Esperion Therapeutics, Inc. Aktie

Ladies and gentlemen, thank you for standing by, and welcome. [Operator Instructions] Please be advised that today's conference call will be recorded.

I would now like to hand the conference over to Tiffany Aldrich, Head of Corporate Communications for Esperion Therapeutics. Please go ahead.

Thank you, operator. Good morning, and welcome to Esperion's Fourth Quarter and Full Year 2025 Earnings Conference Call. With us today are Sheldon Koenig, President and CEO; and Ben Halladay, CFO. Other members of the executive team will be available for Q&A following our prepared remarks.

We issued a press release earlier this morning detailing the content of today's call. A copy can be found on the Investor page of our website, together with a copy of the presentation that we will also be referencing. I want to remind callers that the information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. I caution listeners that management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the business.

These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and in our SEC filings. The content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 10, 2026. We undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call and webcast.

As a reminder, this conference call and webcast are being recorded and archived. We will begin the call with prepared remarks and then open the line for your questions.

I'll now turn the call over to Sheldon.

Thank you, Tiffany. Good morning, everyone, and thank you for joining us. 2025 was a defining and transformative year for our company, representing our strongest performance to date. We fortified our financial foundation, continued our strong commercial execution and reinforced our commitment to the patients who inspire everything we do. Because of this work, we entered 2026 with strong momentum and a clear path forward. We recently introduced our Vision 2040, which defines our long-term ambition and the road map to achieve it. I'm proud to say we are already executing on that vision.

Our planned acquisition of Corstasis Therapeutics significantly enhances our company and demonstrates our Vision 2040 strategy in action. It is a transformational step that will give us 2 powerful global franchises to grow, our global bempedoic acid portfolio and Enbumyst, a first-in-class intranasal diuretic addressing meaningful needs in heart failure care. This combination of addressing bad cholesterol and heart failure will align with our existing cardiology footprint, accelerate growth and most importantly, offer patients more impactful, patient-friendly options across the continuum of cardiometabolic disease.

The acquisition of Corstasis is a catalyst for additional long-term value and a testament to our commitment to building a larger and sustainably profitable company. Our priority is to grow these 2 franchises to their multibillion-dollar potential.

Turning to the progress we've made building the U.S. bempedoic acid franchise, we achieved strong prescription growth and broadened payer coverage as we focused our sales and marketing efforts on statin-intolerant patients, which represents a significant market opportunity. Together, this allowed us to drive Q4 year-over-year sales by 38%, increase retail prescription equivalents by 34% and expand the number of unique health care practitioners prescribing NEXLETOL and NEXLIZET by nearly 25%. We anticipate 2026 to continue this momentum, driven by our strong reimbursement and expect favorable positioning in the U.S. dyslipidemia guidelines, which should be released imminently.

In addition, the American College of Cardiology scientific statement on inflammation and cardiovascular disease formally recognized the link between inflammation measured by hsCRP and ASCVD. The authors provided call to action to implement broad screening of hsCRP for primary and secondary prevention patients in combination with LDL-cholesterol screening. Importantly, the American Heart Association corroborated this recognition in its hsCRP toolkit for professionals in which bempedoic acid is recognized as an agent to reduce hsCRP.

I will remind everyone that NEXLETOL and NEXLIZET are the only non-statins proven to reduce hsCRP by up to 46%. Looking ahead, we are advancing our 2 triple combination programs and expect to complete the clinical and regulatory requirements to commercialize in 2027. Based on published data, triple combination therapies have demonstrated the potential to reduce LDL-cholesterol up to 70%, a level of efficacy that could rival current injectables and emerging oral treatments.

Now turning to our continued international expansion. Our global partners delivered yet another year of substantial growth. Daiichi Sankyo Europe increased fourth quarter royalty revenue by 51% compared with fourth quarter 2024. They expanded access to 30 countries, including receiving favorable payer reimbursement and launching in France and have treated more than 700,000 patients to date. During the fourth quarter, our Japanese partner, Otsuka, successfully launched NEXLETOL in Japan following regulatory approval and a highly favorable national health insurance price listing. Early market reception has exceeded even the most optimistic expectations, with Japan representing the world's third largest market for cardiovascular disease prevention. And given the strong pricing environment, we believe this momentum positions us for significant and sustained growth in 2026 and beyond. Additional launches and regulatory progress continue across Canada, Israel, Australia and New Zealand.

Moving on to our pipeline progress. We continue to advance a new generation of highly specifically ACLY inhibitors, targeting serious metabolic and inflammatory diseases. We nominated ESP-2001 as our next development candidate for the treatment of primary sclerosing cholangitis, or PSC, a devastating disease with no approved therapies. ESP-2001 is now advancing through IND-enabling studies, and we plan to be in the clinic by the end of this year. Collectively, our progress across commercial execution, pipeline advancement and global expansion reinforces the strength of the strategy we have put in place and sets us up for a powerful next phase of growth.

Now let me turn to a review of our exciting agreement to acquire Corstasis Therapeutics. This transaction will provide us with global rights to its FDA-approved therapy, Enbumyst, a first-in-class intranasal diuretic approved in September 2025 for the treatment of edema associated with congestive heart failure, hepatic disease and renal disease. This acquisition is a highly strategic and transformational step for Esperion. It will expand our presence beyond chronic lipid management into a large complementary cardiometabolic market and meaningfully accelerate our growth trajectory.

In addition, Corstasis is advancing a subcutaneous pipeline, including a multi-dose pen injector, which has the potential to unlock additional market opportunities. Enbumyst is available now to address a significant unmet need and aligns directly with our U.S. cardiology-focused commercial infrastructure, enabling immediate cross-selling synergies with the physicians already prescribing NEXLETOL and NEXLIZET.

Enbumyst was developed in partnership with cardiologists specializing in heart failure, who recognized the fact that 1 in 4 patients are readmitted to a hospital within 30 days, driving significant health care costs, despite current products in the market attempting to address this. To reduce readmission rates and provide an easy-to-use at-home treatment, these cardiologists developed Enbumyst, a differentiated patient-friendly alternative to oral and injectable diuretics. As the only nasal spray loop diuretic, it bypasses GI absorption issues, offers rapid onset and supports at-home management of fluid overload. This creates a compelling opportunity to reduce hospital admissions and readmissions, an area of profound unmet need in heart failure, where nearly 2/3 of the 1 million hospitalizations each year are primarily for diuresis, many of which may be avoidable.

Financially, this acquisition provides Esperion with a highly attractive entry point into a $4-plus billion U.S. outpatient market -- heart failure market and significant runway for utilization growth. Moving forward, our plan is to fully leverage our commercial team's cardiovascular sales presence to scale adoption and accelerate revenue contribution.

We are also planning our strategy to launch Enbumyst in ex U.S. markets as we have global rights. The transaction is expected to close in the second quarter of 2026. Enbumyst strengthens our foundation, expands our commercial reach and uniquely positions us to attack the growing global cardiometabolic disease epidemic now and into the future.

With that, let me turn the call over to our Chief Financial Officer, Ben Halladay, for a review of our financials.

Thank you, Sheldon. Good morning, everyone, and thank you for joining us today. Our fourth quarter and full year 2025 financial results can be found in the press release we issued this morning and more detail will be included in our upcoming 10-K.

2025 was the company's best year on record, and our financial results reflect the important advances the team has made. We continue to make progress through 2025 towards sustained profitability and our commitment to growing the bempedoic acid franchise has laid the groundwork that enabled us to enter into new markets and diversify our revenue streams.

We ended the year with $55 million less in debt by paying off the 2025 convertible note stub. And thanks to our disciplined approach to expense management, we ended the year with $167.9 million in cash. We are still in a strong cash position, and we are well capitalized to successfully implement the Enbumyst launch.

Fourth quarter 2025 total revenue was $168.4 million, an increase of 144%. U.S. net product revenue was $43.7 million compared to $31.6 million for the comparable period in 2024, an increase of approximately 38%. Collaboration revenue was $124.7 million compared to $37.6 million for the comparable period in 2024, an increase of approximately 232%, driven by a onetime payment of $90 million received from Otsuka related to regulatory approval and favorable NHI price listing, increases in royalty sales within our partner territories and product sales to our collaboration partners from our supply agreements.

Turning to the rest of the P&L. For the fourth quarter 2025, research and development expenses were $13.9 million compared to $11 million for the comparable period in 2024, an increase of approximately 26%.

Selling, general and administrative expenses were $41.4 million compared to $36.9 million for the comparable period in 2024, an increase of 12%. The increase quarter-over-quarter was primarily related to increased legal costs associated with the ANDA litigation.

As mentioned before, we ended 2025 with $167.9 million in cash and cash equivalents and a balance sheet that continues to improve every year. Our strong stable balance sheet gives us the opportunity to build not only our NEXLETOL and NEXLIZET franchise, but to integrate Corstasis and successfully launch Enbumyst as well.

Our new operating expense guidance updated to reflect modest increases shows the strong synergies we expect between our product lines. We now project full year 2026 operating expenses to be in the range of $225 million to $255 million, including $15 million in noncash expenses related to stock compensation.

With that, I will now turn the call back over to Sheldon for closing remarks.

Thank you, Ben. In closing, 2025 marked a year of meaningful execution, strategic expansion and business transformation, and we are truly a new Esperion. We strengthened every core dimension of our company from commercial performance to global partnerships, from scientific leadership to long-term strategy. And now we have an agreement to add a synergistic high-value asset with the planned acquisition of Corstasis. We expect this transaction to be a growth accelerant and a foundational building block of our Vision 2040 strategy. We are energized by the opportunities ahead and remain relentlessly focused on delivering innovative therapies to patients, value to shareholders and sustainable long-term growth for our business.

Thank you for joining us this morning. Operator, we are now ready to open the call for questions.

[Operator Instructions] And our first question is going to come from Joe Pantginis with H.C. Wainwright.

So I just wanted to go back and maybe review or get reminded again with regard to Corstasis, which was a nice addition to the sales bag for your field force. So just curious, with the device itself, what is your ability or what is the capacity now with regard to, say, approximate numbers of patients to treat and any capacity needed moving forward? And then what are the potential next steps that are required for the auto-injector?

Great. Thanks, Joe. So as it relates to capacity, we're fine. We're in good shape there. There's nothing really needed. We've got product and we're ready to go. There are physicians right now, some of which are using it, but there's never really a full-scale launch, and that's what we are working on and thinking about. Obviously, we have to wait for the deal to close, which, as we've mentioned before, will sometimes be in early April. And then your second question was related to next steps of the auto-injector.

Auto-injector.

Yes, yes. So we'll plan to update you probably after the deal closes of where we are in the pipeline, but it is something we want to mention because it is coming. And the reason why we're mentioning it is that it just gives physicians choice. What I will say is that one thing that we've heard already from key opinion leaders is the ease of use of this drug. And that's what patients need.

As you know, patients suffering from heart failure, it's very alarming. People can't breathe, they can't sleep, et cetera. And to be able to just put something into your nose and get relief, that's a big deal. So we're focused on that now. And again, the auto-injector will be something in the future that will allow optionality.

And our next question is going to come from Kristen Kluska with Cantor Fitzgerald.

So I wanted to ask one on the ACC guidelines. When looking at their abstract titled online, it certainly gives the hint that we're going to be getting something soon. So just curious if you could talk about the latest that you've been hearing on that front, given the conference is in 2.5 weeks here. And then also what you as a company are doing to prepare for that conference? I know that this will also be an opportunity for the clinicians to get training at the conference, but what can Esperion do to prepare from that side?

Yes. Thanks, Kristen. Let me start off, and I'll kick it over to John to talk about what we're doing as an organization. So the intel was always the fact that we would be getting the guidelines sometime in the first quarter. At one point, we were told early in the first quarter. Obviously, here we are in March. Our best intelligence right now is that it will come out before ACC and will probably come out a week before ACC. We've seen some advertisements online that other people have probably seen by ACC talking about a satellite symposium that they're going to hold sometime in the March 19, March 20, and we're thinking that's probably when they could be released.

So before I turn it over to John, the one thing, again, we don't know what they say, but we feel very confident that we should be well represented. And we also believe that there'll be harmonization between what we saw in Europe and U.S. guidelines. And you heard what I said in our prepared remarks around hsCRP. There's been a lot of references to bempedoic acid even before the guidelines in different areas about where we fit as a therapy, which have all pointed to positive signals. But let me turn it over to John to talk about how we're preparing for it.

Kristen, as you can imagine, the team has been preparing for quite some time for this event, and we have a very in-depth cross-functional plan for the entire organization and the medical community as soon as the guidelines are released. It will range from materials for our customer-facing field members, both medical as well as commercial and the sales team as well as a broad digital program and outreach. So we're ready and waiting.

And on that note, given that we kind of got a little bit of a preview about what to expect in Europe, curious if you've talked to your partners about what has happened to them in the months after and in terms of whether the number -- obviously, you guys as an organization are working closely with physicians, but how much of this was inbound from people that were newly introduced or perhaps getting reintroduced? I know you also launched in the midst of the pandemic here. So is there a potential that people are going to be coming internally to you because they'll be reintroduced to the product with these new guidelines?

So I think what we saw when we actually talked about the CLEAR Outcomes study going back to 2023, you saw this huge bolus of awareness. And some of the things that John talked about and some of the things we'll be doing after ACC, we view this as another opportunity to get a lot of awareness, similar to what Daiichi Sankyo saw when the European guidelines were released. I've told the story before where key opinion leaders in Europe said congratulations to Daiichi Sankyo. And their Chief Executive Officer said, well, because of the guidelines, he said, "Well, it's the first time ever that I hear somebody else talking about what a great product this is other than you." And I think that's what's important is that now you have these third-party guideline writers who are very respected who will be talking about our placement in the guidelines and where we should be utilized. And I think that's going to bring more physicians to the table.

It's also going to help physicians really understand that I do need to be thinking about this therapy with this type of patient and this type of diagnosis, et cetera. So it's nothing but what I would say upside for us as it relates to awareness, prescribing, you name it and we'll be ready. The one thing John and his team, after the European guidelines came out, we are out there 4 days after those guidelines with a detailed aid telling physicians in the United States what Europe had done. It just shows you how quick we can react and be ready. So we will take full advantage of this meeting as a very large awareness event, just like we did in 2023.

And the next question is going to come from Georgia Bank with Jefferies.

Georgia Bank on the line for Jefferies. I guess piggybacking on the conversation around the EU guidelines, maybe you could just talk a little bit about the impacts that you've seen in the U.S. already from those guidelines changed in the EU? And then what kind of incremental impact would you see in the U.S. given the guideline inclusion that's coming, as you said imminently? And any changes in the sales force that you -- going forward and where you see opportunities to add coverage for dial back on territories that might be less profitable?

Do you want to do the territory part, and I'll do the guidelines part.

Yes, sure. So George, good question as it relates to kind of sales force coverage. So we continually evaluate the needs of the organization based on demand, productivity, profitability and the needs of our growing portfolio. Once the Corstasis acquisition closes and we integrate Enbumyst into our operations, we will plan to expand the sales team modestly to ensure appropriate coverage of key settings, including the new markets such as key heart failure clinics and IDNs and health systems for that hospital discharge opportunity. And we look forward to providing additional updates as the year progresses. And we continue to evaluate our coverage in light of the guidelines as well to make sure that we deploy our teams in places where we continue to see success.

Thanks, John. And as it relates to European guidelines and effect on U.S. prescribing and how that sets us up for the U.S., let me just first say, in Europe, it's more qualitative. They don't really get prescription data, et cetera. But as you know, we look at patient data, and you've seen in our presentation that we delivered today and in our prepared remarks, Daiichi Sankyo now has treated over 700,000 patients with this drug. In Germany alone, as you know, you have to use bempedoic acid before you can go to a PCSK9. And that was established even before the guidelines. The guidelines reinforced the decision by AMNOG, which is a division of IQWiG in Germany that makes these health care technology assessments.

We've talked about France. In France, they'll be launching. I know that their guidelines were received very favorably there. It's the second largest market in Europe, and they're already off to a fast start. As you know, Organon has partnered with Daiichi Sankyo to launch there and also in the Nordics.

From a U.S. perspective, again, it's more qualitative and the feedback that we've gotten from the field is that physicians responded very favorably to the European guidelines. And I think the sentiment was, hopefully, we'll see the same thing in the U.S. And I think that's what we're all waiting for. But as it relates to U.S. guidelines and effect on prescribing, similar to the answer I gave to Kristen earlier, we think this is nothing but tailwinds for us. I mean the fact that, again, we can have a third-party advocate, it's important to be in guidelines. And the fact that we would now be in guidelines, this is our first opportunity, that's going to be a really big deal for us. And future competition, which we get questions of, they won't be in the guidelines.

Remember, one of the reasons why we think we'll have prominence in the guidelines and why we have prominence in the European guidelines is because of the 14,000-patient CLEAR Outcomes study, which was a game-changing study. And we'll see why and how that will be interpreted into the U.S. guidelines as well. It's undeniable and just it's data that's important and physicians will be keen to get those guidelines and apply them.

And the next question comes from Serge Belanger with Needham.

The first one regarding the triple combo products. Based on your FDA interactions and the development path you've taken, what kind of label do you expect for these products? Is it going to be similar to the NEXLIZET?

And then secondly, regarding guidance, I guess, for Ben, I know you don't provide top line guidance, but can you give us a little more color on the collaboration revenue line for 2026, just given that there's a couple of moving parts with Otsuka launching in Japan and the manufacturing transfer that's going to affect those numbers?

