Okay, good afternoon, everyone. This is David Anselon from the Piper Biopharma team. Welcome to day two of the Piper Sandler Healthcare Conference. We're excited to have Esperion Therapeutics as our next company, Fireside. We have Sheldon Koenig, President and CEO. We have Ben Halladay, CFO. Thanks, gentlemen, for joining us. Exciting time for all things bempedoic acid. Let's dive right in. Just at a high level, it's been a long journey just to get to a place of strong access, strong volume growth, strong sales growth. With that in mind, just talk about the catalysts. I think this is a good sort of refresher, if you will. Talk about the catalysts that have gotten you to this place, and particularly the broad label expansion in 2024.
Yeah, great. Well, first of all, thanks, David. We really appreciate it. Thanks for being a second time, I think, at this conference. So on behalf of all of us at Esperion, it's always great to be here and represent the organization with both Ben and I and some other team members that we have here. We have John Harlow, our new Chief Commercial Officer, here, and Alina Venezia from Investor Relations. So yeah, it has been a long road. We were just saying with meetings that we had earlier today, we were talking to different investors and saying, you know, remember this time last year where we were? Every year it's gotten better. I'll even go a little bit before the CLEAR Outcomes study because I think it's a tale of two cities, in a sense, where we had a poor capital structure.
We didn't have our outcome study yet. That all changed in April of 2023 when we presented the study. April 2024, we had the label. And it increased our TAM from 10 million- 70 million, allowed us to essentially get out and promote our drug to be used either with a statin or without a statin. We really went after the statin intolerance strategy. And at the same time, we had Ben, who was working on fixing the capital structure. And I think to fast forward to where we are today, we've ended up in this world now where we can do what we're really good at, and that is execution and really to drive that double-digit growth. We fixed the capital structure. We have the label. We're off to the races. And it's early yet, fourth quarter.
It's a little bit later, but a lot of momentum in the third quarter, fourth quarter. We see a lot of momentum. We already see some of the things we've done in the third quarter paying off for the future.
Yep. Another milestone, and this is a more recent one, is the more recent inclusion of bempedoic acid in clinical practice guidelines over in Europe, the ESC guidelines. So can you provide specifics on how bempedoic acid is reflected in those updated guidelines and why that's important?
Yeah, absolutely. So one thing that's interesting. I was just in Munich, and the CEO of Daiichi Sankyo in Europe said to me that he was meeting with some key opinion leaders. And the key opinion leader said to him, "Congratulations." He said, "Congratulations for what?" And he said, "Well, for once, somebody else is talking about the benefits of bempedoic acid and not you. So it's great to hear it from somebody else." And I think that alone is a big deal that these guideline writers, and I was at the presentation, said, "We're making these changes to reflect bempedoic acid based on the fact that this is compelling, practice-changing data from the CLEAR Outcomes." So we had a Class I-A recommendation for the use of our drug in statin intolerant patients who cannot achieve LDL goal.
And there was actually a key figure that was shown in those guidelines that showed the use of bempedoic acid with every lipid-lowering agent. And essentially, that reflected that bempedoic acid should be used as a foundational therapy in lipid lowering. And you may recall, in some of those combinations, even with low-dose statin, we had LDL reduction in excess of 70%. So essentially, the most efficacious LDL-lowering combination that you can get today. So that helped us with the U.S. because we went out and educated the U.S. on the EU guidelines. And I can tell you that cardiologists, primary care physicians were very interested in the EU guidelines and are looking forward to the U.S. guidelines that are coming out shortly, sometime early next year. We think it's going to be just as promising.
Yeah, I guess, and you kind of answered my next question, which is how does this read through to the U.S. guidelines? And I mean, there is a read-through. Can we assume that the updated U.S. guidelines are going to look similar, identical? I mean, any context on how AHA, ACC behaves relative to what we see on the other side of the Atlantic?
