ARROWHEAD PHARMACEUTICALS, INC. — Call Transcript 2026

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. Throughout today's presentation, all participants will be in listen-only mode. After the presentation, there will be an opportunity to ask questions. Instruction will follow at that time. I will now hand the conference call over to Vince Anzalone, Senior Vice President of Investor Relations for Arrowhead. Please go ahead, Vince. Good afternoon, and thank you for joining us today to discuss Arrowhead's results for its fiscal 2026 second quarter ended March 31, 2026. With us today from management, our President and CEO, Dr. Chris Anzalone, who will provide an overview. Andy Davis, Senior Vice President and Head of the Global Cardiometabolic Franchise, who will provide an update on commercialization activities. Dr. James Hamilton, Chief Medical Officer and Head of R&D, who will discuss our development programs, and Daniel Apel, Chief Financial Officer, who will give a review of the financials. Following management's prepared remarks, we will open the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. I'd now like to turn the call over to Chris. Thanks, Vince. Good afternoon, everyone, thank you for joining us today. During the fiscal second quarter, in the period since our last earnings call, we have continued to execute well against our commercial, R&D, and corporate goals. Arrowhead is now on the strongest footing of our history. Your commercial, we have a clear line of sight to expand our commercial opportunities and footprint. Our pipeline is larger than ever. Our discovery capabilities are broader than ever. Our balance sheet is stronger than ever. This is an historic time for our company. We are uniquely positioned to deliver important medicines to patients who need them and to create substantial value for our shareholders. Let's talk about some of our recent progress and begin with commercial. As you recall, the FDA approved REDEMPLO in November 2025 as an adjunct to diet to reduce triglycerides in adults with FCS. FCS is a severe rare disease with an estimated 65 million people in the U.S. living with genetic or clinical FCS, characterized by TG levels that can be 10-100 times higher than normal. This leads to a substantially increased risk of developing acute, recurrent, and potentially fatal pancreatitis. As we reported last quarter, the U.S. REDEMPLO launch was off to a strong start. That momentum has continued into the current quarter, we are now seeing around 30 new prescriptions written each week. More than 400 prescriptions have been written since launch, more than 10% of these have been for patients switching from our competitor's ApoC-III inhibitor. Of course, each prescription needs to be fully adjudicated with payers before becoming paid claims, we offer a robust quick-start program to support these FCS patients in the interim. The volume of physicians writing prescriptions and the number of patients receiving REDEMPLO continues to exceed our initial expectations. With respect to pricing, we updated REDEMPLO's U.S. wholesale acquisition cost, or WAC, to $45,000 per patient per year. This represents a premium to our competitor's WAC pricing. We believe this is appropriate given that clinical data suggests we have a clearly and demonstrably superior product in terms of TG reduction, safety profile, and convenience. As part of the one REDEMPLO unified pricing model, this price is intended to remain consistent across FCS and SHTG if that indication is approved. We continue to see this strategy as potentially simplifying payer contracting and eliminating pricing complexity that could complicate future formulary negotiation. The response from payers to this strategy has been positive, and our interactions to date have been productive. Beyond the U.S., we secure positive regulatory action in four additional geographies for REDEMPLO in patients with genetically confirmed and clinically defined FCS. We received approvals from the Australian Therapeutic Goods Administration, the Chinese National Medical Products Administration, and Health Canada. In addition, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending the approval of REDEMPLO. This is an impressive result achieved by our global regulatory team in a very short period and further reflects the strength of our clinical data in FCS and the value that REDEMPLO offers to patients. REDEMPLO will be available later this year in Canada and we anticipate it will be marketed independently by Arrowhead. Pending a marketing authorization decision from the European Commission, we expect to launch REDEMPLO later this year in select E.U. countries and likely in the U.K. as well. In Greater China, REDEMPLO will be marketed by Sanofi. In addition to our regulatory team, the rest of the R&D organization has performed extremely well and has made progress in the broader portfolio. Our drive to expand our platforms in order to increase the number and types of diseases we can address continues even as we grow as a commercial entity. During the recent period, we have made rapid progress across the pipeline, including programs targeting genes expressed in liver, skeletal muscle, adipose, CNS, and the lung, as well as the first dual functional siRNA designed to silence the expression of two genes with a single molecule. We believe the depth and breadth of our clinical pipeline is unmatched, and we expect to continue to lead the field in innovation. Importantly, many of these programs will have clinical readouts this year, so investors and others may start to properly value the broader pipeline. As we look to near-term clinical data releases, we anticipate four important events. First, the phase III SHASTA-3 and 4 studies of plozasiran in SHTG patients should be ready for top-line data release in Q3. This is an important readout that will drive our anticipated supplemental NDA or sNDA as we seek to expand the population of patients we can treat with plozasiran. We expect to continue to see a favorable safety profile and substantial reduction in TGs, and we are cautiously optimistic that we could see an improvement in acute pancreatitis risk. Second, we expect to have early data from the ongoing phase I/II study of ARO-DIMER-PA in patients with mixed hyperlipidemia in Q3. We believe this will be the world's first clinical data of a single RNAi molecule designed to simultaneously silence expression of two proteins. If we see good reduction of PCSK9 and ApoC-III, and therefore reductions in LDL cholesterol and TGs, we could have a very powerful and unique therapy for roughly 20 million people in the U.S. living with mixed hyperlipidemia. More broadly, the data could provide initial clinical proof of concept for our growing DIMER platform and pipeline. Expect to see additional dual functional DIMERs in the clinic in 2027. Third, we expect to have early data from the ongoing phase I/II study of ARO-MAPT around the end of Q3 or early Q4. As you recall, this is our first candidate using our CNS platform designed to deliver RNAi molecules to the brain via simple subcutaneous administration. Our MAPT targets. ARO-MAPT targets the tau protein, which is increasingly validated for the potential treatments of Alzheimer's and other tauopathies. We believe that positive early data could be substantially disruptive. It could represent a great leap forward in treating tauopathies and more broadly, open the door to using RNAi to treat a broad range of conditions from neurodegenerative disorders to obesity. If early ARO-MAPT data are encouraging, expect a substantial expansion of our CNS pipeline beginning at the end of 2026. Fourth, we expect to provide clinical updates on ARO-INHBE and ARO-ALK7 throughout the second half of the year. Regarding ARO-INHBE, we plan to present additional data at various conferences and launch a phase II study. For ARO-ALK7, we expect to provide additional data from the ongoing phase I/II study. We see these as potentially important therapies for metabolic disorders and represent our first steps into obesity and MASH. We expect to have additional candidates in this space by the end of the year and into 2027. Moving on to financial and portfolio management, Arrowhead took important steps to ensure that we are properly funded to advance our commercial and development portfolio. We also entered into a license agreement for a program that achieved clinical proof of concept, but is not one that we wish to take forward. This is key to Arrowhead's strategy since we are extraordinarily productive in discovery and early development, but cannot commercialize everything independently. Let's talk about the steps we took. First, we dramatically strengthened our balance sheet, allowing us to push multiple programs toward commercialization and potentially through multiple independent and partner launches. During the quarter, we completed the largest fundraising Arrowhead has ever conducted. We closed concurrent public offerings of $700 million of 0% coupon convertible senior notes and $230 million of common stock. Both offerings were several times oversubscribed, reflecting investor confidence in our portfolio and our ability to continue to build value. Second, and just this week, we announced an exclusive worldwide license agreement with Madrigal Pharmaceuticals for ARO-PNPLA3, Arrowhead's clinical-stage program designed to treat a genetically defined population of MASH patients. Under the terms of the agreement, Madrigal will pay a $25 million upfront payment to Arrowhead. Arrowhead is also eligible to receive development, regulatory, and sales milestone payments of up to $975 million. Arrowhead is further eligible to receive tiered royalties up to mid-teens. Madrigal's leadership in the MASH space makes it a natural and attractive partner to advance ARO-PNPLA3 into phase II studies and toward potential commercialization. This transaction with Madrigal underscores Arrowhead's disciplined business development strategy, demonstrating our ability to partner high-potential, clinically validated programs with leading organizations. With that overview, I'd now like to turn the call over to Andy Davis. Andy? Thank you, Chris. Good afternoon, everyone. It has now been approximately five and a half months since the FDA approval of REDEMPLO on November 18, 2025. We continue to be very pleased with the trajectory of the launch. Today, I would like to cover five areas: prescription and patient dynamics, payer coverage developments, pricing strategy, commercial infrastructure expansion, and our international and SHTG outlook. Let's start with prescription and patient dynamics. REDEMPLO's launch continues to build strong and consistent momentum. Through the fiscal second quarter, ending March 31, 2026, we have seen prescriptions accelerating week over week, growing nearly threefold from the start to the end of the quarter. That momentum has continued into the current quarter, with total prescriptions written exceeding 400, representing over 40% growth over just the last four weeks alone. The awareness and conviction driving this prescription growth are encouraging. REDEMPLO awareness among the prescribers who matter most has increased meaningfully. Critically, this awareness has translated into conviction. Nearly all REDEMPLO prescribers surveyed report being satisfied or highly satisfied with the product, and REDEMPLO is perceived strongest on the efficacy outcomes FCS patients care about most: triglyceride reduction and acute pancreatitis risk reduction. The patient mix continues to reflect what we expected. Approximately 85% of prescriptions are from patients naive to the ApoC-III class, a strong signal that physicians are identifying and treating FCS patients who have never had access to an effective therapy. Switch patients largely account for the remainder. Patient persistence data is equally encouraging. Refill activity is accelerating meaningfully, an important early validation of both clinical effectiveness and patient satisfaction for REDEMPLO's once quarterly dosing profile. Geographic distribution of prescribing is balanced across the country. This breadth of prescriber activation across all territories signals that patient identification capability is building at scale across the organization, not just concentrated in a handful of high-volume centers. This gives us confidence in the durability of the prescription growth trajectory. Turning to payer access. We are making meaningful and consistent progress. Our market access team has been actively engaged with the largest payers in the country, covering the vast majority of U.S. lives to support continued patient access. These discussions are proceeding as expected and in some cases have already led to REDEMPLO's improved coverage. Additional formulary coverage decisions are expected in the coming months across both commercial and government segments. A particularly important development in the payer landscape is the diagnostic pathway flexibility that major payers are recognizing. The coverage policies taking shape across major payers reflect both genetic testing and clinical criteria as valid routes to diagnosis. This is critical for ensuring that all appropriate REDEMPLO patients can access treatment, because a meaningful proportion of real-world FCS patients are clinically diagnosed rather than genetically confirmed, and policies that require genetic confirmation as a prerequisite would create an unnecessary and inappropriate barrier. As Chris mentioned, we have made a proactive decision to reduce the list price of REDEMPLO to $45,000 per patient per year. This decision reflects our commitment to optimizing market access for FCS patients and is consistent with our belief that a competitive and rational price point accelerates formulary decisions and reduces friction in the prior authorization process. We have always believed that REDEMPLO's clinical profile is best in class, and the $45,000 per year price point reflects a premium value supported by the clinical evidence. With the FCS launch performing ahead of our expectations and with potential expansion into SHTG on the horizon, we are making deliberate and sequenced investments to scale our commercial infrastructure. I will speak more on this in the future, but the field infrastructure we are building will be sized and structured for both the current expanded FCS accessible population and also the future SHTG opportunity as it unfolds in the future. On international expansion, REDEMPLO received regulatory approval in both Canada and China in January and most recently in Australia last month. All three markets are currently in pre-launch phase as we work through the pricing and reimbursement frameworks in each country. We look forward to providing updates on those timelines as they develop. Also last month, CHMP, the Committee for Medicinal Products for Human Use, recommended E.U. marketing authorization for REDEMPLO in Europe for FCS without requiring genetic confirmation. Consequently, we anticipate an EMA approval decision in the June to July timeframe. We intend to commercialize REDEMPLO directly in Europe, supported by contracted infrastructure which encompasses market access strategy, account management deployment, medical science liaison support, and broader stakeholder engagements, including medical congresses and patient advocacy group engagement. We believe this model is the right approach for Arrowhead and are pleased with the readiness of that team as we approach the anticipated EMA decision. Finally, I want to comment on the SHTG program, which represents the most significant near-term value catalyst for the cardiometabolic franchise. We are approaching what we expect to be a highly meaningful series of milestones. Top-line results from SHASTA-3 and SHASTA-4, our two registrational phase III studies in severe hypertriglyceridemia, are expected in Q3. We head into the data readout with confidence grounded in the strength of REDEMPLO's established mechanism of action and the consistency of the ApoC-III biology we have observed across our full clinical program to date. We intend to present the data at a major medical congress, which we hope will be with a simultaneous publication in a top-tier medical journal. We expect to file an sNDA with the FDA before the end of 2026, with an anticipated regulatory approval based on an expected standard review timeline targeted in second half of 2027. Additional regulatory filings in other jurisdictions are planned to follow thereafter. The SHTG opportunity represents a patient population that is substantially larger than FCS, with over 1 million high-risk patients in the United States alone. The commercial infrastructure investments we are making for FCS today are also designed with that launch in mind. In summary, the REDEMPLO launch is progressing well and continues to exceed our expectations across prescription volume, patient dynamics, and payer access. Physician satisfaction and forward prescribing intents are both extremely strong. Refill activity is accelerating, and we have a series of highly anticipated milestones in the second half of 2026 that we believe will be transformative for the cardiometabolic franchise and for Arrowhead. With that, I'll turn the call over to James Hamilton to discuss the broader R&D portfolio. Thank you, Andy. As Chris mentioned, we have a very broad pipeline with over 20 clinical programs, so I will focus on areas with upcoming readouts. First, I'd like to announce that we are planning to host three webcasts over the coming months as part of our R&D Webinar Summer Series. Each webcast will cover a specific aspect of our pipeline where we expect to have upcoming data readouts this year. These include cardiometabolic, including plozasiran, zodasiran, and ARO-DIMER-PA, obesity, including ARO-INHBE and ARO-ALK7, and ARO-MAPT, including the blood-brain barrier or BBB platform. I'll now give status updates from the quarter on these specific areas. First, let's review the suite of plozasiran phase III studies, SHASTA-3, SHASTA-4, SHASTA-5, and MUIR-3, designed to support supplemental NDA filings to expand the REDEMPLO label beyond genetic and clinical FCS into patients with SHTG. SHASTA-3 and SHASTA-4 together enrolled over 750 patients and have a primary endpoint of change in triglycerides from baseline with key secondary endpoints of acute pancreatitis rates. MUIR-3, which enrolled over 1,400 patients, is designed to supplement the SHASTA studies with additional patient safety data. We are also enrolling patients at high risk of acute pancreatitis into SHASTA-5 to directly assess the ability of plozasiran to reduce the risk of acute pancreatitis as the primary endpoint. Should SHASTA-3 and SHASTA-4 show a statistically significant improvement in acute pancreatitis risk, we will reassess whether there is added value in continuing SHASTA-5. We remain on schedule to complete the blinded portion of the SHASTA-3, SHASTA-4, and MUIR-3 in mid 2026 to support a planned top-line data readout in the third quarter. This would further support our plans for an sNDA submission for SHTG before the end of this year. Before moving on to zodasiran, I'd like to highlight a presentation we made with new long-term efficacy and safety data for plozasiran across a spectrum of patients with hypertriglyceridemia at the American College Cardiology Conference in March. The data were from a two-year open-label extension of the two phase IIb double-blind placebo-controlled studies of plozasiran, SHASTA-2 conducted in adults with severe hypertriglyceridemia, and MUIR, which enrolled patients with hypertriglyceridemia. During the two-year open-label extension, patients saw median reductions in their triglycerides of 83% in SHTG patients from SHASTA-2 and 67% in HTG patients from MUIR, with additional reductions in remnant and non-HDL cholesterol. 96% of SHTG patients achieved TGs below 500 milligrams per deciliter, and 63% achieved TGs below 150 mg per deciliter, with 93% of HTG patients achieving TGs below 150 mg per deciliter. Importantly, no adjudicated acute pancreatitis events occurred in any patient receiving plozasiran during the two-year phase IIb open-label extension study. These findings support the potential of plozasiran as a promising new approach to managing patients with moderate to severe HTG phenotypes who are at risk of AP and potentially other cardiometabolic comorbidities. I'd now like to give a quick update on the YOSEMITE phase III study of zodasiran, which is being developed as a potential treatment for homozygous familial hypercholesterolemia, or HoFH, a rare genetic condition that leads to severely elevated LDL cholesterol and early-onset cardiovascular disease. zodasiran is the fourth investigational RNAi-based candidate developed by Arrowhead to reach late-stage clinical studies. YOSEMITE is designed to enroll approximately 60 individuals with HoFH over the age of 12 who will be randomized 2/1 to receive five doses of 200 mg zodasiran or placebo. The primary endpoint is the % change from baseline to month 12 in fasting LDL cholesterol. Enrollment has been on track, and we are confident that the study can be fully enrolled this year to enable study completion and potential NDA filings before the end of 2027. The last program within cardiometabolic is ARO-DIMER-PA, the first dual-functional siRNA designed to silence the expression of two genes with a single RNAi molecule. ARO-DIMER-PA is being developed as a potential treatment for ASCVD due to mixed hyperlipidemia by silencing expression of both PCSK9 and ApoC-III. In January, we initiated a phase I-IIa placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and effects on LDL cholesterol and triglycerides using single-dose ARO-DIMER-PA in Part I and multiple doses in Part II in up to 78 adults with mixed hyperlipidemia. Enrollment in the study has been rapid. We are on schedule to have sufficient data to provide the first clinical readout in Q3 of this year. This is a very interesting program, and we think the preclinical data has been highly compelling. We have some innovative ideas on late-stage trial designs that potentially accelerate the path to regulatory approval. We're eager to have a first clinical readout to start moving ahead with later studies if supported by initial data. Lastly, I'd like to give an update on the status of the ARO-MAPT first-in-human study. ARO-MAPT is being developed as a potential treatment for tauopathies, including Alzheimer's disease, progressive neurodegenerative disease characterized by cognitive and functional decline. Alzheimer's disease is the most common cause of dementia, affecting an estimated 32 million people worldwide, and is part of a group of neurodegenerative diseases called tauopathies that are marked by abnormal tau accumulation and formation of tau tangles in neurons. Tau-related pathology may be a critical driver of neurodegeneration. Targeting tau is a promising strategy to potentially slow or stop cognitive and functional decline. ARO-MAPT is Arrowhead's first investigational RNAi-based therapy to achieve a new proprietary delivery system, which in preclinical studies has achieved blood-brain barrier penetration and deep knockdown of target genes across the central nervous system, including deep brain regions after subcutaneous injection. This underscores Arrowhead's leadership in the delivery of siRNA to multiple tissues and cell types throughout the body, utilizing our proprietary and differentiated Targeted RNAi Molecule or TRiM platform. In December 2025, we dosed the first subjects in a phase I/II clinical trial of ARO-MAPT. This study is a placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-MAPT in up to 64 healthy subjects and up to 48 patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia. In part 1a of the study, healthy subjects will receive one or three weekly doses of ARO-MAPT or placebo by subcutaneous injection. In parts 1b and part two, healthy volunteers and Alzheimer's disease patients, respectively, will receive multiple escalating doses of ARO-MAPT or placebo. We are nearing completion of enrollment of the single-dose portion of the study in healthy volunteers and have begun enrollment in the multi-dose cohorts in both healthy volunteers and patients with Alzheimer's disease. This keeps us on pace for an initial data readout at the end of Q3 or early Q4. I will now turn the call over to Daniel Apel. Thank you, James, good afternoon, everyone. As we reported today, net loss for the quarter ended March 31, 2026 was $132.7 million, or a loss of $0.93 per share based on 142.4 million fully diluted weighted average shares outstanding. This compares to net income of $370.4 million, or $2.75 per share for the quarter ended March 31, 2025 based on 134.5 million fully diluted weighted average shares outstanding in that quarter. Recall that in the prior year quarter, we recorded over $540 million in revenue solely related to the Sarepta transaction that was executed at that time. Revenue for this quarter totaled $74 million, driven primarily by our licensed and collaboration agreements with Sarepta and with Novartis. Of this amount, approximately $42 million related to the Sarepta collaboration. This includes $28 million from ongoing recognition of the initial Sarepta consideration, $10 million related to reimbursement of incurred preclinical collaboration program costs, and $4 million for our clinical supply provided to them under a clinical supply agreement. In addition, we recognized $20 million of the $200 million upfront payment received from Novartis in October, bringing year-to-date recognition of Novartis upfront to $54 million, with the remaining $146 million to be deferred over