Arrowhead (ARWR) Q4 2026 Earnings Call Transcript

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DATE

Thursday, Nov. 12, 2026

CALL PARTICIPANTS

• Senior Vice President of Investor Relations - Vincent Anzalone
• President and CEO - Dr. Christopher Anzalone
• Senior Vice President and Head of the Global Cardiometabolic Franchise - Andy Davis
• Chief Medical Officer and Head of R&D - Dr. James Hamilton
• Chief Financial Officer - Daniel Apel

TAKEAWAYS

• Net Loss -- $724.2 million, or $5.11 per share, reflecting a onetime $215 million expense related to the acquisition of a priority review voucher.
• Total Revenue -- $450.8 million, representing a decrease year over year from $829.4 million due to the recognition of significant collaboration payments in the prior fiscal year.
• REDEMPLO Product Revenue -- $6.6 million, marking the first full year of commercial sales for the treatment of familial chylomicronemia syndrome.
• New-to-Brand Prescriptions -- 950 at fiscal year end, representing a 63% increase over the prior quarter end.
• Cumulative Prescriptions -- approximately 1,250 as of early Nov., reflecting an additional 300 prescriptions received after the close of the fiscal fourth quarter.
• Weekly Prescription Run Rate -- 50 to 60 per week, an increase from the previous run rate of 20 to 30 per week recorded earlier in the year.
• Unique Prescribers -- over 860 as of early Nov., compared to 640 at the end of the fiscal fourth quarter.
• Payer Coverage -- 160 million lives in the U.S. now have a reimbursement pathway under published utilization management policies for FCS.
• Cash and Investments -- $1.2 billion as of Sept. 30, 2026, providing liquidity to support the transition to a potential blockbuster market launch.
• sHTG Market Opportunity -- $3 billion to $4 billion in estimated annual U.S. sales over time, supported by a target population of 1 million high-risk patients.
• Triglyceride Reductions -- 79% to 81% median reduction from baseline at month 12 in the pooled SHASTA-3 and SHASTA-4 studies.
• Acute Pancreatitis Risk Reduction -- 78% overall reduction in cumulative events versus placebo, increasing to 91% among patients with a prior history of the condition.
• Number Needed to Treat -- 3 patients to prevent one acute pancreatitis event over 1 year in patients with triglycerides above 500 mg/dL and a prior history of pancreatitis.
• Sixth Street Debt Refinancing -- $400 million senior secured term loan at SOFR plus 5.5%, replacing a previous facility that carried a 15% annual interest rate.
• Debt Retirement Discount -- $68 million, negotiated as part of the retirement of the previous credit facility.
• ARO-DIMER-PA Clinical Results -- mean maximal reductions of 89% in PCSK9 and 95% in APOC3 following a single dose in an interim Phase 1/2a analysis.
• ARO-MAPT CSF Tau Reduction -- 73% mean reduction in cerebrospinal fluid total tau at day 105, providing evidence of target engagement in the brain.
• Sarepta Collaboration Revenue -- $317 million recognized during the fiscal year, including a $181 million milestone payment for the second DM1 target.
• R&D Expenses -- $739 million, an increase of $132 million year over year driven by higher clinical candidate costs and manufacturing readiness.
• SG&A Expenses -- $202 million, reflecting a $78 million increase primarily due to the commercial infrastructure build for the REDEMPLO launch.
• U.S. Wholesale Acquisition Cost -- $45,000 per patient per year for REDEMPLO, with management intending to maintain a consistent price across current and future indications.

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RISKS

• Anzalone indicated that the conversion of written prescriptions to paid shipments currently acts as a choke point, requiring substantial work with payers to improve processing rates.
• Hamilton reported that worsening glycemic control was observed in 14.3% of plozasiran-treated patients versus 8.7% in the placebo group, consistent with the progressive nature of the condition.
• Hamilton noted that higher doses of ARO-DIMER-PA at 200 and 400 milligrams resulted in immune-related adverse events, including pyrexia, headaches, and injection site reactions.

SUMMARY

Arrowhead Pharmaceuticals, Inc. (NASDAQ:ARWR) management indicated that the company is transitioning toward a commercial-stage organization as it builds a global cardiometabolic franchise. Management stated that the company is preparing for a potential U.S. launch of plozasiran in severe hypertriglyceridemia (sHTG) during the second quarter of 2027, following a recent supplemental application submission. The company reported a net loss for the fiscal year driven by onetime expenses and increased R&D investment, while maintaining a significant cash position. Strategic priorities include advancing a diverse pipeline of RNAi therapeutics targeting the liver, lungs, muscle, and central nervous system. Management indicated that commercial progress in the initial rare disease market is critical for establishing the infrastructure needed to address larger patient populations.

• The company expects a six-month priority review for its sHTG supplemental application through the FDA STAR pilot program, which may allow for action at least 1 month before the standard goal date.
• Anzalone stated that the clinical validation of blood-brain barrier delivery via subcutaneous injection represents a breakthrough that expands the company's potential to address central nervous system targets.
• Management retains a priority review voucher with an estimated market value of $180 million to $220 million, which is now eligible for sale to a third party.
• The company announced a decision to change its fiscal year end to Dec. 31 to align with the calendar year starting in Jan. 2027.
• ARO-DIMER-PA demonstrated clinical validation of the company's ability to silence two separate genes simultaneously using a single RNAi molecule.
• The YOSEMITE Phase III trial for zodasiran completed enrollment with 70 patients, and management anticipates study completion in mid-2027.
• Management expects to share updates from its obesity programs, specifically focusing on ALK7 monotherapy and tirzepatide combination cohorts, before the end of 2026.

INDUSTRY GLOSSARY

• RNAi (RNA interference): A biological process in which RNA molecules inhibit gene expression or translation.
• sHTG (Severe Hypertriglyceridemia): A medical condition characterized by severely elevated levels of triglycerides in the blood, typically defined as levels exceeding 500 mg/dL.
• FCS (Familial Chylomicronemia Syndrome): A rare genetic disorder that prevents the body from breaking down fats, leading to extremely high triglycerides and risk of pancreatitis.
• STAR (Split Real-time Application Review): An FDA pilot program intended to shorten the review period for supplemental drug applications.
• PRV (Priority Review Voucher): A voucher issued by the FDA that grants an expedited six-month review for a future drug application.
• TRiM (Targeted RNAi Molecule): Arrowhead’s proprietary platform designed to deliver RNAi therapeutics to specific tissues such as the liver, lung, or brain.
• APOC3 (Apolipoprotein C-III): A protein produced in the liver that raises triglyceride levels by slowing their clearance from the bloodstream.

