Ionis Pharmaceuticals Q1 2025 Earnings Call Transcript

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Provided by Quartr
April 30, 2025
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Operator

Good morning and welcome to the Ionis First Quarter twenty twenty five 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.

Wade Walke
Wade Walke
SVP - Investor Relations at Ionis Pharmaceuticals

Thank you, Amy. 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 that we will be discussing today, including a reconciliation of our 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, our Chief Executive Officer Kyle Janae, Chief Global Product Strategy Officer and Beth Haugen, Chief Financial Officer.

Wade Walke
Wade Walke
SVP - Investor Relations at Ionis Pharmaceuticals

Richard Geary, Chief Development Officer Eugene Schneider, Chief Clinical Development Officer Eric Swayze, Executive Vice President of Research and Jonathan Birchall, chief commercial officer, will also join us for the Q and A portion of our 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 consider the risk factors contained in our SEC filings for additional detail.

Wade Walke
Wade Walke
SVP - Investor Relations at Ionis Pharmaceuticals

And with that, I'll turn the call

Wade Walke
Wade Walke
SVP - Investor Relations at Ionis Pharmaceuticals

over to Brett.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Wade. Good morning, everyone, and thanks for joining us today. Before we discuss our Q1 earnings and recent progress, I want to take a moment to acknowledge the rapidly evolving environment we're living in today. Recent changes at the FDA and the introduction of new tariff policies have introduced a degree of uncertainty with the potential for disruption in our industry.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Despite these external uncertainties, Ionis remains well positioned to execute on our strategic priorities, including all of our many value driving catalysts coming up this year and next. We remain focused on our purpose, to drive meaningful value for all Iona stakeholders by successfully bringing better futures to people with serious diseases. We are executing very well against all our strategic priorities. A clear example of our ongoing successes is the completion of two strategic licensing transactions recently, which enabled us to substantially increase our 2025 financial guidance. This includes higher expected revenue and cash, along with improved operating loss.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Raising guidance this early in the year reflects our confidence in our ability to continue executing well, including our ability to deliver transformational medicines to patients, even amid the current volatility, and our commitment and expectation to drive long term value for shareholders. We achieved a major milestone for Ionis with our first independent commercial launch, now successfully underway. I'm pleased to share that in its first full quarter on the market, TrINGOLZA, the first and only FDA approved treatment for familial chylomicronemia syndrome, exceeded expectations. This encouraging start reflects our commercial team's thoughtful planning, outstanding execution, and highlights the commercial capabilities that we have built. Right behind Trincolza is our second independent launch, Donadolorsen, for Hereditary Angioedema, or HAE, which is rapidly approaching.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

The team is laser focused on ensuring success. Donadaluirsen has the potential to become a preferred treatment for AJE, and we remain on track to launch in the third quarter. These launches are just the beginning. We're poised to report data from two Ionis owned Phase III programs later this year, which if positive, will enable us to continue delivering a steady cadence of important medicines to even more patients. These are a second indication for olazarsen, severe hypertriglyceridemia, or SHTG, a large population with high unmet need, and zilganeursen for Alexander disease, a severe, rare leukodystrophy with no approved therapies.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Collectively, these four programs represent needed patient breakthroughs and multibillion dollar revenue potential for Ionis. Additionally, in the next three years, we expect four launches from our late stage partnered medicines currently in development to treat a range of serious life threatening diseases. These medicines are poised to significantly increase our revenues by expanding the reach of Ionis discovered medicines to more patients that are in need. With the recent launch of Trangolza and our upcoming independent and partnered launches, Ionis is on a path to bring important medicines to patients for years to come, positioning us to achieve substantial and sustained revenue growth and positive cash flow. With that, I'll turn the call over

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

to Kyle.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Thank you, Brett. With our first independent launch underway and three additional independent launches planned in the next two years, our commercial team is executing on a focused agenda with substantial growth potential. We're well positioned to build on the early success of Trin Golza while we prepare for our other upcoming launches. Donnitolorsen for HAE is on track for anticipated approval in August, followed by olezarsen for SHTG, which is on pace for Phase III data in the third quarter and a potential launch next year.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Let's start with Tringolza, which had an encouraging debut in the first quarter. Our commercial team executed seamlessly, delivering on all initial launch objectives and exceeding expectations with over $6,000,000 in net product sales in the first quarter. In this first full quarter on the market, we saw strong patient uptake driven by multiple factors. First, we successfully converted nearly all of The U. S.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Expanded access and clinical trial patients to commercial product. Second, as Trangosa is the first and only approved FDA treatment for FCS, early uptake benefited from patients who had been previously diagnosed and were waiting for treatment. And third, our patient finding efforts ahead of launch paid off, contributing to scripts from newly identified and diagnosed FCS patients. Physician engagement has also gained meaningful traction. We've been encouraged by the initial breadth of physicians prescribing Trincolza, with scripts from a mix of specialists across the country.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

At the end of Q1, the initial prescriber mix included approximately 50% cardiologist and 25% endocrinologists, with lipidologists and internal medicine HCPs comprising the rest. Physicians have also reported positive and deeply moving feedback, including one doctor who shared that he was quote, over the moon that this was the lowest his patient's TG levels have ever been. On the access front, coverage and reimbursement dynamics have been favorable. The coverage split for patients on Trangolsa to date is just over 60% commercial and just under 40% government. Importantly, patients, whether clinically diagnosed or genetically confirmed, have received timely access with most receiving coverage through the medical exception process based on clinical diagnosis.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

This underscores both the urgency of the high unmet need and payer willingness to support access ahead of establishing formal policies. As payers establish coverage policies over the next several months, it will be important that these policies support both clinical and genetic diagnosis pathways. To this end, our market access team is actively engaging with payers to enable continued patient access. Through the first quarter, the team had already engaged with payers representing the vast majority of covered lives in The U. S.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

