Esperion Therapeutics, Inc. (ESPR) Earnings Call Transcript & Summary

Good morning, everyone, and welcome to -- welcome as we continue the 40th Annual JPMorgan Healthcare Conference. My name is Nick Lenard. I'm a biotech analyst here at JPMorgan. I'm joined here today by Esperion's President and CEO, Sheldon Koenig, and other members of management who will provide a presentation of the company, followed by a short Q&A session. [Operator Instructions] I'll receive your questions and be happy to ask management on your behalf. And now happy to turn it over to Sheldon for the presentation.

Great. Thank you, Nick. Really appreciate it. It's good to see you today and great to speak to everyone who's attending. On behalf of Esperion Therapeutics, it's our pleasure to have this opportunity to present at the JPMorgan conference. I think we're all ready to head to San Francisco. But hopefully, next year, we'll be doing this live from San Francisco. So thank you again for the opportunity for us to tell a very compelling story about Esperion, a company that's really transformed over the year, and I'm going to go through the details of that transformation and not only what it means for our organization now but even looking to the future. So some forward-looking disclosure statements and disclosures on Slide 2. And I will, for the audience's sake, call out the slide numbers. I know you're actually forwarding these slides yourself. So you'll have an idea of what slide I'm on. So starting with Slide 3. So as I mentioned, Esperion is really evolving into a unique global cardiometabolic biotech. And I think that's very important. I think when you think about Esperion, you may be thinking about the fact that, well, we commercialized 2 products, NEXLIZET and NEXLETOL, in the U.S. And we have partnerships that I'll talk about in the future. But we truly are a global organization, not only with our partnerships, but also with our products that we have in our pipeline. And that's a foreshadowing of something I'll discuss later in our presentation, not only as it relates to our commercialized products, but our pipeline assets, which I think you'll find very interesting. So where did it all start? In 2008, Esperion was established by the founder of Lipitor, Dr. Rodger Newton, who's developed many different cholesterol medicines and is still very active in research and development in cardiometabolic drugs. In 2020, the first products were approved and are already generating revenue. We've been demonstrating consistent growth quarter-over-quarter. And it's really fueled through strong execution and really to become a fully integrated company with both not only commercial capabilities, but I spoke about pipeline but also our research and development. And I think it's really far and few in between that you'll find a mid-small biotech organization that has invested in cardiovascular medicine that's not only commercializing products but also is conducting research and development. So where are we today? Today, again, we are evolving into this global cardiometabolic biotech. And you might be asking yourself, what does he mean by cardiometabolic? Well, obviously, that means LDL lowering, but I'm also going to talk later about other areas such as anti-inflammatory and also glucose lowering. We really want to advance our CLEAR Outcomes trial and our preclinical pipeline assets to reach broad opportunities worldwide. We sit here today essentially a year away from the top line report of the CLEAR Outcomes study, which we'll report out in the first quarter of 2023. It has a very different feel to it. Last year, we said we were 2 years away. But this year, we're only a year away. So Slide 4. We're entering 2022 in a very strong position. Again, we had 2 drugs approved, NEXLIZET and NEXLETOL, that we really think and believe fit a very much unmet need. We have strong intellectual property on these assets. The CLEAR cardiovascular outcomes trial, again, we're a year away from the top line report. We expect 100% mace accumulation in the second half of 2022. We have a very -- operating in a very large attractive cholesterol lowering market with high unmet need. We have a very experienced management team. And I've talked about these global partnerships, strong global partnerships through Daiichi Sankyo and Otsuka, who very much believe in the benefit of NEXLIZET and NEXLETOL and what it means to patient care. And we also conducted in October a recent company restructuring and financing. We reduced our cost burn, and we significantly strengthened our cash balance and really eliminating the cash overhang, which was really the #1 question that we received back in 2021. This is our management team. Many of them you've seen before. I do want to acknowledge Ben Looker. Ben just joined our team. He's our new General Counsel. The one takeaway from this slide I really would want you to have is the fact that many of the individuals here today, not only do they have 25- to 30-plus years in big pharma and biotech experience, but also almost that many years of experience in cardiovascular disease. So on Slide 6, besides the #1 takeaway I want you to have today as it relates to how is Esperion changing, how is Esperion transforming, why to believe in Esperion and what we're doing, the other takeaway is about all of you. We get all very caught up in the questions that we asked from an investment perspective, from a performance perspective. But another message I'd like to deliver is the fact that everyone really needs to think about their cardiovascular health. Cardiovascular disease is still the #1 cause of death worldwide. It's the #1 cause of death in the United States. Today, many of my team members know I was a bit distracted this morning. A very good friend of mine was just rushed to the hospital who had a heart attack, who has 3 blockages, is going through emergency surgery right now, very active individual, et cetera. Please make sure you're addressing your cardiovascular health. I think in light of what we've seen in the past 