IONS

It has been about a month since the last earnings report for Indivior Pharmaceuticals Inc. (INDV). Shares have lost about 5.3% in that time frame, underperforming the S&P 500. Will the recent negative trend continue leading up to its next earnings release, or is Indivior Pharmaceuticals Inc. due for a breakout? Before we dive into how investors and analysts have reacted as of late, let's take a quick look at its most recent earnings report in order to get a better handle on the important catalysts. Indivior Beats Q2 Earnings Estimates, 2026 Outlook Raised Indivior delivered adjusted earnings of $1.15 per share in the second quarter of 2026, up 125.5% year over year and beating the Zacks Consensus Estimate of 97 cents.Total revenues rose 13.6% year over year to $343 million, primarily due to strong U.S. Sublocade performance. The metric beat the Zacks Consensus Estimate of $308 million.Total Sublocade net revenues increased 21% year over year to a quarterly record of $253 million.U.S. Sublocade revenues increased 22% to $238 million, driven by strong dispense unit volume growth, favorable price/mix and gross-to-net adjustments.Dispense unit volume increased 18% year over year, supported by strong market demand and commercial execution.The quarter saw record new patient starts for the company, with roughly 32,816 patients beginning Sublocade treatment. As of June 30, 2026, more than 545,000 U.S. patients had been prescribed Sublocade since launch.U.S. sublingual and other product revenues increased to $57 million compared with $52 million in the prior-year quarter. Rest of World revenues declined 6.5% year over year to $43 million.In the second quarter of 2026, overall U.S. revenues rose to $300 million, up from $256 million a year ago. Indivior's Cost Base Lifts Profitability Indivior continued to improve profitability through disciplined cost management. Adjusted operating expenses declined 33% year over year to $112 million.Adjusted EBITDA surged 111% year over year to $186 million. Balance Sheet & Share Repurchases The company ended the quarter with $249 million in cash and investments, up from $201 million as of March 31, 2026. During the quarter, the company repurchased about 4.7 million shares for $175 million at an average price of $37.52. Indivior Raises 2026 Outlook Reflecting stronger-than-expected commercial performance, Indivior increased its full-year 2026 financial guidance.The company expects net revenues to be in the range of $1.295-$1.365 billion, up from its previous guidance of $1.215-$1.285 billion.Indivior also lifted its total Sublocade net revenues forecast to $1.01-$1.05 billion from $950-$990 million, implying approximately 20% year-over-year growth at the midpoint.The increase in guidance reflects stronger-than-expected dispense-unit growth and improved commercial dispense yields, supported by favorable product mix trends.Adjusted EBITDA is projected at $700-$740 million, up from the prior range of $620-$660 million. The adjusted operating expense outlook was maintained at $430-$450 million. In the past month, investors have witnessed a upward trend in estimates review. Currently, Indivior Pharmaceuticals Inc. has a great Growth Score of A, though it is lagging a lot on the Momentum Score front with a D. However, the stock was allocated a score of B on the value side, putting it in the second quintile for this investment strategy. Overall, the stock has an aggregate VGM Score of A. If you aren't focused on one strategy, this score is the one you should be interested in. Estimates have been trending upward for the stock, and the magnitude of this revision looks promising. It comes with little surprise Indivior Pharmaceuticals Inc. has a Zacks Rank #2 (Buy). We expect an above average return from the stock in the next few months. Indivior Pharmaceuticals Inc. is part of the Zacks Medical - Drugs industry. Over the past month, Ionis Pharmaceuticals (IONS), a stock from the same industry, has gained 8.7%. The company reported its results for the quarter ended June 2026 more than a month ago. Ionis Pharmaceuticals reported revenues of $268 million in the last reported quarter, representing a year-over-year change of -40.7%. EPS of -$0.43 for the same period compares with $0.86 a year ago. For the current quarter, Ionis Pharmaceuticals is expected to post a loss of $0.89 per share, indicating a change of -45.9% from the year-ago quarter. The Zacks Consensus Estimate has changed -1.1% over the last 30 days. The overall direction and magnitude of estimate revisions translate into a Zacks Rank #3 (Hold) for Ionis Pharmaceuticals. Also, the stock has a VGM Score of F. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Indivior Pharmaceuticals Inc. (INDV) : Free Stock Analysis Report Ionis Pharmaceuticals, Inc. (IONS) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

It has been about a month since the last earnings report for Ionis Pharmaceuticals (IONS). Shares have added about 17.2% in that time frame, outperforming the S&P 500. But investors have to be wondering, will the recent positive trend continue leading up to its next earnings release, or is Ionis Pharmaceuticals due for a pullback? Before we dive into how investors and analysts have reacted as of late, let's take a quick look at its most recent earnings report in order to get a better handle on the important catalysts. Ionis reported second-quarter 2026 adjusted loss per share of 43 cents, narrower than the Zacks Consensus Estimate of a loss of 89 cents. In the year-ago period, the company had posted adjusted earnings of 86 cents. The adjusted earnings/loss excludes compensation expenses related to equity awards. Including this special item, the loss was 69 cents per share against the earnings of 70 cents in the year-ago period. Quarterly revenues were $268 million, which beat the Zacks Consensus Estimate of $190.7 million. Yet, the reported figure fell nearly 41% year over year as the comparison was affected by an upfront payment of $280 million received from Japan-based Ono Pharmaceutical in the year-ago period. Excluding the Ono payment, total revenues rose 56% year over year, driven by commercial growth and payments tied to progress across partnered programs. The company’s revenues are divided into two segments — commercial revenues and research and development (R&D) revenues. Commercial revenues, which include net product sales, royalties and other commercial revenues, rose 15% year over year to $119 million. R&D revenues, which include collaborative agreement revenues and Wainua joint-development revenues, fell 57% to $149 million. Tryngolza generated net product sales of $5 million in the second quarter compared with $19 million in the year-ago period. The decline reflected a strategic wholesale acquisition cost reduction that took effect on April 1, 2026, ahead of the broader sHTG launch. Following the drug's approval last month for the broader sHTG indication, management said the launch is off to an encouraging start. Management also noted that underlying FCS demand remained strong, with the highest number of new patients starting treatment since launch, and expects sales to accelerate in the second half of 2026. Dawnzera generated net product sales of $26 million in the reported quarter, up 63% sequentially from $16 million in the first quarter of 2026. Demand was supported by patients switching from other long-term prophylactic therapies, those previously relying only on on-demand treatment and treatment-naive patients. Management also highlighted a growing base of repeat prescribers, indicating physicians’ positive experience with the drug. Royalty revenues increased 9% year over year to $76 million. Spinraza royalties fell 2% year over year to $53 million, while Wainua royalties rose 60% to $16 million. Other royalty revenues were $7 million. Collaborative agreement revenues were $133 million, down nearly 61% year over year. The sharp decline was primarily attributed to an upfront payment of $280 million received in the year-ago period from Ono for out-licensing rights to sapablursen, an investigational therapy for a rare blood cancer called polycythemia vera (PV). Wainua joint-development revenues increased to $16 million, up 33% year over year. Adjusted research, development and patent expenses declined nearly 3% year over year to $192 million, while adjusted selling, general and administrative (SG&A) expenses increased more than 60% to $130 million. The higher SG&A expenses reflected investments supporting the commercialization of Tryngolza and Dawnzera, as well as launch preparations for zilganersen in Alexander disease. Ionis reaffirmed its full-year 2026 revenue guidance of $875-$900 million. The company continues to expect Tryngolza's net product sales of $100-$110 million and Dawnzera's net product sales of $110-$120 million. The company also reiterated its adjusted operating loss guidance of $425-$475 million. Operating expenses are expected to increase in the low-teens percentage range from 2025, while R&D expenses are projected to remain broadly consistent with the prior year. Ionis continues to project year-end cash and investments of more than $1.6 billion while remaining on track for cash-flow breakeven in 2028. In the past month, investors have witnessed a downward trend in estimates revision. The consensus estimate has shifted -10.35% due to these changes. At this time, Ionis Pharmaceuticals has a subpar Growth Score of D, however its Momentum Score is doing a bit better with a C. However, the stock was allocated a score of F on the value side, putting it in the lowest quintile for this investment strategy. Overall, the stock has an aggregate VGM Score of F. If you aren't focused on one strategy, this score is the one you should be interested in. Estimates have been broadly trending downward for the stock, and the magnitude of this revision indicates a downward shift. Notably, Ionis Pharmaceuticals has a Zacks Rank #3 (Hold). We expect an in-line return from the stock in the next few months. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Ionis Pharmaceuticals, Inc. (IONS) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Image source: The Motley Fool. Wednesday, July 29, 2026 at 8:30 a.m. ET Senior Vice President of Investor Relations - Wade Walke Chief Executive Officer - Brett Monia Chief Global Product Strategy Officer - Kyle Jenne Chief Development Officer - Holly Kordasiewicz Chief Financial Officer - Elizabeth L. Hougen Chief Clinical Development Officer - Eugene Schneider Executive Vice President of Research - Eric Swayze Operator: Good morning, and welcome to Ionis Second 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. D. Walke: Thank you, Andrea. 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've also posted slides on our website that accompany today's call. With me this morning are Brett Monia, Chief Executive Officer; Kyle Jenne, Chief Global Product Strategy Officer; Holly Kordasiewicz, Chief Development Officer; and Beth Hougen, Chief Financial Officer. 