Q3 2024 Ionis Pharmaceuticals Inc Earnings Call

Thomson Reuters StreetEvents11-07

Participants Wade Walke; Senior Vice President, Investor Relations; Ionis Pharmaceuticals Inc Brett Monia; Chief Executive Officer, Director; Ionis Pharmaceuticals Inc Eugene Schneider; Executive Vice...

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Brett Monia; Chief Executive Officer, Director; Ionis Pharmaceuticals Inc. Eugene Schneider; Executive Vice President, Chief Clinical Development Officer; Ionis Pharmaceuticals Inc. Kyle Jenne; Executive Vice President - commercial; Ionis Pharmaceuticals Inc. Elizabeth Hougen; Chief Financial Officer, Executive Vice President - Finance; Ionis Pharmaceuticals Inc. Richard Geary; Executive Vice President, Chief Development Officer; Ionis Pharmaceuticals Inc. Good morning, and welcome to the IONA's Third Quarter 2024 financial results conference call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.Thanks, Wade. Good morning, everybody, and thank you for joining us on today's call. This is a pivotal time for Ionis. Nearly five years ago, we set out to execute on a new vi","collect":0,"end_time":0,"defaultTopTitle":"yahoo.com","property":["earning"],"viewcount":null,"language":"en","relate_stocks":{"AZN":"阿斯利康","IONS":"Ionis Pharmaceuticals, Inc"},"translate_title":"2024年第三季度Ionis Pharmaceuticals Inc收益看涨期权","themeId":null,"isJumpTheme":false,"ttsUrl":null,"symbols_score_info":{"IONS":1,"AZN":0.9},"content_text":"Participants\nWade Walke; Senior Vice President, Investor Relations; Ionis Pharmaceuticals Inc\nBrett Monia; Chief Executive Officer, Director; Ionis Pharmaceuticals Inc\nEugene Schneider; Executive Vice President, Chief Clinical Development Officer; Ionis Pharmaceuticals Inc\nKyle Jenne; Executive Vice President - commercial; Ionis Pharmaceuticals Inc\nElizabeth Hougen; Chief Financial Officer, Executive Vice President - Finance; Ionis Pharmaceuticals Inc\nRichard Geary; Executive Vice President, Chief Development Officer; Ionis Pharmaceuticals Inc\nJonathan Birchall; CCO; Ionis Pharmaceuticals Inc\nEric Swayze; Executive Vice President - Research; Ionis Pharmaceuticals Inc\nGary Nachman; Analyst; Raymond James\nJessica Fye; Analyst; JPMorgan Chase & Co\nMike Ulz; Analyst; Morgan Stanley & Co LLC.\nYanan Zhu; Analyst; Wells Fargo Securities, LLC\nLuca Issi; Analyst; RBC Capital Markets\nDavid Lewis; Analyst; Citi.\nJason Gerberry; Analyst; BofA Securities\nJay Olson; Analyst; Oppenheimer & Co. Inc.\nMani Foroohar; Analyst; Leerink Partners\nAndy Chan; Analyst; Wolfe Research, LLC\nPresentation\nOperator\n Good morning, and welcome to the IONA's Third Quarter 2024 financial results conference call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.\nWade Walke\n Thank you, Danielle. 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 the slides on our website that accompany today's call.With me on this morning's call are Brett Monia, our Chief Executive Officer; Eugene Schneider, Chief Clinical Development Officer; Kyle Jenne, Chief Global Product Strategy Officer; and Beth Hougen, Chief Financial Officer. Richard Geary, Chief Development Officer; Eric Swayze, Executive Vice President of Research; and Jonathan Birchall, Chief Commercial Officer, will also join us for the Q&A portion of the call.I would like to draw your attention to slide 3, which contains our forward-looking language statement. During this call, we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail.And with that, I'll turn the call over to Brett.\nBrett Monia\n Thanks, Wade. Good morning, everybody, and thank you for joining us on today's call. This is a pivotal time for Ionis. Nearly five years ago, we set out to execute on a new vision focused on bringing our innovative medicines directly to patients in need. And today, we're on the cusp of achieving that vision with our first planned independent launch just a few weeks away.Furthermore, we anticipate three additional independent launches over the next three years, positioning Ionis to enter a new era marked by delivering a steady cadence of important new medicines to people with serious diseases. Olezarsen represents one of the most meaningful wholly owned opportunities in our late-stage pipeline today. It has the potential to address two important patient populations.With an FDA action date next month, we're ready to first bring Olezarsen to people with familial chylomicronemia syndrome, or FCS, a serious and rare disease that today has no approved treatments in the United States. And with Phase III data in people with severe hypertriglyceridemia, or sHTG, planned for the second half of next year, we expect to bring olezarsen to a much larger patient population in 2026.With significant first-mover advantage in both populations and compelling results already demonstrated in FCS, coupled with our expectation for similarly positive data in sHTG, we believe olezarsen could be the standard of care for both disease indications.In parallel, we're leveraging the capabilities established for WAINUA and olezarsen in our preparations to launch donidalorsen next year, our first-in-class treatment for HAE prophylaxis. We're pleased that our NDA submission was recently accepted for review by FDA with no plan for an AdCom. Our PDUFA date is set for August 21, 2025. And outside the US, our commercial partner, Otsuka, expects to file for marketing approval in Europe soon.We've generated important and compelling positive data from our comprehensive donidalorsen clinical program, including encouraging data from our OASIS-Plus Switch cohort. These results, together with the potential for monthly or every two-month self-administration using an auto-injector, strengthen our belief that if approved, donidalorsen has the potential to advance the treatment paradigm for people living with HAE.Looking further ahead, our next wave of wholly owned opportunities is progressing rapidly and includes our program for Angelman syndrome, ION582. Based on the positive results from the HALOS Phase I/II study and our alignment with FDA on the Phase III study design, we're on track to advance this potentially transformational medicine into Phase III development in the first half of next year.ION582 is an important program in our growing wholly owned neurology franchise, which now includes seven medicines in clinical development. On top of the great progress we're making across our wholly owned pipeline, our partner programs are also advancing very well, allowing more Ionis discovered and developed medicines to reach more and more people, as demonstrated this year with the successful launches of WAINUA and QALSODY.The launch of our first Ionis co-branded medicine this year, WAINUA, for people with hereditary ATTR polyneuropathy continues to progress well with AstraZeneca. WAINUA is now approved and available in major markets, including the US, Canada and the UK; and recently received a positive CHMP opinion in Europe.And we're confident in the potential of WAINUA to address the larger ATTR cardiomyopathy population with our ongoing landmark CARDIO-TTRansform trial on track to deliver the most comprehensive and most robust data set in these patients in the second half of 2026.We believe WAINUA has the potential to be the treatment of choice for the global ATTR population based on its strong efficacy profile in hereditary ATTR polyneuropathy and the freedom of simple, at-home self-administration together with AstraZeneca's global cardiovascular leadership and our leadership in TTR amyloidosis.And we're also pleased that QALSODY, the first approved treatment for a genetic cause of ALS, a medicine that was conceived and discovered by Ionis and commercialized by our partner, Biogen; is now launched and available in Europe and China in addition to the US.Our other partner programs are also progressing well. This includes the ongoing Phase III HORIZON study of pelacarsen for Lp(a)-driven cardiovascular disease being developed by Novartis, with data expected next year, and bepirovirsen in Phase III development with GSK for chronic HBV infection now fully enrolled, with data expected in 2026.Our accomplishments so far this year and the investments we're making move us closer to achieving our goal of bringing a steady cadence of new transformational medicines to patients for years to come and generating increased value for all Ionis stakeholders.And with that, I'll turn the call over to Eugene.