Ionis Pharmaceuticals Q2 Earnings Call Highlights

Key Points

• Second-quarter revenue rose to $268 million, with commercial revenue reaching $119 million, driven mainly by DAWNZERA and early TRYNGOLZA sales. Ionis reaffirmed its 2026 revenue outlook of $875 million to $900 million and ended the quarter with $2.1 billion in cash and investments.
• TRYNGOLZA’s U.S. launch expanded into severe hypertriglyceridemia after FDA approval, generating $5 million in second-quarter sales. Ionis expects payer coverage to broaden through 2026 and 2027 and continues to project more than $3 billion in potential peak annual revenue.
• Eplontersen failed to meet the primary endpoint in the overall phase III ATTR cardiomyopathy study, though Ionis reported TTR reductions and nominally significant results in the monotherapy subgroup. The company is awaiting detailed results while advancing catalysts including zilganersen, pelacarsen, ulefnersen and bepirovirsen.

Ionis Pharmaceuticals NASDAQ: IONS reported second-quarter revenue growth driven by commercial products and partnered research programs, while highlighting the recent U.S. approval and early launch progress for TRYNGOLZA in severe hypertriglyceridemia.

Chief Executive Officer Brett Monia said the company entered the second half of 2026 with commercial momentum, a growing wholly owned pipeline and a goal of reaching cash-flow breakeven in 2028. He also acknowledged that the phase III CARDIO-TTRansform study of eplontersen in ATTR cardiomyopathy did not meet its primary efficacy endpoint in the overall population.

Second-Quarter Results and 2026 Outlook

Chief Financial Officer Beth Hougen said second-quarter revenue was $268 million, while first-half revenue totaled $514 million. Excluding a $280 million one-time payment from Ono in the first half of 2025, revenue rose 56% in the second quarter and 69% in the first half from the comparable periods a year earlier.

Commercial revenue reached $119 million in the second quarter and $226 million for the first six months of 2026, increases of 15% and 27%, respectively. Hougen said the gains were primarily driven by DAWNZERA sales.

• TRYNGOLZA generated $5 million in second-quarter product sales and $32 million in first-half sales.
• DAWNZERA generated $26 million in second-quarter sales and $42 million in first-half sales. Second-quarter DAWNZERA sales increased 63% from the first quarter.
• Research and development revenue was $149 million in the second quarter and $288 million year to date.
• Ionis ended the quarter with $2.1 billion in cash equivalents and short-term investments.

The company reaffirmed its 2026 revenue outlook of $875 million to $900 million. It continues to expect TRYNGOLZA sales of $100 million to $110 million and DAWNZERA sales of $110 million to $120 million for the year. Ionis expects operating expenses to rise in the low-teens percentage range, with a projected non-GAAP operating loss of $425 million to $475 million and year-end cash above $1.6 billion.

TRYNGOLZA Launch Expands Into Severe Hypertriglyceridemia

Ionis said TRYNGOLZA was approved last month as the first and only FDA-approved medicine to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia, or sHTG. The company said it received prescriptions on the day of approval and placed both the 50-milligram and 80-milligram doses in distribution channels within about one week.

Kyle Jenne, chief global product strategy officer, said the launch has begun with prescriptions from cardiologists, endocrinologists, lipidologists and primary-care physicians. Ionis estimates that about 3 million people in the U.S. have sHTG, including roughly 1 million high-risk patients.

Jenne said early payer coverage has been consistent with the product label for patients with triglycerides above 500 milligrams per deciliter, though most early access is occurring through medical exceptions while insurers establish formal coverage criteria. The company expects coverage to broaden through the rest of 2026 and into 2027.

Ionis said physicians are generally using TRYNGOLZA alongside existing standard therapies, such as fibrates, omega-3 medicines or statins. The company expects the therapy to return to revenue growth in the second half as the broader sHTG launch gains momentum and reiterated its expectation for more than $3 billion in peak annual revenue.

Separately, management said demand in familial chylomicronemia syndrome remained strong, with the highest number of patient starts since that launch began. Jenne said competition had not had a meaningful impact on TRYNGOLZA demand in that indication.

DAWNZERA Growth and Neurology Launch Preparations

Ionis said DAWNZERA, its hereditary angioedema prophylaxis medicine, continued to gain adoption in the U.S. market, which management described as primarily a switch market. Jenne said uptake has included patients switching from established preventative therapies, those previously receiving only on-demand treatment and treatment-naive patients.

The company is also preparing for a potential launch of zilganersen for Alexander disease. The FDA granted priority review, with a PDUFA target action date of Sept. 22. Ionis said approximately half of the estimated 300 U.S. patients with Alexander disease have already been identified through ICD-10 codes and patient registries. The company has established an expanded-access program and is preparing patient-support services and outreach to specialized leukodystrophy centers.

Recordati plans to seek approval for zilganersen in the European Union and Japan next year, Ionis said.

Pipeline Catalysts and Eplontersen Setback

Monia said Ionis and AstraZeneca are continuing to analyze the CARDIO-TTRansform study after eplontersen did not meet its primary endpoint in the overall ATTR cardiomyopathy population. He said the medicine produced substantial and durable reductions in transthyretin, or TTR, and nominally significant results in the monotherapy subgroup, but showed no benefit in the combination subgroup. Detailed results are scheduled for presentation at the European Society of Cardiology meeting in August.

Ionis also plans to present long-term TRYNGOLZA data from the CORE and CORE2 open-label extension studies at ESC. Chief Development Officer Holly Kordasiewicz said the presentations will include triglycerides, safety and biomarkers including APOC3, remnant cholesterol and non-HDL cholesterol.

Other anticipated milestones include phase III data for Novartis-partnered pelacarsen in Lp(a)-driven cardiovascular disease, readouts for ulefnersen in FUS-ALS and IONIS-FB-LRx in IgA nephropathy, and an Oct. 26 FDA action date for GSK-partnered bepirovirsen in chronic hepatitis B.

Ionis also completed enrollment in the phase III REVEAL trial of obudanersen for Angelman syndrome, with data expected in the second half of 2027, and initiated a phase I/II study of ION337 in Dravet syndrome. The company advanced ION775 into a phase IIb trial in severe or moderately elevated triglycerides and said it sees potential for semiannual or less frequent dosing.

Finally, Monia recognized Chief Scientific Officer Frank Bennett, whose planned retirement was announced the morning of the call. Monia credited Bennett, one of Ionis' founding scientists, with contributions to the company’s RNA-targeted medicines platform and neurology pipeline.

About Ionis Pharmaceuticals (NASDAQ:IONS)

Ionis Pharmaceuticals, Inc is a biotechnology company focused on the discovery and development of RNA-targeted therapies designed to modulate gene expression. The company's proprietary antisense oligonucleotide (ASO) technology enables the selective binding of short synthetic strands of nucleic acids to messenger RNA (mRNA), thereby inhibiting or altering the production of disease-causing proteins. Ionis' pipeline spans a range of therapeutic areas, including neurological disorders, cardiovascular conditions, metabolic diseases and rare genetic disorders.

Since its founding in 1989 by Dr.

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