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 Dana Powell, 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, Mitch. Good afternoon, everyone, and thank you for joining us today. During the fiscal second quarter, and the period since our last ordinance 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. We're commercial. We have a clear line of sight to expand our commercial opportunities and footprints. 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 commercials. As you recall, the FDA approved RADEPLO in November 2025 as an adjunct to diet to reduce triglycerides in adults with FDS. FDS is a severe, rare disease with an estimated 6,500 people in the U.S. living with genetic or clinical SDS, characterized by TG levels that can be 10 to 100 times higher than normal. This leads to a substantially increased risk of developing acute or current and potentially fatal pancreatitis. As we reported last quarter, the U.S. redemptible launch was off to a strong start. That momentum has continued into the current quarter, and we are now seeing around 30 new prescriptions written each week. Greater than 400 prescriptions have been written since launch, and more than 10% of these have been for patients switching from our competitor's ACO-C3 inhibitor. Of course, each prescription needs to be fully adjudicated with payers before becoming paid clinics, but we offer a robust quick-start program to support these MCS patients in the interim. The volume of physicians writing prescriptions and the number of patients receiving Redemplos continues to exceed our initial expectations. With respect to pricing, we updated Redempolo'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. With the one Redempolo 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 Bayer contracting and eliminating pricing complexity that could complicate future formulary negotiations. 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 a death blow 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 Medicine Agency's Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the approval of Redempo. 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 Redempo offers in patients. Redemplo will be available later this year in Canada, and we anticipate it will be marketed independently by AeroEast. And in a marketing authorization decision from the European Commission, we expect to launch Redemplo later this year in select EU countries, and likely in the UK 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 engineer. During the recent period, we have made rapid progress across the pipeline, including programs targeting genes expressed in liver, cellulose muscle, adipose, CNS, and the lung, as well as the first dual-functional sRNA 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 of 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 3, Shasta 3, and 4 studies of disaster and NSH-TG 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 plizazerine. We expect it 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 faggotitis phase. Second, we expect to have early data from the ongoing phase 1-2 study of of Aerodimer PA in patients with mixed hyperlipidemia, we believe this will be the world's first clinical data of a single RNAi molecule designed to simultaneously silence the expression of two proteins. If we see good reduction of PCSK9 and IpoC3 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 hymns. 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. We expect to have early data from the ongoing phase 1-2 study of AROMAP-T 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 MAP-T targets, sorry, AeroMAP-T 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 Aero MAP-T data are encouraging, expect a substantial expansion of our CNS pipeline beginning at the end of 2020. Expect to provide clinical updates on Aero INHBE and Aero L7 throughout the second half of the year. Regarding Aero INHBE, we plan to present additional data at various conferences and launch a Phase II study. For Aero L7, we expect to provide additional data from the ongoing phase 1-2 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 in the 2020 step. 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 achieves clinical improvement concepts 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 sheets, 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 the best of confidence in our portfolio and our ability to continue to build value. Second, and just this week, we announced the exclusive worldwide license ring with Matigal Pharmaceuticals for Aero PMLA-3, AeroHead's clinical stage program designed to treat a genetically defined population of MASH patients. Under the terms of the agreement, Matigal will pay a $25 million upfront payment to AeroHead. AeroHead is also eligible to receive development, regulatory, and sales milestone payments of up to $975 million. AeroHead is further eligible to receive tiered royalties up to mid-teens. Matigal's leadership in the MASH space makes it a natural and attractive partner to advance Arrowhead Philiate III into phase two studies and toward potential commercialization. This transaction was a matter of underscores Arrowhead's disciplined business development strategy, demonstrating our ability to partner high potential, clinically validated programs. That overview, I'd now like to turn the call over to Andy Davis. Andy? Thank you, Chris, and good afternoon, everyone. It has now been approximately five and a half months since the FDA approval of Redemplo on November 18th, 2025. and 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. Redempla's launch continues to build strong and consistent momentum. Through the fiscal second quarter in the March 31st, 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. Redemptible awareness among the prescribers who matter most has increased meaningfully. Critically, this awareness is translated into conviction. Nearly all Redempla prescribers survey report being satisfied or highly satisfied with the product, and Redempla 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 APOC3 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 and important early validation of both clinical effectiveness and patient satisfaction for DEMPLO's quarterly dosing profile. Geographic distribution of prescribing is balanced across the country. Its 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. And 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 Redempo'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 Redempo patients can access treatment, because a meaningful proportion of real-world SDS 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 Redempo 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 Redempo'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 SDS accessible population and also the future SHTG opportunity as it unfolds in the future. On international expansion, Redempla 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 that they've developed. Also last month, CHMP, the Committee for Medicinal Products for Human Use, recommended EU marketing authorization for Redemplu in Europe for SDS without requiring genetic confirmation. Consequently, we anticipate an EMA approval decision in the June to July timeframe. We intend to commercialize Redemplu 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. Hotline results from SHASTA-3 and SHASTA-4, or two registrational phase 3 studies in severe hypertraglyceridemia, 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 APOC3 biology we have observed across our full clinical program to date. We also intend to present the data at a major medical congress, which we hope will be with simultaneous publication in a top-tier medical journal. We then 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 and other jurisdictions are planned to follow thereafter. The SHCG 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 SDS today are also designed with that launch in mind. In summary, the Redempo launch is progressing well and continues to exceed our expectations across prescription volume, patient dynamics, and payer access. Physician satisfaction and forward prescribing intent 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 plizacirant, zodacirant, and aerodimer PA, obesity, including aero-inhibony and aero-ALC7, and aeronapti, 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 Closasteran Phase III studies, SHASTA-3, SHASTA-4, SHASTA-5, and MIR-3, designed to support supplemental NDA filings to expand the Redemplo label beyond genetic and clinical FCS into patients from 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. MIR-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 in the SHASTA-5 to directly assess the ability of plizacirin to reduce the risk of acute pancreatitis as the primary 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 NEAR 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 or SHTG before the end of this year. Before moving on to Zodassaran, I'd like to highlight a presentation we made with new long-term efficacy and safety data for plisaciran across the 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 2b double-blind placebo-controlled studies of plisaciran. Shasta 2 conducted in adults with severe hypertriglyceridemia and MIR, 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 MIR, with additional reductions in remnant and non-HDL cholesterol. 6% of SHTG patients achieved TGs below 500 mg 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 plozaceran during the two-year Phase IIb open-label extension study. These findings support the potential of plizaciran 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 plizaciran, 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. So, DASRAN 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 two-to-one to receive five doses of 200 milligrams of naceran or placebo. The primary endpoint is the percent change from baselines a month 12 in fasting LDL cholesterol. The role-in 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 aerozymer PA. The first dual-functional siRNA designed to silence the expression of two genes with a single RNAi molecule. Aerodimer PA is being developed as a potential treatment for ASCVD due to mixed hyperlipidemia by silencing expression of both PCSK9 and APOC3. In January, we initiated a Phase 1-2A placebo-controlled dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and effects on LDL cholesterol and triglycerides using single-dose aerodimer PA in Part 1 and multiple doses in Part 2 in up to 78 adults with mixed hyperlipidemia. The moment in the study has been rapid, and we are on schedule to have sufficient data to provide the first clinical readouts 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, and that potentially accelerates the path to regulatory approval. So 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 ARROMAP-T first-in-human study. ARROMAP-T is being developed as a potential treatment for tyopathies, including Alzheimer's disease, a 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 tyopathies that are marked by abnormal tau accumulation and formation of tau tangles in neurons. Tau-related pathology may be a critical driver of neurodegeneration and targeting tau is a promising strategy to potentially slow or stop cognitive and functional decline. ARROMAT-T 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 sRNA 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 AROMAT-T. This study is a placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AROMAT-T 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 Aromat-T or placebo by subcutaneous injection. In Parts 1B and Part 2, healthy volunteers and Alzheimer's disease patients respectively will receive multiple escalating doses of Aromat-T 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 Dana Pell.

