Good day, and welcome to Ionis' First Quarter 2026 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 Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.

Thank you, Sabrina. 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; and Beth Hougen, Chief Financial Officer. Holly Kordasiewicz, Chief Development 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'd like to draw your attention to Slide 3, 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. And with that, I'll turn the call over to Brett.

Thanks, Wade. Good morning, everyone, and thank you for joining us today. Ionis entered 2026 with significant momentum, which continued to accelerate through the first quarter of this year. Our performance to date highlights our strong execution across the business, which positions us to fuel substantial growth for years to come. We are very pleased with the continued success of Tryngolza. Demand continues to grow, reflecting both a compelling clinical profile and strong launch execution by our team. The launch of Tryngolza is now also underway in Europe through our partner, Sobi, expanding access to this transformational therapy for people with familial chylomicronemia syndrome (FCS). We also continue to advance our launch of DAWNZERA. We're very encouraged by the strong early trajectory and the breadth of prescribers across patient segments. Outside the U.S., DAWNZERA received European approval earlier this year and our partner Otsuka has now initiated launch activities across the region. Together, Tryngolza and DAWNZERA give us a strong foundation of successful commercial execution as we look ahead to two additional independent launches this year with more to come. We are on track for the launch of olezarsen in severe hypertriglyceridemia (SHTG), which represents our first independent launch in a broad patient population. We are pleased to have received priority review by the FDA with the PDUFA date of June 30, reflecting the significant unmet need in SHTG and the groundbreaking results from our landmark CORE and CORE 2 studies. In these studies, we demonstrated profound and highly statistically significant reductions in triglycerides and acute pancreatitis events, along with favorable safety and tolerability. Today, based on HCP demand and payer research, we are increasing our annual peak sales estimate for olezarsen from greater than $2 billion to now greater than $3 billion, positioning olezarsen to become Ionis' first wholly owned multibillion-dollar medicine as the new standard of care for treating patients with severe hypertriglyceridemia. Zilganersen for Alexander's disease is our second planned independent launch this year and the first from our industry-leading neurology pipeline. Zilganersen is the first and only medicine to demonstrate clinically meaningful and disease-modifying benefit in Alexander's disease, a devastating and orphan fatal leukodystrophy with no approved treatments today. We submitted our NDA in January, and based on the results of our pivotal study, the FDA accepted our NDA with priority review and a PDUFA date of September 22. Overall, we are on track to have three independent medicines for four indications on the market in 2026: Tryngolza for FCS and SHTG, DAWNZERA for hereditary angioedema (HAE), and Zilganersen for Alexander's disease. This marks a major step in Ionis' evolution into a fully integrated commercial biotech company. Complementing our wholly owned portfolio is our partner pipeline, a rich pipeline that continues to advance toward multiple value-driving events this year. Bepirovirsen, our potential first-in-class medicine for chronic hepatitis B, is on track to launch in the U.S. and Japan this year by our partner, GSK. Just this week, bepirovirsen was granted Breakthrough Therapy designation and accepted for priority review by the FDA with a PDUFA date of October 26. Next month at EASL, GSK will present the unprecedented results of the Phase III program in which bepirovirsen achieved statistically significant and clinically meaningful functional cure rates in patients with chronic hepatitis B. We also remain on track for data from two major cardiovascular outcome trials from our partner pipeline this year: the pelacarsen Lp(a) HORIZON trial in patients with elevated Lp(a) and cardiovascular disease, and the eplontersen CARDIO-Transform trial in transthyretin-mediated cardiomyopathy. Including these programs, along with pepireversen, we expect five partner-led launches by the end of next year, creating a diversified stream of royalties and milestones for Ionis with multibillion dollar potential well into the next decade. In addition to our commercial and pipeline achievements, we also delivered strong financial results in the first quarter. As a result of this strong Q1 performance and outlook for the balance of the year, today, we are announcing a significant improvement to our financial guidance, which Beth will cover in detail in a few moments. Ionis has achieved a great deal lately. Our pipeline and our launches are delivering tremendous value, and we continue to strengthen our financial position. But even more importantly, we are well positioned and committed to build on the success to drive far greater value for patients and our shareholders. And with that, I'll turn the call over to Kyle.

