Core Viewpoint - Ionis Pharmaceuticals and Biogen have decided to terminate the development of their investigational ALS drug, BIIB105 / ION541, due to failure to show efficacy in slowing disease progression as indicated by the ALSpire study results [1][2]. Group 1: Drug Development and Study Results - The decision to halt BIIB105's development was based on topline data from the phase I/II ALSpire study, which showed no reduction in plasma neurofilament light chain (NfL) levels in ALS patients after six months of treatment [2]. - Patients treated with BIIB105 did not show improvements in clinical outcome measures related to function, breathing, and strength [2]. - Ionis intends to advance ION582, an experimental drug for Angelman Syndrome, independently after Biogen opted out of licensing rights for this drug [3][6]. Group 2: Market Performance and Company Impact - Following the announcement, shares of Ionis Pharmaceuticals and Biogen fell by at least 2% in market capitalization [1]. - Year-to-date, Biogen's shares have decreased by 11.1%, while Ionis has seen a more significant decline of 25.6% [3][6]. - Despite the setbacks, Ionis reported positive topline results from the HALOS study for ION582, indicating safety and improvements in cognitive, communication, and motor functions [5][6]. Group 3: Ongoing Collaborations and Future Prospects - Biogen and Ionis have a long-standing partnership that has previously yielded successful drugs like Spinraza and Qalsody for treating ALS [7][8]. - Both companies continue to develop investigational medicines for neurodegenerative diseases, including Alzheimer's and Parkinson's [8].

Core Insights - Ionis Pharmaceuticals announced positive topline data from the HALOS Phase 1/2a study of ION582 for Angelman syndrome, showing safety, tolerability, and significant functional improvements in cognition, communication, and motor function [1][2][5] Company Developments - Ionis will independently advance ION582 and plans to discuss the Phase 1/2a results with regulatory authorities to design a pivotal program [2][4] - Biogen has chosen not to exercise its option to license ION582, allowing Ionis to retain full control over the drug's development [2] Clinical Study Details - The HALOS trial included a three-month multiple-ascending dose study with 51 patients aged 2-50, followed by a long-term extension evaluating higher doses for an additional 12 months [4][8] - Topline results indicated that approximately 65% of patients showed cognitive improvements on the Bayley-4 assessment at six months, with similar improvements in communication and motor skills [6][14] Safety and Efficacy - ION582 was found to be safe and well tolerated across all dose levels, with adverse events consistent with patient medical histories [6][8] - The study demonstrated consistent improvements across various measures, including the Bayley-4 and SAS-CGI-C scales, correlating with positive changes in EEG activity [6][14] Future Plans - Detailed results from the HALOS study are expected to be presented at the upcoming Angelman Syndrome Foundation meeting in July [8] - Ionis is committed to advancing ION582 into a pivotal study, aiming to address the significant unmet need for therapies in Angelman syndrome [4][8]

CARLSBAD, Calif., May 15, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced that management will conduct its 2024 virtual Annual Meeting of Stockholders followed by a general corporate update on Thursday, June 6, 2024. The agenda for the event is as follows: About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, c ...

Ionis Pharmaceuticals (IONS) reported a loss of 98 cents per share for first-quarter 2024, which was narrower than the Zacks Consensus Estimate of a loss of $1.10 per share.The bottom line includes compensation expenses related to equity awards. Excluding these special items, adjusted loss per share was 77 cents against a loss of 68 cents per share in the year-ago quarter.Total revenues were $119 million in the first quarter, missing the Zacks Consensus Estimate of $131.5 million. Revenues declined 1.2% yea ...

