Good morning, everyone, and welcome to the Arrowhead Pharmaceuticals Investor Webcast. At this time, all attendees are in a listen-only mode, and a question and answer session will follow the formal presentations. As a reminder, this call is being recorded, and a replay will be made available on the Arrowhead website following the conclusion of the event. I'd now like to turn the call over to Vince Anzalone, Senior Vice President of Finance and Investor Relations at Arrowhead Pharmaceuticals. Please go ahead, Vince. Thank you, Tara, and thanks everybody for joining us today. We're excited to present the data that we presented yesterday at the European Society of Cardiology in Munich, for what we think is groundbreaking data from the SHASTA-3 and -4 studies of plozasiran. Before we start, just want to make sure everybody knows that we will be making forward-looking statements today, so refer to our SEC filings for risk factors. I also want to remind people that the SHTG indication has not been reviewed or approved by any regulatory authorities around the world, so it should be considered investigational. The results here are preliminary, so they should not be used for HCPs or patients or in product promotion in any way. This is an investor-focused communication today. We're very fortunate today to have two external speakers who are leaders in the field. Dr. Gerald Watts from The University of Western Australia in Perth, who gave our hotline late-breaker presentation yesterday. Also Dr. Børge Nordestgaard from Copenhagen University Hospital, who was the discussant for our presentation yesterday. Here's the flow. Today I'll give a short introduction and a review of Arrowhead generally in the cardiometabolic pipeline. Dr. Jennifer Hellawell, who is Head of Clinical Development at Arrowhead, will talk about severe hypertriglyceridemia or SHTG. Again, Dr. Watts will do an encore presentation of the SHASTA-3 and -4 full results. Dr. Nordestgaard will give a discussion on the results and the clinical implications. Andy Davis, our Head of Cardiometabolic Commercial, will talk about the current status of our commercialization efforts in SHTG. Then I'll give some key takeaways, and then we'll have a little bit of time at the end for you to ask questions to the panel. It'll be a limited amount of time, so we should be able to take maybe five or six questions. I'd ask that you all limit your questions to one. If you have a follow-up, please go back in the queue. Arrowhead. This is a very brief introduction of Arrowhead as a company. As most of you probably know, we're an RNAi therapeutics platform company with a broad pipeline of both wholly-owned and partnered candidates. Importantly, in 2025, we launched our first commercial product in REDEMPLO, which is the trade name for plozasiran. It's currently approved to reduce triglycerides in patients with FCS in the U.S. and the E.U., Canada, Australia and China. We think this is a potential multibillion-dollar opportunity across different future indications. Importantly, we see the potential for multiple independent and partnered launches of other products outside of REDEMPLO over the coming years. Our pipeline is very broad. I will go over a quick overview of what it looks like in a moment. Importantly, we have a good mix of early, mid, late-stage, and now commercial-stage assets, also targeting the most ultra-rare disease, all the way up to the highest prevalence cardiovascular indications. That pipeline has tended to grow by two to three new clinical programs per year, so we are very productive. All of this is built on a proprietary technology platform that we call TRIM, or targeted RNAi molecules. It is optimized for deep and durable gene silencing using the RNAi pathway. We think that Arrowhead is the clear leader in fulfilling the promise of RNAi therapeutics, because we are now capable of bringing RNAi to where disease lives, not just inside the liver. I will show you a slide of the different tissue types we can get to. We do believe that Arrowhead has best in class with liver-expressed genes as well as outside the liver. Lastly, and this is important for any development stage biotech company, we have a strong balance sheet and the financial resources to get to multiple important commercial launches as well as clinical milestones. Those financial resources are complemented and supplemented by additional non-dilutive capital that we expect from existing partnerships with leading pharmaceutical companies. This is a schematic of the seven different cell types that we are working to get the TRIM platform to: liver, lung, skeletal muscle, CNS, adipose tissue, ocular, and cardiomyocytes. Again, we think Arrowhead is the clear leader in fulfilling the long-term promise of RNAi by bringing it to tissues where disease starts. Here is a very long pipeline. Again, the takeaway is we have a broad pipeline, and lots of opportunities for growth. Before I turn it over to Dr. Watts, I just want to give a very brief summary of what we think are the important points of the data that were presented yesterday. In the SHASTA-3 and -4 studies, we achieved triglyceride reductions of about 80% from baseline across the SHTG spectrum. Importantly, more than 90% of the patients on that study got TG levels below 500 mgs per deciliter, which is a key risk threshold for acute pancreatitis. In the studies, we reduced the cumulative AP events, again, across the population by 78%, with a really impressive 100% reduction in the patients at highest risk. Those are patients where their TGs are above 880 mgs per deciliter and have a prior documented history of acute pancreatitis. Again, that 100% risk reduction was extremely impressive, and what we think is paradigm shifting for the treatment of SHTG. Next, we have a consistent and favorable safety and tolerability profile. Frankly, if you look at our AE tables, Gerald will talk about shortly. Everything from prior studies in different patient populations has held. The safety and tolerability profile continues to look either equivalent to what we have seen previously or even better. It is very safe and well-tolerated, which is an important point here. Lastly, these data have also been accepted for publication in a major medical journal, with more details to follow shortly. Now I will turn it over to Jennifer Hellawell, who will talk about the disease of SHTG. Thanks, Vince. Good morning, everyone. Today, I'd like to take a step back and provide an overview of severe hypertriglyceridemia, a vastly misunderstood condition that affects almost one in 100 patients worldwide. Hypertriglyceridemia actually represents a spectrum of disease, with severe