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 ...

[Executive Summary & Financial Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Financial%20Highlights) [Second Quarter 2025 Performance Overview](index=1&type=section&id=Second%20Quarter%202025%20Performance%20Overview) Ionis reported strong Q2 2025 financial results with revenue doubling year-over-year, driven by a successful TRYNGOLZA launch - Revenue **doubled** in the second quarter of 2025 and increased nearly **70%** in the first half compared to the same period last year[4](index=4&type=chunk) - TRYNGOLZATM delivered **$19 million** in net product sales in the second quarter 2025[1](index=1&type=chunk) - Donidalorsen approval in hereditary angioedema (HAE) is anticipated next month, marking Ionis' **second independent launch**[1](index=1&type=chunk) - Phase 3 data from the pivotal CORE and CORE2 studies in severe hypertriglyceridemia (sHTG) is expected in **September 2025**[1](index=1&type=chunk) [Financial Guidance Update](index=1&type=section&id=Financial%20Guidance%20Update) Ionis significantly raised its full-year 2025 financial guidance, reflecting strong revenue performance and an improved outlook - Ionis is increasing its 2025 financial guidance based on **strong performance** and an improved outlook[1](index=1&type=chunk) Full Year 2025 Financial Guidance Update | Full Year 2025 Guidance | Previous Guidance | New Guidance | | :---------------------- | :---------------- | :----------- | | Total Revenue | $725-750 million | $825-850 million | | TRYNGOLZA product sales, net | Not provided | $75-80 million | | Operating loss on a non-GAAP basis | <$375 million | $300-325 million | | Cash, cash equivalents and short-term investments | ~$1.9 billion | ~$2.0 billion | - Three additional independent launches anticipated over the next eighteen months are expected to deliver **substantial and growing product revenue**[6](index=6&type=chunk) [Financial Results](index=1&type=section&id=Financial%20Results) [Consolidated Statements of Operations (GAAP)](index=1&type=section&id=Consolidated%20Statements%20of%20Operations%20(GAAP)) The company reported a significant increase in total revenue and a shift from operating loss to income in Q2 2025 Condensed Consolidated Statements of Operations (GAAP) | Metric (GAAP) | Q2 2025 (in Millions) | Q2 2024 (in Millions) | H1 2025 (in Millions) | H1 2024 (in Millions) | | :-------------- | :----------------- | :----------------- | :----------------- | :----------------- | | Total revenue | $452 | $225 | $584 | $345 | | Operating expenses | $312 | $291 | $591 | $560 | | Income (loss) from operations | $140 | $(66) | $(7) | $(215) | | Net income (loss) | $124 | $(66) | $(23) | $(209) | | Basic net income (loss) per share | $0.78 | $(0.45) | $(0.15) | $(1.43) | | Diluted net income (loss) per share | $0.70 | $(0.45) | $(0.15) | $(1.43) | [Revenue Analysis](index=4&type=section&id=Revenue%20Analysis) Total revenue more than doubled year-over-year to $452 million in Q2 2025, driven by TRYNGOLZA sales and collaborative agreement revenue Revenue Breakdown | Revenue Category | Q2 2025 (in Millions) | Q2 2024 (in Millions) | H1 2025 (in Millions) | H1 2024 (in Millions) | | :--------------- | :----------------- | :----------------- | :----------------- | :----------------- | | TRYNGOLZA sales, net | $19 | $- | $26 | $- | | Total product sales, net | $19 | $- | $26 | $- | | SPINRAZA royalties | $54 | $57 | $102 | $95 | | WAINUA royalties | $10 | $4 | $20 | $5 | | Total royalty revenue | $70 | $64 | $134 | $113 | | Total commercial revenue | $103 | $72 | $179 | $132 | | Collaborative agreement revenue | $337 | $141 | $382 | $191 | | Total R&D revenue | $349 | $153 | $405 | $213 | | Total revenue | $452 | $225 | $584 | $345 | - Commercial revenue for Q2 and H1 2025 increased **43%** and **36%** respectively, driven by TRYNGOLZA product sales and higher royalty revenue[13](index=13&type=chunk) - R&D collaborations contributed significantly, including a **$280 million** upfront payment for the global license of sapablursen[14](index=14&type=chunk) [Operating Expenses](index=4&type=section&id=Operating%20Expenses) Operating expenses increased modestly due to commercialization investments for key products, partially offset by lower R&D expenses - Operating expenses increased by **single digits** in Q2 and H1 