Ionis Pharmaceuticals, Inc.

Good morning, and welcome to IONIS' first quarter 2024 financial results conference call. As a reminder, this call is being recorded. At this time, we'd 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 investor section of the IONIS website to view the press release and the related financial tables we will be discussing today, including the 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 this morning are Brett Monia, Chief Executive Officer, Kyle Genet, Chief Global Product Strategy Officer, and Beth Haugen, Chief Financial Officer. Richard Geary, our Chief Development Officer, Eric Swayze, Executive Vice President of Research, Eugene Snyder, Chief Clinical Development Officer, and Jonathan Birchall, Chief Commercial 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 STC filings for additional detail. And with that, I'll turn the call over to Brad.

Thanks, Wade. Good morning, everybody, and thanks for joining us today. 2024 is off to a great start for IONIS as we continue to execute on our vision to bring better futures to people with serious diseases. With the recent U.S. launch of our first IONIS co-branded medicine, Wainua, Ionis discovered medicines are now reaching even more people living with serious diseases. And we're on the cusp of independently delivering a steady stream of new transformational medicines to patients, beginning with our planned launches of Olasarsen and Donadolarsen. By uniting groundbreaking science and technology with a relentless passion to discover, develop, and deliver new transformational medicines to people in need, we believe Ionis is well-positioned to unlock next-level value. The renewal launch for ATTR polyneuropathy is on track in the U.S. with our co-commercialization partner, AstraZeneca. While its early days in the launch, we're pleased with the collective team's progress. The approval decisions in Europe and Canada, expected later this year, and additional regulatory submissions already completed, we expect to soon bring we knew it to even more patients around the globe. And based on we knew a strong efficacy profile, together with the freedom of simple, at-home monthly self-administration, we believe Wainua is poised to become the therapy of choice for ATTR patients. We continue to advance our CardioTransform study of Wainua for the larger ATTR cardiomyopathy indication with the potential for data as early as 2025. As the largest study ever conducted in this patient population, the landmark CardioTransform trial is on track to deliver the most comprehensive and robust data set. We expect the data we generate will 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 well-positioned to bring RENUID to patients in the U.S. and around the globe. Our next planned launch is for Olisarcin and FCS, a severe rare disease with no approved treatments in the U.S., Olazarsen is also in development for the much larger SHTG patient population with more than 3 million estimated patients in the U.S. alone. By addressing these two indications, Olazarsen represents one of the most meaningful opportunities in our pipeline today. Last month, we presented and published very positive Phase III results for Olazarsen in FCS. In the Phase III balance study in patients with FCS, Olazarsen showed substantial triglyceride reductions. Importantly, for patients, physicians, and payers, Olazarsen also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis, as well as a favorable safety and tolerability profile. Balance is truly groundbreaking, as it is the first trial to demonstrate that reducing triglycerides can reduce the incidence of acute pancreatitis. In addition to the Phase III balance study, We presented and published positive data from the BRIDGE study in patients with high cardiovascular risk and moderately elevated triglycerides. In this study, 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels, reinforcing our confidence in Olazarsen's potential for success in FCS and SHTG. I'm pleased to report that we submitted the MDA for Olazarsen in FCS with the FDA last month, putting Ionis one step closer to our first independent launch. Assuming priority review, we're on track for a potential U.S. approval by the end of this year. We're also preparing to file for regulatory approval in Europe later this year. Olazarsen is poised to be the first approved medicine for FCS in the United States and our strong results to date further increase our confidence that if approved, Olazarsen could be the standard of care for both FCS and SHTG. Our ongoing phase three studies for SHTG continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase three studies in SHTG, core, and essence, with our remaining study, core two, expected to complete enrollment very soon. This puts us on track for SHTG phase three data mid-next year. Following closely behind Olazarsson and FCS is our next expected commercial launch with Donna DeLorsen. our potentially first in-class prophylactic treatment for hereditary angioedema. Early in the first quarter, we reported positive top-line data from the Phase III OASIS-HAE study. Donna Dolorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks. The study also met other important secondary endpoints and had a favorable safety and tolerability profile. We're looking forward to presenting data from the Phase III OASIS and OASIS Plus studies in the late-breaker oral session at the European Academy of Allergy and Clinical Immunology Congress, the IACI Congress, at the end of this month. OASIS Plus includes an open-label cohort for patients rolling over from the Phase III study and a separate cohort that we refer to as the SWITCH study. The SWITCH study is a first-of-its-kind study. evaluating patients who have transitioned to Donald Orson from other prophylactic HAE medications. We plan to hold a webcast in conjunction with the clinical data presentation at IACI. With these positive data in hand, we're working to finalize our regulatory submission to the FDA, which will include both four-week and eight-week dosing options. Additionally, our European commercial partner, Atsuka, is preparing to file for marketing approval in Europe. Based on our Phase III results and the long-term efficacy and favorable safety data seen in the ongoing Phase II open-label extension study, we believe donagloricin, if approved, could evolve the HAE prophylactic treatment paradigm. Beyond our near-term opportunities, we have made important progress in advancing additional areas of our rich pipeline, including our leading neurology franchise. Our leading neurology pipeline today includes 12 medicines, And we remain on track to have six wholly-owned neurology medicines in clinical development by the end of this year. We just recently added one of these medicines to our neurology pipeline with the initiation of the ORBIT study, a first inpatient study for ION356 targeting PLP1 for PMV, a rare X-linked recessive leukodystrophy. In addition to our neurology franchise, we also reported positive Phase II data for ION224, our medicine targeting DGAD2 in development or MASH. These data provided clinical evidence demonstrating for the first time that targeting DGAT2 to reduce hepatic fat production can improve MASH histological endpoints, including improving fibrosis. The study met its primary and key secondary endpoints while also demonstrating that ION224 was safe and well-cholerated. These results support advancing this program to the next stage of development. Since this program is outside of our key focus areas, we intend to license IONT24 to maximize its value for the millions of people living with MASH today. Our accomplishments this year and the investments we're making over the next few years move us closer to achieving our goal of bringing a steady cadence of new transformational medicines to patients for years to come and generating next-level value for all IONA stakeholders. With that, I'd like to introduce Kyle Genet. who recently rejoined Ionis to lead our global product strategy and spearhead our next phase of growth. With his extensive commercial and biopharma leadership experience and familiarity with our programs, Kyle hit the ground running and has already seamlessly added value to our commercial and medical organizations during this very important time. After Kyle provides a brief update on the way NOAA launched and the status of our go-to-market activities for Olazarsen and Diamond-Volorsen, Beth will review our financials, including our first quarter results. And then I'll wrap things up before taking your questions.