clinical manifestations and considerable unmet need across the spectrum. At one end of the spectrum are patients with moderate hypertriglyceridemia, usually defined as triglycerides in the range of 150-500 milligrams per deciliter. This is a condition that affects upwards of 10 million people in the U.S., with substantial ASCVD burden and overlap with other cardiometabolic risk factors. At the other end of the spectrum are patients with familial chylomicronemia syndrome, or FCS, a rare condition characterized by persistent chylomicronemia or triglycerides greater than 880 milligrams per deciliter and an extremely high risk of acute pancreatitis. This condition, of course, can be genetically or clinically diagnosed. However, in the middle of the distribution is severe hypertriglyceridemia. This is generally defined as serum triglyceride levels of greater than 500 milligrams per deciliter. This is a condition that affects approximately one in 100 persons or greater than 3 million people in the United States alone. Severe hypertriglyceridemia can have similarly dire clinical consequences, including an increased risk of life-threatening acute pancreatitis. Much like atherosclerosis, risk in these patients is driven primarily by both higher levels of the causal lipoprotein, in this case, triglycerides, and history of prior clinical events, in this case, acute pancreatitis episodes. For this reason, patients with the highest triglycerides and prior AP events are often referred to as high-risk severe hypertriglyceridemia. This subset is thought to represent about 1 million people in the United States. These patients have an extremely high risk of acute pancreatitis as well, with many patients suffering multiple recurrent attacks and a variety of related severe clinical sequelae throughout their lifetimes. Unfortunately, conventional triglyceride-lowering therapies such as fibrates and omega-3 fatty acids rely primarily on functional lipoprotein lipase, or LPL pathways, which are often dysfunctional in these patients, thereby leading to very modest effects on triglyceride levels. Importantly, until recently, none have been shown to reduce the risk of acute pancreatitis. Apolipoprotein C3, or ApoC3, is a key lipoprotein involved in triglyceride hydrolysis and clearance through both LPL dependent and independent pathways and has recently emerged as a therapeutic target across the spectrum of hyper triglyceridemic disorders. While severe hypertriglyceridemia can sometimes be diagnosed as an incidental finding on routine lipid panels, the patient journey with severe hypertriglyceridemia is typically characterized by an evolution from a hidden, more asymptomatic phase to acute medical emergencies of debilitating abdominal pain, prompting emergency room visits, hospitalizations, and even stays in intensive care units. This period of acute stabilization is then followed typically by discharge to complex, sometimes confusing, long-term outpatient management. The cornerstone of management historically involves extreme dietary restrictions, limiting total fat intake to just 10%-15% of daily calories or under 20-30 grams daily, alongside the complete elimination of alcohol and added sugars. Patients must also aggressively manage secondary risk factors like uncontrolled type 2 diabetes and obesity to improve overall insulin sensitivity. Patients silently struggle with considerable impacts to quality of life as they grapple with fatigue, low energy, and chronic anxiety about the pancreatitis while managing a challenging and limiting lifestyle and medical regimen. With this shared understanding of the dire unmet need and the therapeutic potential of targeting APOC3 with Arrowhead's proprietary TRIM siRNA technology, we undertook our phase III SHASTA program of plozasiran in adults with severe hypertriglyceridemia. It is my pleasure to turn it over to Dr. Gerald Watts to share the results from those studies. Thank you very much. I am most grateful to be here. Mr. Chairman, ladies and gentlemen, potential investors. Jennifer has set a marvelous precedent here for the need for new therapy in this patient group. This is the title of the work that was presented there with a string of co-authors entitled Plozasiran for Severe Hypertriglyceridemia. On the basis of what Jennifer has said already, and risk of pancreatitis, probably its most severe sequela. The SHASTA-3 and the SHASTA-4 pivotal trials, 12 months results. I would like to mention things that are important, too. I mean, SHASTA are two lovely lookout mountains in Northern California. This may well be representative of the potential of this trial to be a landmark trial as those mountains are. The background, again, to reiterate what Jennifer said, that severe hypertriglyceridemia defined above the cutoff points shown up there, 5.6 and 500 milligrams per deciliter. There is about 1% of the population translating probably to 5 to 10 million people worldwide. Increases the risk of acute pancreatitis. These chylomicron particles and triglyceride particles lodge in the pancreas and set off an inflammatory event. It is a heterogeneous disorders driven by multiple factors, genetic factors and secondary causes, overnutrition, obesity, and type 2 diabetes. The next one is an important point, really, that despite best standard of care, many patients don't achieve those treatment goals of less than 5.6, and so that the risk of end organ damage, in particular in the pancreas, acute pancreatitis persists. The opportunities that have arisen is knowledge about APOC3 as a key regulator of the metabolism of triglycerides, and this has now become a validated therapeutic target, with Arrowhead leading the way with its TRIM pathway. Plozasiran is in fact a first-in-class hepatocyte targeted as siRNA that reduces the hepatic synthesis of APOC3 and was evaluated in adults with severe hypertriglyceridemia in these two SHASTA-3 and SHASTA-4 studies. Two trials were undertaken. By way of background, apologies for those who are aware of this is a summary of what APOC3 does that damages triglyceride metabolism on the left-hand side. APOC3 inhibits the breakdown of triglycerides via taking two hits at the lipoprotein lipase-dependent and lipoprotein lipase-independent pathway in the liver. It follows that if you can remove APOC3 out of the system as you can through one injection of plozasiran as shown in the middle of the figure. On the right-hand side, you remove this unwanted inhibitor and that de-represses the activity of lipoprotein lipase and the activity of receptors that clear triglycerides. That is the science behind it. That is one opportunity that one had to redress the balance and