Arrowhead Pharmaceuticals (NASDAQ:ARWR) Q3 2026 Earnings Call

0:00 Welcome to the Arrowhead Pharmaceuticals 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, Vince.

0:27 Thank you, and good afternoon, everyone. Thank you for joining us today to discuss Arrowhead's results for its fiscal twenty twenty six third quarter ended 06/30/2026. With us today from management are President and CEO, Doctor. Chris Anzalone, who will provide an overview Andy Davis, Senior Vice President and Head of the Global CardioVentabolic Franchise, who will provide an update on commercialization activities Doctor. James Hamilton, Chief Medical Officer and Head of R and D, who will discuss our development programs, and Dan Appel, Chief Financial Officer, who will give a review of the financials. Following management's prepared remarks, we will open the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.

1:21 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 ks 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 three results from the global Shasta three and Shasta four studies in patients with severe hypertriglyceridemia or SHTG, and we expect additional results to be presented later this month at the European Society of Cardiology Conference.

2:13 These data made clear to us that Rademplo is needed therapy for SHTG patients. To that end, we announced today that we

2:20 have acquired a priority review voucher which can accelerate the regulatory review process in The United States from ten months to six months, potentially bringing this important medicine to patients as quickly as possible. To me, this is an expression of Arrowhead values, pushed to create the best medicines and being creative and aggressive to rapidly get them to patients who need them. Let's talk about the CHASSA-three and CHASSA-four top line results. Both studies met their primary endpoint in every pre specified secondary endpoint, a clean sweep across two pivotal trials. Median triglyceride reductions from baseline were 7981% in CHASPA-three and CHASPA-four respectively. These results were deep, durable, and remarkably consistent across both studies.

3:06 Just as encouraging, safety and tolerability remained 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 PDFF subgroup, there was no statistically significant difference in mean liver fat content between posaster and placebo. 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 seventy eight percent versus placebo.

3:54 And in the highest risk subgroup patients with triglycerides above eight eighty milligrams per deciliter, and a history of acute pancreatitis, we saw a one hundred percent 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 30, followed by an Arrowhead webcast on August 31. We intend to submit an sNDA to the FDA before the end of twenty twenty six, 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 near term label expansion opportunity, and further strengthen the foundation of our cardiovascular franchise.

4:47 As we consider how we could fit into SHTG therapeutic paradigms, we think of Rodemplo in three ways: safe, simple, and strong. Safe because of the impressive tolerability we saw in the PALISADE Phase III and resulting clean label in FCS, combined with what we saw in CHASTA 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 twenty five milligram dose for all patients rather than having to titrate up. And strong because of the unprecedented reductions in triglyceride levels

5:30 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 Prozaciran 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. Radeblo launch for FCS continued to build real momentum during the quarter.

6:16 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 Demplo's reach outside The United States. In May, Australia's Therapeutic Goods Administration approved Rodemplo 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 Rodemplo the first and only oligo based medicine authorized by the EC for adults with FCS diagnosed through either clinical criteria or genetic testing.

7:13 Together with our approvals in The United States, Canada, China and Australia, the EU authorization gives Ridemplo an approved footprint across five geographies, an important achievement we're very proud. 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 prazasiran to SHTG patients, but also to serve as the basis for a broader cardiometabolic franchise, which we especially include Zodasiran, ArrowDimer PA, obesity treatments, and other candidates you'll 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.

8:01 We view posasiran 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 presented interim phase one2a data for ARO I and HBE in obesity and NASH, and the results were compelling. ARO I and HBE achieved dose dependent, active and E reductions, with a mean maximum reduction over 85% after a single four hundred milligram dose, with effects persisting beyond three months. In a small subgroup of obesity and elevated baseline liver fat receiving at least two hundred 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 two designs and endpoints.