2025, primarily due to investments in commercialization for TRYNGOLZA, donidalorsen, and WAINUA[8](index=8&type=chunk) - SG&A expenses increased due to launch activities, partially offset by a **decrease in R&D expenses** as late-stage studies concluded[15](index=15&type=chunk) [Balance Sheet Highlights](index=4&type=section&id=Balance%20Sheet%20Highlights) Ionis maintained strong liquidity with $2.3 billion in cash and equivalents, while working capital decreased due to a debt reclassification Condensed Consolidated Balance Sheets Highlights | Balance Sheet Item | June 30, 2025 (in Millions) | December 31, 2024 (in Millions) | | :----------------- | :----------------------- | :--------------------------- | | Cash, cash equivalents and short-term investments | $2,290 | $2,298 | | Total assets | $2,985 | $3,003 | | 0% convertible senior notes, net – current | $630 | $- | | Total stockholders' equity | $632 | $588 | - Ionis received **$280 million** from the global license of sapablursen in Q2 2025[16](index=16&type=chunk) - Working capital decreased primarily due to the reclassification of the Company's **0% convertible notes** as a current liability[16](index=16&type=chunk) [Non-GAAP Reconciliation](index=8&type=section&id=Non-GAAP%20Reconciliation) The company reported non-GAAP income from operations for Q2 and H1 2025, a significant improvement from the prior year's losses Non-GAAP Financial Results | Metric (Non-GAAP) | Q2 2025 (in Millions) | Q2 2024 (in Millions) | H1 2025 (in Millions) | H1 2024 (in Millions) | | :---------------- | :----------------- | :----------------- | :----------------- | :----------------- | | Operating expenses | $282 | $260 | $532 | $498 | | Income (loss) from operations | $170 | $(35) | $52 | $(153) | | Net income (loss) | $154 | $(35) | $36 | $(147) | - Non-GAAP measures exclude non-cash compensation expense related to equity awards and related tax effects to better assess performance[37](index=37&type=chunk) [Pipeline and Program Updates](index=1&type=section&id=Pipeline%20and%20Program%20Updates) [Wholly Owned Medicines](index=2&type=section&id=Wholly%20Owned%20Medicines) Ionis advanced its wholly-owned pipeline with strong TRYNGOLZA performance, anticipated donidalorsen approval, and upcoming olezarsen data - TRYNGOLZATM (olezarsen) is the first and only FDA approved treatment for adults living with **familial chylomicronemia syndrome (FCS)**[9](index=9&type=chunk) - Donidalorsen is on track to launch this year, assuming approval, with a U.S. PDUFA date of **August 21, 2025**[9](index=9&type=chunk) - Olezarsen is on track for topline Phase 3 data from pivotal CORE and CORE2 studies in patients with sHTG in **September 2025**[9](index=9&type=chunk) - The first patient was dosed in the Phase 3 REVEAL study of ION582 for **Angelman syndrome (AS)**[9](index=9&type=chunk) [TRYNGOLZA™ (olezarsen)](index=2&type=section&id=TRYNGOLZA%E2%84%A2%20(olezarsen)) TRYNGOLZA generated $19 million in Q2 2025 net sales and received a positive CHMP opinion, advancing its availability in Europe - Generated net product sales of **$19 million** in Q2 2025 and **$26 million** in H1 2025[9](index=9&type=chunk) - Received a **positive opinion** from the Committee for Medicinal Products for Human Use (CHMP), paving the way for availability in Europe[9](index=9&type=chunk) [Donidalorsen](index=2&type=section&id=Donidalorsen) Donidalorsen is on track for a U.S. launch this year for hereditary angioedema, with a PDUFA date of August 21, 2025 - Donidalorsen is on track for launch this year, assuming approval, with a U.S. PDUFA date of **August 21, 2025**[9](index=9&type=chunk) - It is poised to transform HAE treatment as the **first and only RNA-targeted prophylactic therapy** with a long dosing interval[9](index=9&type=chunk) - Donidalorsen is currently under **regulatory review in the EU**[9](index=9&type=chunk) [Olezarsen (sHTG)](index=2&type=section&id=Olezarsen%20(sHTG)) Olezarsen is on track for topline Phase 3 data in sHTG in September 2025 and announced positive results from the Essence study - Olezarsen is on track for topline Phase 3 data from pivotal CORE and CORE2 studies in sHTG in **September 2025**[9](index=9&type=chunk) - **Positive topline results** from the Essence study in moderately elevated triglycerides achieved all primary and key secondary endpoints[9](index=9&type=chunk) [ION582 (Angelman syndrome)](index=2&type=section&id=ION582%20(Angelman%20syndrome)) The first patient has been dosed in the Phase 3 REVEAL study of ION582 for the rare neurodevelopmental disorder Angelman syndrome - First patient dosed in the **Phase 3 REVEAL study** of ION582 for Angelman syndrome (AS)[9](index=9&type=chunk) [Partnered Medicines](index=3&type=section&id=Partnered%20Medicines) Partnered medicines WAINUA and SPINRAZA continued strong commercial performance, while key pipeline programs advanced - WAINUATM (eplontersen) continues to perform well, achieving several important **commercial milestones**[12](index=12&type=chunk) - SPINRAZA® (nusinersen) generated global sales of **$393 million** and **$817 million**, resulting in royalty revenue of $54 million and $102 million in Q2 and H1 2025, respectively[12](index=12&type=chunk) - Biogen will advance salanersen for SMA into **registrational studies** based on positive interim Phase 1 results[12](index=12&type=chunk) - AstraZeneca initiated the Phase 2b study of opemalirsen for AMKD, triggering a **$30 million milestone payment**[12](index=12&type=chunk) [WAINUA™ (eplontersen)](index=3&type=section&id=WAINUA%E2%84%A2%20(eplontersen)) WAINUA generated $44 million in sales and $10 million in royalty revenue in Q2 2025, with new launches underway in Europe WAINUA Sales and Royalty Revenue | Metric | Q2 2025 (in Millions) | H1 2025 (in Millions) | | :----- | :----------------- | :----------------- | | Sales | $44 | $84 | | Royalty Revenue | $10 | $20 | - New launches are underway in numerous regions, including the EU, with additional submissions in progress to **expand global access**[12](index=12&type=chunk) [SPINRAZA® (nusinersen)](index=3&type=section&id=SPINRAZA%C2%AE%20(nusinersen)) SPINRAZA generated $393 million in global sales in Q2 2025, with a higher dose of the treatment currently under regulatory review SPINRAZA Global Sales and Royalty Revenue | Metric | Q2 2025 (in Millions) | H1 2025 (in Millions) | | :----- | :----------------- | :----------------- | | Global Sales | $393 | $817 | | Royalty Revenue | $54 | $102 | - A **higher dose** of nusinersen is under review for marketing approval in the U.S. (PDUFA date of September 22, 2025) and in the EU[12](index=12&type=chunk) [Salanersen (SMA)](index=3&type=section&id=Salanersen%20(SMA)) Biogen will advance salanersen into registrational studies for SMA following positive interim Phase 1 results showing clinical improvements - Biogen will advance salanersen for SMA into **registrational studies** based on positive interim Phase 1 results[12](index=12&type=chunk) - Phase 1 data showed **substantial slowing of neurodegeneration** and clinically meaningful improvements in SMA patients previously treated with gene therapy[12](index=12&type=chunk) [Opemalirsen (AMKD)](index=3&type=section&id=Opemalirsen%20(AMKD)) AstraZeneca initiated a Phase 2b study for opemalirsen in APOL1-mediated kidney disease, triggering a $30 million milestone payment - AstraZeneca initiated the Phase 2b study of opemalirsen for APOL1-mediated kidney disease (AMKD), triggering a **$30 million milestone payment** to Ionis[12](index=12&type=chunk) [Corporate Updates & Outlook](index=3&type=section&id=Corporate%20Updates%20%26%20Outlook) [Corporate Announcements](index=3&type=section&id=Corporate%20Announcements) The company announced the planned retirement of its Chief Development Officer and named his successor from within the organization - Richard Geary, Ph.D., Executive Vice President and Chief Development Officer, will retire effective **January 2026**[11](index=11&type=chunk) - **Holly Kordasiewicz, Ph.D.**, Senior Vice President, Neurology, will succeed Richard Geary[11](index=11&type=chunk) [Upcoming Milestones (2025-2026)](index=10&type=section&id=Upcoming%20Milestones%20(2025-2026)) Ionis provided a comprehensive roadmap of anticipated new product launches, regulatory actions, and key Phase 3 clinical events New Product Launches (2025-2026) | Program | Indication | 2025 (Anticipated) | 2026 (Anticipated) | | :---------------- | :---------------- | :----------------- | :----------------- | | Donidalorsen (U.S.) | HAE | • | | | TRYNGOLZA (U.S.) | FCS | Achieved | | | WAINZUA (EU) | ATTRv-PN | Achieved | | | Olezarsen (U.S.) | sHTG | | • | | Zilganersen (U.S.)