\nEugene Schneider\n Thank you, Brett. Our pipeline has delivered many important achievements this year, including bringing two new medicines to people with serious diseases, eight positive data readouts from our mid- and late-stage pipeline and enrollment completion in 6 Phase III studies.Our progress positions us well to deliver important value-driving events, still to come this year and throughout 2025. These events include several potential regulatory approvals, two launches for wholly-owned medicines and 3 Phase III readouts.In addition to all this, we will continue to expand and advance our pipeline of potentially transformational wholly-owned medicines. We look forward to the upcoming December 19 PDUFA action date for olezarsen and FCS and bringing olezarsen to patients, assuming approval.Our NDA submission was based on a positive Phase III BALANCE study in FCS patients that showed substantial and durable triglyceride reductions with olezarsen treatment. Importantly, olezarsen also demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks.In patients taking our planned commercial dose, we observed a 90% mean reduction in acute pancreatitis events, with only one event in the treatment group, which occurred after nearly one year of treatment. This was compared to 11 events in the placebo group, with the first event occurring after only nine days. Olezarsen also reduced hospitalizations by remarkable 84% and showed a favourable safety and tolerability profile in the study.We're also developing olezarsen for the much larger sHTG patient population. Many patients living with sHTG today are unable to manage their triglycerides with current standard of care. As a result, we believe that olezarsen has the potential to make a meaningful difference in the lives of people living with sHTG. Our comprehensive Phase III program for sHTG fully enrolled. We remain on track for data in the second half of next year.Following closely behind olezarsen is donidalorsen for the prophylactic treatment of hereditary angioedema. Our NDA submission was based on positive data generated from our Phase II study and Phase III program, which includes the OASIS-HAE and OASIS-Plus studies.OASIS-Plus comprises an open-label cohort of patients rolling over from the Phase III study and a separate cohort that we refer to as the Switch study. In the Phase III program, donidalorsen demonstrated an overall sustained mean reduction in HAE attack rates of more than 90% with one year of treatment for both monthly and bimonthly dosing regimens while maintaining a favourable safety and tolerability profile in the study.This reduction translated to high level of disease control and clinically meaningful improvements in quality of life across multiple measures in a vast majority of patients. These positive data were bolstered by the encouraging Switch study results that showed a 62% further reduction in mean monthly HAE attack rates for patients who switched to donidalorsen from their prior prophylactic treatment.Importantly, more than 80% of patients surveyed reported a preference for donidalorsen over their prior treatment. Additionally, we recently presented new long-term Phase II open-label data that showed an overall sustained mean reduction in HAE attack rates of up 96% in up to three years of treatment with monthly or every two months dosing.Based on these robust results, we believe donidalorsen could become a preferred prophylactic treatment for people with HAE. With a PDUFA date of August 21 next year, we look forward to bringing this important medicine to HAE patients, assuming approval. Recent clinical outcomes data in ATTR cardiomyopathy with another TTR silencer further reinforce our confidence in the potential of WAINUA to improve cardiovascular outcomes and people living with this disease worldwide.With over 1,400 patients enrolled, our ongoing cardio transform study is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy. As a result, we expect the data from this study will enable physicians to make more informed treatment decisions in this dynamic treatment landscape. In addition, and as part of our Phase III program, we're conducting advanced cardiac imaging sub studies using MRI and Syntigraphy, which will generate valuable data about the potential benefit of WAINUA in cardiomyopathy patients.We expect the data readout from our Phase III program in the second half of 2026. The rest of our impressive Phase III pipeline is also advancing nicely. Of the nine investigational medicines in Phase III, over half are ones that Ionis is co-commercializing or wholly owned. The vast majority have Phase III data readouts or key regulatory filings expected in the next two years.In addition, Biogen recently presented positive Phase II/III data from the DEVOTE study evaluating higher dose nusinersen in patients with spinal muscular atrophy across all age groups. Building on these positive results and the all characterized profile of SPINRAZA established over the past 10 years, Biogen plans to file for approval with global regulatory agencies for higher dose nusinersen later this year.Biogen is also conducting additional studies evaluating nusinersen in SMA patients previously treated with risdiplam and patients with a suboptimal response to gene therapy. These studies aim to address remaining unmet needs and better informed treatment decisions. Our next wave of wholly-owned medicines now includes seven investigational medicines with three recent study starts to treat both rare and more common neurological diseases.Zilganersen is our medicine in Phase III development to treat Alexander's disease, the type of leukodystrophy with Phase III data expected in the second half of next year. Zilganersen was also recently granted fast track designation by the FDA, reflecting the serious unmet need that exists for this rare disease. We believe ION582, our poly owned investigational medicine for Angelman Syndrome has transformational potential for the tens of thousands of people living with a serious rare disorder.Positive early results from the HALO study of ION 582 and people with Angelman Syndrome demonstrated consistent and encouraging improvement in all key functional areas across multiple assessments, with improvements observed across different ages and genotypes.We also saw favorable safety and tolerability at all those levels, including no discontinuation or adverse events that were considered related to study drug. We had a positive end of Phase II discussion with the FDA, where we reached alignment on a robust and comprehensive Phase III study design. And as a result, we remain on track to advance IM-582 into pivotal development in the first half of next year.Our planned Phase III study focuses on clinical endpoints that reflect the most pressing and meaningful outcomes for people living with Angelman syndrome and their caregivers. And we designed the study to deliver robust data in patients representative of the broader Angelman syndrome population.