Robust Efficacy Anticipated with Pelacarsen in Phase 3 Lp(a) HORIZON Study QALSODY SOD1-ALS (SOD1) SPINRAZA SMA (SMN2) ION859 Parkinson's disease (LRRK2) ION464 Parkinson's disease and Multiple System Atrophy (alpha-synuclein) ION363 FUS-ALS (FUS) ION541 ALS (ATXN2) ION373 Alexander disease (GFAP) Eplontersen ATTR (TTR) ION582 Angelman syndrome (UBE3A-ATS) Tominersen Huntington's disease (HTT) ION260 Spinocerebellar Ataxia Type 3 (ATXN3) ION306 SMA (SMN2) IONIS-MAPTRx Alzheimer's disease (Tau) 24 MAA Accept ...

Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) Q1 2023 Earnings Conference Call May 3, 2023 11:30 AM ET Company Participants Wade Walke - SVP, IR Brett Monia - CEO Richard Geary - Chief Development Officer Beth Hougen - CFO Eugene Schneider - Chief Clinical Development Officer Onaiza Cadoret - Chief Global Product Strategy & Operations Officer Eric Swayze - EVP, Research Conference Call Participants Joseph Stringer - Needham and Company Jessica Fye - JPMorgan Yanan Zhu - Wells Fargo Mike Ulz - Morgan Stanley Yal ...

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 March 31, 2023 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) Delaware 33-0336973 (State or oth ...

• Advanced new MsPA backbone chemistry with enhanced duration into preclinical development • Advance new routes of delivery 1. Non-GAAP – please see reconciliation to GAAP in FY 2022 press release 2. $500M from royalty monetization transaction in January 2023 15 million Establish an integrated commercial organization | --- | --- | --- | |------------------------------------------------------------|---------------------------------------------------------------------------------|----------------------------- ...

Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) Q4 2022 Results Conference Call February 22, 2023 11:30 AM ET Company Participants Wade Walke - SVP, IR Brett Monia - CEO Beth Hougen - CFO Eugene Schneider - Chief Clinical Development Officer Onaiza Cadoret - Chief Global Product Strategy & Operations Officer Eric Swayze - EVP, Research Conference Call Participants Yanan Zhu - Wells Fargo Securities Gary Nachman - BMO Capital Markets Do Kim - Piper Sandler Gena Wang - Barclays Yale Jen - Laidlaw & Co. Paul Matte ...