Full Conference Call Transcript

Operator: Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. [Operator Instructions] I will now hand the conference call over to Vince Anzalone, Senior Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

Vincent Anzalone: Good afternoon. Thank you for joining us today to discuss Arrowhead's results for its 2026 fiscal year ended September 30, 2026. With us today from management are President and CEO, Dr. Chris Anzalone, who will provide an overview; Andy Davis, Senior Vice President and Head of the Global Cardiometabolic Franchise, who will provide an update on commercialization activities; Dr. James Hamilton, Chief Medical Officer and Head of R&D, who will discuss our development programs; and Dan 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.

Dr. Christopher Anzalone: Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. Arrowhead has fundamentally changed over the past 12 months. Where there was once a company that relied solely on great scientific promise, there is now a company that is beginning to translate promise into real patient outcomes and the potential for durable shareholder value growth. We are building a commercial business around REDEMPLO. We have delivered the pivotal data we believe is needed to pursue a much larger market in severe hypertriglyceridemia or sHTG. And we have demonstrated new capabilities that substantially expand what our RNAi platform can do. I believe we approach 2027 with the strongest combination of near-term commercial opportunity and scientific capability in our history.

For the long term, we intend Arrowhead to become a substantial pharmaceutical company that introduces important new medicines into the market virtually every year. We believe we've demonstrated that we have the platforms and development capabilities to do this, and the result could be an engine that improves innumerable patient lives and creates substantial value. But first things first, we need to build a commercial presence that matches the excellence we've built in discovery and development, and we need to demonstrate that we are capable of building out a new market, finding the patients who could benefit from our medicines and growing a profitable business. Simply put, commercial progress with REDEMPLO is critical.

We are focused on continued success serving the FCS market, planning a rapid launch into sHTG and positioning Arrowhead to maximize the sHTG market opportunity. Of course, revenue levels, growth and profitability will ultimately be the only metrics that matter when assessing how we are doing with REDEMPLO. However, that will not tell the full story until after the first several quarters of our planned sHTG launch as payer policies are being worked out, coverage is being secured and provider outreach is initiated. So during this period, we will regularly refer to 3 metrics that we believe capture the breadth and depth of early market penetration.

They are: one, total number of new-to-brand patient prescriptions; two, number of distinct prescribers writing prescriptions; and three, number of lives covered on payer formularies. We believe there are large pools of patients who can benefit from REDEMPLO, and these 3 metrics are intended to reflect how well we are building pipes to reach them. We launched into the narrow FCS market about 11 months ago and are still in the pipe building phase. This work has progressed well. As of September 30, we had 950 new-to-brand patient prescriptions, representing a 63% increase over the prior quarter end. This growth rate continues to increase rapidly as we have added another 300 since then.

At September 30, over 640 distinct individual prescribers wrote first-time prescriptions, and that number has grown to over 860 since then. There are now over 160 million lives covered in payer formularies in the U.S. We are seeing strong demand for REDEMPLO and continue to work with payers to increase the rate at which prescriptions are converted to paid shipments. This is still a choke point, and there is substantial work to do, but we are off to a good start. The pipes we are laying are also -- the pipes we are laying are critical for the FCS market and importantly, directly applicable to the next stage of our business in sHTG.

We intend to enter sHTG with an organization that already understands the medicine, its prescribers and the practical work needed to get patients on treatment. Let's now look forward. We are preparing aggressively for a potential U.S. launch in sHTG in the second quarter of 2027, subject to successful FDA review and approval. The FDA granted plozasiran entry into the Split Real-time Application Review, or STAR pilot program for our planned sHTG supplement. STAR provides a 6-month priority review framework and the possibility of action earlier than the formal goal date. We submitted our sNDA on November 2, so we expect to receive our PDUFA date over the next 50 days or so.

We are very optimistic about the potential for this launch. We believe the clinical profile, the unmet need and the capabilities we are building position REDEMPLO to become the leading treatment in this market. That conviction begins with data. In July, we announced that SHASTA-3 and SHASTA-4 met their primary endpoint and every prespecified secondary endpoint. The detailed results presented at the European Society of Cardiology Congress in August and at the American Heart Association just last weekend reinforced the consistency of plozasiran's activity. Median triglyceride reductions from baseline were 79% and 81% at month 12.

In the pooled analysis, cumulative acute pancreatitis events were reduced by 78% versus placebo across the broad sHTG population study with an impressive 100% reduction in patients at the highest risk of acute pancreatitis. These are results that we believe can change treatment expectations. Physicians see patients whose triglycerides remain dangerously elevated despite existing approaches. Our goal is to deliver those physicians a medicine that can produce deep sustained reductions with a simple quarterly injection, supported by evidence of fewer acute pancreatitis events in the SHASTA-3 and 4 studies. We believe that is a powerful proposition for patients and payers alike. We continue to describe the profile we are pursuing as safe, simple and strong.

Safe reflects the favorable tolerability observed in all of our studies, no increase in liver fat, no hypersensitivity and no notable changes in liver values. Simple reflects a fixed 25-milligram dose administered once every 3 months. We don't expect to need to monitor liver enzymes and there will be no need to titrate the dose up. Strong reflects the depth of triglyceride lowering and the pancreatitis results. The FDA will determine the final sHTG label, but we have a high degree of confidence in this medicine. We continue to see the potential for REDEMPLO to generate $3 billion to $4 billion in annual U.S. sales over time in sHTG.

These are large numbers, but we see many ways to get there. While there are thought to be 3 million to 3.5 million people in the U.S. with TGs greater than 500 milligrams per deciliter, we believe the early adopters will be the population at highest risk within this group. This is comprised of those patients with TGs greater than 880 without a history of pancreatitis and those with TGs greater than 500 that have a history of acute pancreatitis. Together, we believe this population totals almost 1 million people in the U.S. and their enhanced risk of acute pancreatitis would suggest that they are in real need of treatment.

In SHASTA-3 and 4, the number of patients needed to treat in order to prevent a single acute pancreatitis event was 9 in patients with TGs greater than 880 without history of pancreatitis and those with TGs greater than 500 and history of pancreatitis. Within that latter group alone, the NNT was only 3. These are very compelling numbers, and keep in mind that this is just after 1 year. We would expect those NNTs to decrease further over longer treatment periods. Our data suggests that this patient population could benefit from REDEMPLO, but a valid question is how long it will take to educate patients and providers about the need to treat.

There is clearly already some appreciation for this. For instance, we believe that around 1 million people with TGs greater than 500 are on prescription fish oils. This suggests to us that providers already have an urgency to treat TG levels for at least these patients. Remember that these fish oils only reduced TGs by 20% to 30%, while REDEMPLO reduced TGs by around 80% from baseline in SHASTA-3 and 4. Outside the U.S., our business is advancing as well. REDEMPLO became available for prescription, dispensing and reimbursement in Germany in August, following the European Commission's June authorization. In addition, in October, the U.K.

