2 Ionis Leadership Here Today Innovation Day 2025: Accelerating Growth through Life-Changing Medicines OCTOBER 7, 2025 | Nasdaq: IONS Forward-Looking Statements This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis' goals, expectations, fina ...

Core Insights - Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) is recognized as one of the top biotech stocks to invest in, with Leerink Partners maintaining an Outperform rating and increasing the price target from $63 to $68 following positive results for its Alexander disease therapy, zilganersen [1]. Group 1: Company Performance - The 10-meter walk test (10MWT) indicated that Zilganersen demonstrated a statistically significant improvement in stabilizing gait speed, along with steady gains across key secondary endpoints [2]. - Ionis Pharmaceuticals focuses on developing medications for serious medical conditions, particularly in the cardiovascular and neurological disorder sectors [3]. Group 2: Future Outlook - Detailed results from the Zilganersen trial are expected to be presented at an upcoming medical conference, while open-label extension data will provide further insights into the treatment's impact on life expectancy and disease progression in the future [3].

Upgrades Summary - Rothschild & Co Redburn upgraded Kenvue (KVUE) to Buy from Neutral with a price target of $22, down from $22.50, citing a more measured response from the Health and Human Services department regarding Tylenol usage concerns [2] - Rosenblatt upgraded Ciena (CIEN) to Buy from Neutral with a price target of $175, up from $127.50, following an innovation day that highlighted opportunities to network multiple AI data centers [2] - Citi upgraded Riot Platforms (RIOT) to Buy from Neutral with a price target of $24, up from $13.75, due to the company's transition to AI and high-performance computing [2] - JPMorgan also upgraded Riot Platforms to Overweight from Neutral with a price target of $19, up from $15 [2] - Goldman Sachs upgraded Ionis Pharmaceuticals (IONS) to Neutral from Sell with a price target of $65, up from $45, noting the company's transition to a commercial growth story [2] - RBC Capital upgraded Alkermes (ALKS) to Outperform from Sector Perform with a price target of $44, up from $42, based on positive analysis of potential narcolepsy type 2 treatment effects for alixorexton [2]

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]

Group 1 - Ionis Pharmaceuticals has reported positive results from a pivotal study of its experimental medicine, zilganersen, aimed at treating Alexander disease, a rare neurological disorder [5] - The study demonstrated that a 50 mg dose of zilganersen significantly improved outcomes for patients suffering from Alexander disease [5]

Core Insights - Ionis Pharmaceuticals released topline results from a pivotal study of zilganersen for Alexander disease, a rare neurological condition [1] - Zilganersen showed statistically significant stabilization in gait speed, with a mean difference of 33.3% compared to control at week 61 [2] - The drug demonstrated a positive disease-modifying impact, marking a first in AxD treatment [3] Efficacy and Safety - Zilganersen exhibited consistent benefits across key secondary endpoints, indicating slowed disease progression and stabilization [3] - Key secondary endpoints included various patient and clinician global impression scores, showing favorable trends [4] - The safety profile of zilganersen was favorable, with most adverse events being mild or moderate, and serious adverse events were numerically lower in the treatment group [4] Regulatory and Market Impact - Ionis plans to submit a new drug application to the FDA in Q1 2026 and is considering an Expanded Access Program in the U.S. [5] - Following the news, Ionis stock rose by 4.88% to $63.99 in premarket trading [5]

Core Insights - Ionis Pharmaceuticals announced that its experimental drug for brain disorders successfully met the primary endpoint in an early-to-late-stage clinical study [1] Company Summary - Ionis Pharmaceuticals is advancing its drug development for brain disorders, indicating progress in clinical trials [1]

Group 1 - The European Commission has granted final approval for two treatments developed by KalVista Pharmaceuticals and Ionis Pharmaceuticals targeting rare genetic disorders [2][3]

Core Insights - Ionis Pharmaceuticals and Sobi announced the approval of TRYNGOLZA (olezarsen) in the European Union for treating genetically confirmed familial chylomicronemia syndrome (FCS) as an adjunct to diet [1] - The approval was based on a positive opinion from the Committee for Medicinal Products for Human Use [1] - The decision follows positive data from the Phase 3 Balance study, where TRYNGOLZA 80 mg demonstrated efficacy [1]

Company Highlights - Aurinia Pharmaceuticals Inc. (AUPH) has seen solid growth for its product LUPKYNIS, with expected net product sales for 2025 ranging from $250 million to $260 million, up from $216.2 million last year [2][3] - Arrowhead Pharmaceuticals Inc. (ARWR) is preparing for its first commercial launch in 2025, with its lead drug candidate Plozasiran under FDA review, decision expected on November 18, 2025 [4][5] - Beta Bionics Inc. (BBNX) reported a 54% growth in second-quarter net sales, with expectations for full-year 2025 net sales to range between $88 million and $93 million, compared to $65.1 million last year [7][8] - Kiniksa Pharmaceuticals International plc (KNSA) anticipates net product revenue for its drug Arcalyst to be between $625 million and $640 million for 2025, up from $417 million in 2024 [10][11] - Ionis Pharmaceuticals Inc. (IONS) generated net product sales of $19 million in Q2 2025, with a supplemental new drug application expected by year-end [12][14] - Stoke Therapeutics Inc. (STOK) is developing Zorevunersen for Dravet syndrome, with a 52-week high of $24.60 reached recently, representing an 82% gain in less than two months [16][17] - Fortress Biotech Inc. (FBIO) is awaiting an FDA decision on its investigational drug CUTX-101 for Menkes disease, expected on September 30, 2025 [18][21] Stock Performance - AUPH stock increased by 168% over 1.5 years, reaching a 52-week high of $12.87 [3] - ARWR stock gained 65% in less than 9 months, hitting a 52-week high of $31.13 [5] - BBNX stock rose nearly 55% in less than 4 months, reaching a 52-week high of $26.66 [8] - KNSA stock saw a 46% increase in less than four months, touching a 52-week high of $37.34 [11] - IONS stock gained 52% in less than two months, reaching a 52-week high of $64.72 [15] - STOK stock increased by 82% in less than two months, achieving a 52-week high of $24.60 [17] - FBIO stock rose by 61% in less than a month, reaching a 52-week high of $3.97 [21]