time as we fulfill our preclinical obligations. We also recorded $11 million related to the asset purchase agreement between Sanofi and Visirna Therapeutics to develop and commercialize investigational plozasiran in Greater China. Visirna, as you know, is our majority-owned subsidiary with operations in China, and the amount recognized is almost entirely due to the January approval of FCS in that region by the Chinese National Medical Products Administration. As mentioned previously, we are not intending to headline specific REDEMPLO product sales numbers until such time as they become a meaningful driver to our financials. That said, net sales can be derived from our disclosures as the difference between total net revenue and collaboration revenue and represents approximately $1 million for the quarter. This is our first full quarter of REDEMPLO sales, and on a unit basis, that figure compares favorably to the first full commercial quarter of the other approved ApoC-III inhibitor. Turning now to expenses, total operating expenses for the quarter were approximately $215 million, roughly flat with operating expenses in the first fiscal quarter. This compares to $162 million in the prior year quarter, representing an increase of $53 million year-over-year. This increase was driven by $40 million of higher R&D expenses and $13 million of higher SG&A expenses, fully in line with our expectations. The increase in R&D expense was primarily attributable to ongoing progression of our phase III registrational studies for plozasiran and SHTG, as well as our early-stage pipeline programs, including the DIMER and MAPT. Fiscal year-to-date, almost 2/3 of the clinical trial spend can be attributed to our plozasiran phase III studies. As James already mentioned, the registrational SHTG studies for plozasiran should read out in the summer, clinical trial spend for these programs should thereafter moderate accordingly. SG&A expenses increased year-over-year compared to the prior year's second fiscal quarter, driven primarily by ongoing investments to support the commercialization of REDEMPLO. As previously discussed, we are continuing to build our commercial capabilities to fully support the FCS launch. We continue to leverage and invest in these capabilities to support REDEMPLO and FCS while also positioning the organization to support a potential future launch in SHTG. We ultimately expect to leverage these same capabilities for the advancement of zodasiran for the treatment of HoFH. Turning to the balance sheet, cash and investments on hand totaled nearly $1.8 billion as of March 31, 2026. Common shares outstanding at quarter end were 140.69. To provide a little color, in this quarter alone, we brought in over $1 billion, including approximately $850 million net from our January financing transactions, inclusive of a concurrent offering of 0% convertible senior notes and common stock, along with the associated capped call transaction. Other notable inflows in the quarter include the $200 million received from Sarepta upon achieving the second DM1 program milestone, as well as a $50 million Anniversary payment under the Sarepta long-term collaboration agreement. All of this is very much in line with the information provided previously during our February earnings call. We believe our strong balance sheet provides us with significant financial flexibility to support ongoing clinical development, to advance current and future commercialization activities, and to execute against our long-term strategic priorities. With that brief overview, I will now turn the call back to Chris. Thanks, Dan. As we build out our commercial team and focus on efficiently bringing REDEMPLO to the patients who need it, we have not lost sight on continuing to expand our pipeline and ultimately increasing the number of medicines we can offer to a wide variety of patients. Our business has become more complex as we grow in all these areas, we continue to innovate and execute well. We see multiple key potential value-creating events in the second half of 2026 that together speak to our priorities. Here are just a few of the events we are tracking. SHASTA-3, SHASTA-4, and MUIR-3, which is a suite of phase III clinical studies designed to support an sNDA for REDEMPLO in patients with SHTG, is on schedule for completion and top-line readout in Q3. The first clinical readout of ARO-DIMER-PA targeting both PCSK9 and ApoC-III for LDL and TG lowering is also expected in Q3. The first clinical readout for ARO-MAPT is expected around the end of Q3 or early Q4. This is being developed as a potential treatment for tauopathies, including Alzheimer's disease, and is our first program using the CNS delivery platform design to cross the blood-brain barrier after systemic delivery via subcutaneous administration. Additional ARO-INHBE and ARO-ALK7 data releases are planned in 2026 for this novel non-inhibitor strategy, which had quite encouraging early data, particularly in diabetic obese patients in combination with tirzepatide and with liver fat reductions as monotherapy or in combination with tirzepatide. As James mentioned, we are planning to webcast three presentations as part of our summer series of R&D webinars to go over cardiometabolic broadly, obesity, and ARO-MAPT. These can serve as a review of the programs and results to date and as a primer for the potentially important readouts coming up later this year. Thank you for joining us today. I would now like to open the call to your questions. Thank you. At this time, we will now conduct the question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please note that each analyst is permitted to ask one question. Should you have a follow-up question, you will need to get back in queue. Please stand by while we compile the Q&A roster. Our first question comes from the line of Edward Tenthoff from Piper Sandler. Your line is now open. Great. Thank you. Thanks for all the detail in the update today. My question really has to do with looking at the upcoming severe hypertriglyceridemia readouts. When it comes to, I guess, pancreatitis as a secondary, is the plan to pool SHASTA-3 and SHASTA-4? What are sort of the assumptions around pancreatitis? Thank you. Yeah. Hi, Ted. Thanks for the question. This is James. Yeah, you got that right. The plan is to pool both of those studies, SHASTA-3 and SHASTA-4. We'll analyze, do a meta-analysis of those two studies to look at pancreatitis event rates, both rates of events in individual patients and the total number of overall events. I think that's kind of all I can say on that. We're still, you know, we're still blinded and, like we said, should have the data in Q3. Great. Looking forward to that. Thank you. Thank you. One moment for our next question. Our next question comes from Jason Gerberry of Bank of America. Your line's now open. Hey, guys. Thanks for taking my question. Just wanted to probe in a little bit more on the INHBE and ALK7 updates later this year and get your latest thoughts on these modalities. I think investors have soured a little bit on INHBE after the Wave Life Sciences data update. Just wanted to get your perspective on kinda what you need to see from these upcoming readouts to, you know, advance one or both for obesity treatment versus, you know, any alternative potentially considering for a MASH indication. Thanks. Yeah. Hi, Jason. This is James. Sure, happy to cover those questions. you know, we've been saying all along really that we thought that this ARO-INHBE outset and access is interesting, but we thought the approach was to combine with GLP-1s. That's still our standpoint here. We think that there's potential, particularly in the Type 2 Diabetics for additional weight loss on top of tirzepatide or other GLP-1s with either ALK7 knockdown or ARO-INHBE knockdown. What we've seen from the clinical study that we talked about earlier this year from ARO-INHBE, with ARO-INHBE knockdown is really clear redistribution of fat out of the liver, even with monotherapy, but also with combination therapy. Some additional changes, improvements in body composition, reductions in total fat and visceral fat, particularly in that Type 2 Diabetic population. I think that we look forward to more of the same and to sharing more of that liver fat data here, in the, you know, the coming quarter or so. In the second half of the year, providing some additional updates on changes in body composition and some of the other parameters that we showed back in January. Thank you. One moment for our next question. Our next question comes from Brian Cheng of JPMorgan. Hi, guys. This is Ron on for Brian. Congrats on the quarter. Just wanted to ask you, can you guys give more color on the interactions you've had with payers that led to the recent price lowering? What has been the feedback since your competitive action last month? Thank you. Yeah. Hi, Ron. This is Andy. Our interactions with payers to date have been consistent, have been positive, and we're seeing payer policies, and these are public payer policies that reflect the ability to diagnose FCS patients through multiple diagnosis pathways, in particular through the clinical criteria that we saw in PALISADE. Really positive conversations with payers about payer policies and about future coverage. Okay. Just a quick follow-up. Could you guys, how should we think about the impact here to gross to net following the price lowering? Gross. Well, gross to net. Dan can take that. What's our assumption on gross to net with the new pricing policy? I mean, I should answer your second question. We ignore the WAC too, as Chris already explained, to make it, you know, premium price to the competitor there. We are not actually gonna give guidance on gross to net. We have not seen anything substantial in that regard. Nor do we currently expect it. You know, other than things that were statutorily required, such as Medicaid rebates and the manufacturer discount program and the like. We have a policy at the moment not to provide any sort of guidance or on that at this stage. Let's just be clear. The lowering of the WAC from 60-45 had nothing to do with any pushback from payers. To the contrary, I think that those interactions have been quite positive. You know, this is a lowering of the WAC in expectation of an expansion on the market into SHTG and to ensure this, that we are, you know, that the payers would not require a step through with our competitor. As we talked about, you know, we are priced at a premium here. We think that's appropriate, you know, given the characteristics of our drug versus the competitor's drug. We think 45 actually, you know, long term is probably quite a good price in terms of maximizing access to the drug across various subpopulations within SHTG. Great. Thank you so much. You're welcome. Thank you. One moment for our next question. Our next question comes from Michael Ulz from Morgan Stanley. Your line's now open. Hey, guys. It's Abhi Aggarwal come the line for Mike. Thank you for taking our questions and congrats on the quarter. I guess among the patients who were switchers, could you characterize, you know, I guess the motivations for switching to REDEMPLO? Was it due to its clinical profile or, could it be more payer-related? Thanks. Hi, Mike, this is Andy. Thanks for the question. We've seen really diversity of reasons for switch that include efficacy, safety, and tolerability, and a variety of other reasons as well. I wouldn't say there's one particular reason driving switch. There's a multitude of reasons. Okay, great. Thanks for taking our questions. Thank you. One moment for our next question. Our next question comes from Maury Raycroft from Jefferies. Hi, thanks for taking my question. Maybe just a follow-up to Ted's question earlier on SHASTA 3 and 4. Just wondering if there's an updated perspective on whether the blinded AP event rates are tracking in line with your expectations and whether you'd be able to generate enough events by the time the study completes, or could you potentially even keep the study blinded a little bit longer to get an adequate number of total events? Hi, Maury Raycroft, this is James Hamilton. I'll take that question. We're not giving any guidance on or sort of blow-by-blow details on the number of events we're seeing. Suffice it to say we feel comfortable with the number of events we have seen and, you know, the big reveal will be in Q3. No plans to extend the study or stay blinded for a longer period at this time. Got it. Okay. Thanks for taking my questions. Thank you. One moment for our next question. Our next question comes from Mani Foroohar from Leerink. Your line is now open. Hi, you have Valerie from Mani Foroohar. Thanks for taking my question. Congrats on your quarter. Yeah. Can you talk about how the phase III CELIA data from Biogen will inform your strategy for ARO-MAPT? Maybe also, can you just comment on your internal expectations for this readout? Thank you. I don't think any of us caught that. Could you say that again? I think the line is a bit muddled. Oh, sorry. No, yeah. I was asking if you could talk about the phase III CELIA data from Biogen and how it will inform your strategy for ARO-MAPT. You also talk about your internal expectations. Sure, yeah. I can take that. This is James. I'm assuming you're referring to the ASO targeting MAPT from Biogen and Ionis that's supposed to read out here in maybe this quarter or early next quarter. Yeah, I mean, I hope those data look good, and I hope that they show an improvement in the cognitive rating scales. I think that would be broadly positive for Arrowhead and for the tau hypothesis in general. Of course, that study is in Alzheimer's disease, and a positive readout would support our Alzheimer's programs. That being said, even if those data are not positive, I think we can still, we still have the option of pursuing all the other tauopathies, right? A knockdown approach of tau should improve any condition that's really driven by tau gain-of-function or tau pathology. Things like progressive supranuclear palsy or corticobasal degeneration or some of the real specific MAPT gain-of-function frontotemporal dementia disorders. You know, those are all fair game for us as we think about phase IIs and phase III down the road. Hopefully, the Biogen data are positive. If it's not, it's not the end of the world for our program because we can still pursue the tauopathies. Great. Thank you. Thank you. One moment for our next question. Our next question comes from Joseph Thome from TD Cowen. Your line is now open. Hi there. Good afternoon, and thank you for taking my question. Just as we're thinking about the potential outcomes for the SHASTA-3, SHASTA-4 studies later this year, do you expect that you'll have to show differentiated efficacy versus what Ionis has shown in addition to the dosing benefit in order to keep that even slightly premium pricing? Just a point of clarification, are you characterizing the AP events in SHASTA-3, SHASTA-4 the same way that you characterize them in the long-term SHASTA-2 extension that was recently presented? Thank you. Yeah. Why don't I take the second part first about the characterization. The answer is no. The SHASTA-2 study, we used the strict Atlanta criteria to look at pancreatitis events, whereas in the SHASTA-3-4 pooled analysis, we're using this sort of modified Atlanta criteria that has definite, probable, and possible pancreatitis. Regarding the premium pricing, look, let's just see what those data look like. You know, historically, when we look at data side by side, you know, with the large caveat that of course it's difficult to compare different clinical studies, you know, with different patient populations. What we have seen consistently is superior triglyceride reduction, superior safety profile, and of course, superior convenience. We expect those to continue. Should that be the case, then we would expect a premium is still appropriate. Great. Thank you. You're welcome. Thank you. Our next question comes from Patrick Trucchio of H.C. Wainwright. Your line is now open. Hi. Thanks so much. Just regarding your business development strategy, I was hoping you could give us some additional details just in terms of which assets you would be looking to bring forward on your own versus those that you may partner. Just more broadly, how you're thinking about how RNAi kind of fits into the broader genetic medicines, sort of portfolio and how, you know, how RNAi is looking sort of competitively against modalities like gene editing, et cetera. Sure. Look, I think that RNAi is at the forefront of genetic medicine, you know, for the foreseeable future. Look, it's not the right modality for everything. For those diseases that are characterized by the overproduction of something, if we can address that cell type, then RNAi is a very attractive modality. You know, when we think about RNAi versus gene editing, you know, the way I feel at least is that, you know, RNAi is a relatively straightforward and conservative approach. You know, it is a reversible approach. In our hands, you know, we can have very long durability. You can almost get the best of both worlds, where if you have a low needle burden, if you will, but the ability to come off drug, you know, should some new biology, you know, come out to suggest that you don't, you don't actually wanna knock down that gene product. That's not the case in gene editing. I think that gene editing does have a place in the world of medicine. It's just quite unknown right now because I don't know what happens, you know, to these edited genes 10 years from now, and I don't think anybody does. Notwithstanding, as the biology changes, it could be that sometime in the future, we decide that you might not wanna knock down a certain gene product. You know, for those, you know, horrible diseases that are terminal, it could be worth taking a risk to do gene editing. Frankly, for, you know, for all others, if you can address something with RNAi, that feels to me as a, you know, a better approach. Regarding business development, you know, this is a dynamic question. Right now, we feel pretty good about our existing pipeline in terms of that which is wholly owned right now. You know, we like that idea of pushing all these forward ourselves. With the possible exception of C3 inhibitor, we like those programs a lot. Those drug candidates appear to do what they're intending to do, and they seem to be well-tolerated. Those are just really outside of our core focus at present. Those are a couple assets that we could, you know, partner with the right partner at some point. Everything else feels pretty good right now. You know, look, that may change as we talk to other companies and as our pipeline grows. We don't feel real sense of urgency to do additional deals on existing clinical programs other than maybe C3 inhibitor. Thank you. Our next question comes from Amine Chaherli from B. Riley Securities. Your line is now open. Hi, everyone. Congratulations on the quarter. This is Amine Chaherli on behalf of Madison El-Saadi. I just wanted to ask, as you think about the next generation of the DIMER platform, is a construct combining INHBE or ALK7 with a non-overlapping mechanism target, you know, something you're evaluating for obesity or other indications? Thank you. Yes. Can we move on to the next question? Yes. Our next question comes from Luca Issi from RBC Capital Markets. Your line is now open. Oh, great. Hi, team. This is Shelby on for Luca, and thanks for taking the question. Given Ionis has announced a new price at $40,000, and has first-mover advantage, can you walk us through the rationale to continue to price REDEMPLO at a premium versus that par in SHTG, maybe as a way to kind of undercut their pricing since you're coming in second? Just wondering the rationale behind that. Thanks. Thanks, Shelby. As Chris previously mentioned, we do believe REDEMPLO is a best-in-class ApoC-III inhibitor, and that it commands premium pricing as a consequence of that. There are a variety of reasons for that. Chris touched on some of them, including the depth of knockdown for ApoC-III as a target, the depth of TG reduction. We saw that from PALISADE with an 80% reduction from baseline. We saw that with the numerical decrease in acute pancreatitis from PALISADE. We've seen that also with an FDA label that has no contraindications, no warnings, and no precautions. Lastly, with a convenient dosing schedule that's only four injections a year. When you sum up the totality of those attributes, we just believe it's a best-in-class ApoC-III inhibitor, and as a consequence, should be premium priced. Thank you. Our next question comes from Jennifer Jia from Cantor Fitzgerald. Your line is now open. Hi. Thanks for taking my question. This is Jennifer Jia on for Prakhar Agrawal. I'd like to understand a little bit more on the expectations for aroDIMER readout later this year. What efficacy are you hoping to see, and what does it take to take this forward to a larger trial? If it's positive, do you consider going straight to a cardio outcomes trial, or will you still need to complete a phase II? Yeah. Hi, Jennifer, this is James. Happy to address that question. The great thing about this program is that all of the relevant biomarkers, and even, you know, biomarkers that you could use for potentially for approval, are blood-based, right? We can measure PCSK9, we can measure ApoC-III in the blood, and we can measure LDL cholesterol and triglycerides. ApoB, non-HDL cholesterol are all pretty easy for us to measure. That's what we'll be primarily focused on, as well as safety in this initial data readout. In terms of where we go from here, you know, I think we're working on that now. There may be some additional limited phase II work which we could even consider doing as part of this study, but then moving quickly into an outcome study down the road. More to come on the development plan and the study designs, but looking forward to the readout later this year. Great. Thanks. Thank you. Our next question comes from Keay Nakae from Chardan Capital Markets. Your line is now open. Yeah, thank you. Question about the Madrigal licensing agreement for ARO-PNPLA3. Help us understand from a capital allocation strategy perspective why it makes sense for you to do this deal at this time, as opposed to taking the drug further on your own? Yes, good question. Let me just take it back and remind everyone that where PNPLA3, where ARO-PNPLA3 came from. We didn't develop this on our own independently. This was part of our deal with Janssen that was centered around HBV, FSBP, also included a couple of additional targets. This was one of those targets. We developed it for them. They did the phase I. The phase I was compelling. You know, after only a single dose, they saw about a 40% reduction in liver fat in homozygous patients. That was interesting to us. Janssen, as I understand it, decided to get out of MASH, the asset was returned to us. We didn't spend any money on this. As we look at taking this forward, we think it's a really compelling target for a company that's focused in MASH largely. This is a genetically defined population, that's sort of the good news and the bad news, right? You know, the good news is it's quite specific. The challenge there is that there will be, you know, a companion diagnostic component to this. It made sense for us to find, you know, a pure play MASH company to take this forward. Of course, Madrigal is, I think, the best out there right now. It made sense. It didn't really make sense for us to, you know, to spend much money right now to do a phase II. You know, those studies could be a bit long and more expensive than made sense for us. You know, we've got a very large pipeline. We've got some really interesting programs that we are pushing ourselves. I just think that, you know, our ROI is probably better, you know, by allocating capital to those programs that we are more confident that we will hold on to long term. That's where we went. You know, we are thrilled to have Madrigal as a partner. We're thrilled to have them develop that drug. We think it's a good drug. We're thrilled to have them commercialize it eventually. We feel good about the deal. Great. Thank you. Sure. Thank you. This concludes the question-and-answer session. I would now like to turn it back to Chris Anzalone for closing remarks. Thanks, everyone, for joining us today, and we look forward to seeing you in the future. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Speaker 13: Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. Throughout today's presentation, all participants will be in listen-only mode. After the presentation, there will be an opportunity to ask questions. Instruction will follow at that time. I will now hand the conference call over to Vince Anzalone, Senior Vice President of Investor Relations for Arrowhead. Please go ahead, Vince. Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. ladies and gentlemen welcome to the arrowhead pharmaceuticals conference call Throughout today's presentation, all participants will be in listen-only mode. throughout today's presentation all participants will be in listen-only mode After the presentation, there will be an opportunity to ask questions. after the presentation there will be an opportunity to ask questions Instruction will follow at that time. instruction will follow at that time I will now hand the conference call over to Vince Anzalone, Senior Vice President of Investor Relations for Arrowhead. i will now hand the conference call over to vince anzalone senior vice president of investor relations for arrowhead Please go ahead, Vince. please go ahead vince