2 years with COVID, I think we're all worried about getting COVID, if we've already had COVID not getting COVID again. I think many of you have seen, if you're trying to get COVID tests, they're nowhere to be found. I was at Walgreens a few weeks ago, and I saw -- while I was waiting in line, 5 people were desperate to get COVID tests. And in my mind, I was thinking, how can I create the same behavior for them to get their lipids tested? And that's something that we really want to get across. And it's something that we're studying. If you -- if people are so interested in getting their test for COVID, how can we have them have that same behavior regarding getting their lipids tested because, again, heart disease accounts for 1 of 3 deaths in the U.S. and Europe. The CDC estimates heart disease deaths will increase by 25% by 2030. That could be more. Again, I think right now, folks are really focused on COVID and not really thinking about their cardiovascular health. And I think, again, as we see COVID become more of endemic, people are going to return back to their physicians even more and have their cardiovascular health addressed. If we go to Slide 7, there's currently over 18 million patients in need today. Current therapies are falling short for large patient population. So a question we get all the time is, well, people really believe in the LDL hypothesis, why do we need more drugs? Well, we need more drugs because patients are not achieving their goals. Almost 80% of high-risk patients do not meet guideline recommended LDL goals. And we know LDL is a biomarker as it relates to potentially preventing heart attack and stroke. Close to 9 million patients in the U.S. didn't reach their LDL goals despite taking a statin. So again, these are patients that haven't progressed beyond a statin. And raising the dose of a statin doesn't accomplish anything. It only increases your LDL lowering by maybe an additional 6%. And why is this? It's because patients still struggle with their medicines. Up to 20% of patients who could be treated with a statin experience statin intolerance, muscle aches, pain, et cetera. Almost 1/3 of these patients discontinue their statin treatment within a year. So again, just thinking back to the last slide that I showed you, it's the reason why cardiovascular disease is the #1 killer. And close to 10 million patients in the U.S. with high LDL, they aren't even on statins often due to tolerability concerns. So I'll discuss later how we're addressing populations of the 9 million and then the 18 million, and it's really a pre-CVOT and post-CVOT strategy. CVOT being our cardiovascular outcomes trial, the CLEAR Outcomes trial. On Slide 8, I've talked about how we introduced 2 oral therapies back in March of 2020. We're putting a lot of emphasis on NEXLIZET. And I think it's important to note that NEXLIZET is the first tablet in which 2 nonstatins are -- 2 nonstatin therapies to lower LDL are combined. And bempedoic acid is a product that is a very unique mechanism of action. It's unlike any other products that are out there to treat LDL cholesterol. And it's not often, and I say this to our sales force many times, that you have the opportunity to commercialize and get out there and sell a product that's highly differentiated, highly efficacious and safe. And so where do NEXLIZET and NEXLETOL fit? Well, we believe that we are addressing a key gap in existing therapy. We're providing patients with additional options that are adjunct to statin therapy. So if I address your attention to the left on Slide 9, we talk about statins, which are mostly generic. There's 18.3 million patients that could benefit from statins. Not all of them are on that. But in the middle, in the step therapy, as Dr. Steve Nissen likes to call it, there's an ability to continue to lower LDL cholesterol and achieve your goals, and that's with NEXLETOL and NEXLIZET. And we also think there's a nice fit with those patients, obviously who are on ezetimibe and a statin. They can easily transfer over to a NEXLIZET. Now the third option on the right is also available, which are PCSK9s. But keep in mind, I have had the opportunity to not only run the ezetimibe franchise at Merck, but also the Praluent franchise when I was at Sanofi. PCSK9s are injectable therapy. And we know that 4 out of 5 patients would prefer a pill versus an injectable therapy. So again, it really puts us, we feel, in the driver seat of this step therapy of treating cholesterol. And what I mean by that is, if you even go back to the early '90s in the treatment of HIV, it was called a more of a cocktail therapy. It was protease inhibitors added to other products. Today, when you think about oncology, it's several products that are put together. When you think now about cholesterol, a way to think about it is statins plus something else and maybe plus something else. But it's more of a step therapy cocktail approach. And if I address your attention to Slide #10, again, there's a high unmet need in a market that is very large. There's 10s of millions of prescriptions annually in the U.S. I mentioned earlier about how the CDC is thinking that cardiovascular disease is going to continue to increase through 2025, 2030 and beyond. There have been papers that have been written about this. And COVID is also something that's probably going to fuel this growth because patients are not getting out there as much as they could to really address their cardiovascular health. And so again, thinking about the fit of NEXLIZET and NEXLETOL, I want to show you the fit as it relates to more from a medical perspective. And so I'm looking at Slide 11, if I address your attention on the Y axis, if you will, there are certain attributes that we'll look at: dosing; LDL lowering; mechanism of action; hsCRP, which is a measurement of inflammation; and CV outcomes. I will address your attention to NEXLIZET, where LDL lowering in our Phase III clinical trials was approximately 38%. I spoke to our unique mechanism of action, our unique mechanism of action