Takeda Pharmaceutical Company Limited

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference call. Throughout today's recorded presentation, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. I will now hand the conference over to Ben Sancelloni, Vice President of Infectial 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, and in March 31, 2025. With us today from management are President and CEO, Dr. Chris Anzolone, 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, who will present, Chief Medical Officer and Head of R&D, who will discuss our earlier stage development programs, and Ken Miskowski, our outgoing Chief Financial Officer, who is retiring this week, who will give a review of the financials. We also welcome Dan Appel, 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 Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks, please refer to our SEC filings, including our most recent annual report on Form 10K and our quarterly reports on Form 10Q. I'd now like to turn the call over to Chris Anzolone, 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 Aero IT, and he retires at a time of great financial strength to the company. The financial 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 Aerohead, thank you for all the important contributions over the last 15 years. I'm also excited that Dan Appel will join us as our new CFO at a critical time for Aerohead. We expect to make the transition from development stage to commercial stage with the planned 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, mid, and long-term goals. Aerohead 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 culmination of commercial expansion, our extraordinarily productive discovery engine, the increasingly validated nature of our platforms and R&I modality, our large pipeline of clinical stage assets, our strong balance sheet, and clear access to additional non-dilutive capital together provide us with a level of upside potential and stability that I believe is a priority in our industry. This is always attractive, but it's 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 trade-off of stability versus the potential for explosive value growth, I think we have the tools for both. I view our value proposition in the layers. Layer one is plesaserian. Plesaserian constitutes our primary near and midterm value driver and provides a strong base for us. Plesaserian has shown to be a potent triglyceride lowering agent across multiple clinical studies in hundreds of patients. We believe there are three to four million people in the US alone who suffer from severe hyperglyceridemia, 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 mycranemia syndrome, or FCS, and have a PDUFA date of November 18, 2025. We also completed the submissions of a marketing authorization application, or MAA, with the ENA and are working through additional planned submissions in other select geographies. The phase three 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 with had triglycerides go below 80 and 500 milligrams per deciliter, respectively, which are discussing guidelines in the academic literature as important goals for minimizing pancreatitis risk. 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. Plasaurane 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 plasaurane could be an important medicine for them. However, we view this as just the beginning. Shasta three, Shasta four, and year three are phase three 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 five, 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 gains. Regarding the former, Arrow-I and HBE is currently dosing in obese patients and we expect Arrow-ALC 7 to begin dosing in obese patients shortly. Both are designed to intervene in a biological pathway regulating fat storage. Arrow-I and HBE targets hepatocytes with the same trim platform using several ongoing clinical studies and has been in thousands of patients. It is designed to reduce the hepatocyte expression of active in E, which is a ligand for adipose ALC 7. Arrow-ALC 7 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 targeting knocked down with a long duration of uptake that may enable Q4 month, Q6 month, or less frequent administration. Arrow-ALC 7 is designed to reduce the expression of the ALC 7 receptor 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 non-carriers without any apparent safety costs. It is a very intriguing pathway that we believe may fill some important gaps left by standard of arrow-VC treatments, projection-cellulose shortcomings of the GLT-1 GIP class. The possibility of long-acting agents that are well tolerated, spare muscle mass, and enable visceral fat loss without dependence on caloric restriction is exciting. Arrow-I and HBE began dosing a Phase 1-2 study in December 2024 and we anticipate having some initial data by the end of 2025. As I mentioned, we expect Arrow-ALC 7 to begin dosing shortly and we should have some initial data soon after Arrow-I and HBE results become available. Studies in both candidates include single dose and multiple dose monotherapy arms to OB subjects as well as multiple dose arms that include combinations with trisemminide. Our CNS BVB 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 RNA drugs to the brain via simple cell-cutaneous 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, arrow-MAPT, targets the tau protein for potential treatment of Alzheimer's. We expect to follow that with arrow-HTT, licensed dyssorepta against Huntington's disease by the end of the year. In the first half of 2026, we expect to bring arrow-SNCA to the clinic which targets alpha-synuclein for potential treatment of Parkinson's. These are all well validated targets against very important diseases for which effective agents have long been sought and we look forward to seeing how they translate from animals to humans. A third layer of value could come from our other Phase III drugs. We expect to begin enrolling a year-long Phase III study of Sodaciran for homozygous familial hypercholesterolemia, or HOFH, shortly. The HOFH patients treated with Sodaciran in Phase I and Phase II studies give us confidence that it may have a potent LDL-C lowering agent that only requires quarterly dosing in this important at-risk patient population. The stable infrastructure we are building for Sodaciran could easily be leveraged for this population, so this feels like a straightforward, relatively rapid, low-risk, and low-cost expansion of our commercial presence. Sodaciran 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 uninserved patient population. The V. sarana is partnered with Takeda, and they have publicly guided that Phase III studies could complete enrollment this year. They are two-year studies to primary end point. While this is partnered, our economics are substantial. We're 50-50 profit share in the US, -25% royalties ex-US, and up to $527 million of remaining milestones. While we view these as our primary near-inventory value drivers, there are substantial pieces of our business underneath them providing redundancy and additional upside potential. They include four fully-owned additional Phase II-ready clinical programs in AeroC3, AeroCFB, AeroRage, and AeroP and PLA3. Two Phase II programs partnered with GSK against chronic hepatitis B infection and MASH. Another Phase III program partnered with Amgen in Olpasarin. Four Phase I-II clinical programs partnered with Sarefta. Three designated preclinical programs partnered with Sarefta, one of which I already mentioned in HDT. And six additional preclinical programs to be named by Sarefta. And of course, underlying all of this is the discovery engine that we believe is second to none in the siRNA field. We expect it to continue to drive value as a 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 two substantial additional capital to support our work. The Sarefta deal was a critical component of this. During the last quarter, we closed the global license and collaboration agreement with Sarefta and the U.S. Department of Agriculture, materially strengthening our balance sheet. The transaction brought in $500 million as an upfront payment and $325 million through the purchase by Sarefta of Arrowhead CommonSci at $27.25 per share. Arrowhead will also receive $250 million to be paid in annual installments of $50 million over five years. In short term, we have potential to receive an additional $300 million in milestone payments associated with the continued enrollment of the Phase 1-2 study of Arrow D1, 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 tiered royalties on commission 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 in June 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 Gettman. Bruce?