So let me start with the triple combination. Just as a reminder to everyone, the triple combination therapy is bempedoic acid plus ezetimibe plus the statin. So essentially NEXLIZET plus the statin. We're doing 2 different statins, atorvastatin and rosuvastatin. We're looking at a low-dose strategy. If you even look at ESC and what they showed in their presentation of the guidelines, if you look at the addition of a statin such as atorva or rosuva to NEXLIZET, you get close to a 70% reduction in LDL. We've done our own study with atorvastatin 10 milligrams and showed close to a 70% reduction in LDL.

The label itself is -- will not carry the outcomes data that you see in NEXLIZET or NEXLETOL because people know the background of these drugs, statins and also bempedoic acid, whether it be NEXLETOL or NEXLIZET. So it's pretty much just a label without the outcomes data that will speak to efficacy. And we've already market researched this as well, Serge, and physicians get it. And what I will say is that this is something that not only are physicians really interested in, in Europe, but they're really interested in here in the United States. And the reason for that is because there is more of the shift to this polypill within a therapeutic area strategy. And the fact that you can give somebody one pill that will get them to perhaps a 70% LDL reduction speaks to so many benefits as it relates to compliance, persistence, et cetera. So we're excited about it and look forward to the day where we can bring it to market. Ben?

Yes. Serge, thank you for the question. So when it comes to the partnership revenue line, there are a lot of moving parts this year. I mean, first and foremost, we won't have another $91 million in milestones because of the regulatory work that we had in 2025. But primarily, I think the big drivers are going to be, we expect royalties to continue increasing both from the addition of Otsuka as well as the fact that Daiichi Sankyo continues to grow in their existing markets and added France in first quarter of this year.

On top of that, the tech transfer will start flowing through the P&L, and we expect that, that manufacturing will continue to ramp up over the course of this year. So that partner reimbursement line will tick down, but associated with that will actually be an increase in the gross margin based on the margins that we've discussed on these calls before. So a lot of moving pieces, but I think overall, we expect to continue to see that partner reimbursement line continue to add significant value to the company and enhance over the course of the year.

And our next question will come from Jason Zemansky with Bank of America.

Congrats on the quarter. So it seems in the last 2 quarters, while you broadened access on the payer front, there have been a number of concessions. So moving forward, can you discuss what the risks look like for additional concessions in 2026, especially given, as you mentioned earlier, there are potential new competitors poised to enter the market?

Jason, thanks for the question. But can you -- when you say concessions, do you -- what are you speaking to? Are you speaking to price or...

Yes, exactly.

Okay, yes. No, we don't see anything as it relates to concessions. We're set with our contracts. We have a 90% coverage in commercial, 90% now in Medicare. If anything, I think it's competition that's going to have to make concessions. Keep in mind, again, we have an outcome study, competition doesn't. I know you speak to the MK-0616 product. Keep in mind that they don't have outcomes until 2030, and payers really look for outcomes in order to avoid step edits and significant prior authorizations. So we're good. No concessions needed from us.

And the next question is going to come from David Amsellem with Piper Sandler.

I just have a couple. Coming back to the triple combination, what's your market research revealed regarding the extent to which it could expand your overall bempedoic acid franchise patient footprint on both sides of the Atlantic or frankly, globally? That's number one.

Number two, as you think about the triple combo, I mean, the messaging historically has been about statin intolerance. Do you think the triple combo changes that message or muddles that message? And how do you square the triple combo with the historical messaging about statin intolerance and the utility of bempedoic acid in that context? That's number two.

And then lastly, regarding your Vision 2040 plan, maybe just thinking about the sales force and how you're expanding the product offering what is the optimal number over the next 2 to 3 years, I should say, the optimal number of products that you think your commercial organization can carry in its bag, so to speak? Or put differently, what's the extent to which there's going to be other assets you're going to be bringing in over the next couple of years?

Sure. Yes. Let me start off with the triple combination and the excitement in Europe and U.S. and market research. Succinctly, it's very high, David. I mean the fact of the matter is this cardiovascular disease is still the #1 killer. And even despite all the therapies that we have out there, it still is the #1 killer and continues to grow.

The excitement around triple combination has been very high in both Europe and the United States. As a matter of fact, it was reinforced with the European guidelines where the whole emphasis was on triple combination. And there, they talk about triple combination without even having the pill. It's more a combination of therapies to get patients to goal. And I think we finally have reached that point where similar to diabetes, similar to hypertension, one drug does not get you to the goal that you need, you need multiple. So it's very exciting from that perspective.

Regarding statin intolerance, it doesn't muddy the waters at all because remember, the definition of statin intolerance is really 3. One, a patient who doesn't want to take a statin at all; two, a patient who can't tolerate a statin; three, a patient who can take a statin, but only a low dose. And keep in mind, for triple combination, it's really about looking at that low-dose statin with bempedoic acid. So the definition of statin intolerant, as a reminder, is not just a patient who can't take a statin at all. It's just about the dose of a statin. And keep in mind, titrating a statin only gives you a 6% additional LDL efficacy. It's meaningless. That's why it's better just to go to these other therapies. Again, something that was reinforced in the European guidelines, and I think you'll see reinforced in the U.S. guidelines.

Before I turn it over to John to talk about number of representatives, et cetera, because I think there's maybe 2 questions in there, we're good now. We have bempedoic acid, NEXLIZET and NEXLETOL. We're doing the Corstasis acquisition. We talked about Vision 2040 having 5 products. Keep in mind, primary sclerosing cholangitis is a product. If successful, would be out in 2030, 2031. But from a BD perspective, we're good where we are now. We'll call our jets with BD. We'll always look at the environment. But as it relates to number of field personnel, et cetera, just overall, I'll turn it over to John.

Yes. Thanks, Sheldon. David, I look at the question twofold. One is the size of the sales organization and number of reps as well as to your question, the optimal number of products within an existing bag. And it really depends upon, one, the target overlap and the customer call point. It also depends upon where the product or products are within their life cycle. We still are in the early stages of the life cycle of NEXLIZET and NEXLETOL. And obviously, we're in the very beginning stages of the life cycle of Enbumyst. In 2 to 3 years from now, we could envision having a field that has 2 to 4 products in the bag. Again, it depends upon call points, synergies as well as life cycle. And getting beyond that 4 sometimes gets questionable. But we have seen it where more mature products can be in the bag, so it could be 4 or 5. But again, we're not at that stage yet from a maturity and a product life cycle standpoint, but we'll continue to evaluate how the products fit as we evolve into our Vision 2040.

And the next question will come from Paul Choi with Goldman Sachs.

My first question is another one just on the triple combination and that was combinations. And I was wondering if you could any -- offer any narrowing of the range in 2027, where you might potentially file the NDAs for the 2 drugs.

And my second question is on Corstasis. Can you maybe just remind us if there are any clinical development obligations or post-market obligations at this point for Enbumyst? And then also just sort of in '26, whether you anticipate any additional clinical updates from the ongoing clinical development or presentation development programs?

Great. Thanks, Paul. And let me -- well, Ben, why don't you start with the Corstasis one?

Yes, Paul, on the Corstasis side, there are some small PMR studies that need to be done, but we've included all those in the updated expense guidance. They're minimal. It's not something that we really expect to move the needle all too much.

Thanks, Ben. And it relates to triple combination and narrowing down the date. I'm just going to say right now, Paul, we'll continue to update you. But right now, sticking to 2027. There's competitive reasons for saying that as well, but we'll definitely continue to update you on our progress. But again, to me, the triple combination reinforces our commitment to, again, making bempedoic acid franchise as successful as possible while also making our Corstasis acquisition once approved, equally successful.

I am showing no further questions in the queue at this time. I would now like to turn the call back to Sheldon for closing remarks.

Great. Well, thank you so much. I again want to thank everyone for your ability to attend our earnings today. Again, 2025 was just a great year for us, our best year ever, fourth quarter, our best quarter ever and really appreciate all the questions as well. And look forward to updating all of you in the future as we continue along here at Esperion. So thank you so much. Have a great rest of the week.

This concludes today's conference call. Thank you for participating, and you may now disconnect.

Hello, ladies and gentlemen, thank you for standing by. Welcome to Esperion Therapeutics Strategic Update Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to Mr. Sheldon Koenig, President and Chief Executive Officer. Please go ahead, sir.

Thank you, Olivia, and good morning, everyone. Thank you so much for joining us this morning for the exciting news that we plan to deliver to you today and give you more information on it. As you had seen this morning, at 6:00 a.m. this morning, we issued a press release that Esperion Therapeutics and Corstasis Therapeutics announced Esperion's definitive agreement to acquire Corstasis, expanding our cardiovascular franchise with Enbumyst.

Enbumyst is the first and oral-only FDA -- I'm sorry, is the first and only FDA-approved nasal spray loop diuretic for edema associated with congestive heart failure. We expect to leverage Esperion's established cardiovascular commercial infrastructure, and this also synergistically expands our product portfolio and accelerate double-digit revenue growth.

Just to give you some quick information on the economics of the deal. This is an upfront cash payment of $75 million royalties on worldwide Enbumyst sales and up to $180 million in potential milestone payments tied to certain commercial and regulatory achievements.

And turning now to our slide deck, our first slide, forward-looking statements and disclosures. I'll allow all of you to have the opportunity to read through that at your leisure.

You may recall JPMorgan on Slide 3, we discussed Vision 2040. Corstasis Therapeutics acquisition is the Vision 2040 in action. You may recall, we have 3 pillars to support our strategy moving forward into the future.

The first, strengthen and expand the bempedoic acid franchise. We will continue to unlock the multibillion dollar potential of NEXLETOL and NEXLIZET in the United States and globally. We want to build a multi diversified product portfolio. The acquisition of Corstasis allows us to do this. We're able to leverage our established U.S. commercial infrastructure to support product acquisitions, co-promotions, et cetera, and Corstasis is a great example of us using our infrastructure to do so.

And of course, we have our pipeline, and we will continue to advance our next-generation ACLY pipeline with IND-enabling studies in our lead asset ESP2001 for the diagnosis of primary sclerosing cholangitis, more to come with that later in the year. Our overall goal, as we stated, is to achieve at least 5 marketed products by 2040 through a combination of business development and internal pipeline advancement.

Turning to Slide 4. Let me quickly go over the Corstasis Therapeutics acquisition overview. A quick summary of the company, the lead asset Enbumyst, bumetanide nasal spray. This drug was approved in September of 2025 for adults with edema associated with congestive heart failure and hepatic and renal disease, including nephrotic syndrome. The drug has been commercially launched, and it does complement our portfolio, and we'll go in later regarding our target audience, et cetera, and you'll be able to see the synergies that we have to offer.

There'll be additional presentations and pipeline products in development for congestive heart failure and hepatic and renal disease markets in the future. I broadly discussed with you the transaction summary, but again, keep in mind, Esperion will own the global rights to Enbumyst and all pipeline assets.

Turning to Slide 5. I want to discuss with you the strategic rationale. This really builds on Esperion's deep domain expertise in cardiovascular disease and expanding presence in metabolic, hepatic and renal disease. We've talked before in our Vision 2040 that we want to be an organization that acquires products that would fit within the cardiometabolic structure that's currently out there. This acquisition expands Esperion's lipid management focus into complementary treatment for edema and congestive heart failure patients.

Enbumyst offers unique patient-friendly delivery differentiating from oral/injectable competitors and capturing underserved outpatient needs. This also truly accelerates our double-digit revenue growth with high-margin product that is synergistic to Esperion's commercial footprint in cardiology, again, reinforcing the synergies that we have to offer with this deal. It provides compelling entry into a potential USD 4-billion plus addressable outpatient congestive heart failure market at attractive valuation multiples versus peers.

Remember, I talked about the fact that we also have the global rights to this product. For the purpose of today, we'll be focusing on the U.S. market. But as time goes on, we will update you on our exploration of markets in Europe and beyond.

Turning to Slide 6, the growing heart failure epidemic. Congestive heart failure is a growing U.S. epidemic. Congestive heart failure affects more than close to 7 million U.S. adults and is projected to impact over 8 million adults by 2030. The costs the nation estimated $47 billion in 2020 and is expected to increase to $142 billion in 2050. Congestive heart failure affects more than 10% in individuals aged 65 and older and remains the leading cause of hospitalizations in this age group.

Following years of improvement, CHF mortality rates have shifted upward, changing from 108.3 per 100,000 in 2012 to 121.3 in 2019. CHF contributes to 452,000-plus deaths in 2023, and this is nearly 15% of all deaths in the United States. I'll also go as far as say that heart failure is one of those few metrics that hospitals are judged upon as it relates to readmissions. And you'll hear the term frequent flyer used by us many times. These are patients that have to continually come back to the hospital and get diuresed.

One in 4 patients are readmitted within 30 days, driving significant health care costs. And this is what really drove Corstasis in developing this drug to say that we need something better. We need something that can address these folks that are continually being readmitted. The greatest expenditure for CHF treatment is estimated to be $8 billion to $15 billion annually with the most common cost due to need for IV diuretic treatment.

There are 4 million hospital admissions 67% -- close to 70% of admissions are for diuresis only, and the length of stay is 4 to 7 days per admission. Hospital stays for acute decompensated heart failure are prolonged, and this averages close to $12,000 for initial hospitalization.

I will now turn the presentation over to Dr. Dan Bloomfield, who will discuss addressing the unmet need. Dan?

Thank you, Sheldon. On Slide 10, I'll start by talking about the patient journey. You can ignore the text in the white boxes, it's busy, but the main point here is this vicious cycle of patient heart failure, coming into the hospital, going home, getting readmitted.

As Sheldon said, 1 in 4 patients are readmitted to the hospital. So patients diagnosed with heart failure. In the next 2 years, they'll be coming to the hospital for an admission about 2 to 4x. And when they're in the hospital, they get diuresed and fluids taken off and doses of diuretics are increased to avoid future hospitalizations. But in the U.S., especially, there's a real pressure on length of stay and about half of the patients are discharged from the hospital with clear signs of congestion while improved from their admission, still exhibiting [indiscernible] edema that requires further diuresis. And that probably accounts for why 1 in 4 patients are admitted to the hospital within 30 days.

So they go home with high doses of diuretics, they try to get the fluid off and patients will eventually reach back to the dry weight. They will return to their activities of daily living, and they may be home for a couple of months. But eventually, the amount of fluid overload will increase. They'll get short of breath, they'll get edematous and they'll initially go to the doctor's office often to get IV diuretics or have an increased dose of diuretics. But then they'll go home and over time, come back to the emergency room. And then in 4 out of 5 cases, they get admitted to the hospital, but in 1 in 5, they go home from the emergency room.

So this vicious cycle is due in part to the fact that diuretics often become less effective over time. The doses of diuretics are increased over time. And one of the reasons why diuretics become less effective over time or oral diuretics is because when they get edema, they get edema in the gut wall, which reduces absorption and therefore, less of the diuretic dose is actually being absorbed and getting into the blood.

So this cycle affects patient quality of life tremendously. There's always a balance of how much fluid versus the dose diuretics. It's frustrating for caregivers to have these patients come back and forth into the clinic.

I'll go on to the next slide, Slide 11, which offers a vision of how Enbumyst could be an opportunity for intervening in this vicious cycle. Again, patients go home from the hospital, and they may still be volume overloaded. And so as you can see in the lower circle, they can potentially get Enbumyst as a way to continue the diuresis whilst they're home, that's required to get them back to the dry weight.

Over time, they'll eventually end up with volume overload. And again, a time to intervene at that point would be to have them use Enbumyst to get more aggressive diuresis for a period of time and then settle back into their standard or their chronic dose of diuretics. So there's an opportunity to enhance diuresis when they go home from the hospital, and it can be used to avoid hospitalizations as the volume overload or fluid builds up.

On Slide 12, I want to just talk about why Enbumyst stands out. So first of all, it's the only nasal spray diuretic that's out there. It provides rapid absorption. I mentioned it bypasses issues with GI absorption. It's very easy to use for self-administration. It has a similar effect on diuresis and natriuresis and as IV bumetanide, and we believe there will be improved compliance compared to oral tablets and IV injections.

The clinical advantages, it treats edema and heart failure and hepatitis and renal disease. Essentially, if you need to take fluid off, Enbumyst can be used to help facilitate that. The doses can be individualized based on the dose required for diuresis between 0.5 milligrams and 2 milligrams. And as I mentioned before, it reduces hospitalizations risk by enabling at-home diuresis before they reach a stage that they have to be admitted. Bumetanide has been available for decades. It has a very favorable safety profile. And that safety profile is essentially the same as it is with inhaled bumetanide or Enbumyst.

The cost savings will be based on differential pricing, the ease of use. It will overcome the variability of absorption, as I mentioned before, and avoid the need for IV diuretics. And I think it's important to recognize that this addresses a gap in current standard of care.

This is a situation where right now, physicians and nurse practitioners have little choice when patients are buying overloaded and not responding to diuretics to increase the effectiveness of diuretics at home. And so that's a way these folks can avoid having to come to the emergency room or the doctor's office, and that's a gap that exists now that leads to this requirement for extensive care. And it's differentiated in part because of its form factor, it's less burdensome administration to the patients than IV diuretics or, as you'll hear in a second, subcu diuretics.

On Slide 13, I want to compare 2 compounds, Enbumyst and FUROSCIX. FUROSCIX was one of the first therapies or probably the first therapy to offer IV -- offer subcu injections of furosemide or Lasix in the device that infuses the furosemide every 5 hours. It's a device the size of a pretty hefty soft covered book. It's put on to the abdomen. There's a needle that gets injected into the subcutaneous tissue, and then it needs to be infused every 5 hours, but patients have to remain supine or relaxed while that infusion is going on.