And are working toward getting additional policies in place. We're also seeing positive trends beyond coverage, including reimbursement timelines that have exceeded our internal benchmarks, and in the first full quarter of launch, nearly ninety percent of patients had zero out of pocket costs, highlighting the effectiveness of our Ionis Every Step Support program. Ionis Every Step has been instrumental in delivering high quality experience for both patients and providers. More than ninety percent of patients have opted in, receiving support that includes disease and nutrition education, auto injector administration training, reimbursement support, and more. For healthcare providers, the program streamlines prescribing by handling insurance authorization and coverage assistance, as well as coordinating delivery, reauthorizations, and refills.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

We're proud of Trangosa's early momentum, but we know we're still in the early innings. The vast majority of the estimated three thousand people living with FCS in The U. S. Remain unidentified. To close that gap, we're continuing to focus on our patient finding efforts and HCP education, targeting physicians who treat patients with severe hypertriglyceridemia to increase FCS awareness.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

At the same time, our payer engagement efforts will continue to focus on establishing broad, durable access. Backed by an experienced and high performing team, we are well positioned to build on our first mover advantage to bring Tringolsys to patients in need, and keep them on treatment. Building on our foundation in FCS, we're advancing toward the blockbuster opportunity in SHTG with olazarsen. Like FCS, SHTG is a serious condition defined by triglyceride levels over 500 milligrams per deciliter well above the normal level of less than 150. These levels are easily determined through routine fasting blood tests.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

SHTG affects a broad population with many people unable to adequately manage their triglycerides with currently available treatments. This is particularly true for individuals with high risk SHTG, defined as triglyceride levels greater than eight eighty milligrams per deciliter, or greater than 500 with a history of acute pancreatitis or other comorbidities. There are more than 1,000,000 of these especially vulnerable people in The US, which represents our initial target population for olazarsen, assuming approval. As we heard during our recent KOL panel, SHTG represents a significant unmet medical need, and physicians are eager for better treatment options, especially those that can reduce TGs down below pancreatitis risk levels. For example, Doctor.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Alan Brown, a leading cardiologist focused on lipid management, shared that devastating, with patients experiencing recurrent pancreatitis attacks despite best efforts. His primary goal is to reduce the risk of acute pancreatitis, which carries significant mortality and morbidity. Importantly, all three panelists agreed that APOC3 inhibition offers a promising new therapeutic pathway with the potential to help patients dramatically reduce their triglycerides and the associated risk of acute pancreatitis. This view is also shared by other physicians who we've engaged with, including recent discussions at the American Academy of Cardiology Annual Conference with KOLs and community cardiologists. With this conviction to treat, we believe olanzarcen is well positioned to meet the needs of people with SHTG, and we're making excellent progress across clinical and commercial fronts as we prepare for an anticipated launch next year, where we also have first mover advantage.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

We expect data from our supportive safety study, ESSENCE, in the second quarter. We then expect to report data in the third quarter from our global pivotal SHTG studies. These pivotal studies, CORE and CORE-two, are being conducted in our target SHTG population, defined by triglycerides greater than 500 milligrams per deciliter. Baseline characteristics were recently published in the American Heart Journal, showing that fasting median triglycerides at baseline in CORE and CORE II were eight thirty six and seven forty nine milligrams per deciliter, respectively. And across the two studies, nearly half of participants had baseline Tg levels of greater than eight eighty, even though all participants were receiving standard of care therapy.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Additionally, twenty two percent and thirteen percent of participants had a history of pancreatitis in the last ten years prior to enrollment respectively. Importantly, both studies are well powered to show a significant reduction in triglycerides, and it's this reduction that we expect will lead to improvements in clinical outcomes for patients. Assuming positive data, we plan to submit an sNDA before year end. We're also expanding olazarcin's reach. We recently broadened our partnership with Sovi, who will commercialize olazarcin in most markets outside The U.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

S, including in Europe, which is on pace for an FCS approval decision later this year. This agreement expands the reach of Trin Golza to more patients globally, while providing us the opportunity to earn milestone payments and royalties up to the mid-twenty percent range. With significant first mover advantage in both FCS and SHTG, compelling real world data and phase three results in FCS, and confidence in the upcoming data for SHTG, we believe olanzarcen is well positioned to become the standard of care in both indications, transforming treatment for thousands of people and driving long term growth for Ionis. Turning to donnedolorsen, our second anticipated independent launch, we see compelling opportunity to advance the prophylactic treatment for people with hereditary angioedema. We're applying the same discipline and focus that is driving a successful Trangolda launch as we prepare to bring donadolorsen to market.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

More than 20,000 people in The U. S. And Europe are estimated to have HAE. In The U. S, most of these patients are on prophylactic treatment.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

As this market continues to evolve, up to twenty percent of patients annually have switched treatments in search of more effective and convenient options, signaling that current therapies aren't adequately addressing patients' needs. Additionally, a recent Harris poll found that nine in ten HAE patients surveyed are interested in trying new prophylactic therapies, and we believe is uniquely positioned to meet that demand if approved. With strong clinical data, a patient friendly auto injector, and monthly or every other month dosing, we believe donadolorsen checks all the boxes that people with HEE are looking for in a next generation prophylactic treatment. We're building momentum ahead of launch by drawing on learnings and infrastructure from our ongoing Trangolza and Waynua launches. This includes expanding our Ionis Every Step patient support program to address the unique needs of HEE patients to ensure they have a seamless treatment experience.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