Medicines and Healthcare Products Regulatory Agency, or MHRA, authorized REDEMPLO in the United Kingdom for adults with FCS and the U.K. National Institute for Health and Care Excellence, or NICE, issued guidance recommending funding in England and Wales. These milestones expand the foundation of our global cardiometabolic business. Besides our commercial build-out, our discovery engine has delivered 2 important clinical advances. In September, ARO-DIMER-PA demonstrated that one RNAi molecule can silence both PCSK9 and APOC3 in people with mixed hyperlipidemia. That opens an important new approach to ASCVD due to mixed hyperlipidemia and gives us a basis for developing additional medicines that address more than one disease driver at a time.

Then in October, ARO-MAPT produced substantial and sustained reductions in tau measured in the cerebrospinal fluid after subcutaneous administration. We view this as early clinical validation of our ability to deliver RNAi across the blood-brain barrier. The opportunity to address CNS targets with an injection under the skin could dramatically expand the diseases we can pursue. I do not think this breakthrough can be overstated. We intend to move decisively to build on these results. This is the model we have been building for years, establish delivery to a cell type, learn how to do it reliably and then apply that capability to additional targets.

Our clinical work now spans the liver, lung, muscle, adipose tissue and CNS with additional tissue types we can study preclinically. Every successful expansion gives us the potential to create multiple new medicines and additional opportunities for partnerships. Our cardiometabolic franchise illustrates how that can translate into an efficient commercial business. REDEMPLO, zodasiran, ARO-DIMER-PA and our obesity and NASH programs could serve related physician audiences. We intend to build an organization that can support several products through much of the same infrastructure. That is an important part of how we think about growth and long-term returns on the capital we invest.

We have also announced an agreement with Sixth Street to retire our existing debt at a discount to the minimum multiple on invested capital provided for in the existing agreement and to establish a new facility at a lower cost of capital. The refinancing is designed to extend our debt maturity and provide financing terms more consistent with Arrowhead's current stage. We have a great deal to execute, and we are approaching it with urgency. The potential sHTG launch is our most important near-term commercial priority. We believe it can change the scale of Arrowhead's business, while the rest of our pipeline creates opportunities well beyond REDEMPLO.

I'm more optimistic than ever about the patients we can help and the value we can build. With that overview, I'd now like to turn the call over to Andy Davis. Andy?

Andy Davis: Thank you, Chris, and good afternoon, everyone. We are approaching 1 year since REDEMPLO's initial FDA approval and the FCS launch continues to progress. I'll cover 3 measures of this progress: number one, growth in prescriptions; number two, expansion of the prescriber base; and number three, advancements in market access. Then I'll connect them to our planned sHTG launch anticipated in the second calendar quarter of 2027. First, growth in prescriptions. Total new-to-brand prescriptions grew 63% in the fiscal fourth quarter, and that momentum has carried into this quarter, taking us well past 1,250 cumulative new-to-brand prescriptions. On prior calls, I cited a run rate of 20 to 30 new prescriptions per week.

Recent trends support approximately 50 to 60 per week. We are encouraged by the sustained increase in demand. Since expanding our field team this summer, we are reaching substantially more health care professionals, and we are seeing strong interest in REDEMPLO from prescribers across specialties. It's important to note, however, that these are written prescriptions, not paid claims. Moving from prescription to treatment requires patient engagement, benefit verification, physician office support and prior authorization submission and approval. Our dedicated REDEMPLO reimbursement navigator team is heavily focused on educating offices on the reimbursement process to convert this demand into treatment starts and durable access. Second, expansion of the prescriber base. Unique prescribers grew over 50% in the fiscal fourth quarter.

Since then, in the last 5 weeks alone, we added as many prescribers as in the entire fourth quarter, bringing the total as of the first week of November to over 860. We view this as an important indicator of future growth and a productive field engagement with the right providers. The specialty mix is led by cardiology and endocrinology with internal medicine of growing share. These are the same specialties we expect to engage for sHTG should REDEMPLO be approved for that use next year. Repeat prescribing is also building with approximately 27% of prescribers having written for more than one patient.

In recent market tracking research, prescribing physicians report strong satisfaction and high and increasing likelihood to recommend REDEMPLO since launch. Third, advancements in market access. Payers representing the vast majority of U.S. covered lives have published utilization management policies for REDEMPLO and FCS. These policies describe the criteria by which a payer will evaluate a reimbursement request. Additionally, more than 160 million U.S. lives now have coverage for REDEMPLO, with coverage defined as those eligible patients with a reimbursement pathway under the applicable policy criteria. Both of these metrics have grown steadily since launch. Our objective is to expand access for appropriate patients with genetically confirmed or clinically diagnosed FCS and to help practices navigate requirements efficiently.

We are working with payers, specialty pharmacies and physician offices to move prescriptions through the process and reserve points -- and resolve points of friction. Broadening access and improving the patient journey are central priorities as we prepare for a much larger opportunity. Turning to sHTG. Our enthusiasm is high. We are preparing for a potential launch in the second calendar quarter of 2027, subject to FDA approval. Our initial focus is on patients at high risk of acute pancreatitis, including those with triglycerides at or above 880 milligrams per deciliter or above 500 milligrams per deciliter with a prior history of pancreatitis. We have described this as approximately 1 million people in the U.S. within the broader sHTG market.

We have identified more than 20,000 health care professionals across relevant specialties as likely sHTG treaters, and we are well advanced in building our HCP engagement, patient services, distribution and market access capabilities. Our expanded sales team is now largely in place, building relationships and mapping priority accounts in preparation for a potential sHTG launch. What we are learning now will help us execute as the addressable population expands. Our One-REDEMPLO pricing approach supports this transition. The current U.S. wholesale acquisition cost is $45,000 per patient per year, and we intend to hold a consistent U.S. price across FCS and sHTG if the broader indication is approved. We believe that simplicity supports productive payer discussions and a clear value proposition.

Outside the U.S., Germany and the U.K. are now active commercial markets. In the U.K., the reimbursement authority recently issued final guidance recommending REDEMPLO for genetically confirmed FCS, supporting reimbursement in England and Wales, and we are working to serve eligible patients there now. To recap, the FCS launch is showing increased prescription demand, a broadening prescriber base and important advancements in access. This is the progress we intend to carry into sHTG. We believe the opportunity ahead is significant, and our team is preparing accordingly. With that, I'll turn the call over to James.

