Ionis Pharmaceuticals, Inc.

Good morning, and welcome to IONIS' fourth quarter and full year 2025 financial results conference call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walk, Senior Vice President of Investor Relations, to lead off the call. Please begin.

Thank you, Keith. Before we begin, I encourage everyone to go to the Investors section of the IONIS website to view the press release and related financial tables we will be discussing today, including a reconciliation of GAAP to non-GAAP financials. We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me on the call this morning are Brett Monia, our Chief Executive Officer, Holly Kortasiewicz, Chief Development Officer, Kyle Genet, Chief Global Product Strategy Officer, and Beth Haugen, Chief Financial Officer, Eugene Schneider, Chief Clinical Development Officer, and Eric Swayze, Executive Vice President of Research will also join us for the Q&A portion of the call. I would like to draw your attention to slide three, which contains our forward-looking language statement. During this call, we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail. With that, I'll turn the call over to Brett.

Thanks, Wade. Good morning, everybody, and thanks for joining us today. 2025 was a defining year for IONIS, marked by the successful execution of our first two independent launches and multiple positive data readouts across our rich pipeline. These achievements, together with our expectation for multiple additional value-driving events this year, positions IONIS for continued success through 2026 and beyond. Tringolza, The first FDA-approved treatment for familial chylomicronemia syndrome, or FCS, exceeded expectations in its first year on the market. Tringolza's excellent performance was driven by a compelling clinical profile and strong launch execution. Tringolza was also launched in Europe late last year, and we're pleased to see our partner Sobe bring this transformational medicine to more patients. In August, we kicked off our second independent launch with the FDA approval of Donzera, a prophylactic treatment for hereditary angioedema, or HAE. As the first and only RNA-targeted medicine for HAE, Donzera offers a compelling profile that is resonating with prescribers and patients. And just last month, Donzera received European approval, enabling our partner, Otsuka, to bring this important medicine to patients across the region. In 2025, we accelerated this strong momentum with the olizarcin pivotal result in severe hypertriglyceridemia, a broad patient population with high unmet need, further extending our leadership in the development of innovative treatments for diseases associated with high triglycerides. Olizarcin showed highly significant and substantial reductions in triglycerides in acute pancreatitis attacks, establishing olizarcin as the first medicine to demonstrate a benefit in reducing acute pancreatitis risk in this patient population. Based on these groundbreaking phase three results, we were pleased to receive breakthrough therapy designation from the FDA. Additionally, late last year, we submitted the SMDA and anticipate receiving acceptance very soon. Importantly, we are on track to be launch ready by June. We also delivered positive Phase III results for our innovative medicine, Zilgenersen, the first to demonstrate a disease-modifying benefit in Alexander disease, a rare and often fatal neurodegenerative disease. We submitted our MDA in January, and we anticipate approval and launch in the second half of this year. Assuming approval, Zilgenersen will be our first independent launch from our leading neurology franchise. Together, These groundbreaking results meaningfully expand Ionis' commercial opportunity and showcase our commitment to innovation and the power of our platform to deliver first-in-class RNA-targeted medicines for patients with serious diseases. Complementing our rich, wholly-owned pipeline is our partnered pipeline, which targets both rare and highly prevalent life-threatening diseases. We expect multiple Phase III data readouts this year from our partner pipeline. In January, we announced the first of these results with positive top-line data for Bepiravircin, a potential first-in-class medicine for chronic hepatitis B that demonstrated clinically meaningful and unprecedented functional cure rates in the Phase III program. GSK is preparing global regulatory submissions and, assuming approval, expects to begin bringing Bepiravircin to the millions of people living with chronic HPV later this year. Looking ahead, we anticipate results from two major cardiovascular outcome trials, the Pella-Carson LP little a Horizon trial mid-year and the Eplon-Tersen CardioTransform trial in the second half of 2026. In addition, cefaxircin for IJ nephropathy and ulefnircin for FUS ALS are also positioned for phase three readouts later this year. If positive, these outcomes position our partner pipelines to deliver four key additional launches by the end of next year, driving a meaningful increase in our total revenue through royalties and milestone payments for many years to come. With strong momentum across our business, including our first two independent launches, an advancing wholly-owned pipeline, and a robust partner portfolio, Ionis is well-positioned to deliver a steady stream of transformational medicines for patients, thereby driving substantial value and sustained growth. In addition to our very important recent commercial and pipeline achievements, 2025 was also a strong year of financial performance for IONIS. Revenue increased more than 30% over 2024, with growing contributions from our marketed medicines. This significant revenue growth combined with disciplined investment enabled us to exceed our financial guidance. And as Beth will discuss later in the call, This momentum underpins our strong 2026 financial outlook. Importantly, we remain on track to achieve our goal of reaching cash flow break even by 2028. Now, before I turn it over to Holly, I'd like to take a moment to formally introduce her in her new role as Chief Development Officer. Since joining IONIS, Holly has played a central role in building and expanding our R&D neurology franchise, resulting in the creation of an industry-leading pipeline of RNA-targeted therapies for a broad range of rare and common neurological disorders. Holly has also played a strategic role more broadly in creating IONIS' leading research and development organization and brings a deep, deep understanding of our technology. We are pleased to have Holly in our new role and confident she will continue to drive substantial value and continued success for IONIS and all IONIS stakeholders. Now over to you, Holly.