IONS

• GAAP operating loss was $102 million in Q2 2026, versus income of $140 million in Q2 2025; non-GAAP operating loss was $57 million, versus income of $170 million.
• TRYNGOLZA generated $5 million in Q2 2026 U.S. net product sales, with full-year 2026 sales expected to be $100-110 million; DAWNZERA generated $26 million in Q2 2026, with full-year guidance of $110-120 million.
• Cash and short-term investments were $2.1 billion as of June 30, 2026, down from $2.7 billion at year-end 2025, primarily due to repayment of 0% convertible notes.
• Company remains on track to achieve 2026 financial guidance and cash flow breakeven in 2028.

2.02 Results of Operations and Financial Condition · 9.01 Financial Statements and Exhibits

• The company reaffirmed its previously announced financial guidance for fiscal year 2026, which remains unchanged from the guidance provided on April 29, 2026 in its Q1 2026 earnings release.
• The disclosure was made under Regulation FD and is not deemed filed for SEC Section 18 purposes.
• The report includes forward-looking statements regarding 2026 financial guidance and performance, subject to risks and uncertainties.
• The filing was signed by Patrick R. O'Neil, Executive Vice President, Chief Legal Officer and General Counsel.

7.01 Regulation FD Disclosure · 9.01 Financial Statements and Exhibits

• Prespecified subgroup analysis showed nominally significant hazard ratio of 0.71 for eplontersen monotherapy vs placebo; no treatment effect in patients on stabilizer at baseline.
• Secondary, imaging, and biomarker analyses favored eplontersen; large sustained TTR reductions and favorable safety profile observed.
• Trial enrolled 1,432 participants across 130 sites in 20 countries; 57% in each arm received stabilizer at baseline, 24% initiated stabilizer during trial.
• Ionis and AstraZeneca will present full results at ESC Congress in August 2026.

7.01 Regulation FD Disclosure · 8.01 Other Events · 9.01 Financial Statements and Exhibits

• TRYNGOLZA is available in 50 mg or 80 mg doses, self-administered once monthly via an autoinjector, and will be available in the U.S. in July.
• Approval was based on Phase 3 CORE and CORE2 studies, which showed up to 72% reduction in fasting triglycerides at six months and up to 91% reduction in acute pancreatitis events.
• This is Ionis' first independent commercial launch in a prevalent condition; the company will host a webcast on June 24, 2026 at 3:30 p.m. ET.
• The most common adverse reactions were injection site reactions and liver enzyme increases.

7.01 Regulation FD Disclosure · 8.01 Other Events · 9.01 Financial Statements and Exhibits

• The presentation included longer-term MRI-PDFF results from 53 patients who completed 12 months of treatment, about 25% of the MRI-PDFF substudy enrollees.
• Mean hepatic fat fraction levels returned toward baseline after 24 months of treatment with the 80 mg dose of olezarsen.
• Mean changes in hepatic fat fraction were less pronounced in patients who transitioned from the 50 mg dose in the randomized portion to the 80 mg dose in CORE-OLE.
• Olezarsen continued to show a favorable safety profile, and more than 90% of eligible patients from CORE and CORE2 transitioned into and remained in CORE-OLE.

8.01 Other Events · 9.01 Financial Statements and Exhibits

• Ludwig N. Hantson was appointed to the Ionis Pharmaceuticals Board of Directors effective June 4, 2026, immediately following the 2026 Annual Meeting of Stockholders.
• He will receive standard non-employee director compensation under the company's Fourth Amended Non-Employee Director Compensation Policy and will enter into the standard indemnity agreement.
• At the June 4, 2026 Annual Meeting, stockholders elected Spencer R. Berthelsen and Joan E. Herman as directors and approved all five proposals, including an equity plan share increase and auditor ratification.
• The company also previously announced the appointment of Peter N. Reikes to the board effective June 4, 2026.

5.02 Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements · 5.07 Submission of Matters to a Vote of Security Holders · 7.01 Regulation FD Disclosure · 9.01 Financial Statements and Exhibits

• GSK reported positive pivotal Phase 3 data for bepirovirsen, an investigational antisense oligonucleotide for chronic hepatitis B, from the B-Well 1 and B-Well 2 trials.
• In an exploratory analysis, 49% of bepirovirsen recipients achieved a qHBsAg of ≤100 IU/mL one year after end of treatment.
• Bepirovirsen is under priority review by the FDA with Breakthrough and Fast Track Designation, and under review in Europe, Japan, and China; GSK anticipates first regulatory decisions in Q3 2026.
• GSK licensed bepirovirsen from Ionis in 2019; Ionis is eligible for milestone payments and tiered royalties of 10-12% on net sales.

7.01 Regulation FD Disclosure · 8.01 Other Events · 9.01 Financial Statements and Exhibits

• Operating loss narrowed to $118 million on a GAAP basis and $75 million on a non-GAAP basis.
• TRYNGOLZA net product sales were $27 million; DAWNZERA net product sales were $16 million.
• Company raised full-year 2026 total revenue guidance to $875-900 million and reduced non-GAAP operating loss guidance to $425-475 million.
• Olezarsen sNDA accepted for Priority Review with PDUFA date of June 30, 2026; zilganersen NDA accepted for Priority Review with PDUFA date of September 22, 2026.

2.02 Results of Operations and Financial Condition · 9.01 Financial Statements and Exhibits