the gap in treatment, and the other opportunity is the randomized controlled clinical trial. This was the design that was employed. Two trials were undertaken on the basis of advice from the regulators in the U.S., SHASTA-3 and SHASTA-4. Adult patients with severe hypertriglyceridemia were randomized to 25 milligrams of plozasiran or placebo. Exactly the same design with four injections, subcutaneous injections of plozasiran over 12 months, ending with an open label extension study prerequisite as a bridge to potential new therapies for those who it is indicated. That was a study design. Two trials. Quite a challenge running two trials, but they were done and the results will be presented initially individually for those trials and then as a pooled analysis for the acute pancreatitis endpoint, as a pooled analysis for safety endpoints. Who were the individuals that were studied? It is a busy slide and apologies. I will just let you know who they were en masse. The summary is they were mainly middle-aged people who were overweight, male, whites. A history of cardiovascular disease in approximately a third. Diabetes in approximately just over a half. Acute pancreatitis presented in one in five individuals. It was already a proportion of them had acute pancreatitis and this was a very important group as we shall see. The average triglycerides, the mean value was 9-10 millimoles per liter. It appears half the population in the chylomicronemic range and the other half up from 10 millimoles per liter down to 5. HbA1c, which is a measure of glycemic control, was good and important to note that lipid-lowering therapy, which is the best standard of care for this condition at present, namely fibrates, omega-3 fatty acids, statins, ezetimibe, and combination therapy, was taken by the majority of patients as clinically indicated. That was a group of predominantly male adult patients. This was the primary endpoint. The primary endpoint was the triglyceride level, the percentage triglyceride level at 12 months. You can see here at the top are the placebo groups of the two SHASTA trials, and at the bottom is and you can see as we could evaluate a rapid reduction in triglycerides by three months, that was sustained. Here we are. It was within group change of about 80% that remained statistically significant after adjusting for the fall in placebo. We have seen this before in FCS and other trials, that once these patients with hypertriglyceridemia join a trial, actually, they seem to do quite well, and it is consistent and reflects the recommendation that best standard of care is important and, in fact, demon strates that plozasiran actually adds to really super best standard of care. That is important. From the primary endpoint, there is a select cocktail here of secondary endpoints, triglyceride reduction at 10 months. Interesting secondary endpoint, 80% reduction. Remnant cholesterol at 12 months, about 70% reduction, about 50% if you adjusted for the fall in remnants in placebo. Non-HDL cholesterol, about 26%, 20% reduction of adjusting for the fall in placebo. APOC3 and triglycerides at 12 months in a very high-risk group with baseline levels of more than 20 and more than 10 millimoles per liter. All these changes were statistically significant relative to placebo, implying that all these secondary endpoints of the trial were met. This is an important slide. These are the proportion of people in the two trials, SHASTA-3 and SHASTA-4, who attained these goals that Jennifer and Vince referred to. Doctors think in terms of proportion of people getting to goals, easier to think about because that is what you commun icate to patients. Here you can see 90% in the two trials, 90% achieved triglyceride goals of less than 5.6 millimoles per liter, with the placebo actually showing a 50%. 50% of those actually fell below those goals, as you would anticipate from the previous presentations. Turning here on the right to a goal of less than 1.7 millimoles per liter, which is entirely normal in the fasting state, you see here that plozasiran in both trials, as shown here, half, 50% of the population, over 50%, achieved a complete normalization of fasting triglycerides. This is where it very cle arly outdid the effect of super best standard of care. That was a good take-home message that you can really move the distribution from severe to moderate majority and 50% of the entire population down to a normal triglyceride level, explaining why it worked out to be superior to super best standard of care. Turning now to the pool data, we had to join both studies looking at acute pancreatitis to maintain statistical power, a good opportunity, and this again was approved by the regulators. On the left-hand side, you see total events, the total burden of acute pancreatitis, so there may have been some patients who contributed to events. This is a Kaplan-Meier curve, which is an outcome of interest, the total burden of acute pancreatitis in the placebo group and in the intervention group. Clear evidence that there is an 80% relative risk reduction, a 44.1% absolute risk reduction translating into 24 people with the characteristics of this trial that you needed to treat with plozasiran to prevent one acute pancreatitis event or concoction of events in one year. On the right-hand side is the time to first event, and there was a prolongation of an average of about five months. Again, this was statistically significant, 82, with a hazard ratio of approximately 0.26, and that was statistically significant. The other analysis takes it a little bit further, and it is an exploratory but highly important analysis looking at the highest risk groups. In other words, those who at baseline had fasting triglycerides more than 500 milligrams per deciliter and a history of acute pancreatitis. Really quite a marked reduction in the relative risk reduction. Well over 90%, highly sig nificant, 34% absolute risk reduction. Clearly, this group were at a higher absolute risk and then translated into a maximum of three people that needed to be treated to prevent one event. A further analysis in one looked at those with triglycerides of greater than 10 millimoles per liter, 880 milligrams per deciliter, and a history of acute pancreatitis. There was a 100% reduction in the incidence of acute pancreatitis event. Now, these are small numbers, and they were exploratory, but it gives you a feel for what the great potential is of this intervention in people with the characteristics that make them at highest risk of acute pancreatitis. I will give you time to absorb that because this is key data. Moving on again, analysis, both the SHASTA-3 and -4 come into adverse