Speaker 18: Good afternoon, and thank you for joining us today to discuss Arrowhead's results for its fiscal 2026 second quarter ended March 31, 2026. With us today from management, our President and CEO, Dr. Chris Anzalone, who will provide an overview. Andy Davis, Senior Vice President and Head of the Global Cardiometabolic Franchise, who will provide an update on commercialization activities. Dr. James Hamilton, Chief Medical Officer and Head of R&D, who will discuss our development programs, and Daniel Apel, Chief Financial Officer, who will give a review of the financials. Following management's prepared remarks, we will open the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Good afternoon, and thank you for joining us today to discuss Arrowhead's results for its fiscal 2026 second quarter ended March 31, 2026. good afternoon and thank you for joining us today to discuss arrowhead's results for its fiscal 2026 second quarter ended march 31 2026 With us today from management, our President and CEO, Dr. Chris Anzalone, who will provide an overview. with us today from management our president and ceo dr chris anzalone who will provide an overview Andy Davis, Senior Vice President and Head of the Global Cardiometabolic Franchise, who will provide an update on commercialization activities. andy davis senior vice president and head of the global cardiometabolic franchise who will provide an update on commercialization activities Dr. James Hamilton, Chief Medical Officer and Head of R&D, who will discuss our development programs, and Daniel Apel, Chief Financial Officer, who will give a review of the financials. dr james hamilton chief medical officer and head of r&d who will discuss our development programs and daniel apel chief financial officer who will give a review of the financials Following management's prepared remarks, we will open the call to questions. following management's prepared remarks we will open the call to questions Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. before we begin i would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of section 27a of the securities act of 1933 and section 21e of the securities exchange act of 1934 All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. I'd now like to turn the call over to Chris. All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. all statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. for further details concerning these risks and uncertainties please refer to our sec filings including our most recent annual report on form 10-k and our quarterly reports on form 10-q I'd now like to turn the call over to Chris. i'd now like to turn the call over to chris

Speaker 4: Thanks, Vince. Good afternoon, everyone, thank you for joining us today. During the fiscal second quarter, in the period since our last earnings call, we have continued to execute well against our commercial, R&D, and corporate goals. Arrowhead is now on the strongest footing of our history. Your commercial, we have a clear line of sight to expand our commercial opportunities and footprint. Our pipeline is larger than ever. Our discovery capabilities are broader than ever. Our balance sheet is stronger than ever. This is an historic time for our company. We are uniquely positioned to deliver important medicines to patients who need them and to create substantial value for our shareholders. Let's talk about some of our recent progress and begin with commercial. As you recall, the FDA approved REDEMPLO in November 2025 as an adjunct to diet to reduce triglycerides in adults with FCS. Thanks, Vince. thanks vince Good afternoon, everyone, thank you for joining us today. good afternoon everyone thank you for joining us today During the fiscal second quarter, in the period since our last earnings call, we have continued to execute well against our commercial, R&D, and corporate goals. during the fiscal second quarter in the period since our last earnings call we have continued to execute well against our commercial r&d and corporate goals Arrowhead is now on the strongest footing of our history. arrowhead is now on the strongest footing of our history Your commercial, we have a clear line of sight to expand our commercial opportunities and footprint. your commercial we have a clear line of sight to expand our commercial opportunities and footprint Our pipeline is larger than ever. our pipeline is larger than ever Our discovery capabilities are broader than ever. our discovery capabilities are broader than ever Our balance sheet is stronger than ever. our balance sheet is stronger than ever This is an historic time for our company. this is an historic time for our company We are uniquely positioned to deliver important medicines to patients who need them and to create substantial value for our shareholders. we are uniquely positioned to deliver important medicines to patients who need them and to create substantial value for our shareholders Let's talk about some of our recent progress and begin with commercial. let's talk about some of our recent progress and begin with commercial As you recall, the FDA approved REDEMPLO in November 2025 as an adjunct to diet to reduce triglycerides in adults with FCS. as you recall the fda approved redemplo in november 2025 as an adjunct to diet to reduce triglycerides in adults with fcs FCS is a severe rare disease with an estimated 65 million people in the U.S. living with genetic or clinical FCS, characterized by TG levels that can be 10-100 times higher than normal. This leads to a substantially increased risk of developing acute, recurrent, and potentially fatal pancreatitis. As we reported last quarter, the U.S. REDEMPLO launch was off to a strong start. That momentum has continued into the current quarter, we are now seeing around 30 new prescriptions written each week. More than 400 prescriptions have been written since launch, more than 10% of these have been for patients switching from our competitor's ApoC-III inhibitor. Of course, each prescription needs to be fully adjudicated with payers before becoming paid claims, we offer a robust quick-start program to support these FCS patients in the interim. FCS is a severe rare disease with an estimated 65 million people in the U.S. living with genetic or clinical FCS, characterized by TG levels that can be 10-100 times higher than normal. fcs is a severe rare disease with an estimated 65 million people in the u.s living with genetic or clinical fcs characterized by tg levels that can be 10-100 times higher than normal This leads to a substantially increased risk of developing acute, recurrent, and potentially fatal pancreatitis. this leads to a substantially increased risk of developing acute recurrent and potentially fatal pancreatitis As we reported last quarter, the U.S. as we reported last quarter the u.s REDEMPLO launch was off to a strong start. redemplo launch was off to a strong start That momentum has continued into the current quarter, we are now seeing around 30 new prescriptions written each week. that momentum has continued into the current quarter we are now seeing around 30 new prescriptions written each week More than 400 prescriptions have been written since launch, more than 10% of these have been for patients switching from our competitor's ApoC-III inhibitor. more than 400 prescriptions have been written since launch more than 10% of these have been for patients switching from our competitor's apoc-iii inhibitor Of course, each prescription needs to be fully adjudicated with payers before becoming paid claims, we offer a robust quick-start program to support these FCS patients in the interim. of course each prescription needs to be fully adjudicated with payers before becoming paid claims we offer a robust quick-start program to support these fcs patients in the interim The volume of physicians writing prescriptions and the number of patients receiving REDEMPLO continues to exceed our initial expectations. With respect to pricing, we updated REDEMPLO's U.S. wholesale acquisition cost, or WAC, to $45,000 per patient per year. This represents a premium to our competitor's WAC pricing. We believe this is appropriate given that clinical data suggests we have a clearly and demonstrably superior product in terms of TG reduction, safety profile, and convenience. As part of the one REDEMPLO unified pricing model, this price is intended to remain consistent across FCS and SHTG if that indication is approved. We continue to see this strategy as potentially simplifying payer contracting and eliminating pricing complexity that could complicate future formulary negotiation. The response from payers to this strategy has been positive, and our interactions to date have been productive. The volume of physicians writing prescriptions and the number of patients receiving REDEMPLO continues to exceed our initial expectations. the volume of physicians writing prescriptions and the number of patients receiving redemplo continues to exceed our initial expectations With respect to pricing, we updated REDEMPLO's U.S. wholesale acquisition cost, or WAC, to $45,000 per patient per year. with respect to pricing we updated redemplo's u.s wholesale acquisition cost or wac to $45,000 per patient per year This represents a premium to our competitor's WAC pricing. this represents a premium to our competitor's wac pricing We believe this is appropriate given that clinical data suggests we have a clearly and demonstrably superior product in terms of TG reduction, safety profile, and convenience. we believe this is appropriate given that clinical data suggests we have a clearly and demonstrably superior product in terms of tg reduction safety profile and convenience As part of the one REDEMPLO unified pricing model, this price is intended to remain consistent across FCS and SHTG if that indication is approved. as part of the one redemplo unified pricing model this price is intended to remain consistent across fcs and shtg if that indication is approved We continue to see this strategy as potentially simplifying payer contracting and eliminating pricing complexity that could complicate future formulary negotiation. we continue to see this strategy as potentially simplifying payer contracting and eliminating pricing complexity that could complicate future formulary negotiation The response from payers to this strategy has been positive, and our interactions to date have been productive. the response from payers to this strategy has been positive and our interactions to date have been productive Beyond the U.S., we secure positive regulatory action in four additional geographies for REDEMPLO in patients with genetically confirmed and clinically defined FCS. We received approvals from the Australian Therapeutic Goods Administration, the Chinese National Medical Products Administration, and Health Canada. In addition, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending the approval of REDEMPLO. This is an impressive result achieved by our global regulatory team in a very short period and further reflects the strength of our clinical data in FCS and the value that REDEMPLO offers to patients. REDEMPLO will be available later this year in Canada and we anticipate it will be marketed independently by Arrowhead. Pending a marketing authorization decision from the European Commission, we expect to launch REDEMPLO later this year in select E.U. countries and likely in the U.K. as well. Beyond the U.S., we secure positive regulatory action in four additional geographies for REDEMPLO in patients with genetically confirmed and clinically defined FCS. beyond the u.s we secure positive regulatory action in four additional geographies for redemplo in patients with genetically confirmed and clinically defined fcs We received approvals from the Australian Therapeutic Goods Administration, the Chinese National Medical Products Administration, and Health Canada. we received approvals from the australian therapeutic goods administration the chinese national medical products administration and health canada In addition, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending the approval of REDEMPLO. in addition the european medicines agency's committee for medicinal products for human use adopted a positive opinion recommending the approval of redemplo This is an impressive result achieved by our global regulatory team in a very short period and further reflects the strength of our clinical data in FCS and the value that REDEMPLO offers to patients. this is an impressive result achieved by our global regulatory team in a very short period and further reflects the strength of our clinical data in fcs and the value that redemplo offers to patients REDEMPLO will be available later this year in Canada and we anticipate it will be marketed independently by Arrowhead. redemplo will be available later this year in canada and we anticipate it will be marketed independently by arrowhead Pending a marketing authorization decision from the European Commission, we expect to launch REDEMPLO later this year in select E.U. countries and likely in the U.K. as well. pending a marketing authorization decision from the european commission we expect to launch redemplo later this year in select e.u countries and likely in the u.k as well In Greater China, REDEMPLO will be marketed by Sanofi. In addition to our regulatory team, the rest of the R&D organization has performed extremely well and has made progress in the broader portfolio. Our drive to expand our platforms in order to increase the number and types of diseases we can address continues even as we grow as a commercial entity. During the recent period, we have made rapid progress across the pipeline, including programs targeting genes expressed in liver, skeletal muscle, adipose, CNS, and the lung, as well as the first dual functional siRNA designed to silence the expression of two genes with a single molecule. We believe the depth and breadth of our clinical pipeline is unmatched, and we expect to continue to lead the field in innovation. In Greater China, REDEMPLO will be marketed by Sanofi. in greater china redemplo will be marketed by sanofi In addition to our regulatory team, the rest of the R&D organization has performed extremely well and has made progress in the broader portfolio. in addition to our regulatory team the rest of the r&d organization has performed extremely well and has made progress in the broader portfolio Our drive to expand our platforms in order to increase the number and types of diseases we can address continues even as we grow as a commercial entity. our drive to expand our platforms in order to increase the number and types of diseases we can address continues even as we grow as a commercial entity During the recent period, we have made rapid progress across the pipeline, including programs targeting genes expressed in liver, skeletal muscle, adipose, CNS, and the lung, as well as the first dual functional siRNA designed to silence the expression of two genes with a single molecule. We believe the depth and breadth of our clinical pipeline is unmatched, and we expect to continue to lead the field in innovation. during the recent period we have made rapid progress across the pipeline including programs targeting genes expressed in liver skeletal muscle adipose cns and the lung as well as the first dual functional sirna designed to silence the expression of two genes with a single molecule. we believe the depth and breadth of our clinical pipeline is unmatched and we expect to continue to lead the field in innovation Importantly, many of these programs will have clinical readouts this year, so investors and others may start to properly value the broader pipeline. As we look to near-term clinical data releases, we anticipate four important events. First, the phase III SHASTA-3 and 4 studies of plozasiran in SHTG patients should be ready for top-line data release in Q3. This is an important readout that will drive our anticipated supplemental NDA or sNDA as we seek to expand the population of patients we can treat with plozasiran. We expect to continue to see a favorable safety profile and substantial reduction in TGs, and we are cautiously optimistic that we could see an improvement in acute pancreatitis risk. Second, we expect to have early data from the ongoing phase I/II study of ARO-DIMER-PA in patients with mixed hyperlipidemia in Q3. Importantly, many of these programs will have clinical readouts this year, so investors and others may start to properly value the broader pipeline. importantly many of these programs will have clinical readouts this year so investors and others may start to properly value the broader pipeline As we look to near-term clinical data releases, we anticipate four important events. as we look to near-term clinical data releases we anticipate four important events First, the phase III SHASTA-3 and 4 studies of plozasiran in SHTG patients should be ready for top-line data release in Q3. first the phase iii shasta-3 and 4 studies of plozasiran in shtg patients should be ready for top-line data release in q3 This is an important readout that will drive our anticipated supplemental NDA or sNDA as we seek to expand the population of patients we can treat with plozasiran. this is an important readout that will drive our anticipated supplemental nda or snda as we seek to expand the population of patients we can treat with plozasiran We expect to continue to see a favorable safety profile and substantial reduction in TGs, and we are cautiously optimistic that we could see an improvement in acute pancreatitis risk. we expect to continue to see a favorable safety profile and substantial reduction in tgs and we are cautiously optimistic that we could see an improvement in acute pancreatitis risk Second, we expect to have early data from the ongoing phase I/II study of ARO-DIMER-PA in patients with mixed hyperlipidemia in Q3. second we expect to have early data from the ongoing phase i/ii study of aro-dimer-pa in patients with mixed hyperlipidemia in q3 We believe this will be the world's first clinical data of a single RNAi molecule designed to simultaneously silence expression of two proteins. If we see good reduction of PCSK9 and ApoC-III, and therefore reductions in LDL cholesterol and TGs, we could have a very powerful and unique therapy for roughly 20 million people in the U.S. living with mixed hyperlipidemia. More broadly, the data could provide initial clinical proof of concept for our growing DIMER platform and pipeline. Expect to see additional dual functional DIMERs in the clinic in 2027. Third, we expect to have early data from the ongoing phase I/II study of ARO-MAPT around the end of Q3 or early Q4. As you recall, this is our first candidate using our CNS platform designed to deliver RNAi molecules to the brain via simple subcutaneous administration. Our MAPT targets. We believe this will be the world's first clinical data of a single RNAi molecule designed to simultaneously silence expression of two proteins. we believe this will be the world's first clinical data of a single rnai molecule designed to simultaneously silence expression of two proteins If we see good reduction of PCSK9 and ApoC-III, and therefore reductions in LDL cholesterol and TGs, we could have a very powerful and unique therapy for roughly 20 million people in the U.S. living with mixed hyperlipidemia. if we see good reduction of pcsk9 and apoc-iii and therefore reductions in ldl cholesterol and tgs we could have a very powerful and unique therapy for roughly 20 million people in the u.s living with mixed hyperlipidemia More broadly, the data could provide initial clinical proof of concept for our growing DIMER platform and pipeline. more broadly the data could provide initial clinical proof of concept for our growing dimer platform and pipeline Expect to see additional dual functional DIMERs in the clinic in 2027. expect to see additional dual functional dimers in the clinic in 2027 Third, we expect to have early data from the ongoing phase I/II study of ARO-MAPT around the end of Q3 or early Q4. third we expect to have early data from the ongoing phase i/ii study of aro-mapt around the end of q3 or early q4 As you recall, this is our first candidate using our CNS platform designed to deliver RNAi molecules to the brain via simple subcutaneous administration. as you recall this is our first candidate using our cns platform designed to deliver rnai molecules to the brain via simple subcutaneous administration Our MAPT targets. our mapt targets ARO-MAPT targets the tau protein, which is increasingly validated for the potential treatments of Alzheimer's and other tauopathies. We believe that positive early data could be substantially disruptive. It could represent a great leap forward in treating tauopathies and more broadly, open the door to using RNAi to treat a broad range of conditions from neurodegenerative disorders to obesity. If early ARO-MAPT data are encouraging, expect a substantial expansion of our CNS pipeline beginning at the end of 2026. Fourth, we expect to provide clinical updates on ARO-INHBE and ARO-ALK7 throughout the second half of the year. Regarding ARO-INHBE, we plan to present additional data at various conferences and launch a phase II study. For ARO-ALK7, we expect to provide additional data from the ongoing phase I/II study. We see these as potentially important therapies for metabolic disorders and represent our first steps into obesity and MASH. ARO-MAPT targets the tau protein, which is increasingly validated for the potential treatments of Alzheimer's and other tauopathies. aro-mapt targets the tau protein which is increasingly validated for the potential treatments of alzheimer's and other tauopathies We believe that positive early data could be substantially disruptive. we believe that positive early data could be substantially disruptive It could represent a great leap forward in treating tauopathies and more broadly, open the door to using RNAi to treat a broad range of conditions from neurodegenerative disorders to obesity. it could represent a great leap forward in treating tauopathies and more broadly open the door to using rnai to treat a broad range of conditions from neurodegenerative disorders to obesity If early ARO-MAPT data are encouraging, expect a substantial expansion of our CNS pipeline beginning at the end of 2026. if early aro-mapt data are encouraging expect a substantial expansion of our cns pipeline beginning at the end of 2026 Fourth, we expect to provide clinical updates on ARO-INHBE and ARO-ALK7 throughout the second half of the year. fourth we expect to provide clinical updates on aro-inhbe and aro-alk7 throughout the second half of the year Regarding ARO-INHBE, we plan to present additional data at various conferences and launch a phase II study. regarding aro-inhbe we plan to present additional data at various conferences and launch a phase ii study For ARO-ALK7, we expect to provide additional data from the ongoing phase I/II study. for aro-alk7 we expect to provide additional data from the ongoing phase i/ii study We see these as potentially important therapies for metabolic disorders and represent our first steps into obesity and MASH. we see these as potentially important therapies for metabolic disorders and represent our first steps into obesity and mash We expect to have additional candidates in this space by the end of the year and into 2027. Moving on to financial and portfolio management, Arrowhead took important steps to ensure that we are properly funded to advance our commercial and development portfolio. We also entered into a license agreement for a program that achieved clinical proof of concept, but is not one that we wish to take forward. This is key to Arrowhead's strategy since we are extraordinarily productive in discovery and early development, but cannot commercialize everything independently. Let's talk about the steps we took. First, we dramatically strengthened our balance sheet, allowing us to push multiple programs toward commercialization and potentially through multiple independent and partner launches. During the quarter, we completed the largest fundraising Arrowhead has ever conducted. We expect to have additional candidates in this space by the end of the year and into 2027. we expect to have additional candidates in this space by the end of the year and into 2027 Moving on to financial and portfolio management, Arrowhead took important steps to ensure that we are properly funded to advance our commercial and development portfolio. moving on to financial and portfolio management arrowhead took important steps to ensure that we are properly funded to advance our commercial and development portfolio We also entered into a license agreement for a program that achieved clinical proof of concept, but is not one that we wish to take forward. we also entered into a license agreement for a program that achieved clinical proof of concept but is not one that we wish to take forward This is key to Arrowhead's strategy since we are extraordinarily productive in discovery and early development, but cannot commercialize everything independently. this is key to arrowhead's strategy since we are extraordinarily productive in discovery and early development but cannot commercialize everything independently Let's talk about the steps we took. let's talk about the steps we took First, we dramatically strengthened our balance sheet, allowing us to push multiple programs toward commercialization and potentially through multiple independent and partner launches. first we dramatically strengthened our balance sheet allowing us to push multiple programs toward commercialization and potentially through multiple independent and partner launches During the quarter, we completed the largest fundraising Arrowhead has ever conducted. during the quarter we completed the largest fundraising arrowhead has ever conducted We closed concurrent public offerings of $700 million of 0% coupon convertible senior notes and $230 million of common stock. Both offerings were several times oversubscribed, reflecting investor confidence in our portfolio and our ability to continue to build value. Second, and just this week, we announced an exclusive worldwide license agreement with Madrigal Pharmaceuticals for ARO-PNPLA3, Arrowhead's clinical-stage program designed to treat a genetically defined population of MASH patients. Under the terms of the agreement, Madrigal will pay a $25 million upfront payment to Arrowhead. Arrowhead is also eligible to receive development, regulatory, and sales milestone payments of up to $975 million. Arrowhead is further eligible to receive tiered royalties up to mid-teens. We closed concurrent public offerings of $700 million of 0% coupon convertible senior notes and $230 million of common stock. we closed concurrent public offerings of $700 million of 0% coupon convertible senior notes and $230 million of common stock Both offerings were several times oversubscribed, reflecting investor confidence in our portfolio and our ability to continue to build value. both offerings were several times oversubscribed reflecting investor confidence in our portfolio and our ability to continue to build value Second, and just this week, we announced an exclusive worldwide license agreement with Madrigal Pharmaceuticals for ARO-PNPLA3, Arrowhead's clinical-stage program designed to treat a genetically defined population of MASH patients. second and just this week we announced an exclusive worldwide license agreement with madrigal pharmaceuticals for aro-pnpla3 arrowhead's clinical-stage program designed to treat a genetically defined population of mash patients Under the terms of the agreement, Madrigal will pay a $25 million upfront payment to Arrowhead. under the terms of the agreement madrigal will pay a $25 million upfront payment to arrowhead Arrowhead is also eligible to receive development, regulatory, and sales milestone payments of up to $975 million. arrowhead is also eligible to receive development regulatory and sales milestone payments of up to $975 million Arrowhead is further eligible to receive tiered royalties up to mid-teens. arrowhead is further eligible to receive tiered royalties up to mid-teens Madrigal's leadership in the MASH space makes it a natural and attractive partner to advance ARO-PNPLA3 into phase II studies and toward potential commercialization. This transaction with Madrigal underscores Arrowhead's disciplined business development strategy, demonstrating our ability to partner high-potential, clinically validated programs with leading organizations. With that overview, I'd now like to turn the call over to Andy Davis. Andy? Madrigal's leadership in the MASH space makes it a natural and attractive partner to advance ARO-PNPLA3 into phase II studies and toward potential commercialization. madrigal's leadership in the mash space makes it a natural and attractive partner to advance aro-pnpla3 into phase ii studies and toward potential commercialization This transaction with Madrigal underscores Arrowhead's disciplined business development strategy, demonstrating our ability to partner high-potential, clinically validated programs with leading organizations. this transaction with madrigal underscores arrowhead's disciplined business development strategy demonstrating our ability to partner high-potential clinically validated programs with leading organizations With that overview, I'd now like to turn the call over to Andy Davis. with that overview i'd now like to turn the call over to andy davis Andy? andy