The onset is fast and there's very mild site reactions and it's approved for edema weighing in pediatric patients as well as adult patients with kidney disease and chronic heart failure.

In comparison to FUROSCIX, Enbumyst has a single-use nasal spray. There's no needles. You get 2 liters urine out about an hour, and it's very well tolerated. And again, the indications are broader, because you include hepatic syndrome as well as heart failure and renal syndrome compared to on FUROSCIX. It's the first nasal delivery system and is in the process of being launched now. FUROSCIX was launched in 2023.

So the Enbumyst advantage is pretty clear, much easy to use a nasal spray that you have to lie down for 5 hours to get an infusion. The onset is comparable and efficacy is comparable, avoid site reactions. There's a slightly broader indication and it's very easy to use.

And my last slide, Slide 14, is the target audience for presenting this novel innovative form of diuresing patients. So the primary audience are people who take care of heart failure. So cardiologists and heart failure teams are the key decision makers for managing fluid overload in heart failure. But it's not doctors necessarily that are the key people making these decisions.

So advanced practice providers, such as nurse practitioners and physician assistants are the ones who lead frontline outpatient care for decisions on patient's fluid management. And the rapid development of these advanced practice providers over the past 20 years is a sign of the burden to a practice of these patients coming back over and over again. So adding these practitioners really improves the efficiency of the heart failure doctor's office.

As a secondary audience, we hepatologists who treat volume overload and liver disease, again, with oral diuretics may be less effective and nephrologists where patients with complex renal function will also require increased doses of diuretics.

And [indiscernible] audience is important, and that's health care assistance and payers. We believe that this will influence the protocols for managing heart failure patients, coverage decisions and system costs with our increasing focus on value-based care and care at home models.

And with that, I'll turn it back to you, Sheldon.

Thank you, Dan. Thank you so much. Please if you address your attention to Slide 16, I want to discuss the annual U.S. market opportunity. This is a multibillion-dollar opportunity for us. If you look at the patient funnel going from left to right on a cartoon, you can see that there's close to 7 million chronic heart failure patients in the United States. 2.1 million, we believe, are addressable as it relates to the use of Enbumyst. The average cost of Enbumyst per congestive heart failure episode is approximately $2,200. This represents an opportunity of close to $5 billion for us from a market perspective. The value proposition or the goal of therapy is to reduce admissions and readmissions to improve outcomes and lower the cost of care.

Turning to Slide 17. How does Enbumyst fit within our portfolio? Again, we believe that based upon our infrastructure and what we've said in the past, we can lend our infrastructure to effectively launch Enbumyst. Our current portfolio, as you know, is NEXLETOL and NEXLIZET. We have an established chronic cardiovascular risk management know-how within our organization. We have strong relationships with cardiology prescribers. We have existing payer coverage and formulary access and the relationships that go along with that. And we have a proven sales force who has executed in the cardiometabolic space for over 5 years.

From a synergies and fit perspective, we expand from chronic lipid cardiovascular therapy to also acute congestion, volume management and heart failure. And make no mistake. Our attention is on maximizing the bempedoic acid franchise to the multibillion-dollar franchise, it will be and Enbumyst at the same time. We have the same target physicians. We can leverage our existing payer contracts and formulary access, and this also complements oral therapies with this novel nasal delivery that we have with Enbumyst.

As you heard earlier from Dan, Enbumyst adds value in many ways. It addresses an unmet need in outpatient congestion, potential to reduce hospitalizations, and you'll hear more as we continue to launch this drug, our activities from a health economics outcomes research perspective, budget impact model, et cetera. We're differentiated versus FUROSCIX. This is nasal versus an infuser, easier use, better adherence. And I can tell you in many discussions we've already had with key opinion leaders, the one thing that really comes across is that this is easy to use.

The upside from CKD, hepatic congestion indications aligns with our pipeline. As you know, we've talked about our pipeline from a liver perspective. Later this year, you'll hear what we're doing in the kidney area as well. This is a novel differentiated offering that we are just very excited about.

Turning to Slide 18. The combined company, we're perfectly situated to attack 2 of the largest cardiometabolic markets, NEXLETOL, bempedoic acid, NEXLIZET, bempedoic acid plus ezetimibe and now welcome Enbumyst. We're in a strong financial position. We have a diversified product portfolio. We will reach sustainable profitability in 2026, and we've been very consistent about that. Durable cash flows, a strong balance sheet and attractive P&L profile.

Our partnerships and pipeline, we continue the development of what potentially will be the most efficacious lipid-lowering product in the market with our triple combination of combining NEXLIZET with either atorvastatin or rosuvastatin. Corstasis RSQ-786 and 789 is a subcutaneous version of this drug that we're also working on. There's also a potential for a multi-dose and smart infusion system. And later down the line, there's even a potential for a veterinarian indication in heart failure in dogs. ESP-2001, I've mentioned, will be in the clinic by the end of this year, and you'll hear more about our kidney program through the end of 2026.

Turning to Slide 19. This is a strong high-impact opportunity. We talked about the heart failure landscape, close to 7 million adults affected annually in the U.S. 16 million globally. So you can really see the global opportunity. There's an unmet need, limited outpatient options for fluid overload, and there are currently no nasal diuretics currently marketed. Addressable market of 2.1 million annual heart failure episodes per year. The hospitalization burden is close to $20 million. Cost savings and potential exist, and we're going to demonstrate that. And now we have an offering to also address this -- to address the economic aspects.

Strong intellectual property to 2040, so it fits nicely with our Vision 2040. And the growth drivers are aging population, post-COVID CV complications, regulatory support for novel formulations. Heart failure has and always will be a significant unmet need.

Turning to Slide 20. This is Vision 2040 in action, a transformational leap forward. We are perfectly positioned to aggressively attack 2 of the largest cardiometabolic markets, allowing us to further our mission of helping millions of patients worldwide. It's a really proud day for us.

We're really excited about this opportunity, and we're looking forward now to taking your questions. Operator?

[Operator Instructions] Our first question comes from the line of Dennis Ding with Jefferies.

Congrats on the deal. I have one. So is it appropriate to use FUROSCIX as a launch analog? They did $15 million, $35 million and $70 million in the first 3 years, but they also only have 40 cardio reps in the first 2 years before expanding into renal. So given you guys have under 50 cardio reps, should we actually expect a faster launch ramp in terms of revenue for you guys?

Dennis, thank you for your question. Let me start off, and I'll ask John Harlow if there's anything that I missed to also chime in. It's really right now, it was one of the first products, as you heard, that was launched in 2023 to address this need for at-home market. So no analogy is perfect. You can never find in a perfect analogy.

But to your point, I believe with the organization that we have with close to 155 representatives, we also have a very strong managed care reimbursement team. It really goes back to what we've said before from an infrastructure perspective. We also have a very significant health economic outcomes research team, and that will be very important to talk about some of the economic benefits that we mentioned today and publications, et cetera, that we have planned.

We also think that we'll have a significant meeting presence. You heard from Dan that you have to be really tied to the heart failure community, especially in the area of nursing, and we'll be able to address that. So I think there's learnings from the analog. It's not the perfect analog, but it's the closest that you can get to when modeling success. And I do think we will be more successful, yes.

John, did I miss anything?

No. The additional thing, Sheldon, that I would add is that the Corstasis team has launched this product, and we're looking forward to integrating that very small team into our organization and learn from what they've learned on their time in the market for about 3 months and looking to accelerate that growth.

Our next question coming from the line of Kristen Kluska with Cantor Fitzgerald.

Congrats on the acquisition. I actually have a couple of questions. I'll start with one at a time. Just mechanistically, do we see that the gut edema rates and absorption issues are similar amongst the loop diuretics? Or is there a case to make perhaps why one is more favorable than the other? Or is it really just coming down to the route of administration?

Dan, can you speak to gut edema and resistance?

Yes. Thanks, Jonathan. Good question. So it really just boils down to an oral tablet in the gut. All the diuretics are essentially the same in that regard. So gut edema is something that would not be able to be overcome just by changing the drug per se, but really the change in the method of delivery is really what's important.

And with the deal estimated to close in the second quarter, are you assuming that first sales should be coming in maybe starting in the 3Q time line? And how should -- how are you setting expectations for us just as we think about these first few quarters?

Ben, I'll turn it over to you.

Yes. We will have sales in the quarter that we close it. I think we are looking at figuring out how we can do a bolstered launch of this drug as quickly and fastly as possible after integrating it. I will say it will likely take a quarter to fully integrate and get the launch plans in place. So for the first one, I think you will see some revenue, but I think really after that is when it takes off and you start to see the impact of this being in our commercial organization.

Okay. And Ben, can you give us a little bit more color about the split about financing the deal through debt and the royalty stream? How much of this is coming from the Japanese royalty? How much is coming from the credit facility?

Yes. So we'll go into more detail that as we finalize those agreements and get closer to closing this. But I will say it's probably more heavily weighted towards the royalty monetization. The one thing that I really like about this financing structure is it achieves a few different goals that we set out to do, right? We're not releveraging the company after deleveraging it over the last 2 years.

We are keeping dilution to -- we're not diluting. We're keeping this to a nondilutive financing mechanism. But at the same time, it sets us up to have the cash to both do the deal and effectively launch this drug. So in my mind, it's a really great financing structure here. We will go into more details in terms of the full terms, distribution and setup of that as we reach closer to close here. But I think rest assured, this is a great setup for the company and one that really derisks this product, this deal and this launch.

Okay. And one last question, if I may. Just you talked about the opportunity for intervention in 2 key segments maybe to start off. But given the dosing regimen, how should we be thinking about compliance and adherence as well?

John, do you want to address that, compliance and adherence?

Yes. So Enbumyst is really -- it's not intended for chronic use. It's somewhat of a rescue medicine. So adherence and compliance is not something that we anticipated being an issue. It's also a very easy-to-use product. It's in a well-established device, which is used in other marketed products. So we don't anticipate any challenges with adherence or usage.

Thank you, John.

And our next question is coming from the line of Joe Pantginis with H.C. Wainwright.

Nice addition to the sales bag. So I have 2 questions. The first one has, I guess, a bunch of components because it really revolves around the launch of the product. So I appreciate the comment right now that compliance shouldn't be an issue. That's really important. So I guess I want to talk about how is dosing driven? I mean it's at-home based on the information that I've been looking at, there are quantity limits with regard to how much a patient can get at one time, if. I'm correct. Is this something that a patient will self-assess? Do they need to call the doctor? So what sort of parameters triggers at-home dosing?

Let me start, and I'll turn it over to John as it relates to the dosing that's necessary. So Joe, typically, how these patients present, this isn't necessarily for the new -- the very first time a patient has heart failure. This is for that 1 in 4 that keeps returning within 30 days, and they develop symptoms. They have shortness of breath, dyspnea, they can't sleep. They're propping themselves up with pillows, et cetera. They have a history of heart failure, they call their physician. They pretty much know that they're filling with fluid again. They might have edema, et cetera. And I think that's really the trigger point.

That's now. Further down the line, the company, Corstasis was actually working on also a potential wearable or technology that can actually notify the physician that a patient is symptomatic. That's more in the future. But now that's typically what gives away for a patient is they've had heart failure before. They know what it feels like. They know they need to be diuresed, and that usually triggers them to call their physician. John, do you want to speak to dosing?

Yes. So Joe, from a dosing perspective, each device comes in 0.5 milligrams. You can dose up to 2 milligrams a day. And with these patients, both the at-home patient, so prior to a readmission or admission or a discharge patient, patient coming out of the hospital, we anticipate a usage around 5 to 7 days. Obviously, the dosage is going to depend upon the severity of the patient.

No, that's very helpful. And then my second question, I guess, since this is essentially the beginning of the launch here, can you discuss any capacity needs moving forward? And what sort of the addressable population you can go to immediately? Yes, I'll just leave it at there.

John?

Sure. So as Sheldon highlighted earlier in the prepared remarks, we have a cardiovascular team that is focused not just on cardiovascular, but also primary care physicians. We are going to look to add Enbumyst into the bag upon closing. We are also -- there's the hospital marketplace, which is very important, which the current Corstasis team is also calling on those major metropolitan areas. And we are going to look to probably upsize that approach also. Again, there's 2 very important marketplaces. There's the at-home and then there's a hospital discharge. And so we're going to approach both of those based upon the tremendous opportunity that this represents for the organization.

But more towards any potential manufacturing needs for capacity of the actual device?

We believe from a manufacturing standpoint, we're in a good place right now.

Our next question coming from the line of David Amsellem with Piper Sandler.

I have just a few. First, on the competitor product, FUROSCIX. MannKind bought scPharmaceuticals for, I believe, it was $300 million upfront. So you're obviously paying a much lower upfront price point. So I'm just wondering if there's sort of a disconnect in your view here as you think of the 2 assets. I wanted to pick your brain on that. So that's number one.

Number two, can you talk about the work you need to do in terms of access improvements? I know it's a new product, but just talk about Medicare access and Medicaid as well and what you need to do there to maximize assets? And then the last question is on exclusivity runway. How should we think about that?

Thanks, David. I think this is going to be a 3-tiered answer. I'm going to talk about the deal, have Ben Halladay give his comments and then turn it over to BJ Swartz as it relates to market access. So first of all, I can't comment on why MannKind spent close to $315 million on scPharma.

But what I can tell you is that we believe that we have a better product. It's a great deal for us. Ben already talked about how we financed it, how we are not diluting the organization. And it's a drug that's very easy to use. As you know, the current FUROSCIX drug is a pump that you have to wear for 5 hours for an infusion and you have to do that for 5 days. Again, ease of use here is a nasal puff. This is typically a more potent loop diuretic, bumetanide. So I'm just going to say, hey, we're smart, and we did a smart deal.

Ben, any thoughts as it relates to the deal comparison?

Yes. It's -- I mean, you can never compare 2 deals here. I think when you look at the structure that we have put up, the reason that we did it this way is because you had a team over Corstasis who truly believe in the potential of this drug and wanted to share in the upside. So they are very confident that this will be a very successful drug. We agree with that, and we set up a deal that accordingly recognize both of that confidence.

BJ, do you want to speak to market access high level?

Sure. David, you mentioned maximizing access and improvement there. First and foremost, Corstasis has laid the groundwork to engage initially with payers, both from the payer standpoint, distribution, et cetera. But what we look at here is the synergy of our current team, the relationships we have now, the contracts we have in place and leveraging those relationships on top of having our field reimbursement team as well to really work in those centers, as John said, we have the IDNs and those key centers of excellence. We could have that opportunity to use that field team there as well.

And then also, it's just really -- we know that payers are laser-focused in this category just around the readmission. And most admissions to the hospitals around heart failure are about $12,000. So with that said, when you're looking from a CMS perspective, they are very much attuned to heart failure, the cost there and trying to keep those patients out of the hospital for readmission.

So from a health economics outcomes research standpoint, real-world evidence, it will be critical, as Sheldon had outlined, from a budget impact to go to those regional health plans and really look at their actual patient population that is in heart failure and really meet that value proposition and truly have a value-based care discussion as well. I think there was a third question, too. Is there a third question, Sheldon?

No, I think that was it.

Yes. No, actually exclusivity runway. How are you thinking about that?

Ben?

I'll know that they have [indiscernible] patents and what we believe is strong IP out until 2040, as we mentioned in our prepared remarks.

Our next question coming from the line of Jason Zemansky with Bank of America.

This is [ Jackie ] on for Jason. First off, congrats on the deal. So what are your plans? I know you've talked about the sales force a little bit, but do you have any plans to expand? And how do you intend to reach hepatologists and nephrologist offices? And also, I know you started touching on this. But given the recent analogs of similar specialty products, how aggressive is or do you think Medicare will be in terms of management?

Let me just start off as it relates to Medicare. Again, this is a very high unmet need. This is one of the few therapeutic areas where hospitals are judged by CMS on readmission rates, and there's actually a connection between money that they receive for reimbursement of physicians as well and the pools that they are in and how they manage these heart failure patients. I think Medicare is always looking for solutions to better manage heart failure patients. And it's probably one of the few therapeutic areas where they are that aggressive.

John, I'll turn to you as it relates to infrastructure and addressing nephrologists, hepatologists, et cetera.

Yes. Thanks, Jackie, for your question. So obviously, our primary target right now, primary audience is the cardiologists, the congestive heart failure care teams and then the advanced practice providers that are affiliated with those groups. From a secondary audience perspective, we are going through the target overlap analysis as we speak. We have, as you know, deployed a very robust digital approach for NEXLIZET and NEXLETOL, and we're looking forward to deploying similar nonpersonal promotion activities. And so we're going to look at a combined effort of both personal promotion to reach hepatologists and nephrologists as well as a digital approach.

I'm sorry, BJ, did you have anything that you wanted to add regarding Medicare?

Yes. I just think for Medicare, just to put it in perspective, again, I think we had mentioned that heart failure is a top condition targeted by CMS in general around this hospital readmission program that they have, and this is one of the top programs and top conditions that they look at. So I think it's really important that I know that most payers, Medicare payers are also looking for their star ratings through CMS. So this is really important. And so that's where we look at this as an opportunity.

In addition, most Medicare Advantage plans both bear the medical and the pharmacy costs. So in that case, they're enrolled as MAPD plans, and so they're covering both the pharmacy and hospitalizations. And so very focused on that. So I just wanted to give some sense of -- we are laser-focused on that. That's our population, and that's where we will go to ensure that those patients are covered and get the prescriptions needed at the time.

Our next question coming from the line of Serge Belanger with Needham & Company.

