Financial Data and Key Metrics Changes - Ionis Pharmaceuticals has achieved two FDA approvals for wholly owned products in the last twelve months, with commercial launches underway [3][5] - The company reported a significant reduction in triglycerides by 72% and an 85% reduction in acute pancreatitis events in their recent Phase III trial for olazarsen [6][15] - The guidance for the first year of the familial chylomicronemia syndrome (FCS) launch has been increased to $70 million to $80 million [32] Business Line Data and Key Metrics Changes - The first independent launch for familial chylomicronemia syndrome, branded as Trangolza, is off to a strong start [5] - The second independent commercial launch for hereditary angioedema, Donzara, is also underway with positive early feedback [35][36] Market Data and Key Metrics Changes - Severe hypertriglyceridemia affects over three million people in the United States, indicating a large unmet medical need [20] - The target population for the initial launch strategy includes approximately one million high-risk patients who have had acute pancreatitis attacks [21][23] Company Strategy and Development Direction - Ionis aims to leverage its first-mover advantage in the severe hypertriglyceridemia market with a focus on high-risk patients [26][28] - The company plans to submit a supplemental NDA for olazarsen by the end of the year and present full data at a medical congress [16][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the safety and efficacy of olazarsen, highlighting its favorable profile compared to existing treatments [30] - The sentiment in the healthcare community regarding olazarsen and its potential impact on patient outcomes is very positive [15][34] Other Important Information - Ionis is conducting the largest study ever in TTR cardiomyopathy, with results expected in the second half of next year [45][46] - The company is also on track for data from the LP(a) study in 2026, with successful interim analyses completed [51][52] Q&A Session Summary Question: What is the commercial opportunity for olazarsen? - The severe hypertriglyceridemia market presents a significant opportunity with over three million affected individuals, and the company is focusing on high-risk patients [20][21] Question: How does Ionis plan to position against competitors? - Ionis has set a high bar for triglyceride reduction and acute pancreatitis prevention, emphasizing its first-mover advantage [26][28] Question: What are the expectations for the launch of Donzara? - Early feedback indicates strong interest from the HAE community, with the launch executed well so far [35][36] Question: What is the anticipated market share for Donzara? - Ionis expects Donzara to generate over $500 million in annual revenue at peak, with a focus on switching patients from existing treatments [43] Question: How is the company preparing for the upcoming regulatory submissions? - Ionis plans to submit a supplemental NDA for olazarsen and present data at a medical congress, with confidence in including acute pancreatitis in the label [16][19]

Financial Data and Key Metrics Changes - The company has achieved two FDA approvals for wholly owned products in the last twelve months, with commercial launches underway [3][5] - The first independent launch for familial chylomicronemia syndrome, Trangolza, is off to a strong start, and the approval of Donzara for hereditary angioedema has also been secured [5][6] - The company has increased its guidance for the FCS market to $70 million to $80 million for the first year of launch [34] Business Line Data and Key Metrics Changes - The drug olazarsen demonstrated a 72% mean reduction in triglycerides and an 85% reduction in acute pancreatitis events in a recent Phase III trial [6][15] - The severe hypertriglyceridemia (SHTG) market is estimated to have over three million affected individuals in the U.S., with a focus on high-risk patients [21][22] Market Data and Key Metrics Changes - The company is targeting high-risk patients with triglyceride levels above 880 mg/dL, which accounts for about one million individuals in the U.S. [22][24] - The competitive landscape includes drugs like Aerohaz, pravasiran, and GLP-1 analogs, with the company emphasizing its first-mover advantage and unprecedented efficacy [27][30] Company Strategy and Development Direction - The company plans to submit a supplemental NDA for olazarsen by the end of the year and aims to present full data at a medical congress [17][19] - The strategy includes focusing on high-risk patients and building a commercial team to support the launch of olazarsen [24][26] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the safety and efficacy of olazarsen, citing favorable results from previous studies [32] - The company anticipates a strong market reception for Donzara, with early feedback indicating positive sentiment from the HAE community [39][40] Other Important Information - The company is conducting the largest study ever in TTR cardiomyopathy, with results expected in the second half of next year [50][52] - The LP(a) study is also on track, with expectations for significant reductions in cardiovascular risk factors [55][56] Q&A Session Summary Question: What is the company's view on the commercial opportunity for olazarsen? - The company highlighted the significant unmet medical need in the SHTG market, with a focus on high-risk patients who have previously experienced acute pancreatitis [21][22] Question: How does the company plan to position itself against competitors? - The company emphasized its first-mover advantage and the unprecedented efficacy of olazarsen, setting a high bar for competitors [28][30] Question: What are the expectations for the launch of Donzara? - Management indicated that the launch is off to a strong start, with positive early feedback from the patient community and healthcare providers [39][40] Question: What is the anticipated market share for Donzara? - The company expects Donzara to be a $500 million plus drug, with a significant portion of patients switching from existing treatments [46] Question: How is the company preparing for the upcoming regulatory submissions? - The company is focused on gathering data and engaging with payers to demonstrate the value of olazarsen before announcing pricing [36][37]

