Arrowhead Pharmaceuticals (ARWR) Q3 2026 earnings call transcript

I will now hand the conference over to Vincent Anzalone, Senior Vice President of Investor Relations for ARROWHEAD. Please go ahead, Vincent.

Thank you, and good afternoon, everyone. Thank you for joining us today to discuss Arrowhead's results for its fiscal 2026 third quarter, ended June 30, 2026. With us today for management are President and CEO, Dr. Chris Anzalone, who will provide an overview. Andy Davis, Senior Vice President and Head of the Global Cardiometabolic Franchise, who will provide an update on commercialization activities. Dr. James Hamilton, Chief Medical Officer and Head of R&D, who will discuss our development programs. and Dan Appel, Chief Financial Officer, who will give a review of the financials. Following management's prepared remarks, we will open the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meeting of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.

All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. I'd now like to turn the call over to Chris.

Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. ARROWHEAD is now on the strongest footing in its history. Two weeks ago, we reported positive top-line Phase III results from the global SHASTA III and SHASTA IV studies in patients with severe hypercubusor anemia, or SHTG, and we expect additional results to be presented later this month at the European Society of Cardiology Conference.

These data made clear to us that Redempla is needed therapy for SHCG patients. To that end, we announced today that we have acquired a priority review voucher, which can accelerate the regulatory review process in the United States from 10 months to 6 months, potentially bringing this important medicine to patients as quickly as possible. To me, this is an expression of ARROWHEAD values. Push to create the best medicines and be creative and aggressive to rapidly get them to patients who need them. Let's talk about the SHASTA 3 and 4 top-line results. Both studies met their primary endpoint and every pre-specified secondary endpoint, a clean sweep across two pivotal trials. Median triglyceride reductions from baseline were 79% and 81% in SHASTA 3 and SHASTA 4, respectively.

These results were deep, durable, and remarkably consistent across both studies. Just as encouraging, safety and tolerability remain favorable and consistent with everything we've seen in prior studies. We observed no new safety signals, no clinically meaningful differences in routine laboratory measures, no clinically meaningful adverse changes in liver enzymes, no hypersensitivity cases, and no thrombocytopenia signal. In a pre-specified MRI PDFS subgroup, there was no statistically significant difference in mean liver fat content between plosaster and The acute pancreatitis findings are, in our view, the standout results. Across the broad SHTG population, patients with triglycerides above 500 mg per deciliter with or without history of pancreatitis.

Cumulative acute pancreatitis events were reduced by 78% versus placebo. And in the highest risk subgroup, patients with triglycerides above 880 mg per deciliter and a history of acute pancreatitis, we saw a 100% reduction in events. Detailed results are expected to be presented at a hotline late-breaker at the European Society of Cardiology Congress on August 30th, followed by an Arrowhead webcast on August 31st. We intend to submit an FNDA to the FDA before the end of 2026, followed by additional global findings. If approved, SHCG would represent a substantially larger commercial opportunity than FCS, and it would let us utilize the infrastructure we're building today for a much broader patient population. We believe the Shasta results materially de-risk our most important near-term label expansion opportunity and further strengthen the foundation of our cardio-advalid franchise.

As we consider how we could fit into SHTG therapeutic paradigms, we think of Redempla in three ways, safe, simple, and strong. Safe because of the impressive tolerability we saw in the PALISADE PHASE 3 and resulting clean label in FCS, combined with what we saw in CHASTA 3 and 4 across multiple measures, including quiet liver enzymes, no hypersensitivity, and no increase in liver fat. Simple because of quarterly dosing, no anticipated need for liver enzyme monitoring, and a 25 milligram dose for all patients rather than having to titrate up. And strong because of unprecedented reductions in triglyceride levels from baseline across multiple states.

We see this as a clearly compelling value proposition for patients, healthcare providers, and payers. Therefore, the speed at which we can bring disaster into the broader SHCG population is critical. The possibility of shaving four months off the approval process through the primary review of voucher we acquired is important. We have a saying at Arrowhead that is even etched in the floor of one of our facilities. It is that every day matters. This is a driving principle for us from discovery to early development to late-stage clinical to regulatory interactions and ultimately to the last mile, getting important medicines to the patients who need them.

