Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. —

I will now hand the conference over to Vince Anzalone, Vice President, Investor Relations for Arrowhead. Please go ahead, Vince.

Thank you, and good afternoon, everyone. Thank you for joining us today to discuss Arrowhead’s results for its fiscal 2025 second quarter ended March 31, 2025. With us today from management are President and CEO, Dr. Chris Anzalone, who will provide an overview; Dr. Bruce Given, Interim Chief Medical Scientist, who will provide an update on our cardiometabolic pipeline; Andy Davis, Senior Vice President and Head of 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 earlierstage development programs; and Ken Myszkowski, our outgoing Chief Financial Officer, who is retiring this week, who will give a review of the financials. We also welcome Dan Apel, our incoming CFO, who is also with us on the call today. 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 Securi- ties Act of 1933 and Section 21E of the Securities and Exchange Act of 1934. All statements other than statements of historical facts are forward-looking statements and are subject 1 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, 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 Anzalone, President and CEO of the company. Chris?

Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. Before I start, I want to say thank you to Ken and wish him the best in his retirement. Ken has been a valuable member of the Arrowhead team, and he retires at a time of great financial strength to the company. The finance organization that Ken built over the years is very capable and provides strong support to our ambitious development and commercialization plans. From all of us at Arrowhead, thank you for all the important contributions over the last 16 years. I’m also excited that Dan Apel will join us as our new CFO at a critical time for Arrowhead. We expect to make the transition from development stage to commercial stage with the planned launch of plozasiran this year, pending regulatory review and approval. Dan is an accomplished pharmaceutical executive who can make immediate and important impact on our business. Let’s now talk about our business and the progress we’ve made toward our short-, midand long-term goals. Arrowhead is at an important point both in terms of capabilities and potential value as we drive our organization toward our first commercial launch, which we anticipate this year. Following this, we expect multiple additional independent and partner launches over the next few years. The combination of commercial expansion, our extraordinarily productive discovery engine, the increasingly validated nature of our 2 platforms and RNAi modality, our large pipeline of clinical stage assets, our strong balance sheet and clear access to additional nondilutive capital together provide us with a level of upside potential and stability that I believe — indiscernible — in our industry. This is always attractive, but it is even more valuable at a time when biotech markets have been depressed for the past several years and the near-term capital markets are uncertain at best. As the current biotech market weakness causes people to weigh the tradeoff of stability versus the potential for explosive value growth, I think we have the tools for both. I view our value proposition in layers. Layer 1 is plozasiran, constitutes our primary near and midterm value driver, and provides a strong base for us. Plozasiran is shown to be a potent triglyceride lowering agent across the multiple clinical studies in hundreds of patients. We believe there are 3 million to 4 million people in the U.S. alone who suffer from severe hypertriglyceridemia or SHTG, as defined by fasting triglyceride levels above 500 milligrams per deciliter. We are preparing to launch into a small subgroup of this population, patients with familial chylomicronemia syndrome or FCS, and have a PDUFA date of November 18, 2025. We also completed the submission of a marketing authorization application, or MAA, with the EMA, and are working through additional planned submissions in other select geographies. The Phase III data supporting our regulatory submissions were consistent and encouraging. Genetically defined and clinically defined FCS patients responded similarly with reductions in triglycerides of about 80% from baseline. Approximately 75% and 50% of patients who had triglycerides go below 880 and 500 milligrams per deciliter, respectively, which are discussing guidelines and the academic literature as important goals for minimizing pancreatitis risk. 3 These are truly impressive levels to achieve in FCS patients as the mean baseline triglyceride level in the study was approximately 2,500 milligrams per deciliter. Plozasiran was generally well tolerated and showed triglyceride reductions in 100% of patients treated at the primary endpoint of 10 months. Our hope of treating FCS patients is important. This is an historically underserved population, and we believe plozasiran could be an important medicine for them. However, we view this as just beginning. SHASTA-3, SHASTA-4 and MUIR 3 are Phase III studies designed to support a supplemental NDA and other applications on a global basis to enable us to treat a broader SHTG population. These studies are moving rapidly, and we believe they could be fully enrolled this summer. We are also in the process of initiating SHASTA-5, which is an outcome study to specifically evaluate the risk reduction of acute pancreatitis in high-risk patients with SHTG. We think this is an innovative strategy to potentially demonstrate meaningful value for patients, physicians and payers. Our second layer of value, may be our initial obesity candidates and initial CNS candidates. Regarding the former, ARO-INHBE is currently dosing in obese patients, and we expect ARO-ALK7 to begin dosing in obese patients shortly. Both are designed to intervene in a biological pathway regulating fat storage. ARO-INHBE targets hepatocytes with the same TRiM platform used in several ongoing clinical studies and has been in thousands of patients. It is designed to reduce hepatocyte expression of activin E, which is a ligand for adipose ALK7. ARO-ALK7 is the first adipocyte targeted siRNA with a new TRiM platform that in animal models has shown good uptake in adipose tissue and high levels of target gene knockdown with a long duration of effect, that may enable Q4 month, Q6 month or less fre- quent administration. ARO-ALK7 is designed to reduce expression of the ALK7 receptor 4 itself in adipose tissue. Both programs demonstrated substantial reductions in visceral fat versus control, while simultaneously preserving lean mass in animal models. Both targets are also supported by human genetics, where loss of function carriers have favorable body composition and metabolic characteristics compared to noncarriers without any apparent safety costs. It’s a very intriguing pathway that we believe may fill some important gaps left by standard of care obesity treatments addressing some of the shortcomings of the GLP-1/GIP class. The possibility for long-acting agents that are well tolerated, spare muscle mass and enable visceral fat loss without dependence on color restriction is exciting. ARO-INHBE be- gan dosing a Phase I/II study in December 2024, and we anticipate having some initial data by the end of 2025. As I mentioned, we expect ARO-ALK7 to begin dosing shortly, and we should have some initial data soon after ARO-INHBE results become available. Studies in both candidates include single dose and multiple dose monotherapy arms in obese subjects as well as multiple dose arms that include combination with tirzepatide. Our CNS-BBV platform has made great strides in recent years. We have a substantial amount of preclinical data across multiple animal models that make us optimistic that we can deliver potent RNAi drugs to the brain via a simple subcutaneous injection. Delivering large molecule drugs systemically and getting past the blood-brain barrier has been a holy grail virtually as long as complex biological drugs have been developed, and we expect to be in the clinic late this year. Our first candidate, ARO-MAPT targets the tau protein for potential treatment of Alzheimer’s. We expect to follow that with ARO-HTT licensed to Sarepta against Huntington’s disease by the end of the year. In the first half of 2026, we expect to bring ARO-SNCA to the clinic, which targets alpha-synuclein for potential treatment of Parkinson’s. These are all wellvalidated targets against very important diseases for which effective agents have long 5 been sought, and we look forward to seeing how they translate from animals to humans. Our third layer of value could come from our other Phase III drugs. We expect to begin enrolling a year-long Phase III study of zodasiran for homozygous familial hypercholesterolemia, or HoFH, shortly. The HoFH patients – excuse me, the HoFH patients treated with zodasiran in Phase I and Phase II studies give us confidence that they may have a potent LDL – I’m sorry, that it may have a potent LDL-C lowering agent that only requires quarterly dosing in this important at-risk patient population. The sales infrastructure we are building for zodasiran could easily be leveraged to this population. So this feels like a straightforward, relatively rapid, low-risk and low-cost expansion of our commercial presence. Fazirsiran is our drug candidate against AAT liver disease. Our prior studies give us confidence that it could be an effective agent to reverse fibrosis in this largely unserved patient population. Fazirsiran is partnered with Takeda, and they have publicly guided the Phase III studies could complete enrollment this year. They are 2-year studies to primary endpoint. While this is partnered, our economics are substantial with 50-50 profit share in the U.S., 20%, 25% royalties ex U.S. and up to $527 million of remaining milestones. While we view these as our primary near and midterm value drivers, there are substantial pieces of our business underneath them, providing redundancy and additional upside potential. They include four wholly-owned additional Phase II-ready clinical programs in ARO-C3, ARO-CFB, ARO-RAGE and ARO-PNPLA3. Two Phase II programs partnered with GSK against chronic hepatitis B infection in NASH, another Phase III program partnered with Amgen in olpasiran, four Phase I/II clinical programs partnered with Sarepta, three designated preclinical programs partnered with Sarepta, one of which I already mentioned in HTT, and six additional preclinical programs to be named by Sarepta. And of course, underlying all of this is a discovery engine that we believe is second to none in the siRNA field. 6 We expect this to continue to drive value as the basis for many additional wholly-owned drugs and through future partnerships. With all these layers, one can reasonably ask how many of these would be required to create a large, productive, sustainable pharmaceutical company. We indeed have many opportunities to create durable value. Importantly, we believe we have the capital and access to substantial additional capital to support our work. The Sarepta deal was a critical component of this. During the last quarter, we closed the global license and collaboration agreement with Sarepta Therapeutics, materially strengthening our balance sheet. This transaction brought in $500 million as an upfront payment and $325 million through the purchase by Sarepta of Arrowhead common stock at $27.25 per share. Arrowhead will also receive $250 million to be paid in annual installments of $50 million over 5 years. In the short term, we have potential to receive an additional $300 million in milestone payments associated with the continued enrollment of the Phase I/II study of ARO-DM1, which we are on track to achieve during the next few quarters. Taken together, this adds up to $1.375 billion in cash payments. The total potential value of this deal, including upfront payments, equity investments and potential milestones exceeds $11 billion. We are also eligible to receive tier royalties on commercial sales. This will be a transformational deal in any environment. As I mentioned, with the state of biotech equity markets today, we feel very good about not having to raise equity capital at this time to fund our growth as we become a commercial company. We are now funded into 2028 and through multiple important milestones that we think can drive substantial value for our shareholders. With that overview, I’d now like to turn the call over to Bruce Given. Bruce? 7