events. It is a busy table. These are standard outcomes, ranging from all treatment-related adverse events to the most common ones, injection site sensitivity, platelet count, liver enzymes. Down here is a substudy of approximately 36 patients randomized to placebo in 2:1 manner, and 23 to plozasiran. I will just take you through this very briefly. I wo uld first say that the retention rate of patients in the trial was very high, over 90%, and compliance with the four injections almost 100% with no injection site reactions, which is absolutely extraordinary, actually, much more than we see with other siRNAs in our clinical practice and might relate to the way the platform is designed. Treatment-emergent adverse events leading to discontinuation rates were low, 1.2%, similar between the groups. There was no anaphylaxis or systemic hypersensitivity. There was worsening of glycemia using a variety of non-specific endpoints that appeared to be slightly higher with intervention compared with placebo. No clinically meaningful changes in platelet counts, but in fact, no changes at all in the platelet count of note, which was a problem with the earlier interventions that were not GalNAc conjugated. No significant elevations in ALT or AST and none that met this sort of magic law called Hy's Law. It sounds as a law, actually, of the land in a cowboy movie. It comes up, and it is never positive, actually. Again, important relating to this group down here, no statistically significant increases in treatment emergent, increase in hepatic fat fraction when you look at it with magnetic resonance imaging. So very reassuring. Just to give a little bit m ore context concerning glycemic control, the only hard endpoint that could have been defined, but I have to say that this was not a pre-specified endpoint, was glycated hemoglobin, which is a measure of long-term blood sugar control used to monitor people with diabetes. This refers to the absolute values and the relative changes over time. A smidgen of an increase in HbA1c that is exceptionally small and less than 0.25% on their absolute scale with appearance of no significant difference at the end of the intervention. That is the percentage change. Slightly high, but no apparent change from this visual inspection at the end of intervention. So quite reassuring and certainly better than all previous studies with plozasiran and better, really, that that is seen with a competitor agent. So we have reached at the coda of all these movements of this presentation. I'll just reemphasize what the conclusions were. Plozasiran administered every three months reduced triglycerides and acute pancreatitis events in patients with severe hypertriglyceridemia receiving con ventional background therapy and diet. Let me go a bit further, actually, because it was in the trial. The background treatment was actually excellent, super excellent. Triglyceride reductions of 80% were evident at three months and sustained over 12 months with an associated reduction of acute pancreatitis of 80%, a 1% relationship. Over 90% of patients treated with plozasiran dropped their triglycerides below the level that's been used to demonstrate high risk of acute pancreatitis, 5.6 millimoles per liter or 500 milligrams per deciliter, and half of them normalized the level of triglyceride. This is really impressive. This normalization and sustained over 12 months was probably the basis for the reduction in acute pancreatitis. A conclusion related to the high-risk groups, just to drive it home that those in the high-risk group appeared to get the greatest benefit, but there was benefit across all the spectrum of triglycerides from 500 and about 90% of patients with a history of acute pancreatitis and 100% reduction in the. Sorry, I'll say that again. There was over 90% reduction in the relative risk in all patie nts with a history of acute pancreatitis and 100% in the highest risk group. Safety was reaffirmed, and the findings support the value of APOC3-targeted therapy for plozasiran for preventing acute pancreatitis in severe hypertriglyceridemia with significant implications for changing clinical practice once this is approved with a label by the regulators, once this gets into clinical guidelines and a great potential to actually shift practice in a manner consistent with a model of care that has been missing for many years for this high-risk group of patients, something that we need to develop, but as we move along. Thank you for your attention, and congratulations to Arrowhead for funding this study and all the patients who contributed to these difficult studies, actually, two studies. I t's really quite impressive. Thank you, Chris. Thank you. Now I'll hand over to my friend and colleague, and those are my disclosures, Børge Nordestgaard. Through the chair, of course. Thank you so much, Gerald, and thanks for the invitation to be here. As was already said, I was also invited to give the editorial comment yesterday at the Congress here in Munich, European Society of Cardiology. That's what I showed yesterday. I started with this slide to try to show where is the problem. The graph is really showing the distribution of triglycerides, shown on the X-axis, in a typical general population study. 64% has what has been referred to here as normal levels, less than 150 milligram per deciliter, 1.7 millimoles per liter. Then there's 34% that has mild to moderate hypertriglyceridemia, up to 500 milligram per deciliter. Here, after that level, that's what is referred to as severe hypertriglyceridemia, found in typically one in 100 in world populations. What you also can see on this slide is that with the red arrow, way out to the right, there is this genetic condition, familial chylomicronemia syndrome. We often refer to it, roughly one in 1,000,000 has this. Perhaps a little bit more common. They can have various very high triglyceride levels. We now have five different drugs that has tried to reduce triglycerides in these situations. At first, we had three different types of drugs. volanesorsen that had a problem with lowering of platelets, and it was approved in Europe only, but never in the U.S. And then olezarsen from the same company, and now plozasiran. All these three have been shown. What we are moving to now is this much more common condition, namely severe hypertriglyceridemia, one in 100. We already heard from Jennifer Hellawell some numbers for United States and the world also, how common it is. Olezarsen has already showed results for that roughly about a year ago. Now we have this very important study with plozasiran in this quite common condition. What I show here is now that all these five drugs