We've already hired a substantial portion of our field facing team and remain on track to complete hiring and training ahead of the anticipated approval. Our market access team is actively engaging with payers, and our medical affairs team has also been laying the groundwork for a successful launch. Their efforts include showcasing our robust Donnie Dulorsen clinical data and Ionis' technology conferences. For example, at the recent Quad AI meeting, we delivered 11 poster presentations and had robust engagement at our booth, including a dedicated space for unbranded HAE disease awareness campaign. We also capitalized on the conference's San Diego location by welcoming physicians to our campus for deeper in person education about Ionis' science and technology.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Physician feedback continues to be positive, particularly regarding our switch study, which we believe could be a key differentiator in a competitive space. The study showed that people switching to donidolorsen from other prophylactic treatments experienced a further reduction in attacks, and eighty four percent of those surveyed said they preferred donnivolorsen compared to their previous prophylactic treatment. While we recognize that converting people from existing therapies will take time, we're confident that donnivolorsen represents a compelling opportunity to be the preferred prophylactic treatment for many HAE patients. We're excited about the road ahead and well positioned to bring donnivolorsen to people who need it, assuming approval. Our highly experienced, efficient, and scalable commercial organization is delivering tangible results with the Trinolza FCS launch underway.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

And as we build on these efforts, we're focused on maximizing Trinolza's full potential while preparing to successfully execute on our three additional launches planned over the next two years with more to follow positioning Ionis for sustained growth and long term success. With that, I'll now turn the call over to Beth.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

Thank you, Kyle. I am pleased to share today that we are increasing our 2025 financial guidance across all metrics, including raising revenue by more than 20% due to our strong first quarter results and recent successful licensing transactions. We earned $132,000,000 of revenue in the first quarter, which increased 10% year over year. More than half of our revenue came from commercial products, which grew 28% compared to the same period last year. Our increasing revenue reflected the encouraging early performance of the TrINGOLZA launch, marking the first time in our company's history we've reported product revenue.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

In the first full quarter of the launch, Trincalza generated over $6,000,000 in product sales exceeding expectations. As Kyle discussed, we saw good uptake from patients awaiting treatment and from newly identified patients. Our commercial revenue also included $48,000,000 in SPINRAZA royalties from substantial SPINRAZA product sales, which increased 25% year over year. Additionally, we earned $9,000,000 in Waynua royalties. We and our partner AstraZeneca expect Waynua revenue to grow this year, driven by strong US demand and an expanding global footprint following the recent EU approval.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

The remainder of our revenue came from programs under our R and D collaboration, underscoring the important financial contributions of our partnered pipeline. You may have noticed we've streamlined the revenue section of our P and L. We did this to reflect our new chapter as a commercial stage biotech and to plan for numerous independent launches in the coming years. Total non GAAP operating expenses increased less than 5%, reflecting our commitment to disciplined investment and driving operating leverage. As planned, our sales and marketing expenses increased year over year, reflecting our investments in The U.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

S. Launch of Trin Golza and preparations for the upcoming launch of donadolorsen. Our SG and A expenses also included our minority portion of WeiNUA's sales and marketing expenses. R and D expenses decreased year over year as several of our late stage studies recently concluded. Importantly, we continue to appropriately fund our advancing pipeline, with a large majority of our total R and D expenses funding our late stage programs.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

Building on our first our strong first quarter results, we recently completed licensing transactions for sapaglutzin and ex US commercialization rights for olosarcin that meaningfully enhanced our financial outlook. This is the reason we are substantially increasing our 2025 guidance. Last week, we finalized the licensing of sapaglutzin, a medicine outside of our core disease areas of cardiology and neurology, and generating $280,000,000 This transaction enables us to remain focused on realizing the potential of the medicines that we plan to independently bring to patients, while further strengthening our financial position. Additionally, we are eligible to earn significant milestone payments as sapagliflozin advances, together with royalties up to the mid teen percentage range on future product sales. As a result of the substantial license fees, which exceeded the probabilized revenue included in our original guidance, we are increasing our revenue guidance by more than 20%.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

We now expect to earn revenue in the July to $750,000,000 range for the year. Our revenue guidance also includes sizable commercial revenue anchored by stable SPINRAZA royalties and growing way newer royalties. And with our first independent launch underway, we expect increasing product revenues as the year progresses. As the TrINGOZA launch progresses, it's important to remember that FCS is a rare disease with most patients still unidentified and undiagnosed. Therefore, our focus remains on disease education and patient identification, both of which will take time.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

We're also on track to add initial product revenue from our second launch with the FDA action date for donadolorsen set for August 21. In addition to the sapaglutzin revenue we will recognize in Q2, we expect to earn additional R and D revenue from partnered programs later this year. We continue to project our full year 2025 operating expenses to increase in the high single digit percentage range compared to last year. This increase will be driven by SG and A expenses as we invest to support the success of our multiple ongoing and planned launches. We project our R and D expenses to remain steady this year, similar to last year.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

As several of our late stage studies have recently concluded, or are wrapping up this year, we are able to reallocate our resources toward our next wave of opportunities, including ION five eighty two for Angelman syndrome, which we expect to start phase three development shortly. Since our license fee revenue drops entirely to our bottom line, we are improving our non GAAP operating loss guidance by nearly 25% to less than $375,000,000 And we now expect to end the year with $1,900,000,000 in cash. Our strengthened balance sheet and commitment to drive operating leverage positions us well to advance our strategic priorities in this dynamic macroeconomic environment. Looking beyond 2025, we are confident in our ability to deliver sustained revenue growth. The late stage programs we have in our pipeline today represent a significant opportunity, with combined peak sales potential in the multibillion dollar range.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