James Hamilton: Thank you, Andy. The fourth quarter and subsequent period included important progress in our late-stage cardiometabolic programs and clinical validation of 2 new applications of Arrowhead's TRiM platform. I'll begin with plozasiran and then discuss zodasiran, ARO-DIMER-PA, our CNS efforts as well as obesity and NASH. For plozasiran, the SHASTA-3 and SHASTA-4 results give us a strong basis for the sHTG sNDA, which, as Chris mentioned, has been submitted. Both trials evaluated 25 milligrams every 3 months and both met their primary and all prespecified secondary endpoints.

In addition to the triglyceride reductions Chris described, more than 90% of treated patients achieved triglycerides below 500 milligrams per deciliter at month 12 and more than half achieved triglycerides below 150 milligrams per deciliter. In the pooled acute pancreatitis analysis, the overall reduction in cumulative events was 78% versus placebo. Among patients with a prior history of acute pancreatitis, the event rate reduction was 91% with an estimated number needed to treat of 3 over 1 year to prevent one event. In the highest risk group with triglycerides above 880 and the prior history of pancreatitis, there were no events observed in the plozasiran group. These subgroup findings support our focus on patients with substantial ongoing risk.

Safety remained favorable overall and consistent with our previous experience. Treatment-emergent adverse event rates were similar in the pooled placebo and pooled active groups. There were no cases of anaphylaxis or systemic hypersensitivity, no clinically meaningful platelet changes and no meaningful liver enzyme elevations relative to placebo. The MRI sub-study showed no statistically significant change in hepatic fat fraction. Worsening glycemic control was reported more frequently with plozasiran at 14.3% versus 8.7% in placebo, with mean changes in hemoglobin A1C consistent with previous experience and importantly, the progressive worsening of A1C over time. Our regulatory package draws on SHASTA-3, SHASTA-4 and the MiR-3 safety database, working within STAR, which includes priority review, we continue to anticipate an efficient review process.

Entry into STAR reflects the FDA's assessment that the application meets the program's criteria for a potentially meaningful improvement over available therapy on clinically relevant endpoints. Approval and the ultimate label remains subject to regulatory review. Now turning to zodasiran. In July, we completed enrollment in the global Phase III YOSEMITE study in homozygous familial hypercholesterolemia. We enrolled 70 patients above the original target of 60, reflecting strong interest in this population. The trial evaluates quarterly dosing and the change in LDL cholesterol at month 12 as the primary endpoint. We anticipate study completion in mid-2027 and data in the second half of next year with a potential regulatory filing thereafter if the results are supportive.

Our previously stated goal has been an NDA filing by year-end 2027. Next, ARO-DIMER-PA. The interim single-dose results announced in September showed mean maximal reductions of 89% in PCSK9 and 95% in APOC3. The corresponding mean maximum lipid reductions were 65% for LDL cholesterol, 78% for triglycerides, 73% for remnant cholesterol and 66% for ApoB. These are early dose escalation results, with the ability to affect both pathways with one molecule, leading to large reductions in atherogenic lipoproteins is highly encouraging. No drug-related serious adverse events were reported in that interim analysis. Injection site events and headache were the most commonly reported treatment-emergent events and multiple dose assessment continues, and we expect additional clinical data around mid-2027.

We are evaluating a development strategy that could first seek approval based on LDL cholesterol lowering, subject to regulatory agreement. Turning to the CNS. Our October 14 presentation included the first interim healthy volunteer results for subcutaneous ARO-MAPT. At the 12.8 milligram per kilogram regimen administered on day 1 and 15, mean CSF total tau fell 73% by day 105 with a maximum individual reduction of 85%. Day 105 was 90 days after the last dose, and these findings support the potential for maintenance dosing every 3 months or less frequently. ARO-MAPT was generally well tolerated in the interim analysis, and there were no serious treatment-emergent adverse events or adverse events leading to discontinuation.

No persistent anemia or neurobehavioral adverse events were reported. These results provide evidence of target engagement in healthy volunteers. Multi-dose healthy volunteer cohorts are fully enrolled and enrollment in early Alzheimer's, patient cohorts is ongoing. We expect additional healthy volunteer data and Alzheimer's patient data in 2027. We've also begun regulatory discussions around clinical studies in MAPT-associated frontotemporal dementia and progressive supranuclear palsy. We have multiple additional CNS programs in development. As discussed at our October webinar, we are targeting CTAs for 2 wholly-owned candidates around end of 2026 or early '27 and additional CNS clinical entries by the end of 2027. The objective is to apply the CNS delivery capability across a broad set of diseases.

Lastly, we remain on track to share updates from our obesity programs, specifically focused on ALK7 nondiabetic monotherapy cohorts as well as the type 2 diabetic tirzepatide combo cohorts before the end of the year. I will now turn the call over to Dan Apel.

Daniel Apel: Thank you, James, and good afternoon, everyone. I'll provide a brief outline of our financial results for the full fiscal year ended September 30, 2026, and then discuss our financial position following several recent developments. As we reported today, net loss attributable to Arrowhead for fiscal year 2026 was $724.2 million or a loss of $5.11 per share based on 141.6 million fully diluted weighted-average shares outstanding in the year. This compares to a net loss of $1.6 million or a loss of $0.01 per share based on 133.8 million fully diluted weighted-average shares in fiscal year 2025. Two factors drove much of the year-over-year change.

First, fiscal year 2025 benefited from $829 million in collaboration revenue, largely from the initial recognition of the Sarepta and Sanofi arrangement. Second, fiscal year 2026 included a onetime $215 million expense for the priority review voucher we acquired in September. Excluding that expense, net loss would have been approximately $509 million. Turning to revenue. Revenue for fiscal year 2026 totaled $450.8 million compared to $829.4 million in fiscal 2025. Revenue in fiscal 2026 was driven by our license and collaboration agreements with Sarepta, Novartis, Madrigal and Sanofi, together with our first year of commercial sales of REDEMPLO. Of that total, $317 million related to our Sarepta collaboration.

This includes $181 million recognized for the second DM1 milestone, the ongoing recognition of initial Sarepta consideration, reimbursement of incurred collaboration program costs, and revenue under the clinical supply agreement, the $317 million compares to $697 million from the prior year with the year-over-year decrease related to the onetime recognition in 2025 of the transfer of the initial Sarepta licenses. For our Novartis collaboration, we recognized $89 million during the year, nearly all of which relates to the $200 million upfront payment we received in October. As of September 30, 2026, we still carried approximately $113 million of deferred revenue, which will be recognized over time as we fulfill our research and development obligations.

