Arrowhead Pharmaceuticals, Inc.

Welcome to the Arrowhead Pharmaceutical Conference call. Throughout today's recorded presentation, all participants will be in a listen mode only. After the presentation, there will be an opportunity to ask questions. 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 Cardio-Vetabolic 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 Apel, Chief Financial Officer, who will give a review of the financials. Following management's prepared remarks, we will open the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks and uncertainties, please refer to our SEC filings including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. I'd now like to turn the call over to Chris. Thanks, 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 hyperglyceridemia, 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 was needed therapy for SHTG 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 ChASSA III and IV top-line results. Both studies met their primary endpoint and every pre-specified secondary endpoint. . . . . . . and others. The acute pancreatitis findings are, in our view, the standout results. Across the broad SHTG population, patients with triglycerides above 500 milligrams 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 milligrams per deciliter and a history of acute pancreatitis, we saw a 100% reduction in events versus placebo. 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 filings. 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 year-term label expansion opportunity and further strengthen the foundation of our cardiovascular franchise. As we consider how we could fit into SHTG therapeutic paradigms, we think of Redemplo in three ways. Safe, simple, and strong. Safe because of the impressive tolerability we saw in the Palisade Phase III and resulting clean legal NFCS, combined with what we saw in Shasta III and IV 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 mg dose for all patients rather than having to titrate up, and strong because of unprecedented reductions in triglyceride levels from baseline across multiple studies. We see this as a clearly compelling value proposition for patients, healthcare providers, and payers. Therefore, the speed at which we can bring Prozacerin to the broader SHCG population is critical. The possibility of shaving four months off the approval process through the primary review 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 dead below launch for FCS continue 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 Redemplo's reach outside the United States. In May, Australia's Therapeutic Goods Administration approved Redemplo 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 Redemplo the first and only oligo-based medicine authorized by the EC 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 Revenlo 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 Prozaciran to SHTG patients, but also to serve as the basis for our broader cardiometabolic franchise, which we expect to include Zodaciran, Aerodimer 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 Prozaciran 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 Eazl, we presented interim Phase 1-2a data for arrow I and HBE in obesity and MASH, and the results were compelling. Arrow I and HBE achieved dose-dependent active and E reductions with a mean maximum reduction over 85% after a single 400 mg dose, with effects persisting beyond three months. and a small subgroup of obesity and elevated baseline liver fat receiving at least 200 milligrams as monotherapy. 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 Arrow-ALK7 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 Zodaciran and Aerodimer PA. The Zodaciran 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. Aerodimer PA is designed to silence both Apocene-3 and PCSK9, and therefore reduce both LDL cholesterol and triglycerides. We believe this could be a uniquely powerful therapy for 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 Aromap-T at TIDES. This is an important piece of our pipeline and we expect to release early data from our phase one study in September. This is a potentially exciting data set, not only because of the potential of Aromap-T against Alzheimer's disease and other challenges, 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 conjugate. 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 Aero 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 variant with rapid onset durability through at least 24 weeks and no clinically meaningful adverse events observed. Under the agreement, Aero had 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, and we have a high degree of confidence that the overwhelming majority of these could eventually be approved products. We have the potential for a substantial future partner income from 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 Possessory, 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 like to 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 Redemptlo 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. Redemplo 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 Redemplo, with the specialty mix continuing to be led by preventive cardiology and endocrinology, consistent with prior quarters and our expectations at lunch. Patient origination remains steady from prior communications across new to therapy versus switch patients and the volume of physicians writing prescriptions and patients receiving Redemplo 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, Redemplo's U.S. WAC is 45,000 U.S. dollars per patient per year under our one Redemplo unified pricing model, and we believe the value of Redemplo is supported by its highly differentiated efficacy, safety profile and dosing convenience. We've said consistently that we believe Redemplo 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 Redemplo and FCS make our case. 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 plizasterin 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, plizasterin achieved a statistically significant reduction in acute pancreatitis events versus placebo across the broad SHTG 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 plazasterine program to date with no new safety signals, No Clinically Meaningful Liver Findings, and No Hypersensitivity or Thrombocytopenia Signal. We see this dataset as a powerful validation of plasasterin'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 locked 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, plus Asteran achieved deep and durable reductions in triglycerides, 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 plazaciran safety database. We plan on presenting data from this study at a future medical conference. Additionally, during the quarter, plazaciran received Australian and European Commission approval as an adjunct diet in FCS patients. Switching gears to zodaciran in the development for the treatment of homozygous familial hypercholesterolemia, or HOFH, We completed enrollment of the Phase 3 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 AeroDimer PA Phase 1 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 AeroInhibine and the AeroAlk7 programs. As Chris already highlighted, we presented data from the AeroInhibine Phase 1 study demonstrating a 44% reduction in liver fat and 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-inhibit phase IIB clinical trial protocol has been submitted to regulators. The trial is designed to evaluate the effects of various doses of arrow-inhibit E on liver fat, liver histology, body weight, The study is intended to evaluate diabetic and non-diabetic patients as well as those on and not on stable incretin 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 L7 towards the end of this year. Moving on to CNS, we've long held the belief that the CNS represents the next frontier for sRNA 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 sRNA 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 one clinical trial of AeroMapT and 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 MAPT gene and our pre-clinical pipeline, which includes our partner programs. I will now turn the call over to Daniel Apel.