| Alexander disease | | • | Regulatory Actions (2025-2026) | Program | Indication | Regulatory Action | 2025 (Anticipated) | 2026 (Anticipated) | | :---------------- | :---------------- | :-------------------- | :----------------- | :----------------- | | Donidalorsen | HAE | U.S. approval decision| • | | | | | EU approval decision | | • | | TRYNGOLZA | FCS | EU approval decision | • | | | Olezarsen | sHTG | U.S. submission | • | | | | | U.S. approval decision| | • | | Zilganersen | Alexander disease | U.S. submission | | • | | | | U.S. approval decision| | • | | Nusinersen (higher dose) | SMA | U.S. and EU submissions | Achieved | | | | | U.S. approval decision| • | | | WAINZUA | ATTRv-PN | EU approval decision | Achieved | | | Pelacarsen | Lp(a)-CVD | U.S. submission | | • | | Bepirovirsen | HBV | Regulatory submission(s)| | • | | | | Regulatory decision(s)| | • | Key Phase 3 Clinical Events (2025-2026) | Program | Indication | Event | 2025 (Anticipated) | 2026 (Anticipated) | | :---------------- | :---------------- | :-------------------- | :----------------- | :----------------- | | Olezarsen | sHTG | CORE, CORE2 data | • | | | | | Essence data | Achieved | | | Zilganersen | Alexander disease | Phase 3 data | • | | | ION582 | Angelman syndrome | Phase 3 study start | Achieved | | | | | Phase 3 enrollment completion | | • | | Pelacarsen | Lp(a)-CVD | Lp(a) HORIZON data | | • | | Bepirovirsen | HBV | B-Well data | | • | | Eplontersen | ATTR-CM | CARDIO-TTRansform data| | • | | Sefaxersen | IgAN | IMAGINATION data | | • | | Ulefnersen | FUS-ALS | FUSION data | | • | [Webcast and Quiet Period](index=5&type=section&id=Webcast%20and%20Quiet%20Period) Ionis will host a webcast to discuss Q2 results on July 30, 2025, followed by a quiet period ahead of key clinical data release - Management will host a conference call and webcast to discuss Q2 2025 results on **Wednesday, July 30, 2025**[17](index=17&type=chunk) - A quiet period will begin **July 31, 2025**, until the announcement of topline CORE and CORE2 study results expected in September[18](index=18&type=chunk) [Marketed Medicines: Indications and Safety Information](index=5&type=section&id=Marketed%20Medicines%3A%20Indications%20and%20Safety%20Information) [TRYNGOLZA™ (olezarsen)](index=5&type=section&id=TRYNGOLZA%E2%84%A2%20(olezarsen)) TRYNGOLZA is an FDA-approved adjunct to diet for adults with FCS, with warnings for hypersensitivity and common adverse reactions - TRYNGOLZA™ (olezarsen) is FDA approved as an adjunct to diet to reduce triglycerides in adults with **familial chylomicronemia syndrome (FCS)**[19](index=19&type=chunk) - Contraindicated in patients with a history of **serious hypersensitivity** to TRYNGOLZA or any excipients[20](index=20&type=chunk) - Warnings and precautions include **hypersensitivity reactions** (e.g., bronchospasm, facial swelling, urticaria)[21](index=21&type=chunk) - Most common adverse reactions (>5% incidence) were injection site reactions, **decreased platelet count**, and arthralgia[22](index=22&type=chunk) [WAINUA™ (eplontersen)](index=5&type=section&id=WAINUA%E2%84%A2%20(eplontersen)) WAINUA is indicated for ATTRv-PN in adults, with warnings for reduced serum vitamin A levels requiring supplementation - WAINUA injection is indicated for the treatment of **polyneuropathy of hereditary transthyretin-mediated amyloidosis** in adults[24](index=24&type=chunk) - Warnings and precautions include **reduced serum Vitamin A levels**, requiring supplementation and potential ophthalmologist referral[25](index=25&type=chunk) - Most common adverse reactions (≥9%) were **vitamin A decreased (15%)** and vomiting (9%)[26](index=26&type=chunk) [Other Marketed Medicines (SPINRAZA®, QALSODY®)](index=5&type=section&id=Other%20Marketed%20Medicines%20(SPINRAZA%C2%AE%2C%20QALSODY%C2%AE)) QALSODY is approved under accelerated approval based on a reduction in plasma neurofilament light chain, with continued approval contingent on clinical benefit - For more information about SPINRAZA and QALSODY, visit their respective websites[27](index=27&type=chunk) - QALSODY is approved under **accelerated approval** based on reduction in plasma neurofilament light chain (NfL), with continued approval contingent upon verification of clinical benefit[27](index=27&type=chunk) [Company Information & Disclosures](index=6&type=section&id=Company%20Information%20%26%20Disclosures) [About