Good afternoon and welcome to Esperion's virtual KOL event. A question-and-answer session will follow the formal presentation. As a reminder, this call is being recorded, and a replay will be made available on Esperion's website following the conclusion of the event, and now I'd like to turn the call over to Sheldon Koenig, Chief Executive Officer of Esperion. Thank you very much, and good morning, everyone. Welcome to Esperion's Key Opinion Leader Day today with both LeAnne Bloedon, our Head of Clinical Development, and also Dr. Patrick Moriarty. I'm ready to have the first slide, please. If there is no slide, which I do not see, I will go through them by memory. So first of all, I just want to remind everyone that there is a forward-looking statement, so anything said today falls under our normal forward-looking statement and disclosure agreement. You can find it on our website. Just for some background, Dr. Moriarty is a professor of medicine at the University of Kansas Medical Center in Kansas City, Kansas. Go Chiefs. He is the Director of Clinical Pharmacology and the Atherosclerosis and Lipid Apheresis Center. Dr. Moriarty is a Fellow of the American College of Physicians, the American College of Cardiology, the European Society of Cardiology, National Lipid Association, and he was the 2014-2015 President of the International Society for Apheresis. Dr. Moriarty has published well over 100 peer-reviewed articles and chapters ranging anywhere from atherosclerosis to lipoprotein apheresis and vascular inflammation. So at this point, I will turn the call over again to LeAnne Bloedon, our Head of Clinical Development here at Esperion. LeAnne. Great. Thank you, Sheldon, and thank you all for attending today. A special welcome and thank you to Dr. Patrick Moriarty, who is taking time out of his busy day to speak with us, so I'm going to spend about 10 to 15 minutes talking about some of the unique aspects of our clinical development program with bempedoic acid, and I think this will be really nice to serve as the framework when we then get to the open dialogue with Dr. Moriarty. We're going to hear about his clinical experience with bempedoic acid and how he views our products in regards to place in therapy. Okay, so Tiffany, if we can go to the next slide. You know, when we were developing the clinical development program about 10 years ago, we had some of the same issues and challenges with unmet need that we have today. Atherosclerotic cardiovascular disease remains the number one cause of death in the United States and globally. Recent metrics show that 44% of U.S. adults have cardiovascular disease or they're at risk of having a first event. What's disappointing is that over half of these patients are not at the recommended LDL-C goal, which of course is a main risk factor for cardiovascular disease. When you think about adults who need treatment, up to 30% may be unable or unwilling to take recommended statin therapy. Next slide. When we developed the clinical development program for bempedoic acid, we wanted to not only conduct trials that were needed from a registration or regulatory purpose, but we also wanted to make sure that we were evaluating patients with all unmet needs and really looking at populations that would take our products when our products got to the market. So you can see here, not only did we evaluate statins at moderate or high intensity, which is required by the FDA and EMA, but we also evaluated bempedoic acid in combination with low-dose statin therapy and doses below that, and even in patients where their maximally tolerated statin was no statin at all. We were also committed to developing a fixed combination product with ezetimibe so that we could approach both causes of high cholesterol, that is, from the diet as well as the liver. And then finally, in terms of populations with high unmet need, we were committed to not only studying those that were required by regulatory bodies, that is, patients with cardiovascular disease and/or heterozygous FH, but also patients who were primary prevention patients, those that had not experienced a first event, as well as patients who have partial or complete statin intolerance. Next slide, please. This slide shows you the phase III placebo-controlled studies. There were five of them that we conducted to support our primary hyperlipidemia patients. If you look at the far left column in blue, these are the two registration trials. This is your typical studies that our predecessors, as well as those in current development, are performing, which is evaluating the product in patients with cardiovascular disease and/or heterozygous FH. We studied that on top of a maximally tolerated statin where 90% of patients in these two trials were receiving a moderate or high intensity statins on top of other stable lipid-lowering therapies. If you look in the middle column, these two trials are where we are unique. We wanted to have committed trials that were evaluating our products in patients with partial or complete statin intolerance. Now, what's also unique is the population. We studied patients with cardiovascular disease and/or heterozygous FH, but also primary prevention patients. And then finally, if you look at the far right column, you can see the trial that supported the approval of NEXLIZET, which is looking at the combination of bempedoic acid with ezetimibe. And in this trial, we also had patients with cardiovascular disease and/or heterozygous FH, but also high-risk primary prevention patients. These patients were also on maximally tolerated statin therapy on the background of other stable therapies as well. Now, if you look at the bottom two rows, you can see that across all of these studies, we saw statistically and clinically significant reduction in LDL cholesterol as well as high-sensitivity C-reactive protein. Next slide. Okay. Now, this slide gets to our cardiovascular outcomes trial, the CLEAR Outcomes study. This trial is unique in several ways. First of all, it is the trial that validated that reducing LDL cholesterol with bempedoic acid through inhibiting ATP citrate lyase does, in fact, lead to CV risk reduction. It's also unique because we included