(technical difficulty) global Phase III study will enrol approximately 200 infants, children, and adults with Angelman syndrome who have a maternal UBE3A gene deletion or mutation. The trial will be placebo-controlled, which is the gold standard for scientific integrity and enables a simple and straightforward way to operationalize the study.We plan to evaluate two dose levels, dosed quarterly without a loading regimen for approximately one year. Primary endpoint will be improvement in expressive communication as assessed by the Baileys scale for infant and toddler development (technical difficulty), which is an objective and direct clinician-administered assessment instrument. Secondary endpoints include evaluation of overall symptoms of disease severity, cognition, communication, sleep, motor functioning and daily living skills.We observed positive results for these same endpoints in our HALO Phase I/II study with IM 582 treatment. We look forward to sharing our planned Phase III program at the test Global Science Summit this weekend. As our pipeline continues to mature, the remainder of this year and next year is going to be very significant for us in terms of regulatory actions and new product launches, reflecting our transformation to a commercial stage company. Built to come this year are two important regulatory milestones, including the FDA approval decision of olezarsen [for] FCS and following the recent positive CHMP opinion, the potential approval of WAINUA for ATTR polyneuropathy in Europe.As we look to 2025, in addition to bringing olezarsen to people with FCS, we're poised to deliver donidalorsen to people with HAE assuming approval. We're also on track for 3 Phase III data readouts next year. These include two wholly-owned medicines olezarsen for SHTG, a large patient population with high unmet need and zildanersen for Alexander's disease, our most advanced wholly-owned neurology medicine.And our partner, Novartis, expects Phase III data for pelacarsen, first potential treatment targeting LP(a), a major novel independent risk factor for cardiovascular disease. We also expect multiple data readouts next year from our mid-stage pipeline. This includes data from sapovlirsen or potential treatment for polycythemia vera. And ION464, our medicine that targets alpha-synuclein that we're studying in multiple systems atrophy. Positive outcomes for ION464 or sapovlirsen could support advancing these programs into Phase III development.And with that, I'll turn the call over to Kyle.\nKyle Jenne\n Thank you, Eugene. We are pleased with the continued strong progress for the WAINUA US launch with AstraZeneca and hereditary ATTR polyneuropathy, which has demonstrated substantial sequential quarterly growth this year, driven by strong demand. We continued to see good uptake in the third quarter with product sales increasing 44% compared to the second quarter.Patient growth came from patients new to treatment, some switching from other treatments and some using WAINUA as an add-on treatment to their existing therapy. We are also encouraged by the breadth of prescribers. Physicians are reporting that patients are having a positive experience on WAINUA. This includes physicians and patients seeing quality of life improvements, patients' ability to access treatment and patients' ability to easily self-administer WAINUA.And as we and AstraZeneca are progressing our pre-commercialization activities to support the substantial opportunity, WAINUA represents for the ATTR cardiomyopathy population estimated to be between $300,000 and $500,000 worldwide. Ionis has a rich pipeline of potentially life-changing medicines, and we are poised to deliver four independent launches, assuming FDA approvals over the next three years.We are just weeks away from the first launch with olezarsen, where Ionis is leading the way in the triglyceride lowering space. Olezarsen represents a blockbuster opportunity for Ionis. We have substantial first-mover advantage for two indications: FCS and SHTG. Our first planned launch is for FCS, which is a rare and the most severe form of SHTG. We then plan to launch in the much larger SHTG patient population with triglyceride levels of greater than 500 milligrams per deciliter.People with FCS and SHTG suffer from debilitating chronic physical symptoms that impact all aspects of their life. There are no approved treatments for people with FCS in the United States. People with SHTG are severely underserved by current treatment options and in many cases, are unable to reduce triglyceride levels to current recommended guidelines.And in the most severe manifestations of FCS and SHTG, patients can suffer from potentially fatal pancreatitis events that require intensive hospital care. We are right where we should be in preparing for our first independent launch for olezarsen and FCS as we approach our upcoming FDA action date. Since this is a rare underdiagnosed disease, our medical affairs team has been working to increase disease awareness. This includes engaging with KOLs and physicians currently diagnosing and treating FCS patients, such as endocrinologists, lipidologists, and cardiologists.Building on a strong foundation of increasing disease awareness, the team is identifying physicians most likely to prescribe olezarsen and working to identify FCS patients. As with any rare disease launch, it takes time to identify patients, so this work will continue as we build launch momentum. To bolster our field team's efforts, we are executing a tailored omnichannel strategy to drive deeper engagement and real-time insights from patients and health care professionals.We are deploying a world-class patient and caregiver team to provide a seamless customer experience that supports patients initiating and remaining on therapy. The US FCS expanded access program is in place, enabling patients to have access to treatment ahead of potential approval. And now the sales team is trained and in the field calling on potential treaters. All of this, along with the learnings from our co-commercialization launch of WAINUA sets us up to execute successfully on our first independent launch.And as we look beyond our first launch, we plan to further scale our commercial capabilities for SHTG to realize the full blockbuster potential of olezarsen. The team is also preparing to bring donidalorsen, a potential first-in-class medicine to the market next year by leveraging and building upon our efforts and learnings from the WAINUA launch and upcoming olezarsen launch.HAE is a well-defined patient population with an estimated 20,000 people affected in the US and Europe, while prophylactic treatment in the US is well accepted by patients and physicians, the market continues to grow.Additionally, a meaningful segment of patients in the US are switching treatments seeking a better option. Outside the US, acute therapies have historically been the standard of care. However, prophylactic treatments are gaining ground, especially in Europe. Many people with HAE are unsatisfied with the current treatments and are looking for an option that reduces frequency and severity of attacks while also offering good tolerability and convenience.Based on donidalorsen strong clinical data, including the Switch data and the simplicity of monthly or every two-month self-administration be an auto-injector, we believe donidalorsen offers the attributes that many people with HAE are looking for.Therefore, we believe donidalorsen, if approved, could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapies. I am pleased to share that the team is prepared for our upcoming launches. All of our key commercial leaders and their teams are in place today including our Chief Commercial Officer, Market access, patient services and marketing and sales.We have built out a highly experienced top-tier team who have led or contributed to hundreds of product launches. We are executing on all of the initiatives needed to successfully launch our medicines. Importantly, we are ready for our first independent launch, which is just a few short weeks away. We're right where we need to be with three additional launches planned over the next three years with more to follow.With that, I'll now turn it over to Beth.