Speaker 3: Thank you, Chris. Good afternoon, everyone. It has now been approximately five and a half months since the FDA approval of REDEMPLO on November 18, 2025. We continue to be very pleased with the trajectory of the launch. Today, I would like to cover five areas: prescription and patient dynamics, payer coverage developments, pricing strategy, commercial infrastructure expansion, and our international and SHTG outlook. Let's start with prescription and patient dynamics. REDEMPLO's launch continues to build strong and consistent momentum. Through the fiscal second quarter, ending March 31, 2026, we have seen prescriptions accelerating week over week, growing nearly threefold from the start to the end of the quarter. That momentum has continued into the current quarter, with total prescriptions written exceeding 400, representing over 40% growth over just the last four weeks alone. The awareness and conviction driving this prescription growth are encouraging. Thank you, Chris. thank you chris Good afternoon, everyone. good afternoon everyone It has now been approximately five and a half months since the FDA approval of REDEMPLO on November 18, 2025. it has now been approximately five and a half months since the fda approval of redemplo on november 18 2025 We continue to be very pleased with the trajectory of the launch. we continue to be very pleased with the trajectory of the launch Today, I would like to cover five areas: prescription and patient dynamics, payer coverage developments, pricing strategy, commercial infrastructure expansion, and our international and SHTG outlook. today i would like to cover five areas prescription and patient dynamics payer coverage developments pricing strategy commercial infrastructure expansion and our international and shtg outlook Let's start with prescription and patient dynamics. let's start with prescription and patient dynamics REDEMPLO's launch continues to build strong and consistent momentum. redemplo's launch continues to build strong and consistent momentum Through the fiscal second quarter, ending March 31, 2026, we have seen prescriptions accelerating week over week, growing nearly threefold from the start to the end of the quarter. through the fiscal second quarter ending march 31 2026 we have seen prescriptions accelerating week over week growing nearly threefold from the start to the end of the quarter That momentum has continued into the current quarter, with total prescriptions written exceeding 400, representing over 40% growth over just the last four weeks alone. that momentum has continued into the current quarter with total prescriptions written exceeding 400 representing over 40% growth over just the last four weeks alone The awareness and conviction driving this prescription growth are encouraging. the awareness and conviction driving this prescription growth are encouraging REDEMPLO awareness among the prescribers who matter most has increased meaningfully. Critically, this awareness has translated into conviction. Nearly all REDEMPLO prescribers surveyed report being satisfied or highly satisfied with the product, and REDEMPLO is perceived strongest on the efficacy outcomes FCS patients care about most: triglyceride reduction and acute pancreatitis risk reduction. The patient mix continues to reflect what we expected. Approximately 85% of prescriptions are from patients naive to the ApoC-III class, a strong signal that physicians are identifying and treating FCS patients who have never had access to an effective therapy. Switch patients largely account for the remainder. Patient persistence data is equally encouraging. Refill activity is accelerating meaningfully, an important early validation of both clinical effectiveness and patient satisfaction for REDEMPLO's once quarterly dosing profile. Geographic distribution of prescribing is balanced across the country. REDEMPLO awareness among the prescribers who matter most has increased meaningfully. Critically, this awareness has translated into conviction. redemplo awareness among the prescribers who matter most has increased meaningfully. critically this awareness has translated into conviction Nearly all REDEMPLO prescribers surveyed report being satisfied or highly satisfied with the product, and REDEMPLO is perceived strongest on the efficacy outcomes FCS patients care about most: triglyceride reduction and acute pancreatitis risk reduction. nearly all redemplo prescribers surveyed report being satisfied or highly satisfied with the product and redemplo is perceived strongest on the efficacy outcomes fcs patients care about most triglyceride reduction and acute pancreatitis risk reduction The patient mix continues to reflect what we expected. the patient mix continues to reflect what we expected Approximately 85% of prescriptions are from patients naive to the ApoC-III class, a strong signal that physicians are identifying and treating FCS patients who have never had access to an effective therapy. approximately 85% of prescriptions are from patients naive to the apoc-iii class a strong signal that physicians are identifying and treating fcs patients who have never had access to an effective therapy Switch patients largely account for the remainder. switch patients largely account for the remainder Patient persistence data is equally encouraging. patient persistence data is equally encouraging Refill activity is accelerating meaningfully, an important early validation of both clinical effectiveness and patient satisfaction for REDEMPLO's once quarterly dosing profile. refill activity is accelerating meaningfully an important early validation of both clinical effectiveness and patient satisfaction for redemplo's once quarterly dosing profile Geographic distribution of prescribing is balanced across the country. geographic distribution of prescribing is balanced across the country This breadth of prescriber activation across all territories signals that patient identification capability is building at scale across the organization, not just concentrated in a handful of high-volume centers. This gives us confidence in the durability of the prescription growth trajectory. Turning to payer access. We are making meaningful and consistent progress. Our market access team has been actively engaged with the largest payers in the country, covering the vast majority of U.S. lives to support continued patient access. These discussions are proceeding as expected and in some cases have already led to REDEMPLO's improved coverage. Additional formulary coverage decisions are expected in the coming months across both commercial and government segments. A particularly important development in the payer landscape is the diagnostic pathway flexibility that major payers are recognizing. This breadth of prescriber activation across all territories signals that patient identification capability is building at scale across the organization, not just concentrated in a handful of high-volume centers. this breadth of prescriber activation across all territories signals that patient identification capability is building at scale across the organization not just concentrated in a handful of high-volume centers This gives us confidence in the durability of the prescription growth trajectory. this gives us confidence in the durability of the prescription growth trajectory Turning to payer access. turning to payer access We are making meaningful and consistent progress. we are making meaningful and consistent progress Our market access team has been actively engaged with the largest payers in the country, covering the vast majority of U.S. lives to support continued patient access. our market access team has been actively engaged with the largest payers in the country covering the vast majority of u.s lives to support continued patient access These discussions are proceeding as expected and in some cases have already led to REDEMPLO's improved coverage. these discussions are proceeding as expected and in some cases have already led to redemplo's improved coverage Additional formulary coverage decisions are expected in the coming months across both commercial and government segments. additional formulary coverage decisions are expected in the coming months across both commercial and government segments A particularly important development in the payer landscape is the diagnostic pathway flexibility that major payers are recognizing. a particularly important development in the payer landscape is the diagnostic pathway flexibility that major payers are recognizing The coverage policies taking shape across major payers reflect both genetic testing and clinical criteria as valid routes to diagnosis. This is critical for ensuring that all appropriate REDEMPLO patients can access treatment, because a meaningful proportion of real-world FCS patients are clinically diagnosed rather than genetically confirmed, and policies that require genetic confirmation as a prerequisite would create an unnecessary and inappropriate barrier. As Chris mentioned, we have made a proactive decision to reduce the list price of REDEMPLO to $45,000 per patient per year. This decision reflects our commitment to optimizing market access for FCS patients and is consistent with our belief that a competitive and rational price point accelerates formulary decisions and reduces friction in the prior authorization process. The coverage policies taking shape across major payers reflect both genetic testing and clinical criteria as valid routes to diagnosis. the coverage policies taking shape across major payers reflect both genetic testing and clinical criteria as valid routes to diagnosis This is critical for ensuring that all appropriate REDEMPLO patients can access treatment, because a meaningful proportion of real-world FCS patients are clinically diagnosed rather than genetically confirmed, and policies that require genetic confirmation as a prerequisite would create an unnecessary and inappropriate barrier. this is critical for ensuring that all appropriate redemplo patients can access treatment because a meaningful proportion of real-world fcs patients are clinically diagnosed rather than genetically confirmed and policies that require genetic confirmation as a prerequisite would create an unnecessary and inappropriate barrier As Chris mentioned, we have made a proactive decision to reduce the list price of REDEMPLO to $45,000 per patient per year. as chris mentioned we have made a proactive decision to reduce the list price of redemplo to $45,000 per patient per year This decision reflects our commitment to optimizing market access for FCS patients and is consistent with our belief that a competitive and rational price point accelerates formulary decisions and reduces friction in the prior authorization process. this decision reflects our commitment to optimizing market access for fcs patients and is consistent with our belief that a competitive and rational price point accelerates formulary decisions and reduces friction in the prior authorization process We have always believed that REDEMPLO's clinical profile is best in class, and the $45,000 per year price point reflects a premium value supported by the clinical evidence. With the FCS launch performing ahead of our expectations and with potential expansion into SHTG on the horizon, we are making deliberate and sequenced investments to scale our commercial infrastructure. I will speak more on this in the future, but the field infrastructure we are building will be sized and structured for both the current expanded FCS accessible population and also the future SHTG opportunity as it unfolds in the future. On international expansion, REDEMPLO received regulatory approval in both Canada and China in January and most recently in Australia last month. All three markets are currently in pre-launch phase as we work through the pricing and reimbursement frameworks in each country. We have always believed that REDEMPLO's clinical profile is best in class, and the $45,000 per year price point reflects a premium value supported by the clinical evidence. we have always believed that redemplo's clinical profile is best in class and the $45,000 per year price point reflects a premium value supported by the clinical evidence With the FCS launch performing ahead of our expectations and with potential expansion into SHTG on the horizon, we are making deliberate and sequenced investments to scale our commercial infrastructure. with the fcs launch performing ahead of our expectations and with potential expansion into shtg on the horizon we are making deliberate and sequenced investments to scale our commercial infrastructure I will speak more on this in the future, but the field infrastructure we are building will be sized and structured for both the current expanded FCS accessible population and also the future SHTG opportunity as it unfolds in the future. i will speak more on this in the future but the field infrastructure we are building will be sized and structured for both the current expanded fcs accessible population and also the future shtg opportunity as it unfolds in the future On international expansion, REDEMPLO received regulatory approval in both Canada and China in January and most recently in Australia last month. on international expansion redemplo received regulatory approval in both canada and china in january and most recently in australia last month All three markets are currently in pre-launch phase as we work through the pricing and reimbursement frameworks in each country. all three markets are currently in pre-launch phase as we work through the pricing and reimbursement frameworks in each country We look forward to providing updates on those timelines as they develop. Also last month, CHMP, the Committee for Medicinal Products for Human Use, recommended E.U. marketing authorization for REDEMPLO in Europe for FCS without requiring genetic confirmation. Consequently, we anticipate an EMA approval decision in the June to July timeframe. We intend to commercialize REDEMPLO directly in Europe, supported by contracted infrastructure which encompasses market access strategy, account management deployment, medical science liaison support, and broader stakeholder engagements, including medical congresses and patient advocacy group engagement. We believe this model is the right approach for Arrowhead and are pleased with the readiness of that team as we approach the anticipated EMA decision. Finally, I want to comment on the SHTG program, which represents the most significant near-term value catalyst for the cardiometabolic franchise. We are approaching what we expect to be a highly meaningful series of milestones. We look forward to providing updates on those timelines as they develop. we look forward to providing updates on those timelines as they develop Also last month, CHMP, the Committee for Medicinal Products for Human Use, recommended E.U. marketing authorization for REDEMPLO in Europe for FCS without requiring genetic confirmation. also last month chmp the committee for medicinal products for human use recommended e.u marketing authorization for redemplo in europe for fcs without requiring genetic confirmation Consequently, we anticipate an EMA approval decision in the June to July timeframe. consequently we anticipate an ema approval decision in the june to july timeframe We intend to commercialize REDEMPLO directly in Europe, supported by contracted infrastructure which encompasses market access strategy, account management deployment, medical science liaison support, and broader stakeholder engagements, including medical congresses and patient advocacy group engagement. we intend to commercialize redemplo directly in europe supported by contracted infrastructure which encompasses market access strategy account management deployment medical science liaison support and broader stakeholder engagements including medical congresses and patient advocacy group engagement We believe this model is the right approach for Arrowhead and are pleased with the readiness of that team as we approach the anticipated EMA decision. we believe this model is the right approach for arrowhead and are pleased with the readiness of that team as we approach the anticipated ema decision Finally, I want to comment on the SHTG program, which represents the most significant near-term value catalyst for the cardiometabolic franchise. finally i want to comment on the shtg program which represents the most significant near-term value catalyst for the cardiometabolic franchise We are approaching what we expect to be a highly meaningful series of milestones. we are approaching what we expect to be a highly meaningful series of milestones Top-line results from SHASTA-3 and SHASTA-4, our two registrational phase III studies in severe hypertriglyceridemia, are expected in Q3. We head into the data readout with confidence grounded in the strength of REDEMPLO's established mechanism of action and the consistency of the ApoC-III biology we have observed across our full clinical program to date. We intend to present the data at a major medical congress, which we hope will be with a simultaneous publication in a top-tier medical journal. We expect to file an sNDA with the FDA before the end of 2026, with an anticipated regulatory approval based on an expected standard review timeline targeted in second half of 2027. Additional regulatory filings in other jurisdictions are planned to follow thereafter. Top-line results from SHASTA-3 and SHASTA-4, our two registrational phase III studies in severe hypertriglyceridemia, are expected in Q3. top-line results from shasta-3 and shasta-4 our two registrational phase iii studies in severe hypertriglyceridemia are expected in q3 We head into the data readout with confidence grounded in the strength of REDEMPLO's established mechanism of action and the consistency of the ApoC-III biology we have observed across our full clinical program to date. we head into the data readout with confidence grounded in the strength of redemplo's established mechanism of action and the consistency of the apoc-iii biology we have observed across our full clinical program to date We intend to present the data at a major medical congress, which we hope will be with a simultaneous publication in a top-tier medical journal. we intend to present the data at a major medical congress which we hope will be with a simultaneous publication in a top-tier medical journal We expect to file an sNDA with the FDA before the end of 2026, with an anticipated regulatory approval based on an expected standard review timeline targeted in second half of 2027. we expect to file an snda with the fda before the end of 2026 with an anticipated regulatory approval based on an expected standard review timeline targeted in second half of 2027 Additional regulatory filings in other jurisdictions are planned to follow thereafter. additional regulatory filings in other jurisdictions are planned to follow thereafter The SHTG opportunity represents a patient population that is substantially larger than FCS, with over 1 million high-risk patients in the United States alone. The commercial infrastructure investments we are making for FCS today are also designed with that launch in mind. In summary, the REDEMPLO launch is progressing well and continues to exceed our expectations across prescription volume, patient dynamics, and payer access. Physician satisfaction and forward prescribing intents are both extremely strong. Refill activity is accelerating, and we have a series of highly anticipated milestones in the second half of 2026 that we believe will be transformative for the cardiometabolic franchise and for Arrowhead. With that, I'll turn the call over to James Hamilton to discuss the broader R&D portfolio. The SHTG opportunity represents a patient population that is substantially larger than FCS, with over 1 million high-risk patients in the United States alone. the shtg opportunity represents a patient population that is substantially larger than fcs with over 1 million high-risk patients in the united states alone The commercial infrastructure investments we are making for FCS today are also designed with that launch in mind. the commercial infrastructure investments we are making for fcs today are also designed with that launch in mind In summary, the REDEMPLO launch is progressing well and continues to exceed our expectations across prescription volume, patient dynamics, and payer access. in summary the redemplo launch is progressing well and continues to exceed our expectations across prescription volume patient dynamics and payer access Physician satisfaction and forward prescribing intents are both extremely strong. physician satisfaction and forward prescribing intents are both extremely strong Refill activity is accelerating, and we have a series of highly anticipated milestones in the second half of 2026 that we believe will be transformative for the cardiometabolic franchise and for Arrowhead. refill activity is accelerating and we have a series of highly anticipated milestones in the second half of 2026 that we believe will be transformative for the cardiometabolic franchise and for arrowhead With that, I'll turn the call over to James Hamilton to discuss the broader R&D portfolio. with that i'll turn the call over to james hamilton to discuss the broader r&d portfolio

