Arrowhead Pharmaceuticals, Inc.

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 31st, 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 Dan Appel, 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 1936. 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, in 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 are 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 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 6,500 people in the U.S. living with genetic or clinical FCS. 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. Regenblut 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. More than 400 prescriptions have been written since launch, becoming paid claims, 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 Redemptilo continues to exceed our initial expectations. With respect to pricing, we updated Redemptilo's U.S. wholesale acquisition cost, or WAC, to $45,000 per patient per year. This represents a premium to our competitors' 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 or down below unified pricing model, this price is intended to remain consistent across FCS and SHCG if that indication is approved. We continue to see this strategy as potentially simplifying payer contracting and eliminating pricing complexity, Response from payers to the 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 Redempla. 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 Redempla offers to patients. Redempla will be available later this year in Canada and we anticipate it will be marketed independently by Arrowhead. Pending a marketing authorization to AND LIKELY IN THE U.K. AS WELL. IN GREATER CHINA, REDUNBLO WILL BE MARKETED BY CENOPI. 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 INDIVIDUAL. DURING THE RECENT PERIOD, WE HAVE MADE RAPID PROGRESS ACROSS THE LIFE LINE including programs targeting genes expressed in liver, fellow 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 III, and IV studies of plazasterine 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 plazasterine. We expect to continue to see a favorable safety Second, we expect to have early data from the ongoing Phase I-II study of aerodimer 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 APOC3 and therefore reductions in LDL cholesterol NTGs, we could have a very powerful and unique therapy for the roughly 20 million people in the U.S. living with mixed hyperlipidemia. More broadly, the data could provide initial clinical approval 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 Aeromap 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, arrow map 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 teleopathy and, more broadly, open the door to using RNAi to treat a broad range of conditions from neurodegenerative disorders to obesity. If early arrow MAP-T 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 arrow INHBE and arrow LX7 throughout the second half of the year. Regarding AERO-I and HBE, 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 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 myths. 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 approval 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 investor confidence in our portfolio and our ability to continue to build value. Second, in just this week, He announced the exclusive worldwide license agreement with Madrigal Pharmaceuticals for Arrow PMPLA-3, 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 NASH space makes it a natural and attractive partner to advance AERO-B and PLA-3 into Phase II studies and toward potential commercialization. This transaction with Madrigal underscores AERO-Ed'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, and good afternoon, everyone. It has now been approximately five and a half months since the FDA approval of Redemplo on November 18, 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. Redemplo's launch continues to build strong and consistent momentum. In 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. Redemptive awareness among the prescribers who matter most has increased meaningfully. Critically, this awareness is 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 ApoC3 class, a strong signal that physicians are identifying and treating SDS patients who have never had access to an effective therapy, to which 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 example, as one's 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. 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. lines. to support continued patient access. These discussions are proceeding as expected and, in some cases, have already led to Redempto'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 redentlo 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 redentlo 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 SDS launch performing ahead of our expectations and with potential expansion into SHCG 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 SHCG 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 as they develop. Also last month, CHMP, the Committee for Medicinal Products for Human Use, recommended EU marketing authorization for edemplu 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 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. Hotline results from Shasta 3 and Shasta 4, or two registrational phase 3 studies in severe hypertriglyceridemia, are expected in Q3. We head into the data readout with confidence grounded in the strength of Redempto'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 a 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 in other jurisdictions are planned to follow thereafter. The SHCG opportunity represents a patient population that is substantially larger than SCS, with over 1 million high-risk patients in the United States alone. The commercial infrastructure investments we are making for SCS today are also designed with that launch in mind. In summary, the Redemptible 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, Retail 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 plazaciran, zodaciran, and aerodimer PA. Obesity, including aero-inhibinene and aero-ALK7. And AeroMAP-T, 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 Clozaciran Phase III studies, SHA-SA3, SHA-SA4, SHA-SA5, and MIIR-3, designed to support supplemental NDA filings to expand the Redemplo label beyond genetic and clinical SCS 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. MIRA 3, which enrolled over 1400 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 plazaciran 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 MIIR 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 zovastiran, I'd like to highlight a presentation we made with new long-term efficacy and safety data for plazastiran 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 plazaciran. SHASTA-2 conducted in adults with severe hypertriglyceridemia and NIR, 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. 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 milligrams per deciliter, with 93% of HTG patients achieving TGs below 150 milligrams per deciliter. Importantly, no adjudicated acute pancreatitis events Phase IIb open-label extension study. These findings support the potential of plazaciran as a promising new approach in 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 zadaciran, 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. Sodaciran 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 Daciran or placebo. The primary endpoint is the percent 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 aerodimer PA. The first dual-functional siRNA designed to silence the expression of two genes with a single RNAi molecule. Aeroenzymer 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 I-IIa 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 one and multiple doses in part two in up to 78 adults with mixed hyperlipidemia. Enrollment in the study has been rapid, and we are on schedule to have sufficient data to provide diverse 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 potentially, that potentially accelerate 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 Aromap-T first in human study. Aromap-T is being developed as a potential treatment for chiopathies, including Alzheimer's disease, 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 tautopies 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 that potentially slows and functional decline. AROMAT-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 knockout 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 Aromanti. 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 Dan Appel.