Thank you, James, and good afternoon, everyone. As we reported today, net loss for the quarter ended March 31, 2026, was $132.7 million for loss of 93 cents per share based on 142.4 million fully diluted weighted average shares outstanding. This compares the net income of 370.4 million dollars or 2.75 cents per share for the quarter ended March 31st, 2025. It's 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 SREPTA transaction that was executed at that time. Revenue for this quarter totaled $74 million, driven primarily by our licensed collaboration agreements with SREPTA and with Novartis. This amount approximately $42 million related to the SREPTA collaboration. This includes $28 million from ongoing recognition of the initial surreptive 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 recognize $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 obligation. We also recorded $11 million related to the asset purchase agreements between Sanofi and Vicerna, developed and commercialized investigation of pedestrians in greater China. Vicerna, 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 Redempla 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 with the difference between total net revenue and collaboration revenue and represents approximately $1 million for the quarter. This is our first full quarter of redemptible sales, and on a unit basis, that figure compares favorably to the first full commercial quarter of the other approved APOC3 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 is 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 expenses was primarily attributable to ongoing progression of our phase III registration studies for plisasterin and SHTG, as well as our early stage pipeline programs, including the DIMER and MAP-D. Fiscal year to date, almost two-thirds of the clinical trial spend can be attributed to our plisasterin phase III studies. As James already mentioned, the registration of SHTG studies for plisasterin should read out in December, and 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, given primarily by ongoing investments to support the commercialization of Redempto. 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 Redempto, and FCS, while also positioning the organization to support a potential future launch in SH2G. And we ultimately expect to leverage these same capabilities for the advancement of sedation 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. shares outstanding at quarter end were 140.69. To provide a little cover, in this quarter alone we brought in over $1 billion, including approximately $850 million net from our January financing transactions, inclusive of a concurrent alternative 0% convertible senior notes and common stock, along with the associated capital transaction. Other notable inflows in the quarter include the $200 million received from SREPTA upon achieving the second CM1 program milestone, as well as the $50 million anniversary payment under the SREPTA long-term collaboration agreement. All of this is very much in line with the information provided previously during our February earnings class. 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 RegenVlo to the patients who need it, we have not left 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, but 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 the suite of Phase 3 clinical studies designed to support an SNDA for Dumblo in patients with SACG, is on schedule for completion and top line readout in Q3. The first clinical readout of Aerodimer PA, targeting both PCSK9 and APOC3 for LDL and TG lowering, is also expected in Q3. The first clinical readout for AeromavT is expected around the end of Q3 or early Q4. This is being developed as a potential treatment for tauopathy, 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 menstruation. Additional Aero-INHPE and Aero-Valc7 data releases are planned in 2026 for this novel non-imprison strategy, which had quite encouraging early data, particularly in diabetic, obese patients in combination with terzepatide and with liver fat reductions as monotherapy or in combination with terzepatide. 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 AROMAP-T. These can serve as a review of the programs and results today and as a primer to the potentially important readouts coming up later this year. Thank you for joining us today, and I would now like to open a 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 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 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 Tentoff from Piper Sandler. Your line is now open.

