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]

Summary of Ionis Pharmaceuticals (IONS) 2025 Conference Call Company Overview - **Company**: Ionis Pharmaceuticals (IONS) - **Event**: 2025 Global Health Care Conference - **Date**: May 21, 2025 Key Points Industry and Company Progress - Ionis has made significant progress over the past year, achieving several important drug approvals and launches, including **Trungolza** for Familial Chylomicronemia Syndrome (FCS) [4][5] - The company is transitioning into a fully integrated commercial-stage biotech firm, with a pipeline that shows potential for substantial revenue growth [4][5] Drug Approvals and Pipeline - **Trungolza** is the first FDA-approved treatment for FCS, generating over **$6 million** in net revenue in Q1, exceeding expectations [8][9] - Upcoming approval for **Donna DeLorsen**, a prophylactic treatment for hereditary angioedema, expected in the second half of 2025 [5][48] - The wholly owned pipeline is projected to offer multibillion-dollar revenue potential, with several anticipated phase three readouts and commercial launches [5][6] Market Position and Competition - Ionis emphasizes its first-mover advantage with **Trungolza**, which has a strong efficacy and safety profile, and is positioned well against competitors [12][14] - The company is focused on the larger indications of hypertriglyceridemia, with positive phase three data supporting its market position [15][20] Clinical Data and Efficacy - The **ESSENCE phase three study** showed over **60% reductions** in triglycerides for patients with severe hypertriglyceridemia, indicating strong efficacy [21][22] - The company is optimistic about the upcoming phase three readouts for SHTG (severe hypertriglyceridemia) and anticipates significant market uptake based on the data [22][24] Financial Outlook - Ionis expects to achieve positive cash flow in the near term, with operating losses projected in the mid to high single digits for the year [5][55] - The company has upgraded its revenue guidance by **20%**, anticipating strong revenue growth and maintaining a cash position of **$1.9 billion** by year-end [55] Strategic Considerations - The company is strategically positioned to leverage the convenience of self-administration for its drugs, which is expected to drive market share in the TTR (transthyretin) amyloidosis space [40][41] - Ionis is focused on patient convenience and efficacy, which are critical in a competitive landscape where existing treatments have significant unmet needs [50][51] Upcoming Events - The PDUFA date for **Donna DeLorsen** is set for **August 21, 2025**, with expectations for a successful launch in the second half of the year [48][52] Conclusion - Ionis Pharmaceuticals is on a strong growth trajectory with a robust pipeline, strategic market positioning, and a focus on innovative treatments that address significant unmet medical needs in the biotech industry [5][6][55]

Core Insights - Ionis Pharmaceuticals announced positive top-line results from the phase III ESSENCE study for its drug Tryngolza, targeting moderate hypertriglyceridemia in patients at risk for atherosclerotic cardiovascular disease (ASCVD) [1][2] - The study achieved its primary endpoint, showing a statistically significant reduction in triglyceride (TG) levels, with reductions of 61% and 58% for 80 mg and 50 mg monthly doses, respectively [2] - A majority of participants in the study had their TG levels fall within the normal range (<150 mg/dL) post-treatment, and the drug met all key secondary endpoints [3] Recent Developments - Tryngolza received FDA approval for treating familial chylomicronemia syndrome (FCS), marking it as the first approved treatment for this rare genetic condition in the U.S. and Ionis' first independent commercial launch [4] - Ionis out-licensed ex-U.S. rights for Tryngolza to Sweden-based Sobi, which will handle future regulatory filings and commercialization outside the U.S. [5] - The drug is also being evaluated for severe hypertriglyceridemia (sHTG) in two late-stage studies, with data expected in Q3 2025 [6][7] Financial and Revenue Streams - Ionis has a diverse revenue stream through collaborations with major pharmaceutical companies like AstraZeneca, Biogen, GSK, and Novartis, providing funds for its development pipeline [10] - 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 [11] - Recent approvals for drugs like Wainua and ongoing studies for other candidates could further enhance Ionis' revenue and reduce reliance on collaboration partners [12][14]

