Ionis Pharmaceuticals

Ionis posted revenue of $268 million in the second quarter, up 56% year over year, excluding last year's one-time sapablursen upfront payment. Ionis maintained its 2026 guidance of roughly $890 million of revenue at the midpoint, including Tryngolza (olezarsen) net product sales of $105 million.

Why it matters: Ionis continues to demonstrate progress in its transformation from a partnership-driven biotechnology company to a scaled commercial organization supported by four independent product launches underway. The commercial launch for Tryngolza is still very early since its expanded US approval in late June for severe hypertriglyceridemia, but early launch metrics look strong, including encouraging reimbursement progress and broad prescription uptake across primary care and specialty physicians. Despite its recent phase 3 ATTR-CM setback with AstraZeneca, we remain positive on Ionis' risk/reward profile given its expanding commercial portfolio, healthy balance sheet with $2.1 billion in cash and short-term investments, and multiple late-stage catalysts that could support meaningful value creation over the next several years.

The bottom line: We maintain our fair value estimate of $84 per share for narrow-moat Ionis. Shares are currently trading 39% below our valuation. We continue to see Ionis' recent pullback following the phase 3 ATTR-CM trial miss as creating an attractive entry point. We maintain a positive outlook and project roughly 30% annualized revenue growth over the next five years, supported by the commercial success of Tryngolza and additional launches. We forecast total olezarsen sales will exceed $3.5 billion by 2035 and comprise 44% of total revenue.

Coming up: Near-term catalysts include FDA decisions on zilganersen in September and bepirovirsen in October, which we assign 90% probabilities of approval, as well as phase 3 pelacarsen data in the second half of 2026 that could demonstrate lowering Lp(a) may reduce cardiovascular events.

We maintain our fair value estimate of $84 per share for narrow-moat Ionis.

We reduced the probability of approval for eplontersen in ATTR-CM to 10% from 70%, given its phase 3 study missed its primary endpoint. We forecast a small chance of success based on favorable secondary data and the pending release of the full dataset in August 2026.

Wainua is approved in the US and EU for hATTR-PN, but success in ATTR-CM would have been key to expanding its market potential amid competitive pressure from Alnylam's Amvuttra and BridgeBio's Attruby.

Ionis relies on upfront payments and licensing fees from partners, as well as Spinraza royalties, to drive revenue today, but its rapidly advancing portfolio should help diversify revenue. 2025 marked a pivotal year for Ionis, as it executed its first two independent launches, driving strong revenue growth alongside key clinical milestones. Ongoing investment in commercial rollouts and pipeline candidates will maintain operating losses over the next few years, but the successful launch of wholly owned products signals solid commercial execution capabilities and supports long-term value creation.

In December 2024, Ionis received US approval for Tryngolza as the first treatment approved for adults with familial chylomicronemia syndrome, a rare genetic disorder that leads to dangerously high triglyceride levels. Tryngolza’s annual list price was $595,000 for this very rare condition affecting about 3,000 patients in the US.

In September 2025, Ionis reported top-line data from the phase 3 study of olezarsen in severe hypertriglyceridemia. Compared with a placebo, olezarsen lowered triglycerides by up to 72%, and it led to an impressive 85% reduction in acute pancreatitis events. In June 2026, the FDA approved Tryngolza in sHTG, which expands its label to an estimated 3 million patients.

Ionis proactively positioned Tryngolza for the broader sHTG opportunity by reducing the annual list price to $40,000 from $595,000, which should improve patient access and support volume growth. We forecast combined olezarsen sales will exceed $3.5 billion by 2035 and comprise 44% of total revenue.

Ionis received US approval in 2025 for Dawnzera, marking the first and only RNA-targeted prophylactic treatment for hereditary angioedema. HAE is a rare genetic condition that causes sudden and potentially life-threatening swelling in various parts of the body. There are about 20,000 people with this condition in the US and EU. Management has guided to annual peak sales potential for Dawnzera in excess of $500 million, but we think with the January 2026 approval in the EU, this drug could achieve total sales of $775 million by the end of our 10-year forecast.

For Biogen-partnered Spinraza (nusinersen) in spinal muscular atrophy, we expect competition to continue to erode market share. Ionis can earn up to midteens royalties for the drug. As for its partnership with AstraZeneca, we forecast Wainua royalties from Astra will reach roughly $330 million by 2035.

We remain positive on Ionis' risk/reward profile given its expanding commercial portfolio, healthy balance sheet with $2.1 billion in cash and short-term investments, and multiple late-stage catalysts that could support meaningful value creation over the next several years.

Near-term catalysts include FDA decisions on zilganersen in September and bepirovirsen in October, which we assign 90% probabilities of approval, as well as phase 3 pelacarsen data in the second half of 2026 that could demonstrate lowering Lp(a) may reduce cardiovascular events. We maintain our positive long-term outlook and project a five-year compound annual revenue growth rate of roughly 30%.

We assign the firm an 8.6% weighted average cost of capital, heavily driven by our assumption of a 9.1% cost of equity. This cost of equity is consistent with other emerging biotech companies in our coverage and what we view as the systematic risk associated with its shares.

Ionis has proprietary antisense oligonucleotide technology that has led to several approved RNA-based drugs and a steadily growing pipeline, which together support the firm's intangible assets and Morningstar Economic Moat Rating of narrow. Ionis has attracted large partners such as Biogen and Roche, and it has one of the most diverse pipelines in the biotech sector. Even if some of its drugs fail to reach the market, Ionis has reduced development risks by partnering on programs that require large clinical trials. The company continues to replenish its pipeline and improve the safety and convenience of its targeted ASO therapy, and we expect it to gain approval for several additional drugs over the next couple of years, driving excess returns during our forecast period.