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, 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 prior year quarter. Revenue was driven by our license and collaboration agreements with Sarepta, Madrigal, Novartis, and Sanofi, together with commercial sales of Redempo. 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 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 preclinical 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 PMPLA3. 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 the mid-teens. 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 redemptive 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 court. This is more than double the approximately $1 million recorded in fiscal quarter two, 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 expense was 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 of program for plesiosterine in SHCG, as well as increased manufacturing and clinical supply activity. In line with our forecast, this also contributed to the pickup in expenses when compared to fiscal quarter two. Salaries are also higher driven by increased headcount to 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, or potential SHCG launch, and advancement of our 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 a quarter compared to $31 million in the prior year quarter. The increase is primarily driven by ongoing investment and supporting the commercialization of Redempto, 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 plesiosterine, and ultimately Sudha Asaran and HOFH. Turning to the balance sheet, cash and investments on hand totaled approximately $1.6 billion as of June 30, 2026. Common 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 Plozasarin 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 PR and PRB 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 competitors' 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 proposal in, 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 Pladasterin, 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 aerodinama PA The first dual-functional siRNA candidate targeting both PCSK9 and ApoC3 for LDL and TG lowering is expected in September. The first clinical readout for AromapT 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. Additional Arrow INHBE and Arrow Out7 data releases are planned in the fourth quarter for this novel non-incretion 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?

Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please limit one question per person. Please stand by while we compile the Q&A roster. Our first question comes from Maury Raycroft from Jefferies. Your line is now open.

Hi, congrats on the progress and on the shots of the data, and thanks for taking my question. With a question on just the SNDA, getting that submitted by year end 26, can you bookend what that timeline could look like and what the gating factors are for getting that in? And separately, can you talk about expectations for the ESC late breaker data? There's been some debate on median versus mean TG reduction magnitude. and even though there are no static differences on safety, were there any imbalances in liver fat, ALP elevations or glycemic parameters you want to comment on?

Yeah, sure. Mari, this is James. I'll answer the second question. The ESC data, you'll have to wait and see an ESC that we really are under embargo until the conference, so can't discuss any details around the study. In terms of rate limiters for the SNDA, we do plan to have a pre-SNDA 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 SNDA modules and

Got it. Okay. Thanks for taking my questions.

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

Good afternoon. Thanks for taking the question and congratulations on all the progress as well. Maybe just one on AeroMapT. Just if you can remind us what top line data you might share with us in September and what level of knockdown are you looking for and has that sort of evolved at all now that we've seen some of the Biogen data? Thanks.

