Alexander Disease

WAINUATM U.S. launch progressing well; approved in Canada; EU approval decision expected this year Olezarsen PDUFA December 19, 2024 for FCS Positive Phase 3 donidalorsen data for HAE; preparing U.S. and EU regulatory submissions On track to achieve 2024 financial guidance CARLSBAD, Calif., Aug. 1, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), today reported financial results for the second quarter of 2024. "Over the first half of this year, we continued to deliver on our goal to bring a steady cadence of medicines to people with serious diseases. The WAINUA launch for hereditary ATTR polyneuropathy (ATTRv-PN) continues to progress well with AstraZeneca. QALSODY is now approved in the EU, expanding the number of patients who can benefit from the first approved treatment for a genetic form of ALS. And we are well positioned for our first independent launch with olezarsen, which was accepted for Priority Review with a December FDA action date for people with familial chylomicronemia syndrome (FCS), a serious and rare disease with no approved treatments in the U.S. Additionally, we completed enrollment in our Phase 3 olezarsen program for the much larger severe hypertriglyceridemia (sHTG) patient population, keeping us on track for data in the second half of next year. And based on recent positive Phase 3 results, we believe donidalorsen, our second planned independent U.S. launch, is positioned to be a preferred choice for people with hereditary angioedema (HAE)," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We also advanced our next wave of potentially transformational medicines, including announcing plans to independently advance ION582 into a Phase 3 study next year, based on positive data in Angelman syndrome; this program is poised to become the cornerstone of our robust wholly owned neurology pipeline. Our recent achievements, together with multiple upcoming catalysts, position Ionis to deliver next-level value for all stakeholders." Second Quarter 2024 Summary Financial Results(1): Financial Highlights Revenue increased for the second quarter and first half of 2024 by 20% and 8% compared to the same periods last year, respectively, primarily driven by an increase in R&D revenue reflecting the value Ionis' pipeline and technology continues to generate Operating expenses increased in the second quarter and first half of 2024 compared to the same periods last year, reflecting continued strategic investments in late-stage development, including WAINUA for ATTR cardiomyopathy and olezarsen for sHTG, and commercialization efforts for WAINUA, olezarsen and donidalorsen Reaffirmed 2024 financial guidance Recent Marketed Medicines Highlights WAINUA for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $16 million and $21 million resulting in royalty revenue of $4 million and $5 million in the second quarter and first half of 2024, respectively WAINUA for the treatment of adults with ATTRv-PN approved in Canada SPINRAZA for the treatment of spinal muscular atrophy (SMA) generated global sales of $429 million and $770 million resulting in royalty revenue of $57 million and $95 million in the second quarter and first half of 2024, respectively QALSODY for the treatment of SOD1-ALS granted marketing approval in the EU Recent Late-Stage Pipeline Highlights Olezarsen achieved multiple clinical and regulatory milestones that support pursuit of two patient populations with urgent unmet need, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG): FDA accepted the NDA for patients with FCS for Priority Review with a PDUFA date of December 19, 2024 Presented positive Phase 3 Balance study data in patients with FCS with a simultaneous publication in the New England Journal of Medicine Opened Expanded Access Program (EAP) for FCS in the U.S. Completed enrollment for all Phase 3 sHTG studies: CORE pivotal study, CORE2 confirmatory pivotal study and ESSENCE supportive exposure study; on track for data across all three studies in H2:2025 Presented positive Phase 2b Bridge study data in patients with HTG and sHTG with a simultaneous publication in the New England Journal of Medicine Donidalorsen achieved multiple clinical milestones positioning it to become the first RNA-targeted prophylactic treatment for people with hereditary angioedema (HAE): Preparing to submit NDA Otsuka preparing to submit MAA; expanded Otsuka EU commercial licensing agreement to include Asia Pacific Presented positive Phase 3 OASIS-HAE study data in patients treated every four weeks or every eight weeks with a simultaneous publication in the New England Journal of Medicine Presented positive Phase 3 OASISplus open-label extension study data in patients treated every four weeks or every eight weeks Presented positive Phase 3 OASISplus switch study data in patients previously treated with other prophylactic therapies Zilganersen (GFAP) Phase 3 study for the treatment of patients with Alexander disease fully enrolled; on track for data in 2025 Bepirovirsen Phase 3 studies for the treatment of patients with chronic hepatitis B (CHB) fully enrolled; on track for data in 2026 Recent Other Pipeline Updates Presented positive Phase 2 data for ION582 (UBE3A), our wholly owned medicine, in patients with Angelman