with NEXLIZET. It inhibits ACL and NPC1L1. Our hsCRP effect is close to 35%. This is very important because there's a lot of theories out there as it relates to what is the effect of inflammation in atherosclerotic disease. Just coming back to the LDL lowering. In clinical trials, we showed 38%. I can tell you, we get reports from the field on a weekly, monthly basis where physicians who have used NEXLIZET have seen, in some cases, 50% LDL lowering. And so as you go across the X axis, you can see the comparisons of the LDL lowering. We mentioned Leqvio earlier. Again, keep in mind, Leqvio is very different than Praluent and Repatha. Leqvio is an siRNA. Their outcomes are expected in the second half of 2026. And so therefore, very different than Praluent and Repatha that already have established safety. Our outcomes study, again, we believe our study will end the second half of 2022. And I can't say it enough because I like saying it, top line readout first quarter of 2023. And to dig a little bit deeper into the CLEAR Outcomes study, this is an unprecedented study that's assessing cardiovascular risk-reduction of bempedoic acid. This is the first-of-kind study in patients who have statin intolerance. It's in a new class of medicine. There's over 40,000 patients in 32 countries fully enrolled. And it's really also focused on significant underserved population, including almost 50% women being enrolled. I think it surprises many when we show that 50% of women in the study. Why is that important? It's because cardiovascular disease is also one of the #1 killers of women, with breast cancer following. So again, a very important population. There was actually a paper that was presented, I believe it was 2 AHAs ago that showed our effect on women. And I think one other unique attribute of the study is we have potentially a clinically relevant cardiometabolic effects. So the reasons to believe in the CLEAR Outcome study, it's the highest baseline LDL-C of any recent nonstatin study. The entry criteria is 139 milligrams per deciliter. The CV risk reduction is based on absolute LDL-C risk reduction. And there's a longer duration of study allows for fuller assessment of LDL-C lowering impact. Our median duration is close to 4 years. If you compare that to the PCSK9 outcome studies, of which were a bit disappointing, their median follow-up was approximately 2.4 years. And I talked about these clinically relevant cardiometabolic effects, well, that's the anti-inflammatory and glucose-lowering effects that could provide potentially greater risk reduction. And then the last key takeaway on Slide 12, and we recently just announced this in our early release 3 days ago, is that we have achieved 85% MACE accumulation in December of 2021. That puts us about 5 to 6 to 8 weeks ahead of schedule. We still anticipate 100% accumulation in the second half of 2022 and top line results in Q1 2023. And that means for us a very meaningful label expansion potential. It's a question we've been getting all conference. It's really going to help us drive future commercial growth opportunity. And if you remember the patient populations that I talked about earlier in the presentation, the 8 million and the 19 million, it's fully illustrated here on Slide 13. Before CVOT, we have a patient population of close to 8 million patients that we can address with our current label. Post-CVOT, with inclusion of the CLEAR Outcomes study in our label, we can address a patient population size of 19 million. And this is why we repeatedly have stated since October that the CLEAR Outcomes study will be an inflection point for the ramp of NEXLIZET and NEXLETOL. And why is that? Because the potential label implications are a few. Post our CVOT label modifications, we will hopefully remove maximally tolerated dose of statin therapy in our label, and also, which I think is very important, expand to primary and secondary prevention in patients. So again, this will really open the door as it relates to opportunity for us. And if you think about cardiovascular disease, and I've been in the cardiovascular world for a long time, it's a market that is underserved. It is very large. And the fact that a ticket into the gate is to do an outcomes study, it's the reason why these outcomes studies are done to really prove the efficacy, really improve the safety and make the drug more available to a larger patient base. A few days ago, we announced our preliminary U.S. revenue between $12 million and $12.5 million. This actually represented growth of close to 9% to 10%. We also beat consensus. Consensus as it relates to fact sheet was $11.2 million. And that was in the face of massive disruption as we transform the company in October, and I'll go through that in a few other slides. We saw continued RPE growth throughout December. And we're not done yet. Again, we showed consistent quarter-over-quarter growth. And as we go into 2022, we're going to be focusing on our day-to-day business and continuing to show and demonstrate quarter-over-quarter growth in 2022, leading all the way to our CLEAR Outcomes study. If you go to Slide 15, the recent transformation for long-term growth, why did we do this? Because we're really taking a long-term view here at Esperion. We need to optimize our organizational structure. We need to do that to enable growth ahead of our inflection post the readout of the CLEAR Outcomes trial. We saw what was happening as it related to the environment now created by COVID. This environment is not going away. And we, at Esperion, we're ahead of the curve really thinking about what is it that we need to do to have the right organization, the right balance to go to market and market our product to health care professionals. What's that balance of personal and nonpersonal promotion? And so what we've done is we've taken more of a greater shift towards a digital and virtual outreach. You might have seen 2 days ago that Pfizer actually just announced that they'll be taking the same approach with a significant reduction in their sales