We expect our Ionis owned medicines to generate more than $3,000,000,000 in peak annual product sales. This, of course, means that we will continue making investments to bring these medicines to patients. On top of our substantial product revenue opportunity, our late stage partnered medicines could contribute over $2,000,000,000 annually in peak royalties. Notably, nearly all of these medicines are on track to deliver phase three data either this year or next year, setting the stage for potential launches soon after. Together, these upcoming launches are poised to reach hundreds of thousands of patients worldwide.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

And in turn, position Ionis to deliver significant top line growth and reach sustainable positive cash flow, turning scientific innovation into long term value for shareholders. And with that, I'll turn the call back over to Brett.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thank you, Beth. We've accomplished a great deal to get us where we are today, a fully integrated commercial stage biotech company with our first independent launch well underway. 2025 is off to an excellent start, including The U. Tremgosa launch. With additional upcoming launches anticipated, including Donadolorsen for HAE, and a deep commitment to innovation, we're well positioned to drive accelerating value.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

It's through Ionis' innovation that we've established a proven discovery and development engine, which has provided us with with a pipeline of medicines with transformational potential. Our pipeline continues to deliver. We are on track for olanzarcen and zilganeursen Phase III data later this year, that if positive would expand the reach of our medicines to even more patients. And with many additional Phase III data readouts expected next year, we're well positioned to continue bringing a steady cadence of medicines to patients. Our scalable and experienced commercial organization is executing well, as demonstrated by the encouraging start to the TRYNGOZA launch.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Furthermore, our commercial organization has established a solid foundation to support multiple planned product launches in the future. And based on recent successful licensing transactions along with our first quarter results and disciplined financial management, we significantly increased our 2025 financial guidance. Importantly, the progress we've made puts us on a clear path to achieving positive cash flow supported by our expectations for substantial top line revenue growth. And with that, we'll now open the call up for questions.

Operator

Thank you. To ask a question you may press star then one on your telephone keypad. If you're using a speakerphone please pick up your handset before pressing the keys. Please limit yourself to one question and one follow-up. If you have further questions you may reenter the question queue.

Operator

To withdraw your question you may press star then 2. At this time we'll pause momentarily to some of our roster. Actually we'll just go straight to Jay Olson from Oppenheimer.

Jay Olson
Managing Director & Senior Analyst - Biotechnology at Oppenheimer & Co. Inc.

Oh hey, congrats on all the progress and thank you for taking our question. We're curious about olazarcin and any overlap between physician prescribers for FCS and SHTG and how you plan to leverage that. And then related to that, would approximately twenty percent pancreatitis history for the patients enrolled in your pivotal SHTG studies provide sufficient power to show AP reduction, and what level of AP reduction are you targeting? Thank you.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Jay.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Kyle will take the overlap of prescribers for FCS SHTG, and I'll touch on the AP question you had.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yeah, thanks, Jay. First, I mean, the Trignolza launch is really off to an encouraging start. Execution by the commercial team has been very strong. I'm very pleased with where we're at right now. As we discussed, we've been able to convert the EAP and OLE patients.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Those that have been waiting for therapy have begun getting treatment, and we're also identifying new patients. The current targets that we have are a few thousand physicians, as you would expect, based on type that are treating FCS today. These are cardiologists and endocrinologists, and they're seeing SHTG patients, but they're also seeing FCS patients. So that's kind of the runway to get us to SHTG. When you get to SHTG, the population expands obviously upwards of north of a million patients.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

And as we go there, the overlap is quite significant. There are still cardiologists, endocrinologists, and lipidologists treating these patients. They're currently being treated with suboptimal therapies and not getting the goal. And what we're hearing, and we heard this from the KOL panel that we did on April 14, is that there's the realization that reducing triglycerides is directly correlated to AP, and physicians are well aware of that, and they're looking for a better treatment option, and we're looking forward to potentially having positive data and an approval for olanzarcen to be able to help those patients.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Kyle. Jay, obviously you're referring to the AP baseline event data that we reported in our baseline demographics clinical trial design study that we published last month, or earlier this month, where we had twenty two percent in COR and thirteen percent in COR2 patients with a history of AP over the last ten years. I want to emphasize before I get into expectations for AP data from those studies that this is a substantial unmet medical need, large patient population, that HCPs health care providers are ready to treat patients with SHTG even without AP data in hand. This is a large market opportunity, a large unmet need. And what we heard in our HCP panel, and we've heard from other HCPs, that they are looking for a medicine that will substantially reduce triglycerides on top of standard of care, which is exactly how our trial is designed.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

That is the opportunity there. Now with that said, AP is of course is a secondary endpoint in our study as a secondary endpoint is not powered for AP. But we're doing everything we can to increase the powering for the study. For example, we are combining COR and COR2 in our secondary analysis of AP events. And we're looking at AP events at twelve months, whereas the triglyceride primary endpoint is at six months.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

We're extending, we're looking at the maximum amount of time in patients to look at AP data. And of course the FCS data is also encouraging for Trincalza where we reported statistically significant reductions in acute pancreatitis events in our BALANCE study. So take all that into account, but really what we are laser focused on is to demonstrate substantial reductions of triglycerides in SHTG patients, which is what HCPs are looking for to prescribe a medicine like olazarsen.

Operator

The next question comes from Gary Nachman at Raymond James.