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 would 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. With that, I'll turn the call over to Brett. Brett Monia: Thanks, Wade. Good morning, everyone, and thank you for joining us on today's call. Ionis enters the second half of 2026 well positioned to achieve the strategic opportunities that lie ahead. We have the R&D engine, the pipeline, commercial capabilities, and financial discipline we need to execute on and achieve our goals. We are continuing to build momentum across our commercial medicines. And in parallel, we continue to strengthen and advance our wholly owned pipeline to deliver our next wave of important medicines. Last month, we achieved a landmark milestone with the approval of TRYNGOLZA as the first and only FDA-approved medicine to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia or sHTG. Although still early days, we are highly encouraged with our launch momentum to date. In fact, we began receiving prescriptions for TRYNGOLZA on the day of approval. We are also pleased that both the 50-milligram and 80-milligram doses were in the channel within 1 week. Based on its strong profile and the enthusiasm we are seeing in prescribing, we are confident that TRYNGOLZA is well positioned to help a large population of patients in need and become the first Ionis-owned multibillion-dollar medicine. DAWNZERA for hereditary angioedema also continues to gain momentum. We expect DAWNZERA to continue driving growth as it becomes more established in the HAE prophylactic treatment landscape. We also continue to advance our leadership in the development of breakthrough treatments for a wide range of neurological diseases. We remain on track for the anticipated launch of Zilganersen coming up soon, which is positioned to be the first disease-modifying treatment for Alexander disease and the first independent launch from our neurological disease pipeline. Following closely behind Zilganersen is Obudanersen, our medicine for Angelman syndrome, which completed enrollment in the Phase III REVEAL study last month, keeping it on track for data next year. Earlier this month, we also announced the initiation of clinical development for ION337 in Dravet syndrome, expanding our clinical stage neurology pipeline, which now includes 8 medicines that are wholly owned. Complementing our wholly owned pipeline is our partnered pipeline, which includes medicines targeting both rare and highly prevalent diseases, providing significant additional value for Ionis. This includes Bepirovirsen, our medicine for chronic hepatitis B. With the PDUFA target action date of October 26 and additional global filings under review, Bepirovirsen is on track for a global launch this year, positioning it to be a first-in-class medicine for the millions of people around the world living with this disease. Data from the Phase III Pelacarsen Lp(a) HORIZON study in patients with elevated Lp(a) and cardiovascular disease is also a key catalyst coming up in the second half of this year. We were disappointed with the outcome of the CARDIO-TTRansform Phase III study for Eplontersen in ATTR cardiomyopathy that we reported earlier this month. Although Eplontersen demonstrated substantial and durable reductions in TTR, nominally significant results in the monotherapy subgroup and favorable safety, it did not meet the primary efficacy endpoint in the overall population. We and AstraZeneca continue to analyze the data, and we will present the results at ESC in August. Our strong commercial execution, continued pipeline progress and our strong second quarter financial performance underscore the many opportunities we have to continue building substantial value. We remain on track to deliver on our 2026 financial guidance and achieve our goal of cash flow breakeven in 2028. With that, I'll now turn the call over to Kyle, who will speak to the commercial execution of TRYNGOLZA and DAWNZERA and launch preparations for Zilganersen. Holly will then discuss how we are advancing our pipeline, highlighting several important catalysts ahead, and Beth will review our financial results and outlook. And with that, I'll turn it over to Kyle. Kyle Jenne: Thank you, Brett. Our commercial momentum continues to build, positioning us to deliver even greater impact in the second half of the year and beyond. We are executing well against our commercial priorities, including strong progress on the TRYNGOLZA and DAWNZERA launches and preparation for the Zilganersen launch. Beginning with TRYNGOLZA, demand continues to build in FCS, driven by an increasing number of patients initiating and remaining on treatment. As expected, second quarter product sales reflected the reduced TRYNGOLZA wholesale acquisition cost that went into effect on April 1. We updated the price ahead of the anticipated sHTG approval to align with annual payer contracting cycles to accelerate access to TRYNGOLZA. Underlying demand in FCS remains strong with the second quarter delivering the highest number of patient starts since launch began. Together with our commercial execution in FCS and early market access efforts, we've established a strong foundation for the next phase of TRYNGOLZA growth as we launch in the broader patient population. The recent approval of TRYNGOLZA for sHTG marked a defining moment for Ionis. Importantly, it expanded our opportunity to serve millions of people living with severely elevated triglycerides. We were particularly pleased with the TRYNGOLZA label, which includes prevention of acute pancreatitis in the indication statement. The label is supported by the groundbreaking results from the Phase III CORE and CORE 2 studies, which further underscores the importance of preventing acute pancreatitis in people with sHTG. Building on this strong foundation, I'm happy to share that the sHTG launch is off to an encouraging start in the first few weeks. Thanks to the exceptional execution of our commercial team, we began receiving prescriptions on day 1, and both the 50-milligram and 80-milligram doses were in the channel within approximately 1 week. Since the approval, our team is already engaged with many of our top physician targets who care for the majority of high-risk patients. In addition, our omnichannel launch campaign has produced strong engagement, which is further helping to rapidly build awareness of sHTG, apoC-III biology and TRYNGOLZA. There are an estimated 3 million people in the U.S. with sHTG, including approximately 1 million people with high-risk sHTG who have triglycerides above 880 milligrams per deciliter or triglycerides above 500 in a history of acute pancreatitis or other comorbidities. The risk of acute pancreatitis begins to increase at triglyceride levels above 500 and rises exponentially in people with triglycerides above 880. As the first-to-market therapy with a novel mechanism proven to reduce the risk of painful, costly and potentially fatal acute pancreatitis attacks, TRYNGOLZA is well positioned to serve patients across both segments. The majority of high-risk sHTG patients are treated by approximately 20,000 cardiologists, endocrinologists and lipidologists across the U.S. with additional patients treated by primary care physicians. Early in the launch, we are seeing prescriptions from all three specialties in addition to a meaningful contribution from primary care physicians. We've also seen physicians prescribe TRYNGOLZA to people with high-risk sHTG and those with TGs between 500 and 800 milligrams per deciliter with no history of acute pancreatitis. Physicians are prescribing both the 50- and 80-milligram doses, highlighting the importance of dosing flexibility, which enables treating physicians to tailor treatment to the individual needs of each patient. Importantly, we are executing on our market access strategy as planned. We have made good progress obtaining coverage for the broad population in patients with triglycerides above 500 milligrams per deciliter and across both commercial and government plans. Ultimately, we expect the sHTG market to comprise approximately 60% commercial and 40% government covered patients. We also expect payer coverage to continue expanding through the remainder of this year and into next year as payers complete the reviews. We're also making progress in expanding access to TRYNGOLZA outside the U.S. In the EU, Sobi is continuing to advance the launch in FCS, while also actively laying the groundwork for a strong launch in the broader sHTG indication anticipated next year. With this early sHTG launch momentum, TRYNGOLZA is on track to meet our full year 2026 revenue guidance and positioned to achieve our projections for more than $3 billion in peak annual revenue. The DAWNZERA launch also continued to gain momentum. In less than 1 year on the market, DAWNZERA has already captured a meaningful share of the U.S. HAE prophylaxis market, which is largely a switch market. This growth is driven by increasing adoption across all patient segments, including patients switching from existing prophylactic therapies, patients who were previously only using on-demand treatment and treatment-naive patients. Physicians and patients consistently provide positive feedback on DAWNZERA, highlighting DAWNZERA's strong efficacy and favorable safety profile, its differentiated RNA targeting mechanism, the positive switch data, which HCPs describe 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 6 weeks. The base of repeat prescribers continues to grow. This is a key indicator that DAWNZERA is providing substantial benefit for patients and HCPs are having a positive experience prescribing it. Given that most patients on HAE prophylactic medicines are already established on existing therapies, continued penetration will take time. However, the launch fundamentals give us confidence that DAWNZERA will contribute meaningfully to our commercial revenue growth in 2026 and beyond. Outside the U.S., our partner, Otsuka, is making good progress with DAWNZERA and the launch in the EU. Over time, we expect ex-U.S. countries to become an important contributor to overall DAWNZERA's growth. Turning to Zilganersen. We are well prepared for the launch for the treatment of Alexander disease coming up later this year. Based on the positive Phase III results for Zilganersen, we received FDA priority review with a PDUFA date of September 22. We have an expanded access program underway, and our commercial preparations are right on track, centered around 4 key priorities. First, pending approval, we will work to transition patients who are currently receiving Zilganersen through the clinical study or the expanded access program to commercial therapy. Second, we will focus on getting patients already diagnosed with Alexander disease in the U.S. on Zilganersen. It's estimated that about half of the approximately 300 patients in the U.S. are already identified through ICD-10 codes and patient registries. Third, we will drive disease awareness among physicians who care for people with rare neurological diseases, prioritizing engagement with the dozen U.S. leukodystrophy centers. Following approval, we expect these centers as key referral and treatment hubs to play a key -- central role in identifying more patients and providing them with treatment. And fourth, we are building a dedicated patient services platform, which we have designed based on feedback from stakeholders to address the specific needs of the Alexander disease community. Additionally, our customer-facing team is now in place and prepared to rapidly reach patients upon our potential Zilganersen approval. Importantly, we expect to leverage many of the capabilities we are building for Zilganersen for our future neurology medicine launches. We also recently took an important step toward bringing Zilganersen to people with Alexander disease outside the U.S. through our agreement with Recordati. Recordati plans to file for regulatory approval for Zilganersen in the EU and Japan next year with additional global filings to follow. With our first broad patient population launch now underway, growing momentum across our commercial portfolio and a strong pipeline behind it, we believe Ionis is well positioned to bring more important medicines to people with serious diseases. And with that, I'll turn the call over to Holly. Holly Kordasiewicz: Thank you, Kyle. This quarter, we made meaningful progress across our pipeline. TRYNGOLZA's approval for the treatment of sHTG is a significant milestone for Ionis and for patients. TRYNGOLZA's approval was supported by the unprecedented results from the Phase III CORE and CORE 2 studies, in which TRYNGOLZA achieved rapid, substantial and clinically meaningful placebo-adjusted mean reductions in triglycerides of up to 72%. These triglyceride reductions resulted in a profound reduction in acute pancreatitis events by up to 91%. TRYNGOLZA treatment also led to 86% of patients reaching triglyceride levels below 500 mg per deciliter, the threshold that defines sHTG, up to 54% of patients reaching normal triglyceride levels below 150 mg per deciliter and favorable safety and tolerability, which resulted -- were further reinforced by longer-term data from the CORE and CORE 2 open-label extension study, which we recently presented at the National Lipid Association Scientific Session. We will share additional data from the OLE at ESC in August. As Kyle mentioned, the TRYNGOLZA label includes acute pancreatitis risk reduction in the indication statement, which underscores the importance of preventing these debilitating and potentially fatal attacks and further validates our unprecedented results. With this groundbreaking clinical profile, TRYNGOLZA is poised to redefine the treatment of this underserved disease. Beyond TRYNGOLZA, we are advancing a number of promising wholly owned cardiometabolic disease medicines, including ION775, our next-generation medicine for the treatment of sHTG. We recently advanced ION775 into a Phase IIb study in patients with sHTG or moderately elevated triglycerides based on positive Phase I data in healthy volunteers with elevated triglycerides. These