Speaker 7: Thank you, Andy. As Chris mentioned, we have a very broad pipeline with over 20 clinical programs, so I will focus on areas with upcoming readouts. Thank you, Andy. thank you andy As Chris mentioned, we have a very broad pipeline with over 20 clinical programs, so I will focus on areas with upcoming readouts. as chris mentioned we have a very broad pipeline with over 20 clinical programs so i will focus on areas with upcoming readouts First, I'd like to announce that we are planning to host three webcasts over the coming months as part of our R&D Webinar Summer Series. Each webcast will cover a specific aspect of our pipeline where we expect to have upcoming data readouts this year. These include cardiometabolic, including plozasiran, zodasiran, and ARO-DIMER-PA, obesity, including ARO-INHBE and ARO-ALK7, and ARO-MAPT, including the blood-brain barrier or BBB platform. I'll now give status updates from the quarter on these specific areas. First, let's review the suite of plozasiran phase III studies, SHASTA-3, SHASTA-4, SHASTA-5, and MUIR-3, designed to support supplemental NDA filings to expand the REDEMPLO label beyond genetic and clinical FCS into patients with SHTG. First, I'd like to announce that we are planning to host three webcasts over the coming months as part of our R&D Webinar Summer Series. first i'd like to announce that we are planning to host three webcasts over the coming months as part of our r&d webinar summer series Each webcast will cover a specific aspect of our pipeline where we expect to have upcoming data readouts this year. each webcast will cover a specific aspect of our pipeline where we expect to have upcoming data readouts this year These include cardiometabolic, including plozasiran, zodasiran, and ARO-DIMER-PA, obesity, including ARO-INHBE and ARO-ALK7, and ARO-MAPT, including the blood-brain barrier or BBB platform. these include cardiometabolic including plozasiran zodasiran and aro-dimer-pa obesity including aro-inhbe and aro-alk7 and aro-mapt including the blood-brain barrier or bbb platform I'll now give status updates from the quarter on these specific areas. i'll now give status updates from the quarter on these specific areas First, let's review the suite of plozasiran phase III studies, SHASTA-3, SHASTA-4, SHASTA-5, and MUIR-3, designed to support supplemental NDA filings to expand the REDEMPLO label beyond genetic and clinical FCS into patients with SHTG. first let's review the suite of plozasiran phase iii studies shasta-3 shasta-4 shasta-5 and muir-3 designed to support supplemental nda filings to expand the redemplo label beyond genetic and clinical fcs into patients with shtg SHASTA-3 and SHASTA-4 together enrolled over 750 patients and have a primary endpoint of change in triglycerides from baseline with key secondary endpoints of acute pancreatitis rates. MUIR-3, which enrolled over 1,400 patients, is designed to supplement the SHASTA studies with additional patient safety data. We are also enrolling patients at high risk of acute pancreatitis into SHASTA-5 to directly assess the ability of plozasiran to reduce the risk of acute pancreatitis as the primary endpoint. Should SHASTA-3 and SHASTA-4 show a statistically significant improvement in acute pancreatitis risk, we will reassess whether there is added value in continuing SHASTA-5. We remain on schedule to complete the blinded portion of the SHASTA-3, SHASTA-4, and MUIR-3 in mid 2026 to support a planned top-line data readout in the third quarter. SHASTA-3 and SHASTA-4 together enrolled over 750 patients and have a primary endpoint of change in triglycerides from baseline with key secondary endpoints of acute pancreatitis rates. shasta-3 and shasta-4 together enrolled over 750 patients and have a primary endpoint of change in triglycerides from baseline with key secondary endpoints of acute pancreatitis rates MUIR-3, which enrolled over 1,400 patients, is designed to supplement the SHASTA studies with additional patient safety data. muir-3 which enrolled over 1,400 patients is designed to supplement the shasta studies with additional patient safety data We are also enrolling patients at high risk of acute pancreatitis into SHASTA-5 to directly assess the ability of plozasiran to reduce the risk of acute pancreatitis as the primary endpoint. we are also enrolling patients at high risk of acute pancreatitis into shasta-5 to directly assess the ability of plozasiran to reduce the risk of acute pancreatitis as the primary endpoint Should SHASTA-3 and SHASTA-4 show a statistically significant improvement in acute pancreatitis risk, we will reassess whether there is added value in continuing SHASTA-5. should shasta-3 and shasta-4 show a statistically significant improvement in acute pancreatitis risk we will reassess whether there is added value in continuing shasta-5 We remain on schedule to complete the blinded portion of the SHASTA-3, SHASTA-4, and MUIR-3 in mid 2026 to support a planned top-line data readout in the third quarter. we remain on schedule to complete the blinded portion of the shasta-3 shasta-4 and muir-3 in mid 2026 to support a planned top-line data readout in the third quarter This would further support our plans for an sNDA submission for SHTG before the end of this year. Before moving on to zodasiran, I'd like to highlight a presentation we made with new long-term efficacy and safety data for plozasiran across a spectrum of patients with hypertriglyceridemia at the American College Cardiology Conference in March. The data were from a two-year open-label extension of the two phase IIb double-blind placebo-controlled studies of plozasiran, SHASTA-2 conducted in adults with severe hypertriglyceridemia, and MUIR, which enrolled patients with hypertriglyceridemia. During the two-year open-label extension, patients saw median reductions in their triglycerides of 83% in SHTG patients from SHASTA-2 and 67% in HTG patients from MUIR, with additional reductions in remnant and non-HDL cholesterol. This would further support our plans for an sNDA submission for SHTG before the end of this year. this would further support our plans for an snda submission for shtg before the end of this year Before moving on to zodasiran, I'd like to highlight a presentation we made with new long-term efficacy and safety data for plozasiran across a spectrum of patients with hypertriglyceridemia at the American College Cardiology Conference in March. before moving on to zodasiran i'd like to highlight a presentation we made with new long-term efficacy and safety data for plozasiran across a spectrum of patients with hypertriglyceridemia at the american college cardiology conference in march The data were from a two-year open-label extension of the two phase IIb double-blind placebo-controlled studies of plozasiran, SHASTA-2 conducted in adults with severe hypertriglyceridemia, and MUIR, which enrolled patients with hypertriglyceridemia. the data were from a two-year open-label extension of the two phase iib double-blind placebo-controlled studies of plozasiran shasta-2 conducted in adults with severe hypertriglyceridemia and muir which enrolled patients with hypertriglyceridemia During the two-year open-label extension, patients saw median reductions in their triglycerides of 83% in SHTG patients from SHASTA-2 and 67% in HTG patients from MUIR, with additional reductions in remnant and non-HDL cholesterol. during the two-year open-label extension patients saw median reductions in their triglycerides of 83% in shtg patients from shasta-2 and 67% in htg patients from muir with additional reductions in remnant and non-hdl cholesterol 96% of SHTG patients achieved TGs below 500 milligrams per deciliter, and 63% achieved TGs below 150 mg per deciliter, with 93% of HTG patients achieving TGs below 150 mg per deciliter. Importantly, no adjudicated acute pancreatitis events occurred in any patient receiving plozasiran during the two-year phase IIb open-label extension study. These findings support the potential of plozasiran as a promising new approach to managing patients with moderate to severe HTG phenotypes who are at risk of AP and potentially other cardiometabolic comorbidities. I'd now like to give a quick update on the YOSEMITE phase III study of zodasiran, which is being developed as a potential treatment for homozygous familial hypercholesterolemia, or HoFH, a rare genetic condition that leads to severely elevated LDL cholesterol and early-onset cardiovascular disease. 96% of SHTG patients achieved TGs below 500 milligrams per deciliter, and 63% achieved TGs below 150 mg per deciliter, with 93% of HTG patients achieving TGs below 150 mg per deciliter. 96% of shtg patients achieved tgs below 500 milligrams per deciliter and 63% achieved tgs below 150 mg per deciliter with 93% of htg patients achieving tgs below 150 mg per deciliter Importantly, no adjudicated acute pancreatitis events occurred in any patient receiving plozasiran during the two-year phase IIb open-label extension study. importantly no adjudicated acute pancreatitis events occurred in any patient receiving plozasiran during the two-year phase iib open-label extension study These findings support the potential of plozasiran as a promising new approach to managing patients with moderate to severe HTG phenotypes who are at risk of AP and potentially other cardiometabolic comorbidities. these findings support the potential of plozasiran as a promising new approach to managing patients with moderate to severe htg phenotypes who are at risk of ap and potentially other cardiometabolic comorbidities I'd now like to give a quick update on the YOSEMITE phase III study of zodasiran, which is being developed as a potential treatment for homozygous familial hypercholesterolemia, or HoFH, a rare genetic condition that leads to severely elevated LDL cholesterol and early-onset cardiovascular disease. i'd now like to give a quick update on the yosemite phase iii study of zodasiran which is being developed as a potential treatment for homozygous familial hypercholesterolemia or hofh a rare genetic condition that leads to severely elevated ldl cholesterol and early-onset cardiovascular disease zodasiran is the fourth investigational RNAi-based candidate developed by Arrowhead to reach late-stage clinical studies. YOSEMITE is designed to enroll approximately 60 individuals with HoFH over the age of 12 who will be randomized 2/1 to receive five doses of 200 mg zodasiran or placebo. The primary endpoint is the % change from baseline to month 12 in fasting LDL cholesterol. Enrollment has been on track, and we are confident that the study can be fully enrolled this year to enable study completion and potential NDA filings before the end of 2027. The last program within cardiometabolic is ARO-DIMER-PA, the first dual-functional siRNA designed to silence the expression of two genes with a single RNAi molecule. ARO-DIMER-PA is being developed as a potential treatment for ASCVD due to mixed hyperlipidemia by silencing expression of both PCSK9 and ApoC-III. zodasiran is the fourth investigational RNAi-based candidate developed by Arrowhead to reach late-stage clinical studies. zodasiran is the fourth investigational rnai-based candidate developed by arrowhead to reach late-stage clinical studies YOSEMITE is designed to enroll approximately 60 individuals with HoFH over the age of 12 who will be randomized 2/ 1 to receive five doses of 200 mg zodasiran or placebo. yosemite is designed to enroll approximately 60 individuals with hofh over the age of 12 who will be randomized 2/ 1 to receive five doses of 200 mg zodasiran or placebo The primary endpoint is the % change from baseline to month 12 in fasting LDL cholesterol. the primary endpoint is the % change from baseline to month 12 in fasting ldl cholesterol Enrollment has been on track, and we are confident that the study can be fully enrolled this year to enable study completion and potential NDA filings before the end of 2027. enrollment has been on track and we are confident that the study can be fully enrolled this year to enable study completion and potential nda filings before the end of 2027 The last program within cardiometabolic is ARO-DIMER-PA, the first dual-functional siRNA designed to silence the expression of two genes with a single RNAi molecule. the last program within cardiometabolic is aro-dimer-pa the first dual-functional sirna designed to silence the expression of two genes with a single rnai molecule ARO-DIMER-PA is being developed as a potential treatment for ASCVD due to mixed hyperlipidemia by silencing expression of both PCSK9 and ApoC-III. aro-dimer-pa is being developed as a potential treatment for ascvd due to mixed hyperlipidemia by silencing expression of both pcsk9 and apoc-iii In January, we initiated a phase I-IIa placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and effects on LDL cholesterol and triglycerides using single-dose ARO-DIMER-PA in Part I and multiple doses in Part II in up to 78 adults with mixed hyperlipidemia. Enrollment in the study has been rapid. We are on schedule to have sufficient data to provide the first clinical readout in Q3 of this year. This is a very interesting program, and we think the preclinical data has been highly compelling. We have some innovative ideas on late-stage trial designs that potentially accelerate the path to regulatory approval. We're eager to have a first clinical readout to start moving ahead with later studies if supported by initial data. In January, we initiated a phase I-IIa placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and effects on LDL cholesterol and triglycerides using single-dose ARO-DIMER-PA in Part I and multiple doses in Part II in up to 78 adults with mixed hyperlipidemia. in january we initiated a phase i-iia placebo-controlled dose-escalating study to evaluate the safety tolerability pharmacokinetics pharmacodynamics and effects on ldl cholesterol and triglycerides using single-dose aro-dimer-pa in part i and multiple doses in part ii in up to 78 adults with mixed hyperlipidemia Enrollment in the study has been rapid. enrollment in the study has been rapid We are on schedule to have sufficient data to provide the first clinical readout in Q3 of this year. we are on schedule to have sufficient data to provide the first clinical readout in q3 of this year This is a very interesting program, and we think the preclinical data has been highly compelling. this is a very interesting program and we think the preclinical data has been highly compelling We have some innovative ideas on late-stage trial designs that potentially accelerate the path to regulatory approval. we have some innovative ideas on late-stage trial designs that potentially accelerate the path to regulatory approval We're eager to have a first clinical readout to start moving ahead with later studies if supported by initial data. we're eager to have a first clinical readout to start moving ahead with later studies if supported by initial data Lastly, I'd like to give an update on the status of the ARO-MAPT first-in-human study. ARO-MAPT is being developed as a potential treatment for tauopathies, including Alzheimer's disease, progressive neurodegenerative disease characterized by cognitive and functional decline. Alzheimer's disease is the most common cause of dementia, affecting an estimated 32 million people worldwide, and is part of a group of neurodegenerative diseases called tauopathies that are marked by abnormal tau accumulation and formation of tau tangles in neurons. Tau-related pathology may be a critical driver of neurodegeneration. Targeting tau is a promising strategy to potentially slow or stop cognitive and functional decline. ARO-MAPT is Arrowhead's first investigational RNAi-based therapy to achieve a new proprietary delivery system, which in preclinical studies has achieved blood-brain barrier penetration and deep knockdown of target genes across the central nervous system, including deep brain regions after subcutaneous injection. Lastly, I'd like to give an update on the status of the ARO-MAPT first-in-human study. ARO-MAPT is being developed as a potential treatment for tauopathies, including Alzheimer's disease, progressive neurodegenerative disease characterized by cognitive and functional decline. lastly i'd like to give an update on the status of the aro-mapt first-in-human study. aro-mapt is being developed as a potential treatment for tauopathies including alzheimer's disease progressive neurodegenerative disease characterized by cognitive and functional decline Alzheimer's disease is the most common cause of dementia, affecting an estimated 32 million people worldwide, and is part of a group of neurodegenerative diseases called tauopathies that are marked by abnormal tau accumulation and formation of tau tangles in neurons. alzheimer's disease is the most common cause of dementia affecting an estimated 32 million people worldwide and is part of a group of neurodegenerative diseases called tauopathies that are marked by abnormal tau accumulation and formation of tau tangles in neurons Tau-related pathology may be a critical driver of neurodegeneration. tau-related pathology may be a critical driver of neurodegeneration Targeting tau is a promising strategy to potentially slow or stop cognitive and functional decline. targeting tau is a promising strategy to potentially slow or stop cognitive and functional decline ARO-MAPT is Arrowhead's first investigational RNAi-based therapy to achieve a new proprietary delivery system, which in preclinical studies has achieved blood-brain barrier penetration and deep knockdown of target genes across the central nervous system, including deep brain regions after subcutaneous injection. aro-mapt is arrowhead's first investigational rnai-based therapy to achieve a new proprietary delivery system which in preclinical studies has achieved blood-brain barrier penetration and deep knockdown of target genes across the central nervous system including deep brain regions after subcutaneous injection This underscores Arrowhead's leadership in the delivery of siRNA to multiple tissues and cell types throughout the body, utilizing our proprietary and differentiated Targeted RNAi Molecule or TRiM platform. In December 2025, we dosed the first subjects in a phase I/II clinical trial of ARO-MAPT. This study is a placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-MAPT in up to 64 healthy subjects and up to 48 patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia. In part 1a of the study, healthy subjects will receive one or three weekly doses of ARO-MAPT or placebo by subcutaneous injection. In parts 1b and part two, healthy volunteers and Alzheimer's disease patients, respectively, will receive multiple escalating doses of ARO-MAPT or placebo. This underscores Arrowhead's leadership in the delivery of siRNA to multiple tissues and cell types throughout the body, utilizing our proprietary and differentiated Targeted RNAi Molecule or TRiM platform. this underscores arrowhead's leadership in the delivery of sirna to multiple tissues and cell types throughout the body utilizing our proprietary and differentiated targeted rnai molecule or trim platform In December 2025, we dosed the first subjects in a phase I/II clinical trial of ARO-MAPT. in december 2025 we dosed the first subjects in a phase i/ii clinical trial of aro-mapt This study is a placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-MAPT in up to 64 healthy subjects and up to 48 patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia. this study is a placebo-controlled dose-escalating study to evaluate the safety tolerability pharmacokinetics and pharmacodynamics of aro-mapt in up to 64 healthy subjects and up to 48 patients with mild cognitive impairment due to alzheimer's disease and mild alzheimer's disease dementia In part 1a of the study, healthy subjects will receive one or three weekly doses of ARO-MAPT or placebo by subcutaneous injection. in part 1a of the study healthy subjects will receive one or three weekly doses of aro-mapt or placebo by subcutaneous injection In parts 1b and part two, healthy volunteers and Alzheimer's disease patients, respectively, will receive multiple escalating doses of ARO-MAPT or placebo. in parts 1b and part two healthy volunteers and alzheimer's disease patients respectively will receive multiple escalating doses of aro-mapt or placebo We are nearing completion of enrollment of the single-dose portion of the study in healthy volunteers and have begun enrollment in the multi-dose cohorts in both healthy volunteers and patients with Alzheimer's disease. This keeps us on pace for an initial data readout at the end of Q3 or early Q4. I will now turn the call over to Daniel Apel. We are nearing completion of enrollment of the single-dose portion of the study in healthy volunteers and have begun enrollment in the multi-dose cohorts in both healthy volunteers and patients with Alzheimer's disease. we are nearing completion of enrollment of the single-dose portion of the study in healthy volunteers and have begun enrollment in the multi-dose cohorts in both healthy volunteers and patients with alzheimer's disease This keeps us on pace for an initial data readout at the end of Q3 or early Q4. this keeps us on pace for an initial data readout at the end of q3 or early q4 I will now turn the call over to Daniel Apel. i will now turn the call over to daniel apel

