Ionis Pharmaceuticals 2026 Q3 Earnings Call

Please begin. Thank you, Chris.

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 have also posted slides on our website that accompany today's call. With me this morning are Brett Monia, Chief Executive Officer, Kyle Jenne, Chief Global Product Strategy Officer, Holly Kordasiewicz, Chief Development Officer, and Beth Hougen, Chief Financial Officer. 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.

As a result, you are cautioned not to rely on these forward-looking statements. I encourage you to consult the risk factors contained in our SEC filings for additional detail. With that, I will turn the call over to Brett.

Thanks, Wade. Good morning, everyone, and thank you for joining us on today's call. Through the first three quarters of 2026, Ionis has continued to evolve and grow as a commercial-stage biotechnology company, achieving numerous important milestones. In addition to TRYNGOLZA for FCS and DAWNZERA for HAE, our Ionis-owned commercial portfolio now includes TRYNGOLZA for severe hypertriglyceridemia, or sHTG, our first launch in a large patient population, and ZANVASTRO, our first independent launch in neurology. Although two recent phase III readouts did not deliver the outcomes we hoped for, we have achieved a number of other important firsts for patients across our business that position us for further growth. This includes the approval of HIBSAGO for chronic hepatitis B virus in the U.S. and Japan, and positive phase III results for sefaxersen in IgA nephropathy and ulefnersen in FUS-ALS.

Our substantial progress keeps us on track to achieve our full year 2026 total revenue, operating loss, and cash guidance. DAWNZERA's continued positive momentum supports our confidence in achieving its 2026 product sales guidance. For TRYNGOLZA, we are lowering our 2026 full-year revenue guidance to approximately $50 million to reflect the more gradual launch ramp than we had anticipated. As the first and only treatment approved to reduce triglycerides and the risk of acute pancreatitis in people living with sHTG, TRYNGOLZA requires HCPs to adopt a new approach to patient care, which takes time. In these early days, we are encouraged by the fundamentals underlying the launch, including strong physician enthusiasm. We are refining our launch tactics to translate this enthusiasm into action. We have identified key executional priorities and implemented specific initiatives across these priorities, which Kyle will discuss in detail.

Importantly, we remain confident in TRYNGOLZA's multi-billion dollar peak sales potential. Beyond TRYNGOLZA, Kyle will provide further perspective on DAWNZERA and share initial insights on ZANVASTRO. Holly will then go over our recent pipeline progress. Beth will review our third quarter results and outlook for the rest of 2026. With that, I'll turn the call over to Kyle.

Thank you, Brett. I'd like to start by recognizing our highly engaged commercial team for their dedication to bringing important medicines to patients. Their deep expertise, strong commitment to each of our launches, and clear priorities to expand physician adoption and help patients access treatment gives us confidence in our ability to drive growth across our commercial portfolio. Following TRYNGOLZA's June approval for sHTG, HCPs continue to express strong enthusiasm for TRYNGOLZA's compelling clinical profile, including placebo-adjusted mean reductions in triglycerides of up to 72% and a favorable safety and tolerability profile. These triglyceride reductions resulted in a profound reduction in acute pancreatitis events by up to 91%. Physicians also appreciate the dosing flexibility and are prescribing both the 50 and 80 milligram doses, allowing them to tailor treatment to individual patient needs.

For patients, TRYNGOLZA offers the convenience of a once-monthly auto-injector that can be self-administered in about 10 seconds. We are seeing HCPs prescribe TRYNGOLZA for high-risk sHTG patients who are the focus of our initial commercial efforts. These are patients with triglyceride levels of 880 milligrams per deciliter or higher, or 500 or higher with a history of acute pancreatitis or other comorbidities. We are also seeing prescribing beyond our initial focus, consistent with the broad sHTG label. Our post-launch market research reinforces HCPs' strong intent to prescribe TRYNGOLZA. As we establish a new treatment paradigm, we are focused on translating this strong intent to prescribe into action with three executional priorities designed to increase prescribing and help patients move efficiently from prescription to treatment. First, we are focused on broadening the prescriber base, specifically among high-priority physicians who care for high-risk sHTG patients.