results show the potential for an optimized profile characterized by substantial, durable and sustained reductions in apoC-III and triglycerides with the potential for semiannual or less frequent dosing. We look forward to presenting these data on ION775 at ESC next month. And as Brett mentioned, we will also share detailed data from the Eplontersen CARDIO-TTRansform study at ESC. Turning next to our neurology franchise. We remain on track to bring Zilganersen to patients with Alexander disease later this year, assuming approval. This rare, progressive and often fatal leukodystrophy profoundly affects patients and families. And today, there are no approved disease-modifying therapies. Our positive Phase III results marked the first time any therapy demonstrated a disease-modifying impact in these patients. Our next wholly owned Phase III program is Obudanersen for the treatment of Angelman syndrome. Angelman syndrome is a neuro-developmental disorder that causes profound and lifelong physical and cognitive impairment, estimated to affect more than 100,000 people globally. We recently announced that enrollment in the Phase III REVEAL study is complete, which keeps us on track to report data in the second half of next year, bringing us an important step closer to potentially delivering this medicine to families in need. We recently advanced our medicine for the treatment of Dravet syndrome, a rare, severe and lifelong neurological disorder, into a Phase I/II first-in-human study. We advanced ION337 based on encouraging preclinical data, which we believe positions this program to become a best-in-class treatment for this devastating disease. ION337 is our first wholly owned medicine that uses our proprietary NMA chemistry, designed to achieve maximal and sustained modulation of SCN1A with a long dosing interval. Our NMA chemistry is the same breakthrough technology that enables Tonlamarsen to achieve substantial efficacy and favorable safety with annual dosing in a Phase I study in patients with spinal muscular atrophy. Our partner, Biogen, recently advanced Tonlamarsen into Phase III development based on these positive results, positioning it to meet the remaining unmet needs of people living with spinal muscular atrophy. We were also encouraged by the Phase II CELIA data Biogen presented at AAIC for Diranersen in early Alzheimer's disease. These results are the first to demonstrate the significant potential of targeting intracellular tau as a treatment for AD. Diranersen showed significant reductions in CSF tau levels accompanied by a reversal of tau pathology as measured by tau PET. We also saw remarkable effects on cognition as shown by a 34% to 50% slow decline in MMSE versus placebo and a meaningful effect on composite endpoints that include both cognitive and functional domains. Although the Phase II study did not meet the primary endpoint, the totality of these data support Biogen's plan to initiate Phase III development. We are also pleased with the recent initiation of the Phase III INTREPID study of Sapablursen by our partner, Ono. This study is evaluating Sapablursen in people with phlebotomy-dependent polycythemia vera, a rare but potentially life-threatening hematologic disease with significant unmet need. Assuming positive data, Sapablursen would represent an important value driver from our partner pipeline. In Bepirovirsen, our medicine for the treatment of chronic hepatitis B partnered with GSK, is on track for approval in the U.S. and Japan later this year with multiple additional global approvals anticipated next year. Based on positive data from the Phase III B-Well studies demonstrating unprecedented functional cure rates, Bepirovirsen positioned to become a first-in-class treatment for chronic hepatitis B, a disease affecting millions of people around the world. Also in the second half, we expect late-stage readouts from several partner programs, including Pelacarsen for Lp(a) driven cardiovascular disease with Novartis. Ulefnersen for FUS-ALS with Otsuka and Sefaxersen for IgA nephropathy with Roche. Overall, the progress we have made across the pipeline this year reinforces both the strength of our R&D engine and our confidence in the next wave of opportunities to reach more and more patients in need and drive future growth. And with that, I'll turn the call over to Beth. Elizabeth L. Hougen: Thank you, Holly. We delivered strong financial results in the first half of this year, supported by increased revenue from our commercial medicines and meaningful R&D revenue from our partnered programs, while we continued to invest in our long-term growth. Revenues in the second quarter and first half of this year were $268 million and $514 million, respectively, representing significant year-over-year growth of 56% and 69% compared to the same period last year, excluding the $280 million one-time payment we received from Ono in the first half of last year for Sapablursen. Commercial revenue increased to $119 million in the second quarter and $226 million in the first half, up 15% and 27%, respectively, from the same period last year. These increases were driven primarily by DAWNZERA product sales. TRYNGOLZA generated product sales of $5 million and $32 million in the second quarter and first half of this year. The decrease in revenues in the second quarter followed the April 1 reduction in the TRYNGOLZA WAC price, which we implemented strategically ahead of our expansion into the broader sHTG indication. We continue to expect TRYNGOLZA to return to revenue growth in the second half of this year as the sHTG launch gains momentum. DAWNZERA generated $26 million in the second quarter and $42 million in the first half, with second quarter sales increasing by 63% compared to this year's first quarter. Research and development revenue was $149 million in the second quarter and $288 million year-to-date, reflecting continued progress across our partnered pipeline. Operating expenses increased as expected in the second quarter and first half of this year compared to the same period last year, driven by costs associated with commercializing TRYNGOLZA and DAWNZERA, preparations to launch Zilganersen later this year and advancing medicines in our rich pipeline. We ended the second quarter with $2.1 billion in cash, cash equivalents and short-term investments, enabling us to continue investing in our commercial medicines and wholly owned pipeline. Looking to the remainder of the year, our strong first half results keep us on track to achieve our full year 2026 financial guidance. We continue to project full year revenue in the range of $875 million to $900 million, with results weighted slightly more toward commercial revenues. We remain on track to achieve our TRYNGOLZA and DAWNZERA product level guidance. This includes full year TRYNGOLZA product sales of $100 million to $110 million, with TRYNGOLZA expected to return to revenue growth in the second half of this year as the sHTG launch gains momentum. And full year DAWNZERA product sales of $110 million to $120 million, with continued growth forecasted in the second half of this year. Additionally, we anticipate meaningful R&D revenue from existing collaborations, including the potential for additional milestones tied to Bepirovirsen, Pelacarsen and other partnered programs as they advance. On the expense side, we continue to expect 2026 operating expenses to increase in the low teens percentage range compared to last year, driven primarily by sales and marketing expenses related to our ongoing and upcoming commercial launches. We project R&D expenses to remain consistent with last year as several of our late-stage studies conclude and we redeploy resources to earlier-stage programs within our wholly owned pipeline. And as a result of our focus on improving our operating leverage, we expect a non-GAAP operating loss between $425 million and $475 million. This is similar to our 2025 operating loss after adjusting for the onetime Sapablursen license fee we earned last year. And finally, we are projecting a 2026 year-end cash balance of greater than $1.6 billion. With our strong first half financial performance and our outlook for the remainder of this year, we remain on track to achieve our full year 2026 financial guidance and cash flow breakeven in 2028 while continuing to drive substantial growth and longer-term value creation. With that, I'll turn the call back over to Brett. Brett Monia: Thank you, Beth. Our outlook for the remainder of 2026 and beyond reflects Ionis' strength and the substantial opportunity for continued success that lies ahead. We are executing well on our independent launches for TRYNGOLZA and DAWNZERA and are well prepared for our next launch, Zilganersen in Alexander disease anticipated later this year. In addition to driving value through commercial success, we also have many important near- and midterm catalysts from across our development pipeline, each with the potential to further drive substantial value. We are well positioned to continue executing successfully on our commercial launches and to deliver a steady cadence of breakthrough medicines to patients. Now before we move to Q&A, I'd like to take a moment to recognize Frank Bennett, our Chief Scientific Officer, whose planned retirement we announced earlier this morning. Frank is one of Ionis' founding scientists and has helped shape Ionis and advance the field of RNA-targeted medicines. While his leadership helped create this new sector for human therapeutics, some of his greatest contributions were in the field of neurology, which led to the approvals of SPINRAZA for SMA and QALSODY for SOD1-ALS, along with the establishment of a rich pipeline poised to deliver a steady stream of breakthrough treatments for neurological diseases. On behalf of the entire Ionis team, I want to thank Frank for his many contributions, his dedication to patients and the lasting impact he has had on Ionis in the field of oligonucleotide therapeutics. And with that, we'll open the call up for questions. Operator: [Operator Instructions] our first question will come from Jason Gerberry of Bank of America. Jason Gerberry: Just wanted to key in a little bit on an early adoption of TRYNGOLZA. How much of that's being driven by physicians with overlapping FCS patients that they were treating? Is that sort of the core early prescriber in this initial kind of 6 to 9 months? And where physicians are attempting to write prescriptions, can you talk a little bit about the average processing time for them to go from an enrollment form to getting a script covered? Is that through medical exceptions, I assume? So those are my questions. Kyle Jenne: Thanks, Jason. This is Kyle. Happy to cover off on those. First, I'll say that the FCS launch really was important to the launch now in sHTG. Obviously, that laid the groundwork and the foundation for the readiness to bring the drug forward to a prevalent population. Many of the early prescribers are previous treaters of FCS. They have experience using the drug, and they've had really, really positive results from doing so. But we're also seeing more physicians than just the FCS prescribers starting to use TRYNGOLZA for sHTG. The other thing that I'll just mention here is the FCS growth in Q2 and the demand continue to accelerate significantly. Having more treaters and more patients on drug, obviously, will help us accelerate the sHTG launch as well. So the short answer to your question is yes. There are treaters of FCS that are also prescribing, but it goes well beyond that. In terms of process time -- it's really too early to discuss those details. We're just a couple of weeks into the launch. What we've seen from payers so far is very encouraging, not only in terms of the Rx to approval time so far, but also just in terms of our conversations that we're having with the payers where they are beginning to assess sHTG and assess to put coverage criteria in place so that there's a clear pathway for approval. Here early in the launch, the majority of the coverage criteria is going to be through medical exception. That was to be anticipated. And we would expect to see continued coverage improve through the back half of this year and as we start 2027 should look much better. Operator: The next question comes from Ellie Merle of Barclays. Eliana Merle: Can you just elaborate a little bit more in terms of what you're seeing in terms of reimbursement? I know you mentioned that you're seeing reimbursement for TRYNGOLZA, sorry, in patients with triglycerides over 500. But are you seeing any differences