Turning to execution of this last mile, our U. S. or DevLow launch for FCS continued to build real momentum during the quarter. We've seen greater than doubling of prescriptions quarter-on-quarter. Andy will talk through our progress in a moment, including prescription and market access progress, and I think you'll come away as encouraged as we are. This launch in FCS has given us valuable experience and a scalable foundation to build on. Physicians are identifying previously untreated FCS patients, prescribing activities broad, and our team is building the capabilities we'll need for a much larger potential SHTG launch. We also continue to expand with EMPLO's reach outside the United States. In May, Australia's Therapeutic Good Administration approved Redempla as the first and only medicine approved for FCS in Australia, including genetically confirmed and clinically diagnosed adults.

In June, the European Commission formally granted marketing authorization, making Redempla the first and only oligo-based medicine authorized by the E. C. for adults with FCS diagnosed through either clinical criteria or genetic testing. Together with our approvals in the United States, Canada, China, and Australia, the EU authorization gives Revenvlo an approved footprint across five geographies, an important achievement we are very proud of. We're now working through country-specific reimbursement and launch processes while Sanofi leads commercialization in Greater China. All of the commercial infrastructure we are building is intended not only to hopefully bring Przaciran to SHTG patients, but also to serve as the basis for our broader cardiometabolic franchise, which we especially include Zodaciran, Aerodymere PA, obesity treatments, and other candidates you will hear more about in coming quarters.

We're building a large number of potential medicines that could use the same commercial channels, hopefully providing us with substantial scalability and cost-effective growth. We view Fuzasteran as providing us with a strong value foundation. Our intention is to build on that aggressively, and we have made good progress recently toward that end. At EASL, we present an interim phase 1-2a data for ARROWI and HBE in obesity and MASH, and the results were compelling. ARROWI and HBE achieved dose-dependent active and E reductions with a mean maximum reduction over 85% after a single 400mg dose, with effects persisting beyond 3 months.

In a small subgroup with obesity and elevated baseline liver fat receiving at least 200 milligrams of asthma therapy, the placebo-adjusted post-dose reduction in liver fat was 44%. The program has been generally well-tolerated, and we're now engaging regulators on potential Phase II designs and endpoints. We continue to make progress in the ARROWHEAD PHARMACEUTICALS 7 Phase I-II program and expect to release more data from that study in the fourth quarter. Further, we expect to file a CTA for a new obesity candidate against an undisclosed target by the end of this year.

Our June cardiometabolic R&D webinar highlighted Zodacirane, Zodacirane, and Aerodimer PA. The Zodacirane Yosemite Phase III study in HOF patients is fully enrolled, and we expect to have data in Q3, 2027, and hopefully file an NDA by the end of 2027. Aerodyr媒ers' Pa designed to silence both ACoC3 and PCSK9, and therefore reduced both LDL cholesterol and triglycerides. We believe this could be a uniquely powerful therapy to the roughly 20 million people in the United States with both elevated LDL and triglycerides. We expect to release early data from our Phase I study in September. During the quarter, we also presented our subcutaneous CNS delivery work around AeromapT at Tides. This is an important piece of our pipeline, and we expect to release early data from our Phase I study in September.

This is a potentially exciting dataset not only because of the potential of ARROWMAP-T against Alzheimer's disease and other child disease, but also because we think it could provide the first clinical proof of concept that we are able to address brain targets with RNAi using a simple, subcutaneously administered conjugated. Our partnership strategy remains a key part of our model of value proposition. In May, we announced an exclusive worldwide license agreement with Madrigal for ARROW PNPLA-3, a program for a genetically defined MASH population. Phase 1 data showed liver fat reductions of up to 46% after a single dose in homozygous carriers of the PNPLA-3 I-148M variants with rapid onset durability through at least 24 weeks and no clinically meaningful adverse events observed.