During the year, we also recognized a $25 million upfront payment from Madrigal for ARO-PNPLA3 following completion of that license and technology transfer. And we recognized $13.3 million related to Sanofi in Greater China compared to $130 million in the prior year, which related to the upfront consideration received when that agreement closed. Finally, fiscal year 2026 also marked our first year of commercial sales of REDEMPLO with net product revenue of approximately $6.6 million. As both Chris and Andy have mentioned, we are very pleased by the reception from patients, physicians and payers and how the underlying prescription volume and net sales are developing.

While we have consistently stated that FCS revenue will have an immaterial impact to our 2026 financial statements, we continue to invest in supporting this FCS launch and preparing for the potential blockbuster opportunity in sHTG. Turning to expenses. Total operating expenses for fiscal 2026 were approximately $1.16 billion compared to $731 million in fiscal 2025. The $427 million increase includes the $215 million priority review voucher expense. Excluding the voucher, operating expenses were approximately $943 million, an increase of $212 million year-over-year, driven by $132 million of higher R&D and $78 million of higher SG&A expense. R&D for the expense -- year was $739 million compared to $607 million in the prior year.

Candidate costs accounted for $96 million or the majority of that increase. Taken as a whole, these R&D investments supported the positive pivotal sHTG results reported this summer, the advancement of our broader pipeline and our efforts toward commercial manufacturing readiness in Verona. As a reminder, the Verona plant provides us accelerated and enhanced ability to prioritize and make new clinical GMP oligonucleotide drug substance and will be used to support future commercial products, the first one planned being zodasiran. SG&A expense for the year was $202 million compared to $124 million in the prior year. The increase was driven primarily by our investment in the commercialization of REDEMPLO.

As we have discussed, these capabilities more than support the current FCS launch and were built with the intention of being fully leverageable for the potential sHTG launch and ultimately for zodasiran in HoFH. As of today, our commercial organization is largely in place, and we expect only incremental additions as we approach a potential U.S. sHTG launch. Turning now to the balance sheet. Cash and investments totaled nearly $1.2 billion as of September 30, 2026, compared to $0.9 billion a year earlier. Cash used in operating activities was approximately $272 million for the fiscal year. Importantly, that year-end balance is after funding both our operating activities and the $215 million purchase of the priority review voucher.

Common shares outstanding at year-end were approximately 141.3 million. As to the voucher, following the FDA's acceptance of plozasiran into the STAR pilot program in October, it is no longer needed for our planned sHTG supplemental application and is eligible to be sold to a third party. Publicly announced PRV transactions over the last 12 months have ranged from approximately $180 million to $220 million. Purely illustratively, if we were to sell our PRV at prevailing market rates, our cash and investments would be approximately $1.4 billion on a rounded pro forma basis. To be clear, though, we have not entered into a sale agreement and no PRV sale proceeds are included in our reported statements.

Finally, I'd like to highlight the refinancing we recently completed with Sixth Street on November 2. We replaced the prior facility with a new $400 million senior secured term loan and 3-month SOFR-plus 5.5% compared to the prior facility's 15% annual rate. We also negotiated significantly a $68 million discount to the minimum amount required to retire the old facility in 2028. The new loan matures on November 2, 2031, has no scheduled principal amortization before maturity and importantly, eliminates any and all required cash sweeps to Sixth Street tied to product sales, royalty, milestones or any existing or new licensing and partnership proceeds.

To put our debt position in context, our funded debt now consists principally of the $400 million term loan due in November 2031 and $700 million of 0% convertible notes due in January 2032. In other words, no principal payments are required before late 2031. Compared with the retired structure, this materially lowers our borrowing costs, extends maturity and improves our near-term liquidity and flexibility. Taken together, we believe our strong balance sheet with approximately $1.2 billion of reported cash and investments, a transferable PRV with demonstrated market value and a meaningfully lower cost, longer-dated debt structure provides a substantial financial flexibility to support our current clinical and preclinical priorities, current and future commercialization activities and our long-term strategic priorities.

Lastly, and unrelated to our financial position, we announced today our decision to change our fiscal year-end to December to align with the calendar year. The calendar quarter ranging from October to December 2026 will be what is called a transitional quarter period with fiscal quarter 1, 2027 now referring to January through March 2027. We believe this change will ease a number of administrative burdens associated with the September year-end and ahead of a potential sHTG launch will improve company and investor communication. With that brief overview, I will now turn the call back to Chris.

Dr. Christopher Anzalone: Thanks, Dan. I want to close with what we believe the next year can mean for Arrowhead. REDEMPLO has given us our first commercial foundation. We view that as a launching pad that is intended to enable us to address the sHTG opportunity rapidly. We are targeting the second quarter of 2027 for a potential U.S. sHTG launch subject to FDA approval. We believe we have the data to support a highly differentiated medicine, a large population with substantial unmet need and a growing commercial organization that understands how to serve physicians and patients and how to navigate the payer landscape. We intend to build the leading franchise around that combination.

The coming period should also bring important opportunities beyond REDEMPLO, including additional obesity data by the end of 2026, additional ARO-DIMER-PA data in the first half of 2027. [ The 70 Phase ] III readout in HoFH in the second half of 2027, zodasiran NDA filing by the end of 2027, initial patient data from ARO-MAPT in the second half of 2027, new candidates emerging from our dimer and CNS platforms throughout 2027 and the opportunity to receive milestone payments from existing partnerships and the possibility of new deals throughout 2027. We have worked for years to build a company that can repeatedly create important medicines to participate meaningfully in the value they generate.

We now have much more evidence that this model can work. We are commercial, our mid- and late-stage pipeline is advancing and our ability to reach new tissues and targets continues to expand. That is why we are so optimistic. We believe that the next stage of Arrowhead's growth can be substantially larger than the last, and we are working to make that happen. Thank you for joining us today. And I would now like to open the call to your questions. Operator?

Operator: [Operator Instructions] And our first question will come from the line of Maury Raycroft with Jefferies.

Maurice Raycroft: Given that Ionis has set expectations for their early sHTG launch to be softer than expected, do you view that as a company-specific execution issue or evidence that the sHTG market may take longer to develop than anticipated? And how do you reconcile the Ionis comments on broad access and the 1 million people on prescription fish oils with the perception that there may be headwinds to the launch? And I guess, can you help us identify what those headwinds could be?

Dr. Christopher Anzalone: Boy, you jammed several questions into one question. So broadly, look, what we learned from Ionis doesn't affect our expectation in sHTG at all. I think what we've seen from them are some missteps in communication, some missteps in commercial execution, and we don't expect to have those missteps. And so we are full steam ahead towards a rapid launch in sHTG. That's a large market. We have a good differentiated medicine that can address that market, and we are building towards that as we speak. So we are as bullish as ever on our ability to help those patients. look, you've seen our -- the increase in demand as reflected by prescriptions.