Financial Data and Key Metrics Changes - The company reported revenues of $119 million in Q1 2024, with half derived from commercial products, primarily SPINRAZA royalties, and the other half from R&D collaborations [9][10] - Cash and investments at the end of Q1 2024 stood at $2.2 billion, with expectations to end the year with $1.7 billion [5][10] - Operating expenses are projected to increase in the mid to high single-digit percent range compared to 2023, driven primarily by SG&A expenses [10][23] Business Line Data and Key Metrics Changes - The company is preparing for the launch of olezarsen for FCS and SHTG, with positive Phase 3 results indicating substantial triglyceride reductions and a favorable safety profile [21][68] - Donidalorsen is positioned as a next planned launch for HAE, with positive Phase 3 data showing significant reductions in HAE attack rates [77][80] - The WAINUA launch is tracking well, with good uptake among patients and a focus on building a field team to support prescribers [79][80] Market Data and Key Metrics Changes - The market for olezarsen includes over 3 million estimated patients in the US for SHTG, while FCS has a smaller patient population of approximately 20,000 [68] - The company is targeting a concentrated base of treating physicians for HAE, primarily located in large centers of excellence [71] Company Strategy and Development Direction - The company aims to build meaningful relationships with patients and healthcare professionals through an omnichannel strategy, enhancing access to treating physicians [4] - There is a focus on advancing a rich pipeline, with plans to have six wholly owned neurology medicines in clinical development by the end of the year [7][11] - The company is investing in commercial capabilities to support upcoming launches and is leveraging experience gained from the WAINUA launch [23][70] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving a steady cadence of new medicines and emphasized the importance of recent positive data readouts [11][21] - The company anticipates modest revenue growth in subsequent quarters based on regulatory milestones and increased royalty revenues from WAINUA [10][11] - Management highlighted the potential for olezarsen and donidalorsen to address significant unmet needs in their respective markets [21][71] Other Important Information - The company has initiated an expanded access program for olezarsen in the US, allowing patients to access treatment ahead of potential approval [21][71] - The SWITCH study for donidalorsen is the first of its kind, evaluating patient transitions from existing prophylactic treatments [15][20] Q&A Session Summary Question: When will the review timeline for olezarsen be confirmed? - The company expects to hear from the FDA approximately 60 days after submission, which was made in April [13] Question: What are the commercial launch preparations for olezarsen? - The team size for the launch is expected to be competitive, with plans to leverage existing infrastructure from WAINUA [14] Question: What is the timeline for achieving sustained positive cash flow? - Management indicated that the timeline for achieving sustained positive cash flow is being closely monitored, with ongoing investments in key areas [16] Question: What data will be important for the commercial uptake of donidalorsen? - Key data will include patient preferences and efficacy compared to existing treatments, which will be critical for the launch [39] Question: How does the company view the competitive landscape for TTR cardiomyopathy? - Management expressed confidence in their trial design and the robustness of their data compared to competitors [50][52]

