Familial chylomicronaemia syndrome

Kyle Jenne rejoins company to lead commercial strategy Onaiza Cadoret-Manier departing for new career opportunity With broad commercial capabilities in place, Ionis ready to execute on its first independent launches CARLSBAD, Calif., Feb. 29, 2024 /PRNewswire/ --Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that Kyle Jenne has rejoined Ionis as executive vice president, chief global product strategy officer, to lead all aspects of commercialization at the Company. Mr. Jenne has more than 25 years of biopharmaceutical commercial and executive leadership experience and has launched innovative medicines across a broad range of therapeutic areas including cardiovascular, neurology and allergy. Onaiza Cadoret-Manier, chief global product strategy and operations officer, is leaving the company to pursue another opportunity. To support the transition, Ms. Cadoret-Manier will remain in a full-time capacity through March 15, after which she will serve as an advisor for a period of time. "I thank Onaiza for her tremendous vision and contributions in establishing Ionis' foundational commercial organization and capabilities over the last four years as Ionis evolved into a fully integrated biopharmaceutical company. She has built a stellar team of professionals with deep experience across all aspects of commercialization," said Brett P. Monia, Ionis' chief executive officer. "With these core capabilities in place and our first co-commercialization underway for WAINUA™ (eplontersen), we're excited to welcome Kyle back to spearhead our commercial growth as we work to advance a steady cadence of medicines starting with our first potential independent U.S. launches for olezarsen in familial chylomicronemia syndrome and donidalorsen in hereditary angioedema. Kyle's broad commercial and launch experience, coupled with his strong existing relationships at Ionis, will enable him to rapidly and seamlessly add value to our commercial organization during this important time for Ionis and the patients who are counting on us." Mr. Jenne has broad experience in executive leadership roles and expertise in launching and commercializing innovative medicines in the U.S. and globally. He brings deep relevant experience in a wide range of therapeutic areas. Mr. Jenne previously spent five years in commercial leadership roles at Ionis and Akcea, which was fully acquired by Ionis in 2020. His most recent role at Ionis was as EVP & chief commercial officer. During his time at Ionis and Akcea, Mr. Jenne built commercial capabilities in many of Ionis' key disease areas including transthyretin-mediated amyloidosis and familial chylomicronemia syndrome (FCS). He also played a key role in establishing the co-commercialization collaboration with AstraZeneca for WAINUA. Earlier in his career, Mr. Jenne held commercial roles for companies including Schering Plough, King Pharmaceuticals, Acorda Therapeutics and Praecis Pharmaceuticals. "As a fully integrated biopharma company, Ionis is demonstrating its leadership with an innovative pipeline of wholly owned mid- and late-stage investigational medicines, each of which has the potential to meet important unmet needs for people with serious diseases. I am committed to ensuring we fully realize the potential of these innovative medicines to reach patients and their healthcare providers, beginning with the anticipated upcoming launches for olezarsen and donidalorsen," said Mr. Jenne. "On a personal level, I'm thrilled to be back at Ionis working with this incredibly talented and dedicated team." 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, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn. Forward-looking Statements This press release includes forward-looking statements regarding Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. 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 certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2023, and most recent Form 10-Q, which are on the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. WAINUA™ is a trademark of AstraZeneca plc. Company Codes: NASDAQ-NMS:IONS

WAINUA™ approved with launch underway; on track for EU and Canada approval decisions this year Positive Phase 3 olezarsen and donidalorsen data, preparing regulatory submissions for FCS and HAE, respectively Olezarsen granted Breakthough Therapy designation by the FDA for FCS Ionis provides full year 2024 financial guidance CARLSBAD, Calif., Feb. 21, 2024 /PRNewswire/ --Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), today reported financial results for the fourth quarter and full year ended December 31, 2023. "This past year included many remarkable achievements as we continued to advance our vision to bring better futures to people with serious diseases. Ionis achieved two FDA approvals, delivered three positive Phase 3 data readouts, expanded our rich Phase 3 pipeline to nine medicines and advanced our next wave of wholly owned medicines as well as our technology," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "In 2024, we anticipate building on our success with important catalysts and continued value creation. The WAINUA U.S. launch is underway for patients with hereditary ATTR polyneuropathy, and we expect additional approvals in other countries this year. We plan to present positive Phase 3 data for olezarsen in familial chylomicronemia syndrome and donidalorsen in hereditary angioedema, positioning Ionis to independently launch these two medicines. We also anticipate additional readouts from multiple mid-stage programs that, if positive, would advance into Phase 3 development, further strengthening our ability to deliver a steady cadence of potentially transformational medicines for years to