8:50 We continue to make progress in the ARO ALK7 phase onetwo 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 and D webinar highlighted with zodasiran and airodimer PA. The zodasiran Yosemite Phase three study in HL patients is fully enrolled and we expect to have data in Q3 twenty twenty seven and hopefully file an NDA by the end of twenty twenty seven. ARO DYR PA is designed to silence both APOC3 and PCSK9, and therefore reduce both LDL cholesterol and triglycerides. We believe this could be a uniquely powerful therapy for roughly twenty million people in The United States with both elevated LDL and triglycerides.

9:40 We expect to release early data from our phase one study in September. During the quarter, we also presented our subcutaneous CNS delivery work around ARO MAPT 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 ARO MAPT 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 conjugate. Our partnership strategy remains a key part of our model and value proposition. In May, we announced an exclusive worldwide license agreement with Madrigal for ARO PNPLA3, a program for a genetically defined NASH population.

10:29 Phase one data showed liver fat reductions of up to 46% after a single dose in homozygous carriers of the PNPLA3I148M variant with rapid onset, durability through at least 24, and no clinically meaningful adverse events observed. Under the agreement, Arrowhead received a $25,000,000 upfront payment and is eligible for up to $975,000,000 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 $4,000,000,000 per year range.

11:15 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 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 glidesivir, but also look to the engine we have built, and the dozens of new medicines we can bring to patients.

12:08 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 Redemplo 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.

12:56 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 launch. Patient origination remains steady from prior communications across new to therapy versus switch patients, and the volume of physicians writing prescriptions and patients receiving Rodenplo 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.

13:47 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 Rodentlow, 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, Rodentlow's US WAC is US45000 dollars per patient per year under our One Rodentlow Unified Pricing Model. And we believe the value of Rodentplo is supported by its highly differentiated efficacy, safety profile, and dosing convenience.

14:36 We've said consistently that we believe Rodentplo 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. On our commercial infrastructure, our field organization continues to scale in a deliberate sequenced way, size for both the current FCS opportunity and the future SHTG opportunity as it unfolds. Our commercial team's tenure and productivity continued to build, and we're seeing that reflected in the prescription and payer metrics I just walked through.

15:26 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.

16:15 We expect reimbursement will proceed on a country by country basis over approximately the next twelve months, beginning with Germany in the coming weeks. I'll wrap up my remarks with some reflections on what's ahead for plazasiran and SHTG. As Chris highlighted, we recently announced top line results from the Phase three SHASTASI-three and SHASTASI-four studies of plazasiran and severe hypertriglyceridemia, and we believe these are best in class results. Both studies met their primary endpoint with median triglyceride reductions of 7981% for baseline at month twelve and Shasta three and Shasta four respectively, compared to approximately twenty seven percent for placebo. Just as importantly in the pre planned pooled analysis, Plazasiran achieved a statistically significant reduction in acute pancreatitis events versus placebo across the broad SHTG population study, a seventy eight percent reduction in cumulative AP events.

17:10 And in the subset of patients with the very highest risk, those with triglycerides above eight eighty milligrams per deciliter and a prior history of pancreatitis, we saw a one hundred percent reduction in AP events versus placebo. The safety and tolerability profile remained consistent with what we've seen across the plazasiran 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 plazasiran'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 James. Thank you, Andy. I'd like to share our plans for R and D milestones and data readouts throughout the rest of the year, but first let's review the R and D team's accomplishments over the last quarter and beyond.

18:05 We made large strides in advancing our cardiometabolic programs, specifically the Arrowhead team mock databases and analyzed data from MIRROR III, Shasta III and Shasta IV ahead of schedule, culminating in the release of top line Shasta III and Shasta IV data at the end of last month. As already mentioned, Plazasiran achieved deep and durable reductions in triglycerides, translating into statistically significant reduction in acute pancreatitis events. Posasiran 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.

18:54 The MIRROR three trial achieved its intended purpose as a study designed to build the posasiran safety database. We plan on presenting data from this study at a future medical conference. Additionally, during the quarter, plazasiran received Australian and European Commission approval as an adjunct to diet in FCS patients. Switching gears to zodasiran in the development for the treatment of homozygous familial hypercholesterolemia or HoFH, we completed enrollment of the phase three U-seventy 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 of genetically confirmed or clinically defined HoFH.