Thanks, Chris, and good afternoon, everyone. Arrowhead has been working in RNAi interference for nearly 20 years. During that time, we have made great strides creating a modality that is increasingly scalable, reliable, potent and generally well tolerated. We’ve also made great strides bringing RNAi to where it is needed. In addition to delivering to hepatocytes, we are now able to address lung, CNS, muscle, adipose and cardiomyocytes. We have always been a great R&D platform company, and we are now taking the next step forward as we seek our first marketing approval for plozasiran in familial chylomicronemia syndrome or FCS. Most of you will be aware of the results of our Phase III PALISADE study, which was published in the New England Journal of Medicine last year and showed statistically signifi- cant responses on all primary and alpha-controlled secondary endpoints, including a large reduction in the primary endpoint of triglyceride reduction of 10 months as well as reduction in incidence of confirmed pancreatitis in the protocol-defined comparison of placebo and the combined 25- and 50-milligram dose groups. Following pre-NDA discussions with the FDA, a marketing application for approval for use in FCS was submitted on November 16, 2024, and accepted for review by FDA with PDUFA date of November 18, 2025. At this time, we do not anticipate being asked to participate in an advisory committee meeting. We’ve been frequently asked whether the changes in Washington have impacted the review. While we have no special insights into the inner workings of the agency, our im- pression has been that the review is progressing as we would have anticipated, and we know of no FDA personnel or timing changes affecting our program at this time. We have also had routine prefiling meetings with EMA and appointed CHMP rapporteurs that culminated in the submission of a marketing authorization application or MAA on 8 February 28, 2025, which was confirmed to be valid for review on March 20, 2025. Our plan is to seek approval in the U.K. following approval in either the U.S. or Europe by leveraging the international recognition procedure. We’ve also had prefiling meetings with the Canadian and Japanese regulatory authorities and have plans for filing marketing applications in those and other jurisdictions as well. We are hopeful that these filings will lead to Arrowhead’s first commercial launch, possibly beginning as early as late this year. As we ultimately believe that plozasiran will be for FCS patients, this is just the beginning of the story for this important drug. While we were studying plozasiran in FCS, we are also evaluating the drug in much larger patient populations, including severe hypertriglyceridemia or SHTG, defined as patients with fasting triglycerides above 500 milligrams per deciliter but without genetic FCS, as well as in patients with mixed hyperlipidemia. These important studies led to publications last year in the New England Journal of Medicine, JAMA Cardiology and circulation journals. After receiving end of Phase II feedback from FDA and EMA, we have initiated a Phase III program in severe hypertriglyceridemia. This program is designed to meet key standards based on guidance documents from the International Council for Harmonization. Key requirements that drove design considerations include two pivotal placebo-controlled trials in SHTG patients and a safety database of at least 1,500 patients treated with plozasiran compared with placebo for 12 months. Hence, SHASTA-3 and SHASTA-4 are very similar studies designed to demonstrate statistically significant improvement in triglycerides with 25 milligrams plozasiran compared to placebo over 12 months of treatment. The two trials cover around — indiscernible — given the results from the Phase II SHASTA-3 trial, where the primary endpoint in triglycerides at week 24 compared to baseline at the 25-milligram dose was minus 53% with a 9 p-value less than 0.0001. To reach the necessary 50-milligram — indiscernible — safety, SHASTA-3 and SHASTA-4 are supplemented by a supportive MUIR 3 trial in mixed hyperlipidemia. Also blinded comparing 25-milligrams quarterly dose plozasiran versus placebo for 1 year with a planned enrollment of about 1,400 patients. We have previously guided that we expect the last patients to be randomized in the SHTG program this year. Based on enrollment to date, we now anticipate the last patient to enroll sometime this summer. We’ve been encouraged by the enthusiasm of our investigators as indicated by the rapid enrollment and also by a very low premature discontinu- ation rate for adverse events and other reasons. The last patients entered will be treated for 1 year before the database can be locked, the data analyzed and hopefully submissions made to regulatory authorities seeking approval for use in SHTG patients. Thus, before the end of the summer, it should be possible to narrow the potential timing for SHTG supplemental NDA submission. The SHTG program also features a first-of-its-kind study named SHASTA-5 to directly assess the ability of plozasiran to reduce the risk of acute pancreatitis in SHTG patients with a purpose-designed outcome study. We are conducting the study expressly to meet the needs of sophisticated payers, especially outside of the U.S. It is not gaining for the SHTG filings and is unlikely to be complete prior to their submissions. We do hope they will be completed during the review process in Europe and elsewhere to be available for pricing discussions — indiscernible — post approval. We cannot provide precise timing expectations, not only because of uncertain timing to complete enrollment, but also because as an outcome study, treatment will continue until the required number of events have been collected rather than for — indiscernible — for the trial is underway. More information on design will be presented following presentation at major medical meetings. The R&D group is also playing its role in growing the awareness that new treatments are 10 reaching the market for treating FCS. Our medical affairs team reporting into R&D continues to play a vital role in educating the medical community. Our medical science liaisons are actively engaging health care professionals in scientific exchange, helping them better understand and raising awareness of familial chylomicronemia syndrome, the significant unmet medical needs and the growing body of clinical data now available. The team has been present at key medical conferences during this last quarter, including the American College of Cardiology meeting, the European Atherosclerosis Society and British Atherosclerosis Society joint meeting and the European Society of Endocrinology meeting taking place presently. In parallel, our publications team continues to generate and disseminate important data to support these scientific efforts and expand awareness within the clinical community. Most recently at EAS, an abstract authored by experts in the field titled PALISADE, plozasiran decreases risk of acute pancreatitis and improves indices of quality of life in FCS was featured. The authors concluded in the abstract that in patients with FCS, plozasiran markedly reduced triglycerides and risk of pancreatitis with promising changes in indices for quality of life. Those of you who have watched us for a while know that we have another agent in our cardiometabolic pipeline that like plozasiran has very strong support from human genetics. I’m describing zodasiran, an RNAi drug designed to reduce expression of angiopoietin protein like 3 or ANGPTL3. This drug also produced strong results in two Phase IIs, including ARCHES-2 in mixed hyperlipidemia, also published in the New England Journal of Medicine as well as the GATEWAY study in HoFH patients, with data presented last week at the European Atherosclerosis Society Conference. However, as we’ve discussed previously, we saw zodasiran is positioned in the crowded LDL space where the unmet medical need has largely been addressed by statins and PCSK9 inhibitors. But there is an important population where we think zodasiran would 11 make an important contribution without requiring an outsized commitment of resources by Arrowhead. This being for patients with homozygous familial hypercholesterolemia. These patients have exceptionally high LDL cholesterol levels. And because of genetic abnormalities, usually result in very low or absent LDL receptor function are usually not able to get to goal at LDL levels even with maximal statin and PCSK9 therapy. This leaves them with very high risk of suffering cardiovascular events and early mortality. Monoclonal antibody against ANGPTL3 has already been proven effective in these patients, but requires monthly intravenous infusions and can lead to immunologic reactions. We conducted an exploratory Phase II study in this population and saw similar benefit, but with convenient quarterly subcutaneous dosing. Moreover, these patients are usually cared for by physicians which largely overlap the physicians who treat FCS and SHTG, making potential marketing of zodasiran in these patients efficient for us or to be approved. We have designed a Phase III study of similar size to our Phase III PALISADE study comparing zodasiran 200 milligrams quarterly to placebo and expect to be enrolling patients this year. Assuming successful demonstration of safety and efficacy and successful regulatory submissions, zodasiran could join plozasiran in the market as early as 2028 or 2029. As I said at the beginning of my remarks, we hope to see plozasiran emerge as our first commercially available drug to treat FCS patients as early as this year. Based on our expected completion of enrollment in the SHTG Phase III study this summer, we could see SHTG Phase III completion in the summer of 2026 and an sNDA filing shortly thereafter. Interestingly, also before completion of the decade, based on public guidance, progress with Phase III partnered program for olpasiran in Lp(a) and patisiran in liver disease associated with alpha-1 antitrypsin disease could result in approvals for these programs in a similar time frame, as well as with the possibility of some of our less mature partnered 12 programs for important orphan diseases might also find approval in that time frame. It takes patience in this business to see an important new platform rise. We feel there is some good reason to have confidence that RNA interference with joint small molecule drugs and monoclonal antibodies as a foundational technology in drug development, especially as the field, which we see Arrowhead still leading, continues to push into new cell types, opening up additional important diseases to be addressed. I’ll now turn the call over to Andy Davis. Andy?