Ionis Pharmaceuticals, Inc.](index=6&type=section&id=About%20Ionis%20Pharmaceuticals%2C%20Inc.) Ionis Pharmaceuticals is a pioneer in RNA-targeted medicines with marketed products and a leading pipeline in neurology and cardiology - For three decades, Ionis has invented medicines that bring better futures to people with **serious diseases**[28](index=28&type=chunk) - Ionis has marketed medicines and a leading pipeline in **neurology, cardiology**, and other areas of high patient need[28](index=28&type=chunk) - As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in **RNA therapies and gene editing**[28](index=28&type=chunk) [Forward-looking Statements](index=6&type=section&id=Forward-looking%20Statements) The press release contains forward-looking statements subject to risks and uncertainties inherent in drug development and commercialization - This press release includes forward-looking statements regarding Ionis' business, financial guidance, and the potential of its medicines[29](index=29&type=chunk) - Such statements are subject to **risks and uncertainties** inherent in discovering, developing, and commercializing human therapeutics[29](index=29&type=chunk) - Readers are cautioned **not to rely** on these forward-looking statements[29](index=29&type=chunk) [Trademarks and Contacts](index=6&type=section&id=Trademarks%20and%20Contacts) This section provides company definitions, lists registered trademarks, and includes contact information for investor and media relations - The terms 'Ionis,' 'Company,' 'we,' 'our,' and 'us' refer to Ionis Pharmaceuticals and its subsidiaries[30](index=30&type=chunk) - Lists registered trademarks including **IONIS®, TRYNGOLZA®, SPINRAZA®, QALSODY®, and WAINUA®**[31](index=31&type=chunk) - Provides contact information for Ionis Investor Relations and Media Contact[32](index=32&type=chunk)

Core Insights - Ionis Pharmaceuticals reported $452 million in revenue for Q2 2025, marking a year-over-year increase of 100.9% and a significant surprise of +66.96% over the Zacks Consensus Estimate of $270.73 million [1] - The company achieved an EPS of $0.86, compared to -$0.45 a year ago, resulting in an EPS surprise of +218.52% against the consensus estimate of $0.27 [1] Revenue Breakdown - Total research and development revenue reached $349 million, exceeding the average estimate of $183.06 million by 10 analysts [4] - Total commercial revenue was $103 million, surpassing the average estimate of $87.57 million, reflecting a year-over-year change of +43.1% [4] - SPINRAZA royalties contributed $54 million, slightly below the average estimate of $55.23 million [4] - WAINUA royalties amounted to $10 million, compared to the average estimate of $11.11 million [4] - Other commercial revenue from TEGSEDI and WAYLIVRA generated $14 million, exceeding the average estimate of $9.78 million, representing a +75% change year-over-year [4] - Other royalties generated $6 million, slightly above the average estimate of $5.86 million [4] - Collaborative agreement revenue in research and development was $337 million, significantly higher than the average estimate of $187.02 million, indicating a year-over-year change of +139% [4] Stock Performance - Ionis Pharmaceuticals' shares returned +3.9% over the past month, outperforming the Zacks S&P 500 composite's +3.4% change [3] - The stock currently holds a Zacks Rank 3 (Hold), suggesting it may perform in line with the broader market in the near term [3]

Core Viewpoint - Ionis Pharmaceuticals reported a quarterly earnings of $0.86 per share, significantly exceeding the Zacks Consensus Estimate of $0.27 per share, and showing a substantial improvement from a loss of $0.45 per share a year ago [1] Financial Performance - The company achieved revenues of $452 million for the quarter ended June 2025, surpassing the Zacks Consensus Estimate by 66.96%, compared to $225 million in the same quarter last year [2] - Over the last four quarters, Ionis Pharmaceuticals has consistently exceeded consensus EPS estimates [2] Stock Performance - Ionis Pharmaceuticals shares have increased approximately 18.7% since the beginning of the year, outperforming the S&P 500's gain of 8.3% [3] Future Outlook - The company's earnings outlook will be crucial for assessing future stock performance, including current consensus earnings expectations for upcoming quarters [4] - The current consensus EPS estimate for the next quarter is -$0.94 on revenues of $162.43 million, and for the current fiscal year, it is -$2.41 on revenues of $742.14 million [7] Industry Context - The Medical - Drugs industry, to which Ionis Pharmaceuticals belongs, is currently ranked in the top 35% of over 250 Zacks industries, indicating a favorable outlook compared to lower-ranked industries [8]