Speaker 5: Thank you, James, good afternoon, everyone. As we reported today, net loss for the quarter ended March 31, 2026 was $132.7 million, or a loss of $0.93 per share based on 142.4 million fully diluted weighted average shares outstanding. This compares to net income of $370.4 million, or $2.75 per share for the quarter ended March 31, 2025 based on 134.5 million fully diluted weighted average shares outstanding in that quarter. Recall that in the prior year quarter, we recorded over $540 million in revenue solely related to the Sarepta transaction that was executed at that time. Thank you, James, good afternoon, everyone. thank you james good afternoon everyone As we reported today, net loss for the quarter ended March 31, 2026 was $132.7 million, or a loss of $0.93 per share based on 142.4 million fully diluted weighted average shares outstanding. as we reported today net loss for the quarter ended march 31 2026 was $132.7 million or a loss of $0.93 per share based on 142.4 million fully diluted weighted average shares outstanding This compares to net income of $370.4 million, or $2.75 per share for the quarter ended March 31, 2025 based on 134.5 million fully diluted weighted average shares outstanding in that quarter. this compares to net income of $370.4 million or $2.75 per share for the quarter ended march 31 2025 based on 134.5 million fully diluted weighted average shares outstanding in that quarter Recall that in the prior year quarter, we recorded over $540 million in revenue solely related to the Sarepta transaction that was executed at that time. recall that in the prior year quarter we recorded over $540 million in revenue solely related to the sarepta transaction that was executed at that time Revenue for this quarter totaled $74 million, driven primarily by our licensed and collaboration agreements with Sarepta and with Novartis. Of this amount, approximately $42 million related to the Sarepta collaboration. This includes $28 million from ongoing recognition of the initial Sarepta consideration, $10 million related to reimbursement of incurred preclinical collaboration program costs, and $4 million for our clinical supply provided to them under a clinical supply agreement. In addition, we recognized $20 million of the $200 million upfront payment received from Novartis in October, bringing year-to-date recognition of Novartis upfront to $54 million, with the remaining $146 million to be deferred over time as we fulfill our preclinical obligations. We also recorded $11 million related to the asset purchase agreement between Sanofi and Visirna Therapeutics to develop and commercialize investigational plozasiran in Greater China. Revenue for this quarter totaled $74 million, driven primarily by our licensed and collaboration agreements with Sarepta and with Novartis. revenue for this quarter totaled $74 million driven primarily by our licensed and collaboration agreements with sarepta and with novartis Of this amount, approximately $42 million related to the Sarepta collaboration. of this amount approximately $42 million related to the sarepta collaboration This includes $28 million from ongoing recognition of the initial Sarepta consideration, $10 million related to reimbursement of incurred preclinical collaboration program costs, and $4 million for our clinical supply provided to them under a clinical supply agreement. this includes $28 million from ongoing recognition of the initial sarepta consideration $10 million related to reimbursement of incurred preclinical collaboration program costs and $4 million for our clinical supply provided to them under a clinical supply agreement In addition, we recognized $20 million of the $200 million upfront payment received from Novartis in October, bringing year-to-date recognition of Novartis upfront to $54 million, with the remaining $146 million to be deferred over time as we fulfill our preclinical obligations. in addition we recognized $20 million of the $200 million upfront payment received from novartis in october bringing year-to-date recognition of novartis upfront to $54 million with the remaining $146 million to be deferred over time as we fulfill our preclinical obligations We also recorded $11 million related to the asset purchase agreement between Sanofi and Visirna Therapeutics to develop and commercialize investigational plozasiran in Greater China. we also recorded $11 million related to the asset purchase agreement between sanofi and visirna therapeutics to develop and commercialize investigational plozasiran in greater china Visirna, as you know, is our majority-owned subsidiary with operations in China, and the amount recognized is almost entirely due to the January approval of FCS in that region by the Chinese National Medical Products Administration. As mentioned previously, we are not intending to headline specific REDEMPLO product sales numbers until such time as they become a meaningful driver to our financials. That said, net sales can be derived from our disclosures as the difference between total net revenue and collaboration revenue and represents approximately $1 million for the quarter. This is our first full quarter of REDEMPLO sales, and on a unit basis, that figure compares favorably to the first full commercial quarter of the other approved ApoC-III inhibitor. Turning now to expenses, total operating expenses for the quarter were approximately $215 million, roughly flat with operating expenses in the first fiscal quarter. Visirna, as you know, is our majority-owned subsidiary with operations in China, and the amount recognized is almost entirely due to the January approval of FCS in that region by the Chinese National Medical Products Administration. visirna as you know is our majority-owned subsidiary with operations in china and the amount recognized is almost entirely due to the january approval of fcs in that region by the chinese national medical products administration As mentioned previously, we are not intending to headline specific REDEMPLO product sales numbers until such time as they become a meaningful driver to our financials. as mentioned previously we are not intending to headline specific redemplo product sales numbers until such time as they become a meaningful driver to our financials That said, net sales can be derived from our disclosures as the difference between total net revenue and collaboration revenue and represents approximately $1 million for the quarter. that said net sales can be derived from our disclosures as the difference between total net revenue and collaboration revenue and represents approximately $1 million for the quarter This is our first full quarter of REDEMPLO sales, and on a unit basis, that figure compares favorably to the first full commercial quarter of the other approved ApoC-III inhibitor. this is our first full quarter of redemplo sales and on a unit basis that figure compares favorably to the first full commercial quarter of the other approved apoc-iii inhibitor Turning now to expenses, total operating expenses for the quarter were approximately $215 million, roughly flat with operating expenses in the first fiscal quarter. turning now to expenses total operating expenses for the quarter were approximately $215 million roughly flat with operating expenses in the first fiscal quarter This compares to $162 million in the prior year quarter, representing an increase of $53 million year-over-year. This increase was driven by $40 million of higher R&D expenses and $13 million of higher SG&A expenses, fully in line with our expectations. The increase in R&D expense was primarily attributable to ongoing progression of our phase III registrational studies for plozasiran and SHTG, as well as our early-stage pipeline programs, including the DIMER and MAPT. Fiscal year-to-date, almost 2/3 of the clinical trial spend can be attributed to our plozasiran phase III studies. As James already mentioned, the registrational SHTG studies for plozasiran should read out in the summer, clinical trial spend for these programs should thereafter moderate accordingly. This compares to $162 million in the prior year quarter, representing an increase of $53 million year-over-year. this compares to $162 million in the prior year quarter representing an increase of $53 million year-over-year This increase was driven by $40 million of higher R&D expenses and $13 million of higher SG&A expenses, fully in line with our expectations. this increase was driven by $40 million of higher r&d expenses and $13 million of higher sg&a expenses fully in line with our expectations The increase in R&D expense was primarily attributable to ongoing progression of our phase III registrational studies for plozasiran and SHTG, as well as our early-stage pipeline programs, including the DIMER and MAPT. the increase in r&d expense was primarily attributable to ongoing progression of our phase iii registrational studies for plozasiran and shtg as well as our early-stage pipeline programs including the dimer and mapt Fiscal year-to-date, almost 2/3 of the clinical trial spend can be attributed to our plozasiran phase III studies. As James already mentioned, the registrational SHTG studies for plozasiran should read out in the summer, clinical trial spend for these programs should thereafter moderate accordingly. fiscal year-to-date almost 2/3 of the clinical trial spend can be attributed to our plozasiran phase iii studies. as james already mentioned the registrational shtg studies for plozasiran should read out in the summer clinical trial spend for these programs should thereafter moderate accordingly SG&A expenses increased year-over-year compared to the prior year's second fiscal quarter, driven primarily by ongoing investments to support the commercialization of REDEMPLO. As previously discussed, we are continuing to build our commercial capabilities to fully support the FCS launch. We continue to leverage and invest in these capabilities to support REDEMPLO and FCS while also positioning the organization to support a potential future launch in SHTG. We ultimately expect to leverage these same capabilities for the advancement of zodasiran for the treatment of HoFH. Turning to the balance sheet, cash and investments on hand totaled nearly $1.8 billion as of March 31, 2026. Common shares outstanding at quarter end were 140.69. SG&A expenses increased year-over-year compared to the prior year's second fiscal quarter, driven primarily by ongoing investments to support the commercialization of REDEMPLO. sg&a expenses increased year-over-year compared to the prior year's second fiscal quarter driven primarily by ongoing investments to support the commercialization of redemplo As previously discussed, we are continuing to build our commercial capabilities to fully support the FCS launch. as previously discussed we are continuing to build our commercial capabilities to fully support the fcs launch We continue to leverage and invest in these capabilities to support REDEMPLO and FCS while also positioning the organization to support a potential future launch in SHTG. we continue to leverage and invest in these capabilities to support redemplo and fcs while also positioning the organization to support a potential future launch in shtg We ultimately expect to leverage these same capabilities for the advancement of zodasiran for the treatment of HoFH. we ultimately expect to leverage these same capabilities for the advancement of zodasiran for the treatment of hofh Turning to the balance sheet, cash and investments on hand totaled nearly $1.8 billion as of March 31, 2026. turning to the balance sheet cash and investments on hand totaled nearly $1.8 billion as of march 31 2026 Common shares outstanding at quarter end were 140.69. common shares outstanding at quarter end were 140.69 To provide a little color, in this quarter alone, we brought in over $1 billion, including approximately $850 million net from our January financing transactions, inclusive of a concurrent offering of 0% convertible senior notes and common stock, along with the associated capped call transaction. Other notable inflows in the quarter include the $200 million received from Sarepta upon achieving the second DM1 program milestone, as well as a $50 million Anniversary payment under the Sarepta long-term collaboration agreement. All of this is very much in line with the information provided previously during our February earnings call. We believe our strong balance sheet provides us with significant financial flexibility to support ongoing clinical development, to advance current and future commercialization activities, and to execute against our long-term strategic priorities. With that brief overview, I will now turn the call back to Chris. To provide a little color, in this quarter alone, we brought in over $1 billion, including approximately $850 million net from our January financing transactions, inclusive of a concurrent offering of 0% convertible senior notes and common stock, along with the associated capped call transaction. to provide a little color in this quarter alone we brought in over $1 billion including approximately $850 million net from our january financing transactions inclusive of a concurrent offering of 0% convertible senior notes and common stock along with the associated capped call transaction Other notable inflows in the quarter include the $200 million received from Sarepta upon achieving the second DM1 program milestone, as well as a $50 million Anniversary payment under the Sarepta long-term collaboration agreement. other notable inflows in the quarter include the $200 million received from sarepta upon achieving the second dm1 program milestone as well as a $50 million anniversary payment under the sarepta long-term collaboration agreement All of this is very much in line with the information provided previously during our February earnings call. all of this is very much in line with the information provided previously during our february earnings call We believe our strong balance sheet provides us with significant financial flexibility to support ongoing clinical development, to advance current and future commercialization activities, and to execute against our long-term strategic priorities. we believe our strong balance sheet provides us with significant financial flexibility to support ongoing clinical development to advance current and future commercialization activities and to execute against our long-term strategic priorities With that brief overview, I will now turn the call back to Chris. with that brief overview i will now turn the call back to chris

Speaker 4: Thanks, Dan. As we build out our commercial team and focus on efficiently bringing REDEMPLO to the patients who need it, we have not lost sight on continuing to expand our pipeline and ultimately increasing the number of medicines we can offer to a wide variety of patients. Our business has become more complex as we grow in all these areas, we continue to innovate and execute well. We see multiple key potential value-creating events in the second half of 2026 that together speak to our priorities. Here are just a few of the events we are tracking. SHASTA-3, SHASTA-4, and MUIR-3, which is a suite of phase III clinical studies designed to support an sNDA for REDEMPLO in patients with SHTG, is on schedule for completion and top-line readout in Q3. Thanks, Dan. thanks dan As we build out our commercial team and focus on efficiently bringing REDEMPLO to the patients who need it, we have not lost sight on continuing to expand our pipeline and ultimately increasing the number of medicines we can offer to a wide variety of patients. as we build out our commercial team and focus on efficiently bringing redemplo to the patients who need it we have not lost sight on continuing to expand our pipeline and ultimately increasing the number of medicines we can offer to a wide variety of patients Our business has become more complex as we grow in all these areas, we continue to innovate and execute well. our business has become more complex as we grow in all these areas we continue to innovate and execute well We see multiple key potential value-creating events in the second half of 2026 that together speak to our priorities. we see multiple key potential value-creating events in the second half of 2026 that together speak to our priorities Here are just a few of the events we are tracking. here are just a few of the events we are tracking SHASTA-3, SHASTA-4, and MUIR-3, which is a suite of phase III clinical studies designed to support an sNDA for REDEMPLO in patients with SHTG, is on schedule for completion and top-line readout in Q3. shasta-3 shasta-4 and muir-3 which is a suite of phase iii clinical studies designed to support an snda for redemplo in patients with shtg is on schedule for completion and top-line readout in q3 The first clinical readout of ARO-DIMER-PA targeting both PCSK9 and ApoC-III for LDL and TG lowering is also expected in Q3. The first clinical readout for ARO-MAPT is expected around the end of Q3 or early Q4. This is being developed as a potential treatment for tauopathies, including Alzheimer's disease, and is our first program using the CNS delivery platform design to cross the blood-brain barrier after systemic delivery via subcutaneous administration. Additional ARO-INHBE and ARO-ALK7 data releases are planned in 2026 for this novel non-inhibitor strategy, which had quite encouraging early data, particularly in diabetic obese patients in combination with tirzepatide and with liver fat reductions as monotherapy or in combination with tirzepatide. As James mentioned, we are planning to webcast three presentations as part of our summer series of R&D webinars to go over cardiometabolic broadly, obesity, and ARO-MAPT. The first clinical readout of ARO-DIMER-PA targeting both PCSK9 and ApoC-III for LDL and TG lowering is also expected in Q3. the first clinical readout of aro-dimer-pa targeting both pcsk9 and apoc-iii for ldl and tg lowering is also expected in q3 The first clinical readout for ARO-MAPT is expected around the end of Q3 or early Q4. the first clinical readout for aro-mapt is expected around the end of q3 or early q4 This is being developed as a potential treatment for tauopathies, including Alzheimer's disease, and is our first program using the CNS delivery platform design to cross the blood-brain barrier after systemic delivery via subcutaneous administration. this is being developed as a potential treatment for tauopathies including alzheimer's disease and is our first program using the cns delivery platform design to cross the blood-brain barrier after systemic delivery via subcutaneous administration Additional ARO-INHBE and ARO-ALK7 data releases are planned in 2026 for this novel non-inhibitor strategy, which had quite encouraging early data, particularly in diabetic obese patients in combination with tirzepatide and with liver fat reductions as monotherapy or in combination with tirzepatide. additional aro-inhbe and aro-alk7 data releases are planned in 2026 for this novel non-inhibitor strategy which had quite encouraging early data particularly in diabetic obese patients in combination with tirzepatide and with liver fat reductions as monotherapy or in combination with tirzepatide As James mentioned, we are planning to webcast three presentations as part of our summer series of R&D webinars to go over cardiometabolic broadly, obesity, and ARO-MAPT. as james mentioned we are planning to webcast three presentations as part of our summer series of r&d webinars to go over cardiometabolic broadly obesity and aro-mapt These can serve as a review of the programs and results to date and as a primer for the potentially important readouts coming up later this year. Thank you for joining us today. I would now like to open the call to your questions. These can serve as a review of the programs and results to date and as a primer for the potentially important readouts coming up later this year. these can serve as a review of the programs and results to date and as a primer for the potentially important readouts coming up later this year Thank you for joining us today. thank you for joining us today I would now like to open the call to your questions. i would now like to open the call to your questions

Speaker 13: Thank you. At this time, we will now conduct the question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please note that each analyst is permitted to ask one question. Should you have a follow-up question, you will need to get back in queue. Please stand by while we compile the Q&A roster. Our first question comes from the line of Edward Tenthoff from Piper Sandler. Your line is now open. Thank you. thank you At this time, we will now conduct the question-and-answer session. at this time we will now conduct the question-and-answer session As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. as a reminder to ask a question you will need to press star one one on your telephone and wait for your name to be announced To withdraw your question, please press star one one again. to withdraw your question please press star one one again Please note that each analyst is permitted to ask one question. please note that each analyst is permitted to ask one question Should you have a follow-up question, you will need to get back in queue. should you have a follow-up question you will need to get back in queue Please stand by while we compile the Q&A roster. please stand by while we compile the q&a roster Our first question comes from the line of Edward Tenthoff from Piper Sandler. our first question comes from the line of edward tenthoff from piper sandler Your line is now open. your line is now open

Speaker 6: Great. Thank you. Thanks for all the detail in the update today. My question really has to do with looking at the upcoming severe hypertriglyceridemia readouts. When it comes to, I guess, pancreatitis as a secondary, is the plan to pool SHASTA-3 and SHASTA-4? What are sort of the assumptions around pancreatitis? Thank you. Great. great Thank you. thank you Thanks for all the detail in the update today. thanks for all the detail in the update today My question really has to do with looking at the upcoming severe hypertriglyceridemia readouts. my question really has to do with looking at the upcoming severe hypertriglyceridemia readouts When it comes to, I guess, pancreatitis as a secondary, is the plan to pool SHASTA-3 and SHASTA-4? when it comes to i guess pancreatitis as a secondary is the plan to pool shasta-3 and shasta-4 What are sort of the assumptions around pancreatitis? what are sort of the assumptions around pancreatitis Thank you. thank you

Speaker 7: Yeah. Hi, Ted. Thanks for the question. This is James. Yeah, you got that right. The plan is to pool both of those studies, SHASTA-3 and SHASTA-4. We'll analyze, do a meta-analysis of those two studies to look at pancreatitis event rates, both rates of events in individual patients and the total number of overall events. I think that's kind of all I can say on that. We're still, you know, we're still blinded and, like we said, should have the data in Q3. Yeah. yeah Hi, Ted. hi ted Thanks for the question. thanks for the question This is James. this is james Yeah, you got that right. yeah you got that right The plan is to pool both of those studies, SHASTA-3 and SHASTA-4. the plan is to pool both of those studies shasta-3 and shasta-4 We'll analyze, do a meta-analysis of those two studies to look at pancreatitis event rates, both rates of events in individual patients and the total number of overall events. we'll analyze do a meta-analysis of those two studies to look at pancreatitis event rates both rates of events in individual patients and the total number of overall events I think that's kind of all I can say on that. i think that's kind of all i can say on that We're still, you know, we're still blinded and, like we said, should have the data in Q3. we're still you know we're still blinded and like we said should have the data in q3

Speaker 6: Great. Looking forward to that. Thank you. Great. great Looking forward to that. looking forward to that Thank you. thank you

Speaker 13: Thank you. One moment for our next question. Our next question comes from Jason Gerberry of Bank of America. Your line's now open. Thank you. thank you One moment for our next question. one moment for our next question Our next question comes from Jason Gerberry of Bank of America. our next question comes from jason gerberry of bank of america Your line's now open. your line's now open

Speaker 8: Hey, guys. Thanks for taking my question. Just wanted to probe in a little bit more on the INHBE and ALK7 updates later this year and get your latest thoughts on these modalities. I think investors have soured a little bit on INHBE after the Wave Life Sciences data update. Just wanted to get your perspective on kinda what you need to see from these upcoming readouts to, you know, advance one or both for obesity treatment versus, you know, any alternative potentially considering for a MASH indication. Thanks. Hey, guys. hey guys Thanks for taking my question. thanks for taking my question Just wanted to probe in a little bit more on the INHBE and ALK7 updates later this year and get your latest thoughts on these modalities. just wanted to probe in a little bit more on the inhbe and alk7 updates later this year and get your latest thoughts on these modalities I think investors have soured a little bit on INHBE after the Wave Life Sciences data update. i think investors have soured a little bit on inhbe after the wave life sciences data update Just wanted to get your perspective on kinda what you need to see from these upcoming readouts to, you know, advance one or both for obesity treatment versus, you know, any alternative potentially considering for a MASH indication. just wanted to get your perspective on kinda what you need to see from these upcoming readouts to you know advance one or both for obesity treatment versus you know any alternative potentially considering for a mash indication Thanks. thanks