Thank you, Brett. As we enter 2026, Ionis is capitalizing on the exceptional launch momentum we generated in 2025 to drive even greater impact. We are set up for continued success with our independent launches. Tryngolza demand is accelerating. DAWNZERA early launch metrics are tracking extremely well. And enthusiasm continues to build for our upcoming olezarsen launch in SHTG and Zilganersen launch in Alexander's disease. Tryngolza continues to build on the strong performance from last year. Q1 was our strongest quarter in terms of demand with patient starts increasing significantly versus prior quarters and patients on treatment are doing extremely well. Our patient-finding initiatives continue to identify appropriate FCS patients, and we are successfully converting prescriptions to patients on treatment. We are seeing ongoing expansion in both breadth and depth of prescribing with more clinicians initiating Tryngolza and existing prescribers writing additional scripts. Prescribers span a broad mix of specialties, including cardiology, endocrinology and lipidology, which is exactly the prescriber base we want as we prepare for the broader SHTG population. Physicians remain highly satisfied with Tryngolza's overall profile — efficacy, safety, tolerability and the patient experience — and that is translating into an accelerating rate for new patient starts. Additionally, we are highly encouraged by the updated ACC and AHA clinical practice guidelines, which singled out olezarsen as the recommended treatment to lower triglycerides and reduce pancreatitis risk in patients with FCS. Outside the U.S., our partner Sobi is now in the early stages of launching Tryngolza for FCS in Europe. This is expanding access for FCS patients and will bring in additional revenue over time. Following the groundbreaking CORE and CORE 2 data in SHTG, we conducted extensive market research with high-volume lipid specialists, cardiologists and endocrinologists. That work consistently showed a clear understanding that preventing pancreatitis is the key treatment goal in SHTG and that current options fall short. There is strong recognition of olezarsen's differentiated clinical profile, especially the acute pancreatitis data and the very low number needed to treat. HCPs have stated a high intent to prescribe across a range of patient types with initial use expected for individuals with triglyceride levels above 880 mg/dL, or above 500 mg/dL with a history of acute pancreatitis or other high-risk comorbidities, including progressive cardiovascular disease and type 2 diabetes. In line with our commitment to patient access and to a successful transition into the broader SHTG market, we recently announced an important pricing decision for Tryngolza. Effective April 1, we set the new annual wholesale acquisition cost (WAC) to $40,000, which applies to the current FCS indication and will be maintained for the anticipated SHTG indication across both doses. Importantly, by establishing a new price ahead of the June 30 PDUFA date, we are integrating olezarsen into 2027 payer contracting cycles, positioning us for accelerating access following approval. From a go-to-market standpoint, our full U.S. field organization is now in place, trained and deployed. Today, that team is focused on supporting Tryngolza for FCS and deepening our relationships with the key specialists who also treat SHTG. With this expanded footprint, we are positioned to engage approximately 20,000 high-volume SHTG prescribers across the country. The DAWNZERA launch is gaining significant momentum in what is largely a switch market in the U.S. We are seeing increasing adoption across all patient segments: patients switching from existing prophylactic therapies, patients who were previously using on-demand treatment, and treatment-naive patients. Our free trial program has been very effective with a high conversion to paid therapy rate to date. Feedback from both physicians and patients has been consistently positive, highlighting DAWNZERA's strong efficacy, its differentiated RNA-targeted mechanism, the positive switch data, which HCPs described as "differentiating and motivating," and DAWNZERA's patient-friendly profile that includes a self-administered auto-injector that can be stored at room temperature for up to six weeks. We are also seeing a growing base of repeat prescribers, which is a key indicator that DAWNZERA is providing a substantial benefit for patients. While it will take time to fully transition appropriate patients off legacy therapies, especially in a well-established market like HAE, the launch fundamentals give us confidence that DAWNZERA will contribute significantly to the increase in our commercial revenue in 2026 and beyond. Outside the U.S., DAWNZERA is now approved in the EU and our partner Otsuka has initiated launch activities. Over time, we expect ex-U.S. markets to become an important contributor to the global DAWNZERA franchise. Finally, we are preparing for our first independent launch from our neurology portfolio with Zilganersen for Alexander's disease. On the back of the positive Phase III results, we now have FDA priority review with the PDUFA date set for September 22, and our expanded access program is underway. On the commercial side, our focus has been on continuing to strengthen current relationships and build new relationships with a highly specialized community of leukodystrophy and rare neurology HCPs, further advancing partnerships with patient advocacy groups, and ensuring the right support infrastructure is in place for diagnosis, treatment and ongoing care. Our medical affairs team has been engaging with top leukodystrophy centers, sharing data and helping to build awareness of Alexander's disease. Our marketing and access teams are finalizing the launch strategy, and we will hire the customer-facing team closer to approval. Zilganersen is not only an important medicine for people living with Alexander's disease, but it's also a template for how we will commercialize future rare first-in-class neurology therapies emerging from our pipeline. With two independent launches building momentum, two additional launches anticipated this year, and a strong pipeline behind them, we believe Ionis is well positioned to change the lives of patients around the world. With that, I'll turn the call over to Beth.