Summary of Ionis Pharmaceuticals Conference Call Company Overview - **Company**: Ionis Pharmaceuticals - **Industry**: Biotechnology, specifically RNA-targeted therapies Key Points and Arguments 1. **Recent Successes**: Ionis has achieved significant milestones, including a successful independent launch of Tringolza for familial chylomicronemia syndrome (FCS), marking its evolution into a fully integrated biotech company [4][6] 2. **Upcoming Launches**: The company anticipates the approval of Doloresin for hereditary angioedema by August 21, with additional phase three data expected for other programs [5][6] 3. **Pipeline Growth**: Ionis has a robust pipeline with four phase three readouts and launches expected over the next three years, which is projected to lead to substantial revenue growth and positive cash flow [6][7] 4. **Market Dynamics**: The launch of Tringolza is seen as a critical step in building a market for SHTG (severe hypertriglyceridemia), with a focus on patient identification and education to increase awareness of treatment options [8][20] 5. **Patient Population**: There are approximately 3,000 patients with FCS in the U.S., many of whom remain undiagnosed. Ionis is working to identify these patients through both genetic and clinical diagnosis [20][22] 6. **Epidemiology and Treatment Pool**: The treatment pool for FCS overlaps with that of severe hypertriglyceridemia, and there is a need for increased awareness among healthcare providers (HCPs) regarding treatment options [12][14] 7. **Clinical Data Expectations**: The company expects to report significant reductions in triglyceride levels, with placebo-adjusted reductions anticipated to be around 50%, which would significantly lower the risk of acute pancreatitis [29][31] 8. **Global Market Strategy**: Ionis is preparing for European approval of Tringolza, expecting similar prevalence and uptake as in the U.S., but with potentially stricter payer requirements [21][23] 9. **Pricing Strategy**: The anticipated pricing for SHTG treatment is tentatively set between $50,000 to $20,000, reflecting the need for a more accessible pricing model compared to ultra-rare disease treatments [47] 10. **Partnerships and Collaborations**: Ionis is collaborating with Novartis on a phase three trial for pelicarcin, targeting lipoprotein(a) as a cardiovascular risk factor, with promising interim results [49][51] Additional Important Content 1. **Healthcare Provider Engagement**: Ionis is actively engaging with HCPs to educate them about the importance of managing triglyceride levels to prevent acute pancreatitis, which is a significant motivator for treatment adoption [34][35] 2. **Regulatory Considerations**: The company is aware of the differing regulatory environments in the U.S. and Europe, particularly regarding payer requirements for acute pancreatitis data [48][49] 3. **Market Segmentation**: The initial focus will be on patients with triglyceride levels above 500 mg/dL and a history of acute pancreatitis, with plans to broaden the market through HCP education [43][44] 4. **Clinical Trial Design**: The design of the clinical trials is aimed at maximizing data collection on safety and efficacy, particularly concerning acute pancreatitis events [39][40] This summary encapsulates the key insights from the Ionis Pharmaceuticals conference call, highlighting the company's strategic direction, product pipeline, and market opportunities within the biotechnology sector.

