Key Takeaways Ionis posted a smaller-than-expected Q3 loss and a 17% year-over-year revenue increase.Commercial revenue jumped 53% YoY on strong Tryngolza sales and higher Wainua royalties.The company raised its 2025 revenue outlook to $875-$900 million, citing solid drug uptake.Ionis Pharmaceuticals (IONS) reported third-quarter 2025 adjusted loss per share of 61 cents, much narrower than the Zacks Consensus Estimate of a loss of $1.15. In the year-ago period, the company reported an adjusted loss of 72 ce ...

Financial Data and Key Metrics Changes - In Q3 2025, the company generated $157 million in revenue, a 17% increase year-over-year, and for the first nine months, revenue totaled $740 million, reflecting a 55% increase compared to the prior year [23][24] - TRYNGOLZA product sales reached $32 million, representing a nearly 70% increase over the second quarter [23][24] - Royalty revenues increased by approximately 13% to $76 million in Q3, driven by contributions from SPINRAZA and WAINUA [24] - The company raised its 2025 financial guidance, now expecting total revenue between $875 million and $900 million, an increase of $50 million from prior guidance [25][26] Business Line Data and Key Metrics Changes - TRYNGOLZA, the FDA-approved treatment for familial chylomicronemia syndrome, continues to show strong momentum with significant sales growth [5][14] - DAWNZERA, approved for hereditary angioedema, has seen strong early adoption, with initial prescriptions being filled shortly after approval [19][20] - The company anticipates two additional independent launches next year, with olzarsen for severe hypertriglyceridemia and zilganersen for Alexander disease [6][10] Market Data and Key Metrics Changes - The U.S. prophylactic HAE market is well established, with approximately 20% of patients switching treatments annually, indicating a significant opportunity for DAWNZERA [20] - The severe hypertriglyceridemia (sHTG) patient population is estimated to exceed 1 million in the U.S., with many patients struggling to manage triglyceride levels with current treatments [16][17] Company Strategy and Development Direction - The company is focused on executing its commercial strategy for TRYNGOLZA and DAWNZERA while preparing for upcoming launches of olzarsen and zilganersen [22][27] - The company aims to achieve cash flow breakeven by 2028, driving long-term value creation [26][27] - The commercial team is expanding outreach to healthcare providers and enhancing patient identification efforts to maximize the potential of its therapies [15][17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the continued success of TRYNGOLZA and DAWNZERA, highlighting the strong early feedback from physicians and patients [19][20] - The company is optimistic about the upcoming data presentations and regulatory submissions, which are expected to further validate its pipeline and market potential [9][11] - Management emphasized the importance of addressing unmet needs in serious diseases and the potential for multi-billion dollar revenue from its pipeline [7][10] Other Important Information - The company announced the retirement of Richard Geary, Chief Development Officer, recognizing his contributions over the past 30 years [28] - The company is preparing for a significant data presentation at the American Heart Association (AHA) conference, which is expected to highlight the efficacy of olzarsen [38][39] Q&A Session Summary Question: What is the expected launch curve for olzarsen in sHTG? - The company anticipates strong interest from healthcare providers and plans to target approximately 20,000 HCPs covering around 360,000 patients with sHTG [31][33] Question: Any concerns regarding acute pancreatitis events in olzarsen studies? - Management expressed confidence in the groundbreaking results and emphasized that the data will be presented at AHA, with no significant concerns noted [37][38] Question: What are the peak revenue expectations for olzarsen and DAWNZERA? - Peak sales for DAWNZERA are expected to exceed $500 million, while olzarsen is anticipated to surpass $1 billion [39][40] Question: What is the pricing strategy for olzarsen? - The company is still evaluating pricing and will announce final pricing upon approval of the sHTG indication [44][45] Question: How is the early adoption of DAWNZERA progressing? - Early adoption is strong, with both switching patients and newly diagnosed patients starting treatment [72] Question: What is the source of revenue growth for WAINUA? - The revenue growth is primarily driven by new patient identification and the product's performance in improving quality of life [73]