Thank you, Bruce. With the PDUFA date for plozasiran set for November 18, just 6 months away, I’m pleased to share that our commercialization efforts are advancing rapidly and with strong momentum. As discussed by Bruce, the medical affairs team is in the field helping educate the physician universe and facilitating publication of the results of Arrowhead’s clinical trials. We’re also making strong progress in building our commercial sales team. A national sales leader and a full complement of regional sales leaders are now on board and focused on hiring and onboarding top-tier talent with deep rare disease and therapeutic area expertise. Interest has been very encouraging with thousands of resumes in the queue, and we’re on track to fully hire and train our sales force by late summer, ensuring ample time for target validation and disease state education in advance of launch. Our market access team is executing effectively on our pre-approval information exchange or PI strategy directed toward health care decision-makers to help them plan for our potential approval. We’ve now engaged with payers representing a significant number of U.S. covered lives, delivering compelling content on the clinical value and anticipated profile of plozasiran. We’re encouraged by their interest in plozasiran, especially regarding its potential to re13 duce triglycerides and acute pancreatitis risk. Additionally, our analytics team is deploying innovative technologies to identify individuals potentially living with FCS. We’re con- necting with these potential patients through disease state education efforts, including opportunities for them to opt in for continued communication and support. Across our research and stakeholder engagement, the clinical attributes of plozasiran continue to resonate strongly. Our market research suggests that plozasirin’s deep and durable triglyceride reduction is compelling to numerous stakeholders. The PALISADE study showed that plozasiran reduced triglycerides by approximately 80% from baseline as early as month 1. With this effect sustained over 12 months and with limited variability, while placebo subjects showed variable changes ranging from plus 10% to minus 18%. As a reminder, the primary endpoint in PALISADE was the median percent change from baseline in fasting triglyceride levels at month end, where plozasiran demonstrated a placebo-adjusted change of minus 59% with the planned commercial 25-milligram dose. Our market research also suggests that health care providers, caregivers and patients have a strong desire to see triglyceride levels fall below expert guideline threshold, such as 880 milligrams per deciliter and even 500 milligrams per deciliter. In PALISADE, approximately 75% of patients at the 25-milligram dose achieved levels below 880 and ap- proximately 50% achieved levels below 500. Numerous expert guidelines emphasize the importance of maintaining triglyceride levels below 500 milligrams per deciliter as the aspirational goal to reduce acute pancreatitis risk. Finally, we received feedback that patients are looking for a treatment option that minimizes disruption to their lives. Plozasiran shows a favorable dosing and safety profile. And as a reminder, plozasiran is conveniently administered once every 3 months, potentially minimizing treatment burden and improving adherence. As our U.S. launch preparations continue at full speed, we’re equally pleased to report steady progress on our European 14 commercial efforts as well. We’ve already established a field medical presence and are actively engaging in scientific exchange at key European scientific meetings, laying a strong foundation for a successful rollout. We remain on track and deeply motivated by the opportunity to bring investigational plozasiran to individuals living with FCS and their families in both the United States and priority countries outside of the United States. We believe this potential first-in-class siRNA therapy will mark a major advancement, and we’re fully committed to unlocking its patient impact. I’ll now turn the call over to James Hamilton.