Thanks, Chris, and good afternoon, everyone. Herohead has been working in RNA 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 RNA platform company, and we are now taking a next step forward as we seek our first marketing approval for Closacirane and familial chondromycomenia syndrome, or SDS. Most of you will be aware of the results of our Bay Street Palisades study, which was published in the New England Journal of Medicine last year and showed statistically significant 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-MDA discussions with the FDA, a marketing application for approval for use in SDS was submitted on November 16, 2024, and accepted for review by FDA with the due date of November 18, 2025. At this time, we are not anticipating being asked to participate in advisory committee meetings. We can frequently ask whether the changes in Washington have impacted the review. While we have no special insights into the inner workings of the agencies, our impression 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 pre-filing meetings with EMA and appointed CHMP rapporteurs that culminated in the submission of a marketing authorization application, or MAA, on February 28, 2025, which was confirmed to be valid for review on March 20, 2025. Our plan is to seek approval in the UK following approval in either the US or Europe by leveraging the international recognition procedure. We've also had pre-filing 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 ERAH's first commercial launch, possibly beginning as early as late this year. As welcome as we believe that Closas-Rand will be for STS patients, this is just the beginning of the story for this important drug. While we were studying Closas-Rand and STS, we were 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 STS, 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 -of-phase two feedback from FDA and EMA, we have initiated a phase three program in severe hypertriglyceridemia. This program is designed to meet key standards based on guidance documents from the International Council for Harmonization. Key requirements and drug design considerations include two pivotal placebo control trials in SHTG patients, and a safety database of at least 1,500 patients treated with Closas-Rand compared with placebo for 12 months.