Speaker 7: Yeah. Hi, Jason. This is James. Sure, happy to cover those questions. you know, we've been saying all along really that we thought that this ARO-INHBE outset and access is interesting, but we thought the approach was to combine with GLP-1s. That's still our standpoint here. We think that there's potential, particularly in the Type 2 Diabetics for additional weight loss on top of tirzepatide or other GLP-1s with either ALK7 knockdown or ARO-INHBE knockdown. What we've seen from the clinical study that we talked about earlier this year from ARO-INHBE, with ARO-INHBE knockdown is really clear redistribution of fat out of the liver, even with monotherapy, but also with combination therapy. Some additional changes, improvements in body composition, reductions in total fat and visceral fat, particularly in that Type 2 Diabetic population. Yeah. yeah Hi, Jason. hi jason This is James. this is james Sure, happy to cover those questions. you know, we've been saying all along really that we thought that this ARO-INHBE outset and access is interesting, but we thought the approach was to combine with GLP-1s. sure happy to cover those questions you know we've been saying all along really that we thought that this aro-inhbe outset and access is interesting but we thought the approach was to combine with glp-1s That's still our standpoint here. that's still our standpoint here We think that there's potential, particularly in the Type 2 Diabetics for additional weight loss on top of tirzepatide or other GLP-1s with either ALK7 knockdown or ARO-INHBE knockdown. we think that there's potential particularly in the type 2 diabetics for additional weight loss on top of tirzepatide or other glp-1s with either alk7 knockdown or aro-inhbe knockdown What we've seen from the clinical study that we talked about earlier this year from ARO-INHBE, with ARO-INHBE knockdown is really clear redistribution of fat out of the liver, even with monotherapy, but also with combination therapy. what we've seen from the clinical study that we talked about earlier this year from aro-inhbe with aro-inhbe knockdown is really clear redistribution of fat out of the liver even with monotherapy but also with combination therapy Some additional changes, improvements in body composition, reductions in total fat and visceral fat, particularly in that Type 2 Diabetic population. some additional changes improvements in body composition reductions in total fat and visceral fat particularly in that type 2 diabetic population I think that we look forward to more of the same and to sharing more of that liver fat data here, in the, you know, the coming quarter or so. In the second half of the year, providing some additional updates on changes in body composition and some of the other parameters that we showed back in January. I think that we look forward to more of the same and to sharing more of that liver fat data here, in the, you know, the coming quarter or so. i think that we look forward to more of the same and to sharing more of that liver fat data here in the you know the coming quarter or so In the second half of the year, providing some additional updates on changes in body composition and some of the other parameters that we showed back in January. in the second half of the year providing some additional updates on changes in body composition and some of the other parameters that we showed back in january

Speaker 13: Thank you. One moment for our next question. Our next question comes from Brian Cheng of JPMorgan. Thank you. thank you One moment for our next question. one moment for our next question Our next question comes from Brian Cheng of JP Morgan. our next question comes from brian cheng of jp morgan

Speaker 15: Hi, guys. This is Ron on for Brian. Congrats on the quarter. Just wanted to ask you, can you guys give more color on the interactions you've had with payers that led to the recent price lowering? What has been the feedback since your competitive action last month? Thank you. Hi, guys. hi guys This is Ron on for Brian. this is ron on for brian Congrats on the quarter. congrats on the quarter Just wanted to ask you, can you guys give more color on the interactions you've had with payers that led to the recent price lowering? just wanted to ask you can you guys give more color on the interactions you've had with payers that led to the recent price lowering What has been the feedback since your competitive action last month? what has been the feedback since your competitive action last month Thank you. thank you

Speaker 3: Yeah. Hi, Ron. This is Andy. Our interactions with payers to date have been consistent, have been positive, and we're seeing payer policies, and these are public payer policies that reflect the ability to diagnose FCS patients through multiple diagnosis pathways, in particular through the clinical criteria that we saw in PALISADE. Really positive conversations with payers about payer policies and about future coverage. Yeah. yeah Hi, Ron. hi ron This is Andy. this is andy Our interactions with payers to date have been consistent, have been positive, and we're seeing payer policies, and these are public payer policies that reflect the ability to diagnose FCS patients through multiple diagnosis pathways, in particular through the clinical criteria that we saw in PALISADE. our interactions with payers to date have been consistent have been positive and we're seeing payer policies and these are public payer policies that reflect the ability to diagnose fcs patients through multiple diagnosis pathways in particular through the clinical criteria that we saw in palisade Really positive conversations with payers about payer policies and about future coverage. really positive conversations with payers about payer policies and about future coverage

Speaker 15: Okay. Just a quick follow-up. Could you guys, how should we think about the impact here to gross to net following the price lowering? Okay. okay Just a quick follow-up. just a quick follow-up Could you guys, how should we think about the impact here to gross to net following the price lowering? could you guys how should we think about the impact here to gross to net following the price lowering

Speaker 4: Gross. Well, gross to net. Dan can take that. What's our assumption on gross to net with the new pricing policy? Gross. gross Well, gross to net. well gross to net Dan can take that. dan can take that What's our assumption on gross to net with the new pricing policy? what's our assumption on gross to net with the new pricing policy

Speaker 5: I mean, I should answer your second question. We ignore the WAC too, as Chris already explained, to make it, you know, premium price to the competitor there. We are not actually gonna give guidance on gross to net. We have not seen anything substantial in that regard. Nor do we currently expect it. You know, other than things that were statutorily required, such as Medicaid rebates and the manufacturer discount program and the like. We have a policy at the moment not to provide any sort of guidance or on that at this stage. I mean, I should answer your second question. i mean i should answer your second question We ignore the WAC too, as Chris already explained, to make it, you know, premium price to the competitor there. we ignore the wac too as chris already explained to make it you know premium price to the competitor there We are not actually gonna give guidance on gross to net. we are not actually gonna give guidance on gross to net We have not seen anything substantial in that regard. we have not seen anything substantial in that regard Nor do we currently expect it. nor do we currently expect it You know, other than things that were statutorily required, such as Medicaid rebates and the manufacturer discount program and the like. you know other than things that were statutorily required such as medicaid rebates and the manufacturer discount program and the like We have a policy at the moment not to provide any sort of guidance or on that at this stage. we have a policy at the moment not to provide any sort of guidance or on that at this stage

Speaker 4: Let's just be clear. The lowering of the WAC from 60-45 had nothing to do with any pushback from payers. To the contrary, I think that those interactions have been quite positive. You know, this is a lowering of the WAC in expectation of an expansion on the market into SHTG and to ensure this, that we are, you know, that the payers would not require a step through with our competitor. As we talked about, you know, we are priced at a premium here. We think that's appropriate, you know, given the characteristics of our drug versus the competitor's drug. Let's just be clear. let's just be clear The lowering of the WAC from 60-4 5 had nothing to do with any pushback from payers. the lowering of the wac from 60-4 5 had nothing to do with any pushback from payers To the contrary, I think that those interactions have been quite positive. to the contrary i think that those interactions have been quite positive You know, this is a lowering of the WAC in expectation of an expansion on the market into SHTG and to ensure this, that we are, you know, that the payers would not require a step through with our competitor. you know this is a lowering of the wac in expectation of an expansion on the market into shtg and to ensure this that we are you know that the payers would not require a step through with our competitor As we talked about, you know, we are priced at a premium here. as we talked about you know we are priced at a premium here We think that's appropriate, you know, given the characteristics of our drug versus the competitor's drug. we think that's appropriate you know given the characteristics of our drug versus the competitor's drug We think 45 actually, you know, long term is probably quite a good price in terms of maximizing access to the drug across various subpopulations within SHTG. We think 45 actually, you know, long term is probably quite a good price in terms of maximizing access to the drug across various subpopulations within SHTG. we think 45 actually you know long term is probably quite a good price in terms of maximizing access to the drug across various subpopulations within shtg

Speaker 15: Great. Thank you so much. Great. great Thank you so much. thank you so much

Speaker 4: You're welcome. You're welcome. you're welcome

Speaker 13: Thank you. One moment for our next question. Our next question comes from Michael Ulz from Morgan Stanley. Your line's now open. Thank you. thank you One moment for our next question. one moment for our next question Our next question comes from Michael Ulz from Morgan Stanley. our next question comes from michael ulz from morgan stanley Your line's now open. your line's now open

Speaker 1: Hey, guys. It's Abhi Aggarwal come the line for Mike. Thank you for taking our questions and congrats on the quarter. I guess among the patients who were switchers, could you characterize, you know, I guess the motivations for switching to REDEMPLO? Was it due to its clinical profile or, could it be more payer-related? Thanks. Hey, guys. hey guys It's Abhi Aggarwal come the line for Mike. it's abhi aggarwal come the line for mike Thank you for taking our questions and congrats on the quarter. thank you for taking our questions and congrats on the quarter I guess among the patients who were switchers, could you characterize, you know, I guess the motivations for switching to REDEMPLO? i guess among the patients who were switchers could you characterize you know i guess the motivations for switching to redemplo Was it due to its clinical profile or, could it be more payer-related? was it due to its clinical profile or could it be more payer-related Thanks. thanks

Speaker 3: Hi, Mike, this is Andy. Thanks for the question. We've seen really diversity of reasons for switch that include efficacy, safety, and tolerability, and a variety of other reasons as well. I wouldn't say there's one particular reason driving switch. There's a multitude of reasons. Hi, Mike, this is Andy. hi mike this is andy Thanks for the question. thanks for the question We've seen really diversity of reasons for switch that include efficacy, safety, and tolerability, and a variety of other reasons as well. we've seen really diversity of reasons for switch that include efficacy safety and tolerability and a variety of other reasons as well I wouldn't say there's one particular reason driving switch. i wouldn't say there's one particular reason driving switch There's a multitude of reasons. there's a multitude of reasons

Speaker 1: Okay, great. Thanks for taking our questions. Okay, great. okay great Thanks for taking our questions. thanks for taking our questions

Speaker 13: Thank you. One moment for our next question. Our next question comes from Maury Raycroft from Jefferies. Thank you. thank you One moment for our next question. one moment for our next question Our next question comes from Maury Raycroft from Jefferies. our next question comes from maury raycroft from jefferies

Speaker 12: Hi, thanks for taking my question. Maybe just a follow-up to Ted's question earlier on SHASTA 3 and 4. Just wondering if there's an updated perspective on whether the blinded AP event rates are tracking in line with your expectations and whether you'd be able to generate enough events by the time the study completes, or could you potentially even keep the study blinded a little bit longer to get an adequate number of total events? Hi, thanks for taking my question. hi thanks for taking my question Maybe just a follow-up to Ted's question earlier on SHASTA 3 and 4. maybe just a follow-up to ted's question earlier on shasta 3 and 4 Just wondering if there's an updated perspective on whether the blinded AP event rates are tracking in line with your expectations and whether you'd be able to generate enough events by the time the study completes, or could you potentially even keep the study blinded a little bit longer to get an adequate number of total events? just wondering if there's an updated perspective on whether the blinded ap event rates are tracking in line with your expectations and whether you'd be able to generate enough events by the time the study completes or could you potentially even keep the study blinded a little bit longer to get an adequate number of total events

Speaker 7: Hi, Maury Raycroft, this is James Hamilton. I'll take that question. We're not giving any guidance on or sort of blow-by-blow details on the number of events we're seeing. Suffice it to say we feel comfortable with the number of events we have seen and, you know, the big reveal will be in Q3. No plans to extend the study or stay blinded for a longer period at this time. Hi, Maury Raycroft, this is James Hamilton. hi maury raycroft this is james hamilton I'll take that question. i'll take that question We're not giving any guidance on or sort of blow-by-blow details on the number of events we're seeing. we're not giving any guidance on or sort of blow-by-blow details on the number of events we're seeing Suffice it to say we feel comfortable with the number of events we have seen and, you know, the big reveal will be in Q3. suffice it to say we feel comfortable with the number of events we have seen and you know the big reveal will be in q3 No plans to extend the study or stay blinded for a longer period at this time. no plans to extend the study or stay blinded for a longer period at this time

Speaker 12: Got it. Okay. Thanks for taking my questions. Got it. got it Okay. okay Thanks for taking my questions. thanks for taking my questions

Speaker 13: Thank you. One moment for our next question. Our next question comes from Mani Foroohar from Leerink. Your line is now open. Thank you. thank you One moment for our next question. one moment for our next question Our next question comes from Mani Foroohar from Leerink. our next question comes from mani foroohar from leerink Your line is now open. your line is now open

Speaker 17: Hi, you have Valerie from Mani Foroohar. Thanks for taking my question. Congrats on your quarter. Yeah. Can you talk about how the phase III CELIA data from Biogen will inform your strategy for ARO-MAPT? Maybe also, can you just comment on your internal expectations for this readout? Thank you. Hi, you have Valerie from Mani Foroohar. hi you have valerie from mani foroohar Thanks for taking my question. thanks for taking my question Congrats on your quarter. congrats on your quarter Yeah. yeah Can you talk about how the phase III CELIA data from Biogen will inform your strategy for ARO-MAPT? can you talk about how the phase iii celia data from biogen will inform your strategy for aro-mapt Maybe also, can you just comment on your internal expectations for this readout? maybe also can you just comment on your internal expectations for this readout Thank you. thank you

Speaker 4: I don't think any of us caught that. Could you say that again? I think the line is a bit muddled. I don't think any of us caught that. i don't think any of us caught that Could you say that again? could you say that again I think the line is a bit muddled. i think the line is a bit muddled

Speaker 17: Oh, sorry. No, yeah. I was asking if you could talk about the phase III CELIA data from Biogen and how it will inform your strategy for ARO-MAPT. You also talk about your internal expectations. Oh, sorry. oh sorry No, yeah. no yeah I was asking if you could talk about the phase III CELIA data from Biogen and how it will inform your strategy for ARO-MAPT. i was asking if you could talk about the phase iii celia data from biogen and how it will inform your strategy for aro-mapt You also talk about your internal expectations. you also talk about your internal expectations

Speaker 7: Sure, yeah. I can take that. This is James. I'm assuming you're referring to the ASO targeting MAPT from Biogen and Ionis that's supposed to read out here in maybe this quarter or early next quarter. Yeah, I mean, I hope those data look good, and I hope that they show an improvement in the cognitive rating scales. I think that would be broadly positive for Arrowhead and for the tau hypothesis in general. Of course, that study is in Alzheimer's disease, and a positive readout would support our Alzheimer's programs. That being said, even if those data are not positive, I think we can still, we still have the option of pursuing all the other tauopathies, right? Sure, yeah. sure yeah I can take that. i can take that This is James. this is james I'm assuming you're referring to the ASO targeting MAPT from Biogen and Ionis that's supposed to read out here in maybe this quarter or early next quarter. i'm assuming you're referring to the aso targeting mapt from biogen and ionis that's supposed to read out here in maybe this quarter or early next quarter Yeah, I mean, I hope those data look good, and I hope that they show an improvement in the cognitive rating scales. yeah i mean i hope those data look good and i hope that they show an improvement in the cognitive rating scales I think that would be broadly positive for Arrowhead and for the tau hypothesis in general. i think that would be broadly positive for arrowhead and for the tau hypothesis in general Of course, that study is in Alzheimer's disease, and a positive readout would support our Alzheimer's programs. of course that study is in alzheimer's disease and a positive readout would support our alzheimer's programs That being said, even if those data are not positive, I think we can still, we still have the option of pursuing all the other tauopathies, right? that being said even if those data are not positive i think we can still we still have the option of pursuing all the other tauopathies right A knockdown approach of tau should improve any condition that's really driven by tau gain-of-function or tau pathology. Things like progressive supranuclear palsy or corticobasal degeneration or some of the real specific MAPT gain-of-function frontotemporal dementia disorders. You know, those are all fair game for us as we think about phase IIs and phase III down the road. Hopefully, the Biogen data are positive. If it's not, it's not the end of the world for our program because we can still pursue the tauopathies. A knockdown approach of tau should improve any condition that's really driven by tau gain-of-function or tau pathology. a knockdown approach of tau should improve any condition that's really driven by tau gain-of-function or tau pathology Things like progressive supranuclear palsy or corticobasal degeneration or some of the real specific MAPT gain-of-function frontotemporal dementia disorders. things like progressive supranuclear palsy or corticobasal degeneration or some of the real specific mapt gain-of-function frontotemporal dementia disorders You know, those are all fair game for us as we think about phase IIs and phase III down the road. you know those are all fair game for us as we think about phase iis and phase iii down the road Hopefully, the Biogen data are positive. hopefully the biogen data are positive If it's not, it's not the end of the world for our program because we can still pursue the tauopathies. if it's not it's not the end of the world for our program because we can still pursue the tauopathies

Speaker 17: Great. Thank you. Great. great Thank you. thank you

Speaker 13: Thank you. One moment for our next question. Our next question comes from Joseph Thome from TD Cowen. Your line is now open. Thank you. thank you One moment for our next question. one moment for our next question Our next question comes from Joseph Thome from TD Cowen. our next question comes from joseph thome from td cowen Your line is now open. your line is now open

Speaker 10: Hi there. Good afternoon, and thank you for taking my question. Just as we're thinking about the potential outcomes for the SHASTA-3, SHASTA-4 studies later this year, do you expect that you'll have to show differentiated efficacy versus what Ionis has shown in addition to the dosing benefit in order to keep that even slightly premium pricing? Just a point of clarification, are you characterizing the AP events in SHASTA-3, SHASTA-4 the same way that you characterize them in the long-term SHASTA-2 extension that was recently presented? Thank you. Hi there. hi there Good afternoon, and thank you for taking my question. good afternoon and thank you for taking my question Just as we're thinking about the potential outcomes for the SHASTA-3, SHASTA-4 studies later this year, do you expect that you'll have to show differentiated efficacy versus what Ionis has shown in addition to the dosing benefit in order to keep that even slightly premium pricing? just as we're thinking about the potential outcomes for the shasta-3 shasta-4 studies later this year do you expect that you'll have to show differentiated efficacy versus what ionis has shown in addition to the dosing benefit in order to keep that even slightly premium pricing Just a point of clarification, are you characterizing the AP events in SHASTA-3, SHASTA-4 the same way that you characterize them in the long-term SHASTA-2 extension that was recently presented? just a point of clarification are you characterizing the ap events in shasta-3 shasta-4 the same way that you characterize them in the long-term shasta-2 extension that was recently presented Thank you. thank you

Speaker 7: Yeah. Why don't I take the second part first about the characterization. The answer is no. The SHASTA-2 study, we used the strict Atlanta criteria to look at pancreatitis events, whereas in the SHASTA-3-4 pooled analysis, we're using this sort of modified Atlanta criteria that has definite, probable, and possible pancreatitis. Regarding the premium pricing, look, let's just see what those data look like. You know, historically, when we look at data side by side, you know, with the large caveat that of course it's difficult to compare different clinical studies, you know, with different patient populations. What we have seen consistently is superior triglyceride reduction, superior safety profile, and of course, superior convenience. We expect those to continue. Yeah. yeah Why don't I take the second part first about the characterization. why don't i take the second part first about the characterization The answer is no. the answer is no The SHASTA-2 study, we used the strict Atlanta criteria to look at pancreatitis events, whereas in the SHASTA-3-4 pooled analysis, we're using this sort of modified Atlanta criteria that has definite, probable, and possible pancreatitis. the shasta-2 study we used the strict atlanta criteria to look at pancreatitis events whereas in the shasta-3-4 pooled analysis we're using this sort of modified atlanta criteria that has definite probable and possible pancreatitis Regarding the premium pricing, look, let's just see what those data look like. regarding the premium pricing look let's just see what those data look like You know, historically, when we look at data side by side, you know, with the large caveat that of course it's difficult to compare different clinical studies, you know, with different patient populations. you know historically when we look at data side by side you know with the large caveat that of course it's difficult to compare different clinical studies you know with different patient populations What we have seen consistently is superior triglyceride reduction, superior safety profile, and of course, superior convenience. what we have seen consistently is superior triglyceride reduction superior safety profile and of course superior convenience We expect those to continue. we expect those to continue Should that be the case, then we would expect a premium is still appropriate. Should that be the case, then we would expect a premium is still appropriate. should that be the case then we would expect a premium is still appropriate

Speaker 10: Great. Thank you. Great. great Thank you. thank you

Speaker 7: You're welcome. You're welcome. you're welcome

Speaker 13: Thank you. Our next question comes from Patrick Trucchio of H.C. Wainwright. Your line is now open. Thank you. thank you Our next question comes from Patrick Trucchio of H.C. our next question comes from patrick trucchio of h.c Wainwright. wainwright Your line is now open. your line is now open