come." Fourth Quarter and Full Year 2023 Summary Financial Results(1): Financial Highlights Revenue more than doubled for the fourth quarter of 2023 compared to the same period in the prior year and increased 34% for the full year, driven by the successful progression of Ionis' pipeline and technology platform Operating expenses increased compared to the prior year, primarily due to strategic investments to bring eplontersen, olezarsen and donidalorsen to patients 2023 operating loss significantly improved over prior year due to substantial revenue earned during the year Cash and short-term investments of $2.3 billion as of December 31, 2023 enables continued investments to drive increasing value, including supporting our potential upcoming launches Recent Marketed Medicines Highlights WAINUA approved in the U.S., resulting in a $50 million milestone payment from AstraZeneca; launch underway for treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) SPINRAZA continued to be the global market leader for the treatment of spinal muscular atrophy (SMA) with global sales of $1.7 billion in 2023 Recent Late-Stage Pipeline Highlights Eplontersen granted Fast Track designation by the FDA for the treatment of patients with ATTR cardiomyopathy (ATTR-CM) Olezarsen granted Breakthrough Therapy designation by the FDA for the treatment of patients with familial chylomicronemia syndrome (FCS) Olezarsen granted orphan drug designation by the FDA for the treatment of patients with FCS Achieved multiple milestones with donidalorsen for the treatment of patients with hereditary angioedema (HAE): Reported positive topline data from the Phase 3 OASIS-HAE study in patients treated every four weeks or every eight weeks; preparing to submit NDA Licensed European donidalorsen commercialization rights to Otsuka; Otsuka preparing to submit MAA Donidalorsen granted orphan drug designation by EMA Reported positive Phase 2 data from the open label extension study in patients with HAE treated for two years Bepirovirsen granted fast track designation by the FDA for the treatment of patients with chronic hepatitis B (CHB) Recent Other Pipeline Highlights Achieved multiple milestones with ION582 (BIIB121) for the treatment of patients with Angelman syndrome: Completed enrollment in the Phase 1/2 HALOS study in patients with Angelman syndrome; on track for data readout in mid-2024 Presented positive clinical update from ongoing HALOS study at the FAST (Foundation for Angelman Syndrome Therapeutics) Summit Extended the long-term extension portion of HALOS study Sapablursen and ION356 granted fast track designation by the FDA for the treatment of patients with polycythemia vera (PV) and Pelizaeus-Merzbacher disease (PMD), respectively Initiated the Phase 1/2 PrPro of ION717 in patients with Prion disease AstraZeneca licensed ION826 for the treatment of heart failure, resulting in a $36 million payment from AstraZeneca Recent Technology Advancement Highlights Licensed Vect-Horus' blood-brain barrier crossing technology for the development of RNA-targeted neurological disease medicines Fourth Quarter, Full Year 2023 Financial Results and 2024 Financial Guidance "In 2023, we earned substantial revenues due to continued success with our pipeline and technology. As a result, we exceeded our 2023 revenue guidance, which drove a smaller than anticipated operating loss," said Elizabeth L. Hougen, chief financial officer of Ionis. "In 2024, with WAINUA's launch for ATTRv-PN underway, we are adding a new stream of royalty revenue to our substantial and sustained revenues. We will continue to deploy our capital resources toward growth opportunities that can enable Ionis to unlock next-level value. This includes continuing to make significant investments in near-term commercial opportunities, the expansion of our wholly owned pipeline, and advancing our technology, all of which should empower future growth." Revenue Ionis' revenue was comprised of the following: Commercial revenues in 2023 were comparable to 2022. Commercial revenue for 2023 included $240 million from SPINRAZA royalties, which was comparable to 2022. Ionis' commercial revenue in 2023 also included royalties from QALSODY U.S. product sales. R&D revenue significantly increased in 2023 compared to 2022 primarily due to continued success with Ionis' pipeline and technology. As a result, Ionis earned significant partner payments, including $50 million from AstraZeneca for the FDA approval of WAINUA for ATTRv-PN in the U.S., $36 million from AstraZeneca for licensing ION826 and payments from Ionis' new collaborations with Otsuka, Roche and Novartis. Operating Expenses Ionis' operating expenses increased for the year ended December 31, 2023 compared to 2022 primarily due to certain one-time costs, including a non-cash charge associated with a lease exit and the license fee Ionis paid to Vect-Horus. As Ionis advanced its robust pipeline, study costs increased compared to the same periods in 2022 as many of the Company's Phase 3 studies are either fully enrolled or approaching full enrollment, resulting in higher R&D expenses year over year. R&D expenses for the fourth quarter of 2023 were lower compared to the fourth quarter of 2022, primarily due to the $80 million upfront payment Ionis paid to Metagenomi in 2022. Ionis' SG&A expenses increased year over year primarily due to launch preparation activities for WAINUA, olezarsen and donidalorsen. Balance Sheet As of December 31, 2023, Ionis' cash, cash equivalents and short-term investments increased to $2.3 billion compared to $2.0 billion at December 31, 2022 primarily due to the $500 million Ionis received from Royalty Pharma in January 2023 and significant partner payments throughout 2023. Ionis' working capital also increased over the same period primarily due to the Company's higher cash and short-term investments balance. In 2023, the Company recorded a long-term liability for future royalties due to Royalty Pharma. In June 2023, Ionis issued $575 million of senior convertible notes due in June 2028 with an interest rate of 1.75%. The Company used the majority of the proceeds to repurchase $504 million of its 0.125% convertible notes. 