Core Insights - Ionis Pharmaceuticals announced positive topline results from a pivotal phase III study for its investigational RNA-targeted therapy zilganersen, aimed at treating Alexander disease (AxD) [1][4] Group 1: Study Results - The study met its primary endpoint, showing that patients receiving a 50 mg dose of zilganersen achieved a statistically significant 33.3% stabilization in gait speed compared to the control group, measured by the 10-Meter Walk Test (10MWT) [2] - Treatment with zilganersen demonstrated a favorable safety and tolerability profile, with consistent benefits observed across key secondary endpoints, indicating evidence of slowed disease progression [3][9] Group 2: Regulatory and Market Implications - Ionis plans to submit a regulatory filing with the FDA for zilganersen in Q1 2026, marking it as the first investigational medicine to show a positive disease-modifying impact in AxD [6][4] - If approved, zilganersen will join Ionis' portfolio as the third wholly-owned drug, alongside Tryngolza and Dawnzera, which were approved in the last 12 months [7] Group 3: Financial Performance and Strategy - Year-to-date, Ionis shares have increased nearly 76%, significantly outperforming the industry growth of 12% [8] - Ionis has established collaborations with major pharmaceutical companies, providing funds through license fees and milestone payments to support the development of its wholly-owned pipeline [10] - The company earns commercial revenues from royalties on Spinraza and Qalsody, with ongoing partnerships for other drug developments [11][12]

Core Insights - Ionis Pharmaceuticals (IONS) received FDA's Breakthrough Therapy designation for ION582, aimed at treating Angelman syndrome (AS), a rare neurological disorder [1][4] - Following the announcement, Ionis shares increased by 5.6% [1][6] - Year-to-date, Ionis shares have risen by 84.2%, significantly outperforming the industry average of 12.5% [2] Company Overview - Angelman syndrome affects approximately 1 in 21,000 individuals globally, leading to severe developmental challenges without any approved disease-modifying therapies [2] - The FDA's Breakthrough Therapy designation accelerates drug development and review for serious conditions, providing enhanced guidance and support [4] Clinical Development - The Breakthrough Therapy designation for ION582 was based on positive results from the phase I/II HALOS study, which showed significant clinical improvements in communication, cognition, and motor function [5][6] - Ionis has initiated the phase III REVEAL study for ION582, targeting both children and adults with AS [5][6] Competitive Landscape - Ultragenyx Pharmaceuticals is also developing GTX-102 for AS, which has received similar Breakthrough Therapy designation from the FDA [7] - Both ION582 and GTX-102 are in phase III development, creating competition for the first FDA approval for AS [8]

Core Insights - Ionis Pharmaceuticals reported second-quarter 2025 adjusted earnings per share (EPS) of 86 cents, significantly exceeding the Zacks Consensus Estimate of 27 cents, compared to an adjusted loss of 24 cents in the same period last year [1] - Total revenues reached $452 million, doubling year-over-year and surpassing the Zacks Consensus Estimate of $271 million [2] Revenue Streams - Ionis has licensed Spinraza to Biogen, which is responsible for its commercialization, and receives royalties from its sales. Spinraza is approved for treating spinal muscular atrophy globally [3] - Ionis also earns royalties from Biogen's Qalsody, approved for treating amyotrophic lateral sclerosis with SOD1 mutations, launched in the U.S. in 2023 and in the EU in May 2024 [3] - The FDA approved Wainua (eplontersen) for treating hereditary transthyretin-mediated amyloid polyneuropathy in December 2023, co-marketed with AstraZeneca in the U.S. [4] - Following Wainua's U.S. launch, Ionis began receiving royalties from AstraZeneca, which are included in commercial revenues [5] Commercial Revenue Performance - Commercial revenues rose 43% year-over-year to $103 million, driven by Tryngolza product sales and Wainua royalties, exceeding the Zacks Consensus Estimate of $88 million [7] - Tryngolza contributed $19 million in sales, up from $6 million in the previous quarter, indicating strong launch momentum [8] - Spinraza royalties totaled $54 million, down 5% year-over-year, with sales of $393 million, reflecting an 8% decline compared to the previous year [8] - Wainua royalty revenues amounted to $10 million, with sales of $44 million recorded by AstraZeneca [9] R&D Revenue Growth - R&D revenues surged 128% year-over-year to $349 million, driven by a $280 million upfront payment for out-licensing rights for a rare blood cancer drug to Ono Pharmaceutical [12] - Collaborative agreement revenues totaled $337 million, compared to $141 million in the year-ago quarter [13] Cost and Guidance Updates - Adjusted operating costs rose 8% year-over-year to $282 million, with SG&A costs increasing 42% to support commercialization efforts [14] - Ionis raised its 2025 revenue outlook to $825-$850 million, up from the previous guidance of $725-$750 million, reflecting strong uptake for Tryngolza [15] - The adjusted operating loss is now expected to be between $300-$325 million, down from previous guidance of less than $375 million [18] Updates on Wholly-Owned Candidates - Tryngolza is being evaluated in three late-stage studies for severe hypertriglyceridemia, with positive data from the ESSENCE study [20] - Donidalorsen is under FDA review for hereditary angioedema, with a decision expected next month [21] - Zilganersen is in a late-stage study for Alexander disease, with data expected in 2025 [22] Partnered Candidates Developments - AstraZeneca and Ionis are developing Wainua for ATTR-CM, with data from the phase III CARDIO-TTRANSform study expected in the second half of 2026 [23] - Novartis is developing pelacarsen for elevated Lp(a)-driven cardiovascular disease, with data expected this year [24] - AstraZeneca initiated a phase IIb study on opemalirsen for APOL1-mediated kidney disease, triggering a $30 million milestone payment to Ionis [25]