Yeah. It's always hard to really predict, but we think that it's going to be similar, that they're going to follow the lead of what has been seen at ESC and with those guidelines, and whether you're from Europe, whether you're from the United States, these key opinion leaders, cardiologists, etc., they look at both sides, and I think you say it well, like almost a harmonization.
Yeah, I think the last time guidelines came out, which is a reminder, was 2019, right, before bempedoic acid was even on the market. There was a stark difference between U.S. guidelines and European guidelines. And I think there was a major criticism of the U.S. side is that they deviated from the European guidelines. And so I think there's a big push to make sure they're the same this time around. Maybe not identical, but I think, as Sheldon mentioned, our placement in the European guidelines, we couldn't have had a better outcome if we wrote them ourselves. So if we're even remotely as favorable as Europe, I think we'll be in a very good position for the United States perspective.
Just help contextualize for us how the rank-and-file cardiologists, even general practitioners who have large practices focused on cardiometabolic patients, I mean, how they behave based on these treatment guidelines. How influential are these guidelines?
Definitely with cardiologists, it's influential. And you think about cardiologists, this cascade of knowledge, if you will, even on a regional basis. It starts with the cardiologist. You have a lot of primary care physicians that look up to cardiologists to see what they're doing, how they're practicing. And when you can point to something on paper, and it doesn't take long to say, "Doctor, this is where this drug fits." Again, it's the credibility of someone else recommending it over and beyond the message that we're giving. I would just add, we think this is going to give us tremendous tailwinds as we go into 2026 when these guidelines come out. That's how important we think they are.
I mean, if you think about it, we understand the guidelines will come out at the end of January, early February, and then ACC is going to be used as a training ground. And so essentially, you'll have physicians being trained. Okay, after statin, who comes next, Nexletol, Nexlizet? I mean, that's a huge awareness opportunity for us.
Yeah, yeah. No, that makes a lot of sense. All right, so in terms of commercial positioning, and obviously, this is not really a guidelines question, but this is sort of more positioning based on your outcomes data, your label. Can you talk about how you're positioning bempedoic acid in a pretty varied treatment landscape? You've talked a lot about statin intolerance. You go on your website, you go on the Nexletol Nexlizet website, it's also there. But you do have a broad label.
It's not just about statin intolerance. Help us better understand the product's fit versus, say, ezetimibe and also the PCSK9 and the other non-statins?
Yeah. Just a couple of things in the definition of statin intolerance. I'll be quick. Statin intolerance is if you can't take a statin or you just refuse to take a statin, you don't want to, or you can take a low-dose statin. We're talking about upwards and over 20 million patients have fit in that category. So very broad. I think how we compare to other agents, and I'll just stick with Ezetimibe and injectable PCSK9s. If you take a look at the add-on market, in the past, we've been using adjunct. I like add-on because these are products you add on. It's easier to understand. Ezetimibe is almost 70% of the add-on market. The rest is PCSK9. The advantage we have over a drug like Ezetimibe is, one, our outcome study.
We have this effect of hs-CRP lowering, which, as you might have seen, the AHA just came out and said, "For patients, you should be doing blood work to detect what their hs-CRP is because atherosclerosis is an inflammatory disease." That's a big deal, and that's why we think we get some of the results that we get. For instance, another differentiation is we're the only non-statin oral that can claim primary prevention. We show that we have 39% reduction in primary prevention. That's not only because of our LDL reduction, but also, I think, because of our hs-CRP reduction. We think that's very important. So that's how we kind of position ourselves against ezetimibe, and you'll get more bang for your buck. Versus PCSK9, we're not out there saying, "Hey, use us instead of PCSK9." We think we're a natural fit.
There's just an article that was printed in circulation about two months ago. It surveyed patients, and it showed that most patients prefer an oral pill versus an injectable and are even willing to take less on efficacy just so they can have an oral pill versus injecting themselves, etc. I would say after the primary prevention data that was just reported by Amgen, they showed a 20% reduction. We show a 39% reduction. Not head-to-head, but again, you're seeing this better efficacy, better risk reduction with bempedoic acid. And so long story short, we're out there talking about statin intolerance. That's a beachhead that we start. We're really focusing on that primary prevention message, which really resonates with primary care physicians and cardiologists.