Hence,

SHASA 3 and 4 are very similar studies designed to demonstrate statistically significant improvement of triglycerides with 25 milligrams of Closas-Rand compared to placebo over 12 months of treatment. The two trials hold around 700 patients that are highly highly-tired. Given the results for phase two SHASA 2 trial, where the primary endpoint difference in triglycerides at week 24 compared to baseline at the 25 milligrams was minus 53%, with a p-value of less than 30% of the CLOSAS-RAND versus placebo for one year, with a planned enrollment of about 1,400 patients. We have previously guided and we expect the last patients to be randomized in the SHTG program this year. Based on enrollment today, 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 discontinuation rate for adverse events and other reasons. The last patients entered will be treated for one 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 this summer, it should be possible to narrow the potential timing for SHTG's supplemental NDA submission. The SHTG program also features a first-class study named SHASA 5 to directly assess the ability of CLOSAS-RAND to reduce the risk of acute pancreatitis in SHTG patients with a purpose-designed outcome study. We are conducting this study expressly to meet the needs of sophisticated payers, especially outside of the US. It is not gaining through the SHTG pilot. It is unlikely to be complete prior to those submissions. We do hope that it will be completed during the review process in Europe and elsewhere to be available for pricing discussions with most of the national and famous post-prudence. We cannot provide precise timing assumptions, not only because of uncertain timing to complete enrollment, but also because as an outcome study, treatment will continue into the required number of events to be collected rather than for fixed patients. The screening is underway. And centers currently open for a trial, so 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 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 liaison are actively engaging healthcare professionals in scientific exchange, helping them better understand and raising awareness of familial catalympal neosyndrome, 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 Episclerosis Society and British Episclerosis Society joint meeting, and the European Society of Endocrinology meeting taking place presently. In parallel, our public patient 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, was as for an decreases risk of acute pancreatitis that improves indices quality of life in FCS was featured. The authors concluded in the abstract that in patients with FCS, was as for a markedly reduced triglycerides and risk of pancreatitis with promising changes in indices of quality of life. Those of you who have watched this for a while know that we have another agent in our cardiomargala pipeline that like was as for an as very strong support in hemogenetics. I'm describing Zadaceran, an RNAi drug designed to reduce expression of angioapoid protein like 3 or HPTL3. This drug also produced strong results in two phase twos, including ARTIS2 in mixed hyperlipidemia, also published in the New England Journal of Medicine, as well as the Gateway Study in HOSH patients, with data presented last week at the European Episclerosis Society conference. However, as we've discussed previously, we saw Zadaceran as positioned in the crowded LDL space where the unmet medical need has largely been addressed by statins and PCS commanding computers. But there was an important population we think Zadaceran would make an important contribution without requiring an outsized commitment of resources by ARRHED, this being for patients with homozygous familial hypercholesterolemia. These patients have exceptionally high LDL and cholesterol levels, and because their genetic abnormalities usually result in very low or absent LDL receptor function, are usually not able to get to goal LDL levels, even with maxillostatin and PCSK nanotideris. This leads them to very high risk of suffering cardiovascular events and early mortality. Monoclonal antibody against HPTL3 has already been proven effective in these patients. It requires monthly intravenous infusions and can lead to immunologic reactions. We conducted an exploratory phase two 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 that treat STS and SHTG, making the potential marketing of Zadaceran in these patients efficient for us, or to be approved. We have designed a phase three study of similar size to our phase three palisade study comparing Zadaceran at 200 milligrams quarter to placebo and expect to be in low in patients this year. Assuming successful demonstration of safety and efficacy and successful regulatory submissions, Zadaceran could join Zadaceran in the market as early as 2028 or 2029. As I said at the beginning of my remarks, we hope to see Zadaceran emerge as our first commercially available drug to treat STS patients as early as this year. Based on our expected completion of enrollment in the SHTG phase three study this summer, we could see SHTG phase three completion in the summer of 2026 and an end in SADA filing shortly thereafter. Interestingly, also before completion of the decade, based on public guidance, progress with phase three primary programs for alpaceran and oculolay and faciceran and liver disease associated with alpha-ray atripsin disease could result in approvals for these programs in a similar type of way, as well as with the possibility of some of our less mature department programs for important organ diseases might also find approval at that time. It takes patience in this business to see an important new platform rise to prominence. We feel there is some good reason to have confidence that RNA interferes with joint small biology of drugs and monoclonal antibodies as a foundational technology in drug development, especially as the field which we see arrowheads still leading continues to push into new cell types, opening up additional important disease to be addressed. I'll now turn the call over to Andy Davis. Thank