Under the agreement, Arrowhead received a $25 million upfront payment and is eligible for up to $975 million in development, regulatory, and sales milestones and tiered royalties to mid-teens.

We believe that Arrowhead is something truly unique in biotech today. We have an approved product and positive pivotal data that we believe supports a potentially much larger indication that we think could drive peak sales in the $3 to $4 billion per year range. We have commercial infrastructure that is effective, growing, and capable of being the basis for multiple additional products. We have a set of platforms that enable us to address liver, adipose, muscle, lung, and CNS targets, and we believe virtually everything we have introduced to the clinic has translated from animal models to humans.

By the end of this year, we expect to have 23 individual drug candidates in clinical trials, 11 wholly owned, 12 partnered, We have a high degree of confidence that the overwhelming majority of these could eventually be approved products. We have the potential for substantial future partner income for milestones and royalties, and we have the financial resources to keep this engine running and growing.

So as you look to the patients we can help and the value we can create, of course look to possessor it, but also look to the engine we have built and the dozens of new medicines we can bring to patients.

With that overview, I now let's turn the call over to Andy Davis. Andy?

Thank you, Chris, and good afternoon, everyone. It has now been approximately eight and a half months since the FDA approval of Redempla last November, and we continue to be very pleased with the progress of the launch. Today, I'd like to first walk through where we stand with our FCS launch.

First, prescription and patient dynamics. Second, payer coverage. Third, pricing and competitive positioning. Fourth, commercial infrastructure. And fifth, international expansion. And then finally, turn to some reflections on our recent SHTG clinical trial results. Let's start with prescription and patient dynamics. Redempla prescription volume has more than doubled over the course of the fiscal third quarter, and that momentum has continued into the current quarter. We have supported more than 400 unique prescribers of Redemplot, with the specialty mix continuing to be led by preventive cardiology and endocrinology, consistent with prior quarters and our expectations at launch.

Patient origination remains steady from prior communications across new-to-therapy-versus-switched patients, and the volume of physicians writing prescriptions and patients receiving Redemplot for FCS continues to exceed our internal targets. In recent market tracking studies, healthcare professional respondents indicate steadily increasing awareness and depth of product knowledge with consistently high marks for Redemplo, both in absolute terms and relative to competition.

Turning now to payer coverage developments, we continue to see strong momentum in the publication of payer policies and overall coverage across payer segments. Redemplo now has favorable policies in place for the most significant payers, and overall coverage is progressing at a fast trajectory for the brand. We expect the remaining coverage gap to continue closing over the coming months.

Our market access team remains focused on ensuring both genetically confirmed and clinically diagnosed FCS patients have access to Redemplo, and nearly all published payer policies reflect the ability for physicians to diagnose FCS patients using clinical criteria alone Next pricing and competitive positioning As a reminder Redempla US WAC is per patient per year under our one Redempla unified pricing model and we believe the value of Redempla is supported by its highly differentiated efficacy safety profile and dosing convenience We've said consistently that we believe Redemplow offers physicians and patients a best-in-class option, and we remain confident that both the clinical data and the commercial model we've built position us well in FCS as we head towards the potential launch in SHTG.

Ultimately, we believe physicians and patients should have the freedom to choose the therapy that best fits a given patient's clinical profile, and we'll continue to let the product profile of Redemplow and FCS make our case. On our commercial infrastructure, our field organization continues to scale in a deliberate, sequenced way, sized for both the current FCS opportunity and the future SHTG opportunity as it unfolds.

Our commercial team's tenure and productivity continue to build, and we're seeing that reflected in the prescription and payer metrics I just walked through. Importantly, if the launch timing for SHTG is accelerated, as we expect, we will be ready. Just this past week, in fact, we onboarded the next wave of field personnel. This team will be in the field this month, educating stakeholders on FCS and Redemplo.