primary prevention patients as well as secondary prevention patients. And then finally, it's unique because it is the only trial where there is outcomes data in patients with statin intolerance, both complete and partial, which is really a group of patients who have a high unmet need. Now, the primary endpoint was a four-component MACE, which consisted of cardiovascular death, non-fatal MI, non-fatal stroke, or coronary revascularization. So in this study, which consisted of nearly 14,000 patients, which were followed for over 3.4 years, we see a statistically significant reduction with bempedoic acid compared to placebo in our primary endpoint. It was a hazard ratio of 0.87, which is a relative risk reduction of 13%. If you look at the figure, you can see that the Kaplan-Meier curves start to separate as early as six months, showing the benefit of bempedoic acid. If you look to the right, you can see our MACE-3, which was our key secondary endpoint, resulted in a hazard ratio of 0.85 or a 15% relative risk reduction. Looking at non-fatal myocardial infarction, there was a 27% risk reduction, and coronary revascularization resulted in a 19% risk reduction. Next slide, please. Now, as I mentioned before, CLEAR Outcomes is the only non-statin FDA-approved drug with data in patients with primary prevention. This data shows here what we saw in that group of nearly 4,200 patients. Looking at the same MACE-4 endpoint, you can see with bempedoic acid, there was a 32% relative risk reduction in MACE-4. This had a number needed to treat of 43. When you look at the harder endpoint of MACE-3, you then see a 39% relative risk reduction. And impressively, looking at cardiovascular death as a component, we saw a hazard ratio of 0.57, which is equivalent to a 43% relative risk reduction. You can see here from the Kaplan-Meier curves, as we saw in the overall population, also in primary prevention patients, you start to see that visual separation of the Kaplan-Meier curves as early as six months, showing the early benefit of bempedoic acid. Next slide, please. Now, this slide looks at the risk reduction of major vascular events based on the LDL lowering of different populations in CLEAR Outcomes. And this is based on using methodology from the Cholesterol Treatment Trialists' Collaboration, which has looked at patients who received statins in nearly 30 trials in over 175,000 patients who have received statin therapy. That group has concluded that for every reduction in LDL cholesterol of one millimole per liter, you get a 22% major vascular event risk reduction. And that is what's shown here in the dotted line. So when we look at data from CLEAR Outcomes, we wanted to look at four different populations and see how our data compared to the statin data. So the blue box represents the overall intent to treat group, which consists of patients that were randomized to drug, irrespective if they stayed on drug or not during the trial. The green box represents the on-treatment group, which are those patients that did stay on treatment for the duration they participated. And we have the secondary prevention patients represented as a purple box, and then primary prevention patients represented as an orange box. You can see that in the intent to treat, the on-treatment, as well as secondary prevention patients, the level of CV risk reduction with bempedoic acid is similar to that achieved with statins. It's pretty much on the line for these three groups. Now, when you look at the primary prevention patients, it is well above the line, suggesting that you get a greater CV risk reduction based on the LDL-C lowering in this group. And you know, this is actually not that surprising based on additional data from the CTT group with statins. So let's go to the next slide. Now, this is also data from the same Cholesterol Treatment Trialists' Collaboration. And what they did is they, again, looked at all of their statin data, but this time they looked at patients without vascular disease, which is at the top. They also looked separately at patients with cardiovascular disease. So I want you to look at the top portion, which is primary prevention patients. The two rows I have highlighted in pink are showing you that in patients that are at lower risk, even within the primary prevention group, you get a greater CV risk reduction per one millimole per liter. What this suggests is that you get a bigger bang for your buck, if you will, in terms of reducing LDL-C cholesterol. It shows the importance of treating as early as we can in the atherosclerotic process, and that will give us a larger CV risk reduction based on the LDL-C lowering. Again, this supports what we've seen in CLEAR Outcomes in patients with primary prevention, where we saw that larger CV risk reduction based on the LDL-C lowering in that group. Okay. If we go to the next slide. In terms of safety, we now have safety demonstrated in almost 10,000 bempedoic acid treated patients across the phase III trials I just reviewed. The data here is from CLEAR Outcomes because it's our largest and longest trial, so with exposure up to six years, bempedoic acid was generally well tolerated with the similar safety profile to placebo. You can see the first three rows here. When we look at any adverse event, serious adverse events, or adverse events leading to discontinuation, we see that the data is well balanced with placebo. You see myalgia here because this is a population of statin intolerance, and we looked at muscle side effects, and myalgia was the most common side effect reported in both treatment groups. However, when you look at bempedoic acid versus placebo, you can see it's about 1% less in bempedoic acid, so there's no increased risk. When you look at discontinuation due to myalgia, it's also balanced with placebo. Now, bempedoic acid is associated with small increases in uric acid based on a known mechanism that occur early. They're stable over time, and it's reversible upon discontinuation. Because of that small increase, we look at risk of gout. Gout reported in CLEAR Outcomes was low across both treatments. There was about a 1% higher incidence of gout in bempedoic acid compared to placebo. When you