2024 Financial Guidance The Company's 2024 guidance reflects its plan to deploy its capital resources toward growth opportunities, including continued investments in its near-term commercial opportunities, expanding its wholly owned pipeline and advancing its technology platform. Additionally, the Company expects to continue earning substantial revenue from its commercial portfolio and partnered programs. Webcast Management will host a conference call and webcast to discuss Ionis' fourth quarter and full year 2023 results at 11:30 a.m. Eastern time on Wednesday, February 21, 2024. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company's fourth quarter and full year 2023 earnings slides click here. For more information about SPINRAZA and QALSODY, visit and , respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s). INDICATION for WAINUA™ (eplontersen) WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA™ (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. 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, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn. Ionis' Forward-looking Statement This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies. 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 certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2022, and most recent Form 10-Q, which are on the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. QALSODYTM is a trademark of Biogen. SPINRAZA® is a registered trademark of Biogen. WAINUATM is a registered trademark of the AstraZeneca group of companies. *In October 2022, Ionis entered into a sale and leaseback transaction for several of its real estate assets. As a result, the Company recognized a $150 million gain on sale of real estate assets in the fourth quarter of 2022. The Company excluded the gain on sale of real estate assets and the related tax effect from its non-GAAP amounts for the applicable periods. Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP income (loss) from operations, and non-GAAP net income (loss) were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. In 2022, Ionis' non-GAAP net loss excluded the gain on real estate assets related to the sale and leaseback transaction and the related tax effects. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations. Key 2024 Value Driving Events(1) Company Codes: NASDAQ-NMS:IONS

CARLSBAD, Calif., Feb. 15, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to the investigational medicine olezarsen for the treatment of familial chylomicronemia syndrome (FCS), a rare, genetic disease characterized by extremely elevated triglyceride levels and recurrent acute pancreatitis (AP). The FDA grants Orphan Drug designation to therapies intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the U.S. at the time of designation. "People living with FCS are in urgent need of a medicine that may help stabilize their triglyceride levels and reduce the risk of life-threatening AP attacks," said Sam Tsimikas, M.D., senior vice president, global cardiovascular development of Ionis. "If approved, olezarsen has the potential to be the standard of care in the U.S. for the treatment of FCS. We are deeply committed to advancing this important medicine that has the potential to be transformative for people and families living with FCS." FCS prevents the body from breaking down fats, which can result in fasting triglyceride levels that can range from 10 to 100 times higher than normal levels.1,2 People with FCS are at high risk of AP, or inflammation of the pancreas, which often results in hospitalization and can be life-threatening.3 In severe cases, vital organs such as the heart, lungs, kidneys and pancreas can be damaged.4 Under the FDA's Orphan Drug Act, orphan drug status provides incentives, including tax credits, grants and waiver of certain administrative fees for clinical trials, and seven years of market exclusivity following drug approval. About Olezarsen Olezarsen is an RNA-targeted investigational LIgand Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials. About FCS FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact one to two people per million worldwide. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. People living with FCS are sometimes unable to work, adding to the burden of disease. Currently, there are no U.S. FDA-approved therapies for the treatment of FCS and standard triglyceride lowering therapies are generally ineffective in patients with FCS. People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to adhere to diets to navigate the health risks associated with FCS. 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, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn. Forward-looking Statements This press release includes forward-looking statements regarding olezarsen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. 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 certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2022, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. 1 Pallazola et al. Eur J Preventive Cardiol 2020 27:2276-2278. 2 Gaudet D, et al. N Engl J Med. 2014;371:2200-2206. 3 Chyzhyk V, Brown AS. Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis. Trends Cardiovasc Med. 2020;30(2):80-5. 4 "Pancreatitis." WebMD. . SOURCE Ionis Pharmaceuticals, Inc.