We saw a good, what, 63-or-so percent increase from quarter-to-quarter in number of prescriptions, but then an additional 30% increase just over the last 4 to 5 weeks Same thing with the increase in prescribers, another 30-or-so percent increase just over the last 4 to 5 weeks. And so we see a lot of demand out there waiting for REDEMPLO to be available for sHTG individuals. And also, look, we've got some structural advantages as it relates to an sHTG launch just because we are a second. We are able to see what has been done in the market, and I think adjust accordingly.

We are also having early discussions with payers to hopefully allow us to hit the ground running with respect to payers once we are approved in sHTG. I think we're doing a good job in preparation for that. As we talked about, the slow piece of this has been what we call the middle of the funnel. So once prescriptions are written, we have to go through a number of machinations with payers in order to get paid shipments. We're working through that. And I think that our expectation is that we should be able to work through that even quicker in sHTG because we are talking about it right now.

Operator: One moment for our next question. And that will come from the line of Jason Gerberry with Bank of America.

Jason Gerberry: A follow-up just kind of on the competitor launch. You guys have said twice, I think, on this call, rapid launch, but then also said it will take several quarters. I wasn't sure if the several quarters was into the TRYNGOLZA launch or several quarters into the REDEMPLO launch. And maybe because you guys highlighted communication and kind of expectation setting, is your definition of a rapid launch on sort of the metric that you guys outlined like NBRx as opposed to revenue. So I just wanted to perhaps clarify that so everybody's level set.

Dr. Christopher Anzalone: And do you want to start with that?

Andy Davis: Yes. Thanks for the call, Jason. I'm happy to comment. As we have mentioned at the outset of this call, the 3 leading indicators that we will be tracking and looking to consistently report to you and others are the 3 metrics you mentioned at the outset of the call, that's new-to-brand prescriptions, which is largely synonymous with new patients. breadth of prescribers. So are we able to communicate to the prescribers who are interested in educating. And number three, how are we navigating the payer space that is through the metric of coverage. And we have mentioned that in FCS alone, we currently have 160 million lives covered for REDEMPLO and FCS.

We think that is a very good number at this place in the launch. And so these are the 3 leading indicators that we'll continue to report on as we define what would be a rapid launch for REDEMPLO into sHTG as well. Yes. And look, we're not walking away from revenue. Obviously, revenue is important. Our point here is that in the early stages of the launch, that may not tell the entire story. So while we'll be talking about revenue and how we increase that, I think it's also important to look at these other 3 metrics to see how growth is going and to see how market penetration is going as we work with payers.

And as you know, it just takes a little bit of time to get these policies in place and have coverage in place.

Operator: One moment for our next question. And that will come from the line of Mike Ulz with Morgan Stanley.

Michael Ulz: Maybe just another follow-up on REDEMPLO and the pending launch here. Just wanted to get your thoughts on potentially providing guidance. What's the current thinking there? Is that something you might share next year at some point? Or any thoughts there would be helpful.

Dr. Christopher Anzalone: Yes. Unfortunately, it's just too early to provide guidance. We will be happy to do that when we can. We have just filed our sNDA. We don't have a PDUFA date yet, much less a label. And so we need to see what that label looks like. We need to have some experience working with payers. As I mentioned, we are starting to do that right now, even prior to an sHTG label. So I think that, that can move relatively rapidly. But until we have better visibility on those key features, it's just too early to provide guidance.

Operator: And our next question that will come from the line of Brian Cheng with JPMorgan.

Lut Ming Cheng: Just shifting away from sHTG here. On the obesity update in the coming weeks, what do you need to see to define success for the ALK7 monotherapy and the tirzepatide combo? And when you talk about new deals, is this an area where you think that the new deal should happen?

Dr. Christopher Anzalone: James, do you want to take the first? [indiscernible].

James Hamilton: Yes, sure. I can talk a little bit about -- I can't set sort of the hurdles that we plan to get over. But in terms of data that we'll be sharing by the end of the year and expect to see the changes in body composition based on MRI. Of course, we'll share safety and knockdown and then probably some changes in body weight as well.

Unknown Executive: Yes. And relating to the deals, -- let's see. I can't give you too much guidance on this. I think maybe it's easier to tell you what's off the table. We are running towards an sHTG launch with plozasiran, with REDEMPLO. We see that as a cornerstone of our burgeoning commercial infrastructure in cardiometabolic and beyond. And so given that, at least in the United States, we have yet no appetite in partnering there. Within CNS, ARO-MAPT is really, really interesting. We have something of real scarcity. We have the ability to deliver oligonucleotides to the brain that is initially clinically validated. We're very excited about that.

And we are interrogating a drug that is targeting a gene target that is well validated, somewhat validated in Alzheimer's, but very well validated in primary tauopathies. And so it's hard for us to imagine doing a partnership around ARO-MAPT at this point. Look beyond that, there could be areas within obesity. There could be areas within NASH that makes some sense to us. Certainly, on the complement side, there could be something that makes sense to us. And then just on the discovery side, we have a number of things that are characterized by grade scarcity and our ability to deliver oligonucleotides to the brain via simple subcutaneous injection. We have really interesting clinical proof of concept there.

There's a lot of good CNS targets that we will go after ourselves as wholly-owned drug candidates, but there's room there to do partnerships with other folks as we have with Novartis so far. I think, same thing with other delivery, say, into the adipose, into lung, those are also scarce. So there's a number of ways we can go. We'll just have to look at opportunities and decide how those opportunities could fit in with our strategy going forward with the cardiometabolic franchise that we are building and with CNS franchise that we're building.

Operator: One moment for our next question. And that will come from the line of June Lee with UBS.

Joon Lee: Congrats on the progress. Going back to REDEMPLO, what's the depth of conversations with payers you can have prior to the FDA approval without a label? How are you taking advantage of this time between now and approval to ensure maximum access and conversion of script to reimbursement upon approval?

Andy Davis: Thanks, Joon. This is Andy. Good question. So we are able to interact with payers using a pre-approval information exchange deck, which essentially articulates the value proposition of REDEMPLO, both clinically and economically. And so we are able to engage with both the clinical and negotiating teams of the large payers in a pre-approval context, and we're presently doing that now, and we'll continue to do that up until the approval of REDEMPLO expected in the second quarter of next year. Yes. Look, that was -- we were confident that we could do that, which is why we bought Priority Voucher. We're happy to report that we don't need that any longer and we can sell it.