look at the discontinuation rates due to gout, it was very low in both treatment groups, 0.1% and balanced. And then finally, in CLEAR Outcomes, we had about 42% of patients who at baseline had prediabetes. And so when you look at the risk of getting diabetes in the trial, there was no increased risk with bempedoic acid compared to placebo. Next slide. And this is my last slide. So now we have data from CLEAR Outcomes that is in our label, which we achieved in 2024. And the label has been updated to expand the indication. And this is in both of our products. So you know, we see that NEXLETOL and NEXLIZET are the obvious next step when you think about reducing CV risk. So you think about when I first started this presentation and I talked about the unmet need. We have this available non-statin therapy that can address that need. Again, they're the only products that are indicated with CV risk reduction in primary prevention and secondary prevention. And we get significant LDL lowering using an oral agent that can be used with or without a statin. If we go to the next slide, basically, I now want to open up the call to speaking with Dr. Patrick Moriarty on his real-world experience with bempedoic acid. So again, thank you, Dr. Moriarty, for joining us. Hi, LeAnne. Thank you for inviting me. Yeah. Good. So why don't we start out maybe with you just giving a brief introduction of your background as well as where you practice clinically? Well, Sheldon gave a little bit of background from my work, but I am, as you mentioned, the director of clinical pharmacology, which this division here at KU started at the Lipid Clinic in 1960. So they've been at the Lipid Clinic here for 65 years now. And we were involved with clinical trials dealing with dyslipidemia and so forth. But when I became director about 25 years ago, I initiated a lipid apheresis program too, which is a device, kind of like dialysis, that filters your blood and lowers your bad LDL and Lp(a) cholesterol by 80% in two or three hours. And we are now the largest center in North America. We treat more patients with this device at the University of Kansas than all of Boston, New York, Chicago, LA combined even. It's an amazing therapy that works, lowering LDL and inflammatory markers and so forth. And we did, like I mentioned, clinical trials with bempedoic acid and a lot of other lipid-lowering medications. And we're quite active in this activity. And I'm glad to see your drug has come out, particularly for primary prevention, which I think is not being addressed more aggressively for atherosclerosis than it should be. Like hypertension, it's not waited until someone develops secondary events from hypertension. It's treated right away, and I think when we look at atherosclerosis and risk factors like LDL and other ApoB proteins, it should be addressed right away. The earlier, the better to prevent the disease from developing. Okay. Great. Yeah, so maybe tell us a little bit about the types of patients that you see clinically, and are they often referred to you? We have a diverse group of patients. Classically, we see a lot of patients with familial hypercholesterolemia of age, which are genetically predisposed, patients with high Lp(a), which is now being tested quite extensively. Also, we see diabetic patients with dyslipidemia, triglycerides, low HDL. So we see a potpourri of all types of patients, and our referral base is primary care, cardiologists, endocrinologists, and so forth. So we get quite a diverse group of referrals and patients. Okay. Good. So when you think about your primary prevention patients and your secondary prevention patients, are there certain factors that come into play when you think about how you want to manage these patients? Well, when secondary prevention patients are presented, we are more aggressive, obviously, because they've already had the event that we're trying to prevent, another event. So we get very aggressive with them after that. And in primary prevention, we usually go low and slow to develop, depending on their age and their so-called risk, and their need of lowering their risk factors as best we can. We have dieticians that look at their diet. I recommend exercise as a part of my regimen. I like to recommend a device called a WaterRower, which is a device that uses 85% of your muscle groups that helps burn up 1,000 calories in one hour. So it's a good device. So it's a combination of pharmacotherapy and lifestyle that we aggressively add to our regimen of treatment for these patients. Okay. Okay. Great to know. So maybe before we start talking about bempedoic acid, your experience there, let's talk a little bit about statin intolerance. So in 2022, the National Lipid Association released a position paper, as you know, that defined partial and complete intolerance with an incidence rate perhaps up to 30%. So just curious how often you come into contact with these patients and then also how that impacts how you manage them. Well, we see quite a few statin-intolerant patients that are referred to us, close to 50%, actually. I coin these patients in my clinic delicate flowers because, like delicate flowers, they need to be nurtured and delicately treated in order to grow. There is a genetic predisposition to having statin intolerance, but that's a minority compared to patients we really see. I think most of it's somewhat supratentorial where they've heard someone had a problem with a statin or their relative did, or they have a high anxiety, and any aches and pains, they assume to be related to a statin. We go very slow with these patients in the sense of therapy. We'll put them on once-a-week statin to start them off, some of them, particularly with rosuvastatin since it has a very long half-life, with very good success. We published that 10, 15 years ago. But the consistency of statin intolerance related to that, as you showed in your trials, the placebo had a higher risk of myalgias than your product did. And I was the first author of the ODYSSEY ALTERNATIVE Trial using a PCSK9 inhibitor. And we showed in that study, compared to placebo, that placebo was causing more adverse events than the drug itself. So statin intolerance is a very