force in the U.S. We significantly reduced our operational expense in the full year of 2021 and full year 2022 to generate an estimated annualized cash savings of at least $80 million. So we really were cognizant of our cash burn and we looked at how can we reduce our cash burn. If you think about Slide 14 that I showed to you, if I had to think about this presentation, again, if I could mold those 2 slides together, the fact that we had this magnitude of disruption and we just started to implement our strategy essentially in November, very late, we're still able to demonstrate this growth. So we're excited about approaching 2021 as we get into this first quarter. And so just to give you an example of how we're doing that, we're really optimizing our commercial engagement process through a triad approach of personal promotion, peer-to-peer exchange and digital promotion. From an in-person, educational, communication perspective, really targeting cardiologists, endocrinologists and PCPs, we have found through some significant analysis and doing return on investment work, utilizing digital assets to have peer-to-peer networks, we saw a great return on that. We're investing more there. And we're really focusing not only on our existing prescribers with our high potential specialists. We've also just recently partnered with a contract sales organization that will be hitting the field. They'll be taking more of a virtual approach. And they'll be hitting -- they're in training right now, but they'll be starting to become operational in approximately 1 week. If I address your attention to Slide 17, this really shows now our financial strength to deliver on growth. Recent financing and adjusted cost base extends our cash through CVOT readout. And I think that's very important. One of the questions that we were getting a lot last year as well, if you go and raise money, you're just going to get to your CVOT results, then what's going to happen? Well, here now, we not only have achieved money to get to our readout of our data but also to give us runway post that readout and to give us the opportunity to make choices of what we need to do to scale our business up. I've already spoken about our preliminary revenue. Again, we're very happy about that, but there's more work that needs to be done. Our cash on hand right now is $309 million. Again, this includes Q4 2021 cash, cash equivalents, restricted cash and investment securities. And I think something that's forgotten often is the fact that we have significant future ex-U.S. collaboration milestones from Daiichi Sankyo and Otsuka of close to $1.2 billion. Just focusing on Daiichi Sankyo, we have a $300 million milestone with them, which is based upon the completion of the CLEAR Outcomes study and the inclusion of that data in the label. On Slide 18, I spoke about this in the beginning of the presentation. Our medicines have been approved in 30-plus countries. This week alone, we just launched in Belgium. Germany and U.K. are the leading markets for Daiichi Sankyo. They have actually over 28,000 patients as of the fourth quarter on drug in Germany. This is more than the PCSK9s combined. In the U.K., they just recently launched the drugs, and they have about 900 patients on the drug in the UK. And they are, again, expanding into other markets. Our partners in Japan, with Otsuka, they've just commissioned their Phase II study in Japan. And we have $600 million in milestones and development costs here as well. I think it's important to know, though, that these working relationships with Daiichi Sankyo and Otsuka are highly collaborative. We work as one company. With Daiichi Sankyo, we meet on a weekly basis. We have a great partnership. And as I mentioned earlier, all fully invested in the success of bempedoic acid, specifically NEXLETOL and NEXLIZET. On Slide 19, we have a growing pipeline. It's beyond bempedoic acid. We have an oral PCSK9 inhibitor, which is going into the preclinical stage. And we also have a next-generation ACL inhibitor. Let me start with our oral PCSK9 inhibitor. We believe this is one of the best platforms as it relates to development of an oral PCSK9. I think the market is hot on this subject right now with Merck's presentation of their Phase II data at the last AHA. Our next-generation ACL inhibitor, we're excited about this because we're not only looking at LDL specifically but looking at, again, that cardiometabolic aspect. We also see activity in oncology, NASH, kidney disease and even potentially neurological disorders. And it really speaks to the differentiation of the mechanism of action of ACL inhibition. And so we're going to be speaking more about that this year. In the past, we've been really focusing on NEXLIZET and NEXLETOL, which is still our priority. But we, right now, in the first half of 2022 are really looking at pipeline asset lead identification. In the second half of 2022, we'll be holding a Research and Development Day to talk more about these pipelines and where we stand with them. What's also very exciting about that second half of 2022 is the fact that we will anticipate achieving 100% MACE in the CLEAR Outcomes study, and we have the potential of having an IND submission for our oral PCSK9. The first half of 2023, the CLEAR Outcomes top line results, the first quarter of 2023, I want to be clear is when we expect the top line results and then potentially filing our SD&A submission for NEXLETOL in the second half of 2023. So with that, I know I'm a bit over, but I want to say thank you to everyone here that is participating at the JPMorgan conference. Again, really appreciate your interest in Esperion and what we're doing at Esperion. Again, we are transforming this organization. And we are growing this organization as it relates to our 2 lead products that are currently commercialized with NEXLIZET and NEXLETOL. And before we go to Q&A, I'll remind you all again, please do whatever you can for yourselves and your family members, et cetera, to check your own cardiovascular health. Thank you.