Yeah, and payers too.
And payers, yeah. Yeah.
Can you talk about your commercial infrastructure in the U.S.? I don't know if you can say how large the sales force is now in terms of headcount, but how many practitioners are you calling on? Just talk us through sales force expansion and even further headcount expansion down the road.
I'll start with the number of physicians we're calling on and what we're planning to do. And maybe I'll turn it over to you for a potential expansion. So currently, our representatives, personal promotion call on 20,000 physicians. So they're actually visiting these offices. 60,000 physicians we're calling on using our digital assets. And I've always said, and I know we have because we do the ROI on it, we found that right balance between personal promotion and digital. Currently, that's where we're at. 2026, we'll be calling on 80,000 physicians with our digital resources. And I don't want to be or forget about consumers because we do have a consumer arm. We do have our direct-to-consumer commercial that started. We are expecting 16 million impressions. We have over 8 million impressions so far. So don't have the ROI on that, but we do think it's going to be successful.
Maybe you can talk about how we're thinking about expansion of the sales.
Yeah. So I think the company is at a very unique position right now, right? We know that guidelines are coming. We know there's about to be this massive awareness event. And at the same time, you've seen we've settled a lot of the litigation. So we know that the lifetime of this drug is much further than we had originally anticipated. So you plan those two profiles kind of very differently. So internally, we've been recalibrating what we think of a total sales force number should be. We're looking to expand and kind of dive in on the heels of that awareness campaign with the guidelines and really drive that adoption. John's in the audience. I don't want to speak on his behalf, but we're viewing what that sales force footprint should look like.
But I mean, I think we can easily see adding somewhere 20- 30 additional reps in those key geographies. The key account manager programs have been very successful for us. But it's not just about sales rep, as Sheldon mentioned. We know a third of our prescriptions come from physicians who have never seen an in-person sales rep. That speaks to the success of that digital campaign. And expanding that is also a priority for us as well.
So what about a broadcast media campaign? Because I mean, I'm not to say that you're going to do what Amgen's doing with Repatha, but there are Repatha commercials. And there's promotion sensitivity, of course. So how do you think about broadcast components? Is that something that's an important part of patient activation?
They spent $50 million on their direct-to-consumer advertising that you see on TV. We don't have $50 million to spend, nor would I want to spend that much. I feel that with less than actually $2 million that we've spent on doing DTC on connected TV, we're getting far better return. Again, I think we partner with a very good group in how we target patients and how we target these media outlets, and so far, so good. It's paying off.
Okay. Let's talk about payer access. So I know it looks a lot better. But let's drill down a little bit and talk about access regarding both commercial and government lives and how we should think about net realized price/gross to net, all the fun stuff. Yeah.
I'll start with the coverage, and this guy will do the gross to net. But coverage, the word I use is pristine. We have 90% commercial coverage, all essentially in preferred position. In Medicare, we have 85% commercial coverage, recently boosted by the acquisition or the ability of Kaiser to put our drugs on formulary. And that's important because Kaiser typically doesn't put branded products on their Medicare formulary. So we feel really good about that. Pull-through, that's what we need to do. This is the first time in my career where we don't hear as an issue that we don't have the coverage. And that coverage is solely based upon the clinical data that we saw from the CLEAR Outcomes data. So I feel really good about it, and we can talk about it.
Yeah. I mean, gross to net, I think we're in a great place. We're in what I would call steady state at this point. The contracts have been turned on. We're locked into those rebate rates, so I don't see price deterioration as an issue anywhere in the foreseeable future. To Sheldon's point, this is really just about maximizing that volume under the current construct, and I think we're in very good shape from a gross-to-net standpoint, so I wanted to dive more into payer dynamics, so with Amgen and with Repatha, they've made some major concessions on price, and I'm not just talking about the price cut several years back when they cut the price 60%. I'm talking about year to year, you see high single-digit erosion in net realized price. You also see a lot of volume growth.