But we saw a big opportunity to have those discussions early, particularly if we could have accelerated approval or the possibility for accelerated approval. But also, let's look at what this says about our data. If our data were ambiguous, if there were clear warts on this -- on REDEMPLO, it would be much more difficult to have these early conversations with payers. We don't see that as the case. And so the fact that there are payers talking to us right now before we have a label, I think is indicative of the power of this medicine and the unambiguous value proposition that we've got.

Operator: And that will come from the line of Edward Tenthoff with Piper Sandler.

Edward Tenthoff: Great. And I apologize if someone asked this, I don't think anyone has. But the pelacarsen miss and the data at AHA, any read-through or do you guys have any thoughts on Amgen partner, olpasiran with the OCEAN trial, I think maybe next year? And again, I apologize if someone asked this, I'm trying to listen to everything you guys are saying.

Dr. Christopher Anzalone: Ted, it's great to hear you. So as you know, we are largely out of olpasiran. We monetize those royalties. We still have milestone payments, of course, but we monetize those royalties. And we don't have good visibility on when Amgen may finish this or have data. We have no more visibility than anybody else. But from just my perspective, I don't know that the book is closed on Lp(a). My recollection is this -- that Novartis showed something like 77% reduction in Lp(a). Olpasiran is much better than that. I think that Amgen was seeing better than 90%, 95% reduction in Lp(a). That could make a difference. Of course, the baseline characteristics also could make a difference.

I believe that the Amgen studies have a bit of a higher baseline Lp(a) numbers than Novartis. So that can make a difference as well. So we'll see where that goes. The data were unfortunate with [ pelacarsen ], but I don't think the book is closed.

Operator: One moment for our next question. And that will come from the line of Eric Joseph with Citi.

Unknown Analyst: This is Charles on for Eric. Congrats on the quarter and the year. Maybe one from us on ARO-DIMER-PA sort of registration strategy. Do you mind spending on why you're seeking approval first on the LDL-C lowering versus perhaps a composite-based endpoint? More clarity would be great.

James Hamilton: Yes, sure, Charles. I can take that. Of course, this is all subject to agreement with regulators. But the LDL cholesterol is probably one of the most validated surrogate endpoints out there, and that's our thought is that if we could get -- we get approval and get on the market with an LDL endpoint in the mixed hyperlipidemia population, that would be great. The triglyceride component of mixed hyperlipidemia, that is more of a surrogate for the sHTG population, less so and less widely accepted for the less severe mixed hyperlipidemia population. So that's why we're focusing on LDL at least for now.

And if we can -- we're able to do that, that's a relatively quick time to approval to a fairly large market. We look forward to continuing to see data with ARO-DIMER-PA and to start to have discussions with regulators.

Operator: One moment for our next question. And that will come from the line of Prakhar Agrawal with Cantor.

Prakhar Agrawal: Maybe firstly, on REDEMPLO and sHTG. On the payer side, do you think you're at the right pricing range given some of the initial friction that's happening with the Tryngolza launch? You obviously have the flexibility of seeing what's happening on the market and change accordingly. So I just wanted to see the latest thoughts on pricing to get broad access. And secondly, if I can sneak in one more. On the ARO-DIMER data at AHA, efficacy is obviously great. But if you can talk about some of the detailed safety data in the fat portion. I think there were some injection reactions in pyrexia. So wanted to understand how long these events lasted?

Are these going to be single dose effect and implications for the MAD dosing?

Andy Davis: Thanks, Prakhar, for the question. This is Andy. We do believe we have the right pricing range here for REDEMPLO, and there are 2 kind of leading indicators that give us confidence. The first would be the currently published policies related to Tryngolza and sHTG, which do appear to have policy criteria consistent with label. We are optimistic that we will see in the future similar policy criteria to label for REDEMPLO. And then second, we are engaging with payers, as we mentioned, through the pre-approval information exchange process. And we haven't received pushback through those conversations with payers about the pricing range for sHTG. So we think we're in a great spot.

And look, and you mentioned the friction related to price. I don't know that we have seen that. There is always friction early between writing a prescription and working with payers to get that paid. It just takes a little bit of time to establish those processes. We're doing that now. I don't know that, that is price related. James, do you want to talk about?

James Hamilton: Yes, I can cover the question on the dimer safety. Like you said, what was presented in the SAD component of the study at some of the higher dose levels, 200, particularly 200 and 400 milligrams, we saw some immune-related AEs, specifically pyrexia, headaches, some ISRs. In terms of the ISRs, I mean they're generally consistent with what we've seen and what others have reported with siRNA therapeutics in terms of duration of activity. I'd say when it comes to dose selection, we still don't have all the data.

We need to get the PD and the safety data for all of the MAD cohorts through their second dose and then pick what looks the cleanest and what gives us the best combination of knockdown and safety.

Dr. Christopher Anzalone: Yes, I think that's critical that the data that you've seen so far is just single-dose data. We would expect for at least some doses, a further step down upon second dosing. So we will see what the right doses are. I think there's a reasonable chance that it's going to be less than 200 milligrams.

Operator: And one moment for our next question, and that will come from the line of Luca Issi with RBC.

Jiayi Yuan: Congrats on the quarter. This is Cassie for Luca. And coming back to the APOC3 launch and REDEMPLO, both you and Ionis have described having another competitor in the market as a tailwind. Recently we've learned that the Quick Start program that Ionis has adopted is essentially a bridge program before patients get covered. So wanted to get your thoughts on if REDEMPLO follows a similar playbook here for FCS, given that many of the patients may be first-to-therapy and not yet approved.

And related to it, is there a version of the world where maybe you don't see as many of your patients having to go through such a program, because one, going back to the point of having a competitor in the market, it would be a tailwind providers are already pretty comfortable with the APOC3 class by the time REDEMPLO arrives; and two, for REDEMPLO, perhaps you're getting some switch patients who already qualified coverage. Any color on how we should think about your new-to-class versus same-class switch patients, both in FCS and the upcoming SHTG launch, would be super helpful.

Andy Davis: Yes, thanks, Cassie, I can take the first part of that question. So like any rare disease launch, we do have a quick start bridge program ourselves and a patient assistance program so patients can start therapy while coverage is being established. And so we would expect a quick start program to be in place for SHTG as well, should we be -- should we indicated for that next year. What matters to us is that patients in the end convert to paid therapy as payer policies are put in place, and what matters is that persistence is high once these patients are on therapy.

So we will be heavily focused on ensuring that appropriate patients can get on REDEMPLO, whether that's through a paid claim or through a quick start program as their coverage is being determined, and helping support them with our patient access program so they can remain on therapy.

Operator: One moment for our next question, and that will come from the line of Andrea Newkirk with Goldman Sachs.