Q2:2025 Business Update and Financial Results July 30, 2025 Nasdaq: IONS 1 On Today's Earnings Call Eugene Schneider, M.D. Chief Clinical Development Officer Eric Swayze, Ph.D. Executive Vice President, Research 2 Brett Monia, Ph.D. Chief Executive Officer Kyle Jenne Chief Global Product Strategy Officer In this presentation, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark ...

Core Viewpoint - Ionis Pharmaceuticals reported a narrower adjusted loss in Q1 2025 compared to the previous year and exceeded revenue expectations, driven by strong sales from its licensed products and new drug approvals [1][2][6]. Financial Performance - The adjusted loss per share for Q1 2025 was 75 cents, better than the Zacks Consensus Estimate of a loss of $1.11 and an adjusted loss of 77 cents in the same quarter last year [1]. - Total revenues reached $132 million, surpassing the Zacks Consensus Estimate of $120 million, marking an 11% increase year over year [2]. - Commercial revenues amounted to $76 million, a 29% increase year over year, exceeding the Zacks Consensus Estimate of $67 million [6]. - R&D revenues declined 7% year over year to $56 million, but still beat the Zacks Consensus Estimate of $50 million [10]. Revenue Streams - Ionis earns royalties from Biogen on the sales of Spinraza and Qalsody, with Spinraza royalties totaling $48 million, up 26% year over year [7]. - Wainua generated $9 million in royalty revenues, with sales recorded at $39 million by AstraZeneca [7]. - Tryngolza contributed $6 million in product sales during its first quarter of recognition [6]. Cost Structure - Adjusted operating costs rose 5% year over year to $249 million, with SG&A costs increasing by 52% to support commercialization efforts [11]. - R&D costs decreased by 6% as several late-stage studies concluded [11]. Guidance and Future Outlook - Ionis raised its 2025 revenue guidance to between $725 million and $750 million, up from over $600 million, reflecting new licensing deals [12]. - The adjusted operating loss is now expected to be less than $375 million, improved from the previous guidance of less than $495 million [15]. - The company anticipates ending 2025 with approximately $1.9 billion in cash, up from a prior projection of $1.7 billion [16]. Drug Development Updates - Tryngolza is under evaluation in three late-stage studies for severe hypertriglyceridemia, with data expected in 2025 [18]. - Donidalorsen is awaiting FDA approval for hereditary angioedema, with a decision expected by August 21, 2025 [19]. - Zilganersen is in a phase III study for Alexander disease, with data expected in 2025 [20]. Partnerships and Collaborations - AstraZeneca and Ionis are co-marketing Wainua for hereditary transthyretin-mediated amyloid polyneuropathy in the U.S. and have plans for further development in other forms of amyloidosis [21]. - Ionis has out-licensed rights for a rare blood cancer drug to Ono Pharmaceutical, receiving an upfront payment of $280 million and potential milestone payments [23].