Thank you, Andy. First, I’d like to provide a status update on our two early-stage obesity programs, ARO-INHBE and ARO-ALK7. ARO-INHBE is designed to reduce expression of activin E, which is a ligand for adipose ALK 7, while ARO-ALK7 is designed to reduce expression of the ALK7 receptor itself, both of which are involved in regulating adipose storage fats. These programs have the potential to reduce visceral fat mass while simultaneously preserving lean mass, which we demonstrated in preclinical models and are now evaluating in clinical studies. ARO-INHBE began dosing in December of 2024 and is progressing on our planned time line. As a reminder, the Phase I/II study will evaluate ARO-INHBE monotherapy administered to obese otherwise healthy volunteers in both single and multiple dose escalation cohorts. The SAD cohort dosing is now complete and the multi-dose monotherapy cohorts are actively enrolling. The study is also evaluating multiple doses of ARO-INHIBE in combination with tirzepatide, and these combination cohorts are actively enrolling now on our planned time line. 15 We anticipate the ARO-ALK7 clinical program will be up and running shortly. The design of this study is very similar to the ARO-INHBE study with SAD and MAD monotherapy cohorts and MAD cohorts in combination with tirzepatide. This study will also enroll obese otherwise healthy volunteers. Both studies are designed to assess safety, tolerability, pharmacokinetics, pharmacodynamics and multiple exploratory obesity efficacy endpoints. We anticipate that some initial data may be available for ARO-INHBE around the end of 2025 and potentially for ARO-ALK7 shortly thereafter. Our muscle-targeted programs partnered with Sarepta, ARO-DUX4 for FSHD and ARODM1 for myotonic dystrophy type 1 also continue to make good progress in the Phase I/II studies, which are ongoing. While the decision to release data will be made jointly with Sarepta, it is our expectation that initial data release is possible in 2025. Lastly, I want to highlight some top line results from Part 2 of the Phase I/II clinical study of ARO-C3 designed to reduce production of complement component 3 as a potential therapy for various complement-mediated diseases. In patients with IgA nephropathy or IgAN, ARO-C3 achieved deep and sustained reductions in alternative pathway complement activity and proteinuria. The max mean reductions in C3 was 89%, with AH50, which is an alternative pathway hemolytic assay reduced by 85%. ARO-C3 also led to an important improvement in proteinuria with a mean reduction in spot UPCR of 41% and a maximum individual reduction of 89% from baseline up through week 24. ARO-C3 was generally well tolerated and the observed duration of effect is supportive of once every 3 months or less frequent subcutaneous dosing. We are very pleased with these results and are planning to present fuller data set at the upcoming European Renal Association or ERA Congress in June. I will now turn the call over to Ken Myszkowski. 16