Core Insights - Ionis Pharmaceuticals' shares surged 35% following positive results from late-stage studies CORE and CORE2 for its drug Tryngolza (olezarsen) targeting severe hypertriglyceridemia (sHTG) [1][12] - Both studies achieved their primary endpoint, demonstrating significant placebo-adjusted reductions in triglyceride (TG) levels [2][3] Study Results - At the 80 mg dose, Tryngolza resulted in TG reductions of 72% in CORE and 55% in CORE2 after six months; at the 50 mg dose, reductions were 63% in CORE and 49% in CORE2 [3] - The treatment also significantly reduced acute pancreatitis (AP) events by 85% compared to placebo over 12 months [5][12] Regulatory and Market Potential - Tryngolza was previously approved by the FDA for familial chylomicronemia syndrome (FCS), marking it as the first approved treatment for this condition [6] - Ionis plans to seek FDA label expansion for Tryngolza to include sHTG, targeting a much larger market of approximately 3 million affected individuals compared to 3,000 with FCS [10][8] Collaborations and Revenue Streams - Ionis has partnerships with major pharmaceutical companies like AstraZeneca, Biogen, GSK, and Novartis, providing funds through license fees and milestone payments [14] - The company earns commercial revenues from royalties on Spinraza, which treats spinal muscular atrophy, and is also involved in marketing Qalsody for amyotrophic lateral sclerosis [15] Future Developments - Ionis is expanding its portfolio with several wholly-owned candidates in late-stage studies, including drugs for Alexander's disease, ALS, and Angelman syndrome, with expected commercial launches in the next three years [19]

Core Viewpoint - The article discusses the challenges and findings related to the ASO drug BIIB078, developed for treating C9orf72-associated ALS (c9ALS), highlighting its distribution in the central nervous system (CNS) and the lack of clinical benefits despite its presence [4][8]. Group 1: Drug Development and Mechanism - C9orf72-associated ALS is caused by the expansion of the G4C2 repeat sequence in the first intron of the C9orf72 gene, leading to toxic RNA transcripts and dipeptide repeat proteins (DPR) [7]. - BIIB078 is an ASO drug targeting an 18-base pair sequence in the C9orf72 gene, aiming to degrade the toxic G4C2 repeat transcripts [3]. - Preclinical studies indicated that BIIB078 could silence the G4C2 repeat transcripts and reduce the burden of toxic DPR proteins [3]. Group 2: Clinical Trial Outcomes - Clinical trials of BIIB078 in c9ALS patients failed to meet any secondary endpoints and did not demonstrate clinical benefits, leading to the termination of its development in March 2022 [3]. - Despite widespread distribution in the CNS, BIIB078 did not effectively reduce toxic proteins or pathological changes, nor did it improve clinical outcomes [8]. Group 3: Research Findings - A recent study published in Cell analyzed the effects of BIIB078 on c9ALS patients, revealing that while the drug achieved extensive CNS distribution, it did not significantly reduce toxic protein levels or alter disease pathology [4][5]. - The study found an increase in inflammatory biomarkers, indicating a persistent immune response, and an unexpected interaction with the RNase T2 enzyme [8][14]. - The research provides critical insights into the drug's distribution, efficacy, and inflammatory response, which could guide future clinical trial designs [5][13].