have now shown to reduce acute pancreatitis, and the rough number for all five studies is 80% reduction. It is extremely consistent. Either you have the very severe genetic condition, familial syndrome, or you have the broader condition, severe hypertriglyceridemia, roughly an 80% reduction by using these type of drugs that are all APOC3 inhibitors. We already heard about how the mechanism is. Side effects, from what Gerald Watts showed us, the only thing that really was something in there was worsening of glycemic control, 14% in the active drug versus 9% in the placebo. This is a class effect. This is also seen for the other drugs. There is no mystery about plozasiran in general. Personally, compared to how a bad situation these patients are in, this is really nothing, and many of them already have diabetes, so they would be looked after for the glycemic control anyway. What I really tried to highlight in green, there was very low drug discontinuation. For me, when I see a study like that tells me there is very few side effects that the patient notices. Of course, when you have new drugs like that, we need a lot more follow-up. We need to do that long-term. I am sure both FDA in the U.S.A. and EMA in Europe, they will ask for more security. For now, it looks really promising. On top, the SHASTA-3 and SHASTA-4 baseline, the 757 with severe hypertriglyceridemia, meaning levels above 5.7 millimoles or 500 milligram per deciliter. In these studies, there were 32% that had ASCVD at baseline, 59% diabetes, and 21% acute pancreatitis. Here is one point that I would like to mention for you. Even at the baseline with these here, there actually was more atherosclerotic cardiovascular disease, meaning heart attack or strokes, than acute pancreatitis. Down below, I put some of my own personal data. I have access to all data that lived in Denmark for the last many years. Here I showed the ones from 2008 to 2021, 3.4 million people with triglyceride measurements. All these we looked at here, they had no ASCVD, myocardial infarction, stroke, or acute pancreatitis at baseline. There was 29,000 with severe hypertriglyceridemia at the same level as before. The point I would like to show to you here is that when we look in this group in Denmark, I am sure it will be the same in any other country in the world, then the incidence of acute pancreatitis was 2, and there was 400 cases in total we could find in all of Denmark. Denmark is a special country. We have 100% follow-up. Everybody is captured in the registries. For atherosclerotic cardiovascular disease, heart attack, or stroke, there was 2,000 cases, and the incidence was 18. It is actually, in this group of patients in complete primary prevention, there was five times as much atherosclerotic cardiovascular disease as acute pancreatitis, and on an incidence basis, nine times more. Why do I say that? I think because of the way the patients were recruited, it was acute pancreatitis that we could see an effect on. But long-term for this patient group, there is a big need for further investment, trying to actually go for both diseases, both reduce acute pancreatitis and long-term also atherosclerotic cardiovascular disease. Here is my clinical implication. In blue, I show this is a huge unmet medical need, and I actually worked together with Gerald Watts, he knows very well. Severe hypertriglyceridemia causing acute pancreatitis and also ASCVD. These patients in the past really never had much we could offer them, and particularly ones with the very high levels were very difficult. In green, I show fantastic news now. We now have efficient therapies. These APOC3 inhibitors, where plozasiran is one of the two that is relevant right now to lower triglycerides and acute pancreatitis. For me, I think I would love to see more studies that actually focus on not only preventing acute pancreatitis, but also long-term atherosclerotic cardiovascular disease. With that, I would like to hand over to Andy from Arrowhead. Thank you, Andy. Thank you, Dr. Nordestgaard, and good afternoon, everyone. I would like to walk through what the SHASTA-3 and SHASTA-4 data mean for our commercial opportunity in severe hypertriglyceridemia, building on the clinical results just reviewed. Let us start by level setting on the potential market opportunity for plozasiran. As Jennifer and Dr. Nordestgaard previously set up, severe hypertriglyceridemia is not a single population. It is really a spectrum. At the broadest level, SHTG is defined as triglycerides at or above 500 milligrams per deciliter and affects more than 3 million people in the U.S. Within that, we define a high-risk SHTG segment, triglycerides at or above 880 milligrams per deciliter or above 500 milligrams per deciliter with a prior history of acute pancreatitis affecting approximately 1 million people who carry meaningfully higher AP risk. At the far end of that spectrum, of course, sits clinical and genetic FCS, where triglycerides are persistently elevated above 880 milligrams per deciliter and prior AP history is prevalent. A population of more than 6,500 people, in our estimation, at extremely high AP risk. The SHASTA-3 and SHASTA-4 data we reviewed today, together with the FCS data from PALISADE behind REDEMPLO's FCS approval, now give us clinical evidence across the entire spectrum. What's notable is that plozasiran's value proposition doesn't change as you move across that spectrum. It holds. Across these patient groups, we see deep and sustained TG reduction on the order of approximately 80% from baseline, maintained throughout the treatment period. Over 90% of plozasiran-treated patients in the SHASTA program reached triglyceride levels below 500 milligrams per deciliter, an important risk threshold, at month 12. Importantly, we saw a statistically significant reduction in AP risk. That is, plozasiran reduced cumulative AP events by nearly 80% versus placebo. The safety profile also remains favorable. Notably, we saw no hypersensitivity, no meaningful change in platelets, no clinically meaningful change in liver enzymes, and importantly, no liver fat elevation relative to placebo. Also, the expected physiological change in HbA1c is consistent with the APOC3 inhibitor class. Lastly, dosing remains simple. A convenient 25-milligram dose every three months, just four injections per year, and with no titration required. This consistency across the SHTG spectrum matters commercially. Physicians treating the broader SHTG population won't need to relearn this medicine. The profile they already trust in FCS carries forward. Given that consistency, our initial commercial focus for the SHTG opportunity will be deliberate and