Great. And thanks for all the detail in the update today. My question really has to do with looking at the upcoming SH severe hypertriglyceridemia readouts. When it comes to pancreatitis as a secondary, is the plan to pool SHASTA for three and four? And what are sort of the assumptions around pancreatitis? Thank you.

Yeah, thanks for the question. This is James. Yeah, you got that right. The plan is to pool both of those studies, SHASTA 3 and 4, and 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 a total number of, and 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.

Looking forward to that.

Thank you. One moment for our next question. Our next question comes from Jason Gerberi of Bank of America. Your line's now open.

Hey, guys. Thanks for taking my question. I just wanted to probe in a little bit more on the Inhibi and ALK7 updates later this year and get your latest thoughts on these modalities. And I think investors have soured a little bit on Inhibi after the wave data update. So I just wanted to get your perspective on kind of what you need to see from these upcoming readouts to, you know, advance one or both for obesity treatment versus, you know, in the alternative, potentially considering for a MASH indication. Thanks.

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 inhibiting outset and access is interesting, but we thought the approach was to combine with GLQ-1s, and 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 trisepatide or other GLP-1s with either ALK7 knockdown or inhibiting knockdown. What we've seen from the clinical study that we talked about earlier this year from inhibiting with an hip and knee knockdown is really clear redistribution of fat out of the liver even with monotherapy but also with combination therapy and some additional changes and improvements in body composition reductions in total fat and visceral fat particularly in that type 2 diabetic population so I think that we look forward to more of the same and sharing more of that little liver fat data here in the coming quarter or so, and then 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. Thank you. One moment for our next question.