Yeah, sure, 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? Oh, yeah. So I think that we still We're still aiming for probably that 50% to 60% knockdown. I mean, that level of knockdown seemed to achieve some level of clinical improvement in the Celia study. So I think we've said that all along, and we're kind of sticking with that benchmark of 50% to 60% knockdown.

Thanks, and congrats again.

Thank you. One moment for our next question. Our next question comes from Brian Cheng from JPMorgan. Your line is now open.

Hey, guys.

Thanks for taking our questions and let us add our congrats on the Shasta data.

Early in the call, you talk about the sequencing scale-up of your Salesforce. How big of a Salesforce do you envision that you'll need to reach, and how does that sequence look over the course of the next several months heading into the label expansion decision? Thank you.

Thanks, Brian. This is Andy. Good question. Well, 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 where we'll 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 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, guys.

Our next question.

Our next question comes from Luca Izzi from RBC. Your line is now open.

Oh, great. Yeah, thanks so much for taking my question. Congrats on the progress. Maybe a quick one for James again. Again, you're not commenting on whether there is or there's not a trend in terms of like increasing liver fat. Again, rightly so, given that, you know, the data's still in Barco and ESC. But maybe can you remind us what proportion of all patients in Shasta 3 and Shasta 4 actually received an MRI at baseline in year one? just trying to understand what's the sample size here and how meaningful that analysis will be. So that'll be much appreciated. And then maybe super quickly, now that you have SHAFTA-3, SHAFTA-4 in-house, how should we be thinking about SHAFTA-5? Will you still continue that trial or maybe will you wind that down? Any thoughts there? Much appreciated. Thanks so much.

Yeah, sure. 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's 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 go to roll that study and continuing to to run the study without any changes. Got it.

Thank you, guys.

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

Hi. Good afternoon. This is Dina Ahn for Jason. Congrats on the progress this quarter, and thank you so much for taking our question. Just the first one is on Redemplo and SHTG. First, if you guys have a view on which TG responder analysis you view as maybe more important for establishing that Redemplo is a very strong TG lowering. Is it below that 500 threshold or below that 150? 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 beats per deciliter, 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, you know, both 150 and 500 are important. You know, 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, Dina, 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.

Thank you very much.

Thank you. One moment for our next question. Our next question comes from Joseph Tom from TD Cohen. Your line is now open.

Hi there, good afternoon. Congrats on the progress and thank you for taking my question. For the FHTT market, how do you see the difference in prescribing between the U.S. and European markets or any changes in practice guidelines between the two that we should be thinking about? And maybe of that $3 to $4 billion range that you indicated for Prozacirin, how much of that is U.S.-based versus international markets? Thank you. Yeah, I'll take the easy question. The second question, the majority of that, is the United States, the overwhelming majority of that. Andy, do you want to? Yeah, this is Andy. As far as European market dynamics versus U.S. market dynamics related to triglycerides and acute pancreatitis, 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 significant. important to demonstrating value in the European markets. But those health care 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 health care providers in the United States as well. We'll be the 65th company to tell you that given the uncertainty around MFN, it's very difficult for us to, at this point, to know how these are going to be pursued in SOS markets and what kind of revenue we're going to see from outside the U.S. markets.

Perfect. Thank you.

Thank you. One moment for our next question. Our next question comes from James. Coldis from Stifle. Your line is now open.

Hey, thanks for taking my question and congrats on all the progress.

Maybe one on Trigs and just specifically as it relates to sort of your expectations around the commercial opportunity. You know, with your data out there now, the Ionis launch is sort of underway. Just wanted to get your latest on kind of how we should be thinking about what the right analogs are here and

and maybe more specifically, like how important you think the initial quarters, you know, for this class are to sort of validating or reading on to the size of the overall opportunity here. Thanks so much. Yeah, happy to take that. This is Andy. And I mean, 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 Redemplu 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 Redemplu 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. We think that SHTG is a very large market opportunity. 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 rinse 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 they're We reduced triglycerides 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.