\nElizabeth Hougen\n Thanks, Kyle. This year, we've made significant strides in advancing our pipeline and achieving our business goals, positioning Ionis to deliver on our vision of bringing a steady cadence of innovative medicines to patients in need. To maximize the impact of our potentially transformational medicine and fully realize the opportunities ahead, sustained investment is essential.Consequently, we recently executed an equity offering to extend our cash runway. This strategic move enable us -- enables us to continue investing ahead of our near-term commercial launches, which collectively have multibillion dollar peak sales potential. Additionally, it allows us to continue to independently advance our next wave of wholly-owned medicines to maximize our potential for sustainable revenue growth.We earned revenues of $134 million and $479 million in the three and nine months ended September 30, 2024, reflecting a 7% decrease and 3% increase compared to the same period last year, respectively. Our diversified revenue streams continued to serve us well, including commercial revenue primarily from royalties and R&D revenue from multiple partner programs. SPINRAZA remains the primary source of commercial revenue with $57 million and $152 million of royalties for the third quarter and year-to-date.We were encouraged that US SPINRAZA product sales increased 2% in the third quarter compared to the same period last year. Outside the US, SPINRAZA product sales were impacted primarily due to an annual order from a single country that did not recur in 2024.This onetime loss is not expected to impact fourth quarter sales. WAINUA product revenue continued to reflect accelerating growth on a sequential basis, driven by strong underlying demand, increasing 44% in the third quarter compared to the second quarter. WAINUA product sales were $23 million and $44 million for the third quarter and year-to-date.As a result, our royalties for WAINUA over $5 million and $10 million for the respective period. R&D revenue for the quarter was in line with the same period last year and increased on a year-to-date basis, reflecting the value that our pipeline and technology continues to generate.As planned, our non-GAAP operating expenses increased for the third quarter and year-to-date over the same period last year, excluding certain onetime costs in 2023. The increase was driven by higher sales and marketing expenses as we continue to make investments to prepare for our upcoming independent US launches of olezarsen and donidalorsen.Our sales and marketing expenses also included our minority portion of WAINUA US launch expenses. These investments resulted in our overall SG&A expenses increasing 13% and 26% for the third quarter and year-to-date, respectively. In line with our plan, R&D expenses were essentially flat for the third quarter and year-to-date compared to the same period last year.As we have continued to build our commercial infrastructure and support functions to support our back-to-back planned launches with olezarsen and donidalorsen, we have grown our employee base to just over 1,000 employees.Achieving this milestone with modest expense growth highlights our financial discipline and our commitment to drive operating leverage while advancing our strategic priorities as we transform to a commercial stage company. Our year-to-date results keep us on track to meet our 2024 P&L financial guidance, including revenue of more than $575 million, of which approximately $175 million will come from noncash amortization of partner payments we received in prior years.Our confidence to achieve our 2024 revenue guidance was bolstered by the recent $30 million milestone payment we earned from AstraZeneca for the UK approval of WAINUA. We continue to project our full year 2024 operating expenses to increase by a mid- to high single-digit percentage compared to 2023, excluding the impact of onetime costs last year.And similar to our year-to-date results, the increase will be driven primarily by sales and marketing expenses as we prepare for our sequential independent launches. And with our recent equity offering, we are now projecting that we will end 2024 with $2.2 billion in cash.Looking beyond this year, we plan to deploy our cash to realize the substantial opportunities before us. We will continue to invest in go-to-market preparations for the planned olezarsen and donidalorsen launches. Additionally, with our increased confidence in the potential of WAINUA and olezarsen to address broader patient population, -- we plan to scale our capabilities in line with the significant potential that these important medicines represent.In parallel, we are investing to ensure sustainable growth with our next wave of medicines. This includes pre-commercialization activities and Phase III development for ION582 for Angelman syndrome and ziganersen for Alexander disease. Importantly, we expect our focused investments to drive strong revenue growth and create shareholder value as our medicines reach more and more patients in need. And with that, I'll turn the call back over to Brett.\nBrett Monia\n Thank you, Beth. It's worth emphasizing that the achievements you've heard about today and throughout the last few years position us well as we look to enter a new era for Ionis as a fully integrated commercial-stage biotechnology company poised to directly bring a steady cadence of medicines to people with serious diseases. We've arrived at this point by being focused on a clear vision and a clear set of strategic objectives, which include building and advancing our pipeline and delivering medicines that we conceive, discover and develop directly to patients.Our pipeline has consistently delivered positive Phase II and Phase III data, resulting in the approvals and launches of WAINUA and CalCadi, the anticipated approval and launch of olezarsen this year and the expected approval and launch of donidalorsen next year with much more to come.And in parallel, our partner programs are progressing on track with important Phase III readouts next year and beyond. In addition, we're extending our leadership position in (technical difficulty) therapeutics by expanding and diversifying our technology, further optimizing our capabilities in established therapeutic areas and opening up new disease areas for drug discovery.And we recently further strengthened our financial foundation, providing the means to continue advancing our strategic objectives to power future revenue growth and positive cash flow. All of this sets us up to deliver on our goal to bring new medicines to patients for years to come.And with that, I'll now open the call for questions. Danielle?\nQuestion and Answer Session\nOperator\n (Operator Instructions) GordGary Nachman, Raymond James.\nGary Nachman\n So first on olezarsen for FCS, how soon will you be able to launch post approval? And maybe talk about the expected pricing there. Are you in labelling discussions? And anything to call out on those expectations? And just generally, how we should be thinking about that ramp? And then I have one follow-up.\nBrett Monia\n Gary, we are in labelling discussions. We're pleased with how things are going, but it inappropriate for me to comment further on that since we are in discussions with the FDA. But everything is on track. I'll ask Kyle to address the rest of your question regarding pricing and launch and what our expectations are on timing as well.\nKyle Jenne\n Yes. Thanks, Gary. So like I mentioned in my remarks, we're very pleased with the team that's in place. We're ready to go. Leadership is here. The sales team is in place. Medical affairs is in place. So everything is ready to go for December 19. And in terms of launch timing, we do expect to launch this year and get product into the channel before the end of the year.So that's exciting. In terms of pricing for FCS, we will launch with an ultrarare pricing, which would be expected in this category based on somewhere between 1,000 and 4,000 patients that are appropriate for the therapy.So that pricing will be communicated on approval and look forward to sharing that with you on December 19 or sooner.