Lastly, a word about international expansion. Redemplo is now approved for FCS in the United States, Canada, China, Australia, and the European Union. On the EU approval specifically, Redemplo's label uniquely covers both genetically confirmed and clinically diagnosed FCS patients. That is to say, it's the only therapy in Europe with clinical FCS on label. We view this as a meaningful differentiator, given that a substantial share of real-world FCS patients are diagnosed clinically rather than genetically. We expect reimbursement will proceed on a country-by-country basis over approximately the next 12 months, beginning with Germany in the coming weeks. I'll wrap up my remarks with some reflections on what's ahead for plizasterine and SHTG. As Chris highlighted, we recently announced top-line results from the Phase III, SHASTA III, and SHASTA IV studies of plizasterine and severe hypertriglyceridemia, and we believe these are best-in-class results.

Both studies met their primary endpoint, with median triglyceride reductions of 79% and 81% for baseline at month 12 in SHASTA 3 and SHASTA 4, respectively, compared to approximately 27% for placebo. Just as importantly, in a pre-planned pooled analysis, plisasterin achieved a statistically significant reduction in acute pancreatitis events versus placebo across the broad SHCG population study, a 78% reduction in cumulative AP events. And in the subset of patients at the very highest risk, those with triglycerides above 880 milligrams per deciliter and a prior history of pancreatitis, we saw a 100% reduction in AP events versus placebo.

The safety and tolerability profile remained consistent with what we've seen across the plizasterin program to date, with no new safety signals, no clinically meaningful liver findings, and no hypersensitivity or thrombocytopenia signal. We see this data set as a powerful validation of Plesastron's profile across the full spectrum of SHTG, and it gives us continued confidence in our planned supplemental NDA submission, which remains on track for before the end of this year.

With that, I'll turn the call over to Tim.

Thank you, Andy. I'd like to share our plans for R&D milestones and data readouts throughout the rest of the year. But first, let's review the R&D team's accomplishments over the last quarter and beyond. We made large strides in advancing our cardiometabolic programs, specifically the ARROWHEAD team mocked databases and analyzed data for MIR-3, SHASTA-3, and SHASTA-4 ahead of schedule, culminating in the release of top-line SHASTA-3 and SHASTA-4 data at the end of last month.

As already mentioned, plozaceran achieved deep and durable reductions in triglycerides, translating into statistically significant reduction in acute pancreatitis events. PLOSASERAN also demonstrated a favorable safety profile with no statistically significant difference in liver fat in the treatment group versus placebo. We remain excited about sharing detailed results, which are planned for presentation at the upcoming European Society of Cardiology meeting later this month.

The MIR-3 trial achieved its intended purpose as a study designed to build the PLOSASERAN safety database. We plan on presenting data from this study at a future medical conference. Additionally, during the quarter, plizaceran received Australian and European Commission approval as an adjunct to diet in FCS patients.

Switching gears to zodaceran in the development for the treatment of homozygous familial hypercholesterolemia, or HOFH, we completed enrollment of the Phase III Yosemite study in mid-July. Importantly, the study was designed to enroll 60 HOFH patients. However, due to strong demand, we ended up enrolling 70 patients, all with genetically confirmed or clinically defined HOFH. This is a one-year study, so we expect study completion mid-2027, with data in the second half of 27. Also, in cardiometabolic, the ARRO-DIMER-PA Phase I-2A study in patients with mixed hyperlipidemia is nearing full enrollment, and we plan to share top-line data in September.

Elsewhere in our pipeline, we continue to make progress with both the ARRO-INHIBAN-E and the ARRO-ALC-7 programs. As Chris already highlighted, we presented data from the ARROWHEAD PHASE I study demonstrating a 44% reduction in liver fat in patients with hepatic steatosis baseline. As a reminder, liver fat reductions of better than 30% are generally thought to translate into histologic and potentially clinical benefit. An ARROW inhibiting phase 2b clinical trial protocol has been submitted to regulators. The trial is designed to evaluate the effects of various doses of ARROW inhibiting on liver fat, liver histology, body weight, and body composition in obese patients with MASH. The study is intended to evaluate diabetic and non-diabetic patients as well as those on and not on stable incretent therapy.