Makes sense. Thanks.

Thank you. One moment for our next question. Our next question comes from Madison El Saadi. from B. Reilly Securities. Your line is now open.

Hey, guys. Congrats on the progress, and thanks for taking our question here. Maybe how should we think about the doubling of Rendemplo prescriptions? I guess in terms of weekly run rate, I think 30 per week maybe was the last disclosure you guys put out. And then, relatedly, Has the prescription to drug and arm conversion rate kind of hit the steady state for FCS? And if not, kind of just what are the drivers there? And then secondly, if I can quickly, for ESC, I know you're under embargo, so just a general question. Do you expect the learnings there are more academic in nature or is it something that really kind of facilitates a naive cross-trial comparison and really kind of informs the label? Thanks.

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 runway 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 at the end of the month.

Thank you. One moment for our next question. Our next question comes from Patrick Tortucci from HC Wainwright. Your line is now open.

Hi, everyone. Thank you for taking our questions. This is Luis for Patrick. We're thinking about the launch in the SHCG. Will it be in the highest risk patients? Will it be segmented to the highest risk patients or more broadly across patients with TGs above 500? And the question is directed at how would this reflect on the commercial builds? Would it be a step function or would it be an incremental expansion of the existing FCS field force?

Yeah, thanks for your question. This is Andy. Certainly while we think the 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 we'll continue to look to optimize our field force as we head towards SHGG. 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 who had episodes of pancreatitis. I think that's important. So while we think that that population at greatest risk is going to be the 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 to help physicians and patients understand the risk here.

Great, thank you and congratulations. Thank you.

Thank you. One moment for our next question. Our next question comes from Kay from Chardon Capital Markets. Your line is now open.

Hi, thank you. Now that you have your data, how are you thinking about price differential versus Tringolza?

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 cost for Redemplo, 45,000 U.S. dollars 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 We believe this is the right price for this drug. We think that there is a real reason to price this at a slight premium to our competitor, given what we see as a better safety profile, a better reduction in triglycerides from baseline, a simpler approach with quarterly dosing rather than monthly dosing, a lack of need to, we believe a lack of need have been having titrate up.

Okay, thanks.

Thank you. One moment for our next question. Our next question comes from Jen Jai from Cantor Fitzgerald. Your line is now open.

Hi, this is Jennifer Jai for .

Congrats on the SHASA results.

So for the neuro programs, what other CNS targets are you excited about if the phase 1 and 2 for MAP-T is positive?

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

Yes. Yes, for knockdown, if the MAP-T works out.

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

Great. Thank you. Thank you. One moment for our next question.

Edward Kendoff from Piper Sandler's is our next question. Your line is now open.

Great. Thank you very much. I just wanted to retreat a little bit and go back through sort of what the plans are for marketing now that you're approved in U.S., Canada, Australia, and Europe. Are you directly marketing in each of those? and how or are you using distributors and how are you going to recognize revenues from each of those geographies and then pay out a distributor fee in SCNA to understand those dynamics more? Thank you.

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 Redenflo is not outlicensed, nor have we established distributor relationships in those markets. It's effectively arrowheaded 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, just follow the standard. This is down here. Follow the standard revenue recognition. So as we as we complete a sale to customers in those countries who recognize revenue. So, nothing unique or in that regard.

Is it a net revenue or is there a fee that's paid in FT&A? Thanks so much.

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 is being offered by our commercial partners there, which is kind of like a contract, marketing contract sales, that would show up in marketing and sales costs.

So that would not be part of the net. Super helpful, Dan. Thanks, guys. Keep up. Thanks, Ed.

This concludes the question and answer session. I would now like to turn the call back to Chris and Nathalie Olney 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 air of our PA disclosures as well as MAP-T. Have a great summer.

for your participation in today's conference. This does conclude the program. You may now disconnect.