First one regarding the TAM for the product. I think on Slide 16, I think it's described as potential $5 billion. I also believe MannKind has discussed similar numbers. So just curious how we should think about potential peak sales opportunity? And what are the keys to capturing this large TAM that currently appears untapped?

And then secondly, again, I think MannKind is expecting an auto-injector product approval later this year. How do you think that will change the market dynamics? Is it just replaced infusion product or it really changes the overall market?

Yes. Let me start, Joe. Thank you for your question. I think as it relates to getting to the TAM to be aggressive, it's kind of the plan that we've laid out. Again, we have a very strong infrastructure. I think partnering. This is a -- heart failure is a smaller community as it relates to key opinion leaders. Nurses play a very large role in the use and decision of what drugs are being used as all -- as well.

And again, it's the leveraging of our overall infrastructure. We've already talked about what we would do from a health economics perspective, et cetera. But I think also the biggest aspect here is the product itself. It's very easy to use. It's very convenient. And as it relates to the auto-injectors, we need to hear more about that. I believe it's 5 pens that are necessary to dose, one that actually is launched. We also are working on an auto-injector. But keep in mind that, that's just, again, gives a physician choice of what they want to use.

We've heard from many key opinion leaders that we've spoken to already is that the ease of use of doing the spray in the nose is something that they've been waiting for, for a long time, this type of administration that makes it easy for a patient, get around the oral resistance, do the gut edema, et cetera. So that's why I would say as it relates to how we plan to aggressively go after this.

The last thing I would say before I turn it over to John to see if he has any other comments in that. We've been searching a long time for the right fit. We've said before that we want to make sure that we find a product that fits well within our portfolio that we can leverage our infrastructure and be successful right off the bat that will allow us to have something that's already launched and be accretive as soon as possible. And that's what's led us to the acquisition of Corstasis.

John, have I missed anything as it relates to sales or attacking the potential?

No, that was perfect, Sheldon.

Our next question in queue coming from the line of Paul Choi with Goldman Sachs.

Congratulations, Sheldon and team on the deal. A few quick ones from us, please. First, how are you thinking of time to peak sales? And how do you think about either peak sales or as a percentage share of the loop diuretic market? That's my first question.

And my second question is, can you maybe just update us on how you think on the access side, potential step edits might evolve? Do you assume that patients will have to go through a generic first prior to getting authorization for Enbumyst? Any thoughts or clarity there would be great.

Ben, do you want to comment on peak sales and timing?

Yes. I'd say it's early to draw a line in the sand in terms of peak sales, but I think there's plenty of IP space in terms of us being able to maximize the value of this drug. We think that this is a large market. We think we've shown the ability to execute in a large market, and we are well poised to capitalize on the opportunity. But we're optimistic that there's a good opportunity here to capture a significant portion of the market given the considerable competitive advantages that Enbumyst has over all the other players in that market.

Thanks, Ben. BJ, do you want to address step edits?

Sure. We -- again, I just want to give credit to Corstasis as they really have done their homework prior to with payers as well. In this particular case, I mean, these are sick patients. These are heart failure patients. So they have been on oral meds. They have come into the hospitals again for readmission. So we don't anticipate step edits to be any different than the current products out there.

And really, again, we'll go back to this readmission rate that we keep talking about is for those patients to be readmitted at $12,000 a pop, they really want to make sure that these patients have an at-home option. And so again, step edits from what we see and for Corstasis early work, seem to be normal and where you would think they would be with oral generics first and then taking them at home and then going into the hospital. And then now this provides that at-home option.

I'm showing no further questions at this time. I will now turn the call back over to Mr. Sheldon Koenig for any closing comments.

Great. Thank you very much. Again, I just want to emphasize that today is a very important day for Esperion. I'd like to say that we're really changing what this organization looks like, now entering into large -- 2 large therapeutic areas, our bempedoic acid franchise, which has been very successful, and we'll continue to make it successful. And now with the addition of Enbumyst and the fact that we also have global rights to Enbumyst, again, really changes the way to think about our organization as a global organization. And we'll come back to you in the future as it relates to our plans outside of the United States.

Again, the goal of the Enbumyst therapy is to reduce admissions and readmissions to improve outcomes and lower the cost of care. This is a very high unmet need area, and we're proud to be a part of addressing that need. Again, I want to thank everyone for their questions today. We look forward to continuing to update you in the future, and have a great rest of the week. Take care.

This concludes today's conference call. Thank you for your participation, and you may now disconnect.

Great. Good afternoon, everyone. My name is Jess Fye. I'm a biotech analyst at JPMorgan, and we're continuing the 44th Annual Healthcare Conference today with Esperion. So first, you're going to hear a presentation from the company, and then we're going to have a Q&A session after that. So for everyone in the room, when you have a question, just raise your hand so someone can bring you a microphone for the webcast. And if you're listening online, you can submit questions on the portal. I can ask them up here.

So with that, let me pass it over to Esperion's CEO, Sheldon Koenig.

Great. Thank you, Jess, and good afternoon, everyone. On behalf of Esperion and all the employees that work there, it's always a privilege to be here at the JPMorgan Conference and really appreciate the time to talk about our Vision 2040. And really, what it's about is executing today while building for tomorrow. So what has got us here, first, forward-looking statements. I won't read all of these, but they're on our website, should you want to read them.

Esperion at a glance. Right now, as you know, we're commercializing NEXLETOL, which is bempedoic acid and NEXLIZET, bempedoic acid plus ezetimibe. We're in a very strong financial position. We hope to reach sustainable profitability in 2026. We have durable cash flows, a strong balance sheet and a very attractive P&L profile. Our partnerships and pipelines will dive into deeper in this presentation. As you know, we are working on the triple combination. I'll cover that in depth later.

But as a reminder, it's essentially NEXLIZET plus a low dose of atorvastatin and a low dose of rosuvastatin, which gets to an LDL efficacy of anywhere between 65% and 71% there's actually a Phase IIa study that actually demonstrates this as well. ESP-2001, we first talked about this last year at our R&D Day. This is a drug for the indication of primary sclerosing cholangitis. This is an orphan disease, very much unmet need. I'll go into the specifics of this drug and where we will be in 2026 with it.

And then also just other discovery programs, our kidney program, et cetera, which we'll discuss more in the second half of 2026. But what got us here? Well, we have a multiyear proven track record of execution. And I just said to Jess and maybe a bit of a chip on our shoulder, but I'm going to say it again. This is the first JPMorgan in about 4 years where we've come, and there's no overhang. There's no convertible debt. There's no RIP agreement, et cetera. There's no worry about cash. This is all about how do we execute and build a bigger and stronger organization. That's being done with a consistent U.S. commercial execution, our global partner execution with Daiichi Sankyo in Europe and the recent launch of bempedoic acid in Japan by our partners, Otsuka.

We've demonstrated disciplined financial management, and we will continue to do that. And our pipeline execution is a result of the fact of the growth that we've been able to demonstrate with our bempedoic acid franchise, we can spend some time and investments in our pipeline. And it's really created a very strong year for us.

Let's go over the results quickly. Again, from a U.S. perspective, and we issued a press release this past Sunday where we preannounced. And when we look at our U.S. net sales, we talked about a range of $156 million to $160 million. Total revenue of $400 million to $408 million. Our retail prescriptions equivalent grew 34% year-over-year. And our preliminary cash currently is $168 million. I would dare to say that not many companies are putting up numbers like this regardless of what therapeutic area they are in, and we're extremely proud of the growth that we've demonstrated. This has been the strongest year in Esperion's history. And it's really driven by our commercial execution.

Our commercial execution drove significant growth. You see a little button on the right side, can't take a statin, make NEXLIZET happen. Just so everybody knows, statin intolerance is not just the inability of not taking a statin. Some people don't want to take a statin, some people can't take a statin because of muscle ache, et cetera. But some people can take a statin, a low-dose statin, and we can either be [ losed ] alone for those cases or people who are taking a statin, they can use NEXLIZET or NEXLETOL.

This is a large unpenetrated market of over 70 million. And keep in mind, when the CLEAR Outcomes study came out in 2023, and we received our label -- actually in 2024, and we received our label in 2025. It expanded our TAM from 10 million to 70 million patients. This is one of the largest markets, one of the largest therapeutic areas that's out there.

And how did we achieve such success? Well, our growing adoption, 34% growth, retail prescriptions year-over-year. we've shown 25% year-over-year growth in physicians writing the drug. Over 45,000 physicians now write this drug, and we have broad payer coverage. We have 90% coverage in commercial, 90% coverage in Medicare. It's all preferred, and we are not disadvantaged to any other lipid-lowering therapy. And the reason for that was the robustness of the CLEAR Outcomes study.

And so a year-end review, if you just take a look across of the pillars, our U.S. commercial growth, again, I've talked about the range, our market exclusivity, and this is important, we had 4 ANDA settlements last year. The largest one was Dr. Reddy in September, where all of these generic filers have settled for the year 2040. Now there's 5 others that remain, and we're currently in discussions with them. The only thing I would say is we feel very confident, hence, the reason for Vision 2040. We're planning beyond 2031. We're planning for the next 14 years to continue to make our #1 priority, NEXLIZET and NEXLETOL stronger. I always say high tide floats all boats that allows us to make investments in other areas such as our pipeline advancement that I mentioned earlier.

Also from a global expansion perspective, again, Japan just recently launched. I can tell you they're off to an extremely good start, and they've only been in the market for 1 month. We signed partnerships with HLS in Canada, Neopharm in Israel and CSL Sequirus in both Australia and New Zealand. All of these markets to launch by the end of 2026. And our partner milestones, we've received over $91 million in partner milestones this year. Just a quick side note in our total revenue, if you remove milestones and adjust on a like-like basis, our total revenue grew 60%, 6-0, 60% year-over-year.

So with that said, it's time to build on the future. Our Vision 2040 is grounded in proven execution and defines how we scale Esperion into a global multiproduct pharmaceutical company. How are we going to do that? It's really built on 3 building blocks. We're going to move from execution to ambition. Again, 2040 is 14 years from now. That's a long time, and it's our runway to allow us to be a bigger organization. Our #1 priority, as I mentioned, strengthening and expanded the bempedoic acid franchise. We believe this is a $1 billion opportunity in the United States. We know it's a $1 billion opportunity in Daiichi Sankyo in Europe. And just as a fact, we think Daiichi Sankyo will achieve $500 million sales in euros by the end of 2026, early 2027. So they're well on their way.

Build a diversified multiproduct portfolio, and I'll go into depth with this a little bit later as I go deeper into each one of these building blocks. And of course, advance the next-generation ACLY pipeline. Our ambition is to achieve at least 5 marketed products by 2040 through a combination of business development and internal pipeline advancement. And when we speak about business development, what we speak about is how do we leverage our infrastructure and help companies who have an asset who are unable to market or commercialize the product on their own because they don't have the same type of infrastructure that we do.

We've spent a lot of time building and fixing this company. And trust me, we're not going to do anything to ruin that. We're not going to do anything that would cause dilution, et cetera. We're looking at smart ways to bring in assets to help, again, make us a stronger organization.

So let's focus on the first building block, which is strengthening and expanding the bempedoic acid franchise. Really, if we take a look at what are the major catalysts, the biggest one that's going to come into play is going to be by the end of February. These are the new U.S. guidelines that ACC/AHA will be coming out with. I want to remind everyone, if you haven't had a chance, please take a look at the ESC guidelines that came out September 4 of last year, where bempedoic acid was essentially viewed as a foundational therapy in lipid-lowering therapy.

Essentially, no longer can you use one agent to get to goal. Similar to hypertension and diabetes, it's all about combination therapy. And what the European Society of Cardiology said in their first late-breaking session to start off the meeting was the reason why bempedoic acid was added to the guidelines was due to compelling and practice-changing data. That's the CLEAR Outcomes study, 14,000 patients, which shows that we have a 27% reduction in fatal and nonfatal MI, 19% reduction in revascularization. And if you look at primary prevention, your time to a first event reduction by almost 40%, 39% to be specific.

We will, of course, as I mentioned, continue to deal with the market exclusivity and the ANDA filings. Our commercial investment, I'll give guidance later, is steady, but we believe we have found the right balance between personal and digital promotion, and we do ROI analysis on every dollar we spent from a commercial perspective. Oral triple combination will be a game changer. And let me dig a little bit deeper into that right now.

I've already talked about what the LDL reduction could be. I'll say it again. This has the opportunity to be a game changer from a perspective in one pill, you have the most efficacious LDL-lowering drug and a physician has the choice of either using NEXLETOL on their own, NEXLIZET or going to these combination therapies. Just as a quick aside, this is a regulatory pathway that is essentially bioequivalence and stability. And our hope is that we'll launch these products sometime in the second half of 2027.

And what's really interesting, and I think what really ties up the strength of our franchise is when people think about Esperion, they think about us as a U.S. company. I want you to change your mindset. I want you to think about bempedoic acid is a global franchise. What this cartoon demonstrates is where we've been present. I've mentioned many of these countries already. I've talked about what Daiichi Sankyo has been doing, Japan off to a great start. Israel is a small market, but nonetheless, they'll be launching this year. Australia and New Zealand is some significant opportunity, and Canada is a very large market.

Currently, today, we are approved in 41 countries. And a side note, all those approvals, all the regulatory aspects, et cetera, were done by the regulatory department at Esperion. So I always want to say congratulations to them because that's a lot of the work, and they did a great job.

Now let's move on to building a diversified multiproduct portfolio. And what do we mean by this? So we want to grow our portfolio through partnerships. And I'll direct your attention to the cartoon in the center. We're really focused on cardiometabolic assets. What you see here are just a few, heart failure, lipid management, obesity, I would even put diabetes in there. And then we're also looking at areas of kidney and rare and orphan disease, and that also complements the work that we are doing at our pipeline.

Why are we doing this? What does this mean? Well, we're leveraging our established U.S. commercial infrastructure. I've always said this before, we're not as big as a Merck, a Sanofi, all companies I worked at, but we have functions that those companies do. We just do it at a smaller scale, and we've been very successful in doing it. We're not looking for multibillion-dollar acquisitions. We can't afford multibillion-dollar acquisitions. We're looking for acquisitions that make sense, financially affordable, nondilutive and will be accretive immediately.

And when I say accretive immediately, I don't want my Chief -- new Chief Commercial Officer, John Harlow, to get scared. But if we do a deal on Wednesday, I want to start selling it on Thursday. That's what we're looking for. We're looking for assets that are either close to approved, are approved, nothing that's in the clinic. So stay tuned. We've been having a lot of conversations with organizations. We've screened a lot of organizations. We passed on many products. We're taking our time. We want to make sure we find the right one, and I'm certain that we will.

And then the last building block, if you will, is really advancing the next-generation ACLY pipeline. And I want to spend some time and just talking about what we're doing from an R&D perspective. We're leveraging the world-class ACLY platform to expand the pipeline. And how we're doing that is, again, our partnership with Evotec, with Steve Pinkosky, who's in charge of Research and Development at Esperion. He is doing a lot of work in virtual screening. He has a lot of knowledge, and that's allowing us to do a lot of high throughput screening.

The 8 million compounds that you see is not an exaggeration. We literally have been using artificial intelligence through our partnerships in order to screen what are some compounds that really make sense. And we've gotten down to the point where there's 500 compounds with different indications that we're looking at, whether it's in liver or in kidney. And we've developed and we've come up with some multiple lead compounds. I want to focus on one right now, and that's primary sclerosing cholangitis, PSC, a unmet need driven significant market opportunity. If you haven't seen the R&D Day that we conducted in April 24 of last year. I would encourage you, it's on our website. It's about 4 hours long.

But what's nice about it is it's a mix of key opinion leaders, our science and patient testimonials. And there are several patients, one of which who's needed 2 liver transplantations. There's another patient who's a teenager. I can tell you, ever since we've done that R&D Day, we have gotten letters from family members, either has a sister, a daughter, a brother, is there any way I can get this drug now? Is there any way I can help in the studies, et cetera? Obviously, we're very early. We don't have a drug yet, and we're still going through initial studies. But that's why we're here. This is the type of work that we do in biotech, and this is the type of work that we're doing at Esperion.

There's currently 76,000 patients who are diagnosed both in the U.S. and Europe. On an annual basis, and this is greater than a $1 billion market opportunity. There's really no approved therapies that actually address the disease or the injury at the liver. And we feel, based upon our mechanism, we actually do address the disease and potentially could save off liver transplantation and potentially extend life. So where we are currently from a program perspective is we'll have some data coming out in the summertime, and this is data that will allow us to go to IND. And our hope will be that we will be in the clinic before the end of 2026 with ESP-2001.

I want to give everyone just a quick transition, our operating expense guidance. Again, we're not giving revenue guidance, but our operating expense guidance, full year R&D is $40 million to $50 million. Our 2026 SG&A, $170 million and $195 million. Our OpEx overall guidance, $210 million to $245 million. This reflects, of course, our continued investment in U.S. commercial execution. If there's one takeaway I really want folks to have, that is not only will we be a successful company in the years to come and continue to grow, the only way we can do that is to invest and grow the bempedoic acid franchise, our #1 priority. These dollars also support ESP-2001, our development of the triple combination and maintains focus on our investment spend and return on investments.

So to summarize, again, from execution to ambition, it's focused on 3 building blocks: strengthen and expand the bempedoic acid franchise. We're doing that by showing year-over-year growth, quarter-over-quarter growth and double digits, almost in every single category. Build a diversified multiproduct portfolio, bring in a product that will be accretive immediately and picking the right one and advance our next-generation ACLY pipeline.

This is the team, and I want to congratulate all the folks that are on this slide for working together, persevering for the last couple of years to get us to the point that we are, which, as far as I'm concerned, is a monumental success. And with that, just quick safety information because I showed a button of can't take a statin and make NEXLIZET it happen. Everyone quickly read that, and we're ready to go for questions.