in how payers are treating the coverage of patients with triglycerides over 880 versus those over 500? And then just a second question. What are your expectations for WAINUA sales in polyneuropathy now after the CARDIO-TTRansform data, given much of the polyneuropathy patients are mixed phenotype? Kyle Jenne: Yes. Thanks, Ellie. Let me -- I'll start with the TRYNGOLZA question. We are seeing coverage to label. The label is very strong here, right, greater than 500. It does not limit patients over 880. It does not limit a history of acute pancreatitis. So the conversations that we've had with payers and what we've seen from the early approvals through the medical exception process has all reflected the actual indication statement in the label, which is what we expected based on our payer research going into the launch. So it will take a little bit of work for the HCPs as expected at launch to do these prior authorizations to provide a letter of medical necessity potentially to justify the background therapy that the patient has been on and what their triglyceride levels are. But that's all very consistent with what we expected the policies to represent. So I think things are on track, and we're very encouraged by the early interactions and discussions that we've had with payers. On the WAINUA side, demand continues to be strong for the hereditary polyneuropathy patient. The challenge that we are seeing on the WAINUA side is with the mixed phenotype patient where AMVUTTRA has an indication for both polyneuropathy and cardiomyopathy. But otherwise, physicians are having very positive experience prescribing and treating these patients and feedback has been very strong in terms of control of TTR and knockdown, control of polyneuropathy symptoms, payer access and coverage and the ability to self-administer with an auto-injector. So we expect sales to continue in polyneuropathy, and the teams continue to do a nice job. Operator: The next question comes from Gary Nachman of Canaccord Genuity. Gary Nachman: So for sHTG, are you finding that most of these patients are already on some TG lowering or lipid-lowering drugs? Are they switching to TRYNGOLZA or adding TRYNGOLZA on top of their other treatments? And are there any real true naive patients that are being put on drug at this point? And then just what are you hearing from physicians on TRYNGOLZA's profile as a monthly subcu? And has there been any real concerns with the elevated liver fat holding back prescribing at all? And how are you communicating that? Kyle Jenne: Yes. Thanks, Gary. So the short answer to the first question is we're seeing a mix of patients. The majority of these patients obviously are high-risk sHTG patients. They're above 500 -- the majority of these patients have been on some sort of background therapy, which is very consistent with our CORE and CORE 2 trials. I mean, almost 100% of the patients were on some sort of fibrate or omega-3 or statin in the clinical trial. And that's consistent with how HCPs are using standard of care today and doing everything they can to try to get triglycerides lowered below 500 and get these patients out of the risk of acute pancreatitis, but have just been unable to do so. So the majority of these patients are on background standard care therapy, and they are adding TRYNGOLZA to those patients in order to get the benefit of up to 72% risk reduction in triglycerides. And up to a 91% reduction in acute pancreatitis. So they're using it very consistent with the way that the clinical trial was designed and the way that HCPs have been treating these patients up to this time. The profile is coming across very strong. First, I'll just mention the indication statement, having AP represented there really reflects the outcome of treating high triglycerides and what that means for patients and what that means for HCPs that are trying to treat these patients and get them out of harm's way of acute pancreatitis. The monthly auto-injector is very well received. It's low dose. It's very easy to use. The patients can take it once a month. They don't have to try to figure out is it month 1 or month 2 or month 3. And we're finding that consistent with the FCS launch, adherence and persistency and patients are starting and staying on and doing very well on the monthly administration with the auto-injector. And for hepatic fat, I'll turn it over to Brett. Brett Monia: Yes. Thanks, Kyle. And Gary, thanks for the question. So we are -- we believe that the evidence that the effects on the liver fat, small increases in liver fat we see is an on-target effect is very convincing. And prior to us presenting the data at National Lipid Association earlier this year, -- we didn't even have pushback at that time from HCPs on concerns over the small increases in liver fat, especially because there was no association with any clinical sequelae. There were no clinical complications associated with the small increases in liver fat that we saw. That was further reinforced when we presented the NLA data, the data NLA, which we showed that with continued treatment that the increase in liver fat was returning to baseline. Again, long-term treatment, no association with clinical sequelae. So that was just reinforced there. And as we continue to evaluate patients in the long term -- even further long-term open-label extension, again, we're not seeing any emerging adverse events in the study. So no concerns on the HCP community, and that's been further reinforced with long-term data. Operator: The next question comes from Moritz Reiterer of Guggenheim Securities. Moritz Reiterer: This is Moritz on for Debjit. I have two questions. The first one on TRYNGOLZA. How, if at all, has the recent plozasiran data changed your outlook for TRYNGOLZA? And the second one on HORIZON, what's your confidence in the trial? And should the HORIZON disappoint, how are you thinking about your path to profitability? Brett Monia: Yes. So Moritz, thank you for the question. We believe we have -- based on everything we've seen so far, we continue to believe that we have a best-in-class medicine when you look at the totality of the data for the treatment of sHTG. And when you look at the triglyceride lowering that Holly summarized in her prepared remarks and the overall reduction in acute pancreatitis, along with safety and tolerability and first-mover advantage also, we have no concerns about competition. We continue to reiterate our peak product sales in the U.S. of being $3 billion plus. So there was no surprises in any data that has emerged since we've launched. With respect to HORIZON, our confidence remains -- continues to be the same, high. We believe that Lp(a) is a cardiovascular risk factor, independent risk factor. The evidence is overwhelming. We have the right drug. The baseline demographics lays it all -- manuscript lays it all out on the powering assumptions in that study. and the drug has been well tolerated. And we're looking forward to the results in the -- later this year. And then -- I'm sorry, the third part of the question was? Moritz Reiterer: Should the trial disappoint, what's the route to profitability? Elizabeth L. Hougen: Yes. So I would say in the event that Pelacarsen Phase III were not to be positive, it would not have an impact on our 2026 financial guidance. It would put some pressure on our ability to achieve our goal of cash flow breakeven in 2028. But I want to emphasize that's a very important goal for us at Ionis, and we will work very, very hard to achieve that goal. Operator: The next question comes from Mike Ulz of Morgan Stanley. Michael Ulz: Maybe a few just on ION775. Just curious if you can give us a sense of what data we might expect at the upcoming ESC meeting, maybe in terms of endpoints, level of follow-up, et cetera, there? And then maybe just secondly, as we think about time lines for this program, maybe you can share how you're thinking about that in terms of path to market, number of clinical studies? And is there ways to sort of shorten that just given your experience with the core programs? Holly Kordasiewicz: This is Holly. Thank you. The ION775 data that we'll be sharing at ESC, it's year-long data, its safety as well as our efficacy and activity data on our key biomarkers. So it should be a very interesting data set for everybody to view. In terms of where we're at, so we are in the Phase IIb study right now. Of course, we are using all of our previous learnings to accelerate the program as much as we can. We haven't discussed timing externally, but we are absolutely using everything that we've learned from our previous programs and data sets to apply to this program. Brett Monia: Yes. And just to add to that, Mike. So you'll see the long-term data on triglycerides in the mildly elevated triglyceride population and the durability that 775 is offering, as Holly mentioned in her prepared remarks, this is at least a twice a year or even less frequent dosing opportunity. So it's a pure play on convenience. We don't believe that we can do much better than the efficacy that TRYNGOLZA is already presenting. I mean it's a best-in-class efficacy profile. It's really allowing us to get to maybe twice a year or once a year dosing. And that's what we're going to focus on. And the data will show apoC-III reductions that support that conclusion, triglyceride reductions that support that conclusion as well as the good tolerability. And also just to add, the enrollment is going well for -- although it's early innings for the Phase IIb study, it's going well. And our focus is to get that study done, the selected dose and move to Phase III as quickly as possible, but it's still too early to put time lines on when we can get that done. Operator: The next question comes from Yanan Zhu of Wells Fargo Securities. Yanan Zhu: For sHTG, I was wondering, based on the first few weeks of launch, how does that early momentum track with your internal expectation, especially in relationship to the full year guidance? Apparently, you made that guidance without any firsthand experience of the launch. So just curious, are you -- do you think you're ahead of that internal expectation at this point of time or in line? And for CARDIO-TTRansform, I was wondering, is there a regulatory path for monotherapy and could any of the data to be presented at ESC inform how you and AstraZeneca think about any potential regulatory path? Brett Monia: Thanks, Yanan. I'll take the first -- the second question first, and then I'll hand it over to Kyle to talk about how the sHTG is tracking with respect to guidance and so on. So we and AstraZeneca continue to review the data from the CARDIO-TTRansform study. There's a lot of data. We're preparing to present at ESC. We present -- referring to publish. We have several public presentations at ESC, including the CARDIO-TTRansform study, the combination subgroup as well as a meta-analysis study that is being conducted by an independent group of academic physicians. As far as regulatory path, AstraZeneca is weighing all their options, Yanan. They're still going through the data. There's a lot to process there. So there's nothing new to report with that. And the data at ESC, I think, will support all the conclusions we've made already, which is very clear that in the group that was on monotherapy at baseline, so no tafamidis at baseline, the efficacy in the composite primary endpoint as well as the secondary endpoints are in line with the silencer class. There was no benefit in the combination group. And you'll see that data in quite detail at the ESC meeting. Kyle? Kyle Jenne: Yes. Thanks, Yanan. I'll say internally, we are absolutely meeting the expectations of the launch here, keeping in mind that we're only 4 or 5 weeks into this, so it's very early. The key priorities right out of the gate, obviously, is to get drug into channel. We did that within 1 week. Both the 50- and 80-milligram doses were in channel very, very quickly, allowing the prescriptions that were coming in early, if approved by the payer to be able to go out directly to patients and get patients on drug very quickly. So a lot of this is operational at the very beginning. And based on the launches of TRYNGOLZA in FCS and DAWNZERA in HAE, we had a really good experience recently of launching drugs and making sure that we did this expeditiously and effectively. And it's exactly what we've done with sHTG. So I'm very pleased with the team's execution there. The other components, things around training, for example, training of the field teams, approval of materials, deployment of content, those