WAINUATM launch on track; EU and Canada approval decisions expected this year Olezarsen NDA submitted to FDA for FCS; preparing EU regulatory submission Positive Phase 3 donidalorsen data for HAE; preparing regulatory submissions On track to achieve 2024 financial guidance CARLSBAD, Calif., May 7, 2024 /PRNewswire/ -- 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 supported by robust data positioning olezarsen to make a profound difference for people with FCS," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We look forward to presenting positive Phase 3 donidalorsen data, along with data from our open-label extension and 'switch' studies in patients with HAE at EAACI later this month, setting the stage for Ionis' second independent launch. Additionally, we have multiple upcoming data readouts from our mid-stage programs that, if positive, could advance into Phase 3 development, further strengthening our ability to deliver a steady cadence of potentially transformational medicines for years to come." First Quarter 2024 Summary Financial Results(1): Three months ended March 31, 2024 2023 (amounts in millions) Total revenue $119 $131 Operating expenses $269 $245 Operating expenses on a non-GAAP basis $238 $218 Loss from operations ($150) ($114) Loss from operations on a non-GAAP basis ($119) ($87) (1)  Reconciliation of GAAP to non-GAAP basis contained later in this release. Financial Highlights Revenue for the first quarter of 2024 earned from numerous diverse sources, including a new source of royalty revenue with the launch of WAINUA in the U.S. Continued strategic investments to bring WAINUA, olezarsen and donidalorsen to patients drove increased operating expenses in the first quarter of 2024 compared to the same period last year Cash and short-term investments of $2.2 billion as of March 31, 2024 enable continued investments to drive increasing value, including supporting our planned upcoming launches 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 $5 million in the first partial quarter of launch resulting in royalty revenue of $1 million for Ionis in the first quarter of 2024 SPINRAZA for the treatment of spinal muscular atrophy (SMA) generated global sales of $341 million resulting in royalty revenue of $38 million in the first quarter of 2024 Biogen presented new positive neurofilament light chain (NfL) biomarker data from the Phase 4 RESPOND study of SMA patients adding further evidence supporting the potential benefit of SPINRAZA in infants and toddlers who had unmet medical needs after treatment with gene therapy Recent Late-Stage Pipeline Highlights Eplontersen granted Fast Track designation by the FDA for the treatment of patients with ATTR cardiomyopathy Olezarsen achieved multiple milestones advancing it closer to potentially addressing two distinct populations of patients with urgent unmet need, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG): Submitted NDA to the FDA for FCS Presented positive Phase 3 Balance study data in patients with FCS with a simultaneous publication in the New England Journal of Medicine Presented positive Phase 2b Bridge study data in patients with HTG and sHTG with a simultaneous publication in the New England Journal of Medicine Opened Expanded Access Program (EAP) for FCS in the U.S. Granted Breakthrough Therapy and Orphan Drug designations by the FDA for the treatment of patients with FCS Completed enrollment of the Phase 3 CORE pivotal study and ESSENCE supportive exposure study for sHTG; CORE2 confirmatory pivotal study on track to fully enroll mid-year Donidalorsen achieved multiple milestones advancing it closer to potentially becoming a first-in-class RNA-targeted prophylactic treatment for people 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 Opened EAP for HAE in the U.S. Granted Orphan Drug designation by EMA Bepirovirsen granted Fast Track designation by the FDA for the treatment of patients with chronic hepatitis B (CHB) Recent Other Pipeline Highlights Reported 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) First Quarter 2024 Financial Results "Our first quarter results keep us on track to achieve our 2024 financial guidance. With the launch of WAINUA in the U.S. underway, we are excited to add WAINUA royalties to our meaningful revenues in the first quarter. We believe WAINUA is uniquely positioned in this growing market to address the needs of ATTRv-PN patients who remain significantly underserved, especially as it is the only approved medicine with monthly dosing that can be self-administered via an auto injector," said Elizabeth L. Hougen, chief financial officer of Ionis. "We continued to invest our capital resources in our near-term commercial opportunities, wholly owned pipeline and technology. We expect our modest expense growth this year to be driven by our activities to support the WAINUA launch and planned launches for olezarsen and donidalorsen with R&D expenses approaching steady state as several late-stage studies have recently ended. We believe the investments we are making today and plan to make over the next few years position Ionis to drive increasing value for patients and stakeholders." Revenue Ionis' revenue was comprised of the following: Three months ended March 31, 2024 2023 Revenue: (amounts in millions)      Commercial revenue: SPINRAZA royalties $38 $50 WAINUA royalties 1 - Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 9 7 Licensing and other royalty revenue 11 11 Total commercial revenue 59 68 Research and development revenue: Amortization from upfront payments 42 16 Milestone payments 7 23 Collaborative agreement revenue 49 39 WAINUA joint development revenue 11 24 Total research and development revenue 60 63 Total revenue $119 $131 Commercial revenue in the first quarter of 2024 included a new source of royalty revenue with the launch of WAINUA in the U.S. during the first quarter of 2024. While the number of patients on SPINRAZA treatment remained consistent globally, royalties decreased year over year primarily due to the timing of shipments in several markets outside the U.S. Ionis' commercial revenue in the first quarter of 2024 also included royalties from the net sales of QALSODY, which Biogen launched in the second quarter of 2023. R&D revenue in the first quarter of 2024 included increased revenue from the amortization of upfront payments compared to the same period last year due to the new collaborations Ionis entered into last year with Roche and Novartis. This increase was offset by decreases in milestone payments due to timing and WAINUA joint development revenue, which decreased as development activities relating to ATTRv-PN wound down with the launch of WAINUA underway. Operating Expenses Ionis' operating expenses increased in the first quarter of 2024 compared to the same period 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. R&D expenses increased compared ...