Thanks for that, Sheldon. [Operator Instructions] First, let's start out with a question. You mentioned quarter-over-quarter growth of sales leading up to the CVOT readout. Can you talk about the dynamics of that and how you expect it to grow there and shortly after? And when can we potentially see an inflection pending positive results?

Sure. So I'll turn it over to Eric Warren, who's our Head of Sales and Marketing, to address that.

Yes, absolutely. Thanks for the question, Nick. It's great to be here. And the bottom line is you can expect consistent growth from us over the course of the next several quarters leading up to CLEAR Outcomes. Why will we be able to deliver that growth? Because of our balanced commercialization model that Sheldon shared with you, so the personal promotion, digital as well as peer-to-peer. We've rightsized our personal promotion to fit into the current environment. We've augmented this with the contract sales team that Sheldon alluded to that will start on territory virtually the second half of the year. We're tracking every one of the tactics in our 3-pronged approach. And obviously, we can scale those depending upon the return. Now CLEAR Outcomes, as Sheldon mentioned, Q1 2023 is the data readout. The team is actively preparing for those data. Now we can anticipate that starting with the readout some impact, obviously not related to personal promotion or any kind of promotion until the label change happens. But you can start to see the impact through scientific exchange, guidelines, et cetera. And then ultimately, when we unlock a promotion in the beginning of 2024, you can expect further trend breaks.