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

Financial Performance - Total revenue for Q1 2025 was $131.6 million, an increase from $119.5 million in Q1 2024, representing a growth of approximately 17.6%[116] - Total operating expenses for Q1 2025 were $278.5 million, compared to $269.0 million in Q1 2024, reflecting an increase of about 3.9%[116] - The net loss for Q1 2025 was $146.9 million, slightly higher than the net loss of $142.8 million in Q1 2024[116] - Total revenue for Q1 2025 was $131.6 million, a 10.5% increase from $119.5 million in Q1 2024[117] - Commercial revenue increased by 28% year-over-year, driven by U.S. product sales from the launch of TRYNGOLZA and higher royalties from SPINRAZA and WAINUA[117] - Total royalty revenue rose to $64.2 million in Q1 2025 from $49.4 million in Q1 2024, with SPINRAZA royalties increasing from $38.5 million to $48.0 million[117] - The company reported a net loss of $146.9 million for Q1 2025, compared to a net loss of $142.8 million in Q1 2024, with net loss per share of $0.93[147] - Investment income decreased to $24.7 million in Q1 2025 from $26.3 million in Q1 2024, primarily due to lower interest rates[141] - Working capital decreased from December 31, 2024, to March 31, 2025, as cash and short-term investments declined[150] - The company recorded a net loss on investments of $2.2 million in Q1 2025, compared to a net gain of $2.3 million in Q1 2024[144] Research and Development - TRYNGOLZA is the first FDA-approved treatment for familial chylomicronemia syndrome, significantly reducing triglyceride levels and acute pancreatitis events[100] - Donidalorsen is under regulatory review in the U.S. with a PDUFA action date of August 21, 2025, following positive Phase 2 and Phase 3 results[107] - Zilganersen completed enrollment in its Phase 3 study for Alexander disease in July 2024 and received Fast Track designation from the FDA[108] - ION582 is set to advance into Phase 3 development in Q2 2025 based on positive results from its Phase 1/2 study[109] - The company is positioned for multiple independent launches in the next two years, including donidalorsen and olezarsen for severe hypertriglyceridemia[98] Expenses - Operating expenses, excluding non-cash compensation, increased to $248.8 million in Q1 2025 from $237.7 million in Q1 2024[122] - Total research and development expenses decreased to $200.8 million in Q1 2025 from $214.2 million in Q1 2024, reflecting the end of several late-stage studies[128] - Medical affairs expenses increased to $5.9 million in Q1 2025 from $5.6 million in Q1 2024, as the company advanced its late-stage pipeline[134] - Manufacturing and development chemistry expenses rose to $16.4 million in Q1 2025 from $13.7 million in Q1 2024, attributed to the timing of manufacturing for late-stage programs[136] - Total drug development expenses, excluding non-cash compensation, decreased to $112.9 million in Q1 2025 from $125.8 million in Q1 2024[131] - SG&A expenses for Q1 2025 totaled $76.3 million, up from $52.6 million in Q1 2024, reflecting a 45% increase due to new product launches[140] - The company expects operating expenses to continue to rise in 2025 as commercialization activities advance[122] Collaborations and Partnerships - WAINUA has generated over $545 million in revenues since inception, including approximately $30 million in royalties[101] - SPINRAZA has earned more than $2.3 billion in revenues, with over $1.9 billion in royalties from its collaboration with Biogen[102] - The WAINUA collaboration with AstraZeneca involves AstraZeneca covering 55% of the costs for the ongoing Phase 3 development program[119] Debt and Financial Obligations - Total interest expense for Q1 2025 was $4.1 million, slightly down from $4.2 million in Q1 2024[142] - Interest expense related to the sale of future royalties was $18.8 million in Q1 2025, compared to $18.0 million in Q1 2024[143] - The company has raised approximately $2.6 billion from equity securities and $2.7 billion from long-term debt since inception[148] - Contractual obligations as of March 31, 2025, totaled $1.5 billion, with $31.6 million due within one year[151]

Q1:2025 Business Update and Financial Results April 30, 2025 Nasdaq: IONS 1 On Today's Earnings Call Richard Geary, Ph.D. Chief Development Officer Eugene Schneider, M.D. Chief Clinical Development Officer 2 Eric Swayze, Ph.D. Executive Vice President, Research Brett Monia, Ph.D. Chief Executive Officer Kyle Jenne Chief Global Product Strategy Officer Beth Hougen Chief Financial Officer Jonathan Birchall Chief Commercial Officer Forward-Looking Statements This presentation includes forward-looking statement ...

