Release Details

CARLSBAD, Calif.--(BUSINESS WIRE)--Aug. 20, 2026-- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced that new data in the management of severe hypertriglyceridemia (sHTG) will be presented at the European Society of Cardiology (ESC) Congress 2026, taking place August 28 – 31 in Munich. Presentations include one-year data from the open-label, long-term extension study of TRYNGOLZA® (olezarsen), recently approved in the U.S. as the first and only treatment for sHTG to reduce triglycerides and the risk of acute pancreatitis, and Phase 1 data in hypertriglyceridemia for ION775, an investigational siRNA and next-generation follow-on to TRYNGOLZA with the potential for semiannual or less frequent dosing.

“People living with sHTG face the risk of potentially life-threatening acute pancreatitis attacks, which can cause prolonged and recurrent hospitalizations and organ failure, underscoring the urgency to lower triglycerides below the guideline-recommended levels,” said Sam Tsimikas, M.D., senior vice president, global cardiovascular development, Ionis. “The recent approval of TRYNGOLZA, the first and only approved treatment for sHTG to reduce triglycerides and the risk of acute pancreatitis, highlights Ionis’ leadership in sHTG and marks a new era in the management of this serious disease. The data being presented at the ESC Congress further reinforce our leadership and commitment in the field as we advance science and innovative medicines with the potential to transform the lives of people living with sHTG.”

TRYNGOLZA was approved by the U.S. Food and Drug Administration for sHTG in June 2026. An indication extension application for TRYNGOLZA in sHTG is under review by the European Medicines Agency, with Sobi holding commercialization rights in the EU. ION775 is in development for sHTG and is currently being investigated in a Phase 2 study.

Key Presentation Details:

• Long-term efficacy and safety of olezarsen in patients with severe hypertriglyceridemia
  • Oral Presentation: Friday, August 28, 8:33 – 8:57 a.m. CEST
  • Presenting Author: Robert Giugliano, M.D.

• ION775, a long-acting siRNA targeting APOC3: single-dose, 12-month results in participants with moderate hypertriglyceridemia
  • Oral Presentation: Friday, August 28, 11:35 – 11:45 a.m. CEST
  • Presenting Author: Sotirios (Sam) Tsimikas, M.D.

Additionally, Ionis and partner AstraZeneca will present data from the CARDIO-TTRansform Phase 3 trial of eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). Presentations include a detailed analysis of the Phase 3 data and a subgroup analysis of eplontersen in patients receiving stabilizer treatment. A meta-analysis of eplontersen and another silencer therapy in combination with stabilizers in ATTR-CM will also be presented by an independent academic group.

Presentations will be available on the Ionis website once each embargo lifts.

INDICATIONS

Familial Chylomicronemia Syndrome (FCS)
TRYNGOLZA (olezarsen) is indicated as an adjunct to diet to reduce triglycerides (TG) in adults with familial chylomicronemia syndrome (FCS).

Severe Hypertriglyceridemia (sHTG)
TRYNGOLZA is indicated as an adjunct to diet to reduce TG and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG ≥500 mg/dL).

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.

Liver Enzyme Abnormalities
TRYNGOLZA can cause increases in liver enzymes and hepatic fat in adults. Increases in liver enzymes were more frequently reported with the 80 mg dose as compared with the 50 mg dose. Consider liver enzyme testing before TRYNGOLZA initiation or an increase in dosage and when clinically indicated thereafter. If persistent elevations in liver enzymes occur, consider dose interruption and/or dose reduction. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue TRYNGOLZA.

ADVERSE REACTIONS
Adverse Reactions for FCS
Most common adverse reactions in patients with FCS (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count, and arthralgia.

Adverse Reactions for sHTG
Most common adverse reactions in patients with sHTG (incidence ≥2% higher than placebo) were injection site reactions and liver enzyme increases.

Please see full Prescribing Information for TRYNGOLZA. Please see Important Safety Information throughout and full Prescribing Information for TRYNGOLZA.

About the CORE and CORE2 Studies
CORE (NCT05079919; n=617) and CORE2 (NCT05552326; n=446), conducted with The TIMI Study Group, are Phase 3 global, multicenter, randomized, double-blind, placebo-controlled trials investigating the safety and efficacy of olezarsen for severe hypertriglyceridemia (sHTG). Participants aged 18 and older with triglyceride levels ≥500 mg/dL were enrolled. Participants were required to be on standard of care therapies for elevated triglycerides. At baseline, 47% and 37% of participants had fasting triglycerides ≥880 mg/dL in CORE and CORE2, respectively. Participants were randomized to receive 50 mg or 80 mg of olezarsen or placebo every four weeks via subcutaneous injection for 12 months.

About Severe Hypertriglyceridemia
Severe hypertriglyceridemia (sHTG) is defined by very high triglycerides (≥500 mg/dL) and characterized by an increased risk of acute pancreatitis and other serious health complications. Considered a medical emergency, acute pancreatitis causes debilitating abdominal pain that often requires prolonged hospitalization, can lead to permanent organ damage and can become life-threatening. Preventing the first attack is key. In people with a history of acute pancreatitis episodes, the risk of future attacks is even greater. Current standard of care therapies for sHTG and lifestyle modifications (such as diet and exercise) do not sufficiently or consistently lower triglyceride levels or reduce the risks of sHTG in all patients. More than 3 million people are living with sHTG in the U.S., including approximately 1 million who are considered high risk. High-risk sHTG includes those with triglycerides ≥880 mg/dL or triglycerides ≥500 mg/dL and a history of acute pancreatitis or other comorbidities.

About TRYNGOLZA® (olezarsen)
TRYNGOLZA® (olezarsen) is an RNA-targeted therapy designed to lower the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. TRYNGOLZA is approved in the United States as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL). TRYNGOLZA is also approved in the United States, European Union and other countries for adults with familial chylomicronemia syndrome (FCS), a rare form of sHTG. Visit TRYNGOLZA.com for more information.

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 Ionis.com and follow us on X (Twitter), LinkedIn and Instagram.

Ionis Forward-looking Statements
This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of TRYNGOLZA, ION775, Ionis' technologies and other products in development. 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, 2025, 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. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals^® and TRYNGOLZA^® are trademarks of Ionis Pharmaceuticals, Inc.

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Ionis Investor Contact:
D. Wade Walke, Ph.D.
IR@ionis.com 760-603-2331

Ionis Media Contact:
Hayley Soffer
media@ionis.com 760-603-4679

Source: Ionis Pharmaceuticals, Inc.