Great. And maybe just shifting back to the digital virtual outreach. Kind of can you talk us through the process of how you've settled on the 40% sales force reduction? Really, what gives you confidence in the remaining reps are able to kind of drive sufficient growth amongst the [indiscernible] and successful startups.

Eric will address that in a second. But first of all, we didn't settle on anything. Settling is a word where you just say, oh, this is what we'll do, right? As I mentioned in our presentation, we did some very significant analysis on return on investment to really think about what was needed. All of us on this call come from companies where work that needs to be done to make those types of decisions have to be very informed and very detailed. So our way of getting to the numbers that we've achieved to really rightsize this organization have been informed by data, and that's how we've gotten to the point that we are today. And we've shown that it's working. Eric?

Yes. Thanks, Sheldon, and thanks, Nick. Yes, so you're right, Nick, we did take out 140 individuals from our personal promotion system. Obviously, that's never an easy endeavor. These are real folks, real families, et cetera. But there was a fair amount of inefficiency and promotion. And that was really driven by the environment that we're in now and access to HCPs. The math showed us that we could take us, our organizational presence in the personal promotion, down to 80 individuals and still maintain coverage of more than 90% of the prescribers and prescriptions. So we were confident that we could create really concentrated, meaningful geographies for the territory managers and demonstrate growth. And as I've noted, for Q4, 9% growth from a script perspective validates our model. I'll remind you that these changes were put into effect the middle of October, so very early in the fourth quarter, yet we're still able to see that level of improvement from a script perspective. And then just a reminder that we've got that supplemental team, again, coming in from a contract sales organization in about a week's time that will further augment our personal promotion efforts.

Great. How are you kind of plan to get the larger Medicare providers to utilize your contracts or that you have in place in 2022, particularly around efforts to drive greater pull-through and awareness? And kind of at what point will kind of those efforts start to translate into greater contract utilization. I believe you mentioned commentary on that in the past.

Yes. I can take that one. I think it's first best to address this question by discussing the success that we've been having getting prescriptions through where there's no associated rebate liability now. Our reject rates are actually not higher where we don't have access compared to where we do have access. And we have had access working -- success working the required prior authorizations with the program that we put in place that are, for the most part, to label and not unreasonable. Most importantly, we've completed a segmentation analysis down to territory level in order to capitalize on a targeted pull-through campaign where we have preferred coverage. And via our prescription support program, we work with offices to address the required prior authorizations across payers with the appropriate documentation appeal, denials and to your exception requests. And we've had great success in this program. We've actually maintained and actually retained 20% of the patients. We already have 3,000 patients in the program, and we're really looking forward to continued growth in that regard.

Great. Maybe switching to CLEAR Outcomes. I know you talked about it a bit in the presentation, but could you please walk us through the key design elements of CLEAR Outcomes. Kind of if we go off the cholesterol clinical trials data, relationship between LDL-C and MACE, based on the baseline of the patients enrolled, what degree of LDL-C lowering would you get at 15% relative risk reduction? And what would you get at a 20% relative risk reduction?

Joanne?