complex situation for patient populations. And And your product has been shown to be quite effective in our patients who have this history. And we tell them the mechanism of action being it's isolated to the liver, and it's a pro-drug until it gets in the liver to be activated by the enzyme. Explain the pathophysiology and the pharmacokinetics of a drug really helps the patient compliance in certain ways. Okay. Good. Good. So yeah. So then now maybe we kind of switch gears a little bit to talking more about your experience with bempedoic acid, either as NEXLETOL or NEXLIZET. So tell us a little bit how you utilize the products, and does it differ in the populations that you treat, meaning primary prevention, secondary prevention, or those with statin intolerance? Well, we still follow the standard pathway of a statin first in patients if they haven't been on the statin. And then we try if they've been on a statin with intolerance, then we'll do the low-dose dosing of maybe once a week or something of that nature. And if they have this intolerance that after one day of dosing of a statin, they have problems, we then move on to other classes like ezetimibe and then bempedoic acid. And then finally, we might, if LDL is what we're needing to lower, we might add on a PCSK9 inhibitor as our fourth regimen. So we stick kind of that standard protocol of oral medications with diet and exercise. And then eventually, if the oral medications don't work, move on to a higher, more potent and hence more invasive therapy with the PCSK9 inhibitors. Okay. Okay. Good. So tell us, are there any differentiating factors with bempedoic acid that helps you decide in what populations or how to use the product when you're thinking about what non-statin therapies you want to utilize? Well, safety, as you brought up in your trials, is one. Effectiveness in the sense of what it does in the sense of lowering LDL. And third, its mechanism of action, not only lowering LDL, but you showed the lowering of CRP, which was quite dramatic. The CRP is a measuring of vascular inflammation. And when you look at vascular inflammation to atherosclerosis, it's like looking at a fire, and inflammation is kerosene to that fire. So if you have inflammation in your vascular system with an atherosclerotic plaque, that further destabilizes the plaque's susceptibility to rupture by the inflammatory products that are in the vascular system. And your drug, as you showed, lowered the CRP quite dramatically, almost equal when it was in combination with ezetimibe. It was almost one-to-one LDL and CRP reduction. And statins can lower HSCRP. Unfortunately, PCSK9 inhibitors don't. And additionally, as you know, I suggested on the CLEAR trial, the CLEAR Outcomes trial, to look at other markers, particularly something called RDW, Red blood cell distribution width, which is part of the indices in the CBC, it's a Complete Blood Count. It's also a marker of inflammation, but chronic inflammation. And additionally, it's a marker of increased blood viscosity, meaning your blood becomes more viscous when you have this high RDW in your system, which could be detrimental to microvascular diseases. And RDW has been shown to be an independent risk factor for cardiovascular disease. In fact, in the ODYSSEY OUTCOMES trial using PRALUENT or alirocumab, I was the first author of a paper looking at RDW in the ODYSSEY OUTCOMES trial. And we found that the RDW level predicted cardiovascular mortality irrespective of age, gender, LDL, or hsCRP. Unfortunately, like CRP, PCSK9 inhibitors do not have an effect on RDW levels. And we found in the CLEAR Outcomes trial that your product actually lowers RDW. And the lowering of the RDW showed a significant correlation to the event reduction. We haven't published the paper. It was presented at the ESC in London this past September, but the publications underway. We're working on it now to get it out in the near future. Okay. Great. Yeah. Well, thank you for going through some of those differentiating factors that kind of play a role into what products you choose to manage your patients. So can you talk a little bit about how well your patients on bempedoic acid have done from an LDL-C lowering perspective as well as safety and tolerability? How have they been doing? Well, in the combination with ezetimibe and NEXLIZET, we see about up to a 40% reduction of LDL and another reduction of this hsCRP. And also, like I showed you, we talked about the RDW. In the beginning, when your product first came out, there was always a pushback by providers and so forth for cost. And now, though, it's really changed and more patients are being approved by their providers without a high copay or refusal. So it's become a more commonly prescribed medication now since it was about just six months ago. It's really developed into more of an extensive use by our patients. Oh, good. Oh, that's really good to hear. We've been working hard to work with managed care groups and make sure their user criteria is aligned with our labels. So it's good to hear that you're having very positive experience and that's improved. That's wonderful. So I would love to get your thoughts. I mean, you were obviously involved in CLEAR Outcomes, and you mentioned some of the data you presented. What's your overall impression of the data from CLEAR Outcomes? And has this impacted how you use the products clinically? It has, for sure. Putting both primary and secondary together in a trial like this is really not commonly done in the past. It was quite intuitive of the company to bring in both primary and secondary risk patients together in this trial to see how well this product does on patients with dyslipidemia and risk. And as you presented in your slide presentation earlier, the primary prevention patients actually did better in the sense of% reduction, validating, which I mentioned earlier, that initiating therapy for atherosclerosis should start as early as it can. And I think the data and the guidelines are going to be pushing that down the road that you don't wait until you have the secondary event because this is a lifelong disease. It takes decades to develop significant plaque for susceptibility of