syndrome; preparing for meetings with global regulators ahead of planned Phase 3 study start in H1:2025 Presented positive Phase 2 data for ION224 (DGAT2) in patients with metabolic dysfunction-associated steatohepatitis (MASH) Initiated the Phase 1/2 Orbit study of ION356 (PLP1) in patients with Pelizaeus-Merzbacher disease (PMD) Discontinued development of IONIS-FB-LRx for geographic atrophy (GA) and ION541 for amyotrophic lateral sclerosis (ALS) following completion of Phase 2 studies showing favorable safety profiles and good target engagement, but insufficient efficacy to advance into Phase 3 development Second Quarter 2024 Financial Results "Ionis is at a critical inflection point. We have achieved important development and regulatory milestones for WAINUA, olezarsen and donidalorsen, all of which have significant potential to help patients in need. In parallel, we continue to advance our next wave of potentially transformational medicines," said Elizabeth L. Hougen, chief financial officer of Ionis. "To drive next-level of value creation for all stakeholders, we remain focused on strategically investing our capital to fully unlock the potential of our promising near-and longer-term portfolio. Our investments are focused on go-to-market preparations for our upcoming planned olezarsen and donidalorsen launches. And with our increased confidence in the potential of WAINUA and olezarsen to address broader patient populations, we are planning additional investments to scale our capabilities in line with the significant potential that these important medicines represent. Additionally, we are investing in our next wave of medicines, including pre-commercialization activities and Phase 3 development for ION582 for Angelman syndrome, which we plan to start in the first half of next year. We expect our investments today and in the years ahead will position Ionis for sustainable growth for years to come." Revenue Ionis' revenue was comprised of the following: Commercial revenue in the second quarter and first half of 2024 included a new source of royalty revenue with the launch of WAINUA in the U.S. in late January 2024. Ionis' commercial revenue in the second quarter and first half of 2024 also included royalties from the net sales of QALSODY, which Biogen launched in the U.S. in the second quarter of 2023 and in the EU in the second quarter of 2024. R&D revenue in the second quarter and first half of 2024 increased compared to the same periods last year primarily due to the amortization of upfront payments from the new collaborations with Roche and Novartis that Ionis entered into during the second half of last year. In addition, license fees increased year over year as a result of new collaborations Ionis entered into during the second quarter of 2024, including the expanded donidalorsen licensing agreement with Otsuka, which now includes the Asia-Pacific region in addition to Europe. These increases were partially offset by the decrease in WAINUA joint development revenue, which decreased as development activities relating to ATTRv-PN wound down with the launch of WAINUA for this indication. Operating Expenses Ionis' operating expenses increased in the second quarter and first half of 2024 compared to the same periods in 2023, consistent with expectations. SG&A expenses increased year over year primarily due to the launch of WAINUA in the U.S. and launch preparation activities for olezarsen and donidalorsen, including establishing the field team for olezarsen. R&D expenses decreased in the second quarter and were essentially flat in the first half of 2024 compared to the same periods last year as several late-stage studies have ended. Balance Sheet As of June 30, 2024, Ionis' cash, cash equivalents and short-term investments decreased to $2.1 billion compared to $2.3 billion at December 31, 2023. The Company plans to continue deploying its capital resources toward growth opportunities, and as previously guided, projects to end 2024 with $1.7 billion in cash, cash equivalents and short-term investments. Ionis' working capital also decreased over the same period primarily due to the Company's lower cash and short-term investments balance. We expect to make increased strategic investments in the years ahead, with a focus on late-stage programs, wholly owned assets, and our next wave of innovative medicines. Webcast Management will host a conference call and webcast to discuss Ionis' second quarter 2024 results at 11:30 a.m. Eastern time on Thursday, August 1, 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 second quarter 2024 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 Ionis.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, 2023, and most recent Form 10-Q, which are on file with 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. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUATM is a registered trademark of the AstraZeneca group of companies. Ionis Investor Contact: D. Wade Walke, Ph.D. [email protected] 760-603-2331 Ionis Media Contact: Hayley Soffer [email protected] 760-603-4679 Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net 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. 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) SOURCE Ionis Pharmaceuticals, Inc.