Thank you, Kyle. The strong operational execution you've heard about this morning translated into very strong first quarter financial results. We delivered year-over-year revenue growth and maintained disciplined expense management while continuing to invest in our current and upcoming independent launches. First quarter total revenues were $246 million, an increase of 87% compared to the first quarter of 2025. This increase was driven by year-over-year commercial revenue growth from Tryngolza and DAWNZERA and substantial R&D revenue, including approximately $95 million of milestone payments from multiple partnerships. Commercial revenue increased over 42% year-over-year in the first quarter, driven in large part by Tryngolza and DAWNZERA growth. Tryngolza delivered over $27 million in product sales reflecting continued strong demand that was offset by an anticipated decline in net price. DAWNZERA contributed meaningfully to commercial revenue, delivering $16 million in the first quarter, an increase of 125% compared to the prior quarter. Collectively, our expanding commercial portfolio positions us for robust revenue growth and is expected to represent an increasing share of total revenue year-over-year. Operating expenses for the quarter were in line with expectations and increased 29% year-over-year, primarily driven by commercial investments supporting Tryngolza and DAWNZERA and launch readiness activities for olezarsen in SHTG and Zilganersen in Alexander's disease. We ended the quarter with cash of approximately $1.9 billion. The change in cash from year-end 2025 was primarily related to $633 million we used to repay our 0% convertible notes, which were due on April 1. The strength of our balance sheet is the result of our prudent fiscal management which enables us to make strategic investments as we advance and launch our wholly owned medicines. Our Q1 performance underscores the value of our diversified revenue model, which combines growing commercial revenue with substantial and recurring R&D revenue from partner programs. Based on our strong year-to-date financial results, accelerating launch momentum and positive outlook for the rest of the year, we are improving our 2026 financial guidance. We now expect total revenue in the range of $875 million to $900 million, an increase of $75 million versus prior guidance, with total revenue weighted slightly more towards commercial revenues. For the first time this year, we are also providing product-level guidance for Tryngolza and DAWNZERA. We expect Tryngolza product sales to be between $100 million and $110 million for the full year and generally in line with 2025 full-year Tryngolza revenue. Our guidance assumes a significant decline in second quarter Tryngolza revenue based on the updated price effective April 1 and a steady return to growth after the June 30 approval for SHTG. We are projecting DAWNZERA product sales to be between $110 million and $120 million for the full year. Our guidance assumes DAWNZERA will continue to be a significant contributor to year-over-year growth in 2026, with revenue steadily increasing as the launch advances. We also anticipate significant R&D revenue from existing collaborations, including potential development and regulatory milestones across our partnered portfolio, demonstrating that R&D revenue is indeed an important financial accelerator. In fact, we recently learned that the first patient initiated treatment in the Phase III program for salanersen, which triggered a $45 million payment, will be recognized in the second quarter. Over the balance of the year, we also are eligible to earn additional milestones tied to sapoblirson, vibrope lacarsen, pelacarsen and other partnered programs as they advance. We expect our 2026 operating expenses to increase in the low-teen percentage range compared to last year. This modest increase reflects our commitment to financial discipline as we bring multiple medicines directly to patients and advance our pipeline. The key drivers of expense growth will be sales and marketing investments to support Tryngolza and DAWNZERA and to ensure successful launches for olezarsen in SHTG and Zilganersen in Alexander's disease assuming approvals. We anticipate our R&D expenses to remain steady this year, similar to last year. As late-stage studies reach completion, we are redeploying our resources towards the drugs in our pipeline that we expect to fuel our next phase of growth. Our focus on improving operating leverage is enabling us to drop the full increase in revenue guidance to the bottom line. As a result, we expect a non-GAAP operating loss between $425 million and $475 million, a $75 million improvement over our previous guidance. This is similar to our 2025 operating loss after adjusting for the one-time sapablirson license fee we earned last year. We are projecting a 2026 year-end cash balance of greater than $1.6 billion. This reflects the repayment of the 0% convertible notes, which were due on April 1. The strength of our balance sheet, combined with our diversified revenue streams, supports our continued strategic investments in ongoing and planned launches as we advance our wholly owned pipeline. Our financial outlook reflects accelerating commercial launches, a progressing pipeline and a diversified revenue base, positioning us for continued growth and keeping us on track for cash flow breakeven in 2028. And with that, I'll turn the call back over to Brett.

