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]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 Form 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the Quarterly Period Ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934 For the transition period from _____ to _____ Commission file number 000-19125 Ionis Pharmaceuticals, Inc. (Exact name of Registrant as specified in its charter) (State or other jurisdiction of in ...

Core Insights - Ionis Pharmaceuticals reported strong second-quarter results with adjusted earnings of 85 cents, a significant improvement from an adjusted loss of $35 million a year ago, and beating analysts' expectations of a 52-cent loss [1] - Revenue for the first quarter of 2025 increased by 10% to $132 million, surpassing the consensus estimate of $125.32 million, driven by higher commercial revenue [1] Revenue Performance - Ionis' revenues more than doubled to $452 million, exceeding the consensus of $282.95 million, primarily due to the successful launch of Tryngolza and increased royalty and R&D revenues [2] - Tryngolza generated net product sales of $19 million in the second quarter of 2025 and $26 million in the first half of 2025 [2] Product Developments - Tryngolza received a positive opinion from the Committee for Medicinal Products for Human Use, with a European Commission decision expected by Q4 2025 [3] - Wainua generated sales of $44 million in the second quarter of 2025, resulting in royalty revenue of $10 million [3] - Spinraza generated global sales of $393 million, leading to royalty revenue of $54 million [4] Financial Guidance - Ionis raised its fiscal 2025 sales guidance from $725 million-$750 million to $825 million-$850 million, compared to the consensus estimate of $754.67 million [6] - The company expects a 2025 adjusted operating loss of $300 million-$325 million, an improvement from previous guidance of less than $375 million [7] Market Reaction - Following the announcement, Ionis stock rose by 5.23% to $43.65 [7]

Financial Data and Key Metrics Changes - In Q2 2025, Ionis Pharmaceuticals reported revenue of $452 million, a twofold increase year over year, and $584 million for the first half of 2025, representing a nearly 70% increase compared to the prior year [30][31] - Non-GAAP net income for the quarter was $154 million, reflecting strong financial performance [31] - The company raised its 2025 revenue guidance by $100 million, now expecting between $825 million and $850 million in revenue for the year [34] Business Line Data and Key Metrics Changes - The launch of Trincolza generated $19 million in net product sales for Q2, marking a threefold increase quarter over quarter [10][32] - Royalty revenues increased by approximately 10% to $70 million in Q2, supported by contributions from SPINRAZA and WAYNUA [32] - Ionis anticipates $75 million to $80 million in Trincolza product sales for the full year [34] Market Data and Key Metrics Changes - The coverage mix for Trincolza patients is approximately 60% commercial and 40% government, with over 90% of patients paying $0 out of pocket since launch [12] - The company is targeting over 3,000 physicians and has reached more than 30,000 healthcare providers through its marketing efforts [14] Company Strategy and Development Direction - Ionis is focused on expanding its pipeline with multiple upcoming launches, including Donavolorsen for hereditary angioedema, which is expected to receive FDA approval soon [7][9] - The company aims to leverage its first-mover advantage in both familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG) markets [15][71] - Ionis plans to continue investing in its late-stage programs while maintaining disciplined capital management [35] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the continued commercial success of Trincolza and the upcoming launch of Donavolorsen, highlighting the strong therapeutic profiles and unmet needs these products address [5][9] - The company anticipates a steady cadence of independent and partnered launches over the next few years, contributing to sustained revenue growth and positive cash flow [37] Other Important Information - Ionis is preparing for an innovation day on October 7 to highlight its pipeline and advancements in drug discovery [38] - The company is also set to initiate a quiet period starting July 31, which will be lifted upon data announcement from the CORE and CORE II studies [39] Q&A Session Summary Question: How is the TRINGOZA FCS launch progressing? - The company reported strong execution with a threefold increase in Q2 sales, effective patient identification efforts, and favorable reimbursement trends [41][43] Question: What triglyceride lowering is expected in the upcoming SHTG readout? - The company expects a reduction of 58% to 62% in triglyceride levels, which is considered clinically meaningful for physicians [48][49] Question: What is the status of Donavolorsen's launch preparations? - The company confirmed that everything is in place for the launch following the expected FDA approval on August 21 [50][54] Question: How does the company view competition in the market? - Management believes that patients are willing to switch to Donavolorsen due to its strong profile and ease of use compared to existing treatments [78] Question: What is the expected acute pancreatitis (AP) event rate in the CORE and CORE II studies? - The company confirmed that there will be more AP events in the CORE and CORE II studies combined than in the FCS BALANCE study, but specific numbers were not disclosed [64][104]