PresentationAt this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.Good morning, and welcome to Ionis Conference Call to discuss Olezarsen CORE and CORE2 top line data. As a reminder, this call is being recorded.D. WalkeSenior Vice President of Investor Relations Thank you, Ludy, and thank you to everyone who has joined us today as we discuss the groundbreaking top line results from the landmark CORE and CORE2 studies o ...

Summary of Ionis Pharmaceuticals Conference Call on Olicerzine Results Company Overview - **Company**: Ionis Pharmaceuticals (IONS) - **Focus**: Development of olicerzine for severe hypertriglyceridemia (SHTG) and other lipid-related conditions Key Industry Insights - **SHTG**: Severe hypertriglyceridemia is characterized by fasting serum triglyceride levels ≥ 500 mg/dL, leading to increased risk of acute pancreatitis (AP) and associated complications - **Market Need**: Over 3 million people in the U.S. are affected by SHTG, with more than 1 million at high risk for AP due to triglyceride levels above 880 mg/dL or a history of pancreatitis [12][13] Core Study Results - **Olicerzine (Olazarsen)**: Demonstrated significant efficacy in reducing triglyceride levels and AP events - **Primary Endpoint**: - CORE study: 63% reduction in fasting triglycerides with 50 mg dose, 73% with 80 mg dose (placebo-adjusted) [19] - CORE II study: 63% reduction with 50 mg, 88% with 80 mg (placebo-adjusted) [20] - **Acute Pancreatitis Events**: Achieved an 85% reduction in adjudicated AP events across both studies [21] Safety and Tolerability - **Safety Profile**: Favorable safety and tolerability observed, with adverse events balanced across treatment groups; injection site reactions were the most common [22] Commercial Strategy - **Launch Plans**: - Anticipated launch in the U.S. in the second half of next year, with preparations already underway [30] - Focus on high-risk SHTG patients, particularly those with triglycerides > 880 mg/dL or a history of pancreatitis [29] - **Sales Force Expansion**: Plans to scale the sales organization to reach approximately 20,000 healthcare providers (HCPs) specializing in cardiology, endocrinology, and lipidology [94] Regulatory and Market Potential - **Regulatory Filings**: Supplemental NDA submission planned by year-end for SHTG indication, with additional global filings expected next year [30] - **Market Opportunity**: Potential for olazarsen to become a blockbuster drug, addressing a significant unmet need in the SHTG patient population [83] Financial Considerations - **Pricing Strategy**: Pricing to be announced upon approval, reflecting the value of olazarsen in reducing triglycerides and AP events [39] - **Comparison to Competitors**: Olazarsen is expected to outperform existing treatments like Vascepa, which has shown modest triglyceride reduction and no proven benefit in reducing AP [84] Additional Insights - **Patient Population**: Approximately 60,000 patients in the U.S. have triglyceride levels > 500 mg/dL with a history of AP, representing a critical target market [102] - **Future Studies**: Full data from CORE and CORE II studies to be presented at a medical congress later this year, including detailed analysis of secondary endpoints [30][101] This summary encapsulates the key points discussed during the conference call regarding Ionis Pharmaceuticals' advancements with olicerzine, its market potential, and the strategic direction for addressing the needs of patients with severe hypertriglyceridemia.

Group 1 - The article promotes a weekly newsletter focused on stocks in the biotech, pharma, and healthcare industries, aimed at both novice and experienced investors [1] - The newsletter provides insights on key trends, catalysts driving valuations, product sales forecasts, and integrated financial statements for major pharmaceutical companies [1] - The author, Edmund Ingham, has over 5 years of experience in covering biotech, healthcare, and pharma, and has prepared detailed reports on more than 1,000 companies [1]