you, Bruce. With the Biduza date for plesastor insect for November 18, just six 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 arrowheads clinical trials. We're also making strong progress in building our commercial sales team. The 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 data education in advance at lunch. A market access team is executing effectively on our pre-approval information exchange or PI strategy directed toward healthcare decision makers to help them plan for our potential approval. We've now engaged with payers representing a significant number of US covered lives, delivering compelling content on the clinical value and anticipated profile of plesastor. We're encouraged by their interest in plesastor, especially regarding its potential to reduce triglycerides and acute pancreatitis risk. Additionally, our analytics team is deploying innovative technologies to identify individuals potentially living with FCS. We're connecting with these potential patients through disease data education efforts, including opportunities for them to opt in for continued communication and support. Across our research and stakeholder engagement, the clinical attributes of plesastor continue to resonate strongly. Our market research suggests that plesastor's deep and durable triglyceride reduction is compelling to numerous stakeholders. The Palisades study showed that plesastor reduced triglycerides by approximately 80% for baseline as early as month one. But 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 and fasting triglyceride levels at month 10, where plesastor demonstrated a placebo-adjusted change of minus 59% with the planned commercial 25-milligram dose. Our market research also suggests that healthcare providers, caregivers, and patients have a strong desire to see triglyceride levels fall below expert guideline thresholds, 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 approximately 50% achieved levels below 500. Numerous expert guidelines emphasized 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. Plesastorin shows a favorable dosage and safety profile, and as a reminder, plesastorin is conveniently administered once every three months, potentially minimizing treatment burden and improving adherence. As our US launch preparations continue at full speed, we're equally pleased to report steady progress on our European 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 plesastorin to individuals living with STS and their families in both the United States and priority countries outside the United States. We believe this potential -in-class siRNA therapy will mark a major advancement, and we're fully committed to unlocking its patient's impact. I'll now turn the call over to James Haines. Thank you, Andy. First, I'd like to provide a status update on our two early-stage obesity programs, Aero-Inhibit E and Aero-Alk 7. Aero-Inhibit E is designed to reduce expression of activity, which is a lignin for adipose-alk 7, while Aero-Alk 7 is designed to reduce expression of the ALK 7 receptor itself, both of which are involved in regulating adipose storage effects. 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. Aero-Inhibit E began dosing in December of 2024 and is progressing on our planned timeline. As a reminder, the phase 1-2 study will evaluate Aero-Inhibit E monotherapy administered to obese, otherwise healthy volunteers in both single and multiple dose escalation cohorts. The SAG cohort dosing is now complete and the multidose monotherapy cohorts are actively enrolling. The study is also evaluating multiple doses of Aero-Inhibit E in combination with terceptide and these combination cohorts are actively enrolling now on our planned timeline. We anticipate the Aero-Alk 7 political program will be up and running shortly. The design of this study is very similar to the Aero-Inhibit E study with SAG and MAD monotherapy cohorts and MAD cohorts in combination with terceptide. This study will also enroll obese, otherwise healthy volunteers. Those 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 Aero-Inhibit E around the end of 2025 and potentially for

Aero-Alk 7 shortly thereafter. Our muscle targeted programs partnered with Sarepta,

AeroDUX4 for FSHC and AeroDM1 for myotonic district B type 1 also continue to make good progress in the phase one two 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 wanna highlight some top line results from part two of the phase one two clinical study of AeroC3 designed to reduce liver production of complement component three as potential therapy for various complement mediated disease. In patients with IGA necropathy or IGAN, AeroC3 achieve deep and sustained reductions in alternative pathway complement activity and proteinuria. The max mean reduction in C3 was 89%, serum age age 50, which is an alternative pathway hemolytic acid reduced by 85%. AeroC3 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. AeroC3 was generally well tolerated and the observed duration of effect is supportive of once every three 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 Niskowski.