Our next question comes from Brian Chang of J.P. Morgan.

Your line is now open. 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 and what has been the feedback

since your competitors action last month thank you yeah hi ron this is andy so our interactions with payers today have been have been consistent have been positive and 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 Palisades. So, really, really positive conversations with payers about payer policies and about future coverage.

And just a quick follow-up, could you guys, how should we think about the impact here to gross to net following the price lowering?

What's our assumption on gross to net with the new pricing policy?

Yeah, so we, I mean, we ignore the, I actually asked you a second question, we ignore the WAC to, as Chris already explained, to make it, you know, premium price to the competitor there. We are, we are not actually going to give guidance on gross to net. We have not seen anything substantial in that, we don't know what we currently expect it. you know, other than things that were statutorily required such as Medicaid relays and the manufacturing discount program and the like. So, but we have a policy at the moment not to

provide any sort of guidance or on that at this stage. And let's just be clear, the lowering of the WAC from 60 to 45 had nothing to do with any pushback from payers to the contrary. I think that those interactions have been quite positive um you know this is this is a lowering of the of the whack in uh expectation of um of an exchange on the market into fhtg and to ensure that that that we are you know that that um that we would the payers would not require a step through uh with our competitor um as we talked about 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. And we think 45 actually, you know, long-term is probably quite a good price

in terms of maximizing the best of the drug across various subpopulations.

Great. Thank you so much. Thank you. One moment for our next question. Our next question comes from Mike Olds from Morgan Stanley. Your line is now open.

Hey, guys. It's Avinova coming to 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 Redempla? Was it due to its clinical profile, or could it be more payer-related?

Hi, Mike. This is Andy. Thanks for the question. We've seen really diversity of reasons for a switch that include efficacy, safety, and tolerability, and a variety of other reasons as well. So 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 Mary Raycroft from Jefferies hi

thanks for taking my question maybe just a follow-up to Ted's question earlier on shots of three and four 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?

Yeah, hi, Mario. This is James. I'll take that question. So we're not giving any guidance 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. But no plans to extend the study or stay blinded

for a longer period of this time. Okay, thanks for taking my questions.

Thank you. One moment for our next question. Our next question comes from Manny Farruhar from LIRINC. Your line is now open.

Hi, you have found for Manny. Thanks for taking my question. Congrats on the culture. So, yeah, can you talk about how the phase 3 serial data from Biogen will inform your

strategy for ARROMAP-T?

And maybe also can you just comment on your internal expectations for this rebound? Thank you.

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

Sorry. No, yeah, I was asking if you could talk about the phase 3 serial data from Biogen and how it will inform your strategy for ARROMAP-T. and you'll also talk about your general expectation.

Oh, I can be in life, thank you. Sure, yeah, I can take that. This is James. So, the—I'm assuming you're referring to the ASO starting 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 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 still have the option of pursuing all the other tauopathies, right? because a knockdown approach of tau should improve any condition that's really driven by tau gain of function or tau pathology. So things like progressive supernuclear palsy or corticobasal or dementia or MAG-T gain of function, frontotemporal dementia disorders, those are all fair game for us. Hopefully the biogen data are positive. If it's not, it's not the end of the world for our program. Great. Thank you.

Thank you. One moment for our next question. Our next question comes from Joseph Tome from TD Cohen. 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 JASA 3-4 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? And then just a point of clarification, are you characterizing the AP events in SHASTA-3-4 the same way that you characterize them in the long-term SHASTA-2 extension that was recently presented? Why don't I take the second part first about the characterization? The answer is no. So 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 to modify the Atlantic criteria. Definite, probable, and regarding the premium pricing, let's just see what those data look like. You know, historically, when we look at data side-by-side, you know, with a 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 service ride reduction, superior safety profile, and, of course, superior convenience. We expect those to continue, and should that be the case, then we would expect. Great. Thank you.

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. And then just more broadly, how you're thinking about how RNAi kind of fits into the broader genetic medicine sort of portfolio and how RNAi is looking sort of competitively against modalities like gene at an egg, et cetera?