Thank you, Jim, and good afternoon, everyone. As we reported today, our net income for the quarter ended March 31, 2025, was $370.4 million or $2.75 per share based on 134.5 million fully diluted weighted average shares outstanding. This compares to a net loss of $125.3 million or $1.02 per share based on 123.3 million fully diluted weighted average shares outstanding for the quarter ended March 31, 2024. Revenue for the quarter ended March 31, 2025, was $542.7 million. No revenue was recorded in the quarter ended March 31, 2024. Revenue in the current period relates to our license and collaboration agreement with Sarepta. As you know, the agreement with Sarepta was significant and included many assets, including clinical assets, preclinical assets and other assets to be developed. Counting guidance requires that we allocate consideration to several items, including the value of the licenses we transferred, the ongoing work of certain clinical trials that we will oversee as well as expected obligations regarding future assets to be developed. Initial fixed contract revenue to be allocated included the upfront payment of $500 million, the premium paid on the stock purchase of $84 million and $250 million related to the 5-year annual milestone payments. This totals to about $834 million, majority of which was allocated to the license agreements and recognized immediately, and the balance will be recorded as we fulfill our performance obligations. We recognized revenue of $542.7 million during the quarter ended March 31, 2025, and we expect the balance to be recognized over the period that we satisfy these performance obligations. These obligations include overseeing certain clinical trials as well as performing R&D work related to future clinical candidates. We expect $90 million to $125 million of revenue to be recognized over the next 12 months, solely related to the revenue recognition of the initial fixed contract revenue. The balance will be recognized over the next 5 years – 517 or-so years, most of which will be recognized in the first half of that time period. We also expect future revenue related to cost reimbursement for certain discovery and manufacturing activities. Future near-term milestones of $300 million related to the DM1 program are expected to be earned in the next few quarters and will be recorded in their entirety as revenue at that point as with any other future milestone payments and royalties. Total operating expenses for the quarter ended March 31, 2025, were $161.5 million compared to $126.2 million for the quarter ended March 31, 2024. Key drivers of this change were increased candidate costs as the company’s pipeline of clinical candidates both increased and advanced into later stages of development. Net cash provided by operating activities during the quarter ended March 31, 2025, was $460.1 million compared with net cash used in operating activities of $92.4 million for the quarter ended March 31, 2024. Increase in cash provided by operating activities is driven by the cash received for the Sarepta agreement. Turning to our balance sheet. Our cash and investments totaled $1.1 billion at March 31, 2025. Our common shares outstanding at March 31, 2025, were 138.1 million. With that brief overview, I will now turn the call back to Chris.

Thanks, Ken. Arrowhead is in a strong and stable position as a business, and we have made meaningful progress toward our long-term goal of developing and ultimately commercializing new innovative medicines for millions of patients. We are on schedule to launch plozasiran this year, pending regulatory approval with what we think is a best-inclass profile with meaningful differentiation from currently available therapies in FCS. We are also well on our way to fully enrolling this summer our suite of Phase III studies 18 designed to support regulatory submissions for the large SHTG patient population. We are funded into 2028 and potentially through multiple launches of wholly owned and partnered programs in late-stage development. In addition, we believe our technology platform is the broadest and best in the field, giving us many opportunities to receive additional capital inflows from business development in areas that are outside of our core commercial focus. Thank you for joining us today. And I would now like to open the call to your questions.

— Operator Instructions — And our first question comes from Maury Raycroft of Jefferies.

Congrats on the progress. And best wishes to Ken, and welcome, Dan. For INHBE and ALK7, you’ve noted that the goal there is not to compete with GLP-1s, but to be used in combination. What’s the latest you’re seeing on how you’re setting expectations for initial monotherapy and potential combo data? I guess, what you want to see in the initial update, including changes on weight loss, body composition and relevant biomarkers?

Yes. Thanks, Maury. So look, we’re not giving any guidance on what we expect to see because this is a first-in-human study. The AML data were compelling. We saw good weight loss as a monotherapy. We saw good weight loss in combination with tirzepatide. This is – as you know, this is a new pathway that we think could fill some of the massive amounts of white spaces in the GLP-1/GIP current standards. So look, we’re looking forward to seeing what we see. Our – the real benefits here, we think, are potentially not just weight loss but quality of weight loss. Are we seeing the loss 19 of visceral fat? Are we seeing a retention of lean muscle mass? We saw that in animal models, we hope to see that in humans as well. And also in animals, we did not see – this was not the result of caloric restriction, it was in the context of normal feeding. That would also be – that sort of thing would be helpful in humans. So look, let’s just see what we see. I think we’ll have our first flood of data towards the end of this year, and then it should be data-rich, gosh, virtually every quarter for the next year or so after that.

And our next question comes from Jason Gerberry of Bank of America.

Just ahead of the plozasiran FDA review decision, I’m wondering how you think about the robustness of your pancreatitis data and how that might look or feel a little bit differently in the package insert. I noticed TRYNGOLZA just as a mention of the numerical incidence reduction in the clinical section. And I’m wondering if you guys feel like based on PALISADE that you might get maybe a more robust front page reference to the pancreatitis benefit. Anything you can just offer on the potential aspects of label differentiation would be much appreciated.

Yes. This is Bruce. We haven’t had any labeling negotiations with the FDA at this point, which as you would expect, I mean we’re still in the midst of the review process and label negotiations come later. So it’s really impossible for me to estimate how they may view things. We obviously like our data quite a bit. We did our study differently in that we looked at patients that had confirmed pancreatitis using the Atlanta criteria, while Ionis used – they developed a scale that also included possible and probable "pancreatitis" which actually don’t meet the Atlanta criteria as definite pancreatitis. 20 So frankly, it’s a little bit of an apples and orange comparison. And I really don’t know how that might play out during labeling discussions or even in the market. But it is a little bit apples to oranges. We went, I guess, what you might say is the more conservative route. We think especially, for instance, with payers in Europe, especially that might turn out to be important. But it’s – clearly, these drugs are extremely helpful, not just in reducing triglycerides, but also in turning that reduction in triglycerides into reduced abdominal pain and pancreatitis. So we’ll see. I really can’t give you any guidance for what labeling is going to look like. In our business, we do the studies, we submit, the FDA reviews and the FDA decides. So ultimately, it’s going to be up to them. We’ll obviously discuss it with them, but I can’t speak for them at all.