Thank you, James, and good afternoon, everyone. As we reported today, net loss for the quarter ended March 31, 2026. It was $132.7 million for a 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, or $2.75 per share, for the quarter ended March 31st, 2025. It's done $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 disruptive transaction that was executed at that time. Revenue for this quarter totaled $74 million, driven primarily by our license and collaboration agreements with Sarepta and with Novartis. On 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 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 obligations. We also recorded 11 million related to the asset purchase agreements between Sanofi and Vicerna, developed and commercialized investigational investment 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 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, 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 Redemplo 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 expense was primarily attributable to ongoing progression of our Phase III registration studies for prozacrin and SHTG, as well as our early-stage pipeline programs, including the DIMER and MAP-T. Fiscal year to date, Almost two-thirds of the clinical trial spend can be attributed to our plasastrum phase three studies. As James already mentioned, the registration of SHTG studies for plasastrum should read out in December, and clinical trial spend for these programs should thereafter moderate accordingly. SG&A expenses increase year-over-year compared to the prior year's second fiscal quarter, driven primarily by ongoing investments to support the commercialization 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 . And we ultimately expect to leverage these same capabilities for the advancement of 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 ALTERNATIVE ZERO PERCENT CONVERTIBLE SENIOR NOTES IN COMMON STOCK ALONG WITH THE ASSOCIATED CAPITAL CONSACTION. OTHER NOTABLE INFLOWS IN THE QUARTER INCLUDE THE $200 MILLION RECEIVED FROM SEREPTA UPON ACHIEVING THE SECOND PM1 PROGRAM MILESTONE AS WELL AS THE $50 MILLION ANNIVERSARY PAYMENT UNDER THE SEREPTA LONG-TERM COLLABORATION AGREEMENT. ALL OF THIS IS VERY MUCH IN LINE WITH THE INFORMATION PROVIDED PREVIOUSLY DURING OUR FEBRUARY EARNINGS 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,

A 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 III, SHASTA IV, AND MIRA III, WHICH IS THE SUITE OF PHASE III CLINICAL STUDIES DESIGNING SUPPORT AND SNDA FOR GUN BLOWING 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 aeronavT is expected around the end of Q3 or early Q4. This will be developed as a potential treatment for tauopathies, including Alzheimer's disease, and is our first program using the CNS delivery platform design Additional arrow INHPE and arrow ALK7 data releases are planned in 2026 for this novel non-ingredient strategy, which had quite encouraging early data, particularly in diabetic obese patients in combination with triseptide and with liver fat reductions as monotherapy or in combination with triseptide. 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 ARROWMAP-T. 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 and 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 1 1 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, thank you, 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, 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 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 the total number overall events. And I think that's kind of all I can say on that. 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 Gerbery 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 NHDB and ALK7 updates later this year and get your latest thoughts on these modalities. And I think investors have soured a little bit on NHDB 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 see you know, advance one or both for obesity treatment versus, you know, any 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 with GLP-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 prozepatide or other GLP-1s with either ALK7 knockdown or inhibin E knockdown. What we've seen from the clinical study that we talked about earlier this year from inhibin E with inhibin E knockdown is really 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 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 in January.

Thank you. One moment for our next question.

Our next question comes from Brian Chang. of JP Morgan.

Your line is now open. Hi, guys. This is Ron on for Brian.

Congrats on the quarter. Just wanted to ask, can you guys give more color on the interactions you've had with pairs 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 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 Palisades.

So, really, really positive conversations with payers about payer policies.

and about future coverage.

Okay, 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?

Well, gross-to-net, Dan can take that.