Thank you, Beth. First quarter and our outlook for 2026 underscore the strength of Ionis today. With two successful independent launches underway, two more independent launches anticipated this year, a robust pipeline advancing toward multiple near- and mid-term catalysts and a solid financial position that supports the continued investments we are making to maximize the value of our commercial medicines and pipeline. With all these key elements in place, we're confident in our ability to accelerate revenue growth and deliver increasing value for patients and for all Ionis stakeholders. Now in closing, I want to highlight that this week at Ionis, we are holding our annual YWeek. It's a time when our employees come together to hear directly from patients and caregivers about their personal stories and reinforce our purpose, which is bringing better futures to people in need. I've never been prouder of the impact we are having on patient lives and clinical medicine, and I'm even more excited about the greater impact we are positioned to make in the near term and sustainably well into the future. And with that, we'll now open the call up for questions. Sabrina?

The first question comes from Jessica Fye of JPMorgan.

So you once again raised peak expectations for Tryngolza. Can you just spend a little time elaborating on what enabled you to increase it from at least $2 billion at JPMorgan to now at least $3 billion? And can you also talk about your expectation for gross-to-net on Tryngolza following this price reset?

Yes. Jess, thank you for the question. So our increase in peak product sales for Tryngolza in SHTG and FCS combined in the U.S. to $3 billion was based on several factors. As you recall, we increased the peak sales to $2 billion in January based really solely on the Phase III data and some preliminary HCP demand research that we had conducted. The demand was very high. Since then, we've completed our HCP demand research. But more importantly, we completed our payer research, which landed on our $40,000 annual WAC price, so price as well as priority review. Those are the biggest drivers of the increase in peak sales that we have put out today. As far as gross-to-net, we're not commenting on that at this time.

The next question comes from Mike Ulz of Morgan Stanley.

Congratulations on the progress. Maybe just a question on the Tryngolza trajectory for the year. You mentioned return to growth in the second half, really driven by the SHTG launch. Just curious in some of your market research, are you picking up on maybe any pent-up demand? Could we anticipate a bolus early in the launch here, just given the groundbreaking data?