Thank you, James and good afternoon, everyone. As we reported today, our net income for the quarter ended March 31st, 2025, was $370.4 million or $2.75 per share based on the $134.5 million fully diluted weighted average shares outstanding. This compares to the net loss of $125.3 million or $1.2 per share based on $123.3 million fully diluted weighted average shares outstanding for the quarter ended March 31st, 2024. Revenue for the quarter ended March 31st, 2025 was $542.7 million. No revenue was recorded in the quarter and in March 31st, 2024. Revenue in the current period relates to our license and collaboration agreement with Sarepta. As you know, the agreement with Sarepta was significant. It included many assets, including clinical assets, pre-clinical assets, and other assets to be developed. Accounting 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 pay on a stock purchase of $84 million, and $250 million related to the five 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 31st, 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 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 five years, five or so years, most of it 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 DM-1 program are expected to be earned in the next few quarters and will be recorded in their entirety as revenue at that point, as would any other future milestone payments and royalties. Total operating expenses for the quarter ended March 31st, 2025 were $161.5 million compared to $126.2 million for the quarter ended March 31st, 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 31st, 2025 was $460.1 million compared with net cash used in operating activities of $92.4 million for the quarter ended March 31st, 2024. Increase in cash provided by operating activities is driven by the cash received for the SUREPTA agreement. Turning to our balance sheet, our cash and investments totaled $1.1 billion at March 31st, 2025. Our common shares outstanding at March 31st, 2025 were $138.1 million. With that brief overview, I will now turn the call back to Chris.

Thanks, Ken. Aramad 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 Lodaster in this year pending regulatory approval with what we think is a best in class profile with new full differentiation from currently available therapies in FCS. We are also well on our way to fully enrolling in the summer our suite of phase three studies designed to support regulatory submissions for the large FHTG patient population. We are funded into 2028 and potentially through multiple launches of Holyon and partner 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 and below 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. Thank you.

To ask a question, please press star one one on your telephone keypad and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, we ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster. And our first question comes from Maury Raycroft of Jeffreys, your line is open.

Hi, congrats on the progress and thanks for taking my question and best wishes to Ken and welcome Dan. Let's see, for Inhibini and ELK7, you've noted that the goal there is not to compete with GLIP-1s but to be used in combination. What's the latest you're saying on how you're setting expectations for initial monotherapy and potential combo data? I guess what you wanna see in the initial update including changes on weight loss, body composition and relevant biomarkers.

Yeah, thanks Maury. We're not giving any guidance on what we expect to see because this is a first in human study. The AMO data were compelling. We saw good weight loss. As a monotherapy, we saw good weight loss in combination with trisepatitis. 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 we're looking forward to seeing what we see. The real benefits here we think are potentially not just weight loss but quality weight loss. Are we seeing a loss 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. 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. So 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.

Got it, that's helpful. Okay, thanks for taking my question.

You're welcome. Thank you. And our next question comes from Jason Gerberi of Bank of America. Your line is open.

Hey guys, thanks for taking my question. Just ahead of the plazocirin 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 Tringold that just as a mention of the numerical incidence reduction in the clinical section and I'm wondering if you guys feel like based on a policy 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, thanks.

Yeah, hi, 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 labeling negotiations come later. So it's really impossible for me to estimate how they made use of it. We obviously like our data quite a bit. We did our study differently in that we looked at it patients that had confirmed pancreatitis using the Atlanta criteria, while Ionis used, they developed a scale that also included possible and probable quote unquote pancreatitis, which actually don't meet the Atlanta criteria as definite pancreatitis. So frankly, it's a little bit of an apples and oranges 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 a more conservative route that we think especially for instance, with payers in Europe especially, that might turn out to be important, but clearly these drugs are extremely helpful, not just in introducing triglycerides, but also in turning that reduction triglycerides into reduced abdominal pain and pancreatitis. So we'll see, I really can't give you any guidance for what labeling is gonna look like. In our business, we do the studies, we submit the FDA reviews and the FDA design. So hopefully it's gonna be up to them. We'll obviously discuss it with them,

but I can't speak for them at all. And let me say that 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 3D and Shasta 4 studies, we are looking at abdominal pain. The real thing to focus here on is how low can we get triglycerides. And as you mentioned in the fair response, fair remarks as well, we presented in the past, we get something like 75% of patients in that phase three study below 880 and something like 50% below 500. And that's

a real feat for these FDS 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. Got it. Thanks guys.

Thank you.

And our next question comes from Ellie Murrell of UBS. Your line is open.

Hey, this is Jasmine on for Ellie. Thanks so much for taking your question. So first purple is Azaziran and SATG. Just on the 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 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 Zodasteran, can you clarify your current expectations in terms of potentially expanding beyond HOSH here? Thanks.