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

Yeah, so we, I mean, we ignore the, I actually asked you the same question. We ignore the why-to-net. Chris already explained, to make it premium price to the competitor there. We are not actually going to give guidance on gross to net. We have not seen anything substantial in that regard, no, to be currently expected. Other than things that are statutorily required, such as Medicaid relays and the manufacturing discount program and the like. But we have a policy at the moment not to provide any sort of guidance 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 repairs. To the contrary, I think that those interactions have been quite positive. This is a lowering of the WAC in expectation of an expansion on the market into FHTG and to ensure that that we would, the payers would not require a step through

Great.

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

Hey, guys. Savinova on 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 pay-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.

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 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?

Yeah, hi, Mari. This is James. I'll take that question. So 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. But no plans to extend the study or stay blinded for a longer period of this time.

Got it. Okay. Thanks for taking my questions.

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

Hi. You have the phone for Manny. Thanks for taking my question. Congrats on the culture. So, yeah, can you talk about how the for your data from our general informal strategy for our map team? And maybe also can you just comment on your internal expectations for this feedback? Thank you.

I don't think any of us caught that.

Could you say that again? I think that 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 formed a strategy for Aromapti. And you also talked about internal expectations.

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 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, 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 corticobasilar dementia or some of the real specific MAPT gain of function from the temporal dementia disorders. Those are all fair game for us as we think about phase twos and phase three down the road. So 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 tele-operatives.

Great.

Thank you. Thank you. One moment for our next question. Our next question comes from Joseph Tone 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 Shasta 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? Thank you.

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 modified Atlanta criteria that has definite, probable, and possible pancreatitis. And regarding the

Great, thank you.

Thank you. Our next question comes from Patrick Trucchio of HC 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 with. 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, 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. 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, you know, RNAi is a relatively straightforward and, you know, if you will, like the ability to come off drugs should some new biology 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 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 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 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, this is a dynamic question. Right now, we feel pretty good about our existing pipeline. with the right partner at some point. Everything else feels pretty good right now. You know, that may change as we talk to other companies and as our pipeline grows, but we don't feel a real sense of urgency to do additional deals on existing clinical programs other than maybe C3.

Thank you.

Our next question comes from Amineh Chaharelli from B. Riley Securities. Your line is now open.

Hi, everyone. Congratulations on the quarter. This is Amineh Chaharelli on behalf of Madison Alsati. I just wanted to ask, as you think about the next generation of the Dimer platform, Is a construct combining inhibin E or ALK7 with a non-overlapping mechanism target, you know, something you're evaluating for obesity or other indications? Thank you.

Yes. Okay. We can move on to the next question. Yes.

Our next question comes from Luca Easy from RBC Capital Markets. Your line is now open.

Oh, great. Hi, team. This is Shelby. I'm for Luca, and thanks for taking the question. 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 Demplo at a premium versus that PAR and SHTG, maybe as a way to kind of undercut their pricing since you're coming in second? Just wondering the rationale behind that. Thanks.

Yeah, thanks, Shelby.

As Chris previously mentioned, we do believe for Demplo as a best-in-class ApoC3 inhibitor, and 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 ApliC3 as a target, the depth of PG 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 AQC3 inhibitor, and as a consequence, should be premium priced.

Thank you.

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 Giaon 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 complete 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 PCST9, we can measure APOC3 in the blood, and we can measure LDL cholesterol and triglycerides, ApoB, 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 redoubt. In terms of where we go from here, I think we're working on that now. There may be some additional limited phase two work, which we could even consider doing as part of this study, but then moving quickly into an outcome study down the road. So 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 Kia Nikkei from Chardon Capital Markets. Your line is now open.

Yeah, thank you. Question about the magical 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, good question. So let me just take it back and remind everyone that where PMPLA-3, where aero PMPLA-3 came from. We didn't develop this on our own independently. This was part of our deal with Janssen. It was centered around HPV, FTSV, but also included a couple of additional targets. This was one of those targets. So we developed it for them. They did the phase one. The phase one was compelling. After only a single dose, they saw about a 40% reduction in liver fat in homozygous, in homozygous. So that was interesting to us. Janssen, as I understand it, decided to get out of MASH, and so 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, and that's sort of the good news and the bad news, right? The challenge there is that there will be, you know, a companion diagnostic on to this. And it made sense for us to find, you know, a pure play MASH company to take this forward. And, of course, Mederville is, I think, the best out there right now. So it made sense. It did really make sense for us to, you know, to spend much money right now to do a phase two, 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. And I just think that 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. So that's where we went. You know, we are thrilled to have Navigable as a partner. We're thrilled to have them develop that drug. I think it's a good drug.

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. 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.