Kyle, would you take that, please?

Yes, Mike, I appreciate that. And I think what's important first is the strong performance that we saw in Q1 in terms of demand. It's the best quarter that we've had in terms of the FCS patient population, the number of scripts that were received and the number of patients that are starting on therapy. So that actually lends us a lot of confidence, not only in the FCS space, but also as we get closer to the June 30 PDUFA date in SHTG, I think it's indicating that there is a lot of interest in using olezarsen very broadly in this patient population. In terms of the launch in SHTG, we do know that there are a number of patients that are waiting, especially the patients that have a history of acute pancreatitis, patients that are above 880 mg/dL, and those are really the patients that we're going to focus on out of the gate. The trajectory, I think, is going to be modest at the beginning here in 2026. I think the revenue guidance that Beth shared of $100 million to $110 million is consistent with that expectation, and we'll see it steadily grow over time with that focus being on the highest risk patient population. But some of the dynamics here, as typically seen, is it takes some time for the HCPs to be educated on the label. We've got to get those patients into those centers in order to get the prescriptions and then get the execution of the scripts to turn into patients on treatment. So it will be a build over time, and it will accumulate, and we expect modest and steady growth throughout the back half of this year.

The next question comes from Gary Nachman with Canaccord Genuity.

Congrats on the progress. So again, on SHTG, just talk about how you expect the payer access to ramp up, the timing of that, when you think it will really kick in — and you got updated guidelines for FCS. Will you be able to get that for SHTG as well? And how long before you think you could expand to a less severe patient population over time?

Sure. On the payer access piece, Gary, part of the price change decision that we made on April 1 to change the WAC price to $40,000 is directly tied to working with those payers. It fits into the annual review cycle as they're getting ready for their 2027 decisions to be made. So we believe that it will help us get ahead of SHTG a little bit, not only in 2026, but also will help us in anticipation of SHTG access in 2027. That being said, some payers will actually wait for the final label before they make coverage decisions because they want to see the indication statement and the information in the label, including acute pancreatitis and other clinical study data. So it will take a little bit of time. Some payers follow a standard policy of reviewing in 6 to 9 months. But we hope that we'll be able to get ahead of that with the payers that do review earlier by making that price change and also with our current interactions that we're having leading up to the SHTG approval. So we're going to work quickly, and I think we're in a good spot right now in terms of the way that we're approaching the payers.

And Gary, to your other question, we were very pleased by the fact that the cardiovascular treatment guidelines for FCS singled out Tryngolza as the treatment of choice for this disease indication. We applaud the aggressiveness that they are taking to update their guidelines for treatments, and we believe that SHTG will be part of that in the future, which we believe Tryngolza will be a treatment of choice for severe hypertriglyceridemia. They've been very supportive of the new treatments that are coming out, and we think that they will move pretty quickly. We're also pleased by the fact that they have updated their guidelines on Lp(a) testing, which bodes well for a potential positive Phase III readout for pelacarsen and the subsequent launch. It's great news for patients, and it's great news for our pipeline.

In terms of the less severe patient population, we'll start with the over 880 mg/dL and over 500 mg/dL with history of acute pancreatitis. Those same physicians that are treating that patient population also have patients that are 500 to 880 mg/dL, for example. The education will be ongoing. We're targeting the right HCP segments — cardiology, endocrinology and lipid specialists — so they'll see a mix of those patients. I think some of those patients will already be picked up, especially if they have comorbidities such as type 2 diabetes and/or ASCVD, but the broader population will take a little bit of time for awareness and for more data and experience using olezarsen in the SHTG population. There's a lot of optimism and a lot of excitement around the category and around the use of a product like this because HCPs have never seen the triglyceride-lowering effects they'll see on top of standard of care and they've never seen the outcomes in acute pancreatitis like they saw with the CORE and CORE 2 data.

Next question comes from Chi Meng Fong on for Jason Gerberry with Bank of America.