And let me just add here more broadly. The biology here is clear. In these patients, the higher the triglycerides, the higher the risk of pancreatitis, the higher the risk of abdominal pain. And so the goal here is to get triglycerides as low as you can. So while we are monitoring for pancreatitis, of course, and in the SHASTA-4 studies, we are looking at abdominal pain. The real thing to focus here on is how low can we get triglyceride. And as I mentioned in the prepared response, prepared remarks as well as we presented in the past, we get something like 75% of patients in that Phase III study below 880 and something like 50% below 500. And that’s a real feat for these FCS patients who, as you mentioned, came into a study with a mean triglyceride level of 2,500. I think that’s what we need to focus on here.

And our next question comes from Ellie Merle of UBS. 21

This is Jasmine on for Ellie. So first for plozasiran in SHTG, just on acute pancreatitis, can you talk about what the latest is that you’re expecting for your baseline rate of AP in your population for SHASTA-3 and SHASTA-4? And what do you think the magnitude of effect that you think that you can show here is? And then just quickly, second on zodasiran. Can you clarify your current expectations in terms of potentially expanding beyond HoFH here?

Let me take the second one first with zodasiran. The expansion beyond HoFH would be in potentially some sort of high-risk HeFH population. And that’s actually something we discussed with the agency and proposed a narrow approach of looking only at those patients that despite maximal therapy, we were not able to get to the goal of LDL reduction that would be associated with the greatest reduction of risk. They just weren’t comfortable with that because they thought – well, I can’t speak for why, but they – maybe because they thought it was going to set precedent. But they – to get into HeFH, they wanted a full program, multiple adequate well-controlled trials about 1,500 patients or more safety, et cetera. And it didn’t make sense to us to go after such a sliver of high-risk patients with a very expensive, very long program. So we’re going to stay focused on HoFH. And we do not anticipate at this time that we would expand zodasiran beyond HoFH. It’s just not feasible, it’s not a good use of our resources. Going back to plozasiran. If I understood your question of what we think the mean, the entry triglycerides might look like and what sort of response we might see, you would expect the chests are pretty good that we’ll pretty much replicate what we saw in Phase II. And in Phase II, the mean triglycerides in the SHTG population in that study were around 90 – I think, maybe 850 to 900. And as I said, our placebo-adjusted change was 53% 22 reduction. So substantial large reductions in triglycerides, which is why we said this trial is really – these trials are really overpowered because even with a smaller trial in Phase II, we have p-value of 0.001. So it should be an impressive – can’t say it will, but it should be an impressive – we expect it to be an impressive reduction in triglycerides. But the mean enrollment triglycerides around – did I get your question right, Ellie? Did I understand your question?

Yes. We also were just interested in the mean of what you expect for acute pancreatitis kind of at baseline?

In the pancreatitis study. Okay. Well, I would expect that’s going to be closer to the FCS to the PALISADE baseline. So I would expect that the pancreatitis study baseline, it won’t surprise me if it’s around 2,000. It could be a little bit lower because patients, especially when they’ve had a history of pancreatitis, they’re more susceptible to repeat pancreatitis even at lower values. But it won’t shock me if it turns out to be somewhere around 2,000.

Our next question comes from Patrick Trucchio of H.C. Wainwright & Company.

Congrats on all the progress. I was actually curious about your ARO-C3 and ARO-CFB programs and your latest thinking regarding the potential positioning of these compounds in complement-mediated diseases and how you’re viewing these compounds. Are they core to your portfolio or there’s potential here for partnering?

23 Sure. I’ll take the second part of that, and I’ll the first part more for James. Look, we are open to discussing partnerships for C3 and Factor B. Those drugs, at least in my mind, those drugs work. They do what they’re designed to do. They lower C3 and the lower Factor B respectively. And we think there’s a number of places they can go. If we – if push came to show, we could certainly build out a commercial presence within a fairly narrow set of opportunities. But if we can find the right partnerships, I think that would be more beneficial to us. We’ll just see if we can find the right partnerships with the right economics. And right now, it’s too early to tell. James, do you want to talk about some of the opportunities?

Yes, sure. So the data that we talked about earlier today with ARO-C3, of course, that’s the IAN data. We’re still pending some data in the C3G population with that molecule. And of course, ARO-CFD is also applicable or could be used in those renal disease populations, potentially in some of the hematologic complement-mediated indications as well. And we think based on what we’ve seen so far with ARO-C3 that it stacks up pretty well against the other complement-mediated drugs approved or being studied in the renal indications. In terms of proteinuria reduction, we talked about the 41% reduction in proteinuria with ARO-C3. I think that relative to what else is out there is pretty competitive, particularly when you look at the infrequent dose administration that can be used with RNAi dosing every 3 or every 4 months, that could have some advantages.

And our next question comes from Andrea Newkirk of Goldman Sachs.

James, maybe one for you as you think about entering the obesity space. How are you thinking about advancing both ARO-ALK7 as well as ARO-INHBE through clinical develop24 ment? And do you have interest or capacity to advance both? Or would you look to make a decision of one versus the other following the initial data sets?

Sure. Yes. So our thoughts with those that from a cost standpoint, it doesn’t cost us that much to do the preclinical and at least the Phase I development. And we have AROINHBE, which targets the hepatocyte expression uses the so-called GalNAc technology for delivery. That technology is pretty well vetted. We know what the safety profile at least of the platform is, and we know that we should be able to knock down the gene target in the hepatocyte. In contrast, ARO-ALK7 uses a completely different platform. The animal data look really compelling with that molecule, the platform has never been in humans before. So presumably, there’s a little bit more risk there just because the platform hasn’t been derisked. Our thought was to take both of those through Phase I and then get a look at the data at both the safety and the PD and efficacy data and then choose one to move forward, and there may be opportunity for partnership either with one or both of those potentially. But that was the thought of why we brought both of them into the clinic. And let’s also be clear, these – I do not expect these to be our last two obesity assets with our ability to address adipocytes and our ability to address potentially CNS via this bloodbrain barrier platform that we’ve got. There are a ton of really compelling metabolic and obesity targets that I think you’ll see coming down the pipe in the near term as well.