\nGary Nachman\n Okay. Great. And then just on the Phase III Angelman study. So will there be any interim looks over the course of the year since it's a one-year endpoint any monitoring of these patients required on the safety side? And maybe just comment if there was any back and forth in terms of the right primary endpoint for these patients or if there was easy agreement there with the FDA?\nBrett Monia\n Very briefly, Gary. The -- we have no plans for an interim look at data during the course of the Phase III REVEAL study. It's a robust study design. And as you all know, Gary, we have a very strong relationship with the neurology division of the FDA. We came in with our proposals. And after some minor back and forth, the FDA was fully supportive of our proposal. So it was very little negotiating at the end of Phase II meeting.\nOperator\n Jessica Fye, JPMorgan.\nJessica Fye\n I have a question about the timing for cardio transform. So I think enrollment completed on July 31, 2023, and 140 weeks after that is April 6, 2026. And in the past, you talked about that readout coming in the first half of '26, then mid-'26. And now it sounds like data in the back half of '26. So did anything change with the approach to that study? For example, I think I recall the follow-up originally being planned is up to 140 weeks for those who entered the trial towards the end having variable but a little bit shorter follow-up than that.So is the plan now to follow all patients out to 140 weeks? Or are you really just budgeting like a full three months or more for data cleanup and analysis?\nBrett Monia\n Thanks, Jess. We're really, really continue to be very pleased with not only the conduct of the Phase [III] cardio transform study, but the design of the study is set up to deliver the richest, most comprehensive data set ever delivered in -- for an investigational medicine for TTR cardiomyopathy. And we think that, that is going to provide a very significant advantage once we get to the market with our partner, AstraZeneca.Prior to recent outcome data with another silencer in this class for this disease indication, we were considering the possibility of an early readout. However, it is very clear to us and our partner in AstraZeneca that the best decision would be to run the study out towards full completion in which all patients completed 140 weeks of treatment. So that's the only change really.And the last part of your question is exactly on -- if you do the arithmetic and you look at 140 weeks, last patient in compared to when we announced that we completed enrollment it brings you to about midyear of 2026, and then you need to close the database, you need to go through the blocking and tackling and then read the study out. So there's nothing there has changed except that we have made a decision to go to full completion through 140 weeks.\nOperator\n Mike Ulz, Morgan Stanley.\n It's (technical difficulty) on the line for Mike. Yes, I guess just on FCS, given that it's a pretty small patient population, can you -- could you be able to give us some color on approximately how many patients you've identified and with the competitor possibly coming to market just a few quarters after you. What's your confidence in being able to potentially saturate the market before they can reach it.\nBrett Monia\n Yes. Thanks for the question. First, I'll just reiterate, we're really excited about the launch, and we're ready to go. We've been in this space for quite some time. And fortunately, we've had our medical affairs team in the field educating physicians and spending time talking about the diagnosis of FCS and the importance in the way that these patients, unfortunately, are being impacted by their disease.Recently, we have the sales organization that has been hired and is now in place as well. And they've been deployed, not only are they profiling accounts, but they're also educating around how to identify these patients and physicians are beginning to assess who could potentially have FCS within their within their practices.Keep in mind, we have an EAP that has been established in the US. We also have open-label extension that is ongoing. So there are patients that are currently being treated and benefiting from therapy, fortunately. We are continuing to talk about the launch and figuring out exactly where these patients reside, that will go on for quite some time, as you would expect, being that FCS is a rare disease, as a treatment comes to market.And as you mentioned, olezarsen potentially will be the first indicated treatment for FCS. We expect that patient identification will go up because as physicians know that there's a treatment available, they will be looking to figure out where these patients are, bring them in, and obviously, I get them started on olezarsen.So the nine-month plus lead that we have over the competition, I think, is very relevant and will allow us to secure a good launch in a bolus of patients upfront and we continue to do that patient identification longer term, and we expect that ramp to continue over time.\nMike Ulz\n Okay. And then just as a quick follow-up. I guess, how quickly do you expect to be able to enrol patients from the open-label extension as well as the early access program onto paying commercial drug?\nBrett Monia\n Yes. That's a process that can happen pretty rapidly. We expect to be able to communicate things once we have the approval for olezarsen, the commercial approval. And we have a patient support program in place, and we'll be able to obviously communicate appropriately with those offices that have those patients and be able to get prescriptions in fairly quickly and start that transition.So I don't want to put an exact time frame on it, but we have a plan in place in order to execute that transition, and we're very confident in being able to make that happen.\nKyle Jenne\n Yes. And just to add to that, Avi, just as a reminder, that will be in the United US patients in the open-label extension that are in the US Obviously, the balance today was a global study. and it will take time to get the approvals in Europe, elsewhere enrol those patients in.\nOperator\n Yanan Zhu, Wells Fargo Securities.\nYanan Zhu\n Great. Congrats on the progress. Maybe first, a couple of very quick follow-ups to earlier questions and answers. On FCS, I was wondering, how do you anticipate the payer dynamic given that this is likely a highly priced drug. Would that reimbursement dynamic to the launch in any way? And for the ATTR cardiomyopathy program, I was just wondering, you just talked about the 140-day full completion.Is there any possibility or desire to expand it further, given that Alnylam study had some of the secondary end points out to 42 months. And I have a follow-up after that.\nBrett Monia\n And I'll take the (technical difficulty) question, Kyle, I'll take the FCS payer dynamics question. So again, as you know, we're really like this trial design, most comprehensive study ever conducted in this patient population. And we are committed to reading it out to its completion through 140 weeks in second half.Of course, we will do what makes the most sense for the drug WAINUA to have the most robust data set as possible, of course, the trial. So that's something that we and AstraZeneca will continue to think about and potentially act on, but we'll do what's best for the drug. On the STS payer dynamics.\nKyle Jenne\n Yes. We've done a lot of work with the payers as you would expect in terms of pricing and also educating them on FCS as an ultraorphan ultrarare disease, excuse me, in the potential patient population that resides there. The EPI for this is between 1 and 13 per million, which takes us in at most up to the 4,000 patient range in the US.Payers as they're looking at this, doing their budget impact models and understanding their exposure rate potentially within the disease area in the way that these patients are going to present have been very accepting and very understanding of the price point in which they expect to see olezarsen -- we launched at.The approval process from a prior authorization standpoint will be a question in the learning as we go into the launch. But what we do know is that we have a good pathway here. We've got great data sets, not only in terms of triglyceride lowering that are deep, that are sustained. The patients can self-administer this drug. But we also have great data around hospitalizations and hospitalization rates.And so that information, combined with the patient population that is anticipated to be treated by these physicians, we expect the payers to work effectively through the process, get these prior authorizations approved and ultimately get patients on drug very quickly.