On olezarsen in SHTG, could you give us an update on the levels of liver fat you've observed in the CORE open-label extension studies — to what extent those open-label extension study data have been incorporated into the NDA as the FDA reviews the totality of the safety data — and when would you expect to present the updated OLE data later this year?

Yes. Let me start, Chi. Thank you for the question, and then I'll pass it on to Eugene. We're very pleased with the ongoing open-label extension data that we're continuing to accumulate with respect to MRI assessment of hepatic fat fraction. As you recall, the increases in hepatic fat that we saw were relatively minor and are consistent with other modalities that have taken that silencing approach in lowering APOC3 in this patient population. It's completely logical based on the mechanism of APOC3 inhibition, which leads to a rapid and substantial clearance of triglycerides in large part through the liver. We've always felt that the observations in liver fat that we've seen would be transient, and that's what we're seeing in the long-term extension data: a return toward baseline in liver fat. Again, no clinical sequelae associated with anything in the long-term extension. We look forward to presenting the data in the second half of this year at a major medical congress. Eugene, do you want to provide an update on regulatory?

Yes. The applications are under review and everything is going as planned. Of course, the emerging safety data has been provided to the agency as part of routine day 90 safety updates, so that's under review now with no questions asked so far.

The next question comes from Tejus on for Eli Merle with Barclays.

In FTE, you have a set of competitor readouts coming up later this year. Curious just how you would frame those data in the context of the space and if any outcomes there would impact your peak sales view in SHTG.

We'd rather not comment on competitor data that doesn't exist yet today. We're looking forward to seeing any additional data that comes out this year, next year and years to come in SHTG from other programs. All I'll say is that the Phase III data that we presented at the American Heart Association late-breaking clinical trials session last year is incredibly compelling. It's a very high bar with respect to efficacy, safety and tolerability: an 85% reduction in acute pancreatitis, which has resonated very well in the HCP community, and a 72% reduction in triglycerides on top of standard of care. We're focused on our program. We're ready to launch in June, and we'll leave it at that. I'll just add that this is a large market — greater than 3 million patients potentially addressable here. We have a lot of confidence in the greater than $3 billion peak that we've put out there. That's really based on the Phase III clinical trial outcomes that we have, our HCP demand research, the comprehensive payer research that we've done and also the final pricing decision that we made. So we stand behind the increase, and we're excited about launching this program and getting it to as many patients as possible after the June 30 PDUFA date.

The next question comes from Jay Olson with Oppenheimer.

Congrats on the quarter, and thank you for this update. Maybe I'll shift gears to DAWNZERA. Can you talk about how you expect the competitive landscape to evolve in HAE and any feedback that you're getting from patients and physicians on DAWNZERA? And any color that you're getting on what percent of patients are currently on every 8-week dosing?

Yes, happy to, Jay. Thanks for the question. The competitive landscape obviously is evolving. Keep in mind that in the United States, over 75% of the patients are currently on a prophylactic treatment. This is a switch market as we understand the dynamics to be. We are really pleased with the momentum that we're seeing in terms of the interest in using DAWNZERA, which is the first RNA-targeted therapy modality to treat these patients. The patient and HCP feedback has been extremely positive when they've been able to transition over to DAWNZERA or start as a treatment-naive patient. What led into this in terms of our market research is consistently being played out in the market. This is about efficacy, tolerability and convenience, and all three of those attributes are stacking up very nicely with the profile of DAWNZERA, and patients are responding very positively to the therapy. The majority of patients start on a 4-week dosing schedule to make sure that they are well controlled during the transition and then they have the option per the label to move to every 8 weeks if they choose to do so. So as early in the launch as we are right now, you would anticipate that the majority of patients would be on a 4-week regimen. We expect over time that many will progress to an 8-week schedule as they do well on therapy, and we saw that in the clinical trial as well. Patients are doing great. Momentum is very strong, and we're encouraged by what we're seeing in terms of the metrics with the launch at this point.