the vascular disease development. So the earlier you start treating the risk factor, I believe, and data is showing this now, the longer you extend the prevention of developing another or first cardiovascular event. So primary prevention is something that we talk about, but we don't actually always practice enough in clinical practice. And I think you're going to be seeing more of that. Okay. Great. Yeah, we agree. And I'm glad you commented that you've seen patient access, and so we continue to get the product to your patients who are in need. Can you comment, again, when we think about non-statin options, from your perspective in working with your patients, is there a real desire to try oral therapies before injectables? For sure. For sure. For a majority of patients, it's a priority because, as you know, injecting into your skin is more aggressive and more invasive than just a pill in your mouth, and people are used to taking pills regularly since childhood, so these are very complex consequences they have to hurdle to do the shots. Even though the shots that we use, be it PCSK9 inhibitors and so forth, they're very safe in their method of administration, but it's still a complex process, and it raises the price of the therapy no matter what. An injectable therapy is going to be costly for a patient, and some patients cannot really comply with that need to have that done once a week or once every two weeks, depending on what kind of dosing is being requested for this, so I think the pills definitely, oral medications definitely outweigh the injections. Okay. Okay. Thank you. So one last question, I think then we'll open it up to the audience to see what questions. But Dr. Moriarty, I'm interested in hearing your perspective on some novel mechanisms or routes of administration that are currently in development to lower LDL cholesterol, namely CETP inhibition as well as oral PCSK9. So as someone who's been involved in many, many years in working with companies, testing these products in your patients, I'd love to hear your perspective. Well, starting off, let's say, with the PCSK9 inhibitors, I was involved in many of the ODYSSEY Outcomes Trials. I was first author of two of the ODYSSEY studies, the ODYSSEY ALTERNATIVE, as I mentioned earlier, ODYSSEY ESCAPE, which was using alirocumab in patients on apheresis. I also did a similar trial with Amgen with their REPATHA, and other trials with Amgen. I'm still doing some more now. They're a great drug for lowering LDL by 60%-70%. But unfortunately, the outcome data, be it the ODYSSEY OUTCOMES or the Amgen FOURIER trial, which were the two major phase III trials, if you looked at the data, the patients who had the significant clinical cardiovascular event, which there was a percentage, which was similar, by the way, to the CLEAR trial, even though your LDL reduction was almost a third of what was shown in the PCSK9 trials, the event rate was about the same. And the absolute risk reduction was about the same. But they found in the ODYSSEY OUTCOMES in the 48 trial, if you had a normal Lp(a), your event reduction was not significant. If your Lp(a) was very high and the PCSK9s have a modest effect on Lp(a), that showed a significant benefit of cardiovascular event reduction if the Lp(a) was high. As I mentioned earlier, the hsCRP and RDW levels are not changed like they are with your drug, with PCSK9 inhibitors. For some reason, which is very interesting, and we don't know why, if you're lowering LDL by 60% and you can't lower inflammatory markers on top of that, it's very strange. And we don't understand that lack of mechanism. So I've kind of readdressed my usage of the PCSK9 inhibitors in the recent year or so based on this knowledge that if their Lp(a) is not elevated, then even lowering an LDL by 60% might not have as much bang for the buck as you expect. Now, that needs all still to be worked out, but the data is there to show you. Now, with the CETP inhibitors, I've been associated with them over the years, and they're an incredible class of drug effects in the sense of lipids raising HDL to 100%. Now with these newer versions, they can lower LDL and Lp(a) quite dramatically. I'm still, and there's outcome studies going on now, as you know, but I'm still kind of worried about the effect on the HDL. It might raise the HDL, but it looks like the HDL raises a kind of a dysfunctional HDL because it lacks increased particle number, which has been shown to be quite much associated with HDL functionality. So the jury's still out from CETP inhibitors. Hopefully, the newer versions that are under investigation that lower LDL and Lp(a) more aggressively than the other ones might counteract the negative effect it has on HDL and result in outcome data that's positive in the sense of reducing cardiovascular events. So hopefully, these studies will be coming out with positive results in the near future. Okay. Well, thank you. Sheldon, operator, I think we're good to change it over to the open portion. Thank you. At this time, we'll conduct a question-and-answer session. As a reminder to ask a question, you'll need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Now, first question comes from the line of Dennis Ding of Jefferies. Your line is now open. Hi. It's Georgia on for Dennis. Thank you for taking our questions. We wanted to understand in more detail about what proportion of your patients are you prescribing BEM currently, and where does that ultimately go with preventing you from using BEM more frequently? Thank you. That's for you, Dr. Moriarty. That's directed to me. Well, again, we used to think we needed LDL cholesterol and we need other types of cholesterol. But Goldstein and Brown who discovered the LDL receptor and won the Nobel Prize for that will tell you publicly and privately that LDL is a toxin, has no physiological need for our activity as immune systems. Like tonsils and appendix, we've grown out of that need. And when you're born, most patients' LDL is in the 30s. And if you think you needed LDL at that moment where you're replicating cells and the cell membrane has a ratio of cholesterol to phospholipids, that would be it. But you don't. And there's no LDL in the brain. In