And our next question comes from Luca Issi of RBC.

Congrats on the progress. Maybe, Bruce, circling back on a prior question, can you just 25 maybe remind us how you’re thinking about SHASTA-5 study design? What patients will be enrolled? And maybe most importantly, how many patients do you need to actually hit the stat? So if you can talk about powering assumptions, that would be much appreciated. And then maybe bigger picture on plozasiran. Chris, how are you thinking about commercialization of the molecule ex U.S.? Are you planning to do that by yourself? Or you’re still looking for a partner? Anything you can talk there, much appreciated.

Yes. So again, this trial will be, we believe, the first ever trial we’re demonstrating a benefit in pancreatitis as the primary endpoint. So it’s similar to a MACE trial from the standpoint of we’re going to count events. And when we hit a certain number of events, we’ll analyze. We haven’t yet divulged what that number of events is, I think we probably will in the future. But so far, we haven’t. But we have a pretty good idea of, obviously, what that is. But we also haven’t said how many patients we’re targeting. But again, my guess is that we may continue to involve depending on sort of what the rate of pancreatitis is that we’re seeing in the early days. But the trial itself is a trial enriched from the perspective that it requires that patients have had a history of pancreatitis including history of pancreatitis in the recent past, which those patients are at higher risk of pancreatitis than hyper triglyceride patients that have never had a pancreas event. But again, no one have done a trial like this before. So understanding exactly what the observed risk will be is something that we’ll get some understanding. And of course, all be blinded, but we’ll get some understanding as the trial gets underway, I think it’s moving. And that will certainly tell you. But it’s certainly not the size of a CVOT or anything like that, it’s much smaller given the reduction of pancreatitis we saw in PALISADE, for instance. But as you know, we haven’t – I think we’ll give more detail in the future, but we’re not ready to give all the deep detail at this point. 26

Luca, so regarding your question on plozasiran. So as you know, we’re full set ahead in the U.S. for FCS and then potentially SHTG open. Rest of the world, we are open to finding partners. We are preparing right now in Europe. Andy, can discuss how we’re approaching that right now.

Yes, Luca. So we think the European markets, in particular, the large four European markets in the U.K. lend themselves extremely well to commercialization for a rare disease like FCS. Many of these patients on their patient journey or triage through a small number of centers of excellence. And so with limited infrastructure and resources, we believe we’re able to help these potential FCS patients through those centers of excellence. And so as far as priority markets outside the U.S., those large markets in Europe and the U.K. and also Canada are a priority for us.

Our next question comes from Edward Tenthoff of Piper Sandler.

So important to note that you guys are — indiscernible — reviewed. Do you anticipate an AdCom or anything like that? And what other steps are you taking in preparation for hopeful approval and likely launch?

Well, as far as the AdCom goes, we’ve not been advised that there’s an expectation for an AdCom. So at this time, we don’t think AdCom is in our future. As you probably know, I mean, the agency can change their opinion on that at any time if data develops in their analysis that makes them want to have an AdCom for some reason. But at this point, there’s no anticipation of AdCom. So the likelihood, I suppose it’s lower every day, we 27 get closer to a potential improvement. We can’t say we won’t have one because they can decide at any time that they need it. But we don’t see it though. And then the second part, I guess, is?

The second part was what actions are we taking to be ready for launch.

Yes. So I mean I guess we talked a bit about that. From the R&D perspective, we are – we had an educational vision under our medical affairs function and then the cells. So that’s very much just a matter of helping physicians to be ready for a new drug coming into the FCS space, where really there hasn’t been any promotional effort up until the Ionis launch we’ve ever really for us. So there’s a big...

And Bruce, do you think the launch of Ionis is helpful in terms of sort of priming the pump a little bit there? And then hopefully, you guys coming in with a better therapy after?

Well, look, I think any orphan disease that has had essentially no approved therapies has always benefited from as much educational effort as you can get. And history tells us, and I could quote many examples where the first approved drug really did not fully reopen that market. It often takes two or more companies to be promoting into a space, even an orphan space, to really get those markets to open up and grow. So it’s paradoxical because people might take you better off being alone. In many ways, you’re actually better off when there are multiple competitors. And yes, they find it out who gets the most share in the end. But actually, the more educational noise, the better when you’re trying to open up a market like FCS and the exact same will be true for SHTG 28 as well. More noise is better than less. And yes, the best drug usually wins the share battle, but the pie gets much bigger with more education going on.

Our next question comes from Mike Ulz of Morgan Stanley.

Maybe just another one on plozastiran and the upcoming FCS launch. It sounds like you guys are making good progress in launch prep, but maybe you could just talk about or remind us the U.S. patient population and then some of the progress you’re making identifying patients and if there’s any way to try and accelerate that trend?

Yes. Thanks for the call, Mike. You’d be familiar with the epidemiological data suggesting that the prevalence of FCS in the United States would be 1 to 13 per million. And so that spans anywhere from the hundreds of patients in the U.S. to mid-single digit thousands. And we think the variability around the single-digit thousands is really around whether you think about genetic FCS or even clinically diagnosed FCS. That’s why there’s some variability there. As a reminder, of course, in PALISADE, we studied plozasiran in both genetically confirmed and clinically diagnosed patients and showed similar results. And so that’s how we think about the broader market for FCS. As far as patient identification, I would say that our internal team here, our analytics team and our marketing team is comprised of seasoned professionals who have cut their teeth in cardiometabolic and lipid specifically and are really using the latest technologies to patient find, and ultimately to support those individuals who may have FCS and don’t know that they have FCS. So patient finding will be absolutely critical as we move into the space as it is with any ultra-rare condition. And we feel like we have the people and the capabilities to excel there. 29

And our next question comes from Mayank Mamtani of B. Riley Securities.

Congrats to Ken for 16 years of service. Just maybe on the – quick follow-up on the SAD data. Is there anything that you can or willing to share what maybe the learnings there were. And on the MAD Part 1b and Part 2, which is the combination. Are those sequential? Or are they happening in parallel? And I’ll just have one follow-up for Ken, if I may.