As the study is under regulatory review, we plan on sharing trial details once agreed upon with regulators. We intend to provide an obesity data update primarily focused on ELF7 towards the end of this year.

Moving on to CNS, we've long held the belief that the CNS represents the next frontier for siRNA therapeutics. with a large number of gene targets amenable to a gene silencing approach. Historically, the field has been severely limited by the requirement of intrathecal administration. This is a limitation ARROWHEAD hopes to remove with pioneering technology designed to deliver S-RNA therapeutics across the blood-brain barrier. AeroMAPT is ARROWHEAD's first molecule based on this delivery platform. MAPT gene encodes for the tau protein. Abnormal tau accumulation is widely believed to be a critical component of the pathologic cascade leading to Alzheimer's disease. Additionally, other forms of abnormal tau accumulation are known to directly cause MAPT variant frontotemporal dementia as well as progressive supernuclear palsy.

A Phase I clinical trial of ARROWMAP-T in Healthy Volunteers is reaching full enrollment, and the second phase of this study in Alzheimer's patients is actively enrolling. As Chris mentioned, we are targeting this September for top-line data release from the Healthy Volunteers. This will be a very important data readout, as it could pave the way for later-stage telepathy clinical trials. Additionally, achieving successful NAPTG silencing will validate the platform for use in numerous additional CMS programs in our pre-clinical pipeline, which includes our partnered programs.

I will now turn the call over to Danico.

Thank you, James, and good afternoon, everyone. As we reported today, net loss for the quarter into June 30, 2026, was $194.3 million, or a loss of $1.36 per share. This is a report based on 143.4 million fully diluted weighted average shares outstanding. This compares to a net loss of 175.2 million or loss of $1.26 per share for the prior year quarter and to June 30, 2025, based on 139 million fully diluted weighted average shares outstanding in that quarter. Revenue for the quarter totaled approximately $75 million compared to $28 million in the the prior year quarter. Revenue was driven by our license and collaboration agreements with Sarepta, Madrico, Novartis, and Sanofi, together with commercial sales of Adempo.

Of the total, approximately $26 million related to the Sarepta collaboration, mainly from ongoing recognition of initial consideration under that agreement, as well as reimbursement of certain clinical and manufacturing expenses. With the Novartis collaboration, we are We recognize approximately $20 million in the quarter, bringing fiscal year-to-date revenue recognition to approximately $75 million. As of June 30th, of the initial $200 million of cash received upfront, approximately $125 million of consideration remains in deferred revenue, and will be recognized over time as we fulfill our pre-clinical research and development obligations. We also recognize the full $25 million upfront payment from Madrigal, following completion of a license and technology transfer for ARROW PMP LA3. As previously announced, ARROWHEAD remains eligible to receive up to $975 million in development, regulatory, and sales milestones, as well as tiered royalties on future commercial sales ranging from the high single digits to Finally, we recognize approximately $1.2 million for transitional services and commercial FCS supply to Sanofi under our license agreement for Greater China.

As previously mentioned, we are not intending to headline specific Redemplo product sale numbers until they become a meaningful driver to our financials. That said, commercial revenue can be derived from our disclosures as a difference between total revenue and collaboration revenue and represented approximately $2.4 million for the quarter. This is more than double the approximately $1 million recorded in Fiscal Quarter 2, and we have been very encouraged by the continued progress we are seeing in lunch. Turning now to expenses, total operating expenses for the quarter were approximately $245 million, compared to $193 million in the prior year quarter.

The $52 million year-over-year increase was driven by approximately $36 million of higher R&D expense and $16 million of higher SG&A expense. R&D expenses approximately $198 million. The increase year-over-year was primarily attributed to a $32 million increase in candidate costs, reflecting continued progression of our pipeline through clinical development, including the Phase III registration program for Plesopterin and MSHCG, as well as increased manufacturing and clinical supply activity. In line with As far as our forecast, this also contributes to the pickup in expenses when compared to Fiscal Quarter 2. Salaries are also higher, driven by increased headcounts, support manufacturing operations, and a broader clinical pipeline. As James discussed, Shasta 3 and Shasta 4 have now read out with positive top-line results.