Summary of Ionis Pharmaceuticals Conference Call Company and Industry Overview - **Company**: Ionis Pharmaceuticals (IONS) - **Industry**: Biotechnology, specifically focusing on RNA-targeted therapies for rare diseases, including hereditary angioedema (HAE) Key Points and Arguments 1. **FDA Approval of Donzara**: Ionis announced the FDA approval of Donzara for preventing attacks of hereditary angioedema in patients aged 12 and older, marking a significant milestone for the company and patients [4][2][10] 2. **Unique Treatment Profile**: Donzara is the first and only RNA-targeted therapy for HAE, offering strong efficacy, long-term durability, and the longest dosing interval of every eight weeks using a low-volume auto-injector [4][7][18] 3. **Market Potential**: The approval of Donzara is expected to contribute to a multi-billion dollar revenue potential for Ionis, with plans for additional launches in the coming year [6][36] 4. **Clinical Data**: Clinical trials demonstrated a 94% mean reduction in HAE attack rates for patients treated with Donzara for one year, showcasing its effectiveness compared to prior treatments [15][24] 5. **Patient Preferences**: 84% of patients surveyed preferred Donzara over their previous prophylactic treatment, indicating strong market demand for the new therapy [27][22] 6. **Launch Strategy**: Ionis has a dedicated sales force of approximately 70 members targeting about 1,000 prescribers who treat 90% of HAE patients, ensuring efficient market penetration [72][19] 7. **Pricing Strategy**: Donzara is priced at $57,462 per dose, which is competitive with existing therapies in the HAE market. The annualized cost for patients on a four-week dosing schedule is approximately $747,000 [31][40] 8. **Patient Support Programs**: Ionis has established financial assistance and reimbursement support programs to ensure patient access to Donzara, including a free trial program for new patients [30][31] 9. **Future Developments**: Ionis is also pursuing regulatory approval for Donzara in Europe and has additional therapies in the pipeline, including treatments for severe hypertriglyceridemia and Alexander disease [34][36] Additional Important Content 1. **Unmet Needs in HAE Treatment**: Despite existing treatments, many patients are dissatisfied, with up to 20% switching therapies annually, highlighting the demand for new options [21][22] 2. **Safety Profile**: Donzara has a favorable long-term safety and tolerability profile, which is crucial for patient acceptance and adherence [18][24] 3. **Market Dynamics**: The U.S. HAE market is characterized as a switch market, with many patients likely to transition from existing therapies to Donzara due to its compelling profile [60][70] 4. **Educational Efforts**: Ionis is focused on educating healthcare providers about Donzara's benefits and the switch data to facilitate patient transitions from other therapies [88][102] This summary encapsulates the critical aspects of Ionis Pharmaceuticals' conference call regarding the launch of Donzara, its market strategy, and the anticipated impact on patients and the company.

DAW N Z E R AT M F DA A P P R OVA L N a s d a q : I O N S August 2025 Forward-Looking Statements This presentation includes forward-looking statements regarding the therapeutic and commercial potential of DAWNZERA (donidalorsen), Ionis' technologies, and Ionis' other products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to cer ...

Core Viewpoint - Ionis Pharmaceuticals has gained market attention due to its strong Q2 performance, leading to an upgrade in stock rating by Morgan Stanley to "Buy" with a target price of $62, indicating a potential upside of approximately 45% [1][3]. Financial Performance - In Q2, Ionis reported total revenue of $452 million, a significant year-over-year increase of 100.8%, and earnings per share of $0.70, reversing from a loss of $0.45 per share in the same period last year [1][5]. - The company expects full-year revenue growth of 17%-20%, reaching between $825 million and $850 million, while analysts predict revenue of $869.6 million for the year [5][7]. Product Highlights - The successful launch of Tryngolza, a treatment for a rare genetic disorder, was a key highlight in the Q2 report, achieving net product sales of $19 million in its second full quarter [3][4]. - Approximately 60% of patients using Tryngolza have commercial insurance, and over 90% of patients do not incur out-of-pocket costs, contributing to its commercial success [3][4]. Pipeline and Future Catalysts - Ionis has a robust late-stage pipeline with several drugs in clinical phases 2-3, including Donidalorsen, which is expected to be approved for hereditary angioedema treatment [4][5]. - Upcoming catalysts include the anticipated results from the Phase 3 trial for severe hypertriglyceridemia (SHTG) expected in 2026, and the release of top-line data for the SHTG trial in September [3][4]. Analyst Sentiment - Other analysts, including those from Oppenheimer and Wells Fargo, maintain "Buy" ratings on Ionis stock, with target prices ranging from $65 to $77, reflecting confidence in the company's growth trajectory and strategic execution [7][8]. - Among 23 analysts covering the stock, 15 have a "Strong Buy" rating, indicating strong market confidence in Ionis's future performance [7][8].