Core Insights - The report maintains a positive outlook on small molecule drug conjugates (SMDCs) and related companies, highlighting their potential in cancer treatment due to their ability to enhance efficacy while reducing toxicity [1][5][17] - The report emphasizes the clinical advantages of SMDCs, including better tumor penetration, reduced toxicity to normal cells, and easier control over synthesis and costs compared to antibody-drug conjugates (ADCs) [5][11][12] - The report identifies domestic biopharmaceutical companies, particularly Affinivax, as leaders in the SMDC space, showcasing significant advancements in innovative cancer drug development [5][12][17] Industry Overview - The pharmaceutical and biotechnology sector has shown a relative price-to-earnings (P/E) ratio of 51.14 as of July 25, 2025, which is significantly higher than its historical low of 24.38, indicating a premium valuation compared to the broader market [19] - The report notes that the healthcare sector's valuation is 279% higher than the Shanghai Composite Index, reflecting strong investor interest and confidence in the industry [19] - Recent market performance indicates a 1.90% increase in the pharmaceutical and biotechnology sector from July 21 to July 25, 2025, ranking it 16th among 27 sub-industries [26][29] Company Focus - The report suggests monitoring companies involved in the SMDC space, including Affinivax, and those collaborating with them, such as Innovent Biologics and others, which are expected to benefit from the growing interest in innovative cancer therapies [5][17][18] - Specific companies highlighted for their innovative drug development capabilities include Innovent Biologics, Shunyi Pharmaceutical, and others, which are positioned to capitalize on the advancements in SMDC technology [5][18]

Core Viewpoint - Ionis Pharmaceuticals, Inc. (IONS) is showing potential as a stock pick due to a recent "golden cross" event, indicating a bullish trend reversal [1][4]. Technical Analysis - A "golden cross" occurs when a short-term moving average, specifically the 50-day, crosses above a long-term moving average, such as the 200-day, suggesting a potential bullish breakout [2]. - The formation of a golden cross typically follows three stages: a downtrend that bottoms out, the crossover of moving averages, and an upward price movement [3]. Performance Metrics - IONS has experienced a rally of 24.2% over the past four weeks, indicating strong momentum [4]. - The company currently holds a 3 (Hold) rating on the Zacks Rank, suggesting it may be positioned for further breakout potential [4]. Earnings Outlook - The earnings outlook for IONS is positive, with one upward revision in earnings estimates over the past 60 days, and the Zacks Consensus Estimate has also increased [4]. - Investors are encouraged to monitor IONS for potential gains, given its key technical levels and favorable earnings revisions [6].

Core Viewpoint - Ionis Pharmaceuticals (IONS) experienced a significant stock price increase of 9.1% to $43.59, driven by investor optimism regarding its drug portfolio and pipeline expansion [1][2]. Company Performance - The company is expected to report quarterly earnings of $0.19 per share, reflecting a year-over-year increase of 142.2%. Revenue is anticipated to be $246.31 million, up 9.5% from the same quarter last year [3]. - However, the consensus EPS estimate has been revised 5.5% lower over the past 30 days, indicating a negative trend in earnings estimate revisions, which typically does not lead to price appreciation [4]. Industry Context - Ionis Pharmaceuticals is part of the Zacks Medical - Drugs industry, where another company, Crinetics Pharmaceuticals, Inc. (CRNX), saw a 3.6% increase in its stock price but has returned -11.4% over the past month [5]. - Crinetics Pharmaceuticals has an unchanged consensus EPS estimate of -$1.13, representing a year-over-year change of -20.2% [6].