Great. Thank you. So as a reminder, if there's a question in the room, just raise your hand and someone will bring over a microphone. But maybe I'll start just on the commercial side. I was hoping you could expand a little bit on your top commercial priorities for 2026 and how you're going to measure success?

Yes. So our top priorities really are obviously to continue the momentum that we started in 2025. So we're going to continue this growth. A couple of things that we are doing. We've actually expanded our personal promotion to go from 20,000 to 40,000 physicians now. This is a mix of both primary care and cardiologists. Our digital footprint, we're actually expanding. We were targeting 60,000 physicians. We're now going to 80,000 physicians. Just a quick fact, we've noticed or we've measured that 25% of physicians that are just contacted via a digital asset. So an e-mail or a banner ad, they've written the drug without personal promotion. So it really speaks to the fact that we have found this balance between personal promotion and digital.

The other thing that's really going to help us is the guidelines that come out. For once, it's not going to be us just talking about the benefits this product is and how well it works, but it's also going to be third-party guideline writers.

And just as an a quick aside, I can tell you that after the European Society guidelines came out, 4 days after that, our representatives had a detail aid where they were allowed to go and educate physicians in the U.S. to show what they were doing in Europe. And then just as it relates to our investment, we're always looking at different areas within our investments where we can either dial up or dial down because we do return on investment of every initiative that we do. And if we see something that's working better than something else, we'll divert dollars there.

You talked about expanding the sales force in '26. What is your view of the optimal size and structure to maximize reach, especially in primary care?

Yes. So right now, we have 155 sales representatives. We have 15 reimbursement managers, 1 per region. We have 15 regions. And we are currently assessing where we need to either add or maybe even dial down in some situations where territories aren't profitable. Once we do that, we can decide what is the real add. But we're currently in that process. I think right now, we believe we have the optimal size sales force. And there could be some areas where there's large windshield times where we could add another representative, et cetera. But it goes back to that right balance. We have found the right balance between personal promotion and digital promotion. I won't mention company names, but we look at performance on a 13x 13-week basis. And there's companies out there selling lipid-lowering drugs with bigger budgets than ours, and we've been outgrowing them on a 13x 13-week basis because I think we have been very smart about how to apply these dollars, where to send digital targeting versus personal promotion.

What are you seeing right now in terms of prescriber mix of primary care versus cardiology or other specialties? And how do you see that evolving?

Yes. Right now, it's about 50% primary care physicians, 40% cardiologists, and there's a 10% other. There's endocrinologists and some other mix. That's about right. I mean if you look at ezetimibe, Zetia, the branded name as an analogy, it was about 60-40, 60% primary care, 40% cardiologists. That was more a function of just the amount of primary care physicians there are. And it's good because primary care physicians feel as though they can control and manage the patient without having to do a cardiology referral. So that's the mix right now. It was kind of 50-50, and it's starting to move a little bit.

Got you. You mentioned kind of digital marketing. Can you talk a little bit more about sort of patient activation in addition to prescriber activation? And what are the next steps in that area?

Yes. So based upon the success that we had this year, we decided to go and activate consumers, and we did that in 2 ways. One, we started a non-branded consumer website. And then we also started to do essentially direct-to-consumer advertising, but not direct-to-consumer advertising that you see on national TV, we did it through connected TV. So Hulu, Netflix, et cetera. I think we've driven close to 3 million consumers to our website since we've done direct-to-consumer. I might be off a little bit on that number, but it's somewhere in that area. The impressions we are looking for were 18 million impressions. In October, and we don't have the final numbers yet, we are already above 6 million impressions. It's a 60-second non-skippable commercial. And when we did market research, we found that 75% of the people watching it did not try to hit a skip button, which was important. 25% did. But 75% is a pretty good number.

So we're going to continue to looking at activating consumers in different ways. There's different strategies that we can do. And so when you think about it in whole, we're really looking at all the segments. We're activating physicians. Obviously, we're working with our payers to get access. We've done that. We're working with consumers so that they'll think about their health, go to a physician, ask about this drug. Whether we like it or not, statins are the foundation of therapy. And I should say whether we like it or not, a lot of people don't want to take a statin, don't like statins, really are looking to address their cardiovascular health, and this helps educate them as well. There's a reason why cardiovascular disease is the #1 killer in the world. And if we can be a part of the solution, so that's not, we're going to try to help educate physicians or patients as well.

Question from the audience?

So my question is on manufacturing responsibilities of bempedoic acid. So how is it split between yourself and Daiichi? Is Daiichi responsible for both U.S. and non-U.S. markets for manufacturing? And the second question related to this is that we do see COGS a bit on a higher side. So is there scope for gross margins to improve from here on?

Yes, great. I actually think that might be one of Jess's questions, too, so I can answer that now. So we do all the manufacturing. We do the manufacturing for Daiichi Sankyo and Otsuka. I think what you're potentially referring to is the tech transfer that we agreed upon. We just actually had a meeting with Daiichi Sankyo this morning about the progress of the tech transfer. Currently, they have approval and they will start manufacturing NILEMDO. NILEMDO is NEXLETOL, that's bempedoic acid on itself. And NEXLIZET, they should have approval by the end of the year to manufacture that.

Now with that said, also, we do want to make sure that they're manufacturing quality product, of course, et cetera, it's important for us. And we've been working with them closely. Should that schedule persist, we're going to see a vast improvement in our gross margins. We're going to see a decrease in our working capital, and we're very excited about that. So we're working with them closely. The question is timely because 7 a.m. Pacific Time, we had that meeting with the Head of Manufacturing and Marketing, and we feel really good about where they are in the process right now.

Maybe coming back to commercial and specifically kind of on the access side. So you've talked about how prior auth and reimbursement barriers have largely been addressed. What, if any, are the remaining hurdles to broader adoption? And how are you supporting prescribers and patients to ensure frictionless access?

Yes. So let me start first with the access. I mentioned this briefly. We have 90% access with Medicare, 90% in commercial. The split of the 2 is approximately 50-50. I can see Medicare probably growing a little bit more. Prior authorizations were the largest headwinds for these products before the CLEAR Outcomes study. In order to get bempedoic acid, it used to be you had to go through multiple statins and ezetimibe. One of our biggest ambitions and it worked was when we had the CLEAR Outcomes study, which were presented in April 2024, label 2025, we went to payers and we said to them, you need to change your prior authorizations, otherwise, we won't pay rebates. What does that mean? You've got to remove the step edits. And we gave them until June to do that, and they all did it.

And so we actually have a detally that actually says getting NEXLIZET or NEXLETOL has gotten easy or it's never been easier than now. The co-pay, I think one of the biggest misperceptions is with Medicare and our competitor has done this, I think, with Medicare, there's a thought that the co-pay is $138. It's actually only $35 in Medicare. And so we're making sure we educate physicians on that. But there are some plans, SilverScript, Caremark, Aetna, there's no prior authorization at all. You can write the drug. And that's very unusual for branded products.

So I think the biggest challenge for us is still the education of what the perception of price is and what the real price is, and we've got that handled. But for us, it's just about greater pull-through. It's getting out there, getting to the right physicians and pulling through more. The average physician is writing more NEXLETOL and NEXLIZET than they ever had. It used to be somewhere in the 1.5. It's above 3, approaching 4. And we'd like to see that depth increase. We're seeing the breadth increase. We want to work more on the depth increasing. And we think post guidelines, we're going to see that.

1.5 going to 3 and from there, what is that metric?

That's just looking at number of prescriptions that they are writing on a weekly basis.

Okay, weekly.

Yes, weekly. Yes. There was a question right here.

What's going to be the effect on the oral PCSK9 now that Merck has voucher.

Can you repeat the question?

Yes. So I'll answer on behalf of Merck, a company I used to work at. So yes, they could be on the market, obviously, this year. They pretty much have publicly have stated they're going after injectable PCSK9. Rob Davis, their CEO, actually put out a message on LinkedIn that specifically said that. I think the biggest drawback for that product is the fasting. Remember, these are chronic asymptomatic therapies, and you can't see your LDL lowering and you can't feel it. And I know personally, when I wake up in the morning, I'd like to drink coffee and have something to eat, and I like to eat something before I go to bed and I don't sleep 8 hours, and so I can't take the drug. So that's, I think, going to be the biggest issue for the drug is the fasting.

More importantly, though, their outcomes. The ticket to the game in cardiovascular medicine is outcomes. And that's one of the biggest hurdles we faced until we had the CLEAR Outcomes study. I went through all the reasons and how we've overcome them. So their outcomes, the CORALreef study won't be available until late 2029, early 2030, and we can talk about it then. So...

And then what about if the Lp(a) takes off as a major diagnostic gets covered and everybody gets screened for Lp(a)...

Yes. I mean, personally, I just got screened for Lp(a). So let's just talk a little bit about Lp(a). Lp(a) is genetic. You can't really modify it via diet or exercise. You can keep doing that, but it's not really going to have an effect. Keep in mind, if you take a look at the study for both alirocumab and evolocumab, so ODYSSEY and FOURIER, they both had comparable Lp(a) reductions, not too far different than the new Amsterdam product as well, and they had no effect on residual risk reduction in their outcome studies.

So I think the biggest question is how modifiable is it? That's the question that all the key opinion leaders are saying. In the key opinion leaders I've spoken to, which is a lot of them, I think it's 50-50, 50% think, yes, maybe there's something that can be done 50% that can't. But I think something that can be done that is recognized as a marker by AHA is reducing hsCRP. And I want to remind everybody that bempedoic acid reduces hsCRP, a marker for inflammation by 36%. We know atherosclerosis is an inflammatory disease. And we have a drug that we know if you modify hsCRP, it helps. We think that's why we have the results that we have from the CLEAR Outcomes study. But the jury is still out for Lp(a), and we'll have to wait and see. We have no effect on Lp(a).

Can you give us an update on your Otsuka partnership in Japan? Like what's the status of the launch there?

Yes. So Ben and I actually just came -- and Patty, we actually just came back from Japan, and they've been on the market for a month. I can't say what Ben has been saying to investors, but it's been robustly positive. I mean they have done -- in a month, it's amazing how much they've sold. And in Japan, you're limited in the first year of how much product you can actually sell. It's more of a government rule. They have over 700 people in Japan that are marketing and selling this drug. They're very committed. Japan is the third largest lipid market after the United States and Germany. And so a great partnership there. They'll be embarking on the pediatric study soon, which could give them an additional 2 years of patent exclusivity as well. So they're highly motivated and they're doing a great job. And keep in mind, we have a royalty stream that tiers from 12% to 30% with them as well. So it's another stream of revenue that comes into the organization for us.

So you've talked about transitioning to sustainable profitability. With that in mind, what are your priorities going to be for capital allocation?

Yes. So we gave our guidance earlier in the presentation, and we don't see any type of deviation from that. Again, we're being very diligent in our spend. And the goal is -- it's not the only goal. We have a few goals this year, as you know, but the goal is to reach some type of sustainable profitability in the 2026 time frame. We're almost there. We're close. And again, that's a big turnaround considering where we were when you and I first started asking questions 4 years ago. So we feel good about what we've achieved, and we'll be sure to update folks on a quarterly basis.

So maybe asking it slightly differently. let's assume you get there and the company is generating cash, then what are you going to do with it?

Yes. So I think what we want to do there is really focus on our pipeline and also are there potential other assets. Again, keeping in mind, we put a goal out there of having 5 assets by 2040. If you're counting NEXLETOL and NEXLIZET counts is 1, PSC should it makes it counts as 2. And so 3 more to go. If there's something that we could bring in sometime soon that again would be immediately accretive, there's 3, and we'll see what happens over the next 14 years.

But I think it allows us to reinvest into also the bempedoic acid franchise and continuing to make that bigger. There's things that we can do from a life cycle management perspective that we have a lot of ideas as it relates to bempedoic acid and even combination therapies with other products. So it's something that's on the drawing board. And once we get there, we can think about how to prioritize them.

So over the course of the week, we've heard a number of companies talking about how they're hunting for assets. So how do you position Esperion to compete for assets with other companies that want to acquire as well?

Yes. A lot of the companies are bigger companies with a lot of money to spend. Some of those -- we had someone today saying that they can do acquisitions up to $1 billion to $2 billion. We're looking at -- there are some companies out there, and there's a lot of them, and we don't have time to go into all of them today. They have 1 person, 3 people, 4 people. They have a product that could potentially generate $30 million, $40 million a quarter. And these are not the companies that big pharma is interested in or midsized pharma is interested in. If anything, some of these companies have products that big pharma discarded and these companies took them and develop them. And so we can play in that area, and we have support from people that would say, hey, if you ever need any help, we could help you, et cetera. But we're not looking for things that are large. We can only afford so much, I guess, is the best way we could say it. And we're not going to do anything that would cause dilution to the organization to bring something on either.

Maybe thinking about the pipeline, what are the next milestones the Street should be watching for? And how are you going to communicate progress on the pipeline?

Yes. So in the June, July time frame, we're somewhere around bio. We hope to have 2 final tox studies done on PSC. And so we'll be -- we're having lots of discussions. We've had a few of us meet with investors this week. We've had 2 people, Tony and Patty, who are in the audience going to different companies are interested in our pipeline, and we've been updating them of what's happening. But as soon as we are IND-enabled, we'll be issuing a press release on that. And we hope to, again, be there sometime late 2026. And also during our quarterly earnings and so forth, if there's updates, we'll make sure we talk about it.

So maybe just the last one. You're talking about a Vision 2040. How do you see this company kind of evolving over time?

How I see it over time is something that's going to be very exciting. It's a company that is going to continue to grow the bempedoic acid franchise, make investments in our pipeline, conduct our business development. It's a company that's going to get larger. And I think that's what's exciting about it. You and I talked right before the conference or right before the interview that this company a few years ago from a capital structure was in pretty bad shape.

This is the first JPMorgan where we've come where there's no overhangs and we can really focus on execution and building this to a bigger company. And then the question is strategics, et cetera. We have to operate the organization as though we're going to be on our own, and that's what we're doing. I do think though we're creating something that's very exciting that's going to capture the interest of many people as we continue this march forward.

Great. Great. So we'll stop there. Thank you.

Great. Thank you. Thank you, everybody.

Good morning. Welcome to the Jefferies London Healthcare Conference. My name is Dennis Ding, biotech analyst here at Jefferies.

I have the pleasure of hosting Esperion Therapeutics and CFO, Ben Halladay here. Welcome.

Thank you for having us.

So before we kick it off, why don't you make some opening remarks in terms of just the progress over the last several years and importantly, what has happened this year, some of the accomplishments? And then how you're thinking about 2026?

Yes. There's a lot to unpack with that question. I'll do my best to keep it minimal.

So I'll go back to April of 2024 when we received our cardiovascular outcomes trial updated label, which really kind of took the shackles off for how we could sell this drug and set up the uptake on that. It was a pretty watershed moment for the company, took our addressable market from about 10 million patients to 70 million. It's been really exciting since then. We've shown double-digit growth quarter-over-quarter. We've had on the heels of that major payers to the reimbursement landscape. We've gone from being a drug that was kind of a niche product in a smaller population to now what has been described as one of the most broadly labeled cardiovascular drugs out there.

So we've really hit the ground running with that label update. Since then, I think we're showing that demonstrated growth. We're showing the progress against the payers that we would like to have. Selfishly also, we've done some really great work on the capital structure. We've been able to rightsize a lot of the debt that we have had in this company. And I'm happy to say with our $55 million stub, that has also been paid down. So we will end this year with less debt than we went into, which is kind of my goal every single year.

And yes, it's really a great story that I think even though it's been phenomenal progress in the last year, the best is yet to come. We're looking at really down guidelines updates in early next year. This is the first time that we will have bempedoic acid in the new guidelines in the United States, and that's coming off the heels of spectacular guidelines in the European Union that candidly could not have been better had we written them ourselves.

So it's an exciting time for Esperion. And yes, we've shown some really great progress over the last year. But I think the next year is -- the best is yet to come, let's put it that way.

Yes. And then maybe you can elaborate a little bit more on the guidelines and what's coming in the U.S. I feel like over the last several years, we've just been waiting for guidelines to get updated.

It's been a [ long wait ]. Yes.

Finally coming in early '26. So talk about what you expect there? Do you think that it will look in line with the European guidelines that just got updated? And just how much of a tailwind do you think it will be for the U.S. business?

Yes. I think, so a little bit of context. In Europe in September, ESC published their new guidelines, which gave bempedoic acid a Class Ia recommendation pretty much across the board by itself in combination. And the reason they did is because they put us in the same class as someone who has demonstrated benefit in both clinical and practice to show a reduction of cardiovascular risk, which is a very, very strong recommendation. We've been saying this for a while, but it's nice to have that external validation.

When we look to the U.S., we expect guidelines to come out early 2026. So January, February time frame, they'll be published with ACC being the training ground for those guidelines. And I would expect in the U.S. that those guidelines would be pretty similar to Europe. There was kind of a disconnect the last time they put guidelines out, and it caused a lot of confusion, we'll put it that way.

And so I think there's a strong push to make sure that they're very similar between both the U.S. and Europe in terms of how they're recommended, where drugs are placed and where we fit in the formulary. So even if they're half as good as Europe, we'll be in great shape, but we expect them to be very much in line with what we saw coming out of Europe.

Over the last few years, how much of a barrier has it been in terms of the guidelines, not including bempedoic acid? And do you think that this update will significantly unlock that potential there because there are millions and millions of patients in the U.S. with high cholesterol, right? Relative to your revenue base, which is growing double digits, which is great, but there's still a huge spread. So like how much of that opportunity do you think will be unlocked from these updated guidelines?