\nYanan Zhu\n Got it. Very helpful. Then I just have a question about the Phase III design for the Angelman syndrome study. Could you compare and contrast your design with Ultragenyx design Obviously, the primary endpoint is different.And I think that's congrats on getting expressive communication as the primary end point. But in terms of whether it's placebo controlled versus sham control patient age range -- can you talk about the design differences and what the implications might be for enrollment speed and data.\nBrett Monia\n Yes. I prefer not to comment on other people's trial design, but I can focus on our trial design. You hit on some of the some of the key differentiating features, I think, in our trial design already in your question. We really like a trial design.We think it's the right trial design for the most definitive outcome in our Phase III REVEAL study. We -- first of all, I have to start with the fact that we have a proven platform. We have a platform that has delivered SPINRAZA, (technical difficulty) and several mid-stage pipeline readouts in CNS diseases.Well with good safety and efficacy, including our HALO Phase I/II study in Angelman's, where we showed strong benefit across all endpoints that were measured, including communication, cognition, and motor function and more.Our Phase III trial will examine a broad age group, including children, adolescents, and adults. Our study will examine two dose groups, which we think is going to be very important to maximize the probability for success and strong success, especially (technical difficulty) since we are looking at different age groups in the study.Thirdly, our study, because we have three cohorts will be randomized 2:1. We think patients will like that. Patients don't like going on placebo when they're suffering with debilitating disease like Angelman's. They have an opportunity to benefit -- have a greater probability to be on treatment and receiving benefit because it is a 2:1 randomization.And I also want to mention that the doses we're examining in the Phase III study or the mid- and high dose that we examined in the Phase I/II study, where we showed strong efficacy at both doses, all with very good tolerability.So there's not going to -- we don't expect any surprises here with these doses. As far as placebo control versus sham, as Eugene said in his prepared remarks, placebo-controlled trials is a gold standard in trial conduct. It is viewed by regulatory agencies as the preferred trial design produces the most definitive outcomes without bias, and it's the way to go.Furthermore, we have treated now several thousands of patients with intrathecal bolus injection with our molecules with our chemistries, all with very good safety and tolerability. And that was certainly very important to the FDA that convinced them that a placebo-controlled trial is the trial that is appropriate for -- in our study. So we have a very well-designed study, and we're looking forward to getting it started in the first half of next year.\nOperator\n Luca Issi, RBC.\nLuca Issi\n Maybe if I can circle back on a prior question, Eugene. You're obviously using express communication as a primary endpoint versus obviously your competitors using cognition. Can you just talk about you think the former is the better way to go versus the latter, any call there, I much appreciate it. And then on APOC3, I think ElaLily discontinued their siRNA going after APOC3 wondering what was your reaction to the news and how we should think about implications for your program?\nEugene Schneider\n Sure. Thanks for the question, Luca. I'll start with the Angelman question. And I'm not sure I would necessarily characterize it as the best endpoint. It's certainly the end point that is the strongest in terms of our support from our early phase experience from the PAVO study.It is the one that has very robust results in various age groups and both dose regimens. It's also the endpoint, the expressive communication based on all of the surveys that were conducted in this space in this patient population and community is the endpoint that families indicate consistently as the most important one, they would like to see benefits in a new treatment.So again, from the perspective of having the evidence from our proof-of-concept study as well as combination of being an area that is certainly very problematic for people living in Angelman and their caregivers.We feel that this is the right endpoint to put at the top of the hierarchy right? So it is what we have proposed and provided. We thought was very good, compelling argument and certainly got buy-in from the agents. Rich, do you take the APOC3 question?\nRichard Geary\n Yes, I'll give it a shot. So we don't know internally what Lilly's reasons were. But -- they are looking at a strong position -- strongly positioned drug in (technical difficulty) is a fast mover and they would be coming in behind. But I think the other piece to this was Lilly was very much looking at cardiovascular risk APOC3 and deemed it to be high risk and may have also added into their discomfort.\nBrett Monia\n I'll just add to that, Richard. Thank you. They came to the conclusion on evaluating an APOC3 inhibitor in a cardiovascular indication like an outcome trial. They came to our conclusion we made several years ago, I guess, just recently. We believe that the unmet need is not in that space nor do we believe that, that is the -- that is something we're pursuing for APOC3.We believe that the unmet need is in severe hypertriglyceridemia. We're pleased to see that they came around and so we saw several years ago.\nOperator\n David Lebowitz, Citi.\nDavid Lewis\n In terms of your launches for donidalorsen and olezarsen. Even that these are really the first more significant launches that you're doing yourself. Could you describe how the sales operation is coming together? What the sales team will look like for both indications and how you intend to receive, especially with respect to HAE given that it's a very competitive market.\nKyle Jenne\n Yes. Let me turn that over to Jonathan Birchall, our CCO, to talk specifically about those details.\nJonathan Birchall\n Thanks, Kyle. We're definitely making good progress. In fact, we're ready to go with the olezarsen and FCS launch. And we've got all the commercial functions in place market access, patient services, omnichannel commercial operations as well as the brand teams.And some months ago now, we completed the hiring of the field force think Kyle talked about the size of the opportunity there. And we're very comfortable with both the quality of the candidates that have joined Ionis and also the size of the commercial field force to really maximize the olezarsen opportunity and FCS.As you can imagine, there's a lot of synergy with the second donidalorsen launch in HAE across the commercial functions. We've just started the hiring for the Head of Sales, which is really the last commercial function that we are putting in place.And that process will complete through the first half of next year in preparation for launch in the second half of next year -- couple of about the competitive marketplace there. We're very comfortable with the data package that we've got for donidalorsen and the commercial capabilities we're building out that we're certainly ready to be competitive in what while very competitive.It still remains an underserved market.