19:42 This is a one year study, so we expect study completion mid-twenty twenty seven, with data in the second half of twenty seven. Also in cardiometabolic, the Arrow Dimer PA Phase one-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 ARO Inhibit E and ARO ALK7 programs. As Chris already highlighted, we presented data from the arrow inhibiting phase one study demonstrating a 44% reduction in liver fat in patients with a pagocytosis baseline. As a reminder, liver fat reductions of better than 30% are generally thought to translate into histologic and potentially clinical benefit.

20:35 An ARO inhibitor phase 2b clinical trial protocol has been submitted to regulators. The trial is designed to evaluate the effects of various doses of ARO inhibitor E on liver fat, liver histology, body weight and body composition in obese patients with NASH. The study is intended to evaluate diabetic and non diabetic patients as well as those on and not on stable increasing 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 ALK7 towards the end of this year.

21:21 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 siRNA therapeutics across the blood brain barrier. ARO MAPT 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.

22:09 Additionally, other forms of abnormal tau accumulation are known to directly cause MAPT variant frontotemporal dementia, as well as progressive supranuclear palsy. A phase one clinical trial of ARO MAPT in healthy volunteers is reaching full enrollment, 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 tauopathy clinical trials. Additionally, achieving successful NAT T gene silencing will validate the platform for use in numerous additional CNS programs in our preclinical pipeline, which includes our partnered programs.

22:56 I will now turn the call over to Daniel Hill. Thank you, James, and good afternoon, everyone. As we reported today, loss for the quarter ended 06/30/2026 was $194,300,000 or a loss of $1.36 per share, based on 143,400,000 fully diluted weighted average shares outstanding. This compares to a net loss of $175,200,000 or a loss of $1.26 per share for the prior year quarter ended 06/30/2025, based on 139,000,000 fully diluted weighted average shares outstanding in that quarter. Revenue for the quarter totaled approximately $75,000,000 compared to $28,000,000 in the prior year quarter.

23:43 Revenue was driven by our license and collaboration agreements with Sarepta, Madrigo, Novartis and Sanofi, together with commercial sales of Vidempo. Of the total, approximately $26,000,000 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 recognized approximately $20,000,000 in the quarter, bringing fiscal year to date revenue recognition to approximately $75,000,000 As of June 30, with the initial $200,000,000 of cash received upfront, approximately $125,000,000 of consideration remains in deferred revenue and will be recognized over time as we fulfill our preclinical research and development obligations.

24:37 We also recognized the full $25,000,000 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 nine seventy five million dollars 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 recognized approximately $1,200,000 for transitional services and commercial FCS supply to Sanofi under our license agreement for Greater China.

25:15 As previously mentioned, we are not intending to headline specific Redemptor 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 2,400,000 for the quarter. This is more than double the approximately $1,000,000 recorded in fiscal quarter two, and we have been very encouraged by the continual progress we are seeing in launch. Turning now to expenses, total operating expenses for the quarter were approximately CAD245 million compared to CAD193 million in the prior year quarter. The CAD52 million year over year increase was driven by approximately CAD36 million of higher R and D expense and $16,000,000 of higher SG and A expense.

26:09 R and D expense was approximately $198,000,000 The increase year over year was primarily attributed to a $32,000,000 increase in candidate costs, reflecting continued progression of our pipeline through clinical development, including the Phase III registration program for plazosin 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 were also higher driven by increased headcount to support manufacturing operations and a broader clinical pipeline. As James discussed, Shasta three and Shasta four have now read out with positive top line results.

26:56 Accordingly, we expect costs associated with active execution of those studies to begin to moderate down over time beginning in fiscal twenty twenty seven. At the same time, we will continue to invest in regulatory activities, commercial supply readiness for potential SHCG launch and advancement of our broader pipeline. The quarterly R and D expense will continue to be highly influenced by program timing and clinical activity. SG and A expense was approximately £47,000,000 in the quarter compared to £31,000,000 in the prior year quarter. The increase was primarily driven by ongoing investments supporting the commercialisation of Rodento, 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.