Accordingly, we expect costs associated with active execution of those studies to begin to moderate down over time, beginning in fiscal 2027. At the same time, we will continue to invest in regulatory activities, commercial supply readiness for potential SHCG launch, and advancement of a broader pipeline. The quarterly R&D expense will continue to be highly influenced by program timing and clinical activity. SG&A expense was approximately $47 million. The increase is primarily driven by ongoing investments supporting the commercialization of Redempo, including commercial headcount, marketing and launch support, and other outside services. Given the opportunities we are seeing in FCS, we have expanded and are continuing to expand our commercial footprint and our capabilities where appropriate. We're building these capabilities to support the current FCS launch, but we've designed them to scale, supporting potential future indications for plizoceran and ultimately sodasoran and HOFH.

Turning to the balance sheet, cash and investments on hand totaled approximately $1.6 billion as of June 30, 2026. Commons shares outstanding at quarter end were $141.1 million. As we have disclosed we have entered into an asset purchase agreement for an issued FDA priority review voucher which we plan to use with our upcoming SNDA submission for plizacirin in SHCG Under the terms of the APA, we will pay the current holder $215 million in closing, which we expect to occur in our fiscal fourth quarter following HSR clearance. According to our projections, should we gain approval in SHCG, the increase in present value of redemplum, Simply as a result of shifting our launch aspirations and uptake curve forward by four months, provides a greater than 3x return on the PRV investment.

Further, it is easy to layer, on top of that, incremental value that we might expect to achieve commercially, should we be able to shorten our competitor's first mover advantage. As a concluding remark, we believe that our strong balance sheet provides significant financial flexibility to support ongoing clinical development, current and future commercialization activities, and our long-term strategic priorities.

With that brief overview, I will now turn the call back to Chris.

Thanks, Dan. We've made so much progress during the first half of the year, and the second half of 2026 is equally packed with potentially important and value-creating events. First, we want to move as quickly as possible to get our SNDA submitted for plizasteran, supported by the strong clinical data from the SHASTA-3 and SHASTA-4 studies. The priority review voucher we acquired could help us get this important new medicine to patients with SHTG as rapidly as possible.

Physicians and patients are eagerly anticipating this medicine, so we are working hard to make it happen. Beyond the DASERAN, we have some important data readouts and events planned before the end of the year that could represent important de-risking and potential value-creating events. These readouts include the following. One, the first clinical readout of AerodynoPA, the first dual-functional siRNA candidate targeting both PCSK9 and APOC3 for LDL and TG lowering, is expected in September. Two, the first clinical readout for ARROWMAP-T being developed as a potential treatment for tauopathies, including Alzheimer's disease, representing our first program using the subcutaneously administered CNS delivery platform designed across the blood-brain barrier after systemic delivery. This is expected in September. And three, additional ARROWI in HBE and ARROWHEAD 7 data releases are planned in the fourth quarter to this novel non-incorporation strategy, which has quite encouraging early data in obesity and NASH.

With that, thank you for joining us today, and I would now like to open the call to your questions. Operator?

Mari, this is James. I'll answer the second question. The ESC data, you'll have to wait and see. At ESC, we really are under embargo until the conference, so we can't discuss any details around the study. In terms of rate limiters for the SMDA, we do plan to have a pre-SMDA meeting with FDA, and then subsequent to our discussions with the agency would file the submission. So for the time being, for our team, it's really all about generating SMDA modules and study reports and whatnot. and finalizing the data that we need for the FARM by the end of the year.

I can take that one also. So this will only be healthy volunteer data. We'll be discussing primarily safety and then total tau knockdown. There's not a lot of other biomarkers that we can measure in the healthies. So it's just safety and pharmacodynamic dose range finding study in the healthies. And then, sorry, what was the other part of the question? What knockdown was? Oh, yeah. So I think that we're still aiming for probably that 50 to 60 percent knockdown. I mean, that level of knockdown seemed to achieve some level of clinical improvement in the CELIA studies. So I think we've said that all along, and we're kind of sticking with that benchmark of 50 to 60 percent knockdown.