Similar to other biotechnology and pharmaceutical firms under our coverage, we think Ionis faces environmental, social, and governmental risks related to US drug price policy reform and the ongoing potential for product governance issues, including litigation. While we have factored these threats into our analysis, we don't see them as material to our valuation or moat rating for Ionis.

Ionis holds a dominant intellectual property position in the field of antisense oligonucleotides, using human genetics data and the effects of known genetic variations to validate new programs. Most of Ionis' ASOs prevent RNA from being translated into a protein that drives disease, although approved spinal muscular atrophy drug Spinraza modulates splicing to increase protein levels. Even as patents on older forms of technology expire, Ionis maintains layers of intellectual property protection, with patents on individual therapies and next-generation technologies (typically allowing smaller doses or more convenient administration) to renew this protection over time. For example, patents on the firm's generation 2.0 technology expired in 2023, but generation 2.5 and LICA—ligand conjugated antisense—delivery technology have extended protection through 2027 and 2034, respectively.

Ionis also has lengthy patent protections on individual drugs, including Spinraza (patent until 2030), Wainua (through at least 2034), Tryngolza (approved by the FDA in December 2024), and Dawnzera (approved by the FDA in August 2025). We think Ionis' Dawnzera has a best-in-class profile in hereditary angioedema, a rare, potentially life-threatening condition that causes severe recurring swelling in the body. We think this drug could achieve total sales exceeding $700 million by the end of our 10-year forecast period.

Ionis’ portfolio is a mix of partnerships and wholly owned projects. Outsourcing its higher-cost clinical trials to larger pharmaceutical firms helps avoid major value destruction, even if several programs fail to reach the market. Ionis typically partners on larger opportunities after completing smaller proof-of-concept studies and maintains full rights to treatments for diseases that are rare or have midsize patient populations. Research and development expenses kept Ionis in the red before 2018, and while Ionis turned a profit in 2019-20 due to significant collaboration revenue from new, expanded, and advancing partnerships, we expect continued operating losses through 2028.

The pipeline has several therapies using the firm's liver-targeting LICA technology, which allows lower dosages and reduced side effects while improving potency and convenience. For example, Ionis’ older-technology drug Tegsedi was approved in 2018 as a once-weekly injection for polyneuropathy in hereditary ATTR amyloidosis, but with a black box warning on its prescribing label for thrombocytopenia (low platelet count) and glomerulonephritis (kidney disease). Alnylam's infused drug Onpattro, approved two months earlier, has a better safety profile and has seen better commercial success. In addition, Pfizer's oral Vyndaqel/Vyndamax has been approved for another amyloidosis indication, cardiomyopathy, which does overlap with polyneuropathy and could pull some patients onto this convenient and cheaper regimen. Ionis' next-generation LICA drug Wainua (for amyloidosis) has demonstrated improved potential over Tegsedi. It received approval in the US in December 2023 and received a positive opinion by the Committee for Medicinal Products for Human Use in the European Union in October 2024. Additionally, Tryngolza (for severe hypertriglyceridemia) has demonstrated improved potential over Ionis’ older drug Waylivra. It received FDA approval in December 2024, marking Ionis’ first independent commercial launch as it historically depended on larger pharmaceutical firms for commercialization efforts. Ionis will be focused on Tryngolza’s commercialization efforts in the US market. Another cardiology LICA program, pelacarsen (partnered with Novartis), is likely to target millions of patients with an elevated risk of heart disease.

In neurology, RNA therapies can reach their intended targets via intrathecal administration into spinal fluid, directly preventing the production of toxic proteins. The approval of Spinraza in 2016 and Qalsody in 2023 provided a solid foundation for Ionis' neurology pipeline. Partner Biogen's reported Spinraza revenue of roughly $2 billion annually in 2019-21 declined to $1.55 billion in 2025 as Biogen added new patients at lower price points and sees some share loss to newer treatments like one-time gene therapy Zolgensma (Novartis) and oral small-molecule treatment Evrysdi (Roche). However, share loss could be mitigated thanks to Ionis’ progress with a higher-dose version of Spinraza and next-generation drugs that could see dosing every nine months or yearly, instead of every four months.

Ionis is retaining full rights to several programs in neurology, including pivotal programs for Angelman syndrome and Alexander disease. As Ionis’ pipeline continues to develop, we think it is likely that the firm will see returns above our assumed 8.6% cost of capital by 2030.

Ionis' antisense technology and intellectual property estate have allowed the firm to create an entirely new class of therapeutics for difficult-to-treat diseases.

Antisense therapeutics have the potential to gain access to well-studied targets in the cell that are currently deemed "undruggable," and Ionis could capture this low-hanging fruit in a wide range of diseases.

Ionis has attracted big-name partners like Biogen and Roche, and it has one of the broadest pipelines in the biotech sector.

Beyond recent strong collaboration revenue, Ionis has historically been unprofitable, and RNA-based therapies have had a long path to market.

While Ionis targets several rare genetic disorders, including amyloidosis and spinal muscular atrophy, the space is attracting greater biopharma competition.

Ionis partnering with large pharma firms limits the economic profits the company can derive from a successful drug.