PART I FINANCIAL INFORMATION [Financial Statements](index=5&type=section&id=ITEM%201%3A%20Financial%20Statements) This section presents the unaudited condensed consolidated financial statements for Q1 2024 vs. Q1 2023, including balance sheets, operations, and cash flows with detailed notes Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2024 | December 31, 2023 | | :--- | :--- | :--- | | **Total Assets** | **$2,763,928** | **$2,990,072** | | Cash and cash equivalents | $348,889 | $399,266 | | Short-term investments | $1,857,327 | $1,931,935 | | **Total Liabilities** | **$2,467,413** | **$2,603,386** | | **Total Stockholders' Equity** | **$296,515** | **$386,686** | Condensed Consolidated Statement of Operations Highlights (in thousands, except per share data) | Metric | Q1 2024 | Q1 2023 | | :--- | :--- | :--- | | Total Revenue | $119,497 | $130,524 | | Total Operating Expenses | $269,010 | $244,672 | | Loss from Operations | $(149,513) | $(114,148) | | **Net Loss** | **$(142,803)** | **$(124,323)** | | **Net Loss Per Share (Basic & Diluted)** | **$(0.98)** | **$(0.87)** | Condensed Consolidated Statement of Cash Flows Highlights (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2024 | | :--- | :--- | | Net cash used in operating activities | $(149,938) | | Net cash provided by investing activities | $76,105 | | Net cash provided by financing activities | $23,570 | | **Net decrease in cash and cash equivalents** | **$(50,377)** | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes provide detailed explanations of the company's accounting policies and specific financial statement items, covering revenue recognition, collaborative arrangements, investments, and convertible debt Revenue Breakdown (in thousands) | Revenue Category | Q1 2024 | Q1 2023 | | :--- | :--- | :--- | | **Commercial Revenue** | **$59,593** | **$67,768** | | SPINRAZA royalties | $38,455 | $50,247 | | WAINUA royalties | $1,125 | $— | | Other commercial revenue | $20,013 | $17,521 | | **R&D Revenue** | **$59,904** | **$62,756** | | Collaborative agreement revenue | $49,345 | $38,334 | | WAINUA joint development revenue | $10,559 | $24,422 | | **Total Revenue** | **$119,497** | **$130,524** | - Revenue from the Biogen relationship was **$59.2 million** (50% of total revenue) in Q1 2024, down from **$70.5 million** (54% of total) in Q1 2023[50](index=50&type=chunk)[52](index=52&type=chunk) - The liability related to the sale of future royalties to Royalty Pharma increased to **$525.1 million** as of March 31, 2024, with an estimated effective interest rate of **13.5%**[74](index=74&type=chunk)[75](index=75&type=chunk) - As of March 31, 2024, outstanding principal balances included **$575.0 million** (1.75% Notes due 2028), **$632.5 million** (0% Notes due 2026), and **$44.5 million** (0.125% Notes due 2024)[77](index=77&type=chunk)[80](index=80&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=23&type=section&id=ITEM%202%3A%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on the company's financial condition and operational results, including business overview, critical accounting estimates, and liquidity - The company has five marketed medicines: SPINRAZA, QALSODY, WAINUA, TEGSEDI, and WAYLIVRA, with WAINUA launched in the U.S. in January 2024 for ATTRv-PN[89](index=89&type=chunk)[93](index=93&type=chunk) - The pipeline includes nine medicines in Phase 3 development for eleven indications, with key programs like olezarsen for FCS and sHTG, and donidalorsen for HAE[89](index=89&type=chunk)[96](index=96&type=chunk) - As of March 31, 2024, the company had cash, cash equivalents, and short-term investments totaling **$2.2 billion**[209](index=209&type=chunk) [Results of Operations](index=25&type=section&id=Results%20of%20Operations) This subsection details financial performance for Q1 2024 vs. Q1 2023, showing decreased total revenue and increased operating expenses from R&D and SG&A - The year-over-year decrease in total revenue was primarily due to lower SPINRAZA royalties (**$38.5 million** vs **$50.2 million**) and declining WAINUA joint development revenue, partially offset by new WAINUA royalties and increased amortization[109](index=109&type=chunk)[110](index=110&type=chunk) Operating Expenses (in millions) | Expense Category | Q1 2024 | Q1 2023 | | :--- | :--- | :--- | | Research, development and patent | $214.2 | $197.8 | | Selling, general and administrative | $52.6 | $45.5 | | Cost of sales | $2.2 | $1.3 | | **Total Operating Expenses** | **$269.0** | **$244.7** | - SG&A expenses increased primarily due to the U.S. launch of WAINUA and launch preparation activities for olezarsen and donidalorsen, while R&D expenses rose due to the timing of late-stage program activities[114](index=114&type=chunk) [Liquidity and Capital Resources](index=31&type=section&id=Liquidity%20and%20Capital%20Resources) This part discusses the company's funding sources, working capital, and contractual obligations, noting historical financing through collaborative agreements, product revenues, and equity/debt sales - The company has financed operations primarily through collaborative R&D agreements, product revenues, equity sales (approx. **$2.1 billion** net proceeds since inception), debt issuance (approx. **$2.7 billion**), and a **$0.5 billion** sale of future royalties[139](index=139&type=chunk) Contractual Obligations as of March 31, 2024 (in millions) | Obligation | Total | Due in < 1 year | Due in > 1 year | | :--- | :--- | :--- | :--- | | 1.75% Notes | $620.3 | $10.1 | $610.2 | | 0% Notes | $632.5 | $— | $632.5 | | 0.125% Notes | $44.6 | $44.6 | $— | | Operating leases | $274.9 | $20.6 | $254.3 | | **Total (selected)** | **$1,583.1** | **$75.9** | **$1,507.2** | [Quantitative and Qualitative Disclosures about Market Risk](index=33&type=section&id=ITEM%203%3A%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) The company discloses its exposure to market risks, primarily interest rate risk from investments and foreign currency exchange rate risk, which are deemed immaterial - The company's primary market risk exposures are to changes in interest rates on its short-term investments and foreign currency exchange rates[147](index=147&type=chunk)[148](index=148&type=chunk) - A hypothetical **10 percent** change in foreign exchange rates during the presented periods would not have had a material impact on the condensed consolidated financial statements[148](index=148&type=chunk) [Controls and Procedures](index=33&type=section&id=ITEM%204%3A%20Controls%20and%20Procedures) Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were effective as of March 31, 2024 - Based on an evaluation, the Chief Executive Officer and Chief Financial Officer concluded that the company's disclosure controls and procedures were effective as of March 31, 2024[150](index=150&type=chunk) - No changes in internal controls over financial reporting were identified during the latest fiscal quarter that have materially affected, or are reasonably likely to materially affect, these controls[151](index=151&type=chunk) PART II OTHER INFORMATION [Legal Proceedings](index=33&type=section&id=ITEM%201%3A%20Legal%20Proceedings) The company states that there are no pending material legal proceedings to which it is a party or of which its property is the subject - There are no pending material legal proceedings to which the company is a party[84](index=84&type=chunk)[152](index=152&type=chunk) [Risk Factors](index=33&type=section&id=ITEM%201A%3A%20Risk%20Factors) This section details significant risks and uncertainties that could adversely affect the company's business, financial condition, and results of operations - Key risks include the company's limited experience in commercializing medicines, reliance on third parties, and the need for market acceptance and adequate reimbursement for its products[156](index=156&type=chunk)[158](index=158&type=chunk)[164](index=164&type=chunk) - SPINRAZA faces significant competition from onasemnogene abeparvovec and risdiplam, which has previously led to decreased revenue for the product[173](index=173&type=chunk)[175](index=175&type=chunk) - The company is heavily dependent on its collaborations with partners like Biogen (for SPINRAZA and QALSODY) and AstraZeneca (for WAINUA) for development, funding, and commercialization[181](index=181&type=chunk)[184](index=184&type=chunk) - The business has a history of losses, with an accumulated deficit of approximately **$1.9 billion** as of March 31, 2024, and future profitability is not guaranteed[211](index=211&type=chunk) [Other Information](index=53&type=section&id=ITEM%205%3A%20Other%20Information) This section discloses the adoption or termination of Rule 10b5-1 trading plans by the company's Section 16 officers and directors during the quarter - Several officers and directors, including B. Lynne Parshall, Joseph Klein, III, Joseph Baroldi, Eugene Schneider, Elizabeth Hougen, and Patrick O'Neil, adopted or terminated Rule 10b5-1 trading plans during Q1 2024[254](index=254&type=chunk) [Exhibits](index=54&type=section&id=ITEM%206%3A%20Exhibits) This item lists the exhibits filed with the Form 10-Q, including an advisory services agreement, CEO/CFO certifications, and iXBRL financial statements - Exhibits filed with the report include an Advisory Services Agreement, certifications by the CEO and CFO pursuant to the Securities Exchange Act, and iXBRL data files[255](index=255&type=chunk)

