Ionis Pharmaceuticals, Inc.

Good morning and welcome to the IONIS fourth quarter and full year 2023 financial results conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw a question, please press star, then two. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Wolk, Senior Vice President of Investor Relations, to lead off the call. Please begin.

Thank you, Megan. Before we begin, I encourage everyone to go to the Investor section of the IONIS website to view the press release and related financial tables we will be discussing today. including a reconciliation of gap to non-gap financials. We believe non-gap financial results better represent the economics of our business and how we manage our business. We have also posted slides on our website that accompany today's call. With me this morning are Brett Monia, Chief Executive Officer, Richard Geary, Chief Development Officer, and Beth Haugen, our Chief Financial Officer. Eric Swayze, our Executive Vice President of Research, Eugene Snyder, Clinical Chief Clinical Development Officer, and Oneza Katare, Chief Global Product Strategy and Operations Officer, 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. At Ionis, we are proud of our scientific heritage. We have united groundbreaking science and technology with a relentless passion to discover and develop new transformational medicines. And now that we have validated the broad applicability of our RNA targeting platform, we're on the brink of independently delivering our medicines directly to patients. Over the next several years, we expect to successfully launch multiple medicines on our own while continuing to expand our technology so that we can address the needs of even more patients. This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Ionis. And we're already off to a great start in 2024. In fact, just yesterday, the FDA granted breakthrough therapy designation to old Sarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence showing that the therapy may offer substantial improvement over available treatment. Before we get to all the other exciting things planned for this year, I'll first recap some of our key achievements in 2023. First, we received two FDA approvals for Ionis discovered medicines, CALSATI for SOD1 ALS and Wainua for ATTR polyneuropathy. CALSATI is the first drug approved to treat a genetic form of ALS. It was granted accelerated approval in the U.S. early last year for patients with SOD1 ALS. And we are also pleased to cap off a highly successful year with the approval of Wainua for ATTR polyneuropathy in late December. The Wainua launch is well underway in the U.S. through our co-commercialization partnership with AstraZeneca, and we're executing on our strategy to bring Wainua to patients globally with additional potential approvals in Europe and Canada this year and more regulatory submissions and approvals on the way. Based on its strong overall profile, including highly positive phase 3 data, which we reported last year, together with the freedom of simple at-home monthly self-administration, we believe LENUA is very well positioned to become the therapy of choice for ATTR patients who remain underserved by current therapies. With a larger ATTR cardiomyopathy indication, we continue to advance our CardioTransform study as planned. As the largest study ever conducted in this patient population, CardioTransform is positioned to be a landmark study designed to deliver a very rich data set. We expect the data we generate to enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. And with AstraZeneca's global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we are very well positioned to bring renewal to patients in the U.S. and around the globe. We also recently delivered positive Phase III top-line data readouts for two additional important medicines, olazarsin in FCS and donazolarsin in HAE. In the Phase III balance study in patients with FCS, olazarsin showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the U.S. and EU this year. Positioning. olzarsen for potential approval in the U.S. by the end of the year, assuming we get priority review. With this timing, we expect olzarsen to be our next approved medicine and our first independent launch. We were also pleased with the positive top-line data we reported last month from the Phase III OASIS-HAE study of dominovirus for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donna Dolores met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing our regulatory submission to the FDA, which will include both every four-week and every eight-week dosing. We expect Donna Dolores to be our second independent U.S. launch. Additionally, our partner, Otsuka, preparing to submit for marketing approval in Europe. Based on our Phase III results and the durable efficacy and favorable safety data seen long-term in the ongoing Phase II open-label extension study, we believe Donna DeLorsen could be an attractive new treatment option for patients with HAE. We look forward to presenting the full Phase III data for both Ola Zarsen and Donna DeLorsen later this year. We also made significant progress expanding our rich Phase III pipelines. Last year, we began the year with six medicines in Phase III development, and this year, we began with nine medicines in Phase III. These new Phase III additions include Zilgenersen, our wholly-owned medicine for Alexander disease, and two partner programs, Bepiravirsen for chronic HPV and Ionis FBLRX for IgA nephropathy. We also continued to make great strides last year in advancing our industry-leading RNA targeting technology. We advanced our first bicycle siRNA muscle targeting like a drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood-brain barrier. Most recently, their novel protein-based approaches to systemically deliver our medicines to the CNS. This adds to our multi-pronged approach to traverse the blood-brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position as well for a catalyst-rich 2024. Today, Ionis is at a key inflection point with the recent approvals of two medicines three positive phase three readouts, and numerous upcoming phase three readouts expected over the next couple of years. And at the same time, we've also made great progress across the rest of our rich pipeline and advanced our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come. We will continue to focus on building and advancing our wholly owned pipeline. which will position us to deliver even more medicines directly to patients. We expect that the investments we're making over the next few years will drive an outsized opportunity to earn multibillion-dollar revenue from our proprietary pipeline, generating next-level value for all Iona stakeholders. And with that, I'll turn the call over to Richard to discuss our recent pipeline progress. Next, Pat will review our 2023 financial results and provide our 2024 financial guidance. And then I'll wrap things up before taking your questions. Richard?