They're clearly making a calculation here on making concessions on price and driving better access. They have primary prevention data. Wondering how Amgen's behavior on price may or may not inform how you think about your strategy to maintain access over time. I realize it's a different class. It's a different drug. It's an injectable. It is more expensive. Does what Amgen is doing influence you in any way?
The questions really around the cash-paying customer because, again, with the coverage that we have, the copays that whether you're on Repatha or our drug is essentially the same, commercial or Medicare. Medicare, it's about $45. Commercial, somewhere between $25 and $35. For the cash-paying program, we were ahead of this three years ago. I mean, you say it yourself. Our drug is cheap. It's cheaper with a cash program. We have good Rx for that. We established that about three years ago. I know that they recently, as part of the Trump administration, came along and said, "Hey, we're going to reduce our price for cash-paying patients." I can tell you that our cash price is still less than their cash price. And we already talked about the primary prevention data. Again, I'll just focus on ours. We show a 39% reduction.
As far as I know, that's still the best out there.
And we have a very strong payer benefit model that we have shown and worked with the payers on, showing the cost of Nexlizet to the actual clinical benefit that the patient perceives. I think it's actually won awards at different conventions. So it's a very compelling cost-benefit model that we have worked out with the payers that they're very much on board with.
Essentially our budget impact model.
Yep. So let's look at Europe and wanted to get your thoughts on uptake of bempedoic acid in Europe, other territories. And well, it's a two-part question. Let's talk about uptake, and then let's talk about your economics from ex-US partners.
Sure. So Europe is doing phenomenal. They have over 600,000 patients now on the drug. I was just recently there meeting with Daiichi Sankyo, Europe. They showed me their launch curves of all of their countries. Just to give you an example, U.K., which is always a very difficult market to do well in, it's probably their best-performing market, followed by Germany, Belgium, Italy, etc., just growing at phenomenal rate, high double digits. And it's been further enhanced by the guidelines. They're already getting early feedback, and they're feeling quite confident of their performance. And Ben, you can speak to the economics from a cash-paying perspective.
Yeah. I mean, so from a royalty stream, it's 15%-25%, which is a very healthy royalty stream. As you mentioned, we clean up the cap structure. We did sell that royalty stream to help clean up some of the capital structure. But I'll point out that that was a cap deal. That stream will revert back to us at some point. And Daiichi's done such a great job with it that the date that we thought we'd get it back when we did the deal has been progressively moved up since then. So I mean, I think that'll be back in our hands within the next few years.
Yep. And what about Japan? I mean, that's recent approval. So remind us how you're thinking about the opportunity there and also what your economics are in Japan.
Yeah. We're super excited about Japan. We're actually heading out there next week to help them celebrate the launch. As you saw, we received the $90 million milestone. So very excited about that as well. It's the third largest market in the world, and I mentioned this fact to someone earlier today. They have 750 people, employees dedicated to the launch of bempedoic acid in Japan. I mean, they're really behind this drug, and yeah, we're excited about the results that they'll see when you talk about the economics.
Yeah. I mean, that approval ended up better than we ever could hope for, to be honest, especially on the reimbursement side and the pricing. I think they're very well poised to do really well in that market. Again, the economics are about the same. But I think as far as what people underappreciate is the size potential of that market. We think that with how long they'll have that and the number of patients it could possibly address, I mean, it could be as sizable as Europe potentially.
Yep. So I wanted to ask you about potential competition. So you've got the oral CETP of ezetimibe. I believe we get secondary prevention data later in 2026. So let's start with that. So can you talk to how bempedoic acid stacks up versus that class?
I know there's a lot of history there, but just help us understand how you think bempedoic acid stacks up versus ezetimibe specifically?