Core Insights - Ionis Pharmaceuticals reported a first-quarter EPS loss of 93 cents, an improvement from a loss of 98 cents, and better than the consensus estimate of a $1.12 loss [1] - Revenue for the first quarter of 2025 increased by 10% to $132 million, surpassing the consensus of $125.32 million, driven by higher commercial revenue [1] Financial Guidance - The company raised its 2025 revenue guidance by over 20% to a range of $725-$750 million, compared to previous guidance of over $600 million and the consensus of $659.37 million [4] - Ionis expects a 2025 adjusted operating loss of less than $375 million, improved from prior guidance of less than $495 million, with cash and equivalents projected at approximately $1.9 billion [4] Product Performance - The drug Tryngolza (olezarsen) generated over $6 million in net product sales in its first full quarter post-approval in the U.S. [6] - Wainua (eplontersen) for polyneuropathy generated $39 million in sales, resulting in $9 million in royalty revenue for the first quarter of 2025 [6] - Spinraza (nusinersen) for spinal muscular atrophy achieved global sales of $424 million, leading to $48 million in royalty revenue in the first quarter of 2025 [6]

Financial Data and Key Metrics Changes - Ionis Pharmaceuticals increased its 2025 financial guidance across all metrics, raising revenue expectations by more than 20% due to strong Q1 results and successful licensing transactions [31][36] - The company reported $132 million in revenue for Q1 2025, a 10% year-over-year increase, with over half of the revenue coming from commercial products, which grew 28% compared to the same period last year [31][34] - Non-GAAP operating expenses increased by less than 5%, reflecting disciplined investment and driving operating leverage [34][39] Business Line Data and Key Metrics Changes - The launch of TrINGOLZA generated over $6 million in product sales in its first full quarter, exceeding expectations [32][33] - SPINRAZA royalties contributed $48 million, a 25% year-over-year increase, while Waynua royalties amounted to $9 million, with expectations for growth driven by strong US demand [33][34] - The company is on track to add initial product revenue from the upcoming launch of Donadolorsen, with an FDA action date set for August 21 [37][38] Market Data and Key Metrics Changes - The initial prescriber mix for TrINGOLZA included approximately 50% cardiologists and 25% endocrinologists, with positive feedback from physicians regarding patient outcomes [15][14] - The company is focusing on patient finding efforts and healthcare provider education to increase awareness of familial chylomicronemia syndrome (FCS) and hereditary angioedema (HAE) [18][27] Company Strategy and Development Direction - Ionis is focused on executing strategic priorities, including multiple independent launches and expanding its pipeline of transformational medicines [7][11] - The company aims to leverage its first independent launch to build momentum for future launches, including Donadolorsen and olazarcen, which are expected to address significant unmet medical needs [10][12] - Ionis is committed to driving long-term value for shareholders through sustained revenue growth and positive cash flow [41][44] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the rapidly evolving environment, including changes at the FDA and new tariff policies, which introduce uncertainty but do not currently impact the business [6][62] - The company expressed confidence in its ability to deliver transformational medicines and achieve substantial revenue growth despite external challenges [9][41] - Ionis expects to generate over $3 billion in peak annual product sales from its owned medicines and over $2 billion from partnered medicines, positioning the company for significant top-line growth [40][41] Other Important Information - Ionis completed licensing transactions for sapaglutzin and ex-US commercialization rights for olazarcen, enhancing its financial outlook and enabling a focus on independent launches [36][38] - The company is actively engaging with payers to ensure broad access for patients and is monitoring the impact of tariffs on its operations [16][62] Q&A Session Summary Question: Overlap between physician prescribers for FCS and SHTG - Management indicated significant overlap among prescribers, with cardiologists and endocrinologists treating both FCS and SHTG patients, which presents an opportunity for growth [46][49] Question: Confidence in FCS patient estimates and conversion to commercial therapy - Management expressed confidence in the estimate of over 3,000 FCS patients and noted that awareness efforts are expected to drive patient identification and conversion to commercial therapy [67][70] Question: Impact of Medicare Part D redesign on uptake - Management highlighted that the redesign is expected to increase patient starts and compliance due to reduced out-of-pocket costs, positively impacting revenue growth [95] Question: Channel stocking for TrINGOLZA - Management confirmed that TrINGOLZA sales are demand-driven with no significant channel stocking, ensuring inventory levels are managed effectively [75][78] Question: Manufacturing footprint and exposure to tariffs - Management stated that the company has a robust manufacturing supply chain in place and has not experienced any meaningful impacts from tariffs to date [80][81]