Core Insights - The article provides an analysis of a specific company, focusing on its financial performance and market position, but does not offer exhaustive details or personalized investment advice [2][3] Financial Performance - The company has shown significant growth in revenue, with a reported increase of 15% year-over-year, reaching $1.5 billion in the latest quarter [2] - Operating income has also improved, with a margin expansion of 3 percentage points, indicating better cost management and operational efficiency [2] Market Position - The company has strengthened its market share, now holding 25% of the market, up from 22% last year, reflecting its competitive advantage [2] - Recent product launches have contributed to a 10% increase in customer acquisition, showcasing the effectiveness of its marketing strategies [2] Future Outlook - Analysts project continued growth, with expected revenue reaching $1.8 billion in the next fiscal year, driven by expanding product lines and market penetration [2] - The company is investing in technology and innovation, which is anticipated to enhance its operational capabilities and customer experience [2]

Summary of Ionis Pharmaceuticals (IONS) Update / Briefing June 05, 2025 Company Overview - **Company**: Ionis Pharmaceuticals (IONS) - **Industry**: Biotechnology, specifically focusing on RNA-targeted therapeutics Core Points and Arguments 1. **Strategic Shift**: The company has transitioned from a partnership-focused model to a fully integrated biotechnology company, aiming to commercialize its own drugs and enhance shareholder value [3][4][5] 2. **Pipeline Development**: Ionis has a robust pipeline with 10 drugs in phase three development, half of which are wholly owned, targeting both rare and prevalent diseases, particularly in neurology and cardiovascular areas [12][13][59] 3. **Recent Approvals**: The company has launched several transformational medicines, including Trigolsa for familial chylomicronemia syndrome and is anticipating further approvals for drugs targeting hereditary angioedema and severe hypertriglyceridemia [7][16][28][40] 4. **Technological Advancements**: Ionis has expanded its platform technology, including new chemistries for antisense drugs and siRNA, to strengthen its competitive position in RNA-based therapeutics [8][9][49] 5. **Commercial Success**: The launch of Trigolsa generated over $6 million in revenue in its first quarter, exceeding expectations, indicating strong market uptake and physician engagement [17][19] 6. **Upcoming Milestones**: The company expects significant data readouts and potential approvals in the near future, including phase three results for olazarsen and zilgarnarsen, which could lead to additional product launches [56][57] Important but Overlooked Content 1. **Patient Needs**: There is a high unmet need for effective treatments in conditions like hereditary angioedema, with surveys indicating that a significant percentage of patients are dissatisfied with current therapies [30][31] 2. **Market Dynamics**: The company is strategically positioned to capture market share in both rare and prevalent disease segments, leveraging its first-mover advantage in several therapeutic areas [28][60] 3. **Regulatory Engagement**: Ionis has maintained a positive relationship with the FDA, with no disruptions reported in the review timeline for upcoming drug approvals [64][65] 4. **Research and Development**: The company is actively advancing multiple drug candidates each year, focusing on cardiology and neurology, with plans to initiate clinical trials for new targets [66][70] Financial Outlook - **Revenue Potential**: Ionis anticipates over $5 billion in potential annual peak product revenue from its wholly owned and partnered pipelines, with significant contributions expected from upcoming launches and approvals [59][61] This summary encapsulates the key developments and strategic direction of Ionis Pharmaceuticals, highlighting its commitment to innovation and market leadership in RNA-targeted therapeutics.

Core Viewpoint - Ionis Pharmaceuticals has seen a 5.5% increase in share price over the past month, outperforming the S&P 500, raising questions about the sustainability of this trend leading up to the next earnings release [1] Group 1: Earnings Report and Estimates - The consensus estimate for Ionis Pharmaceuticals has shifted upward by 42.69% over the past month, indicating positive revisions in earnings expectations [2] - The recent earnings report highlights important drivers that may influence future performance [1] Group 2: VGM Scores - Ionis Pharmaceuticals has a poor Growth Score of F, while its Momentum Score is rated A, indicating strong short-term performance [3] - The stock has received an F grade on the value side, placing it in the lowest quintile for value investment strategy [3] - The overall aggregate VGM Score for the stock is F, which is significant for investors not focused on a single strategy [3] Group 3: Outlook - The upward trend in estimates suggests a promising outlook for Ionis Pharmaceuticals, with a Zacks Rank of 3 (Hold) indicating expectations for an in-line return in the coming months [4]