Yes. So as far as a barrier up to now, I wouldn't really call it a barrier. Where it really helps you is with the market access on the payer side, but we have a spectacular market access team that got us on that formulary and got us in that good placement even without the guidelines.

So it helps us hold that position. It maybe helps us clean up some of the prior authorization and formulary. We're down to very few plans with a step edit it might help us there. But where it really helps us is on the awareness, to your point.

If you go back to ACC 2023, when we announced the results of the cardiovascular outcomes trial, pre-label but when it was published, we saw almost a doubling of our adjunct share overnight because of that awareness from it. And I think having the guidelines update is -- it's a similar awareness event in that -- we're now front and center. And when people go to reference those guidelines, it's a simple choice.

Okay. And I remember the story over the last 12 to 18 months has just been around updating the UM criteria in the U.S. Are we there yet in terms of -- or are you guys there yet in terms of getting where you want to be in terms of access? How much room is there left going to 2026? Or is 2026 just more about execution and penetration into this market?

Yes. 2026 is 100% execution. And I'm actually joined here by John Harlow, new Chief Commercial Officer. And so I keep saying it's a John problem, execution. But no, it's entirely pull-through of those changes that we made to the managed care side this year and the second half of last year. So I've never seen a drug with better positioning and better access than this drug.

The prior authorization process went from being the most burdensome barrier to any physician getting this to it's now just an afterthought. We have field reimbursement managers out there even helping in the situations where you do have a prior authorization. And our approval rates went -- we're in the high 80% for the majority of our plans in terms of an approval rate, which, in my mind, is unheard of.

So from an access standpoint, I would say we're done. We've got it in place. Now we are at the point where it's about pull-through of those plans and making sure that we can give the physicians the confidence that when they know when they prescribe it, they'll get it. And I think we're there that we can start having that message out there.

Okay. Can you go into a little bit more detail in terms of where bempedoic acid is being used? Whether it's from PCPs or cardiologists, has that mix shifted over the last 12 months as well as just comments on like which types of patients are getting bempedoic acid?

Yes, it has shifted, and I think a lot of it comes from that label update now the prior April, given the sort of broadening of that label and the inclusion of statin intolerance. That was the key update to the label that we had.

And so with that, we saw a shift from a majority cardiologists because prior to that, we were strictly ASCVD patients. Now it's anyone unwilling or unable to take a statin. And we're, I think, now at 60% primary care, about 40% cardiologists. And I would expect to continue to see that trend shift towards the primary care just given the type of patient we're going after, right? It's statin intolerant.

We have -- our tagline that we use with physicians is after a statin, we're next. And plays on the names, it's very catchy. People like it. They were buttons about it. So I think with that, this is a tool that primary care physicians have wanted and have needed for a while because prior to us, your option was ezetimibe, which is not very favorably seen, has low LDL-C lowering has no outcomes benefit. But when used in conjunction with us, really can accelerate the benefits or PCSK9, which primary care physicians tend to have to refer to a cardiologist for so they lose the patient.

So this is something they've been clamoring for. This is something they're excited about. And that's where a lot of our focus has been given both the new label and the primary prevention of cardiovascular events in our label.

How does your commercial team or sales force -- like how does it look like right now, given that it seems like the focus will be on PCPs going forward. Remind us how many reps you have? How many reimbursement managers? And do you plan on kind of expanding that or doubling down going after the PCPs?

Yes. So we have 155 sales representatives and 5, what I'll call key account managers, and that's -- their reps that kind of provide double coverage in some of the key territories. So we are looking at expanding that out given the fact that we have guidelines coming out in the next year, we really want to capitalize on that event.

What that number exactly is, we're still figuring out internally. But I mean, there's a huge opportunity here. And I'll point out on top of guidelines, we also have had a lot of successful patent wins over the last year, which we think can also give us an opportunity to drive peak revenue longer, higher, better.

So we're looking to expand past the 155. What that exact number is, like I said, we're not -- we're still figuring out internally. But even with the 155, we reach about 70% of the target market from an in-person personal marketing standpoint. And then with what is a very successful digital campaign on top of that, we're able to get that up to, I think, about 90% coverage of the potential market that this drug can be in.

And when you say 70% covered, what do you mean by that? And like how sensitive is this market to, I guess, repeat visits from a rep? You know I mean?

So 70% of the potential patients that are out there. And we've seen -- this is a very promotionally sensitive market. So having those repeat touches, and that's one of the reasons why we're looking at expanding to have more frequent hit points with a rep or with the digital hits because we've just seen phenomenal ROIs on that.

But yes, it is very promotionally sensitive. There's a lot of touch points. But candidly, this is a drug that every physician should be writing every week. And that -- those frequent touch points help drive that.

Can you talk us through just the rationale or like maybe some of the pushes and pulls behind expanding the sales force, right? You said you have around 150, 155 right now, but like how do you think about expanding it to like 175 versus 225 or 250, et cetera? Like how are you thinking about that?

So we look at -- I go back to ECON 101 here. We do look at a marginal return on the sales reps, and we have a pretty robust model in terms of how we look at each incremental rep gives you certain incremental percentage of that target audience.

And so we can really definitively say where does that marginal return crest and that's where we target. And the one thing that we do, given the updates to the coverage and given the updates to guidelines, that potential is higher, which is kind of why we're relooking at it now. So we'll take a good look at where that investment makes the most sense to top off.

Yes. And you can kind of sort of see where I'm going with this in terms of how do we think about the cost structure of the business today and then 2026. I know you probably won't give guidance in terms of OpEx today, but it seems like it would be incrementally higher than it is in 2025?

I think the keyword is incrementally, we're not going from 155 to 500 reps. I'll just -- let me say that very straightforward now. We're talking 30, 40 additional reps at most.

So it's a few million more. It's not doubling, it's not tripling. It's a manageable -- I mean, I think we've known each other long enough that I'm not someone that loves to blow up the spend rate here, and we'll always manage expenses accordingly. But it's something that I think will be reasonable, but we can definitively say we'll come with the incremental revenue that can justify it.

Right. And then to sort of tie into that, you guys talked about getting to sustainable profitability in Q1. Is that already kind of like baked into some of those comments in terms of the sales force expansion?

Yes. I think the sales force expansion is incremental to that as long -- same with the guidelines, right? When we started making the profitability statements, we had not even seen or had any idea what the European guidelines would look like at that point. So all of that has not been factored in, I think, is incremental to kind of some of the statements that we've made.

But yes, I mean, that's why I said the best is yet to come because we're -- we keep saying we're on the press becoming a legitimate company here. But yes, we will see a dramatic shift in being that cash burning company into one that's generating, I would say, pretty substantial return next year.

Okay. And then maybe talk a little bit about the Otsuka situation in terms of -- you guys got, I think, tentative pricing approval or final approval. So remind us of that situation and then the milestones that would be coming to Esperion?

Yes. So more exciting news over the course of this year. Japan received approval for bempedoic acid in their market in September, I believe, is when we got the formal approval of that. On the heels of that pricing also comes, which is the next big milestone for them.

We received tentative pricing a few weeks ago. I think we're waiting on the final approval. Along with those regulatory steps, there are substantial milestones associated with them up to $120 million we will put a press release out in the coming days that kind of gives the final number along with a launch update in Japan. We'll do it in conjunction with Otsuka. But yes, we're very excited about that. It's the third largest lipid market in the world. The pricing we got was very good, and we are very excited for what will come from that market.

Okay. Perfect. And then I would have to ask around just the competitive landscape here. There are many other oral therapies coming on to the market, whether it's a PCSK9 or CTAP inhibitor, et cetera. Just how you -- and I totally appreciate the LOE situation being more like 2040s, which is great. But how are you thinking about the market over the next, let's call it, 3 to 5 years for bempedoic acid?

A few different ways. One, I will point out, we are on the market now. We have an outcomes trial and a very positive outcomes trial now that is in our label with the payer access that we would expect to come from that.

So we're already out building market share and building that awareness. And the guidelines that I'll point to next year will include us. They will not include these new therapies. And the comment you made earlier about how it takes so long to get a guidelines update here that we can expect to be the only ones mentioned in guidelines for a while. So that helps.

I think on top of that, our competitive landscape is one that we're keeping an eye on, but frankly, don't feel super threatened by. Back at AHA this last month, I think the Merck drug published a lot new data that kind of reinforced our confidence on that one. I think the big thing, the LDL-C lowering is where we expected it to be. But they have a massive food effect that is, I think, going to have a big problem in the real world in terms of getting patients to adhere to that.

And we also learned it's not just food, it's also water. So not only can you not eat, you also can't drink in the fasting period for this drug. And the CETP inhibitor that's out there, I think we have a lot of question marks on that given the difficulties that class of drugs has shown, their data has been minimal that they've put out, but the data that we have seen just sort of reinforces that there's a long way for that drug to come in terms of showing that we would feel confident they'll show a positive outcomes benefit.

Yes. Okay. Now taking a step back, I mean, your revenue base is growing. You guys are going to get a significant amount of milestones. You guys are going to get to profitability in 2026. You guys will be generating cash flow -- sorry, in 2026. You guys have also mentioned about doing some BD in terms of leveraging your existing sales force. So how much of a priority is that in 2026? And like what type of asset would you be interested in?

Yes. It's been a priority in 2025 as well. And I think we've had a lot of very good conversation, a lot of good pathways of potential ways we could go. And we're looking at drugs that are either about to be approved or have already been approved, but whose companies need an infrastructure to sell, right?

We have -- if you want to sell a drug, we have everything. We have reps, we have the compliance team, we have the supply chain team. Anything you could possibly need to commercialize a drug in the United States, we have those capabilities. And there are a lot of companies out there with one product and no infrastructure who are about to launch that could leverage our infrastructure. So I would say we're -- we have a couple of opportunities that we're in the final stages of that we're looking at.

And in 2026, it will be about pulling those through and launching those potential products. So I'm very excited about this because this is all incremental to the top line, and we're looking at opportunities that would be a pretty straightforward plug and play with our -- wouldn't require additional investment. And it would just add to that top line and add to that value proposition next year.

Would you look at something specific to lipid-lowering therapies or maybe...

We're not pigeonholing ourselves to lipid-lowering therapies. And if we're just going to get in the guessing game of who we're talking to, welcome that, fine. But cardiometabolic is the way that we're approaching it. And I think more important than the indication is the call point overlap, right?

We're calling on primary care. We're calling on cardiologists. And if it makes sense from a sales and marketing pitch to be able to have that conversation with a physician, then it makes sense to us. I think the indication itself, we're somewhat agnostic to as long as it makes sense from that commercialization effort.

Okay. Perfect. Now you guys also kind of announced some early pipeline this year, which has been quite a remarkable shift in terms of where Esperion was as a company 5 years ago and where it is today, right? And I appreciate that it's still early, but talk about the pipeline, why PSC? Where do you see the opportunity there for you guys?

Yes. So I'd encourage anyone listening to take a look at our R&D Day that we did back in April. I'm a commercial guy. I genuinely don't know what happens before Phase II, so I'm going to do my best to describe this.

So we did an R&D Day on the PSC product. And just as a little bit of context, bempedoic acid is a first-in-class ATP citrate lyase inhibitor. And since launching bempedoic acid, we have learned a significant amount about the therapeutic potential in that class of drugs. And we have started coming up with new compounds that are targeted on much more specific areas outside of lipids.

So the first one that we announced was PSC. The reason we're looking at PSC and the KOLs at R&D, they said it great. If you go back 25 years, they're having the exact same conversation about to a PSC patient 25 years ago as they are today. Really no developments in that area. It's a brutal condition that it's either liver transplant or death. And we believe that we have a compound that not only can help mitigate the symptoms of that, but actually reverse the damage done by PSC.

So we think it's a multibillion-dollar opportunity given the market. It's a fast, relatively cheap compared to a 14,000-patient outcome trial path to market. So we're excited about the opportunity. We think we have something that's really valuable in this space that can help a lot of patients in a very, very nasty disease.

Okay. And when is that going to Phase I?

So we're in the IND-enabling work now. We will likely have that sometime in the next 12 months, and then Phase I would start immediately after that.

Okay. And should we be expecting more coming out of the pipeline?

We do have other assets that we will discuss. It's -- I think this is one of the coolest things that we do because there are very few companies out there that are both commercializing a product and have a pipeline. We do have other assets in the next -- we call it the next-gen program, in our next-gen program that target [ others, ] kidney being one of them. I would say stay tuned for those, but a similar thought and similar concept as the PSC.

Sort of very interesting because Esperion is a cardiovascular company, right? But then now you've got this pipeline going to essentially rare diseases.

Skipping our tone rare disease.

Which is very interesting and quite, I think, cost effective, relatively speaking. So is that kind of like more of a focus area for the company over the next 3 to 5 years? Just to kind of invest into the pipeline and rare diseases, et cetera.

Yes. Yes. I mean, look, bempedoic acid is still our bread and butter. We are still going to be focused on commercializing and a rising tide floats all boats. But over the next, call it, 5 to 10 years, I think you'll think of Esperion more holistically as just a pharmaceutical company than a cardiovascular company, given the shift into rare disease as well as cardiometabolic, I think we'll be touching across the value prop chain for patients in a variety of different indications.

Yes. Okay. In the last minute or 2, just remind us your cash position.

Yes. So pro forma after Q3, I think we're sitting at about $170 million. I think we'll be in very good shape from -- this is the first time I say we're well capitalized now, and we can execute on everything that we want to execute on.

Like I said, the substantial milestones will be coming in, in the coming days. So we'll end the year with plenty of cash to be able to execute on everything I just spoke about.

Okay. Perfect. Well, thank you so much, Ben. Thanks for joining us.

Thanks for having us.

Good day, everyone. My name is Leila, and I will be your conference operator today. At this time, I would like to welcome you to Esperion's key opinion leader Investor event, Breaking the Statin Intolerance Barrier, Closing the Care Gap in Cardiovascular Health. [Operator Instructions] At this time, I would like to turn the call over to Sheldon Koenig, President and CEO for Esperion.

Thank you so much. Good afternoon, everyone, and thank you for joining us for this most important segment on Statin Intolerance Barrier, Closing the Care Gap in Cardiovascular Health. If we can go to the next slide, please. So our forward-looking statement and disclosures. I won't read it, but it will be available on our IR site.

Next slide. So this is our agenda today. First of all, I just want to thank our speakers who have joined us today, Dr. Fatima Rodriguez, who -- all of our speakers will be introducing themselves in the later half of this session. Dr. Dharmesh Patel; and LeAnne Bloedon, our Vice President, Head of Development, who will also be giving a presentation post my remarks.

Our agenda today, opening and introduction. The next segment will be when treatment becomes a barrier, empowering patients to stay on therapy and then a question-and-answer session with both Dr. Fatima Rodriguez and Dr. Dharmesh Patel. And again, we thank them for joining us today for this most important segment.

Next slide. So just a quick coverage of recently, as you know, Esperion Therapeutics, we held our Q3 earnings and again, delivered consistently on strong execution. The third quarter was a strong quarter for us. As a matter of fact, the third quarter was one of the strongest third quarters we actually have ever posted in the company's history.

Our Q3 total revenue was $87.3 million, which represented close to a 70% year-on-year growth. And our Q3 U.S. net product sales was $40.7 million, which represents a 31% year-on-year growth. As many of you know, we finalized agreements with four generic manufacturers. One of the largest ones, Dr. Reddy actually settled with us in the third quarter. And as you know, the settlements now take us to the year 2040.

And as we mentioned in our prepared remarks in the third quarter, we'll actually be talking about our 2040 vision later in the year and going into next year. We showed a 9% increase quarter-over-quarter in retail prescription equivalents. And something that was also very exciting is at the ESC meeting this year, bempedoic acid received a Level 1A recommendation in updated ESC/EAS guidelines for management of dyslipidemia.

LeAnne will go into some greater comments regarding that. Next slide. So just to give you an idea as it relates to statin intolerance and what we are doing as it relates to performance and some of the initiatives that we're taking. Currently, the NEXLETOL and NEXLIZET franchise are outpacing the broader lipid-lowering market.

We're delivering growth that has exceeded all other non-statin therapies, including branded competitors. Just as it relates to leadership expansion, we recently announced that John Harlow will be joining us as our Chief Commercial Officer, and many of you will get to meet him at the Jefferies Conference, which begins on November 17. We've actually conducted our own market research to really look at the market opportunity.

And it's really interesting to note that approximately 50% of patients who begin statin therapy, either discontinue treatment or had over a 6-month gap in therapy within 2 years, representing a significant opportunity for NEXLETOL and NEXLIZET. We talk all the time how cardiovascular disease is the #1 killer in the country in the world. This is just another fact of how patients are unable or unwilling to take therapy as it relates to statins today.

Brand momentum, we launched our new tagline campaign, can't take a statin, make NEXLIZET happen, targeting statin-intolerant patients. And I would also say that quantitative data has shown that healthcare professionals were really showing gains in awareness and the use of NEXLETOL and NEXLIZET. This is primarily due to not only the clinical profile of our products, but also the ease in getting our products with the access we have both commercially and in Medicare.

Our commercial performance, we had a 9% increase, as I said, in our total RPEs. We had a 7% increase in total number of prescribers. Our total prescriber base now exceeds over 30,000 healthcare practitioners. And the one thing that I didn't mention that's not on the slide is we recently introduced our direct-to-consumer advertising on connected TV on September 22 and further enhanced that on October 10 by being on channels such as Disney+, Hulu, et cetera.