focused. We're prioritizing the high-risk SHTG segment. Shaded here, patients with triglycerides at or above 880 milligrams per deciliter and those with triglycerides between 500 and 880 milligrams per deciliter who also carry a prior history of acute pancreatitis. These are the patients with the greatest clinical urgency. Importantly, we're not starting from zero here. A subset of this high-risk segment, as shown here in the small blue boxes, already meets the clinical criteria for FCS, and REDEMPLO is reaching these patients today. Recurrent hospitalization for unexplained abdominal pain, a family history of HTG-induced pancreatitis, or a history of pancreatitis are all criteria that support a clinical FCS diagnosis, and patients presenting this way are being identified and treated under our current label. To summarize, this is not a strategy of chasing the full addressable SHTG population on day one. It's a strategy of going first where clinical need, payer willingness to pay, and the evidence supporting REDEMPLO are greatest. To put a number on that clinical urgency, in the high-risk segment defined as TGs at or above 880 or above 500 milligrams per deciliter with a prior history of acute pancreatitis, seen here in the green outline, the number needed to treat with plozasiran to prevent one acute pancreatitis event is nine patients over one year. For those patients with a prior history of AP, irrespective of TG cut point, shown here in the blue rectangle, the number needed to treat is a remarkable three over one year. NNT reflects how many patients need to be treated to prevent one event. The lower the number, the greater the impact per patient treated. An NNT in the single digits, like we see here, represents a landmark result and demonstrates compelling value to payers when assessing cost benefit. Also, it's a number we believe will strongly resonate with physicians who treat this population. Turning now to our go-to-market approach. We've identified over 20,000 healthcare professionals across largely four specialties, lipidologists, endocrinologists, preventive cardiologists, and internal medicine and primary care, who treat the roughly 1 million high-risk SHTG patients in the U.S. today. This is a targeted call plan. These four specialties concentrate the patients we're prioritizing, and it allows us to direct our commercial resources efficiently as we prepare for a potential SHTG launch. Finally, our commercialization efforts are already well advanced. Our medical education and communication strategy is developed, and our medical science liaisons are in the field conducting scientific exchange. Our marketing and market access strategy is developed, and we're executing compliantly against key go-to-market activities. The expansion and optimization of distribution channels and patient services are well underway. Regulatory interactions are planned in the near term, and we're building toward day one readiness across patients, providers, and payers. In short, much of the planning and infrastructure required to support a potential SHTG launch is already in motion, well ahead of any regulatory decision. With that, I'll turn the call back to Vince. Thanks, Andy, and thanks to all the speakers today. This was a really great set of presentations. I appreciate it. Takeaways. What's important? I think it goes without saying that Arrowhead Pharmaceuticals is thrilled with these data. This is going to sound like hyperbole, but this is really the slam dunk or the home run or the grand slam or whatever sports analogy you want to use, for what we had hoped for with these data. It's really phenomenal. Plozasiran continues to demonstrate an attractive profile and importantly, a consistent and favorable safety and tolerability profile. Second, as Andy just mentioned, it's an extraordinarily compelling value proposition across the board for physicians, for patients, and for payers. Andy highlighted this, but I want to highlight it again. An NNT of 24 over a year for the overall study population in SHTG is already impressive and potentially paradigm-shifting for the treatment. When you go to the high-risk patients, the one who've had a prior history of AP, an NNT of three. Just to put some perspective on that, this is oversimplified, but essentially it means all you have to do in that population is treat three patients to prevent one event of acute pancreatitis. As a review, acute pancreatitis is a very severe and chronic and recurrent and frankly, very costly thing for the healthcare systems to treat. Again, this is a really compelling value proposition across the board. Next, we are still on schedule to file our SNDA to request approval for the SHTG population before the end of this year. Just a reminder that we did recently purchase the priority review voucher, which potentially accelerates our path to launching in this large population in the U.S. Then again, as Andy Davis just mentioned, our launch readiness efforts are well underway. Over the long term, we see this opportunity in SHTG just in the U.S. potentially being a $3 billion-$4 billion a year opportunity. We are really just getting started with lipid disorders. There is a lot of information in this slide. I am not going to cover all of it, but just to orient yourself, on the left side is elevated LDL and the diseases that that leads to. On the far end of the spectrum, the most severely elevated LDL is HoFH or homozygous familial hypercholesterolemia. For that part of the population, we have an investigational product called zodasiran which we also presented some data from a small substudy in China today at the Congress. Those data look really promising, and we hope that zodasiran becomes an important medicine for that part of the population. As you go to the far right, these are diseases characterized by elevated TGs. Again, the most severe is FCS, both clinically and genetically diagnosed. Then the SHTG population, which we talked about today. Then in the middle of this, in the intersection of elevated TGs and elevated LDL is a population called mixed hyperlipidemia. That is a patient population with persistently elevated LDL, persistently elevated TGs, and a high risk of ASCVD. We have a new dual functional siRNA product called ARO-DIMER-PA that is investigational. It is in a phase I-II study right now directly in mixed hyperlipidemia patients. It is a drug that targets both the PCSK9 gene and the APOC3 gene simultaneously in one drug. It is a really phenomenal technology that we are extraordinarily excited about that we will have our first readout for the first-in-man study next month in September. Again, more to come on that shortly. But the