fact, there's no ApoB lipoproteins within the brain. The only cholesterol that's in the brain is HDL. The blood-brain barrier blocks all ApoB-containing lipoproteins like LDL, Lp(a), chylomicrons, triglycerides, and so forth. They can't get in a normal brain. So the goal is to get an LDL down as low as you can. When I first started practicing in this field of dyslipidemia, I remember the goals was an LDL less than 200. Then it went down to 160, and it went to 130, and it went to 100, and it went to 75. Now we're down to 55, and it's still going in the direction that we know. Because the data keeps on showing the lower you go, the better off you are in the sense of atherosclerosis and cardiovascular risk down the road through pharmacotherapy. There's been some data showing where LDLs that are low due to lifestyle, being starvation or cancer, is not associated with cardiovascular risk reduction. That's true because it's not related to pharmacotherapy. It's related to other disease processes, be it starvation or in cases of cancer, so the lower you can get it, the better off you are, and genetics plays a role too, obviously. Patients with FH and so forth, other kinds of genetic dyslipidemias, have a higher propensity of developing disease early. Because if you have a genetic disease, it starts when you're born, not later on in your life when you're developing poor life habits. This is something that's genetic, and it starts right off the bat. Your early development of disease, which I find in my FH patient population, can occur quite rapidly. You need to address that because this LDL can start causing its nasty results of atherosclerosis at a very early age if you have it genetically. Aggressive management is important. If a statin cannot be successful in getting that patient to goal based on intolerance or based on lack of goal, then adding on another regimen such as ezetimibe or, in this case, bempedoic acid is a safe and effective way in treating these patients. I hope that answered your question. Thank you. One moment for our next question. Our next question comes from the line of Joe Pantginis of H.C. Wainwright. Your line is now open. Hi, everybody. Thanks for hosting today's call and the details provided. So Dr. Moriarty, sort of looking towards the future, when you talked about, obviously, the hierarchy that you use with regard to drugs, I'm curious first if you're seeing the potential for switching to bempedoic acid proactively versus seeing statin intolerance. That's a good question. I think based on previous data, I was involved in a lot of the statin trials, so I go that far back, and the effectiveness of them when they're tolerated and the price of them compared to bempedoic acid. Now they're pennies a pill based on their lack of patent and now they're all generic. I think only one's still non-generic, but they're all generic now, so they're pennies a pill. So for cost saving and so forth, and based on previous data, I use a statin as a first line to see what the outcome is. With that being said, I think what bempedoic acid, what they did in combination with ezetimibe was quite dramatic in the sense of the LDL reduction going up to close to 40% or more, and the hsCRP reduction kind of max equal amount. So you're looking at not just a reduction of the ApoB-like proteins, you're looking at a reduction of the inflammatory milieu that's associated with it equally. It would be wonderful to maybe add another drug to that combination of maybe a statin and do a triple dosing of this, so a triple combination of the three. But until this develops, I think a statin is going to be out there for a long time, being that the price of it and the baseline data that we have associated with it. Because statin is also lowering inflammation on top of lowering LDL. So I think you're going to see statins front and center for a long time until things change. No, that's very helpful. And I guess you actually hit a great segue to my second question where you talked about the potential for triple combination and potentially having the statin as well. Do you have any other mechanisms that you think would be potentially promising to combine with NEXLETOL and NEXLIZET? Yeah. I would say a statin would be perfect. I brought up that story of RDW. I don't know if I confused you with that. And it's a marker that's been known for 20 years to be a risk factor because of its chronic inflammatory process. And because the half-life of a red blood cell is 30 days, it would take you three or four months to get the change of the inflammation because it lowers the RDW. It's a chronic marker of inflammation. Like hsCRP can change over a day. It can change in 24 hours because it's an acute phase reactant. Additionally, RDW measures something that hsCRP doesn't. It measures something called RBC deformability, meaning a red blood cell change in shape. If you have a young red blood cell, it's like a half-filled water balloon, which can perfuse capillaries quite effectively because it changes shape because the red blood cell is larger in size than the capillary. Whereas an old red blood cell is like a raisin, and it gets hard and stiff, and it can't perfuse, so it increases microvascular ischemia. A high RDW is associated not only to inflammation but to this rheology problem of microvascular perfusion. This drug, bempedoic acid, lowers it. Statins have shown a modest effect on lowering RDW also. So if you put these two together, you'll see the benefit. In fact, if you remember the trial, how familiar are you with clinical trials with these cholesterol medications? There's a study called JUPITER. Have you ever heard of that? Sure. Absolutely. Okay. Good. Well, they looked at HSCRP and JUPITER. And what did they find? They found that HSCRP reduction with the statin was a major driver for the cardiovascular event in that trial, along with the LDL. Did you know they did another study, post-hoc analysis of that same group of patients, and they looked at the baseline RDW in that study? And you know what they find? That the baseline RDW predicted cardiovascular mortality in that group irrespective of HSCRP. And the beauty of RDW, it's a free product. It's an industry in