The next question comes from Moritz Reiterer with Guggenheim Securities.

I'll continue on DAWNZERA. Your 2026 guidance for DAWNZERA is essentially above what consensus was going into the quarter. So I was just trying to understand a little bit better what data drove this guidance number. And also if you could comment a little bit more on the current mix between new patient starts versus switches and how you expect this to evolve through the end of the year.

Yes, I'd be happy to touch on that. We had a very strong first quarter, $16 million in net product sales, a 128% increase over Q4. The momentum we're seeing in the market, the dynamics and the receptivity by both HCPs and patients as they get started and gain experience with DAWNZERA are the drivers behind our confidence. In terms of new patient starts, the majority are switches — this is a switch market, greater than 75% of the patients are on a prophylactic therapy in the United States. So it's going to take time to build revenues quarter-over-quarter, but it's happening the way that we expected based on the trends seen in Q4 and Q1. In addition to switches, we are seeing some patients who haven't been on prophylactic therapy before start on DAWNZERA, as well as patients who were using on-demand therapy previously. Those three patient segments support a strong profile for DAWNZERA. We have a differentiated mechanism of action, and our sales execution and market access teams are doing a great job supporting patients to get started and stay on treatment.

The next question comes from Steven on for Yaron Werber with Cowen.

Congratulations on the progress. On the collaborative revenues for the rest of the year and maybe 2027, can you talk about what you're projecting because those came out a bit higher than consensus may have expected? Further on Zilganersen, can you talk about how many patients awareness efforts have found and any new updates to the size of the market? You had mentioned before that about 50% of patients have been identified. Any updates on sizing there would be helpful.

Sure. On collaborative revenue for this year, think about it this way: we've raised our total revenue guidance for 2026 to $875 million to $900 million. That is slightly weighted towards commercial revenue. We've already recognized approximately $95 million in milestone payments plus our ongoing collaborative revenue, which put us well over $100 million of revenue in the first quarter. We've got a host of other milestones that we could potentially earn over the remainder of this year, plus our ongoing collaborative revenue from revenue-sharing and amortization. Those items give us confidence in the overall collaborative revenue for this year. For 2027, there are some very large potential milestones tied to approvals we could see, particularly with pelacarsen. Those milestones are likely to drive collaborative revenue in 2027.

Do you want to start and then Kyle can take the second part?

For Zilganersen, we are very excited about this program. This will be our first anticipated neurology launch and could be transformational for people with Alexander's disease. Our approach will focus on patients currently in the clinical trial to help maintain their access to treatment, patients enrolled in the expanded access program which is ongoing, and then identifying additional patients. We believe there are approximately 300 or so Alexander's disease patients in the United States, and about 50% of those have been identified to date. Some are on treatment already. We are expanding our omnichannel and non-personal promotional campaigns to identify more patients, and we are partnering with top leukodystrophy centers and patient advocacy groups. Patient identification will be a key focus while ensuring we take care of patients on treatment today and those awaiting treatment who have already been identified.

The next question comes from Luca Issi with RBC Capital Markets.

A quick question on Tryngolza. What drove the quarter? Product sales appear down 35% versus the fourth quarter — what drove the weakness here? And it looks like AstraZeneca is flagging the availability of the drug now as a prefilled syringe to be administered by a healthcare provider. Did that have a negative impact on gross-to-net? Any color there is much appreciated.

In Q1, we continued to see very strong demand in terms of patients on therapy as well as new patient starts. Demand is still there. Oftentimes, you see some January-February pressure as it relates to reauthorizations and the timing of those reauthorizations, which drove some of the pressure early in the quarter. But we expect to see that pick up in subsequent quarters and return to revenue growth as we move into Q2 and beyond in the U.S. You asked about the prefilled syringe. That is being offered for optionality — flexibility of dosing — and to allow HCPs to determine if they want to use the auto-injector or treat patients in some major centers with the prefilled syringe. It's optionality for the program and is not impacting gross-to-net at this point. It's way too early to see any impact of that. So keep an eye towards future quarters. This market is growing rapidly, and we remain focused on execution.