Let me take the second one first with Zodasteran. I, you know, the expansion beyond HOSH, you know, would be in potentially some sort of high risk, you know, HESH population. And that's actually something we discussed with, you know, with the agency and proposed a, you know, a narrow approach looking only at those patients that, you know, despite backscalp therapy, 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, you know, maybe because they thought it was going to set precedent. But, you know, they, you know, to get into HEFH, they wanted a full, you know, a full program, you know, multiple adequate, well-controlled trials, you know, about 1,500 patients or more, safety, et cetera. And it didn't make sense to us, you know, 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 the DASFREM, but beyond HOFH. It's just not, it's just not feasible. It's not a good use of our resources. Going back to Plesastra, if I understood your question of, you know, what we think the mean, you know, entry triglycerides might look like and what sort of response we might see, you know, we would expect the tests are pretty good and we'll, you know, we'll pretty much replicate what we saw at phase two. And in phase two, you know, the mean triglycerides in the SHTG population in that study, we were around 9,000, I think, maybe 8,000, 8,000. And as I said, you know, our placebo adjusted change was, you know, 53% reduction. So substantial, you know, large reductions in triglycerides, which is why we said that this trial's really, you know, these trials are really overpowered because even with a smaller trial, phase two we had p-value invested in 42001. So, you know, it will, it should be an impressive, can't say it will, but it should be an impressive, we expect to be an impressive reduction in triglycerides.

But the mean enrollment, triglycerides probably would be, you know, a lot of that. Did I read your question right, Ellie? Did I understand your

question?

Yeah, we also were just interested in the mean of what you expect for acute pancreatitis, kind of a baseline.

Oh, in the pancreatitis study, okay. Well, I would expect that's going to be, you know, closer to the FCS, to the Palisade baseline. So I would expect that the pancreatitis study baseline, you know, it won't surprise me if it's around 2000. Could be a little bit lower because, you know, patients, especially when they've had a history of pancreatitis, you know, they're more susceptible to repeat pancreatitis even at lower values. But it won't shock me if it turns out to be somewhere you don't allow 2000.

Okay, thanks so much, very helpful.

You're welcome.

Thank you.

Our next question comes from Patrick Tuchio of HC Wainwright & Company, your line is open.

Thanks, good afternoon and congrats on all the progress. I was actually curious about your Aero C3 and Aero CFB programs and your latest thinking regarding the potential positioning of these compounds and complement mediated diseases and how you're viewing these compounds. Are they core to your portfolio or there's potential here for partnering? Thanks.

I sure I'll take the second part of that and I'll leave the first part and more for James. You know, we are open, you know, discussing partnerships for C3 and Factor B, those drugs, at least in my mind, those drugs work, you know, they do what they're designed to do, they lower C3 and they lower Factor B more effectively. And we think there's a number of places they can go. If push came to shove, 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 to really help. James, do you want to talk about some of the opportunities? Yeah, sure. So we, the data that we talked about earlier today with Aero C3, of course, that's the IGAN data, we're still pending some data in the C3G population with that molecule. And of course, Aero CFV is also applicable to 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 Aero C3 that it stacks up pretty well against any 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 Aero 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 an RII, dosing every three or every four months. That could have some advantages. Yes. Thank you.

And our next question comes from Andrea Newkirk of Golden Facts, your line is open.

Good afternoon, thanks for taking our question. James, maybe one for you as you think about entering the obesity space, how are you thinking about advancing both Aero-ELK7 as well as Aero-NHB through clinical development 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, yeah, so our

thoughts with those, from a cost standpoint, it doesn't cost us that much to do the preclinical and at least the phase one development and we have Aero and Hibony, which targets the hepatocyte expression, uses the so-called Galnet technology for delivery. That technology is pretty well-fetted. 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, Aero-ELK7 uses a completely different platform. The animal data was really compelling with that molecule but 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 de-risked. Our thought was to take both of those through phase one and then get a look at the data, both the safety and the PD and efficacy data and then choose one to move forward and then maybe opportunity for partnership either one or both of those potentially. But that was the thoughts of why we brought both of them into the clinic. And let's also be clear, I do not expect these to be our last two obesity assets with our ability to address the hepatocyte and our ability to address potentially CNS via this blood-brain 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 plate in the near term as

well. Okay, thank you so much. Thank you.