types of things went extremely well. Our omnichannel capabilities are operating exactly as planned. So we've been able to give notice about the approval to tens of thousands of HCPs that see patients with high triglycerides. So building awareness and making sure that there's an understanding that there's a product now available to treat those patients. Payer engagements and patient services are the other two areas that I would highlight, which have both gone very well. So operationally, I'm very pleased with the team, and we're off to a very good start with the launch. In terms of full year guidance, the $100 million to $110 million, we are still confident in that based on the FCS performance that we saw earlier in the year and based on the early signs and signals that we're seeing, combined with the very strong label that we achieved for TRYNGOLZA and sHTG. Operator: The next question comes from Yaron Werber of TD Cowen. Yaron Werber: Congrats on the progress. Maybe, Kyle, two questions for you commercially. On sHTG, one of the questions we've been getting is, do you think there's going to be sort of an initial pent-up demand or bolus or some clinics already kind of triaging patients to get treated with TRYNGOLZA now that it's approved? And then secondly, for DAWNZERA, I mean, you're seeing very nice kind of quarter-over-quarter growth. You mentioned, obviously, it's a switch market. What sort of is the main competitor at this point? And how are you -- what are you seeing in terms of demand? Kyle Jenne: Yes. Thanks for the questions. In terms of pent-up demand, we believe this is going to be a gradual build and a moderate build over time for a couple of reasons. Number one, this is a new mechanism and a new treatment, and it takes some time to educate the HCPs. Number two, we've got to get those patients into the clinic to see these HCPs. So we've got to drive that awareness and interest to the patient so that they're motivated to get into these clinics and be treated. And then the third component is the payer access piece that I discussed earlier, right? We've got medical exception process here early on as we're gaining the utilization management criteria with payers. So it will take a little bit of time for that to build and grow. I expect that to happen through the back half of this year and then 2027 is where we will really see the launch begin to build and pick up as HCPs gain more experience and more patients begin to come in and be treated for sHTG. On the DAWNZERA side, I couldn't be more pleased with how the team is performing and how we are building the momentum. Q2, we did $26 million in revenue. It's up 63% over Q1. This is less than 1 year in the market, and we've got meaningful share of a market that is a switch market. We're seeing switches. We're also seeing patients that are being treated with on-demand only therapies be started on DAWNZERA and also naive patients. But as you would expect, there are multiple therapies in the class, and they have different profiles. What we know from the switch data is that some patients have an efficacy challenge, some have a tolerability challenge and some have an experience in duration of treatment issue, right, where they're having to take the drug too frequently. So it depends on which drug it is, but we are seeing switches from all of the prophylactic therapies out there and HCPs are having very positive experiences prescribing and they're coming back to use the drug more and more, which we're very encouraged by. Operator: The next question comes from Akash Tewari of Jefferies. Manoj Eradath: This is Manoj on for Akash. Just one from our end. Do you expect GTX-102 to demonstrate a meaningful efficacy trend in the upcoming Angelman readout? And how should we think about the potential read-through from that data to expectations for ION582. Brett Monia: Can you repeat the question, please? We didn't quite get that. Manoj Eradath: For the Angelman upcoming readout for GTX-102, how should we think about the read-through from that data to your program? Brett Monia: Yes, yes. Holly Kordasiewicz: Yes. This is Holly. I'd be happy to take that. So the Ultragenyx data readout, we're expecting that later this year. That will teach us a couple of things. One of the big things that we're looking for from that is to understand the placebo effect that patient population will have. That's not something that we know from this. So we are looking to do that. In terms of the read-through to our program for the Ultragenyx data itself, you have to remember that those are very different molecules. So they're dosing at a much lower dose than we're dosing. So we hope that they have positive effects that are encouraging for the community. However, if they don't, it will likely be because we -- that they're dosing lower than we are for our study. Brett Monia: Yes. And I'll just add to that, that our research organization has done a very nice job benchmarking Obudanersen with our ION582 with other molecules that are out there that are in development, and we don't see any potency advantages of any other molecule compared to ION582. So we have a highly potent molecule. And as Holly said, we've been able to dose to the maximum dose that we've set out to dose to drive efficacy as an 80-milligram quarterly dose. So looking forward to emerging data and looking forward to reading out our study next year. Operator: The next question comes from Salveen Richter of Goldman Sachs. Tommie Reerink: This is Tommie on for Salveen and just two on TRYNGOLZA. So in FCS, maybe some more color on the impact from switches from Arrowhead and on the capture of new starts, if you're seeing any? And on sHTG, maybe if you could lean more into what you're seeing from the primary care side. Kyle Jenne: Yes. Thanks, Tommie. We've seen no meaningful impact from the competition in FCS. Q2 was by far our strongest demand quarter and the highest quarter that we've had for new patient starts. The profile of TRYNGOLZA is being very well received by HCPs. HCPs that are using TRYNGOLZA for the first time are looking to come back to it. And when they see the triglyceride lowering and the ability to self-administer with the auto-injector, the profile is stacking up very, very strong in terms of the way that they need to treat these patients and the way that the patients feel and are doing on treatment once they get initiated. On the primary care side of things, part of the audience of the 20,000 HCPs that we have targeted that are treating these sHTG patients at high risk also are from the PCP audience. So they are seeing these patients. And I think the predominant prescriptions we're going to get are going to be from cardiology, endocrinology and lipidology. But I just think it's important to note that PCPs are seeing these patients. and they are willing to prescribe and they're interested in trying to treat these patients on their own because they've been trying to do so with standard of care with fibrates, omega-3, statins, et cetera, and just have been unsuccessful up to this point. So we will continue the very broad awareness and disease education to all specialties that are seeing these patients. And early on, we've got very positive indicators across the board. Operator: The next question comes from Luca Issi of RBC. Luca Issi: Maybe, Kyle, one more for you on the launch of severe hypertriglyceridemia. Obviously, clear enthusiasm here from the KOL community to prescribe the drug. However, we have heard from a couple of docs that one of the barriers is that there's no dedicated ICD-10 code specifically for severe hypertriglyceridemia. So doc needs to use codes for related conditions like hyperchylomicronemia syndrome or maybe hyperglyceridemia. And so that can sometimes create some barriers, some confusions to get the drug reimbursed. Is that consistent with what you've been hearing? And if so, can you talk about how you're planning to address that? And then maybe second for TTR cardiomyopathy, Brett, if I can circle back to the prior question, you mentioned at ESC, you will present this meta-analysis done by an independent group of physicians. Can you maybe just expand a little bit more on that? What's the purpose of that analysis? And how should we think about the implication of that analysis for the broader field? Kyle Jenne: Yes. Thanks, Luca. On the ICD-10 code side, I'll start by saying that has been on our radar for quite some time, and it's something that we are looking for opportunities to help the community come up with an ICD-10 code that they can use to explicitly reference sHTG. So that work is ongoing with the agencies, and we'll see what we can do in order to help that happen. But in terms of reimbursement, there are other things that they can use to justify the appropriate use of the drug and get reimbursement. First is the labeled indication. Second is to support that labeled indication with the patient's medical history and reference the drugs that those patients are being treated on as well as the triglyceride levels that the patients still exhibit even though that they're on those medications. So doing a prior authorization, including a letter of medical necessity is pretty standard for a specialty product like this at launch. And we're working with the different HCPs in order to make sure they understand what's required in order to do that and also supporting them in a compliant way so that they can do that successfully. Brett Monia: And Luca, I'm going to ask Holly to take the question about expanding on the meta-analysis at ESC. Holly Kordasiewicz: Yes. So the meta-analysis is really focused on the silencer class and understanding the totality of data within that class, including our new CARDIO-TTRansform data and comparing them both as monotherapies as well as on top of the stabilizers. Brett Monia: That's the main presentation. It's going to be comparing those 2 studies as single agents as well as combination. Operator: The next question will come from Jessica Fye of JPMorgan. Jessica Fye: I was curious about ION337 for Dravet. Can you help us think about when we might see the Part 1 data from the Phase I/II? And just given the long lead time for Zilganersen, how might 337 differentiate? Holly Kordasiewicz: Yes, I'm happy to take that one. So for 337, we just started dosing. So it's too early to talk about time lines, but we are -- there's a lot of enthusiasm from the community. The KOLs know Ionis and know our technology and are -- we're excited to get that moving quickly as is the community. In terms of differentiation, because we're using our new NMA technology, it's more potent than the MOE chemistry, our previous chemistry that we used for splice modulation. So you get increased potency and then allows you to spread out your dosing interval and increase your efficacy. Brett Monia: I think we have time for one more question. Operator: Our last question comes from Eric Joseph of Citi. Eric Joseph: Just thinking about the upcoming core OLE data at ESC, maybe just a little bit of expectation setting there. What incremental endpoints in addition to the NLA presentation are of interest? Or would you have us focus on there? To what extent, I guess, is ongoing AP event rate something that you're tracking in the OLE portion? And then just perhaps a clarifying question on the strategy with 775. Is the goal here predominantly to be a convenience player of TRYNGOLZA in sHTG? Or is there an expansion opportunity in moderate HTG that you think is worth pursuing? And if so, what would a TPP look like there? Brett Monia: Yes. Thanks, Eric. I'll ask Holly to talk a little bit about what we're planning to present at ESC on the long-term data on CORE and CORE 2. I'll take 775. So the goal is primarily -- we're primarily focused right now on severe hypertriglyceridemia. 