the CBC. You don't have to pay for it like an HSCRP. You're looking at two modalities of cardiovascular risk: inflammation and rheology, which is not really looked upon, as you know, in cardiology because blood, unlike water and plasma, is a non-Newtonian fluid, meaning its viscosity changes depending on stresses put upon it, which can affect microvascular disease, which is also why they get atherosclerosis in only certain arteries and no veins because of flow dyna mics. Did that answer your question? Thank you very much for all the details. Yeah. You're welcome. I just wanted to interject, Joe, thank you. Just as a reminder to everyone, Daiichi Sankyo Europe is currently developing a triple combination therapy with NEXLIZET and a statin. They're actually looking at potentially doing it with two statins: atorvastatin and also rosuvastatin. The good news for Esperion, this is not a financial conference, of course, is that though we will also have royalties between 15%-25% when that comes to market, probably the end of December or the end of December, the end of 2027. We can go to the next analyst question, please. Thank you. One moment for our next question. Our next question comes from the line of Tom Shrader of BTIG. Your line is now open. BTIG. Thank you. A couple for Dr. Moriarty, and then if I could follow up with the company, I'd love to. Thank you for holding the nice event. Dr. Moriarty, what details of the CVOT matter most for you? And in sort of details, when you're considering a patient for bempedoic acid, are they usually already on Zetia, or are you generally offering them the combination pill? In my practice, because I deal with a lot of statin-intolerant patients, and I learned from years ago, you always go with one drug first before you add another one on. If someone hasn't been on Zetia, I'm not going to put them on NEXLIZET right off the bat because if they do complain of whatever they might complain of relating to the drug, I won't know which one it is. Therefore, I'll have to restart one at a time. I usually go with the Zetia first. Cost is important. If it's a primary prevention patient, I have time to work my way up. I know with ezetimibe, you're getting a 20% reduction of LDL. So I know this patient, which is probably going to need a 40%, will eventually be needing to add the NEXLETOL or bempedoic acid to make the NEXLIZET with the patient. So I go a little bit at a time, depending, again, on the situation of the patient and what history they have and what status of the disease they have. Rarely, I might just go right to a NEXLIZET depending on their high risk and medical. Thank you. One moment for our next question, and our next question comes from the line of Paul Choi of Goldman Sachs. Your line is now open. Hi. Thank you. Good afternoon, and thank you for taking our questions. I have two for Dr. Moriarty. My first is, since the label changed to include primary prevention in the label, can you maybe comment on what mix of your primary preventions patients have gone on to NEXLETOL or NEXLIZET therapy? And my second question, Doctor, is as you think about the various conversations you have at your institution, if there are any, can you maybe share what the one or two reasons are among your fellow practitioners that there may be any reluctance to or reticence to prescribe NEXLETOL or NEXLIZET at this point, given the label change and the public availability of the outcomes data? Thank you very much. Well, on my primary prevention patients, how many are on NEXLETOL is the question. In the past year, I would say a good percentage are now based on their need of LDL goal. They'll probably already been on a statin or ezetimibe, and then if they're not still at goal, I'm very aggressive on treating my patients in the sense of getting them to goal above and beyond what usually is recommended for efficacy and for safety. So I would say a good percentage of my primary prevention patients who are referred to me, obviously, from cardiologists and endocrinologists based on either resistance to therapy or non-compliance, so forth. And your second question was? The second question was, what, if anything, would prevent you from writing bempedoic acid? Paul, I believe I phrased that correctly. No. No. No. Yeah. Yeah. I was just curious what reticence. Yeah. Yeah. What reasons have your colleagues expressed in terms of reticence for prescribing? Lack of knowledge. I just got to—if I need to mention this, I got an email from my cardiologist here at KU, along with the primary care physician that's taking care of a doctor here at KU, as a patient. And the cardiologist had the patient on NEXLETOL and also on a statin and asking me what else and a PCSK9 inhibitor and asking what else they could do. And I told them, "Well, you could change the NEXLETOL to NEXLIZET." And I told them it was a combination of bempedoic acid and ezetimibe. And they didn't even know that. They didn't even know it existed. So the market is still naive and young in the understanding of the value of bempedoic acid. And from my experience of other subclasses of lipid-lowering therapies, it takes a while to educate the medical society of the value of a new product. I still see cardiologists who won't measure Lp(a). They're still resistant to doing that. And even though lipid apheresis is approved for treating Lp(a), and 60 of my patients, I'm treating for Lp(a) and cardiovascular disease with lipid apheresis. But some cardiologists and some clinicians, particularly family practitioners, will stay away from it. Ignorance is bliss. They feel, "Why should I measure something I can't do anything about?" And that's all changing. The European and Canadian guidelines recommend universal testing for everyone. When these new drugs are coming down the pike, the antisense, the RNA interferences that we're involved with next year coming out, you'll be hearing about Lp(a) on the 29th, everybody. And you'll be hearing more about bempedoic acid. I think when we get this RDW paper, I hope out soon. I have plans of submitting it to the European Heart Journal. I think we'll have success in doing that. We'll educate clinicians about the value of looking at this drug class and how well it works, and not just lowering LDL, but lowering inflammation, in this case, rheology, which I think is a valuable benefit. So right now, it's not used aggressively enough by clinicians, I feel, by the lack of knowledge of its benefit at this point. But I think it's going to change. Great. Okay. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Kristen Kluska of Cantor Fitzgerald. Your line is now open. Hi. Thank you for hosting this event for us today. Dr. Moriarty, can you talk about the steps that you're taking to work with patients to treat them earlier in their pre or current vascular disease journey, considering the data show this could correspond to the greatest response now that there is a safe oral drug on the market? Well, patients refer to me. I spend time sitting down with them and going through what atherosclerosis is, describing its mechanism of action and emphasizing the risk factors associated with it, and also the consequences, be it cardiac, cerebrovascular, PAD, and so forth, and also diseases associated with it, be it hypertension, diabetes, and so forth, and showing outcome data. I actually give them published trials. And some people think that's too over the top, but some patients love to get educated. And I find the more compliant patient is a more educated patient. The more they understand the pathophysiology and mechanism of action of therapy, the more compliant they are taking their medications. And that's, I think, why we get referrals from a lot of clinicians in the area because of our ability of getting patients on board, understanding why something is being used for them to treat and prevent future events related to it. Thank you. One moment for our next question. And our next question comes from the line of Serge Belanger of Needham. Your line is now open. Good morning. Thanks for hosting the event. A couple of questions for Dr. Moriarty. First, on NEXLETOL and NEXLIZET, can you describe the level of access for the products since the label update and how it now compares to the other brand non-stats in terms of prior authorizations and any remaining restrictions for prescribing? And then my second question regarding obicetrapib. We got phase III data last month, and the company reported a one-year MACE endpoint in the 20% range. I believe it was an exploratory endpoint. Just curious about your perspective about that and how you think it could progress over time in the longer outcomes trial. Thank you. Well, as I mentioned earlier, the approval by providers for bempedoic acid has dramatically changed in the last six months where my nurse is not getting as many denials from the providers for the patients. So it's really improved quite dramatically. And it's not at the level of statins, but you have to show that they tried statins. In some cases, they tried ezetimibe, and they're still not at goal or they couldn't tolerate it. And the resistance by providers of not approving bempedoic acid to that next level has gone way down for us. Regarding your talking about the CETP inhibitor trial, again, I hope that the trials show success compared to the first generation of the CETP inhibitors, being complete failures to a certain degree. I hope the more aggressive a benefit it has on ApoB lipoprotein, the LDL or the Lp(a), counteracts the so-called negative effect on HDL functionality. HDL is a very complex lipoprotein, unlike LDL, which only has ApoB bound to it. HDL has all these other proteins: A1, A2, C2, C3, E2, 3, 4, M, F, D, serum amyloid A, ApoC-III. All these proteins bind and unbind the HDL, which changed their functionality, which has been shown to be, in certain situations, a priority. The question is, is the lowering of the other ApoB-like proteins with this new class more aggressively going to counteract the harm it does to HDL? Like I said earlier, time will tell. Hopefully, the preliminary data that you mentioned will come out to be successful in reducing events. I'll tell you one thing. I just presented at the AHA our lipid apheresis data, and we showed over five years on patients with cardiovascular disease, high Lp(a), a 90% reduction in cardiovascular events. 90. We reduced LDL and Lp(a) by 70%-80% acutely, chronically by 40%-50%. We reduced all these inflammatory markers: CRP, fibrinogen, ICAM, VCAM, tissue factor, Galectin-3, and reduced blood viscosity, as I mentioned earlier, by 20%-30%. I tell my patients I'm changing their blood from ketchup to tomato juice. The microvascular perfusion is greatly enhanced. It works. It's a multifactorial therapy that reduces all these things besides just ApoB lipoprotein. And that's why I love the beauty about bempedoic acid because it then moves into that field of inflammation, the CRP and the RDW, but also the rheology. So you're doing a very good mechanism of reduction of risk factors to improve vascular flow and reduce atherosclerosis. Thank you. This concludes the question-and-answer session. I'll now turn it back to Sheldon for closing remarks. Great. Thank you so much. First of all, again, I want to thank LeAnne. Did an excellent job. Thank you, LeAnne. And Dr. Patrick Moriarty, thank you so much for taking the time today. I was at ESC. I saw your presentation regarding RDW, and I think we're all really looking forward to that paper. There was one question that Tom Shrader had asked, and he sent me from BTIG. His second question was, "What were some of the things that stood out for the CLEAR Outcomes study?" We're out of time. But in the beginning, you mentioned the fact that the company studied both secondary and primary prevention and that those were the two attributes. So again, thank you so much for the time. I want to thank everybody that joined this call. And again, we have not really done a key opinion leader day in a very long time. I think the last one was right before the CLEAR Outcomes study. Stay tuned again. Quick commercial, April 24th. We'll have a Research and Development Day as well. And we look forward to speaking to everyone soon. So have a great rest of the week. Go, Chiefs. Go, Birds. Let's see what happens. Thank you for your participation in today's conference. This has concluded the program. We now disconnect.