This is Andy. Good question. While I won't go into the details of the size of our field force for SHTG, I would tell you that we'll be moving from Effectively addressing over 5,000 HCP targets to a world that will be addressing over 20,000 HCP targets across both the specialists that I've mentioned previously, and also potentially those primary care physicians who act like specialists. So we would anticipate the final onboarding of the optimization of our field force to happen before the end of the year as we prepare for a potential accelerated launch in SHTG in the second quarter of next year.

Thanks, Luca. So, for the initial question, like I said before, we're under embargo. I can't really give any details around the SHASTA 3 or SHASTA 4 study, but we'll present all of that at ESC. For SHASTA 5, we don't have any plans to terminate that study right now. The plan would be to continue that and maybe get a better idea of what our label is going to look like before we make any decisions to stop the study. So for the time being, it's kind of status quo. We're continuing to roll that study and continuing to run the study without any changes.

And then just a second one, if I could squeeze it in. Will your priority review voucher allow you to get Part D coverage for Redemplo for most of 2027, or is it just the second half of 2027? I'll take the first question around responder analysis. I mean, again, you're going to have to wait until ESC to see the actual data on the responder analysis. But, you know, I mean, for SHTG 500 mcs per deciliter is the threshold, and it's thought to be below that. You should reduce the risk for acute pancreatitis, which is really where we're focused with the drug right now.

Yeah, I think both 150 and 500 are important. It's our goal to get as many below 500 as possible, but certainly if we can normalize a large percentage of these patients, that's a very attractive tool for physicians.

And on the – sorry, what was the question on the priority voucher? If your PRV will allow you to get Part D coverage for most of 2027, or is it just the second half of the year, like more towards the end of the year?

Yeah, so, Gina, as we normally would, we'll be pursuing both payer policies and coverage for SHTG as rapidly as possible. So, our market access team, as soon as the data is published in the coming month or so, will be interacting with payers to inform them of the data and prepare for eventual policy development and coverage throughout 2027.

The overwhelming majority of that.

Andy, you want to? Yeah, and this is Andy. As far as European market dynamics versus U. S. market dynamics related to triglycerides and acute pancreatitis, You know, both are extremely important. These markets, from a payer perspective, are very outcomes-based. So, the fact that we demonstrated a statistically significant reduction in the pooled analysis for Shasta 3 and Shasta 4 is incredibly important to demonstrating value in the European markets. But those healthcare practitioners in Europe recognize that AP and ongoing AP is a function of elevated triglycerides and whether or not you have a prior history of AP. And so that's the same as the healthcare providers in the United States as well.

But you know we be the 65th company to tell you that given the uncertainty around MFN it very difficult for us to at this point to know how these are going to be pursued in ex markets and what kind of revenue we going to see from outside the US markets Perfect.

Yeah, happy to take that. This is Andy, and as with any launch, of course, you want to get out of the gates quickly, so we'll be hyper-focused on ensuring that our providers are well-educated on the value of Redemplo and SHTG, and we'll also simultaneously, of course, be working with payers to get policies published and coverage in place in order to accelerate the ramp of Redemplo and SHTG. As you would know, there is a high degree of overlap between those prescribers who are writing for familial chylomicronemia syndrome and those who will also write for SHTG. These are, of course, those who have an interest in lipidology. There are about 1,500 of those individuals in the United States across specialties.

So we think the ramp that we're seeing in FCS bodes well for the ramp we would expect to see in SHTG also.

And I'll give you a qualitative answer also. But we think that SHCD is a very large market opportunity. There's an awful lot of patients who have triglycerides that we really need to help get under control. We're convinced of that. Our KOLs are convinced of that. However, this is going to be a relatively slow run because this is a brand new market. We are in the education business, and so it's going to take a bit of time for us to get the word out. Because look, the world is not used to looking at TGs closely because there have been, in part at least, because there have been no good ways to really reduce travisorides until now.

And so this is all a good thing for patients. It's just going to take a bit of time to educate those patients and educate physicians.