takeaway here is that Arrowhead Pharmaceuticals is already active across the spectrum of lipid disorders. That is only growing. We foresee in the future additional products in the cardiometabolic space, and we are building our commercial infrastructure to support potentially multiple products. So what does that look like in the short term? Over the coming years, even with just the programs that we have disclosed, that we have talked about, we do see the possibility for multiple independent launches. As I mentioned, we launched REDEMPLO and FCS in 2025. We hope to file our SNDA for plozasiran for SHTG before the end of this year. Provided we receive a positive review and approval, our hope is that we launch that in 2027. Following that, the HoFH study of zodasiran should read out around the middle of next year, which would set us up nicely for the next commercial launch for Arrowhead Pharmaceuticals in 2028. Then beyond that, we have the ARO-DIMER-PA program I mentioned for ASCVD, and then additional programs for obesity and MASH, and then others that are undisclosed at this point. So this is just the start for our commercial franchise. Thank you, everybody. We appreciate the time today, and we have about 10 minutes to open up the call to questions. So Tara, do you want to compile the question list, please? Yes. Thanks, Vince. Just as a reminder to our analysts, we are going to kindly ask that you limit your questions to one. Please hold for a brief moment. Our first question comes from Brian Cheng at JPMorgan. Please go ahead, Brian. Hey, guys. Congrats on the data presentation yesterday, and thanks for taking our questions this morning. We have a question for the physicians on the panel here. Curious, doctors, can you walk us through how you think about the acute pancreatitis effects that we are seeing here in the SHASTA-3 and -4, and how that fares against olezarsen? How will that ultimately impact your decision-making if both options become available today? Thank you. I would be happy to start, Børge Nordestgaard. For me right now, this is such a huge unmet medical need. There is such a huge market out there for patients that need this treatment. I am actually not thinking of competitors between the two companies. I am thinking of the two companies together could work together with the same strategy toward all the clinicians to find as many as possible of these patients. There are so many of them out there. I actually see it as a big advantage that there are two different companies that will try to make clinicians find the right patients and refer them to the doctors that see these types of patients. Gerald, what is your point? Yeah, I totally agree. I think when there are two really good products, there is a feed-forward mechanism, and everyone can be a winner. There are advantages in the direction of plozasiran in terms of we have not seen a deterioration in liver fat. The liver enzyme changes are very good. The HbA1c is not statistically significant. At the end of the day, it is the clinical consultation and the patient choice. I would rather have an injection for every three months, really, rather than every month for a start, and you want to inject themselves every month. There will be people who would like a short-term injection in terms of they got fear of side effects and reversibility. One can think of clinical situations where that would be indicated, but I would have thought the less frequent injection site reactions, and the fact that these injections are not there are no injection site reactions of note, which is extraordinary, actually, would put plozasiran in an advantage point, really. But there are sort of subtle differences, and that ultimately depends on how the doctor mounts it and what the patient's perspective is on this. The price of the two products. That's always such an important factor. That's a difficult one. Let's have another question. Thanks, Brian. Tara, do we have another question on, ready? Yes. Our next question comes from Mike Ulz at Morgan Stanley. Please go ahead, Mike. Morning. Thanks for taking the question, and congrats on the data as well. Maybe another question for the two physicians. Just when plozasiran potentially comes available next year, are you going to be targeting your high-risk patients initially, primarily? Or would you might go more broad into the mild and moderate patients as well? Thanks. I can start. Børge Nordestgaard. What should I say? It's again, depends on the price. If it was very inexpensive, many more patients would have it. What I do see historically is that when some new drug come into the market, then many physicians tend to be somewhat conservative. They will always start with the highest-risk patient. The ones with the highest triglyceride would be one thing, but certainly also the one for acute pancreatitis. But as experience grow and the price is right, a lot of patients will be offered this type because there's really nothing we can do for them today. Yeah, I would agree with that. Coming back to the price per clinical practice, we like to risk stratify. Everywhere you go, coronary heart disease, pneumonias, you risk stratify. So people are going to be risk stratified, and it would be significantly easier. Again, I don't want to talk too much about the cost-effectiveness, really, to actually fund something where the risk is high. They'll try to contain that. But clinical practice is stepped, so the first thing patients will enter and they're on the ACC/AHA guideline-recommended dietary care fibrates, and their triglycerides will drop. They will have to go through that. It's the residue that has persistent elevation in triglyceride to which you would have to follow that line. The study's excellent in showing what the effectiveness of very good background care is. So that will have to be part of the formula. Thank you. Great. Thanks for the questions, Mike. Our next question comes from Maury Raycroft at Jefferies. Please go ahead, Maury. Hi. Thanks. I'll add my congrats on the great data. Wondering if you're providing more details on the breakdown of AP events. We're probably splitting hairs a bit, but in our back calculation, we see an imbalance of events in patients without prior history of AP, where there were three to four events in the plozasiran arm versus none in placebo. Is there anything unique about those patients, and is there any risk that doctors could reserve plozasiran for patients with prior AP? I'll turn that to James to cover. Before James goes into it, we do have a publication pending. There'll be more detail there. There's not a ton we can talk about, but James can talk more. Sure. Well, the answer to the