Gary Nachman
Gary Nachman
Managing Director - Equity Research at Raymond James Financial

Hey, thanks for taking the questions and nice quarter. So, on DonaDuloresyn, just talk a bit more about what you're doing ahead of the PDUFA date internally to prepare for that launch. Know, patients that are

Gary Nachman
Gary Nachman
Managing Director - Equity Research at Raymond James Financial

going to be

Gary Nachman
Gary Nachman
Managing Director - Equity Research at Raymond James Financial

switching, how you're thinking about that transition, I guess, the first year of launch? And just in terms of access, how long you think that process is going to take? And then just as a follow-up, know, Brad on the macro dynamics, you just highlighted it briefly, but just talk a bit more what you think the expected impact from tariffs is going to be to the overall business just based on the current trade policy and just in terms of your conversations with FDA, if you're seeing any sort of signs of potential delays, whether with PDUFA dates or starting clinical studies? Thank you.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Great. Kyle, on the launch.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yeah. What we know about the HAE market is this is largely an unsatisfied market. We see approximately twenty percent of patients that are moving between prophylactic treatments in The U. S. On an annual basis.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

We also recently released the Harris Poll that showed that nine out of ten patients are interested in trying new therapies in this space. So there's definitely an opportunity here in the Donnie D'Lorson profile in terms of efficacy, tolerability, and convenience is offered all in one single treatment. And when we start talking about switching patients and the dynamic of why patients want to switch, it's one of those three reasons that they're looking for something new and different. We're going to be able to provide Donadolorsen in a way that demonstrates reductions in attacks, improved tolerability, and they're only going to have to take the treatment every four or every eight weeks. So the profile is very, very strong there.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

In terms of switching patients, what we need to do is we need patients to advocate for themselves, and we need physicians to understand what these patients are experiencing. And that's the work that we're doing right now. We're being informed by patients, and we're also beginning to communicate directly with HCPs what the need is in this market and setting ourselves up to be able to talk about how and why to switch these patients and why it's important for that to happen. But this is a switch market. We will begin the ramp hopefully in Q4, and we anticipate peak sales being greater than $500,000,000 for Donnie DeLorson.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

And with a concentrated prescriber base, we can have a very targeted sales force to go out and do that, which is currently being hired and trained and going to be deployed well in advance of the PDUFA date.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Kyle. To your other question, Gary, we are obviously carefully monitoring changes that the new administration is bringing both at the FDA and at the macro level on tariffs, etcetera. At the FDA, today we're pleased to report that we've had no changes in any of the programs that we've been discussing with the FDA. Everything is on track. As mentioned earlier, DonatoLaurin's PDUFA is on track for August 21.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

And the discussions we're having are the exact discussions we should be having at this stage of the review process. Same is true for our other discussions with the FDA, INDs and so on. So everything appears to be going well with the FDA at this time despite the changes that are occurring. We'll of course keep on monitoring that. With respect to other changes, tariffs, etcetera, that too we have not seen any meaningful impact on our business to date.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

That includes costs or that we have to potentially absorb for drugs that are already launched or future drugs. With respect to commercial supply and clinical supply, that is also going very well. We have sufficient supplies in place to support the Trangosa launch and the Dona del Vorcen launch. And they're ready to go and support those launches for the near term. And for our clinical trials, we make drug here at Ionis as well as with some CMOs, but we have a lot of redundancies in the supply chain to support our clinical trial studies with respect to supply.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

So it's obviously a fluid situation that we're monitoring very carefully and building contingencies to manage. However, to date we have not had any impact with respect to tariffs or with the FDA on our business.

Operator

The next question comes from Datti Chattopadhyay at Guggenheim.

Debjit Chattopadhyay
Managing Director at Guggenheim Partners

Hey, good morning, and thanks for taking my question. On the FCS launch, how confident is the team on the 2,000 plus FCS patient estimate? And how quickly can you convert these patients to commercial therapy before you have significant price erosion with a launch in SHTG? Thank you.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

John, can you take that please?

Jonathan Birchall
Jonathan Birchall
Senior VP & Chief Commercial Officer at Ionis Pharmaceuticals

Yeah, happy to take that. I think while the epidemiology varies between one and thirteen per million, we're fairly confident in those 3,000. The genesis of your question though really is how quickly can we identify them. I think as Kyle outlined, we obviously had clinical trial patients that we've been able to convert onto covered product very quickly.

Jonathan Birchall
Jonathan Birchall
Senior VP & Chief Commercial Officer at Ionis Pharmaceuticals

In the prelaunch phase, we were definitely very successful in engaging with our target audience and identifying FCS patients. And that's helped drive our initial uptake in the product. But in every month as more and more physicians become aware, we're finding more and more patients. And that's very encouraging for the outlook that we've got for FCS. I definitely think this is an underserved community with a very debilitating disease.

Jonathan Birchall
Jonathan Birchall
Senior VP & Chief Commercial Officer at Ionis Pharmaceuticals

And as that awareness grows, both amongst HCPs, but importantly through a lot of the work we're doing with omnichannel, we're going to find more and more patients in the next eighteen months prior to the SHTG launch. Obviously with positive data and potential approval from the FDA, as soon as that indication expands, we'll be addressing the far larger population, the specifics of FCS become less apparent. And price erosion?

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

So yeah, in terms of price, we priced at the FCS launch appropriately with the 3,000 patient population out there, right? And that's how we ended up at the price point that we did and the value that Tringosa brings to that patient population. As we think about moving forward for SHTG, that population is going to be exponentially higher, right, 1,000,000 plus addressable in terms of the population. If we look at the marketplace, typically drugs that have a million or so patients addressable are in the specialty pricing range of 10,000 to $20,000 for example. We've got some work to do to figure out what the pricing will be ultimately in this category based on the data that supports the program itself, which we'll know later this year.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

And we'll go back and do some more research and then obviously announce the price when we receive approval for the SHTG indication.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Again, we're very encouraged by the Trigolza launch to date. It is early days, of course, but we expect to be commercializing Trigolza in FCS for a year and a half to two years before SHTG commercialization will kick in.

Operator

The next question is from Jessica Fry at JPMorgan.

Jessica Fye
Jessica Fye
Managing Director & Equity Research Analyst - Biotechnology at JP Morgan

Hey, guys. Good morning. Thanks for taking my questions. I just had a couple. Maybe I missed this, but was there any channel stocking for Tringolsys captured in that 1Q number?