Sure. Look, I think that RNAi is at the forefront of genetic medicine, you know, for the foreseeable Now, look, it's not the right modality for everything, but 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. But, you know, when we think about RNAi versus gene editing, you know, the way I feel is that RNAi is a relatively straightforward and conservative approach, right? You know, it is a reversible approach. And in our hands, you know, we can have very long durability, so you can almost get the best of both worlds where you have a low needle burden, if you will, like the ability to come off drug, you know, should some new biology, you know, come out to suggest that you don't actually want to knock down that gene product. That's not the case in gene editing, and I think gene editing does have a place in the world of medicine. And it's just quite unknown right now because I don't know what happens, you know, to these edited genes 10 years from now. I don't think anybody does, notwithstanding as the biology changes and it could be that sometime in the future we decide that you might not want to knock down a certain gene product. So, you know, for those, you know, horrible diseases that are terminal, it could be worth taking a risk to do gene editing. But, frankly, for all others, if you can address something with RNAI, that feels to be 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, in fact, we really 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, and so those are a couple of assets that we could, you know, partner with. Everything else feels pretty good right now. You know, but that may change, and as our pipeline grows, but but we don't feel um we don't feel real sensitive to additional deals on existing

clinical programs other than maybe thank you our next question comes from amine chaharelli from b riley securities your line is now open hi everyone uh congratulations on the quarter uh

this is amine chaharelli on behalf of madison al-sadi um i just wanted to ask as you think about the next generation of the dimer platform is a construct combining uh inhibin e or alc 7

with a non-overlapping mechanism target you know something you're you're evaluating for for obesity

or other indications thank you yes okay we move on the next question yes our next question comes

from luca ec from rbc capital market your line is now open oh great hi team this is shelby on

for luca and thanks for taking the question uh given ionis has announced a new price at 40k and has first mover advantage can you walk us through the rationale to continue to price for them below at a premium versus that par and shtg um maybe as a way to kind of undercut their pricing since you're coming in second just wondering the rationale behind that yeah thanks shelby as as

As Chris previously mentioned, we do believe Redemplu is a best-in-class APOC3 inhibitor in that it commands premium pricing as a consequence of that. And there are a variety of reasons for that. Chris touched on some of them, including the depth of knockdown for APOC3 as a target, the depth of TG reduction. We saw that from Palisade with an 80% reduction from baselines. 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. And then 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 ECO-C3 inhibitor and as a consequence should be premium price.

Thank you.

So, our next call, our next question comes from Jen Gia from Cantor Fitzgerald. Your line is now open.

Hi, thanks for taking my question. This is Jennifer Gia on for Pekar Agrawal. I'd like to understand a little bit more on the expectations for Aerodimer readout later this year. So, what efficacy are you hoping to see and what does it take to take this forward to a larger trial? And if it's positive, do you consider going straight to a cardio outcomes trial, or will you still need to compute a phase two?

Yeah, Jennifer, this is James. Happy to address that question. So the great thing about this program is that all of the relevant biomarkers and even biomarkers that you could use for potentially for approval are blood-based, right? We can measure ECST-9, we can measure A plus C3 in the blood, and we can measure LDL cholesterol and triglycerides, ApoV, non-HDL cholesterol are all pretty easy for us to measure. So 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. And there may be some additional limited phase two work, which we could even consider doing as part of it.

Thank you. Our next question comes from Kiye Nikkei from Chardon Capital Markets. Your line is now open.

Yeah, thank you. Question about the Madrigal Licensing Agreement for PMPLA, 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, it's a good question, where PMFLA-3, where Aero PMFLA-3 came from. We didn't develop this on our own independently. This was part of our deal with Janssen HPV, but also included a couple of additional targets. This was one of those targets. So we developed it for them. invaded the Phase I. The Phase I was compelling. After only a single dose, they saw about a 40% reduction in liver fat in homozygates patients. So that was interesting to us. Janssen has a genetically defined population and that's sort of the good news and the bad news, right? Question and answer

session. I would now like to turn it back to Chris Anzalone for closing remarks. Thanks everyone for joining us today. 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.