\nOperator\n Jason Gerberry, Bank of America.\nJason Gerberry\n Just a couple on the pelacarsen readout next year. First, with the primary, you're looking at this 90 mg per (technical difficulty) subgroup. If the event reduction looks more compelling in this subgroup, clinically meaningful, how does that alter the addressable market, which I think you guys have framed about [$8] million to [$10] million for secondary prevention, high-risk Lp(a) greater than 70. But how does that change if it's 90 or greater?And then ultimately, the other question is just what underpins your confidence that you'll have the events to read out around middle of next year versus the potential need to run that trial out longer? I think your assumed event rates a couple of percentage points higher than what we've seen in like the typical LDL lowering trials in the past.So just kind of wondering, I assume that there's been some assessment of rates on a binded basis and that sort of underpins and firms up the outlook for timing next year. But I just wanted to confirm on that.\nKyle Jenne\n Yes. So thanks, Jason. Those are very good questions. They're probably best for Novartis. -- you're asking some very specific detailed answers to that. But in short, certainly, Novartis has been watching the blinded event rates all along. They have regular oversight meetings in which they examine those, and they're based on the events that they're seeing in the study. They're confident they've reiterated recently that they plan to read the study out next year. And if successful, they would also plan to file next year.So that is based on the events that they're seeing in the study for sure. Regarding the 70 versus 90, if the study hits on 90 but not on 70, it will be a somewhat smaller indication. It will be people above 90. But it's still a massive, massive patient population that were to happen. The boat were to hit, but the 90 was more compelling than the 70. I don't think that would have a significant impact.I mean there are these people -- I mean, normal Lp(a) in the 30 range or so. And so even people with 70 milligrams (technical difficulty) with a history of cardiovascular disease are in desperate need for treatment like talocarcin. So I think that if the study hits on regardless of the risk reduction was greater in 90 versus 70, I think it will be indicated for all those patients. with the history of CBD. Again, to emphasize, this is a massive patient population, which there are no effective treatment options available today.\nOperator\n Jay Olson, Oppenheimer.\nJay Olson\n Congrats on all the progress. Does the Phase III study design for (technical difficulty) support regulatory filings ex-US? And if so, how are you thinking about ex-US partnering opportunities for 582? And then -- and then I had a follow-up if I could.\nBrett Monia\n Yes. So the Thanks, Jay. The -- we're wrapping up. We're getting close to getting alignment with the EU on the Phase III trial design for an human syndrome. We don't see any roadblocks there or anything that's going to cause us to significantly change anything about the study design to get approval in Europe.As far as OUS partnerships for commercializing Angelman's, it's very early. It's too early to comment on that. As you know, we have an OUS commercial partner for donidalorsen and we're making great progress for olezarsen, we expect soon. there will be a time that Ionis will emerge from the US market for commercialization.Maybe Angelman's could be that program or maybe something else. It's just too early to -- for us to draw any conclusions there. But it's certainly an area of active conversation within Ionis.\nJay Olson\n Great. Super helpful. And then we had a question on 269, your APP ASO. It's great to see research being done in Down syndrome based on the huge unmet need in that population. Can you talk about the rationale for choosing that indication to start with and maybe elaborate on the development strategy and any plans for other indications and differentiating features for your program versus other RNA therapeutics.\nBrett Monia\n Yes. I'd like our way to comment on the rationale for us starting in down syndrome patients first. And then Eugene, maybe you can comment on additional potential indications. Eric?\nEric Swayze\n Yes, sure. Thanks, Brett. Well, so Down syndrome is due to triplications of chromosome [21] and APP is on that chrome zone. So they have an extra copy of the APP gene, which causes what you'd expect from having extra gene copies, you get an accumulation of excess amyloid and down syndrome patients are known to have early onset of Alzheimer's disease and dementia relating from accumulation of excess amyloid.So it was a logical thing for us to look at, and we know that and the down syndrome community has been a little bit underserved, and we think it's a great place to go with a drug that lowers production of a gene product when you have a disease caused by excess gene. So that's really the logic for going into the patient population. We know there's a great need there. And it makes sense for our technology.And I'll just add one more thing on the technology. This is -- we've been working on chemistry of our drugs, and this is the first MSPA backbone chemistry of our drug going into clinical development, and we expect this to give us improved duration of effect of one benefit of the chemistry, which we hope to see in the trial.\nEugene Schneider\n Yes. So further indications, of course, are TBD and the first proof-of-concept experiment and overproduction, clear overproduction of ATP model is critical. But certainly, the most logical one is sporadic AD or forms of AD that are perhaps a little bit better described.This approach to kind of addressing the overproduction problem first and then moving into larger indications that are at least thought to be mostly clearance problems, if you will, of APP is probably somewhat similar to what we're doing with WAINUA, right?So the kind of the initial indication with focusing on hereditary then where we could suppress production of TTR and prove that it's beneficial. And then following with the broader, more heterogeneous group that includes wild-type that is mostly thought to be a clearance problem -- is something that we potentially could think of as an analogue.So we are certainly thinking of AD and potentially other relatively more common indications than Down syndrome. But down syndrome experiment is going to be really, really critical for us.\nOperator\n Mani Foroohar, Leerink.\nMani Foroohar\n I know a lot of pipeline questions have been answered. I want to circle back on the growth in TTR polyneuropathy, obviously, accelerating from where your revenue base was prior product. Perhaps a question that is for both you guys and AstraZeneca, that you have some insight. To what extent are we seeing patients switching from the existing oligo therapy, which is two, three months, then may lose some efficacy at the end of that time horizon. -- to your at-home therapy with eplontersen?And what -- so what proportion of your growth is coming from patient switching versus previously untreated patients who are getting up once.\nBrett Monia\n Yes. Thanks for the question, Mani. The growth strategy here in a market that is largely underdiagnosed, less than 20% of these patients are currently on a treatment is really about identifying new patients and securing those patients to initiate treatment from the very beginning.WAINUA and the strategy there, obviously, is playing out. That's why we saw the 44% growth quarter-over-quarter. The profile is exactly what we had expected to benefit these patients in terms of quality of life, the efficacy that they're seeing and the ability to self-administer. So the question about switching, it is happening.I don't want to quantify that. But what I would say is it's occurring because there is a request from patients and physicians see the benefit of patients being able to self-administer with a simple used auto injector. It's a differentiating feature here within the category. Patients are getting reimbursed very quickly from a market access standpoint.Our patient engagement manager team, they're connecting directly with these patients, having very productive conversations with them about getting initiated on WAINUA and what to expect. And overall, the patients are performing very well, and we expect to continue to see the growth in the naive patient population.I expect that we will still see some switches, and we will probably see some combination as well for the mixed phenotype patient in which some of these patients have hereditary polyneuropathy and could benefit from a silencer such as WAINUA.