ION582 showed robust and consistent benefit in communication, cognition and motor function in a broad patient population evaluated with a comprehensive set of assessment tools that collect input from parents and clinicians 97% of patients in the medium and high dose groups saw improvement in overall Angelman syndrome symptoms as measured by the SAS-CGI-C Improvements on the Bayley-4 in cognition, communication and motor function exceeded those observed in natural history studies Ionis plans to initiate Phase 3 development in H1 2025 Ionis to host webcast on Monday, July 22 at 8:00am ET CARLSBAD, Calif., July 22, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive results from the completed multiple ascending dose (MAD) portion of the Phase 1/2 open-label study of ION582 in people with Angelman syndrome (AS) demonstrating consistent and encouraging clinical improvement on measures assessing all functional domains including communication, cognition and motor function. Overall, 97% of people in the medium and high dose groups saw an improvement in overall AS symptoms as measured by the Symptoms of Angelman Syndrome–Clinician Global Impression-Change (SAS-CGI-C). ION582 showed favorable safety and tolerability at all dose levels in the study. Detailed results will be presented in a company webcast today and at the 2024 Angelman Syndrome Foundation (ASF) Family Conference in Sandusky, Ohio on July 24, 2024. "Ionis looks forward to collaborating with investigators, regulators and members of the Angelman syndrome community to initiate Phase 3 development for ION582 in the first half of 2025," said Brett Monia, Ph.D., chief executive officer of Ionis. "Ionis has pioneered the discovery and development of groundbreaking medicines for serious neurological conditions including spinal muscular atrophy and amyotrophic lateral sclerosis. These encouraging results from the HALOS study position ION582 to be the cornerstone of Ionis' next wave of transformational, wholly owned medicines for neurological conditions, which currently includes five clinical-stage programs." AS is a serious, rare neurodevelopmental disorder that is caused by a loss of function in the maternal UBE3A gene. It affects an estimated 1 in 21,000 people worldwide and presents in early childhood as profound and severe developmental delays in motor, language and cognitive functioning, seizures and ataxia. ION582 is an investigational antisense medicine designed to unsilence the normal paternal UBE3A gene to increase production of the UBE3A protein in the brain. "Angelman syndrome is a serious neurodevelopmental disorder with life-long impairments and dependence on caregivers, for which we currently have only supportive care," said Lynne Bird, M.D., professor of clinical pediatrics at UC San Diego and HALOS study investigator. "We are very encouraged by these promising data with ION582, showing consistent improvements over what we observe in the natural course of the disease." HALOS Study Results HALOS included 51 people with AS, and allowed participants aged two-50 to enroll. Results presented today are from the final timepoint of the completed MAD portion of the study at six months. These results include: ION582 showed favorable safety and tolerability at all dose levels. Evidence of consistent benefit observed across all ages and genotypes as well as clinical improvement observed across key functional areas: Improvements in communication, cognition and motor function exceeding the Angelman Syndrome Natural History Study (NHS) were observed on the Bayley-4, an objective and direct clinician-administered assessment of clinical functioning. See details in Table 1 below. Clinical improvements were observed across key functional areas in the Vineland-3 and Observer-Reported Communication Ability (ORCA), which are both parent-reported assessment tools. 97% of participants showed clinically meaningful overall improvement on the SAS-CGI-C, which evaluates clinicians' impressions of AS symptoms in study participants. Table 1: Majority of Participants Demonstrated Benefit in Nearly all Domains Assessed in the HALOS Study1 The percent of participants who improved across the four AS tools evaluated in HALOS is noted below. These results exceed the improvements seen in the NHS, where available, in which people with AS show profound developmental delay from birth through adulthood with function remaining stable with essentially no improvement after ~4 years of age. Ionis plans to meet with regulators to review and confirm their Phase 3 study design later this year, which puts the company on track for a pivotal study initiation in H1 2025. Webcast Ionis will hold a webcast today at 8:00am ET to discuss this update. Interested parties may access the webcast here. A webcast replay will be available for a limited time. About the HALOS Study The global, open-label, multiple-ascending dose (MAD) Phase 1-2a study (NCT05127226) includes 51 patients with Angelman syndrome (AS) aged two – 50 across 11 sites in six countries. Part 1 of the HALOS trial was a three-month, MAD study which evaluated three doses of ION582, with final assessments at six months. All eligible patients transitioned into the Part 2 long-term extension (LTE) portion of the study, which is evaluating the two higher doses of ION582 for an additional 12 months. Part 3 of the study will evaluate eligible patients for up to an additional four years. The primary endpoint is safety and tolerability of multiple doses of ION582 administered by intrathecal administration. Key exploratory measures include change in measures of clinical function: communication, cognition, motor function, sleep, seizures and daily living skills. About ION582 ION582 is an investigational antisense medicine designed to inhibit the expression of the UBE3A antisense transcript (UBE3A-ATS) and increase production of UBE3A protein, for the potential treatment of Angelman syndrome (AS). In 2022, the U.S. Food and Drug Administration (FDA) granted ION582 Orphan Drug designation and Rare Pediatric designation. About Angelman Syndrome (AS) AS is a rare, genetic neurological disease caused by the loss of function of the maternally inherited UBE3A gene. AS typically presents in infancy and is characterized by profound intellectual disability, balance issues, motor impairment, and debilitating seizures. Most patients are unable to speak. Individuals with AS have a normal lifespan but require complete care from a caregiver. Some symptoms can be managed with existing medicines; however, there are no approved disease modifying therapies. About Ionis' Neurology Franchise Ionis has been at the forefront of discovering and developing leading neurological disease medicines, including SPINRAZA® (nusinersen), the first approved treatment for spinal muscular atrophy, WAINUATM (eplontersen), a medicine to treat hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and QALSODY® (tofersen) for SOD1-ALS. The clinical-stage portfolio includes 11 therapies, of which five are wholly owned by Ionis. Ionis' investigational portfolio includes medicines for which there are few or no disease modifying treatments, such as rare diseases including amyotrophic lateral sclerosis (ALS) and Alexander disease and more common conditions such as Alzheimer's and Parkinson's disease. 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 Ionis.com and follow us on X (Twitter) and LinkedIn. Ionis Forward-looking Statements This press release includes forward-looking statements regarding Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, ION582, 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 file with the SEC. Copies of these and other documents are available at . 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. Ionis Pharmaceuticals Investor Contact: D. Wade Walke, Ph.D. - [email protected] - 760-603-2331 Ionis Pharmaceuticals Media Contact: Hayley Soffer - [email protected] - 760-603-4679 SOURCE Ionis Pharmaceuticals, Inc.

