of GAAP to Non-GAAP Basis:

#### Condensed Consolidated Operating Expenses, Loss From Operations, and Net Loss (In Millions) <br>

---

| | | | | |
|:---|:---|:---|:---|:---|
|  | Three months ended<br> September 30, | Three months ended<br> September 30, | Nine months ended<br> September 30, | Nine months ended<br> September 30, |
|  | 2025 | 2024 | 2025 | 2024 |
|  | (unaudited) | (unaudited) | (unaudited) | (unaudited) |
|  **As reported research, development and patent expenses according to GAAP** | $218 | $220 | $636 | $656 |
| &nbsp;&nbsp;&nbsp; Excluding compensation expense related to equity awards | (21) | (22) | (61) | (67) |
|  **Non-GAAP research, development and patent expenses** | $197 | $198 | $575 | $589 |
|  **As reported selling, general and administrative expenses according to GAAP** | $97 | $61 | $263 | $180 |
| &nbsp;&nbsp;&nbsp; Excluding compensation expense related to equity awards | (10) | (10) | (29) | (26) |
|  **Non-GAAP selling, general and administrative expenses** | $87 | $51 | $234 | $154 |
|  **As reported operating expenses according to GAAP** | $317 | $282 | $907 | $843 |
| &nbsp;&nbsp;&nbsp; Excluding compensation expense related to equity awards | (31) | (32) | (91) | (94) |
|  **Non-GAAP operating expenses** | $286 | $250 | $816 | $749 |
|  **As reported loss from operations according to GAAP** | $(160) | $(148) | $(167) | $(364) |
| &nbsp;&nbsp;&nbsp; Excluding compensation expense related to equity awards | (31) | (32) | (91) | (94) |
|  **Non-GAAP loss from operations** | $(129) | $(116) | $(76) | $(270) |
|  **As reported net loss according to GAAP** | $(129) | $(140) | $(152) | $(350) |
| &nbsp;&nbsp;&nbsp; Excluding compensation expense related to equity awards and related tax effects | (31) | (32) | (91) | (94) |
| **Non-GAAP net loss** | $(98) | $(108) | $(61) | $(256) |

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#### Reconciliation of GAAP to Non-GAAP Basis
As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations.

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#### IONIS PHARMACEUTICALS, INC.

#### Condensed Consolidated Balance Sheets

#### (In Millions)

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| | | |
|:---|:---|:---|
|  | September 30,<br>2025 | December 31,<br>2024 |
|  | (unaudited) | |
|  Assets: |  |  |
| &nbsp;&nbsp;&nbsp; Cash, cash equivalents and short-term investments | $2240 | $2298 |
| &nbsp;&nbsp;&nbsp; Contracts receivable | 25 | 92 |
| &nbsp;&nbsp;&nbsp; Other current assets | 254 | 230 |
| &nbsp;&nbsp;&nbsp; Property, plant and equipment, net | 106 | 94 |
| &nbsp;&nbsp;&nbsp; Right-of-use assets | 242 | 162 |
| &nbsp;&nbsp;&nbsp; Other assets | 166 | 127 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total assets | $3033 | $3003 |
|  Liabilities and stockholders' equity: |  |  |
| &nbsp;&nbsp;&nbsp; Current portion of deferred contract revenue | $77 | $79 |
| &nbsp;&nbsp;&nbsp; 0% convertible senior notes, net – current | 631 | - |
| &nbsp;&nbsp;&nbsp; Other current liabilities | 195 | 229 |
| &nbsp;&nbsp;&nbsp; 1.75% convertible senior notes, net | 567 | 565 |
| &nbsp;&nbsp;&nbsp; 0% convertible senior notes, net | - | 629 |
| &nbsp;&nbsp;&nbsp; Liability related to sale of future royalties, net | 545 | 542 |
| &nbsp;&nbsp;&nbsp; Long-term lease liabilities | 263 | 162 |
| &nbsp;&nbsp;&nbsp; Long-term obligations, less current portion | 29 | 52 |
| &nbsp;&nbsp;&nbsp; Long-term deferred contract revenue | 108 | 157 |
| &nbsp;&nbsp;&nbsp; Total stockholders' equity | 618 | 588 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Total liabilities and stockholders' equity | $3033 | $3003 |

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**Key 2025 and 2026 Value Driving Events**<sup>(1)</sup>

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| | | | |
|:---|:---|:---|:---|
| **New Product Launches** | **New Product Launches** | **New Product Launches** | **New Product Launches** |
| **Program** | **Indication** | **2025** | **2026** |
| DAWNZERA (U.S.) | HAE | Achieved |  |
| TRYNGOLZA (U.S.) | FCS | Achieved |  |
| WAINZUA (EU) | ATTRv-PN | Achieved |  |
| Olezarsen (U.S.) | sHTG |  | •  |
| Zilganersen (U.S.) | Alexander disease |  | •  |

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| | | | | |
|:---|:---|:---|:---|:---|
| **Regulatory Actions** | **Regulatory Actions** | **Regulatory Actions** | **Regulatory Actions** | **Regulatory Actions** |
| **Program** | **Indication** | **Regulatory Action** | **2025** | **2026** |
| Donidalorsen | HAE | U.S. approval decision | Achieved |  |
| Donidalorsen | HAE | EU approval decision |  | •  |
| TRYNGOLZA | FCS | EU approval decision | Achieved |  |
| Olezarsen | sHTG | U.S. submission | •  |  |
| Olezarsen | sHTG | U.S. approval decision |  | •  |
| Zilganersen | Alexander disease | U.S. submission |  | •  |
| Zilganersen | Alexander disease | U.S. approval decision |  | •  |
| Nusinersen<br> (higher dose) | SMA | U.S. and EU submissions | Achieved |  |
| Nusinersen<br> (higher dose) | SMA | U.S. approval decision | Refiling process<br> on track | Refiling process<br> on track |
| WAINZUA | ATTRv-PN | EU approval decision | Achieved |  |
| Pelacarsen | Lp(a)- CVD | U.S. submission |  | •  |
| Bepirovirsen | HBV | Regulatory submission(s) |  | •  |
| Bepirovirsen | HBV | Regulatory decision(s) |  | •  |

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| | | | | |
|:---|:---|:---|:---|:---|
| **Key Phase 3 Clinical Events** | **Key Phase 3 Clinical Events** | **Key Phase 3 Clinical Events** | **Key Phase 3 Clinical Events** | **Key Phase 3 Clinical Events** |
| **Program** | **Indication** | **Event** | **2025** | **2026** |
| Olezarsen | sHTG | CORE, CORE2 data | Achieved |  |
| Olezarsen | sHTG | Essence data | Achieved |  |
| Zilganersen | Alexander disease | Phase 3 data | Achieved |  |
| ION582 | Angelman syndrome | Phase 3 study start | Achieved |  |
| ION582 | Angelman syndrome | Phase 3 enrollment completion |  | •  |
| Pelacarsen | Lp(a)-CVD | Lp(a) HORIZON data |  | •  |
| Bepirovirsen | HBV | B-Well data |  | •  |
| Eplontersen | ATTR-CM | CARDIO-TTRansform data |  | •  |
| Sefaxersen | IgAN | IMAGINATION data |  | •  |
| Ulefnersen | FUS-ALS | FUSION data |  | •  |

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(1) Timing expectations based on current assumptions and subject to change.

<br> • Indicates that the milestone is anticipated in the respective year.

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