\nMani Foroohar\n Great. And a quick follow-up. Your Oligo competitor has talked about in part for the cardiomyopathy market but also in polytropic a belief that those patients who are receiving an in-office therapy the Medicare Part B may have less out-of-pocket or more favorable reimbursement from a facility perspective than an at-home Part D therapy.Can you clarify whether or not you're seeing any headwinds whatsoever from patient auto pocket costs, reimbursement headwinds, et cetera, that would support or refute that competitive argument counter detail.\nBrett Monia\n Yes. I think the short answer is, with the inflation Reduction Act and the changes for out-of-pocket expenses on Medicare Part D access to care has gone up significantly within that channel. You're seeing that across not only this category, but I think across all Medicare Part D products ultimately out-of-pocket expenses for patients within WAINUA, the majority of them pay nothing on the commercial side of the business because we have programs to help support those patients.And then in the Medicare population, keep in mind you have Medicare Advantage and then you have the other population that have some supplemental or some support with their Medicare reimbursement.And so a lot of those patients are paying very little to nothing because of the way that they have their Medicare Part D plan reimbursed through a secondary insurer. So overall, very, very good access to care with WAINUA, greater than 75% to 80% of these patients have very little out-of-pocket expenses, and we have the opportunity to help them accordingly with the programs that we have in place.\nOperator\n Andy Chan, Wolfe Research.\nAndy Chan\n So regarding the Doni launch in HAE, so a fraction of these patients, my understanding is either on androgen therapy, they're not on (technical difficulty) , there's not (technical difficulty). Do you believe that there's an opportunity there to convert these patients to Doni? Or do you just believe that they're very part of reach? And on the side note, do you think payers are going to begin to play favourites in this market because it's kind of becoming crowded.\nBrett Monia\n Yes. Let me make a couple of intro comments and then I'll turn it over to Jonathan for his perspective as well. The patients that are not on therapy today in the US market, they're approximately 20% to 25% of the overall population. And there are varying reasons that they would not be on treatment yet.One would be potentially the current therapies have some sort of aspect that they're not interested in or don't feel comfortable with, or the other aspect is maybe the frequency of tax or whatnot are not severe enough that they feel that they can manage their disease otherwise.We do believe that there's an opportunity to address this population in three different ways. One, our patients new to therapy, so newly diagnosed patients that are coming in. The second area are the switch patients, which is going to be the bolus of about 75% of the patients in the US that are currently treated on a therapy for HAE could potentially move over to donidalorsen.And then the third bucket is the one that you just described, which are the ones that have been diagnosed but are not treated today with a prophylactic -- and we believe that with the profile like donidalorsen, we could potentially capture all three of those buckets based on the way that the data is coming together. Jonathan, anything to add there and then also with payers.\nJonathan Birchall\n No, not really. I think the only thing I would add is, despite the treatment options that have increased in more recent years, -- we know from claims data, there's a large proportion of patients who do switch therapies every year. and some of the patient advocacy group, their survey show that patients are still having breakthrough attacks on the current treatment.So we definitely think there's an opportunity for patients to switch to a new treatment like donidalorsen. And with the payer environment, the full spectrum of treatments -- and we're still comfortable that the payers will support the market at the current prices, given the fairly well-established treatment population to date.\nBrett Monia\n Thanks, Andy. And looking at the clock, we have time for one more question, please.\nOperator\n Akash Tewari, Jefferies.\n This is (technical difficulty) on for Akash. On Angleman you previously showed that you could show a shift towards EEG pattern normalization -- in the long-term extension, are you continuing to see the same EEG benefit that you reported at earlier for a six-month time points?And also, are you thinking about this as an endpoint of clinical efficacy or more of a make -- and is there any sense of variation in the signal to noise for EEG given that you're looking at both adults and children?\nBrett Monia\n Yes. So -- we certainly will continue to measure EEGs in our long-term extension as well as in our Phase III trial design. It will be exploratory and viewed more as a biomarker. It's really -- we're really using this to more better understand the biology in people living with Angelman syndrome and to determine whether or not there's any predictive value of an -- of an abnormal EEG pattern with respect to disease progression different as to your question, the other part of your question is different age groups, whether there's any impact there.We know that adults have been much more muted abnormal EEG pattern than children. We want to study that. We want to study that with treatment too. However, the EEGs will be more exploratory in nature in our trial. And we just haven't done the assessment in long term in our LTE study yet to comment on how that data is looking like.We will examine a new data cut from our LTE at some point in the future, and we're looking forward to sharing that at the right time. But it's a very good question. So thank you for that. And with that, I'd like to thank everybody who joined us and asked great questions participated in our call today.I know we've accomplished a lot, a great deal and have substantial opportunities ahead here at Ionis. And we look forward to sharing updates on the progress we're making regularly as we move forward. So until then, thanks, everybody, and have a great day.","kind":null,"is_publish_news":true,"is_publish_highlight":false,"is_publish_live":false,"is_publish_wemedia":null,"editions":null,"column":"","sentiment":"0","news_tag":"","news_rank":0,"symbols":[],"gpt_button":1},"commentList":[],"isCommentEnd":true,"newsSizeData":{"likeSize":0,"commentSize":0,"repostSize":0,"favoriteSize":0,"likeStatus":false,"favoriteStatus":false},"APP":{"userAgent":"Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)","isDev":false,"isTTM":true,"deviceId":"web-server-community-laohu8-v3","version":"4.29.1","shortVersion":"4.29.1","platform":"web","vendor":"web","appName":"ttm","isIOS":false,"isAndroid":false,"isTiger":false,"isTHS":false,"isWeiXin":false,"isWeiXinMini":false,"isWeiBo":false,"isQQ":false,"isBaiduSwan":false,"isBaiduBox":false,"isDingTalk":false,"isToutiao":false,"isOnePlus":false,"isHuaWei":false,"isXiaomi":false,"isXiaomiWebView":false,"isOppo":false,"isVivo":false,"isSamsung":false,"isMobile":false},"href":"/m/news/2481927405"}