Zilganersen is the first investigational medicine in clinical development for people with Alexander disease, a rare, life-threatening neurological condition CARLSBAD, Calif., July 18, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that it has completed enrollment in the pivotal trial of zilganersen (ION373), an investigational RNA-targeted medicine in development for the treatment of children and adults with a rare, progressive and ultimately fatal neurological disorder known as Alexander disease (AxD). The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT). Topline data are anticipated in the second half of 2025. AxD is estimated to occur in an estimated one in one million people in the U.S. and can present throughout life.1-3 The disease is a result of genetic variants in the glial fibrillary acidic protein (GFAP) gene that disrupt the structure and function of astrocytes in the brain. AxD is generally characterized by cognitive dysfunction and progressive neurologic deterioration, including loss of independence and the ability to control muscles for large movements, swallowing and airway protection. Zilganersen is designed to stop the excess GFAP that accumulates because of disease-causing variants in the GFAP gene, with the goal of slowing or stabilizing disease progression in people living with AxD. "Current approaches to disease management for Alexander disease can mitigate some symptoms of AxD but do not address the underlying cause or slow disease progression. Our zilganersen study is the first trial to evaluate an investigational medicine designed to address the underlying cause of Alexander disease," said Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis. "We are grateful for the dedication and support from the patients, families and investigators in the Alexander disease community, whose partnership has made this milestone possible." About the Zilganersen Study The global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) is a Phase 1-3 study (NCT04849741), which enrolled patients aged two to 65 with Alexander disease (AxD) across 13 sites in eight countries. Participants were randomized in a 2:1 ratio to receive zilganersen or control for a 60-week double-blind treatment period. At 60 weeks, all participants will receive zilganersen for a 180-week open-label treatment period, followed by a 28-week post-treatment follow-up period. The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT) at the end of the double-blind treatment period. Secondary endpoints include change from baseline in patients' self-identified Most Bothersome Symptom (MBS) Score, Patient Global Impression of Severity (PGIS) Score, Patient Global Impression of Change (PGIC) Score and Clinician Global Impression of Change (CGIC) Score at the end of the double-blind treatment period. The study includes an open-label sub-study in eligible participants under the age of two years with AxD, which will continue to enroll into 2025. About Zilganersen (ION373) Zilganersen is an investigational antisense oligonucleotide medicine being developed as a potential treatment for people with genetically confirmed Alexander disease (AxD). Zilganersen is designed to stop the excess glial fibrillary acidic protein (GFAP) production that accumulates because of disease-causing variants in the GFAP gene. In 2020, the U.S. Food and Drug Administration (FDA) granted zilganersen Orphan Drug designation and Rare Pediatric designation. In addition, the European Medicines Agency (EMA) granted zilganersen Orphan Drug designation in 2019. About Alexander Disease (AxD) AxD is a rare, progressive and ultimately fatal neurological disease that affects a type of cell in the brain called astrocytes. Astrocytes have multiple roles in the brain to support neurons and oligodendrocytes, including maintenance of the myelin sheath that protects nerve fibers. AxD is caused by disease-causing variants in the glial fibrillary acidic protein (GFAP) gene and is generally characterized by cognitive dysfunction and progressive neurologic deterioration, including loss of independence and the ability to control muscles for large movements, swallowing and airway protection, though symptoms can vary depending on age of onset. AxD usually leads to death within 14-25 years after symptom onset. There are no disease modifying medicines approved for patients. 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 Ionis.com and follow us on X (Twitter) and LinkedIn. Ionis Forward-looking Statements This press release includes forward-looking statements regarding Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, zilganersen, 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 file with the SEC. Copies of these and other documents are available at . 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. Ionis Investor Contact: D. Wade Walke, Ph.D. [email protected] - 760-603-2331 Ionis Media Contact: Hayley Soffer [email protected] - 760-603-4679 SOURCE Ionis Pharmaceuticals, Inc.