Financial Data and Key Metrics Changes - Ionis Pharmaceuticals reported revenue of $452 million for Q2 2025, a twofold increase year over year, and $584 million for the first half of 2025, an increase of nearly 70% compared to the prior year [29][30] - Non-GAAP net income for Q2 was $154 million, reflecting strong financial performance [29] - The company raised its 2025 revenue guidance by $100 million, now expecting between $825 million and $850 million in revenue for the year [32][34] Business Line Data and Key Metrics Changes - Trincolza generated $19 million in net product sales for Q2, representing a threefold increase quarter over quarter [8][30] - Royalty revenues increased by approximately 10% to $70 million in Q2, supported by contributions from SPINRAZA and WAYNUA [30] - Ionis anticipates $75 million to $80 million in Trincolza product sales for the full year [33] Market Data and Key Metrics Changes - The coverage mix for Trincolza patients is approximately 60% commercial and 40% government, with over 90% of patients paying $0 out of pocket since launch [10][11] - The company is targeting over 3,000 physicians and has reached more than 30,000 healthcare providers to increase awareness and patient identification for Trincolza [12][70] Company Strategy and Development Direction - Ionis is focused on launching multiple independent therapies, with Trincolza being the first and Donadolorsen expected to follow shortly after FDA approval [5][6] - The company aims to leverage its first-mover advantage in both familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG) markets [12][70] - Ionis plans to continue investing in its pipeline, with expectations of four potential launches by 2027 targeting serious conditions [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing commercial success of Trincolza and the upcoming launch of Donadolorsen, highlighting the strong therapeutic profiles and unmet needs being addressed [4][5] - The company anticipates continued revenue growth and positive cash flow in the coming years, supported by a robust pipeline and disciplined capital management [34][35] Other Important Information - Ionis is preparing for an innovation day on October 7 to highlight its pipeline and advancements in drug discovery [37] - The company is actively engaging with payers to ensure smooth market access for its upcoming products [15] Q&A Session Questions and Answers Question: Can you provide more details on the Trincolza FCS launch and expectations for the second half of the year? - Management highlighted strong early momentum with $19 million in Q2 sales and effective patient identification efforts, expecting continued growth through the second half of the year [44][46] Question: What level of triglyceride lowering is expected in the upcoming SHTG readout? - The company anticipates a triglyceride reduction of 58% to 62%, which is considered clinically meaningful for physicians managing these patients [48][49] Question: How is the launch readiness for Donadolorsen progressing? - Management confirmed that all preparations are in place for the anticipated launch following the August 21 PDUFA date, with a strong regulatory and clinical data foundation [56][57] Question: What insights can you provide regarding competition in the HAE market? - Management noted that existing prophylactic treatments are not fully satisfying patients, indicating a strong willingness to switch to Donadolorsen due to its favorable profile and self-administration convenience [78][80] Question: Can you clarify the expected acute pancreatitis (AP) event rates in the CORE and CORE II studies? - Management confirmed that the cumulative AP event rate in the CORE and CORE II studies is expected to be higher than in the FCS BALANCE study, but specific numbers will be provided in the upcoming data release [65][66]

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)

Ionis Pharmaceuticals (IONS) reported $452 million in revenue for the quarter ended June 2025, representing a year-over-year increase of 100.9%. EPS of $0.86 for the same period compares to -$0.45 a year ago. Here is how Ionis Pharmaceuticals performed in the just reported quarter in terms of the metrics most widely monitored and projected by Wall Street analysts: View all Key Company Metrics for Ionis Pharmaceuticals here>>> Shares of Ionis Pharmaceuticals have returned +3.9% over the past month versus the ...

Ionis Pharmaceuticals (IONS) came out with quarterly earnings of $0.86 per share, beating the Zacks Consensus Estimate of $0.27 per share. This compares to a loss of $0.45 per share a year ago. These figures are adjusted for non-recurring items. This quarterly report represents an earnings surprise of +218.52%. A quarter ago, it was expected that this drug discovery and development company would post a loss of $1.11 per share when it actually produced a loss of $0.75, delivering a surprise of +32.43%. Over ...

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]