Next slide. So we've really been strengthening our patient reach and market access, as I mentioned. We're driving awareness through innovative digital campaigns and broadening reimbursement coverage. As I mentioned, our award-winning Lipid Lurkers, we've started our connected TV campaign. And I can tell you, we thought that we would have -- well, our target is 18 million impressions.

We already have shown greater than 6 million impressions in the beginning or since October. So what that means is that these are the number of people are actually watching this commercial. It's a non-skippable commercial, it's 60 seconds. So we're really creating a lot of consumer awareness and consumer activation through this commercial. From an access perspective, we have achieved 87% Medicare and 86% commercial approval rates.

And this has moved significantly higher, especially since we've introduced field reimbursement managers. The co-pays on average are $29 and $36, respectively, for a 30-day supply. And this really reflects the growing payer confidence and improved access for patients. As a matter of fact, I think the easiest way to think about this from a commercial perspective, 9 out of 10 patients can get our drug. And from a Medicare perspective, 8 out of 10 can get our drug.

It really reinforces the fact that getting NEXLETOL and NEXLIZET has never been easier. So we've created a lot of momentum as we get to the end of the year. We've continued our investment in our -- both our digital marketing to expand our reach and drive sustained growth. I can tell you we're already off to a fantastic start in the fourth quarter. And a lot of that was due to investments that we made in the third quarter.

We're confident that these programs will continue to really fuel our performance. And again, we're really excited about the future as it relates to Esperion moving forward and excited about this that we're doing today. And with that said, I'll turn it over to LeAnne. LeAnne?

Thank you, Sheldon. And thank you all for attending today, and a special thank you to Drs. Patel and Rodriguez for taking time out of their busy schedule, especially on the heels of the American Heart Association meeting. So really, I want to spend some time today just providing some background to serve kind of as a framework for us to have a really robust discussion with both physicians.

So next slide. So let's start with the definition of statin intolerance. So the National Lipid Association defines statin intolerance as one or more side effects associated with statin therapy, which either goes away or improves when the dose of the statin is reduced or discontinued. And NLA indicates that up to 30% of U.S. adults experience some degree of statin intolerance.

So if you look here at the bottom, it's really a spectrum. From the left side, we have patients who have complete tolerance. So they have the ability to tolerate the statin at the therapeutic dose needed. Oftentimes, we think of these patients as moderate or high-intensity statin. Partial intolerance is the inability to tolerate a therapeutically required statin dose. So these patients may be on a low-dose statin, maybe some alternative dosing, every other day dosing. And then complete intolerance is the inability to tolerate a statin at any dose.

Next slide. So we know now really well the risk factors for statin intolerance. And I want to highlight just a few here on the left side. Females are at increased risk for statin intolerance as well as older individuals. And these are really two groups of patients that really need LDL-lowering therapy who -- if you have high LDL-C. We know that females are underdiagnosed and not treated aggressively as males.

And we know that as individuals get older, it becomes a challenge to treat individuals because of just complications you have as you get older in life. So for someone experiencing statin intolerance with these patient characteristics, it becomes even more of a challenge. Statin intolerance can affect quality of life. The most common symptoms that are reported are statin-associated muscle symptoms, although there are other symptoms and signs that the patients report that have statin intolerance.

Next slide. The most concerning thing, of course, is that patients with statin intolerance remain at high cardiovascular risk. So statin intolerance contributes to non-adherence. About 29% of patients discontinue their statin within the first year of having -- based on statin intolerance. We know that patients with statin intolerance compared to those with high adherence to statin have an increased risk of about 50% of having coronary heart disease or a recurrent myocardial infarction.

So the National Lipid Association has really recognized this risk in cardiovascular disease in this subset of patients. And so their recommendation is as the physician is trying to identify a tolerable statin dose, they should consider starting non-statin therapy. Next slide. So I want to talk about another issue that's related but is distinct, and that is statin refusal. And this is really becoming a growing challenge. What I mean by that is when a patient rejects a physician's statin recommendation, it's often due to fear of side effects like muscle pain or concerns about long-term safety or the disbelief in the proven benefits of statins.

If you look here to the left, this is data from a recent large study in the United States, where it was in 24,000 statin-naive patients. In that group, 20% or 1 in 5 people at high CV risk did not accept their initial healthcare providers' recommendation for statin therapy. Now what that means is it's going to take longer time to get to goal. And so these patients remain also at high CV risk.

If you look on the right here, you can see from the same study in the patients who accepted their healthcare providers' recommended statin, they were able to get to an LDL less than 100 in about 1.5 years as opposed to almost being 4.5 years in patients who did not accept their physicians' recommended statin.

Next slide. So turning now to bempedoic acid. This is really a therapy we developed here to address statin intolerance. What do I mean by that? Well, bempedoic acid is a prodrug. And in order to get activated, it requires the enzyme ACSVL1. That enzyme is not present in skeletal muscle. So therefore, bempedoic acid is not active in skeletal muscle, and we've proven this in studies we've done.

So bempedoic acid targets the liver or the hepatocyte. There, the enzyme ACSVL1 is present. It activates bempedoic acid in which -- at which point bempedoic acid inhibits ATP citrate lyase, which is in the cholesterol synthesis pathway. It prevents the substrate citrate going to acetyl-CoA. So you are disrupting that cholesterol synthesis pathway. It's above where statins act. So just like statins, bempedoic acid then indirectly increases the LDL receptors to grab more cholesterol from the blood, thereby reducing cholesterol levels.

Next slide. So the bempedoic acid clinical development program was really unique. And I say that because we evaluated the drug across the full spectrum of statin use. So this table here represents the Phase III studies we did with bempedoic acid. So the first two in blue are CLEAR Harmony and CLEAR Wisdom. In those two studies, 90% of patients were on a moderate or high-intensity statin.

The next two CLEAR Serenity and CLEAR Tranquility were performed in patients with statin intolerance, where 18% were partial intolerant and 82% were complete. The 053 trial was the bempedoic acid plus ezetimibe registration trial to support NEXLIZET. That trial actually had about 2/3 patients on moderate or high intensity, 1/3 with complete statin intolerance and a small portion also of partial intolerant patients.

And then finally CLEAR Outcomes, of course, is the only study even out there, outcome study in patients with statin intolerance. In our study, we had 78% with complete statin intolerance. So of course, in all of these studies, bempedoic acid significantly reduced LDL cholesterol. And then also significantly reduced hsCRP. And I wanted to highlight that there is a recent scientific statement put out by the American College of Cardiology around inflammation and cardiovascular disease, which really highlights the importance of measuring hsCRP in both primary and secondary prevention patients because it is an independent risk factor.

And even irrespective of LDL-C, if persistent elevated hsCRP above 3 persists, this really puts patients at increased risk of cardiovascular disease. Within this statement, bempedoic acid is mentioned, and it's commented that it lowers hsCRP between 20% and 30%, which is really a similar magnitude as LDL-C lowering.

Next slide. So I just wanted to mention the CLEAR Outcomes used a real-world statin intolerance definition. So in this study, patients could have failed two or more statins at any dose or one statin at any dose and unwilling to attempt a second statin or they were advised by their physician not to do so. And as a reminder, we did allow partial statin intolerance, which was defined as having an average daily dose below the lowest dose you see here for each statin, which is generally the starting approved dose.

Next slide. So just quickly, I wanted to remind everybody of the data from CLEAR Outcomes, which, again, the only outcomes trial in patients with statin intolerance. We had close to 14,000 patients, 30% were primary prevention, 70% were secondary prevention patients. Bempedoic acid significantly reduced the primary endpoint, which was a MACE composite 4 of CV death, nonfatal MI, nonfatal stroke or coronary revasc by 13% compared to placebo.

You can see that on the left with the number needed to treat 63. You can start to see the Kaplan-Meier curve start to separate at about 6 months. And then on the right, you can see, and this is based on our statistical hierarchy, MACE-3 was reduced by -- significantly by 15%, nonfatal MI 27% and coronary revasc by 19%.

Next slide. And as a reminder, in the 30% of our patients who were primary prevention patients, we saw a greater reduction in the primary endpoint and all of the secondary endpoints as well. So MACE-4 was reduced by 32% compared to placebo. Again, you start to see those curves separate beginning at 6 months. On the right here is the statistical hierarchy in order.

So we see MACE-3 is reduced by 39%, nonfatal MI is reduced by 37%. And even when you get to cardiovascular death, you see a hazard ratio of 0.57. Now the study was not powered to detect all of these events in primary prevention patients. So this data is not type 1 controlled.

Next slide. And this is to point out that the safety has been well demonstrated with bempedoic acid. We had almost 10,000 patients receive bempedoic acid across our Phase III trials, which demonstrated very well tolerable and safe product compared to placebo.

And I'll also mention that starting in the U.S. in 2020, our products have been available. They're now approved in 41 countries. So we continue to get robust safety data from a post-marketing perspective, really supporting the benefit risk of bempedoic acid.

Next slide. Okay. As Sheldon mentioned, we were really excited to see the ESC/EAS guideline update in August of this year, which really highlights the importance of non-statin therapies and specifically bempedoic acid. And so non-statin therapies with proven cardiovascular benefit, including bempedoic acid, received a Class 1 Level A, the highest recommendation that was alone or in combination for patients unable to take statin therapy.

And bempedoic acid specifically received a Class I level B in statin-intolerant patients. What I think is really nice that was included in the guidelines is this figure to the left, which really shows the efficacy you can get with bempedoic acid in combination with all the available therapies alone or in combination with ezetimibe, statins and even PCSK9. So the clinician has a lot of flexibility in getting that patient to goal.

Next slide. And this is my last slide. So this last slide is really to let you know that Esperion is very dedicated to the educational component around the risks of statin intolerance and that there are alternatives. So we have developed material, as you've heard Sheldon say for physicians, for physicians to use with patients and direct-to-consumer, so direct-to-patient advertising.

So we're really committed and proud of our educational components. And I think next slide. Yes. Okay. Great. So that is my last slide. So what I want to do now is open it up to discussion with Drs. Patel and Rodriguez. And what I would like to do is have you both start out. If you could just provide a brief background, including your clinical practice, that would be great. So Dr. Patel?

Good afternoon. I'm Dharmesh Patel. I'm a cardiologist, I think, represents many cardiologists in the country. I'm on the trenches seeing patients every day. I'm in private practice with an academic affiliation. I'm seeing patients from Memphis, Tennessee, Mississippi and all around the Southeast of America, the heart belt, unfortunately, of the United States. And I serve one of the sickest states in the country. So heart disease is important and really excited to be on this call. So thank you.

Thank you so much for the invitation. I am Fatima Rodriguez, and I'm a preventive cardiologist at Stanford University. So I lead our Lipid Clinics. I see a lot of patients with statin intolerance, and I have an academic practice. So again, a lot of -- many of the patients that I see are referred especially because of inherited lipid disorders or because of prior intolerance to statins.

Thank you both. So I think what would be really helpful is just to kind of start off by getting your perspective on the scope of the problem, statin intolerance, statin refusal. If you could speak from your experience and also what you know even as a researcher, but also your clinical practice. And if there are certain patient characteristics that you've seen, it'd be great to hear your experience. Dr. Rodriguez, do you want to start?

Sure. I'm -- again, I'll have to just admit that I have a very niche practice because I lead preventive cardiology. So by the time patients come to me, many of them have tried statins before and are unable or unwilling to take statins. I'll say that I've been in practice as an attending for about 10 years, and I used to spend a lot of my time trying to try different statins, different combinations, different even days, every other day dosing.

And now that we have so many drugs available to lower LDL, I don't do that anymore, and I really focus on that figure that you showed from the ESC guidelines, which is what agent can we use that makes sense for this patient to lower their risk and that risk is really proportional to a degree of LDL lowering.

Yes, I'll piggyback, Fatima, I don't know how you feel about it, but our patients appear to have a stronger perception when they walk into the doctor's room now about what they will and what they won't take. I'm not sure if it's social media or what have you, but a lot of my patients who were taking statins don't want to take statins now.

I think it's really important, as Fatima said, we now have so many therapies for LDL lowering. I was really excited about bempedoic acid. That was the first oral LDL-lowering therapy since ezetimibe in 2002. So it was very welcomed. And the fact that it was -- had indications or data in primary and secondary prevention, I really thought that was great.

Great. Thank you both. So just kind of continuing around the patients you see, what are the common reasons you hear why patients maybe won't -- if they won't start a statin or if they're ready to stop? What do you hear?

Yes. And I really love the way that CLEAR Outcomes trial was designed because it was -- they're either unable or unwilling. And again, we know that's very, very common in clinical practice. I think many patients are -- even if they don't have actual side effects, even perceived side effects are really important. And for a drug that's a daily drug that's meant to take lifelong, adherence is a huge issue.

And for whatever reason, again, it could be side effects. And I say, I think in my practice, probably 10% of patients have true statin intolerance as defined by the definitions that you discussed. But a much larger portion have I think some sensitivity, some intolerance or some unwillingness to take the statin.

And those are the patients that I worry about most because we know that not being adherent to an LDL lowering agent, whichever it is, is associated with adverse outcomes. Women absolutely are much more likely to have statin intolerance and that's something I see in my practice as well as patients who take -- many other conditions have other medications, which is very common in the secondary prevention and also in the primary prevention groups.

Yes. I think what I love about the CLEAR Outcomes trial is it really represents the patients I see. As you said, Fatima, 46% female, 40-odd percent diabetics, some patients on a low dose of statins, 1 in 5. I just love the fact that it was one of the first trials that highlighted females, first and foremost.

And on top of that, I just think it truly highlights what we see in primary care and in secondary care. As a cardiologist, I'm seeing primary care, too. The worried well or the patients who don't have access to the primary care doctor, so I feel that the trial represents best the patients that I see on a day-to-day basis.

Okay. So then maybe we talk a little bit about the management of these patients, right? So you've got them there. What do you do? Kind of what's your algorithm to train these patients? And does it differ for primary versus secondary prevention patients?

Absolutely, because I think the data is very compelling across all the studies that have been done across therapies. The real enemy here is LDL cholesterol and we're trying to lower it. And the lower is better. Of course, the degree of lowering is proportional to your degree of baseline risk. So the strategies are more intensive for those that have a higher LDL.

I see a lot of patients with heterozygous FH, patients who've had a clinical ASCVD events. We learned over the weekend at the American Heart Association that even patients that just have coronary artery calcium to atherosclerosis are a very high risk of events, but they're targeting the LDL. It's all about bringing that LDL down. And we fortunately have many tools to do that, and NEXLIZET is one of those tools.

Yes. I think we're pushing to get numbers back on track and get some national qualities about numbers. I think LDL levels are very important. And I think what we are learning is the early you start therapy and the longer you start therapy, the better you do overall. So I think the census I felt from the AHA was let's start earlier, let's start more aggressively and that will downstream, reduce further cardiovascular events, even in "the people that have not had prior cardiac events."

Yes, absolutely. Okay. Great. So for NEXLETOL and NEXLIZET, are there particular -- I guess what do you -- where do you see our products most valuable? And how do you use the products? And if you could also comment on your experience from an effectiveness and safety perspective, that would be great.

Well, I think it's clear that this drug was designed for statin-intolerant patients. And again, I tend to -- with unable or unwilling to take statins, which is a large portion of patients. Even though some patients are able to take a small amount of statin, and again, that's helpful as an add-on therapy.

In my practice, I almost always use it in combination with ezetimibe, so NEXLIZET, and we saw that's pretty impressive LDL lowering of 38% on average, some patients more, some patients a little bit less. It's a great oral alternative to statin, and it's really the only oral alternative that is available, especially for our primary prevention population.

Very well tolerated. Again, access issues have definitely improved over time, and we've seen that in our practice where really the patients who need them are able to get it without many issues from the insurance companies.

Yes. And Fatima, I don't know how you feel about this, but I love the fact that it's diabetic neutral, maybe even favorable, we can't say that, but it's at least diabetic neutral. And then, of course, the fact that well, it's very well tolerated. And I tell my patients, this is a therapy that basically is not broken down by the skeletal muscle.

So you should not be getting some of those anticipated side effects that we have been seeing with statins. And the other fact I was trying to get back to was the hsCRP as a clinician, inflammation drives atherosclerosis. And I think when I speak to my colleagues, everybody agrees the fact that hsCRP certainly is a predictor, at least enhancing risk factor from the ACC guidelines for atherosclerosis. We all believe that. And the fact that bempedoic acid does reduce hsCRP by about 23-odd percent, I think, is very well received by me and my colleagues, Fatima, how do you feel about that?

Yes, I agree. And I'm not so sure outside of the preventive cardiology world, how many people know this. So I do think it's important that we raise education around the CRP. But certainly, in our community in preventive cardiology, Dharmesh and I are part of the American Society of Preventive Cardiology, where all of us think about this.

But certainly, inflammation is something that is one of the core causal processes that cause advanced atherosclerosis. So anything that we can do to help lower CRP is important. And I have many patients who -- again, that is a true side effective status, and I tell my patients that it can -- especially in people who have a tendency towards diabetes, prediabetes can raise your hemoglobin A1c, especially at the higher doses. So for many of those patients who are otherwise doing everything they can and they're having that bump in their glycemic index, this is a really great alternative.

Go ahead.

We expect that prediabetic, that patient is not "diabetic" yet. There's a lot of those patients in primary prevention that really weighed towards -- against a diabetic pro therapy rather than something that will at least keep the A1c neutral, if not even lower slightly.

Okay. Good. So I'm hearing it sounds like that in terms of differentiating aspects, mechanism is one that's important. HsCRP reductions is another one and neutral on diabetes. Is that safe to say because...