And our next question comes from Luca Isi of RBC. Your line is open.

Oh, great. Thanks so much for taking my question. Congrats on the progress. Maybe Bruce, circling back on a prior question, can you just maybe remind us how you're thinking about SHASTA-5 study design? What patients will you enroll? And maybe most importantly, how many patients do you need to actually hit the stats? So if you can talk about power and efficiency and assumptions, that'd be much appreciated. And then maybe a bigger picture on plazasera and CRS. How are you thinking about commercialization of the molecule XUS? Are you planning to do that by yourself or are you still looking for a partner? I need to talk there, much appreciated. Thanks so much.

Yeah, so again, this trial will be, we believe the first ever trial where demonstrating a benefit in scabiotitis is 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. You know, 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 evolve 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 hypercholesteroid patients that have never had pancreatitis. But again, no one's ever done a trial like this before. So understanding exactly what the observed risk will be is something that we'll get some understanding. Of course, we'll all be blinded, but we'll get some understanding as the trial gets underway, I think it's moving. And that will certainly determine, but it's certainly not the size of a C-bot or anything like that. It's much smaller. Given the reduction of pancreatitis we saw in Palestine, for instance. But we haven't, I think we'll get more detail in the future, but we're not ready to give all the deep detail at this point.

Hey, Luca. So regarding your question on flodasterin, so as you know, we're full speed ahead in the US for FCS and eventually FACG hopefully. Rest of the world, we are open to finding partners. We are preparing right now in Europe. Andy, do you want to discuss how we're approaching that right now? Yeah, Luca, so we think the European markets in particular, the large four European markets in the UK, lend themselves extremely well to commercialization for a rare disease like FCS. Many of these patients on their patient journey are triaged 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 US, those large markets in Europe and the UK and also Canada are a priority

for us. Got it, thanks so much,

guys. Good, thank you. Thank you. And our next question comes from Edward Tenthoff of Piper Sandler, your line is open.

Great, thank you very much, appreciate taking the question. So, you know, important to note that you guys either are reviewed, not fever reviewed. Do you anticipate an adcom or anything like that? And what other steps are you taking in preparation for hopeful approval and likely long-stakes?

Well, as far as the adcom goes, you know, we've not been advised that there's an expectation for an adcom. So at this time, we don't think that an adcom's in our future. As you probably know, I mean, the agency can change their opinion on that anytime 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 an adcom. So the likelihood, you know, I suppose it's lower every day we get closer to potential approval. We can't say we won't have one because they can decide anytime that they need one. But we don't see it though.

And then the second part of the question is. The second part was what actions are we taking to be ready for launch?

Yeah, so I guess we talked a bit about that. From the R&D perspective, we had an educational mission under our medical affairs function and MSLs. So that's very much just a matter of helping the physicians be ready for a new drug coming into the SCS space where really there hasn't been any promotional effort up until the Ionis launch ever really first. So there's a big issue in this.

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? Thank you.

Well, look, I think any, any working 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 think you're better off being alone. In many ways, you're actually better off when there are multiple competitors. Now, yes, they fight 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 SCS and the exact same will be true for SHTT 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 than they are.

That's really helpful, thanks.

Thank you. And our next question comes from Mike Als of Morgan Stanley. Your line is open.

Good afternoon. Thanks for taking the question. Maybe just another one on plazasoran and the upcoming SCS launch. Sounds like you guys are making good progress in launch prep, but maybe you could just talk about or remind us the US 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, thanks.

Yeah, thanks for the call, Mike. You'd be familiar with the epidemiological data suggesting that the prevalence of SCS in the United States would be one to 13 per million. And so that spans anywhere from the hundreds of patients in the US to mid single digit thousands. And we think the variability around the single digit thousands is really around whether you think about genetic SCS or even clinically diagnosed SCS. That's why there's some variability there. As a reminder, of course, in Palisade, we studied plazasoran in both the genetically confirmed and clinically diagnosed patients and showed similar results. And so that's how we think about the broader market for SCS. 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 and party metabolic and lipids specifically and are really using the latest technologies to patient find and ultimately to support those individuals who may have SCS and don't know that they have SCS. So patient finding will be absolutely critical as we move into this space, as it is with any ultra rare condition. And we feel like we have the people and the capabilities to excel there.