775 as a follow-on molecule for this indication, and it isn't primarily a convenience play. I think I mentioned earlier that the efficacy and tolerability, safety profile of TRYNGOLZA and sHTG is difficult to beat. So we'll strive to do that, but it's really a convenience play that we think that we can dose this drug twice a year, maybe once per year based on our Phase I data. And that Phase I data will be presented at ESC. And I think it will be clear how durable 775 is. We'll always consider other indications, but primarily -- and we haven't laid out -- we have not established our Phase III plan yet. We're still working through that. It needs to be we need more Phase II data before we can really make those decisions. But it's really primarily focused on sHTG. And Holly, what can we expect on the long-term data for CORE 2 at ESC? Holly Kordasiewicz: Yes. This is looking at 1 year into the OLE. So of course, we'll be looking at triglyceride levels as well as full safety data and all of the key biomarkers, looking at remnant cholesterol, apoC-III, non-HDL, all of those various markers. Brett Monia: Yes. It's very exciting long-term data on the durability of efficacy as well as lack of any emerging adverse events or anything on the safety side. So thanks for the question, Eric. Thank you, everybody, for joining us today for participating in our call. We really are looking forward to an exciting second half of the year for Ionis, and we look forward to sharing our progress along the way. Until then, thanks, everybody, and have a great day. Operator: The conference has now concluded. 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Ionis Pharmaceuticals IONS reported second-quarter 2026 adjusted loss per share of 43 cents, narrower than the Zacks Consensus Estimate of a loss of 89 cents. In the year-ago period, the company had posted adjusted earnings of 86 cents. The adjusted earnings/loss exclude compensation expenses related to equity awards. Including this special item, loss was 69 cents per share against the earnings of 70 cents in the year-ago period. Quarterly revenues were $268 million, which beat the Zacks Consensus Estimate of $190.7 million. Yet, the reported figure fell nearly 41% year over year as the comparison was affected by an upfront payment of $280 million received from Japan-based Ono Pharmaceutical in the year-ago period. Excluding the Ono payment, total revenues rose 56% year over year, driven by commercial growth and payments tied to progress across partnered programs. Year to date, the company’s shares are down 33% compared with the industry’s nearly 3% decline. Image Source: Zacks Investment Research The company has two wholly-owned marketed drugs — Tryngolza for familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG), as well as Dawnzera for hereditary angioedema. Ionis also earns royalties from partnered medicines. These include the spinal muscular atrophy (SMA) therapy Spinraza and the ALS drug Qalsody, marketed by Biogen BIIB, as well as Wainua, developed and commercialized with AstraZeneca AZN for polyneuropathy caused by hereditary transthyretin-mediated amyloidosis. The company’s revenues are divided into two segments — commercial revenues and research and development (R&D) revenues. Commercial revenues, which include net product sales, royalties and other commercial revenues, rose 15% year over year to $119 million. R&D revenues, which include collaborative agreement revenues and Wainua joint-development revenues, fell 57% to $149 million. Tryngolza generated net product sales of $5 million in the second quarter compared with $19 million in the year-ago period. The decline reflected a strategic wholesale acquisition cost reduction that took effect on April 1, 2026, ahead of the broader sHTG launch. Following the drug's approval last month for the broader sHTG indication, management said the launch is off to an encouraging start. Management also noted that underlying FCS demand remained strong, with the highest number of new patient starts since launch, and expects sales to accelerate in the second half of 2026. Dawnzera generated net product sales of $26 million in the reported quarter, up 63% sequentially from $16 million in the first quarter of 2026. Demand was supported by patients switching from other long-term prophylactic therapies, those previously relying only on on-demand treatment and treatment-naive patients. Management also highlighted a growing base of repeat prescribers, indicating physicians’ positive experience with the drug. Royalty revenues increased 9% year over year to $76 million. Spinraza royalties fell 2% year over year to $53 million, while Wainua royalties rose 60% to $16 million. Other royalty revenues were $7 million. Collaborative agreement revenues were $133 million, down nearly 61% year over year. The sharp decline was primarily attributed to an upfront payment of $280 million received in the year-ago period from Ono for out-licensing rights to sapablursen, an investigational therapy for a rare blood cancer called polycythemia vera (PV). Wainua joint-development revenues increased to $16 million, up 33% year over year. Adjusted research, development and patent expenses declined nearly 3% year over year to $192 million, while adjusted selling, general and administrative expenses increased more than 60% to $130 million. The higher SG&A expenses reflected investments supporting the commercialization of Tryngolza and Dawnzera, as well as launch preparations for zilganersen in Alexander disease. Ionis reaffirmed its full-year 2026 revenue guidance of $875-$900 million. The company continues to expect Tryngolza's net product sales of $100-$110 million and Dawnzera's net product sales of $110-$120 million. The company also reiterated its adjusted operating loss guidance of $425-$475 million. Operating expenses are expected to increase in the low-teens percentage range from 2025, while R&D expenses are projected to remain broadly consistent with the prior year. Ionis continues to project year-end cash and investments of more than $1.6 billion while remaining on track for cash-flow breakeven in 2028. Some important wholly-owned candidates in Ionis’ pipeline include zilganersen and obudanersen. A regulatory filing seeking the FDA’s approval of zilganersen for Alexander disease is currently under review, with a final decision expected by Sept. 22, 2026. Obudanersen is being evaluated in the phase III REVEAL study for treating a rare and serious neurodevelopmental disorder called Angelman syndrome. Data from the study is expected next year. Earlier this month, AstraZeneca and Ionis announced that the phase III CARDIO-TTRANSform study, which evaluated Wainua for cardiomyopathy caused by hereditary TTR amyloidosis, did not meet its primary endpoint. Both companies plan to analyze the full data set to better understand the results and intend to present the findings at the European Society of Cardiology (ESC) Congress next month. Ionis’ partner, GSK plc GSK, is developing bepirovirsen as a potential treatment for patients with chronic hepatitis B virus. While the drug was invented by Ionis, GSK holds global development and marketing rights. A regulatory filing seeking approval for the GSK-partnered therapy is currently under FDA review. A final decision is expected by Oct. 26, 2026. Pelacarsen, in partnership with Novartis, is being developed in a phase III study called HORIZON for elevated Lp (a)-driven cardiovascular disease. Data from the study is expected later this year. Ionis Pharmaceuticals, Inc. price | Ionis Pharmaceuticals, Inc. Quote Ionis currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Ionis Pharmaceuticals, Inc. (IONS) : Free Stock Analysis Report AstraZeneca PLC (AZN) : Free Stock Analysis Report GSK PLC Sponsored ADR (GSK) : Free Stock Analysis Report Biogen Inc. (BIIB) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). 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For the quarter ended June 2026, Ionis Pharmaceuticals (IONS) reported revenue of $268 million, down 40.7% over the same period last year. EPS came in at -$0.43, compared to $0.86 in the year-ago quarter. The reported revenue compares to the Zacks Consensus Estimate of $190.72 million, representing a surprise of +40.52%. The company delivered an EPS surprise of +51.69%, with the consensus EPS estimate being -$0.89. While investors closely watch year-over-year changes in headline numbers -- revenue and earnings -- and how they compare to Wall Street expectations to determine their next course of action, some key metrics always provide a better insight into a company's underlying performance. As these metrics influence top- and bottom-line performance, comparing them to the year-ago numbers and what analysts estimated helps investors project a stock's price performance more accurately. Here is how Ionis Pharmaceuticals performed in the just reported quarter in terms of the metrics most widely monitored and projected by Wall Street analysts: Revenue- Total research and development revenue: $149 million versus the eight-analyst average estimate of $82.44 million. The reported number represents a year-over-year change of -57.3%. Revenue- Total commercial revenue: $119 million versus $107.43 million estimated by eight analysts on average. Compared to the year-ago quarter, this number represents a +15.5% change. Revenue- Royalty revenue- SPINRAZA royalties: $53 million compared to the $51.67 million average estimate based on seven analysts. The reported number represents a change of -1.9% year over year. Revenue- Product sales, net: $31 million versus the seven-analyst average estimate of $29.23 million. The reported number represents a year-over-year change of +60.9%. Revenue- Royalty revenue- WAINUA royalties: $16 million versus the seven-analyst average estimate of $15.23 million. Revenue- Product sales net- DAWNZERA sales: $26 million versus the seven-analyst average estimate of $24.94 million. Revenue- Product sales net- TRYNGOLZA sales: $5 million versus $4.28 million estimated by seven analysts on average. Revenue- Commercial revenue- Other commercial revenue: $12 million compared to the $7.1 million average estimate based on six analysts. Revenue- Royalty revenue: $76 million versus $71.38 million estimated by six analysts on average. Revenue- Royalty revenue- Other royalties: $7 million compared to the $4.28 million average estimate based on six analysts. Revenue- Research and development revenue- WAINUA joint development revenue: $16 million versus $12.86 million estimated by five analysts on average. Revenue- Research and development revenue- Collaborative agreement revenue: $133 million versus $70.79 million estimated by five analysts on average. Compared to the year-ago quarter, this number represents a -60.5% change. View all Key Company Metrics for Ionis Pharmaceuticals here>>> Shares of Ionis Pharmaceuticals have returned -30.3% over the past month versus the Zacks S&P 500 composite's +1.9% change. The stock currently has a Zacks Rank #3 (Hold), indicating that it could perform in line with the broader market in the near term. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Ionis Pharmaceuticals, Inc. (IONS) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

This article first appeared on GuruFocus. Revenue: $268 million in Q2 2026, $540 million in the first half of 2026, representing year-over-year growth of 56% and 69% respectively. Commercial Revenue: $119 million in Q2 2026, $226 million in the first half of 2026, up 15% and 27% respectively from the same periods last year. TRYNGOLZA Product Sales: $5 million in Q2 2026, $32 million in the first half of 2026. DAWNZERA Product Sales: $26 million in Q2 2026, $42 million in the first half of 2026, with a 63% increase in Q2 compared to Q1 2026. Research and Development Revenue: $149 million in Q2 2026, $288 million year-to-date. Cash Position: $2.1 billion in cash, cash equivalents, and short-term investments at the end of Q2 2026. Full-Year Revenue Guidance: Projected to be in the range of $875 million to $900 million for 2026. TRYNGOLZA Full-Year Sales Guidance: Expected to be $100 million to $110 million for 2026. DAWNZERA Full-Year Sales Guidance: Expected to be $110 million to $120 million for 2026. Operating Expenses: Expected to increase in the low teens percentage range for 2026 compared to last year. Non-GAAP Operating Loss: Projected between $425 million and $475 million for 2026. Year-End Cash Balance Projection: Greater than $1.6 billion for 2026. Warning! GuruFocus has detected 6 Warning Signs with IONS. Is IONS fairly valued? Test your thesis with our free DCF calculator. Release Date: July 29, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Ionis Pharmaceuticals Inc (NASDAQ:IONS) achieved a significant milestone with the FDA approval of TRYNGOLZA, the first and only medicine to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia. The company is experiencing strong commercial momentum with TRYNGOLZA and DAWNZERA, with TRYNGOLZA prescriptions starting on the day of approval. Ionis Pharmaceuticals Inc (NASDAQ:IONS) is advancing its leadership in neurological diseases with the anticipated launch of Zilganerse, positioned as the first disease-modifying treatment for Alexander's disease. The company reported strong financial results with significant year-over-year revenue