We are accelerating our education efforts across these specialists and practice teams to increase their understanding of the burden of sHTG, the risk of acute pancreatitis, and TRYNGOLZA's demonstrated ability to reduce that risk. In parallel, we are supporting patient education through HCP conversations with their patients and patient support programs so that people living with sHTG better understand their disease, the importance of treatment, and the role TRYNGOLZA can play in reducing triglycerides and the risk of acute pancreatitis. Our field teams are meeting more frequently with high-priority HCPs who have not yet prescribed to instill a sense of urgency into patient identification and treatment. The goal is to help physicians incorporate TRYNGOLZA into routine care for appropriate patients. From sHTG approval to the end of September, approximately 1,500 prescribers across all anticipated specialties had prescribed TRYNGOLZA.

In the weeks since our field team put these initiatives into action, our initial prescriber base has started to broaden further. Second, we are focused on increasing the depth of prescribing among HCPs who are early adopters of TRYNGOLZA. Since the sHTG launch to the end of September, approximately 24% of prescribers had written more than one prescription. Prescribers want to see how a patient responds to treatment before prescribing more broadly, consistent with how HCPs often adopt new specialty medicines. We saw a similar pattern when we launched in FCS, where physicians became more confident prescribing TRYNGOLZA as they gained experience and observed its impact. While the sHTG population is much broader, our FCS experience gives us confidence that TRYNGOLZA's novel mechanism of action and groundbreaking patient outcomes can support broader prescribing over time.

Our field team is executing on this priority by following up with prescribers to discuss their initial treatment experience and support them in identifying additional patients who may benefit from TRYNGOLZA. Notably, we have seen recent increases in repeat prescribing, suggesting these efforts are starting to have an impact. Third, we are working to make the path from prescription to treatment more efficient. As expected at this early stage of the launch, a majority of TRYNGOLZA prescriptions required a medical exception. Some physicians are hesitant to prescribe newly approved therapies broadly before formal coverage is in place, a pattern seen in other specialty launches, especially in the cardiovascular space. To address this, our dedicated access team is educating physician offices on the reimbursement process and payer requirements. Additionally, we have a Quick Start program that enables patients to begin TRYNGOLZA treatment while coverage is being secured.

The program has been well received, with meaningful utilization to date, and we expect it to continue to expand. Ionis Every Step, our patient support program, also helps eligible patients navigate the insurance process and access treatment. We are working with payers to establish coverage policies and are making good progress. By the end of September, plans representing 33% of commercial lives had added the sHTG indication for TRYNGOLZA to their formularies. Importantly, all current policies provide coverage aligned with the broad TRYNGOLZA label for adults with triglyceride levels of 500 or higher, extending beyond the high-risk patients who represent our initial commercial focus. As payers review the reimbursement policies for TRYNGOLZA, we are on track for additional policies to take effect this year, with more expected throughout 2027.

As we address these early launch dynamics, we remain confident in TRYNGOLZA's potential to achieve more than $3 billion in peak annual sales. That confidence begins with the substantial unmet need. More than 3 million people in the U.S. have sHTG, including approximately 1 million high-risk sHTG patients. TRYNGOLZA's efficacy, dosing flexibility, and self-administered auto-injector provide a compelling profile for these patients. As we establish a new treatment paradigm and build the market, our priorities are clear: broaden and deepen prescribing, and improve payer access to simplify the path to treatment. While we recognize it will take some time for these initiatives to deliver accelerating prescription volume, we are confident our actions position TRYNGOLZA for future growth. Outside the U.S., Sobi continuing to advance the launch in FCS while preparing for the upcoming anticipated broader launch in sHTG following the recent positive CHMP opinion. Turning to DAWNZERA. The launch continues to gain momentum, with product sales increasing substantially each quarter since launch.