The next question comes from Yanan Zhu with Wells Fargo Securities.

Great. You mentioned continued growth in demand for FCS. Could you help quantify that a little bit in terms of percent growth, given that the price change makes it difficult for us to appreciate? And then can you talk about how to think about SHTG in 2027, what kind of growth could we expect from the initial launch quarters in 2026? Obviously, you guided for peak revenue of $3 billion. Any sense of how long that might take? Any color would be super helpful.

Yes, let me start. For FCS, as Kyle mentioned earlier, our first quarter of this year is our strongest quarter to date on patient demand and access to Tryngolza for FCS. That's purely a product of patient finding and the great experiences that HCPs and patients are having with Tryngolza in managing their disease from an efficacy and tolerability standpoint. Demand has never been higher. We're thrilled with what we're seeing, and we think that's going to bode quite well for the SHTG launch trajectory.

I think what's important is to reiterate that in 2026, our revenue guidance for olezarsen is $100 million to $110 million. We expect that to grow steadily over time. As I described earlier, the focus initially will be on the high-risk SHTG patient population — over 880 mg/dL or over 500 mg/dL with a history of acute pancreatitis — and then, as we move into 2027, I would expect more patients to come on board who are broader than that, for example patients with type 2 diabetes or ASCVD. Launch momentum will build as HCPs gain experience seeing the triglyceride lowering and the reduction in acute pancreatitis demonstrated in CORE and CORE 2. That experience and evidence ultimately will help drive the trajectory into next year. As to timing to peak, launches of this magnitude typically take several years to fully ramp to peak, as access, education and payer uptake progress, but we are confident in the long-term opportunity.

The next question comes from Mark on for Salveen Richter with Goldman Sachs.

You touched on DAWNZERA quarterly dynamics. What are the specific drivers for the quarter-over-quarter jump? Are there quarterly dynamics we should be aware of for the rest of 2026? And how are you thinking of these dynamics going into 2027 and beyond?

The quarter-over-quarter growth is coming from the switch cadence that we are expecting to see — this being a switch market. We know there's a need and the profile of DAWNZERA meets that need in terms of efficacy, tolerability and convenience. We have switch data to support how to move patients over from existing prophylactic treatments to DAWNZERA. As HCPs gain experience, we're seeing more prescribers initiating and more repeat prescribing. That, plus payer coverage and the execution of our market access and sales teams, gives us an optimistic outlook for 2026. The $110 million to $120 million guidance for DAWNZERA is aligned with that expectation.

And we have time for one more question, please.

The last question comes from Myles Minter with William Blair.

Congrats on the quarter. Just on the TTR cardiomyopathy market, if I did settle for a potential generic entry for tafamidis in mid-2031 versus something like in 2035, does that change the way you and AstraZeneca are thinking about the cardiomyopathy market moving forward? And how much emphasis are you going to place on the stabilized background therapy subgroup in CARDIO-Transform?

The news that has been emerging this past week on potential generic tafamidis is not terribly surprising to us and is consistent with our product sales guidance that we've put out with AstraZeneca previously. We remain confident that the silencer class will be the mechanism of choice for transthyretin amyloidosis. We believe silencers will be utilized as first-line treatment as well as in patients who progress on stabilizers, and in combination use where appropriate. Our study is designed to generate the data to address whether combination of a stabilizer with a silencer will add further benefit to patients who are progressing on current treatments. It's the largest study ever conducted in ATTR cardiomyopathy and the combination subgroup is quite sizable. We're looking forward to the data in the second half of this year, and we're prepared to submit the NDA by the end of this year and to launch next year. Thank you, Myles, for that question. Thank you, everybody, who joined us today and participated on our call. We're looking forward to an outstanding year and sharing our progress along the way. So until then, thank you, and have a great day, everybody.

Goodbye.

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