growth of 56% in the second quarter and 69% in the first half of the year. Ionis Pharmaceuticals Inc (NASDAQ:IONS) maintains a robust pipeline with promising wholly-owned and partnered programs, including Bepirovirsen for chronic hepatitis B, which is on track for a global launch this year. The company faced a setback with the cardio transform Phase 3 study for eplontersen in ATTR cardiomyopathy, which did not meet the primary efficacy endpoint in the overall population. There are challenges in gaining payer coverage for TRYNGOLZA, with most early coverage being through medical exceptions. The launch of TRYNGOLZA for severe hypertriglyceridemia is expected to be a gradual build, requiring time to educate healthcare providers and patients. Ionis Pharmaceuticals Inc (NASDAQ:IONS) anticipates increased operating expenses in 2026, driven by commercialization efforts and pipeline advancements. The company faces potential pressure on achieving cash flow breakeven by 2028 if certain pipeline programs, like pelacarsen, do not meet expectations. Q: Can you elaborate on the early adoption of TRYNGOLZA and the process for prescription coverage? A: Kyle Jenne, Executive Vice President - Commercial, explained that early prescribers of TRYNGOLZA are often those who previously treated FCS patients. The process time for prescription coverage is still early to detail, but initial payer interactions are encouraging. Coverage is expected to improve through medical exceptions initially, with broader coverage anticipated as the year progresses. Q: What are you seeing in terms of reimbursement for TRYNGOLZA, especially for patients with triglycerides over 500 versus over 880? A: Kyle Jenne noted that reimbursement aligns with the label, which includes patients with triglycerides over 500 without limiting those over 880. Early approvals reflect this, and while prior authorizations are needed, the process is consistent with expectations. Q: Are SHTG patients already on lipid-lowering drugs switching to TRYNGOLZA, or is it being added to their treatment? A: Kyle Jenne stated that most SHTG patients are on background therapies like fibrates or omega-3s, and TRYNGOLZA is being added to these treatments. The drug's profile, including its monthly subcutaneous administration, is well-received, and there are no significant concerns about elevated liver fat. Q: How has the recent pelacarsen data affected your outlook for TRYNGOLZA, and what is your confidence in the Horizon trial? A: Brett Monia, CEO, expressed confidence in TRYNGOLZA as a best-in-class medicine for SHTG, with no concerns about competition. The Horizon trial is expected to show positive results, and any impact on financial guidance would be minimal. Q: What are the expectations for the upcoming ESC meeting regarding ION 775 data, and what is the path to market for this program? A: Holly Kordasiewicz, Chief Development Officer, mentioned that the ESC meeting will present year-long safety and efficacy data for ION 775. The program is in Phase 2b, and while timelines are not disclosed, the focus is on leveraging previous learnings to accelerate development. Q: How is the early momentum of the SHTG launch tracking with internal expectations, and what is the regulatory path for monotherapy in cardiomyopathy? A: Brett Monia stated that the SHTG launch is meeting internal expectations, with operational aspects like drug availability and payer engagement progressing well. For cardiomyopathy, AstraZeneca is reviewing data, and the ESC presentation will provide further insights. Q: Is there an initial pent-up demand for TRYNGOLZA in SHTG, and what are the main competitors for DAWNZERA? A: Kyle Jenne explained that the SHTG launch is expected to build gradually as awareness and payer access improve. DAWNZERA is competing in a switch market, with positive feedback from physicians leading to increased adoption. Q: How does the lack of a dedicated ICD-10 code for SHTG affect TRYNGOLZA reimbursement, and what is the purpose of the meta-analysis at ESC? A: Kyle Jenne acknowledged the challenge of not having a dedicated ICD-10 code but noted that reimbursement can still be achieved through medical history and prior authorizations. Holly Kordasiewicz added that the meta-analysis at ESC will compare silencer class data, including monotherapy and combination studies. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Interested in Ionis Pharmaceuticals, Inc.? Here are five stocks we like better. Second-quarter revenue rose to $268 million, with commercial revenue reaching $119 million, driven mainly by DAWNZERA and early TRYNGOLZA sales. Ionis reaffirmed its 2026 revenue outlook of $875 million to $900 million and ended the quarter with $2.1 billion in cash and investments. TRYNGOLZA’s U.S. launch expanded into severe hypertriglyceridemia after FDA approval, generating $5 million in second-quarter sales. Ionis expects payer coverage to broaden through 2026 and 2027 and continues to project more than $3 billion in potential peak annual revenue. Eplontersen failed to meet the primary endpoint in the overall phase III ATTR cardiomyopathy study, though Ionis reported TTR reductions and nominally significant results in the monotherapy subgroup. The company is awaiting detailed results while advancing catalysts including zilganersen, pelacarsen, ulefnersen and bepirovirsen. The Phase 3 Failure That Sent Biotech Winners and Losers in Opposite Directions Ionis Pharmaceuticals (NASDAQ:IONS) reported second-quarter revenue growth driven by commercial products and partnered research programs, while highlighting the recent U.S. approval and early launch progress for TRYNGOLZA in severe hypertriglyceridemia. Chief Executive Officer Brett Monia said the company entered the second half of 2026 with commercial momentum, a growing wholly owned pipeline and a goal of reaching cash-flow breakeven in 2028. He also acknowledged that the phase III CARDIO-TTRansform study of eplontersen in ATTR cardiomyopathy did not meet its primary efficacy endpoint in the overall population. → This Tiny AI Supplier Could Be More Important Than the Chipmakers Are These 5 Undervalued Stocks Ready to Break Out? Chief Financial Officer Beth Hougen said second-quarter revenue was $268 million, while first-half revenue totaled $514 million. Excluding a $280 million one-time payment from Ono in the first half of 2025, revenue rose 56% in the second quarter and 69% in the first half from the comparable periods a year earlier. Commercial revenue reached $119 million in the second quarter and $226 million for the first six months of 2026, increases of 15% and 27%, respectively. Hougen said the gains were primarily driven by DAWNZERA sales. TRYNGOLZA generated $5 million in second-quarter product sales and $32 million in first-half sales. DAWNZERA generated $26 million in second-quarter sales and $42 million in first-half sales. Second-quarter DAWNZERA sales increased 63% from the first quarter. Research and development revenue was $149 million in the second quarter and $288 million year to date. Ionis ended the quarter with $2.1 billion in cash equivalents and short-term investments. → Refiner Stocks Are Near Record Highs—Can Iran-Driven Margins Keep Them There? The company reaffirmed its 2026 revenue outlook of $875 million to $900 million. It continues to expect TRYNGOLZA sales of $100 million to $110 million and DAWNZERA sales of $110 million to $120 million for the year. Ionis expects operating expenses to rise in the low-teens percentage range, with a projected non-GAAP operating loss of $425 million to $475 million and year-end cash above $1.6 billion. Ionis said TRYNGOLZA was approved last month as the first and only FDA-approved medicine to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia, or sHTG. The company said it received prescriptions on the day of approval and placed both the 50-milligram and 80-milligram doses in distribution channels within about one week. → Innovative ETF Strategies That Are Paying Off This Summer Kyle Jenne, chief global product strategy officer, said the launch has begun with prescriptions from cardiologists, endocrinologists, lipidologists and primary-care physicians. Ionis estimates that about 3 million people in the U.S. have sHTG, including roughly 1 million high-risk patients. Jenne said early payer coverage has been consistent with the product label for patients with triglycerides above 500 milligrams per deciliter, though most early access is occurring through medical exceptions while insurers establish formal coverage criteria. The company expects coverage to broaden through the rest of 2026 and into 2027. Ionis said physicians are generally using TRYNGOLZA alongside existing standard therapies, such as fibrates, omega-3 medicines or statins. The company expects the therapy to return to revenue growth in the second half as the broader sHTG launch gains momentum and reiterated its expectation for more than $3 billion in peak annual revenue. Separately, management said demand in familial chylomicronemia syndrome remained strong, with the highest number of patient starts since that launch began. Jenne said competition had not had a meaningful impact on TRYNGOLZA demand in that indication. Ionis said DAWNZERA, its hereditary angioedema prophylaxis medicine, continued to gain adoption in the U.S. market, which management described as primarily a switch market. Jenne said uptake has included patients switching from established preventative therapies, those previously receiving only on-demand treatment and treatment-naive patients. The company is also preparing for a potential launch of zilganersen for Alexander disease. The FDA granted priority review, with a PDUFA target action date of Sept. 22. Ionis said approximately half of the estimated 300 U.S. patients with Alexander disease have already been identified through ICD-10 codes and patient registries. The company has established an expanded-access program and is preparing patient-support services and outreach to specialized leukodystrophy centers. Recordati plans to seek approval for zilganersen in the European Union and Japan next year, Ionis said. Monia said Ionis and AstraZeneca are continuing to analyze the CARDIO-TTRansform study after eplontersen did not meet its primary endpoint in the overall ATTR cardiomyopathy population. He said the medicine produced substantial and durable reductions in transthyretin, or TTR, and nominally significant results in the monotherapy subgroup, but showed no benefit in the combination subgroup. Detailed results are scheduled for presentation at the European Society of Cardiology meeting in August. Ionis also plans to present long-term TRYNGOLZA data from the CORE and CORE2 open-label extension studies at ESC. Chief Development Officer Holly Kordasiewicz said the presentations will include triglycerides, safety and biomarkers including APOC3, remnant cholesterol and non-HDL cholesterol. Other anticipated milestones include phase III data for Novartis-partnered pelacarsen in Lp(a)-driven cardiovascular disease, readouts for ulefnersen in FUS-ALS and IONIS-FB-LRx in IgA nephropathy, and an Oct. 26 FDA action date for GSK-partnered bepirovirsen in chronic hepatitis B. Ionis also completed enrollment in the phase III REVEAL trial of obudanersen for Angelman syndrome, with data expected in the second half of 2027, and initiated a phase I/II study of ION337 in Dravet syndrome. The company advanced ION775 into a phase IIb trial in severe or moderately elevated triglycerides and said it sees potential for semiannual or less frequent dosing. Finally, Monia recognized Chief Scientific Officer Frank Bennett, whose planned retirement was announced the morning of the call. Monia credited Bennett, one of Ionis' founding scientists, with contributions to the company’s RNA-targeted medicines platform and neurology pipeline. Ionis Pharmaceuticals, Inc is a biotechnology company focused on the discovery and development of RNA-targeted therapies designed to modulate gene expression. The company's proprietary antisense oligonucleotide (ASO) technology enables the selective binding of short synthetic strands of nucleic acids to messenger RNA (mRNA), thereby inhibiting or altering the production of disease-causing proteins. Ionis' pipeline spans a range of therapeutic areas, including neurological disorders, cardiovascular conditions, metabolic diseases and rare genetic disorders. Since its founding in 1989 by Dr. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Ionis Pharmaceuticals Q2 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for July 2026.