Jessica Fye
Jessica Fye
Managing Director & Equity Research Analyst - Biotechnology at JP Morgan

And if so, can you quantify that? Second one, can you just elaborate a little bit more on the sources of upside to the revenue guidance and how of that's driven by commercial product performance versus the licensing deal? And lastly, you kinda touched on this, maybe just a little more specifics. Can you just talk about the manufacturing footprint for Trimgolza, Dining Doloresin, and how you think about possible exposure to tariffs? Thanks.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Sure. So channel stocking, Kyle, for Trungolza?

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yes. The Trungolza sales is currently directly correlated to demand. There was not a large stock end of inventory. It's adequately being managed per the contract that we have in place with the specialty pharmacy, and it's really reflected by demand.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

You want to add anything to that, Beth, as well as then talk about the revenue guidance?

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

Sure. Would just second what Kyle said, that the team has done a wonderful job at managing inventories. And of course, with a rare disease drug like Trigalza, you want to make sure that you're keeping those inventory levels as low as you possibly can and driving inventory in the channel from demand, which is exactly what the team is doing. On the revenue guidance, it's based on obviously a strong Q1. But the vast majority of that raise is related to the licensing transactions we did for sapaglutzin with Ono and the OUS commercial licensing to Sobi for olanzarcen.

Elizabeth L. Hougen
Elizabeth L. Hougen
Executive VP of Finance & CFO at Ionis Pharmaceuticals

So those transactions were, as you can imagine, probabilized in our initial guidance of more than $600,000,000 in revenue. And with the now completion of those transactions, we're increasing our guidance to reflect 100% probability and flowing that through not only revenue, but to our operating loss and to our cash guidance as well.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

And regarding manufacturing, Jess, we have a number of sources for supplying our drugs for both clinical trials, as well as for the commercial launches, including South Korea, Europe, and The US. As I mentioned earlier to one of the other questions, we're well stocked in supply already to support the Trincosa launches, as well as the anticipated launch for Donatilorsen. So all that's in place. We're continuing to monitor any potential impact, but right now there has not been any. And that includes on tariffs as well.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Really we haven't, we're watching it very carefully, but we have not experienced any meaningful impacts. And our guidance stays the same. We just improved our guidance. And that's also factoring in any potential impact of tariffs.

Operator

The next question is from Jason Garberry at Bank of America.

Chi Fong
Chi Fong
VP - Equity Research at Bank of America Merrill Lynch

Hey, this is Chi on for Jason. Thanks for taking our question. Maybe just on a follow-up on TRINGOZA, can you unpack a little bit between the conversion that you see from your expanded access and newly identified patients that were previously not enrolled in any of the prior clinical trials? And understood that this is a market that requires a market building. Are you seeing a steady case of new starts?

Chi Fong
Chi Fong
VP - Equity Research at Bank of America Merrill Lynch

And just a quick follow-up on your Angelman. You guys have it on track for 2Q phase three start. Are there any outstanding staff needed to execute before the Phase III start? Thanks so much.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Okay. Thanks, Chi. I'll take the Angelman's question, which is a brief answer. And then Kyle will take the question with respect to conversion of EAP OLE patients. So a new start.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

So the Angelman study, Phase III study is on track for on time initiation. As a reminder, we had excellent discussions and completion of conversations with the FDA last year. We aligned on our Phase three trial design. We think we have the right trial design, we have the right drug, the right chemical platform to get this study started in the first half of this year, which means it'll get started in this quarter. So very soon we're well on our way.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

What we've also said is that our expectation is to complete enrollment in 2026. So we expect to enroll fairly quickly.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yeah, thanks Brett. In terms of the TRINGOZA launch, very strong patient uptake in Q1 as we were referencing and it's demand driven. The conversion of EAP and OLE patients was obviously a main focus here in moving those patients on to commercial drug. As we mentioned, the majority of those patients converted over, which was exactly what we expected to have happen. The second area of patient population we talked about are those that were waiting for treatment, right?

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

This was kind of the pent up patients that had been treated for years and unfortunately didn't have a therapeutic option available. Those have also many of them have started on treatment as well. And then the identification of new patients is really what we're going to be focused on moving forward. That's the main focus of our work. But in Q1, we had patients from all three of those buckets, but the predominant patient populations were coming from the EAP OLE and the pent up demand patients that had already been identified.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

So our focus really is getting new patients diagnosed, new patients treated, and working them through the payer channel, which we're doing very effectively right now. Jonathan, maybe you can add a little bit.

Jonathan Birchall
Jonathan Birchall
Senior VP & Chief Commercial Officer at Ionis Pharmaceuticals

Yeah, perhaps a little bit of color. We're definitely having success engaging with HCPs to actually find both patients that were identified prior to launch and converting them to covered product, number one. But also number two is the awareness gets out there, finding new patients and becoming aware of patients that we weren't aware of at launch. So that's super encouraging in the first quarter of our launch.

Chi Fong
Chi Fong
VP - Equity Research at Bank of America Merrill Lynch

Thanks so much.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Jim.

Operator

The next question comes from Yaron Werber at TD Cowen.

Yaron Werber
Managing Director, Senior Biotechnology Analyst at Cowen and Company

Right. Thanks so much. Congrats on nice progress. Maybe just a couple of questions from me. The first one on Can you give us a little bit of a sense the Part D redesign now that it's in effect and it's capping patients to $2 out of pocket, how does that going to, do you think sort of, impact uptake, under Part D?