I know we only have four minutes and 42 seconds, so it could take me an hour. I'll tell you what I do in a minute. I think we stack up very well. The fact of the matter is we have our CLEAR Outcomes study. We have both primary and secondary prevention. You said it yourself. They're not studying primary prevention. This is a class that's been flawed four times before. There's a lot that remains to be seen. I think we just wait and see what the PREVAIL study shows. Again, I think they're banking on Lp(a). We'll have to see what that really means. We know what AHA just said about hs-CRP. We show a 22% reduction. I think we stack up very well. You said it yourself. I think, David, in my opinion, there's plenty of room for everyone.
But at the end of the day, I think also with the guidelines coming out, we have a very good head start, and we'll be the partner of choice.
Yeah. And then there's Merck with MK-0616, the oral PCSK9. So that is in both a secondary and primary prevention study, although those are further downstream. But how do you see the head-to-head here? And I know you're going to talk about food effects, so I'm going to ask you about that upfront.
Yeah. No, they certainly have good LDL reduction. But look, the food effect's real. I mean, every day you've got to make sure Merck will tell you, and they said in their press conference that you have to wait 30 minutes until you can eat after you take the drug. But you also have to remember that eight hours before that, you also have to fast for eight hours straight and limited water intake. To do that every day for an asymptomatic disease, I think that's really hard.
Yeah. I think, coupled with the fact that most of the patients taking this drug have medications that they're supposed to take with food. The patient adherence and education is just going to be too much of a hill for people to climb over.
Yep. Yep. Yep. That's all fair points. So let's switch gears. Exclusivity runway. So you did settle with a number of the generic filers. There are some that are remaining, though. So just regarding the recent settlements, just talk through what that means in terms of the minimum exclusivity runway you have now, and then just remind us how many additional filers are still out there.
Yeah. So I think one thing that has been underappreciated with the Dr. Reddy's settlement is that they were the only ones challenging the 2031 patent. So at this point, 2031 is the date. At this possible earliest, anything could happen. So we're very confident about that. But that's not to say that I said earlier we have started planning the business past 2031 at this point. I think we are very confident we will come to a positive resolution with the remaining ones. When that is, we can't say because we're not sitting in their seats. But I think this is a tremendous opportunity for the company. And again, trying to choose my words in a very lawyerly manner here, I would just say we're very confident we'll be well into the 2030s still exclusively selling this drug.
Just a follow-up here. With any of the remaining filers, do you have any Markman hearing dates or any hearing dates whatsoever? Or is this kind of still more in discovery?
So we're still in discovery, but I think some of the hearings are set to be scheduled soon. I think at this point, everyone can substantively see what each side is arguing and make that judgment call of what are my odds here. So I think that's part of what gives us that confidence.
Yep. So let's switch gears to the triple combo with ezetimibe and bempedoic acid. So I'm just trying to better understand your thinking on the value proposition of a triple combo and the extent to which it could expand the sales footprint of the franchise.
Yeah. So the triple combo has the potential to be the most efficacious LDL-lowering pill on the market in one pill. And at ESC, we talked about this quickly, but the theme of ESC was triple therapy that no longer can you get to goal with just one pill, similar to diabetes and hypertension. So that's the value prop, the adherence aspect, the convenience. And we'll do it with both atorvastatin and rosuvastatin.
Yep. And the clinical path forward, just remind us.
Clinical path forward is a bioequivalence study and stability, and we hope to be on the market by the end of 2027.
Terrific. Okay. And I know we have 10 seconds left, so we can't talk about your next-generation ACLY inhibitor in 10 seconds. But just give us a bit of a roadmap in terms of what's going to happen next year regarding the advancement in human studies in primary sclerosing cholangitis.
Yeah. We're really excited about this, ESP-2001, and we'll be IND-enabled by late 2026 and into human before the end of 2026.
Okay. Well, I wish we had more time, but I'll leave it there.
Yeah.
Thanks, Sheldon. Thanks, Ben. Thanks to everyone in the audience.
Thank you.
All right. Thank you, David.