Thank you.

Thank you. Thank you.

And our next question comes from Mayak Mantani of B Riley Securities, your line is open.

Yes, good afternoon Dean. Thanks for taking our questions and congrats to Ken for 16 years of service. Just maybe on the, a 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 one B and part two, which is the combination, are those sequential or are they happening in parallel? And I have just one follow up for Ken.

Yes, sure. On the second part of the question, those, the combo studies and the MAD, non combination 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 20-28 runway guidance, if you could maybe just clarify that. Thanks for taking our questions and congrats, Ken.

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 then we've included those

as well. But we're not providing specifics on that. I'm just saying thank you.

Thank you.

And our next question comes from Manny Farahar of Lyric. Your line is open.

Hey, guys, you have Ryan on for Manny. Thanks for taking our question. Maybe just a quick financial one. I noticed you guys started to pay down that credit facility. Just wondering, should we expect that to continue over the course of the year or was this more of just a one-time pay down to kind of bring that total down? Thanks.

So the one-time 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. Got it, thanks.

Thank you.

And our next question comes from Brendan Smith of TD Cal and your line is open.

Hey, thanks for getting the questions, guys. Maybe just similar to a couple earlier questions, I wanted to ask a little bit more on your latest thing into 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 essential design there and segmentation of that market. Thanks, guys.

Sure, James, why don't you take the MAPT and then I'll take the board question. Sure, so the second question on MAPT, not at this point for the phase one design, it's not entirely finalized yet, but suffice it to say that the main goal of the study will be to evaluate safety and measure PD markers of knockdown of various subtypes of Tau in different populations. So we've knocked specifically pin down subtypes of AD that we plan on studying. And regarding the 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, HCT, Rhineland, 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, ALS and Nibling for Parkinson's. So HCT is already off the docket for right now. We have ALS, Nibling 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 CNSPV platform is gonna 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 as a target. So we're holding onto that for right, 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 that we think many, once we have this platform validated in humans, we're gonna 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 gonna see a large number of additional CNS targets, some of which we'll hold onto, some of which we'll partner.

Got it, sounds good, thanks guys.

Thank you. And our next question comes from Prakhar Agrawal of Cantor Fitzgerald, your line is open.

Hi, thank you for taking my questions and congratulations on the quarter. So IONIS has the phase three SHTG readouts coming soon. If Alders-Arsson achieves statistical significance on pancreatitis events in phase three, how does that work? Does that impact your development strategy to have the pancreatitis reduction data in the label around the time of launch versus waiting for Shasta five to read out? And anything else you will be focusing on when Alders-Arsson's SHTG trial reads out? Thank you.

Well, it'll be interesting to see whether they can

accrue enough events to actually achieve anything there, we'll see. From our perspective, that was not a good enough bet 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 gonna worry the health technology authorities in Europe. So we really felt that it had to be definite pancreatitis from our perspective. But we are adjudicating any pancreatitis that occurs in Shasta three and Shasta four. We have written those studies so that we can merge those two trials for the purpose specifically of both the pancreatitis and the intent to do that. But ultimately, that for us feels like a high risk strategy in all covers 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 European

payers and some other places as well.

Thank you.

And our next question comes from David Lebowitz of Citi. Your line is open.

Hi, everyone, this is Ike Lee on for David Lebowitz. Thank you for taking our question. We have one on pricing for Polisysurin. How do you think about launching this in FCS and then waiting for the SHTG data in the interim? We expect something like Trangosa also getting a label expansion in SHTG and therefore having to move from an ultra rare pricing scheme into something that is a little 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? Thanks.

Sure. I think we can have, and we are having transparent open conversations with payers. Should we be lucky enough to have spodasterin approved in FCS? It's a relatively narrow population, so we would need to get reverse at a high level that is commensurate with open and ultra rare. Should we be lucky enough to have SHASTA 3 and 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 gonna depend upon a lot. So conceptually,

that is our strategy,

but

I can't get more granular than that at

this point. Thank you. I'm showing no further

questions at this time. I'd like to turn it back to Chris Anzolone for closing remarks.

Oh, thanks everyone for joining us today. It is bittersweet to end this call. This is the last time I'm gonna 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 through this happening 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.