Commercialization and Market Challenges - The company has limited experience in commercializing medicines and will need to invest significant resources to develop marketing and sales capabilities[291]. - SPINRAZA revenue has decreased due to lower pricing in the U.S. and increased competition, impacting future sales potential[294][305]. - The company relies on third parties for commercialization, which may lead to lower product revenues and profitability compared to self-commercialization[292]. - The acceptance of the company's medicines by the medical community and third-party payers is crucial for generating substantial revenues[293]. - Regulatory limitations may be imposed on approved medicines, affecting marketing and distribution activities[310]. - The company is dependent on collaboration with Biogen for the development and commercialization of SPINRAZA, which poses risks if Biogen fails to fulfill its commitments[313][314]. - Future product sales may be subject to increased restrictions and pricing pressures from government and third-party payers[300][301]. - The company faces competition from numerous pharmaceutical firms, which may hinder the commercialization of its medicines[302][304]. - The need for post-marketing studies to demonstrate cost-effectiveness may require significant management time and resources[298]. - The company must comply with comprehensive government regulations regarding the manufacture and marketing of its medicines[307]. - The collaboration with AstraZeneca for the development and commercialization of eplontersen includes co-commercialization in the U.S. and AstraZeneca's sole rights in other countries, which may limit revenue if unsuccessful[315]. - A Joint Steering Committee (JSC) with equal membership from both companies oversees eplontersen's development, and disagreements could delay commercialization[316]. - The company is commercializing TEGSEDI and WAYLIVRA in multiple international markets, facing risks associated with regulatory, pricing, and reimbursement conditions[375]. Financial Performance and Position - Total revenue for 2022 was $587.4 million, a decrease of 27.5% from $810.5 million in 2021[406]. - Total operating expenses increased to $997.6 million in 2022 from $840.6 million in 2021, resulting in a loss from operations of $410.2 million[406]. - SPINRAZA royalties contributed $242.3 million in 2022, down from $267.8 million in 2021, with total SPINRAZA product sales decreasing 6% year-over-year[408]. - Total R&D revenue for 2022 was $284.0 million, significantly lower than $468.1 million in 2021, primarily due to a $200 million payment received in 2021 from AstraZeneca[408]. - Cash, cash equivalents, and short-term investments were $1,986.9 million as of December 31, 2022, compared to $2,115.0 million at the end of 2021[406]. - The company has an accumulated deficit of approximately $1.4 billion and stockholders' equity of approximately $0.6 billion as of December 31, 2022[348]. - The company recorded a net loss of $269.7 million in 2022, compared to a net loss of $28.6 million in 2021, indicating a significant increase in losses[441]. - Basic and diluted net loss per share for 2022 was $1.90, compared to $0.20 in 2021, reflecting a substantial increase in loss per share[442]. - The company has raised approximately $2.0 billion from equity securities and $2.1 billion from long-term debt since inception[443]. Research and Development - The company is currently developing seven medicines in Phase 3, focusing on cardiovascular and neurology franchises[405]. - For the year ended December 31, 2022, the company earned $77 million in joint development revenue and incurred $147 million in R&D expenses related to the eplontersen collaboration with AstraZeneca[410]. - R&D expenses, excluding non-cash compensation, rose to $759.4 million in 2022 from $547.4 million in 2021, driven by investments in the late-stage pipeline and licensing of Metagenomi's gene editing technologies[419]. - Total drug development expenses reached $457.7 million in 2022, up from $349.0 million in 2021, reflecting the expansion of Phase 3 studies from three to six[422]. - AstraZeneca is covering 55% of the costs associated with the ongoing global Phase 3 development program for eplontersen[410]. Manufacturing and Operational Risks - The company is expanding its manufacturing capabilities with a new facility in Oceanside, California, which will incur substantial expenditures and require additional staff[319]. - There is limited experience in manufacturing oligonucleotide-based medicines on a commercial scale, and reliance on a small number of suppliers for capital equipment and raw materials poses risks[320]. - Non-compliance with FDA's cGMP regulations could delay or prevent marketing authorizations for medicines, including SPINRAZA and TEGSEDI[321]. - The company relies on third-party manufacturers for TEGSEDI and WAYLIVRA, and any disruptions could limit commercial success[322]. - Distribution agreements with Sobi and PTC for TEGSEDI and WAYLIVRA may result in less revenue than direct commercialization[323]. Compliance and Regulatory Environment - Compliance with healthcare laws is critical, as violations could result in significant penalties and reputational harm[378]. - The company faces risks related to international operations, including regulatory compliance and currency exchange fluctuations[376]. - The company is subject to changing regulations for corporate governance, increasing costs and risks of noncompliance[380]. - Regulatory approval for medicines is uncertain, and failure to obtain timely approvals could negatively impact revenue generation[327]. - Clinical studies may face delays or failures due to various factors, including the COVID-19 pandemic and regulatory scrutiny[335]. - Ongoing geopolitical tensions, particularly the war between Russia and Ukraine, may restrict clinical trial operations and increase costs[337]. Corporate Governance and Internal Controls - The company has provisions in its certificate of incorporation that may discourage third-party acquisitions, potentially limiting shareholder value[366]. - The company assessed the effectiveness of its internal control over financial reporting as of December 31, 2022, and concluded that it maintained effective internal control[473]. - Ernst & Young LLP audited the effectiveness of the company's internal control over financial reporting as of December 31, 2022, and expressed an unqualified opinion[478]. - The company has established disclosure controls and procedures to ensure timely and accurate reporting of required information[470]. Stock and Financing - The market price of the company's common stock ranged from $48.82 to $28.25 per share over the 12 months preceding December 31, 2022, indicating significant volatility[364]. - The company completed a $632.5 million offering of 0% Notes and used $247.9 million of the net proceeds to repurchase $257.0 million of its 1% Notes[369]. - Future sales of approximately 17.5 million shares of common stock upon conversion of 0% Notes and 0.125% Notes could adversely affect trading prices of the company's securities[372]. - The ongoing war between Russia and Ukraine may adversely affect the global credit markets, impacting the company's liquidity and financial condition[374]. - The company may need to raise additional funds through public or private financing, which could dilute existing stockholders' shares[345]. Cybersecurity and Data Risks - The company has invested in cybersecurity measures, but risks remain regarding data breaches that could harm its reputation and lead to financial penalties[361].

Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) Q3 2022 Earnings Conference Call November 9, 2022 11:30 AM ET Company Participants Julie Tepper - Investor Relations Brett Monia - Founder, CEO & Director Richard Geary - EVP & Chief Development Officer Elizabeth Hougen - EVP, Finance & CFO Eric Swayze - EVP, Research Eugene Schneider - EVP & Chief Clinical Development Officer Onaiza Cadoret - EVP, Chief Global Product Strategy & Operations Officer Conference Call Participants Gary Nachman - BMO Capital Markets Yana ...

IONIS | --- | --- | --- | --- | --- | |------------------|-------|-------|-------|-------| | | | | | | | November 9, 2022 | | | | | | Nasdaq: IONS | | | | | | | | | | | On Today's Earnings Call 2 Brett Monia, Ph.D. Chief Executive Officer Richard Geary, Ph.D. Executive Vice President, Development Beth Hougen Chief Financial Officer Eric Swayze, Ph.D. Executive Vice President, Research Eugene Schneider, M.D. Executive Vice President, Chief Clinical Development Officer Onaiza Cadoret Executive Vice President, ...

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 September 30, 2022 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 ...

Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) Q2 2022 Earnings Conference Call August 9, 2022 11:30 AM ET Company Participants Brett Monia - Chief Executive Officer Beth Hougen - Chief Financial Officer Richard Geary - Executive Vice President of Development Eric Swayze - Executive Vice President of Research Eugene Schneider - Chief Clinical Development Officer Onaiza Cadoret - Chief Global Product Strategy & Operations Officer Conference Call Participants Yanan Zhu - Wells Fargo Jessica Fye - JPMorgan Do Kim - ...