Speaker 14: Hi. Thanks so much. Just regarding your business development strategy, I was hoping you could give us some additional details just in terms of which assets you would be looking to bring forward on your own versus those that you may partner. Just more broadly, how you're thinking about how RNAi kind of fits into the broader genetic medicines, sort of portfolio and how, you know, how RNAi is looking sort of competitively against modalities like gene editing, et cetera. Hi. hi Thanks so much. thanks so much Just regarding your business development strategy, I was hoping you could give us some additional details just in terms of which assets you would be looking to bring forward on your own versus those that you may partner. just regarding your business development strategy i was hoping you could give us some additional details just in terms of which assets you would be looking to bring forward on your own versus those that you may partner Just more broadly, how you're thinking about how RNAi kind of fits into the broader genetic medicines, sort of portfolio and how, you know, how RNAi is looking sort of competitively against modalities like gene editing, et cetera. just more broadly how you're thinking about how rnai kind of fits into the broader genetic medicines sort of portfolio and how you know how rnai is looking sort of competitively against modalities like gene editing et cetera

Speaker 4: Sure. Look, I think that RNAi is at the forefront of genetic medicine, you know, for the foreseeable future. Look, it's not the right modality for everything. For those diseases that are characterized by the overproduction of something, if we can address that cell type, then RNAi is a very attractive modality. You know, when we think about RNAi versus gene editing, you know, the way I feel at least is that, you know, RNAi is a relatively straightforward and conservative approach. You know, it is a reversible approach. In our hands, you know, we can have very long durability. Sure. sure Look, I think that RNAi is at the forefront of genetic medicine, you know, for the foreseeable future. look i think that rnai is at the forefront of genetic medicine you know for the foreseeable future Look, it's not the right modality for everything. look it's not the right modality for everything For those diseases that are characterized by the overproduction of something, if we can address that cell type, then RNAi is a very attractive modality. for those diseases that are characterized by the overproduction of something if we can address that cell type then rnai is a very attractive modality You know, when we think about RNAi versus gene editing, you know, the way I feel at least is that, you know, RNAi is a relatively straightforward and conservative approach. you know when we think about rnai versus gene editing you know the way i feel at least is that you know rnai is a relatively straightforward and conservative approach You know, it is a reversible approach. you know it is a reversible approach In our hands, you know, we can have very long durability. in our hands you know we can have very long durability You can almost get the best of both worlds, where if you have a low needle burden, if you will, but the ability to come off drug, you know, should some new biology, you know, come out to suggest that you don't, you don't actually wanna knock down that gene product. That's not the case in gene editing. I think that gene editing does have a place in the world of medicine. It's just quite unknown right now because I don't know what happens, you know, to these edited genes 10 years from now, and I don't think anybody does. You can almost get the best of both worlds, where if you have a low needle burden, if you will, but the ability to come off drug, you know, should some new biology, you know, come out to suggest that you don't, you don't actually wanna knock down that gene product. you can almost get the best of both worlds where if you have a low needle burden if you will but the ability to come off drug you know should some new biology you know come out to suggest that you don't you don't actually wanna knock down that gene product That's not the case in gene editing. that's not the case in gene editing I think that gene editing does have a place in the world of medicine. i think that gene editing does have a place in the world of medicine It's just quite unknown right now because I don't know what happens, you know, to these edited genes 10 years from now, and I don't think anybody does. it's just quite unknown right now because i don't know what happens you know to these edited genes 10 years from now and i don't think anybody does Notwithstanding, as the biology changes, it could be that sometime in the future, we decide that you might not wanna knock down a certain gene product. You know, for those, you know, horrible diseases that are terminal, it could be worth taking a risk to do gene editing. Frankly, for, you know, for all others, if you can address something with RNAi, that feels to me as a, you know, a better approach. Regarding business development, you know, this is a dynamic question. Right now, we feel pretty good about our existing pipeline in terms of that which is wholly owned right now. Notwithstanding, as the biology changes, it could be that sometime in the future, we decide that you might not wanna knock down a certain gene product. notwithstanding as the biology changes it could be that sometime in the future we decide that you might not wanna knock down a certain gene product You know, for those, you know, horrible diseases that are terminal, it could be worth taking a risk to do gene editing. you know for those you know horrible diseases that are terminal it could be worth taking a risk to do gene editing Frankly, for, you know, for all others, if you can address something with RNAi, that feels to me as a, you know, a better approach. frankly for you know for all others if you can address something with rnai that feels to me as a you know a better approach Regarding business development, you know, this is a dynamic question. regarding business development you know this is a dynamic question Right now, we feel pretty good about our existing pipeline in terms of that which is wholly owned right now. right now we feel pretty good about our existing pipeline in terms of that which is wholly owned right now You know, we like that idea of pushing all these forward ourselves. With the possible exception of C3 inhibitor, we like those programs a lot. Those drug candidates appear to do what they're intending to do, and they seem to be well-tolerated. Those are just really outside of our core focus at present. Those are a couple assets that we could, you know, partner with the right partner at some point. Everything else feels pretty good right now. You know, look, that may change as we talk to other companies and as our pipeline grows. You know, we like that idea of pushing all these forward ourselves. you know we like that idea of pushing all these forward ourselves With the possible exception of C3 inhibitor, we like those programs a lot. with the possible exception of c3 inhibitor we like those programs a lot Those drug candidates appear to do what they're intending to do, and they seem to be well-tolerated. those drug candidates appear to do what they're intending to do and they seem to be well-tolerated Those are just really outside of our core focus at present. those are just really outside of our core focus at present Those are a couple assets that we could, you know, partner with the right partner at some point. those are a couple assets that we could you know partner with the right partner at some point Everything else feels pretty good right now. everything else feels pretty good right now You know, look, that may change as we talk to other companies and as our pipeline grows. you know look that may change as we talk to other companies and as our pipeline grows We don't feel real sense of urgency to do additional deals on existing clinical programs other than maybe C3 inhibitor. We don't feel real sense of urgency to do additional deals on existing clinical programs other than maybe C3 inhibitor. we don't feel real sense of urgency to do additional deals on existing clinical programs other than maybe c3 inhibitor

Speaker 13: Thank you. Our next question comes from Amine Chaherli from B. Riley Securities. Your line is now open. Thank you. thank you Our next question comes from Amine Chaherli from B. our next question comes from amine chaherli from b Riley Securities. riley securities Your line is now open. your line is now open

Speaker 2: Hi, everyone. Congratulations on the quarter. This is Amine Chaherli on behalf of Madison El-Saadi. I just wanted to ask, as you think about the next generation of the DIMER platform, is a construct combining INHBE or ALK7 with a non-overlapping mechanism target, you know, something you're evaluating for obesity or other indications? Thank you. Hi, everyone. hi everyone Congratulations on the quarter. congratulations on the quarter This is Amine Chaherli on behalf of Madison El-Saadi. this is amine chaherli on behalf of madison el-saadi I just wanted to ask, as you think about the next generation of the DIMER platform, is a construct combining INHBE or ALK7 with a non-overlapping mechanism target, you know, something you're evaluating for obesity or other indications? i just wanted to ask as you think about the next generation of the dimer platform is a construct combining inhbe or alk7 with a non-overlapping mechanism target you know something you're evaluating for obesity or other indications Thank you. thank you

Speaker 7: Yes. Can we move on to the next question? Yes. yes Can we move on to the next question? can we move on to the next question

Speaker 13: Yes. Our next question comes from Luca Issi from RBC Capital Markets. Your line is now open. Yes. yes Our next question comes from Luca Issi from RBC Capital Markets. our next question comes from luca issi from rbc capital markets Your line is now open. your line is now open

Speaker 16: Oh, great. Hi, team. This is Shelby on for Luca, and thanks for taking the question. Given Ionis has announced a new price at $40,000, and has first-mover advantage, can you walk us through the rationale to continue to price REDEMPLO at a premium versus that par in SHTG, maybe as a way to kind of undercut their pricing since you're coming in second? Just wondering the rationale behind that. Thanks. Oh, great. oh great Hi, team. hi team This is Shelby on for Luca, and thanks for taking the question. this is shelby on for luca and thanks for taking the question Given Ionis has announced a new price at $40,000, and has first-mover advantage, can you walk us through the rationale to continue to price REDEMPLO at a premium versus that par in SHTG, maybe as a way to kind of undercut their pricing since you're coming in second? given ionis has announced a new price at $40,000 and has first-mover advantage can you walk us through the rationale to continue to price redemplo at a premium versus that par in shtg maybe as a way to kind of undercut their pricing since you're coming in second Just wondering the rationale behind that. just wondering the rationale behind that Thanks. thanks

Speaker 3: Thanks, Shelby. As Chris previously mentioned, we do believe REDEMPLO is a best-in-class ApoC-III inhibitor, and that it commands premium pricing as a consequence of that. There are a variety of reasons for that. Chris touched on some of them, including the depth of knockdown for ApoC-III as a target, the depth of TG reduction. We saw that from PALISADE with an 80% reduction from baseline. We saw that with the numerical decrease in acute pancreatitis from PALISADE. We've seen that also with an FDA label that has no contraindications, no warnings, and no precautions. Lastly, with a convenient dosing schedule that's only four injections a year. When you sum up the totality of those attributes, we just believe it's a best-in-class ApoC-III inhibitor, and as a consequence, should be premium priced. Thanks, Shelby. thanks shelby As Chris previously mentioned, we do believe REDEMPLO is a best-in-class ApoC-III inhibitor, and that it commands premium pricing as a consequence of that. as chris previously mentioned we do believe redemplo is a best-in-class apoc-iii inhibitor and that it commands premium pricing as a consequence of that There are a variety of reasons for that. there are a variety of reasons for that Chris touched on some of them, including the depth of knockdown for ApoC-III as a target, the depth of TG reduction. chris touched on some of them including the depth of knockdown for apoc-iii as a target the depth of tg reduction We saw that from PALISADE with an 80% reduction from baseline. we saw that from palisade with an 80% reduction from baseline We saw that with the numerical decrease in acute pancreatitis from PALISADE. we saw that with the numerical decrease in acute pancreatitis from palisade We've seen that also with an FDA label that has no contraindications, no warnings, and no precautions. we've seen that also with an fda label that has no contraindications no warnings and no precautions Lastly, with a convenient dosing schedule that's only four injections a year. lastly with a convenient dosing schedule that's only four injections a year When you sum up the totality of those attributes, we just believe it's a best-in-class ApoC-III inhibitor, and as a consequence, should be premium priced. when you sum up the totality of those attributes we just believe it's a best-in-class apoc-iii inhibitor and as a consequence should be premium priced

Speaker 13: Thank you. Our next question comes from Jennifer Jia from Cantor Fitzgerald. Your line is now open. Thank you. thank you Our next question comes from Jennifer Jia from Cantor Fitzgerald. our next question comes from jennifer jia from cantor fitzgerald Your line is now open. your line is now open

Speaker 9: Hi. Thanks for taking my question. This is Jennifer Jia on for Prakhar Agrawal. I'd like to understand a little bit more on the expectations for aroDIMER readout later this year. What efficacy are you hoping to see, and what does it take to take this forward to a larger trial? If it's positive, do you consider going straight to a cardio outcomes trial, or will you still need to complete a phase II? Hi. hi Thanks for taking my question. thanks for taking my question This is Jennifer Jia on for Prakhar Agrawal. this is jennifer jia on for prakhar agrawal I'd like to understand a little bit more on the expectations for aroDIMER readout later this year. i'd like to understand a little bit more on the expectations for arodimer readout later this year What efficacy are you hoping to see, and what does it take to take this forward to a larger trial? what efficacy are you hoping to see and what does it take to take this forward to a larger trial If it's positive, do you consider going straight to a cardio outcomes trial, or will you still need to complete a phase II? if it's positive do you consider going straight to a cardio outcomes trial or will you still need to complete a phase ii

Speaker 7: Yeah. Hi, Jennifer, this is James. Happy to address that question. The great thing about this program is that all of the relevant biomarkers, and even, you know, biomarkers that you could use for potentially for approval, are blood-based, right? We can measure PCSK9, we can measure ApoC-III in the blood, and we can measure LDL cholesterol and triglycerides. ApoB, non-HDL cholesterol are all pretty easy for us to measure. That's what we'll be primarily focused on, as well as safety in this initial data readout. In terms of where we go from here, you know, I think we're working on that now. There may be some additional limited phase II work which we could even consider doing as part of this study, but then moving quickly into an outcome study down the road. Yeah. yeah Hi, Jennifer, this is James. hi jennifer this is james Happy to address that question. happy to address that question The great thing about this program is that all of the relevant biomarkers, and even, you know, biomarkers that you could use for potentially for approval, are blood-based, right? the great thing about this program is that all of the relevant biomarkers and even you know biomarkers that you could use for potentially for approval are blood-based right We can measure PCSK9, we can measure ApoC-III in the blood, and we can measure LDL cholesterol and triglycerides. we can measure pcsk9 we can measure apoc-iii in the blood and we can measure ldl cholesterol and triglycerides ApoB, non-HDL cholesterol are all pretty easy for us to measure. apob non-hdl cholesterol are all pretty easy for us to measure That's what we'll be primarily focused on, as well as safety in this initial data readout. that's what we'll be primarily focused on as well as safety in this initial data readout In terms of where we go from here, you know, I think we're working on that now. in terms of where we go from here you know i think we're working on that now There may be some additional limited phase II work which we could even consider doing as part of this study, but then moving quickly into an outcome study down the road. there may be some additional limited phase ii work which we could even consider doing as part of this study but then moving quickly into an outcome study down the road More to come on the development plan and the study designs, but looking forward to the readout later this year. More to come on the development plan and the study designs, but looking forward to the readout later this year. more to come on the development plan and the study designs but looking forward to the readout later this year

Speaker 9: Great. Thanks. Great. great Thanks. thanks

Speaker 13: Thank you. Our next question comes from Keay Nakae from Chardan Capital Markets. Your line is now open. Thank you. thank you Our next question comes from Keay Nakae from Chardan Capital Markets. our next question comes from keay nakae from chardan capital markets Your line is now open. your line is now open

Speaker 11: Yeah, thank you. Question about the Madrigal licensing agreement for ARO-PNPLA3. Help us understand from a capital allocation strategy perspective why it makes sense for you to do this deal at this time, as opposed to taking the drug further on your own? Yeah, thank you. yeah thank you Question about the Madrigal licensing agreement for ARO-PNPLA3. question about the madrigal licensing agreement for aro-pnpla3 Help us understand from a capital allocation strategy perspective why it makes sense for you to do this deal at this time, as opposed to taking the drug further on your own? help us understand from a capital allocation strategy perspective why it makes sense for you to do this deal at this time as opposed to taking the drug further on your own

Speaker 4: Yes, good question. Let me just take it back and remind everyone that where PNPLA3, where ARO-PNPLA3 came from. We didn't develop this on our own independently. This was part of our deal with Janssen that was centered around HBV, FSBP, also included a couple of additional targets. This was one of those targets. We developed it for them. They did the phase I. The phase I was compelling. You know, after only a single dose, they saw about a 40% reduction in liver fat in homozygous patients. That was interesting to us. Janssen, as I understand it, decided to get out of MASH, the asset was returned to us. Yes, good question. yes good question Let me just take it back and remind everyone that where PNPLA3, where ARO-PNPLA3 came from. let me just take it back and remind everyone that where pnpla3 where aro-pnpla3 came from We didn't develop this on our own independently. we didn't develop this on our own independently This was part of our deal with Janssen that was centered around HBV, FSBP, also included a couple of additional targets. this was part of our deal with janssen that was centered around hbv fsbp also included a couple of additional targets This was one of those targets. this was one of those targets We developed it for them. we developed it for them They did the phase I. they did the phase i The phase I was compelling. the phase i was compelling You know, after only a single dose, they saw about a 40% reduction in liver fat in homozygous patients. you know after only a single dose they saw about a 40% reduction in liver fat in homozygous patients That was interesting to us. that was interesting to us Janssen, as I understand it, decided to get out of MASH, the asset was returned to us. janssen as i understand it decided to get out of mash the asset was returned to us We didn't spend any money on this. As we look at taking this forward, we think it's a really compelling target for a company that's focused in MASH largely. This is a genetically defined population, that's sort of the good news and the bad news, right? You know, the good news is it's quite specific. The challenge there is that there will be, you know, a companion diagnostic component to this. It made sense for us to find, you know, a pure play MASH company to take this forward. Of course, Madrigal is, I think, the best out there right now. It made sense. We didn't spend any money on this. we didn't spend any money on this As we look at taking this forward, we think it's a really compelling target for a company that's focused in MASH largely. as we look at taking this forward we think it's a really compelling target for a company that's focused in mash largely This is a genetically defined population, that's sort of the good news and the bad news, right? this is a genetically defined population that's sort of the good news and the bad news right You know, the good news is it's quite specific. you know the good news is it's quite specific The challenge there is that there will be, you know, a companion diagnostic component to this. the challenge there is that there will be you know a companion diagnostic component to this It made sense for us to find, you know, a pure play MASH company to take this forward. it made sense for us to find you know a pure play mash company to take this forward Of course, Madrigal is, I think, the best out there right now. of course madrigal is i think the best out there right now It made sense. it made sense It didn't really make sense for us to, you know, to spend much money right now to do a phase II. You know, those studies could be a bit long and more expensive than made sense for us. You know, we've got a very large pipeline. We've got some really interesting programs that we are pushing ourselves. I just think that, you know, our ROI is probably better, you know, by allocating capital to those programs that we are more confident that we will hold on to long term. That's where we went. You know, we are thrilled to have Madrigal as a partner. We're thrilled to have them develop that drug. We think it's a good drug. It didn't really make sense for us to, you know, to spend much money right now to do a phase II. it didn't really make sense for us to you know to spend much money right now to do a phase ii You know, those studies could be a bit long and more expensive than made sense for us. you know those studies could be a bit long and more expensive than made sense for us You know, we've got a very large pipeline. you know we've got a very large pipeline We've got some really interesting programs that we are pushing ourselves. we've got some really interesting programs that we are pushing ourselves I just think that, you know, our ROI is probably better, you know, by allocating capital to those programs that we are more confident that we will hold on to long term. i just think that you know our roi is probably better you know by allocating capital to those programs that we are more confident that we will hold on to long term That's where we went. that's where we went You know, we are thrilled to have Madrigal as a partner. you know we are thrilled to have madrigal as a partner We're thrilled to have them develop that drug. we're thrilled to have them develop that drug We think it's a good drug. we think it's a good drug We're thrilled to have them commercialize it eventually. We feel good about the deal. We're thrilled to have them commercialize it eventually. we're thrilled to have them commercialize it eventually We feel good about the deal. we feel good about the deal

Speaker 11: Great. Thank you. Great. great Thank you. thank you

Speaker 4: Sure. Sure. sure

Speaker 13: Thank you. This concludes the question-and-answer session. I would now like to turn it back to Chris Anzalone for closing remarks. Thank you. thank you This concludes the question-and-answer session. this concludes the question-and-answer session I would now like to turn it back to Chris Anzalone for closing remarks. i would now like to turn it back to chris anzalone for closing remarks

Speaker 4: Thanks, everyone, for joining us today, and we look forward to seeing you in the future. Thanks, everyone, for joining us today, and we look forward to seeing you in the future. thanks everyone for joining us today and we look forward to seeing you in the future

Speaker 13: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Thank you for your participation in today's conference. thank you for your participation in today's conference This does conclude the program. this does conclude the program You may now disconnect. you may now disconnect