Unknown Analyst: This is [ Bernan ]. At the recent Liver Meeting, Regeneron reported some proof-of-concept data for its CIDEB targeted siRNA in an all-comer MASLD population, and I'm just curious in light of this how you view the mechanistic positioning of ARO-PNPLA3, which you are partnered with Madrigal on, recognizing that, that may have efficacy only in a smaller subset of patients. And then in parallel to that, as others have stepped back from HSD to prioritize these other targets, I'm curious what your scientific conviction is in ARO-HSD to drive that clinically meaningful antifibrotic effect that may be independent of steatosis reduction.

James Hamilton: I can take both of those. So the first question about PNPLA3, you'd have to ask Madrigal what their plan is with that in terms of how they plan the development of populations to look at. I would highlight one other presentation that was interesting at AASLD that implied even on GLPs that patients that were homozygous for the I148M PNPLA3 variant seemed to have less of a reduction in liver fat. So there might be an opportunity there for combination therapy. But again, this is all up to Madrigal. And the same is true for HSD really.

That asset, of course, has been licensed to GSK, and so any development plans around where that one would go are up to GSK exclusively.

Operator: One moment for our next question, and that will come from the line of James Condulis with Stifel.

James Condulis: Maybe one going back to trigs here. Just curious what your latest thinking is around how many patients in the U.S. have had a prior pancreatitis event, and just in general, I guess kind of what you think the timeline and path is to really getting broad uptake outside those patients and kind of more of the primary prevention setting.

Andy Davis: Yes. Thanks, James. We estimate there are around 200,000 patients in the U.S. who have a prior history of AP due to high triglycerides. And that range -- there are various estimates on that, but we think that's a fairly good range for your modeling. Clearly, that is the population of highest unmet medical need. It was clearly determined through the data that was reported at AHA this past week, and that of the 2 variables of importance here -- high TGs and prior history of AP, prior history of AP pancreatitis is a very, very key determinant of recurrent AP, and the number needed to treat in those population, that secondary prevention population was incredibly high.

And so clearly that will be a heavy focus for us as we head into the SHTG launch. It's also a high willingness to prescribe from providers and a high willingness to pay from payers. Clearly, it will take some more time over the years to continue to expand into the broader SHTG population. As you would be aware, that high-risk segment we think is about 1/3 of the broader SHTG population, so about 1 million out of 3 to 3.5 million.

So it will take a little bit more time to penetrate that broader SHTG population, and that will largely depend on favorable payer policies, and we do anticipate that those payer policies will allow for penetration of that segment over time.

Dr. Christopher Anzalone: And look, that primary prevention is critical. We know that if you let a patient have a bout of acute pancreatitis, it's more likely that, that person will have another bout of pancreatitis and that it could be even more severe. So it is critical to get these patients on treatment before they're in trouble.

Operator: One moment for our next question. And that will come from the line of Joseph Thome with TD Cowen.

Joseph Thome: Maybe on the obesity ALK7 program, I guess how clear is the FDA guidance on what you would need to do next if the data are supportive? Is there a clear registrational path for a combination approach? And do you see a path forward to study the agent as a monotherapy, or commercially do you not think that's going to be the way to go here, basically, future obesity treatments are going to be some form of combination?

James Hamilton: Well, we've said all along that we think that either one of these, if we study them as a fat-loss or weight-loss drug, would be a combination that would be on top of a GLP-1 or in combination with a GLP-1, and that's still our strategy. In terms of what that development pathway looks like, I mean, the guidance for obesity drugs is a little bit old. I think the 5% weight loss, that may still be relevant, but of course there's a lot of combination products out there. So I would imagine we're not the only company that's having these combination-type questions and discussions with the FDA.

I don't have the definitive answer for you in terms of what this would look like from a development and regulatory pathway for the combination product. That's our plan largely, to continue to look at both of these in combination with the GLPs.

Operator: One moment for our next question. And that will come from the line of Madison El-Saadi with B. Riley.

Madison Wynne El-Saadi: Maybe with focusing on ARO-DIMER, on a patient-by-patient basis, did the biomarker knockdown move together? For example, did anyone achieve deep APOC3 lowering but weak PCSK9 lowering, or the reverse? And then secondly, across the cohorts, is there a responder profile emerging based on triglyceride level?

James Hamilton: Yes, I think in general they move together. Maybe you get a little slightly better APOC3 knockdown at lower doses, but we're able to get plenty of PCSK9 knockdown. So they move pretty much in lockstep as we dose escalate. And so far the response, like we've seen with plozasiran, has been pretty homogeneous. I mean, there's not really patients who we've called non-responders or hyper-responders. So I don't think we can pinpoint any population that's more likely to respond than others, at least not at this point.

Operator: One moment for our next question. And that will come from the line of Patrick Trucchio with H.C. Wainwright.

Patrick Trucchio: Just a follow-up on ARO-MAPT. I'm wondering what the next patient data set is that can connect the CSF total tau lowering to an effect on disease biology, and what result would justify advancing toward a registrational program? And what will determine the sequencing of Alzheimer's disease, MAPT-associated frontotemporal dementia, and progressive supranuclear palsy development?

James Hamilton: So, we're looking at the latter right now, meaning MAPT, FTD and PSP, and we've got study designs for Phase IIs or things that could be adaptive and progress potentially even into Phase III, and having some of those regulatory discussions now. Based on the knockdown data we have from healthy volunteers, we think that showing the knockdown and the safety is sufficient to at least get Phase II studies up and running in those indications. And eventually we'll look more at Phase IIs in Alzheimer's, but we have the Alzheimer's cohorts in the current study up and running, and I'd like to get some data from those cohorts first.

In terms of bridging data, I think the next data points from this program are still going to be in the healthy volunteers, probably the multi-dose healthy-volunteer safety and MAPT reduction data will come out first. Then beyond that, we'll have Alzheimer's patient data, of course, safety and then total tau knockdown, but also starting to look at some of the phospho-tau, the p-tau181, p-tau217, those are probably somewhat bridging biomarkers, indicating that we're influencing, sort of, more disease-relevant biomarkers downstream. And then of course, PET data, the PET tau data will probably come more towards the end of the year.

But those are the next few bridging biomarkers that we anticipate to help us make a call if we want to take something forward into later-stage Alzheimer's development.

Dr. Christopher Anzalone: Yes, I think qualitatively, I think it's fair to say that we are moving quickly in PSP and FTD and slowly in Alzheimer's.

Operator: I'm showing no further questions in the queue at this time. I would now like to turn the call over to Mr. Chris Anzalone for any closing remarks.

Dr. Christopher Anzalone: Thanks, everyone, for joining us today, and I wish you all a nice Thanksgiving holiday in the next couple of weeks.

Operator: This concludes today's program. Thank you all for participating. You may now disconnect.

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