Yaron Werber
Managing Director, Senior Biotechnology Analyst at Cowen and Company

And then, on Chingolza, do you have any sense? I mean, the 6,000,000 is really a great number. That sounds like it's a good baseline from here onwards. From here on, do you already have patients that you think are going to come on board pretty quickly that are diagnosed or, as we kind of think ahead about growth in patient identification, maybe give us some qualitative view on how fast that can be?

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yes. Let me touch on whenua first. AstraZeneca continued to see very strong U. S. Demand for whenua.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

The redesign of Medicare Part D impacted some of the Q1 revenue, but there are a lot of positives that you just emphasized in terms of the out of pocket change that's happening. First of all, I think you're going to see an increased volume from new patient starts because of this. We're seeing cardiologists and neurologists prescribe whenua, and what they're telling us is that, it's going to, number one, increase the number of patients they can treat because of affordability, and number two, they feel like it's going to increase the compliance rates for those patients as well, because they're going to be able to afford their medication moving forward. So I think that has a significant advantage and opportunity for patients overall, and whenua specifically, to be able to demonstrate revenue growth quarter over quarter as we move forward in 2025. I think we're very optimistic about that.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

In terms of the Tringosa question, again, greater than $6,000,000 in the first quarter. We just talked about the three patient buckets that that came from. But we do have additional patients that are being identified currently that are potentially going to go on to, Trangulza. This takes a lot of work, right? 3,000 potential patients in The U.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

S. We're doing a lot of work, not only with our customer facing teams, but also with our omni channel efforts, and the education that we're doing with our medical affairs groups at congresses and in different meetings. So those are the things that we're doing to get the word out about the new treatment option available, how to diagnose FCS patients. But it's going to take some time and some work, but we are encouraged by the number of patients that are coming forward, and we'll work to get them on treatment this quarter and moving forward throughout the year.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Kyle. Remember, Yaron, that Waynu is now launched outside The US and Europe as well. So we're expecting continued revenue growth and based on strong patient demand, not only in The US but also in other geographies as well in 2025 and going forward.

Operator

The next question is from Luka Issy at RBC Capital Markets.

Cassie Yuan
Cassie Yuan
Equity Research Associate - Biotechnology at RBC Capital Markets

Hi, good morning team. This is Cassie on for Luca. Thanks so much for taking the question and congrats on the impressive launch to date for Trincoza. And this question will be on TTR cardiomyopathy. We appreciate still early days as cardio transform has yet to read out, But were you surprised by an item not lowering pricing when they got label extension for cardiomyopathy?

Cassie Yuan
Cassie Yuan
Equity Research Associate - Biotechnology at RBC Capital Markets

And are you planning to follow the same playbook? Or is there a scenario where you compete with them by lowering the price? Any color there would

Cassie Yuan
Cassie Yuan
Equity Research Associate - Biotechnology at RBC Capital Markets

be much appreciated. Thank you.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yeah, in terms of Alnylam strategy, I wasn't too surprised by that. I believe they've got a balance of patients that are hereditary polyneuropathy patients, and, I think they're trying to maintain a price in order to manage their revenues, you know, now and moving forward. And it's up to them kind of how that market evolves, I think, and what they're able to get coverage on for cardiomyopathy. I think that's yet to be determined. In terms of the strategy for Weinua, that's ultimately AstraZeneca's decision in terms of how they navigate that.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

I'm sure there are a lot of learnings in this market, and as the market continues to evolve, we'll take a look in terms of reimbursement and coverage and physician and patient feedback and figure out what the right price point is for Weinua based on the benefit and value that it delivers.

Operator

The next question comes from David Lebowitz at Citi.

David Lebowitz
David Lebowitz
Analyst at Citigroup

Thank you very much for taking my question. When you look at the core trials and the baseline AP data I'm curious as to how the analysis in the trials will actually be carried out. Is it going to be strictly, based on baseline for the overall population relative to, reductions? Will there be additional, studies or analyses on patients that actually had baseline AP events to reduce, but over the smaller denominator? I'm curious to what's prespecified and what could possibly be accepted by the FDA for labeling consideration.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Eugene?

Eugene Schneider
Eugene Schneider
Executive VP, Chief Clinical Development & Operations Officer at Ionis Pharmaceuticals

Yeah, thanks. Thanks for the question. So certainly the analysis of AP events, the prespecified analysis, will look at all events happening during the twelve months exposure in a trial, and obviously comparing the active arm versus placebo. We will look at population that had a baseline, or at baseline reported historical events, but that's a smaller, much smaller subgroup.

Eugene Schneider
Eugene Schneider
Executive VP, Chief Clinical Development & Operations Officer at Ionis Pharmaceuticals

I guess the answer is that the overall analysis will look at all events happening during the trial, comparing the oligosarcin patients.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

And I believe, if I recall, Eugene, we'll also be looking at AP in patients above and below eight eighty in analysis as well. So we'll be carving up the AP data based on history of AP and without and so on. As far as the labeling discussions and getting AP in the label, think that's a data driven outcome that we'll have to talk about with the FDA. But again, as I emphasized earlier, we believe that this is a very substantial unmet need and a very sizable market opportunity for Ionis based on triglyceride lowering. But these patients are suffering from acute pancreatitis and we have a substantial number of patients with a history of AP enrolled in our study.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

So we think we have the right trial design that if we can see it, we have the potential to see it.

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

Yeah, I'll just add that we have AP in the label now for Trin Golza, which is in the FCS population, but that's very beneficial. And then the read through in terms of the connection between triglycerides and lowering of acute pancreatitis, we know from the recent KOL panel that we just had that that's well understood, Brett and Eugene just described.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, David.

Operator

Question comes from Mani Suhar at Leerink.