Yes. So Nick, thank you for the question. As Sheldon outlined, we have important differentiators of our CLEAR Outcomes in the design that poise us for success. So one of them, as Sheldon mentioned, is the fact that for any recent nonstatin trial, we're starting at a very high LDL-cholesterol level of 139 milligrams per deciliter. What's important for the audience to remember is the fact that cardiovascular risk reduction is based on your absolute LDL cholesterol reduction. And as you mentioned in your question, that is informed by the cholesterol treatment trial as collaborative, and that relationship is very consistent. So for every [ 1 mil ] in the U.S., 39 milligrams per deciliter reduction in LDL, you see about a 22% reduction. So talking about our trial, we're currently powered, 90% power for a 15% reduction in cardiovascular events. We arrived at that because based on our label for NEXLETOL in our experience, we get an 18% reduction or about 25 milligrams per deciliter in patients with a 139 cholesterol, which arrives at the 15%. 20% would be more consistent with a 23% reduction in LDL cholesterol, giving you greater absolute LDL cholesterol. Now as much as we're really focused on that 15%, we do know that in our Phase III trials, our non-Outcome Phase III trials in patients not on statins, populations similar to our CLEAR Outcomes that they get about a 24% reduction in LDL. So again, we're confident that we can hit the mark of the primary at 15%. And there's data suggesting that in the unique population of CLEAR, we may have greater efficacy, greater LDL lowering. That's not all. As Sheldon also mentioned, bempedoic acid, NEXLETOL, has significant non-LDL lowering effects. There are modest weight reductions, modest blood pressure reductions, but more importantly, significant reductions in C-reactive protein inflammation as measured by CRP. And in counter distinction to statins, we lower glucose. So patients who have diabetes tend to have better glycemic control. And people who are prediabetic don't become diabetic. Now that's a long answer, but those positive cardiometabolic effects could also provide incremental cardiovascular risk reduction. And for anyone who hasn't listened in, please feel free to listen into our discussion with Dr. Steve Nissen, who is the PI of the CLEAR Outcomes study who has really provided his reasons to believe, many of which I've mentioned just now.

Great. We've got a question here from the portal. With around 85% of events accumulated as of December and kind of noting that you're 5 to 8 weeks ahead of time and tracking, kind of how -- are we thinking that potentially -- like when during second half '22 could you expect to hit the target number of events? And could that push any time lines forward?

Well, Nick, you know what, I believe that we have to maintain the integrity of the study. We are continuing to state that the study will be -- meet its accumulation second half of next year. Yes, I would love for this to continue to accrue ahead. And by all accounts, we are doing that consistently. And we are positive that we'll do that. I don't want to make any conjectures about particular timing coming in earlier than what we've already stated. But all very positive. And the good news is that this study remarkably has put in place COVID mitigation strategies. And if we compare where we are with the study, event accumulation, everything, we are running as we would have anticipated before COVID. And if anything, as you mentioned, almost up to 2 months ahead. So -- but stay tuned. And I'm fairly conservative. I don't know, Sheldon, if you want to say anything different. But I...

I agree with you 100%, Joanne. And just to clarify one point, Joanne mentioned second half of the year -- second half of this year, 2022, will be accumulation of events.

Yes, absolutely. We're coming up on time. Maybe one quick question we can squeeze in. Kind of how quickly after CLEAR Outcomes data, after that reads out in 1Q '23 can you file for the CV risk-reduction indication in the U.S.? And then what about Europe?

So Nick, great questions. Conservatively, we are looking at a 6-month time frame. I know from my experience with other companies, potentially, you can move into as early as 3 months, but we're sticking to 6, we would submit. If we had profound data, we could potentially get a priority review within the U.S., which could keep it within 2023. However, I think more conservatively, we're looking at then after submission an 8 to time -- 8- to 9-month review, which would be similar to the PCSK9 inhibitors which would put us into early 2024.

Okay. Great. Well, it looks like we're just running over time right now. I'm going to thank Sheldon and everyone else from the Esperion team for this great presentation answering our Q&A and everyone who joined us on this call. Have a great rest of the conference.

Great. Thanks, Nick. Thank you, everyone. Take care. Bye.