Yes, sure. On the second part of the question, those – the combo studies and the MAD noncombination studies, those are in parallel. So those are enrolling at the same time. And then I think in terms of what we can share, as Chris said earlier, we’ll have to wait and see later this year what kind of data that we have available.

Okay. Understood. And Ken, what partnership-related milestones are factored in your – this 2028 runway guidance? If you could maybe just clarify that. Congrats again.

So we’ve included the near-term milestones that we expect to get from Sarepta. And beyond that, there are other milestones if we think they’re probable of happening that we’ve included those as well. But we’re not providing specifics on that.

And our next question comes from Mani Foroohar of Leerink.

This is [ Brian ] on for Mani. Maybe just a quick financial one. I noticed you guys started to pay down that credit facility. I’m just wondering, should we expect that to continue 30 over the course of the year? Or is this more of just a onetime pay down to kind of bring that total down?

So the onetime pay down was because of the Sarepta agreement. There will be future payments on that, but it’s only related to times when we have cash flow coming in from milestones and such. So it’s only attributable to when we have some cash that’s coming in.

And our next question comes from Brendan Smith of TD Cowen.

Maybe just similar to a couple of earlier questions. I wanted to ask a little bit more on your latest thinking for the CNS assets. So is the plan as of today to carry those forward internally? Or are you already kind of thinking that these could potentially be partnered or licensed? And then maybe more specifically for MAPT, are there any subsets of the AD population you’ll look to target first? Just kind of wondering how we should think about the potential design there and segmentation of that market.

Sure. Bruce, why don’t you take the MAPT, and then I’ll take the broader question?

Sure. So the second question on MAPT. Not that at this point for the Phase I design. It’s not entirely finalized yet, but suffice to say that the main goal of the study will be to evaluate safety and measure PD markers of knockdown of how various subtypes of talent in different populations. So we’ve not specifically pin down subtypes of PD that we plan on study. 31

And regarding your first question, so as we talked about, our first three candidates in the clinic are expected to be MAPT towards the end of this year for Alzheimer’s HTT, Brian, and that’s already licensed to Sarepta. We expect that to be this year, too, by the end of the year and then first part of next year alpha-synuclein for Parkinson’s. So HTT is already off the docket right now. We have alpha-synuclein and MAPT. We’ve always been clear to potential partners that MAPT is off limits right now. We view that as a potentially very high-value target. Look, we don’t know yet if this CNS-BVV platform is going to translate from animals to humans, we will see. And so this is a bet that we’re making. But we think it’s a good one, given the data we’ve seen in the preclinical models and given the validated nature of MAPT targets. So we’re holding on to that for – at least for right now. We’ll see where that goes in the future. Absolutely, look, we like that target a lot. And if a partner comes in with – if the right partner comes in with the right kind of deal, we would certainly consider partnering that. So that we don’t feel quite as strongly at least in the near term as we do on MAPT. And then look, those are the first three, we think many. Once we have this platform validated in humans, we’re going to run. There’s a number of additional good targets that we are developing internally. And my expectation is if we see that this translates as we hope it does, you’re going to see a large number of additional CNS targets, some of which we’ll hold on to, some of which we’ll partner.

Our next question comes from Prakhar Agrawal of Cantor Fitzgerald.

So Ionis has the Phase III SHTG readouts coming soon, if olezarsen achieved statistical significance on pancreatitis events in Phase III, how does that impact your development 32 strategy to have the pancreatitis reduction data in the label around the time of launch versus waiting for SHASTA-5 to read out? And anything else you will be focusing on olezarsen SHTG trial reads out?

Well, it will be interesting to see whether they can accrue enough events to actually achieve anything there, we’ll see. And from our perspective, that was not a good enough for us to rely on that especially in Europe to do that. Our program is also designed to look at pancreatitis events. Albeit we look at definite pancreatitis, we don’t look at possible cases. We just don’t think that – we think there’s a high chance that that’s going to worry the health technology authorities in Europe. And so we really felt that we had to be – it had to be definite pancreatitis from our perspective. But we are adjudicating any pancreatitis that occurs in SHASTA-3 and SHASTA-4, and we are – we have written those studies, so that we can merge those two trials for the purpose specifically of looking at pancreatitis, and we intend to do that. But ultimately, that for us feels like a high-risk strategy in all-comers SHTG. And again, I think that a purpose-built study rather than a secondary endpoint will be much more agreeable to the payers, the most sophisticated difficult payers in the world, which are mostly the European payers and some other places as well.

And our next question comes from David Lebowitz of Citi.

This is Ike Lee on for David Lebowitz. We have one on pricing for plozasiran. How do you think about launching this in FCS and then waiting for the SHTG data in the interim. We expect something like TRYNGOLZA also getting a label expansion in SHTG and therefore, having to move from an ultra-rare pricing scheme into something that is a little 33 bit cheaper. Is that something on your mind yet as you look towards commercialization? What are your thoughts on potentially having to navigate the ultra-rare versus much more prevalent disease pricing schemes?

Sure. Look, I think we can have and we are having transparent and open conversations with payers. Should we be lucky enough to have plozasiran approved in FCS, it’s a relatively narrow population. And so we would need to get reimbursed at a high level that is commensurate with ultra-orphan. Should we be lucky enough to have SHASTA-3 and SHASTA-4 read out well and get approved for a broader label, of course, we would bring the price down conceptually, so that we know on a more granular level about what those two prices are, we just don’t know at this point. It’s going to depend upon a lot. So conceptually, that is our strategy, but I can’t get more granular.

Thank you. I’m showing no further questions at this time. I’d like to turn it back to Chris Anzalone for closing remarks.

Well, thanks, everyone, for joining us today. It is bittersweet to end this call. This is the last time that I’m going to have Ken on my left during these calls. And as we mentioned in the prepared remarks, I really appreciate his great work for the last 16 years, and I’m going to miss have him here. Having said that, I’m, of course, excited to have Dan on board today to my right, maybe to my left once Ken is gone. But thank you all for joining us today.

This concludes today’s conference call. Thank you for participating, and you may now disconnect. 34 Copyright © 2025, S&P Global Market Intelligence. All rights reserved 35