Yeah, hi, Madison. This is Andy again. Thanks for your question. Yeah, we do see approximately 20 to 30 new prescriptions a week that has been the run rate and consistent with what we have communicated previously. Of course, our teams are very focused on also ensuring that those prescriptions find their way through the funnel, ultimately to shipments to patients. And so our market access team is working incredibly hard to support our payer and our physicians and offices around compliantly navigating the prior authorization process and appeal process.

But as I mentioned, we will have new field personnel in the field educating stakeholders as early as this month. And so I would expect to see also an inflection point both in prescriptions at the top of the funnel, but also in the way those prescriptions filter through the funnel to ultimately those patients shipping.

And on the ESC question, again, I'm just real hesitant to make any additional comments on the data. I've just given the embargo. So we'll see you at the end of the month.

That was good.

This is Andy. Certainly, while we think the top-line results support Redemplo across the spectrum of SHTG patients, naturally, we'll be focused on those high-risk SHTG patients out of the gate. These are, of course, those patients who have the highest unmet need in the view of healthcare professionals and also the highest willingness to pay by payers. And so that'll be our initial focus at launch. As far as scaling of the field force, as I mentioned, we did implement effectively a step function increase in the field force that will go into the field this month and will continue to look to optimize our field force as we head towards SHDG.

And let's be clear. I think that our data suggests that it is important to get people's triglycerides down if they have triglyceride levels above 500, you know, full stop. We had people who had triglycerides below 880 who had episodes of pancreatitis. I think that's important. So while we think that that population at greatest risk is going to be initial market, there is a broader market to address here that I think is important and there are patients that need to be treated. But again, as I mentioned earlier, this is going to be an education play, and it's just going to take a bit of time, you know, to help physicians and patients understand the risk here.

Hi, thank you. Now that you have your data, how are you thinking about price differential versus Tringosa? Yeah, this is Andy. So I won't go into price details or contracting strategy, only to say that you would be aware of the Wholesale acquisition costs for Redemplo $45,000 per year. That does differ from our competitor, and we've communicated previously that we believe that premium is justified based on the product attributes of Redemplo across efficacy, safety, and convenience.

If the question is do we intend to move that price now that we have these data, the answer is no. We believe this is the right price for this drug. We think that there is, you know, real reason to price this at a slight premium to our competitor, given what we see as a better safety profile, you know, a better reduction in triglycerides from baseline, a simpler approach quarterly dosing rather than monthly dosing. You know, a lack of need to, we believe a lack of need to follow the enzymes because we haven't seen those issues. And, you know, a simple 25 milligram dose for all patients rather than having titrate up.

Are you asking what other gene targets are we interested in? Yes.

Sure. So we have a lot of different targets. We haven't disclosed any of those. And in terms of wholly owned programs, we probably won't disclose those until around the time of CTA filing, I'm just giving the competitive nature in the SIRNA space right now. So stay tuned.

Thanks for the question, Edward. Good question. This is Andy again. So, we are marketing into those countries that you mentioned using commercial partners. So, Redempolo is not out-licensed, nor have we established distributor relationships in those markets. It's effectively Arrowhead in operation with our commercial partners in those markets that you mentioned, with the exception of China.

And in terms of revenue recognition? So in terms of revenue recognition, I just follow the standard, so this is down here, follow the standard revenue recognition. So as we complete a sale to customers in those countries, we would recognize revenue. So nothing unique in that regard.

Oh, yeah. No, it's a – I mean, it's similar to the U. S. , so it would be a gross sale. And then in the gross to net, you have to deduct out sort of distribution costs and the like. But if you're asking about the cost to support – that's being offered by our commercial partners there, There's just kind of like a contract, marketing, contract sales. That would show up in marketing and sales calls. So that would not be part of that.

I would now like to turn the call back to Chris and Nazali only for closing remarks. Thanks very much for joining us today. We look forward to speaking with you later in August after ESC and then in September around the ARROWHEAD PA disclosures as well as in MAPT. Have a great summer.