- TRYNGOLZA® (olezarsen) demonstrating early sHTG launch momentum, underscoring multi-billion-dollar revenue potential in large patient population – - Completed enrollment in Phase 3 REVEAL trial in Angelman syndrome - - On track to achieve 2026 financial guidance - CARLSBAD, Calif., July 29, 2026--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company") today reported financial results and provided key updates for the second quarter ended June 30, 2026. "With the approval of TRYNGOLZA in late June, Ionis is bringing the first and only treatment to reduce triglycerides and acute pancreatitis to people living with severe hypertriglyceridemia. We are encouraged by the early launch momentum and look forward to accelerating growth from TRYNGOLZA and our other wholly owned medicines in the quarters and years to come," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "In the second half of this year, we expect multiple important milestones, including approval of zilganersen for Alexander disease, positioning us for our first independent launch from our leading neurology portfolio. We also expect results from the landmark pelacarsen Lp(a) HORIZON cardiovascular outcomes trial and the global launch of bepirovirsen for chronic hepatitis B. With our advancing pipeline and growing commercial momentum, Ionis is on track to deliver accelerating value to patients and all Ionis stakeholders." Second Quarter 2026 Summary Financial Results(1): Second Quarter 2026 Financial Highlights Revenue in the second quarter and first half of 2026 increased by 56% and 69% respectively, compared to the same periods last year, excluding the one-time sapablursen upfront payment recognized in the second quarter of 2025, driven by continued commercial success and substantial R&D revenue from multiple partnerships Operating expenses for the second quarter and first half of 2026 were in line with expectations and increased year over year primarily from investments related to the commercialization efforts for TRYNGOLZA and DAWNZERA and launch preparations for zilganersen in Alexander disease Ended the second quarter of 2026 with cash and short-term investments of $2.1 billion as of June 30, 2026, enabling continued investments to drive value in Ionis’ wholly owned portfolio Second Quarter 2026 Financial Results "Our performance in the first half of this year reflects the strength and resilience of our business. We delivered significantly increased commercial revenue from our independent launches, substantial R&D revenue from multiple partnered medicines and invested in our advancing wholly owned pipeline," said Elizabeth L. Hougen, chief financial officer of Ionis. "Even with the outcome of the CARDIO-TTRansform study of eplontersen in ATTR-CM, our first-half execution and positive outlook for the second half of the year keep us on track to achieve our 2026 financial guidance. We also remain on track to achieve our goal of cashflow breakeven in 2028 and deliver substantial growth and long-term value-creation." Recent Highlights - Wholly Owned Medicines TRYNGOLZA® (olezarsen), the first FDA-approved treatment to reduce triglycerides and acute pancreatitis risk in adults with severe hypertriglyceridemia (sHTG) as an adjunct to diet DAWNZERA® (donidalorsen), the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in patients 12 years of age and older Zilganersen on track to launch this year as the first and only medicine to demonstrate clinically meaningful and disease-modifying benefit in children and adults with Alexander disease (AxD), assuming approval Obudanersen, a potential treatment for Angelman syndrome, completed enrollment in the Phase 3 REVEAL study, with data anticipated in the second half of 2027 ION775, a potential treatment for sHTG, entered a Phase 2 study in people with sHTG and moderately elevated triglycerides (HTG) based on Phase 1 results showing robust triglyceride lowering with potential for extended dosing intervals Recent Highlights – Partnered Medicines SPINRAZA® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $402 million in the second quarter of 2026, resulting in royalty revenue of $54 million WAINUA® (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated global sales of $70 million in the second quarter of 2026, resulting in royalty revenue of $16 million Bepirovirsen, a potential first-in-class treatment of chronic hepatitis B (CHB), on track for global launch this year Salanersen, a potential treatment for SMA, entered Phase 3 development and granted Breakthrough Therapy Designation by the FDA, based on positive interim Phase 1 results demonstrating potential to achieve high efficacy with annual dosing Sapablursen, a potential treatment for polycythemia vera, entered Phase 3 development based on positive Phase 2 data Diranersen (IONIS-MAPTRx / BIIB080), a potential treatment for Alzheimer’s disease, demonstrated benefit in measures of cognition with favorable safety and tolerability in the Phase 2 CELIA study; Biogen plans to advance diranersen into Phase 3 development Revenue Ionis’ revenue was comprised of the following: Commercial revenue for the second quarter and first half of 2026 increased 15% and 27%, respectively, compared to the same periods in 2025. This increase was primarily driven by DAWNZERA product sales. Research and development revenue was also higher in the second quarter and first half of 2026, compared to the same periods in 2025, driven by multiple payments for programs advancing under its R&D collaborations, and excluding the $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. the Company received in the second quarter of 2025. Operating Expenses Operating expenses for the second quarter and first half of 2026 increased year over year, in line with expectations, primarily from investments related to the commercialization efforts for TRYNGOLZA and DAWNZERA and launch preparations for zilganersen in Alexander disease, with full-year expenses remaining on track for low-teens percentage growth year-over-year. Balance Sheet As of June 30, 2026, Ionis’ cash, cash equivalents and short-term investments decreased to $2.1 billion, compared to $2.7 billion on December 31, 2025, primarily due to repayment of the 0% convertible notes on April 1, 2026. Webcast and Other Updates Management will host a conference call and webcast to discuss Ionis’ second quarter 2026 results at 8:30 a.m. Eastern time on Wednesday, July 29, 2026. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company’s second quarter 2026 earnings slides click here. Ionis’ Marketed Medicines TRYNGOLZA® (olezarsen): TRYNGOLZA was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG ≥500 mg/dL) and as an adjunct to diet to reduce TG in adults with familial chylomicronemia syndrome (FCS). For more information about TRYNGOLZA, including the full U.S. Prescribing Information, visit tryngolza.com. DAWNZERA® (donidalorsen): DAWNZERA was approved by the U.S. Food and Drug Administration for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. For more information about DAWNZERA, including the full U.S. Prescribing Information, visit dawnzera.com. WAINUA® (eplontersen): WAINUA was approved by the U.S. Food and Drug Administration for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. For more information about WAINUA, including the full U.S. Prescribing Information, visit wainua.com. For more information about SPINRAZA and QALSODY, visit https://www.spinraza.com/ and https://www.qalsody.com/, respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s). About Ionis Pharmaceuticals, Inc. For more than three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram. Ionis Forward-looking Statements This press release includes forward-looking statements regarding Ionis’ business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development, technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2025, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. TRYNGOLZA® is a registered trademark of Ionis Pharmaceuticals, Inc. DAWNZERA® is a trademark of Ionis Pharmaceuticals, Inc. AKCEATM is a trademark of Akcea Therapeutics, Inc. TEGSEDITM is a trademark of Akcea Therapeutics, Inc. WAYLIVRATM is a trademark of Akcea Therapeutics, Inc. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUA® is a registered trademark of the AstraZeneca group of companies. Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP income (loss) from operations, and non-GAAP net income (loss) were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis’ non-GAAP results is consistent with how Ionis’ management internally evaluates the performance of its operations. Key 2026 Value Driving Events(1) View source version on businesswire.com: https://www.businesswire.com/news/home/20260729215124/en/ Contacts Ionis Investor Contact: D. Wade Walke, [email protected] 760-603-2331 Ionis Media Contact: Hayley [email protected] 760-603-4679

Wall Street expects a year-over-year increase in earnings on higher revenues when Neurocrine Biosciences (NBIX) reports results for the quarter ended June 2026. While this widely-known consensus outlook is important in gauging the company's earnings picture, a powerful factor that could impact its near-term stock price is how the actual results compare to these estimates. The stock might move higher if these key numbers top expectations in the upcoming earnings report, which is expected to be released on July 30. On the other hand, if they miss, the stock may move lower. While management's discussion of business conditions on the earnings call will mostly determine the sustainability of the immediate price change and future earnings expectations, it's worth having a handicapping insight into the odds of a positive EPS surprise. This biopharmaceutical company is expected to post quarterly earnings of $2.24 per share in its upcoming report, which represents a year-over-year change of +111.3%. Revenues are expected to be $894.32 million, up 30.1% from the year-ago quarter. The consensus EPS estimate for the quarter has remained unchanged over the last 30 days. This is essentially a reflection of how the covering analysts have collectively reassessed their initial estimates over this period. Investors should keep in mind that the direction of estimate revisions by each of the covering analysts may not always get reflected in the aggregate change. Price, Consensus and EPS Surprise Estimate revisions ahead of a company's earnings release offer clues to the business conditions for the period whose results are coming out. Our proprietary surprise prediction model -- the Zacks Earnings ESP (Expected Surprise Prediction) -- has this insight at its core. The Zacks Earnings ESP compares the Most Accurate Estimate to the Zacks Consensus Estimate for the quarter; the Most Accurate Estimate is a more recent version of the Zacks Consensus EPS estimate. The idea here is that analysts revising their estimates right before an earnings release have the latest information, which could potentially be more accurate than what they and others contributing to the consensus had predicted earlier. Thus, a positive or negative Earnings ESP reading theoretically indicates the likely deviation of the actual earnings from the consensus estimate. However, the model's predictive power is significant for positive ESP readings only. A positive Earnings ESP is a strong predictor of an earnings beat, particularly when combined with a Zacks Rank #1 (Strong Buy), 2 (Buy) or 3 (Hold). Our research shows that stocks with this combination produce a positive surprise nearly 70% of the time, and a solid Zacks Rank actually increases the predictive power of Earnings ESP. Please note that a negative Earnings ESP reading is not indicative of an earnings miss. Our research shows that it is difficult to predict an earnings beat with any degree of confidence for stocks with negative Earnings ESP readings and/or Zacks Rank of 4 (Sell) or 5 (Strong Sell). For Neurocrine, the Most Accurate Estimate is higher than the Zacks Consensus Estimate, suggesting that analysts have recently become bullish on the company's earnings prospects. This has resulted in an Earnings ESP of +3.77%. On the other hand, the stock currently carries a Zacks Rank of #1. So, this combination indicates that Neurocrine will most likely beat the consensus EPS estimate. While calculating estimates for a company's future earnings, analysts often consider to what extent it has been able to match past consensus estimates. So, it's worth taking a look at the surprise history for gauging its influence on the upcoming number. For the last reported quarter, it was expected that Neurocrine would post earnings of $1.68 per share when it actually produced earnings of $1.94, delivering a surprise of +15.48%. Over the last four quarters, the company has beaten consensus EPS estimates three times. An earnings beat or miss may not be the sole basis for a stock moving higher or lower. Many stocks end up losing ground despite an earnings beat due to other factors that disappoint investors. Similarly, unforeseen catalysts help a number of stocks gain despite an earnings miss. That said, betting on stocks that are expected to beat earnings expectations does increase the odds of success. This is why it's worth checking a company's Earnings ESP and Zacks Rank ahead of its quarterly release. Make sure to utilize our Earnings ESP Filter to uncover the best stocks to buy or sell before they've reported. Neurocrine appears a compelling earnings-beat candidate. However, investors should pay attention to other factors too for betting on this stock or staying away from it ahead of its earnings release. Another stock from the Zacks Medical - Drugs industry, Ionis Pharmaceuticals (IONS), is soon expected to post loss of $0.91 per share for the quarter ended June 2026. This estimate indicates a year-over-year change of -205.8%. Revenues for the quarter are expected to be $189.93 million, down 58% from the year-ago quarter. The consensus EPS estimate for Ionis Pharmaceuticals has been revised 4.1% lower over the last 30 days to the current level. However, a higher Most Accurate Estimate has resulted in an Earnings ESP of +3.30%. This Earnings ESP, combined with its Zacks Rank #4 (Sell), makes it difficult to conclusively predict that Ionis Pharmaceuticals will beat the consensus EPS estimate. The company beat consensus EPS estimates in each of the trailing four quarters. Stay on top of upcoming earnings announcements with the Zacks Earnings Calendar. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Neurocrine Biosciences, Inc. (NBIX) : Free Stock Analysis Report Ionis Pharmaceuticals, Inc. (IONS) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research