Lili Nsongo
VP - Equity Research, Biotechnology at Leerink Partners

Hi, this is Lily on for Mani. First question, digging a little more into the patient and the script for TRYNGOLZA. So you mentioned that the majority of patients were from the open label extension as well as the EAP program. But in terms of the remaining patients or the newly diagnosed and previously diagnosed patients, could you give a little more color on the distribution there between newly diagnosed and previously diagnosed as well as your expectations as how it will evolve quarter to quarter?

Kyle Jenne
Kyle Jenne
Executive VP & Chief Global Product Strategy Officer at Ionis Pharmaceuticals

I don't have too much additional color to add. We're not going to disclose the exact patient numbers or the percentages at this point in time. But we are encouraged at the patient finding work that we've done, the identification of new patients so far, and we believe we'll be able to add incremental patients quarter over quarter as we move forward throughout the year. The launch is going very well, as we talked about, strong patient uptake and strong demand and good payer coverage. So I think we're in a great place.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Yeah, and just to clarify, I don't think we said that the majority of patients are from the open label extension. What we said was that we have obviously patients in the open label extension study from the Phase III trial, which had 66 patients in balance. And then of course we're focused on The US segment of that. Many of those patients, the majority of those patients have converted over to commercial but that doesn't necessarily represent the overall patient population that is on Trigolzia commercially today. Going forward it's going be newly identified patients.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

That's what we would emphasize because those patients that were already diagnosed as well as the clinical trial patients, did a good job. We are doing a good job converting those patients, but going forward it's all about patient identification. So we have a lot of work to do.

Jonathan Birchall
Jonathan Birchall
Senior VP & Chief Commercial Officer at Ionis Pharmaceuticals

Yeah, one thing I'll add is we're definitely finding new patients, just to be transparent around that. I mean, it's very difficult to seek a diagnosis for a condition where it doesn't ultimately change the treatment. So as awareness builds, clinical experience builds, there's far more motivation to see these patients, and they're definitely out there, they definitely exist.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

I think we have time for one more question.

Operator

The last question comes from Mike Ulz at Morgan Stanley.

Michael Ulz
Michael Ulz
Analyst at Morgan Stanley

Hey guys, thanks for taking the question and for squeezing me in. Maybe just a follow-up on olicersen and SHTG. It looks like you narrowed the timing of that data slightly for the core and core two studies to 3Q from the second half previously. Just curious, any reason behind that? And then secondly, maybe just to clarify, will that initial update from those studies include the twelve month AP data?

Michael Ulz
Michael Ulz
Analyst at Morgan Stanley

Thanks.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Thanks, Mike. No, nothing really behind it. Just as we get closer to the data readouts and we get through everything we need to get through, all the blocking and tackling to read out the top line data, provide more clarity. So yes, we have provided more precision Q2 ESSENCE data, Q3 core and core two top line data.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

With respect

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

to AP readouts, we don't expect AP in the ESSENCE study, of course, just to confirm that. These are mildly elevated patients with triglycerides. Don't have many AP events. This is a safety study to support these exposure database that's necessary for a highly prevalent disease in the eyes of the FDA. So really we're focused on triglyceride lowering in that study and safety.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

And I just also want to emphasize that the percent reductions in triglycerides that we expect in essence is not a reflection of what we would expect in core SHTG. And that's because these patients are only mildly elevated. So we're expecting good substantial reductions in TGS, but not to the magnitude of what we would expect in CORE. In the top line data for CORE and CORE II, we're still working that out, whether we will have the AP data in time for that top line data, but we'll be focused on there principally the triglyceride reductions and safety for CORE and CORE two. And if we have the AP data at that time, we certainly share it in our top line announcement later this year.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

So thanks for the question, Mike. Thanks everybody for participating and all the great questions. I'd like to really emphasize that looking forward, we're excited about building on our momentum throughout the year and sharing our additional achievements with all of you along the way. So thanks again for participating, and we'll talk soon.

Brett Monia
Brett Monia
Chief Executive Officer at Ionis Pharmaceuticals

Have a great day.

Operator

Goodbye.

Executives
    • Wade Walke
      Wade Walke
      SVP - Investor Relations
    • Brett Monia
      Brett Monia
      Chief Executive Officer
    • Kyle Jenne
      Kyle Jenne
      Executive VP & Chief Global Product Strategy Officer
    • Elizabeth L. Hougen
      Elizabeth L. Hougen
      Executive VP of Finance & CFO
    • Jonathan Birchall
      Jonathan Birchall
      Senior VP & Chief Commercial Officer
    • Eugene Schneider
      Eugene Schneider
      Executive VP, Chief Clinical Development & Operations Officer
Analysts
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Key Takeaways

  • Raised 2025 guidance: Ionis increased its full‐year 2025 revenue guidance by over 20% to $650–$750 million, improved operating loss outlook, and boosted cash expectations to $1.9 billion, driven by strong Q1 results and licensing deals.
  • Successful Tringolza launch: In its first full market quarter, Tringolza generated >$6 million in net product sales for familial chylomicronemia syndrome, exceeding expectations through patient conversions, pent-up demand, and robust payer coverage.
  • Upcoming independent launches on track: Donadelorsen for hereditary angioedema is set for Q3 launch, while pivotal Phase III readouts for olanzarcen in severe hypertriglyceridemia and zilganersun in Alexander disease are expected later this year.
  • Rich late-stage pipeline: Ionis owns four independent programs with multibillion-dollar peak sales potential and has four partnered late-stage candidates due to launch by 2028, positioning for sustainable revenue growth and positive cash flow.
  • Disciplined financial management: Non-GAAP operating expenses grew <5% in Q1, reflecting controlled R&D investments and strategic SG&A increases to support multiple launches, demonstrating operating leverage.
AI Generated. May Contain Errors.
Earnings Conference Call
Ionis Pharmaceuticals Q1 2025
00:00 / 00:00

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