27:53 We're building these capabilities to support the current FCS launch, but we've designed them to scale supporting potential future indications for plazosin and ultimately sildosiran and HOFH. Turning to the balance sheet. Cash and investments on hand totaled approximately £1,600,000,000 as of 06/30/2026. Common shares outstanding at quarter end were 141,100,000. 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 clozastrin in SHCG. Under the terms of the APA, we will pay the current holder $215,000,000 at closing, which we expect to occur in our fiscal fourth quarter following HSR clearance.

28:45 According to our projections, should we gain approval on SHTG, the increase in present value of ridemplo, simply as a result of shifting our launch aspirations and uptake curve forward by four months, provides a greater than 3x return on the 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.

29:34 Thanks Dan. We've made so much progress during the first half of the year, and the second half of twenty twenty six 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 posazaran, supported by the strong clinical data from the Shasta three and Shasta four studies. The priority review voucher we acquired, it 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 blazasteride, 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 ARO DYMO PA, the first dual functional siRNA candidate targeting both PCSK9 and APOC3 for LDL and TG lowering, is expected in September.

30:32 Two, first clinical readout for ARO MAPT 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.

30:51 And three, additional ARO INHBE and ARO AL7 data releases are planned in the fourth quarter for this novel non encryption 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 session. Please stand by while we compile the Q and A roster.

31:40 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 twenty six, 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?

32:29 Yeah, sure. Maury, this is James. I'll answer the second question, the ESC data, you'll have to wait and see at 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 study reports and whatnot and finalizing the data that we need for the funding by the end of the year.

33:22 Got it. Okay. Thanks for taking my questions. Thank you. One moment for our next question. Our next question comes from Mike Ulz 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 Arrow Map T. 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?

34:07 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 a safety and pharmacodynamic dose range finding study the healthies, and then sorry, what was the other part of the question? What knocked Oh in 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 improvements 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.

35:01 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 set our congrats on the Shasta data Early in the call, you talked about the sequencing scale up of your sales force. How big of a sales force 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.

35:49 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 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 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.

36:32 Thanks guys. Our next Our next question. Question comes from Luca Izzi from RBC. Your line is now open. Oh, great. Yes. Thanks so much for taking my question. Congrats on all 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 the data is still embargo at ESC. But

37:03 maybe can you remind us what proportion of all patients in chapter three and chapter four 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 that'll be much appreciated. And then maybe super quickly, now that you have chapter three and chapter four in house, how should we be thinking about chapter five? Will you still continue that trial or maybe will you wind that down?

37:29 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 three or Shasta four study, but we'll present all of that at ESC. For Shasta five, we don't have any plans to

37:52 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 enroll that study and continuing 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 on for Jason. Congrats on the progress this quarter, and thank you so much for taking our question.

38:42 Just the first one is on redemplo and SHTG. Just curious 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 Redundeplo for most of 2027 or is it just the second half of twenty twenty seven? I'll take the first question around responder analysis. Mean, again, gonna have to wait until ESC to see the actual data on the responder analysis, but that you know I mean for SHTT five hundred mgs 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.

39:48 Yeah, I think both one hundred fifty and five hundred 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. 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.

40:37 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 FHT market, how do you see the difference in prescribing between The US and European markets or any changes in practice guidelines between the two that we should be thinking about?

41:30 And maybe of that 3 to $4,000,000,000 range that you indicated for plazasiran, how much of that is US based versus international markets? Thank you. Yeah, I'll take these questions. The second question, majority of that is The United States, the overwhelming majority of that. Andy, do want to take Yeah, and 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 three and Shasta four is incredibly important to demonstrating value in the European markets.