CARLSBAD, Calif., May 7, 2024 – Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), today reported financial results for the first quarter ended March 31, 2024. "Ionis is off to a great start in 2024, as we continue to execute on our vision to bring better futures to people with serious diseases. The WAINUA launch for hereditary ATTR polyneuropathy is progressing well with AstraZeneca. And we are one step closer to our first independent launch with our NDA submission for olezarsen, which is supporte ...

Ionis Pharmaceuticals (IONS) came out with a quarterly loss of $0.98 per share versus the Zacks Consensus Estimate of a loss of $1.10. This compares to loss of $0.87 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of 10.91%. A quarter ago, it was expected that this drug discovery and development company would post a loss of $0.78 per share when it actually produced a loss of $0.06, delivering a surprise of 92.31%.Over the last fo ...

Wall Street analysts expect Ionis Pharmaceuticals (IONS) to post quarterly loss of $1.10 per share in its upcoming report, which indicates a year-over-year decline of 26.4%. Revenues are expected to be $131.51 million, up 0.4% from the year-ago quarter.Over the past 30 days, the consensus EPS estimate for the quarter has been adjusted downward by 1.2% to its current level. This demonstrates the covering analysts' collective reassessment of their initial projections during this period.Prior to a company's ea ...

The market expects Ionis Pharmaceuticals (IONS) to deliver a year-over-year decline in earnings on higher revenues when it reports results for the quarter ended March 2024. This widely-known consensus outlook is important in assessing the company's earnings picture, but a powerful factor that might influence its near-term stock price is how the actual results compare to these estimates.The stock might move higher if these key numbers top expectations in the upcoming earnings report, which is expected to be ...