question for me is that those data, including the de tails around event rates in subpopulations, are currently embargoed. As we mentioned, we've been accepted as a manuscript at one of the major medical journals, so stay tuned and we'll be able to talk about that once the manuscript is out there. I guess I would add one other thing. Keep in mind that this study, these secondary endpoints were pre-specified and pooled across the study population. We hit statistical significance across the study population. That's a critical thing to keep in mind. That's really what we're excited about, that we hit stats on that. Got it. Thank you. Congrats again. Thanks, Maury. Our next question comes from Prakhar Agrawal at Cantor Fitzgerald. Please go ahead, Prakhar. Yeah. Thank you for taking my questions and congrats on the data as well. Maybe a question for the KOLs here. What in your view are the key safety events where plozasiran differentiates versus Ionis' olezarsen or lower injection reactions and lower hypersensitivity rate enough of a differentiation for you to prefer plozasiran as the APOC3 drug of choice, and your view on the liver fat and the glycemic worsening data for plozasiran compared to olezarsen. Thank you. Well, that's an important question. The rates of glycemic effect or pro-glycemic effects are the lowest recorded so far in the trials. Their assessment is based on a number of diffuse endpoints, including impaired glucose tolerance, just the need to increase anti-diabetic medication. So it's difficult to make much out of that 5% ab solute difference between placebo and active intervention. The HbA1c increase is very minor and not clinically significant. It seems to peter out and come back to baseline with improved therapy. So there are no concerns there, and I can say that as someone who was actively involved. Your HbA1c goes up a little, you intensify treatment, and you end up with an HbA1c at the end of the study better than when you came in. I don't have any specific concerns about that. We happen to be part of the education and upskilling. I understand that it was highly statistically significant in the other study, as was the increase in liver fat. I don't have any specific concerns about that. As Børge said, really, it's a very high-risk group, metabolic syndrome with diabetes and HbA1c, and these things are going to happen, really. There was no adverse current events. The injection site reactions were very favorable. No concerns from my point of view anyway. Just a small comment from mine. The safety profile of plozasiran in this study was excellent. Compared to how high-risk patients we talk about treating, it's no worries. Clinicians, patients should not be worried at all. In addition to that, the advice, the open label of the various trials that you've done informs you that it's not a continuing exponential effect. It seems to adjust itself back to business as usual. It's a temporary event. The open label extension of this particular trial will also inform, as Børge correctly said, the more data that we've got in the long term, the better. Thank you. Tara, unfortunately, we are already one minute over, but we have time for one last question. Great. Yeah. Our last question comes from Jason Gerberry at Bank of America. P lease go ahead, Jason. Hey, guys. Thanks for squeezing me in. Just a quick one for the doctors. Do you guys see any clinical hurdles to switching a patient from olezarsen to REDEMPLO? Do you want to see any switch studies done, or do you think that the decision to switch comes down to how onerous the prior authorization hurdle is to making that switch? Thanks. You want to start, Gerald? Well, switching injections from one to the other does happen in clinical practice, from monoclonal antibodies to siRNAs. In clinical practice, if you are not tolerating a drug, I think with olezarsen, you may actually increase the dose if you have not got sufficient efficacy. But again, at the 80 milligram dose, there are lots of problems with this agent, as we have shown, as they have shown. I think there would be not so much switch from or an increased escalation of dose, but whether you should switch over from olezarsen to plozasiran. Again, it is a patient preference issue. Who wants to inject themselves every month, really, when you can inject yourself every three months? That may come up. But there will be people, argument's sake, I think of clinical situations, ladies planning pregnancies that do not want a prolonged plozasiran effect may decide to go for short-term injections. It is more in the fa vor of plozasiran than olezarsen, to be quite frank. But I would like to say, I said it before, I really hope for now these patients can get some new drugs. For me, being interested in preventing of different diseases, atherosclerotic cardiovascular disease, acute pancreatitis, I would much rather see that the companies try to find new patients because there is so many out there that are trying to switch from one drug to another one. We know many patients, when they get used to one drug and they do not have any major problems, they actually prefer just to stay on the same drug. So that is what we also see in clinical practice. Unless there is a really compelling evidence, like clearly more side effects or completely different change in price or something like that. Yeah, we would tend to agree with that, and I would make this point, too, from an investment perspective. We, as investors, you have seen over the last few decades a good amount of innovation and a lot of progress on the LDL space and the LDL side of this equation. On the TG side, you really have not. Now to have two options, one that is approved in SHTG and hopefully pending a successful review and approval for plozasiran, two new options and really dramatic treatment effect that just did not exist with current standard of care. We view this as a growth opportunity for both companies, frankly, and a really untapped commercial market. As Andy mentioned, we think there is 3.5 million patients alone in the U.S., not to mention all of the rest of world patients that just do not have access to effective therapy. Now we think that changes over the coming years. We think there is room for pharmaceutical innovation in this space. To the good of the greater good. That's right. Patients are the beneficiaries, and the physicians like Dr. Watts and Dr. Nordestgaard that treat them. Again, thank you, everybody. We are, again, thrilled with these data, and we appreciate your interest, and stay tuned for publication. Again, as I mentioned earlier, stay tuned for initial first-in-man data for the ARO-DIMER-PA program next month. Thank you.