42:16 But 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 we'll be the sixty fifth 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 ex US markets and what kind of revenue we're going to see from outside The US markets. Perfect. Thank you. Thank you. One moment for our next question.

43:10 Our next question comes from James Koldis from Stifel. 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. 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? Maybe more specifically, like how important you think the initial quarters for this class are to sort of validating or reading onto the size of the overall opportunity here? Thanks so much. Yeah, happy to take that. This is Andy.

43:59 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 Redemplo and SHTG. And will 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, about fifteen hundred 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.

44:49 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 rant, because this is a brand new market, we are in the education business, 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, there have been no good ways to really reduce triglycerides until now. And so, but 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.

45:43 Makes sense, thanks. Thank you. One moment for our next question. Our next question comes from Madison Elsadi from B. Riley Securities. Your line is now open. Hi, 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 ARWR conversion rate kind of hit the steady state for FCS?

46:35 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 lingual? 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 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.

47:26 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 patient shipments. And on the ESC question, again, I'm just real hesitant to make any additional comments on the data, just given the embargoes, so see you at the end of the month.

48:15 Sounds good. Thanks, Alex. Thank you. One moment for our next question. Our next question comes from Patrick Tortucci from H. C. Wainwright. Your line is now open. Hi, everyone. Thank you for taking our questions. This is Luis in for Patrick. We're thinking about the launch in SHTG. 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 five hundred? And the question is directed at how would this reflect on the commercial builds? Would it be a step function or would be an incremental expansion of the existing FCS field force?

49:10 Yeah, thanks for your question. This is Andy. Certainly, we think the top line results support Redemplo across the spectrum of SHTG patients, naturally will 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. 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.

49:55 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, full stop. We had people who had triglycerides below eight eighty, 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, 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.

50:44 Great, thank you. And congratulations. Thank you. Thank you. One moment for our next question. Our next question comes from Keith from Chardan Capital Markets. Your line is now open. Hi. Thank you. Now that you have your data, how are you thinking about price differential versus Trincosa? 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 of $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.

51:43 Yet if the question is, do we intend to move that price now that we have the data, the answer is no. We believe this is the right price for this drug. We think that there is 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 a monthly dosing, a lack of need to we believe a lack of need to follow over enzymes because we haven't seen those issues. And a simple twenty five milligram dose for all patients rather than having to titrate up. Okay, thanks.

52:30 Thank you. One moment for our next question. Our next question comes from Jen Ji from Cantor Fitzgerald. Your line is now open. Hi. This is Jennifer Gia for our overall congrats on the shots of results. So for the neuro programs, what other CNS targets are you excited about if the phase one, two for map to positive? Are you asking what other gene targets are we interested in? For knockdown, if the map keyword found. Sure, so we have a lot of different targets. We haven't disclosed any of those.

53:20 And 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 siRNA space right now. So stay tuned. Great, thank you. Thank you. One moment for our next question. Edward Kandoff from Piper Sandler's is our next question. Your line is now open. Great. Thank you very much. I just wanted to read through a little bit and go back through sort of what the plans are for marketing now that you're approved in US, Canada, Australia, and Europe.

54:14 Are you directly marketing in each of those? And how or are you using distributors? And how does are you going to recognize revenues from each of those geographies and then pay out a distributor fee in SG and A? Just want 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 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.

55:06 And in terms of revenue recognition? So in terms of revenue recognition, just follows the standard, so this is Dan here, following 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? Is it a net revenue or is there a fee that's paid in SG and A? Thanks so much. Oh yeah, no, it's similar to The US, 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 been offered by our commercial partners there, just kind of like a contract marketing contract sales that would show up in marketing and sales costs. That would not be part Super of helpful, Dan. Thanks, Thank you, Bob.

56:12 Thanks, Ed. This concludes the question and answer session. I would now like to turn the call back to Chris and Nathalie only for closing remarks. Thanks very much for joining us today, and we look forward to speaking with you later in August after ESC, and then in September around the Arrowhead RPHA disclosures, as well as the MAPT. Have a great summer. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.