That's very safe to say. I think as Fatima mentioned, in clinical practice, I know half the time we may use NEXLETOL. But in clinical practice, we're using NEXLIZET predominantly with a 38% reduction in LDL, which is quite substantial. And certainly, as has been said, we may use it as monotherapy, we may use it as a backup on the statin therapy, which is a reduced dose. But the combination works very well.

We know from the like the GOULD data, 36% of females and 48% of males who are high risk are stuck on monotherapy. And so this is where I really welcomed bempedoic acid because it was another adjunct of therapy, which could further reduce LDL further. And I think it'd be fool to think that statins are the end all be all of everything. We know this. I mean 84% of patients who have had an event will not get to goal with just simply statin therapy.

Yes. And I think we certainly moved that direction with blood pressure management, [indiscernible] therapy, focusing on the tailoring really the level of LDL lowering with the intensity of therapy. And especially as we get -- we really have these lower LDL targets, even in a patient that can tolerate statins, it's maybe not enough for many patients, especially depending on the baseline LDL level, you need adjuvant therapy.

So the combination and even combination therapy off the bat is something that we're moving to in our practice, certainly endorsed by the European guidelines to really not -- you don't have to wait to get somebody see how they do because we know that clinical inertia, the waiting for LDL to come down, sometimes we never have the opportunity to intensify therapy.

This is no different to hypertension or diabetes. It probably will take combination therapy attempts to get to goal, just like in hypertensive, 67% of patients use combination therapy. I think it would be fair to say that most of our patients will need some combination of therapies.

Okay. And do you -- you mentioned -- like you said, the ESC guidelines were really supporting combination therapy. Do you think the U.S. guidelines will follow suit with combination therapy?

I think the U.S. guidelines will endorse lower LDL targets and again, focusing on LDL as the quality metric. And now that we have so many different therapies, especially therapies like this that have outcomes that have proven cardiovascular benefits, then the guidelines will just by definition, require the use of non-statin therapy, sometimes upfront in order to be able to get to LDL levels under 55, which I think will be the goal for many of our patients in either a very high-risk primary prevention or secondary prevention.

But the European guidelines do what I do in my practice, which is they go even lower and LDLs under 40 for very high-risk patients, which is what we do in our practice, but I would say is off-label with the U.S. guidelines.

Okay. Let me ask you this, like in the -- with current approved therapies, how much is having an oral option, trying an oral option important to your patients? And does that differ in primary prevention patients versus secondary?

Absolutely. And I think it's positive that there are many options in preventive cardiology for us to lower LDL. But many patients are fairly close and they -- and just starting an injection is just not something they're interested in every 2 weeks, self-administered or even the inclisiran is obviously another option, but that doesn't have outcomes data, like coming to the healthcare facility.

So you're just like you just need a little something, you need another pill, I mean another pill is obviously much easier. And it's -- almost all of my patients, I'm sure Dharmesh feels the same way, take pills. So that is not disrupting the routine in any way. It's just adding one more pill. And again, for me, I tend to use NEXLIZET. So that is actually a combination pill to really bring that LDL down.

Yes. I mean I think -- I would not be honest if I didn't say that GLP-1 agonist did change the perception of injections. So they have certainly changed it a bit. But again, most patients do not want to take an injection once every 2 weeks or what have you. I think they prefer taking oral therapy.

And I think the difference with GLP-1s, I completely agree with Dharmesh, most of my patients don't want to take statins, all my patients want to take GLP-1s. So I think there's just something that they feel it, they see it. You don't feel cholesterol until you have an event. You don't -- again, you're not getting repeat lipids if you're not big -- you need that feedback. So it's a very different patient experience.

We've made cholesterol very confusing to our patients in terms of the ratio, so like I have a good -- I just saw somebody and they're like the lab value said my LDL was okay. But we know that's actually the normal for -- which is actually probably even too high of LDL under 130 for a high-risk patient is obviously not acceptable. So we've made it very confusing, and I really appreciate all the work you're doing to try to educate our patients around the importance of lowering LDL to improve cardiovascular outcomes.

I think another message is a lot of my patients will say, well, I'll just diet and exercise in primary prevention. But we know that only 25% of your cholesterol synthesis is from what you eat. 75% of your cholesterol synthesis is from what your liver makes. So having those messages and those meaningful discussions with your patients also changes their perception of cholesterol, is not necessarily a lifestyle issue. It's sometimes more genetic and what your genetics are.

And I just had -- and that's an important message for patients, and we've seen this with the lipoprotein A that they're like, that's not my fault. It's just my body makes so much lipoprotein A. So I just had a patient and I saw in clinic last week who's lost quite a bit of weight on tirzepatide, no change in LDL. LDL is 120, now it's 119. So that was a real eye-opener for this patient that they're like, it's really not lifestyle.

It could not be doing better. They've lost weight, they're exercising, so their liver is synthesizing too much cholesterol. And I think that was actually a very motivating factor for our patients to start LDL lowering therapy.

If my memory does serve me right, Fatima, I think those GLP-1 tests, the LDL reduction was like 3% or something if my...

Very minimal even with weight loss. But I think we see this, right, that hypertension tends to respond really well, diabetes, for sure, with weight loss. LDL cholesterol, in particular, not so much. I mean -- and again, it's triglycerides definitely, but I see this a lot in my practice that -- but there's always, always that human, let's give it a try.

I really want to try diet and exercise, but I don't want to fail and have to take a medication. So hopefully, just raising awareness on the fact that your body is making too much cholesterol. And even normal amounts of cholesterol, it may be too high for you, and this is a completely modifiable risk factor that we can control with safe and tolerated medications.

You're right. To your point, the NLA guidelines just said recently that a level of -- LDL level of 10 to 40 is okay.

Yes. How low can you go? I think that's another one that there's no danger to having very low cholesterol. I always tell my patients that the main side effect is that you live longer.

That's right.

That's good. So sticking to kind of the path around education. And I know you all don't have much time at all. But if you have a patient who you're struggling with the statin challenges of following what you've recommended or they have statin intolerance and can't take it -- what are some -- what do you tell that patient to try to get them to now do what you want them to do and understand their risk?

Yes. And I'm sure Dharmesh agrees with this. I think one of the most powerful tools that I use in my clinic now is imaging. So things like a coronary artery calcium scan. Because I think when you plug in numbers in risky equations, particularly for women, and particularly for younger adults, those numbers are not very impressive. They're hard to interpret.

People like to think about proximate risk as opposed to 10-year risk and 30-year risk. So I often use imaging tools and usually imaging that they've already had in our health care systems to show them the process of atherosclerosis. This is your heart. You just had a CT scan done for another reason. You have plaque in your arteries. And that just, well, what is plaque. That is what causes the buildup of a plaque in your arteries causes a heart attack, but we can help fix this. We can make -- stabilize this plaque, prevent heart attacks.

So to me, that's been a really powerful tool. And again, like I mentioned earlier, I've changed my practice over the past couple of years where I don't -- it's great to have some statin at the highest dose possibly tolerated. We know these drugs are safe. They've been around forever, great data. But whatever that is, even if it's 2.5 of rosuvastatin is better than nothing, but I quickly pivot and say, if that's not an option, let's not wait until I see you in 6 months, let's go ahead and get the ball rolling and start another therapy.

Yes. And I tell my patients, these therapies are your chemotherapy for your heart. I mean if you had a cancer, you take anything that would "solve it." But we seem to think that cancer kills more people than cardiovascular, absolutely not. The complete opposite. Cardiovascular is the #1 killer in the United States. And as Fatima eloquently said, right now in cardiology, things are changing really, really quickly. We are now having technologies that can tell us how patients are truly doing within the vascular beds.

So it's changed because we know the data up to 50% of patients have no symptoms before their first heart attack. 63% of those patients are not even taking any lipid-lowering therapies before they quote, "first heart attack." So there is so many patients out there who we can risk stratify with these different technologies now. Talk about the amount of narrowing, the characterization of the plaque, is it soft? Is it hard?

And hopefully, all these pieces of information will be able to fast individualize therapy to the individual patient, more like a personalized therapy approach. And so all these therapies that are out there will have a role and a place in our patients for sure. The number of lives that will be affected are so huge. We're not doing a good job just doing primary prevention. We're doing an awful job in secondary prevention. The amount of potential here and opportunity is unsurmount.

Well, this has been fabulous and your passion, your expertise, your knowledge just comes through so great. So I've loved the discussion. I think I'm sure there's lots of questions from our audience. So I think what we'll do now, operator, is turn it over to you to kind of facilitate the questions.

[Operator Instructions] Our first question will come from Paul Choi with Goldman Sachs.

Just for both Dr. Patel and Dr. Rodriguez, can you maybe provide some background information for us on how many -- what percentage of patients at your respective institutions are currently on NEXLETOL or NEXLIZET in terms of the eligible population or percentage of total patients that go through your institutions?

And my second question is, as you think about the use of NEXLETOL and NEXLIZET in the statin-intolerant population, the drug and other modalities have been around for a few years. Can you maybe comment on what you think is the biggest barrier to adoption? Is it price? Is it insurance? Is it awareness? Any color from your perspective and your experience would be helpful.

Great. I was going to see if I could look it up with like a search tool. I would say that I have a -- my practice is probably not representative of the U.S. eligible practice because I have a lipid clinic and people that can't tolerate statins tend to preferentially come to my clinic.

I would guess that probably the use of my patients is around 20% of my patients are some sort of bempedoic acid product, it probably -- it's certainly much, much lower across my institution. And that's a little bit because of awareness, and this is really across all non-statin therapies, even ezetimibe, right, that's been around for a while and it's generic because of a lack of awareness of the -- it takes it -- I just read somewhere that it's like it takes 10 years from a guideline to be released for full implementation.

So -- and again, we're cardiologists, we're a preventive cardiologist, so we're a little bit more niche. Even within our cardiology community, I get a lot of referrals from general cardiologists to say, "Hey, my patient can't tolerate a statin." Can you just -- can you help?

But because we have really good data on primary prevention, this is exactly the medication, and it's an oral medication, it's an easy medication to take that I think we really need primary care doctors to be familiar with, to be comfortable with. We -- I'll tell you that everything that we do for patients from the clinician side, it's really how easy it is to get and the buy-in from the patient. And a lot of us, I mean, unfortunately, I don't do the prior auths myself or the paperwork myself, but I often will say that it's the ease of getting the drug to the patient and explain to the patient that this non-statin option is available.

Yes. And if you just about population-based medicine, I mean, you've got 40 million to 50 million adult diabetics out there. And this really is -- Fatima and I represent the very top of the pyramid. I mean the amount of people that could and should be on this therapy is unbelievable. If you just simply put the diabetics, for example, 40 million to 50 million diabetics, LDL goal should be less than 70 if you have one risk factor.

I can guarantee you that 50%, 60%, 70% of those patients may not be at goal. I'd say 50% aren't even on lipid-lowering therapy, just to give you some general population-based medicine. We can't even get not more than 20% of patients who've had a cardiac event to a goal of 55 just to give you some perception, a person that's had a heart attack, only one in five of them will get to the ECDP guideline threshold of 55. So when you talk about primary care, the problem is even bigger.

And just being very honest, healthcare professionals are seeing lots of patients every single day. It's not just cholesterol that's on the problem list. There's about five to seven things going on, diabetic with arthritis with heart failure and sleep apnea. So as healthcare professionals, we sometimes lose that physician inertia being honest and a little bit of physician fatigue. But I think the message about we have therapy for primary prevention in those higher-risk subset populations, I think that message will go a long way.

Yes. Maybe I would just add. Dr. Patel and Dr. Rodriguez, it's not so much -- and Paul, not to redo your question, and thank you for your question. It's not so much how many patients are on the drug, but how many patients could be. And it speaks to -- and I think I've heard this at every seminar since I am on Zocor back in 2003, we collectively aren't doing a good enough job to educate patients, activate patients, et cetera, so that they know that they have this silent killer.

They don't feel anything. They feel okay. But meanwhile, here they have a problem and that's why we went over some of the things that we're trying to do as well to activate consumers, educate them, et cetera, and create more of that awareness. So this is something I think that will continue for a very long time regardless of drug.

Yes. I couldn't agree more, Sheldon. And I think the important thing here, there's obviously a lot of different drugs either in development or already available. The enemy is LDL. And I think if every company raises awareness about LDL being a completely modifiable risk factor, a causal risk factor for heart attacks, stroke, PAD that's really the win.

And I'll tell you that we're just not doing a good job at this. I do a lot of research on this in guideline gaps like why are we just not doing this. And I even do some -- that we look at medical records and we try to understand this rationale why are physicians -- there's is so -- lack of awareness of new LDL targets. Particularly in our stroke patients, people think that you need LDL cholesterol for the brain and all these myths, right, that have obviously been debunked.

So even within our own physician community, there's a lot of lack of understanding, even cardiologists, my colleagues who do something else, electrophysiology, general cardiology. So I would say that Dharmesh and I are very passionate about lipids, and we're aware of all the therapies and all the different options, but that's just not the case.

But I think bempedoic acid in particular, has a huge reach in the primary care population, potential that probably has not been realized because it's oral, it's easy. There's really nothing that you have to worry about. And again, it's the next obvious kind of add-on therapy for primary prevention when you're trying to get someone to go or in those patients who are unable or unwilling to take statins.

As soon as I say it's not a statin, patients' ears perk up for whatever reason that is, I'm just letting you know that's what happens.

It's the anti-statin campaign on TikTok.

Yes. No, it's pretty unbelievable.

Your next question will come from Joe Pantginis with H.C. Wainwright.

Can you hear me?

Yes.

Great. So look, as NEXLETOL and NEXLIZET building in visibility, especially after CLEAR Outcomes, I have a two-pronged question. So going back to the chart that LeAnne showed earlier with all the different combinations that you're looking at, number one, how many combinations can you really try with one patient, number one.

And as you're looking at new potential assets coming through, I would love to get your thoughts on the recent -- from this weekend, very exciting data at Merck, Amgen and Ionis, for example, how do you think NEXLIZET and NEXLETOL might fit in with those assets and how BPA might be complementary, sorry, with many of the existing and future assets.

Well, I think, I'll just say for me that it's such an exciting time to be a preventive cardiologist because we do have so many tools in the toolbox, not just statins that are either existing or are in the pipeline. I think a lot of it is going to be personalized because there are so many patients with hyperlipidemia. There are so many patients at high risk of cardiovascular disease that I don't think one is going to just take over everything because it really has to be personalized hopefully in the background of statin therapy.

We even heard this weekend at American Heart Association, the extreme option, which is one-and-done gene editing, right, for LDL. I'll tell you that the uptake of that will be quite low from the beginning, maybe for the highest risk populations and everything, always starts with the highest risk populations when you start developing a new compound and then eventually makes its way to other populations.

But I don't think it's going to take away from bempedoic acid. I don't think it's going to make it obsolete anyway. I think it's just going to raise awareness about non-statin therapies that can improve outcomes if these compounds end up having positive outcomes. So I think it's additive, and I think it's great.

And people are going to say, "Hey, is it an oral option? Is it an easy option?" So I think a lot of those factors are how is it administered? How does it interfere with people's lives? What degree of LDL lowering because there is a real difference between degree of LDL lowering for the therapies if someone is almost at goal. And do they just need a little bit more than maybe just bempedoic acid monotherapy versus adding the NEXLIZET.

Yes. I think the data that came out this weekend was exciting. As you said, Fatima, everyone is going to be a winner, I feel. And one thing -- great thing about bempedoic acid is it can be used with any, I believe, of the therapies that will describe this weekend. Even the Merck data with the oral PCSK9 was good. Remember, you have to be fasting 6 hours before and not drink or eat anything for 30 minutes after, fantastic. The [ facility's ] data was data with high-risk patients who had not had a prior cardiac event. [ Entry's ] inclusion data was slightly different. The CAC score was 100. I think from the CLEAR Outcomes it was 400, different subsets of patients.

But the great thing I noticed or I took back from that is even if you look at the primary prevention subgroup in CLEAR Outcomes, the diabetics, which was about 30-odd percent, when you look at the risk reduction in 3-point MACE and 4-point MACE, the [ status ] is 29 and 26. CLEAR Outcomes is 36 and 30.

Even if you look at the CCT data looking at how "your therapy compares to statins?." You can see that in the primary prevention graph, the hazard ratio of 0.55 for bempedoic acid in primary prevention. So the point I'm trying to make is bempedoic acid is not going anywhere. If anything, personally speaking, I think it will be embraced more and more by healthcare professionals moving forward. I think our biggest issue has been lack of knowledge by healthcare professionals that this therapy can be used if and when.

And LDL targets, right? I think there's is still lot of -- the 2013 cholesterol guidelines were just set it and forget it. And I think the data that has come out across all these therapies has just really proven the LDL hypothesis that lower is better, longer is better. And again, adherence is really important. So this is -- I tell my patients, LDL is the same thing. I think about smoking. It's pack years of LDL exposure. So you need a therapy that you can tolerate over time to have that lower LDL over time.

Let's not forget what LDL lowering with NEXLIZET, I mean which is bempedoic acid and ezetimibe that's about 38%. That's the same efficacy as a moderate to high dose intensity statin. So it's not like 38% is pretty, pretty impressive in combination.

Your next question will come from Jason Zemansky with Bank of America.

Maybe a follow-up as far as other targets in dyslipidemia. But you mentioned a lot of hsCRP. How important is Lp(a). And does the fact that bempedoic acid doesn't seem to have an effect on this is that an issue at all?

I think it's good that doesn't raise it, right? Lp(a) is an exciting -- and again, there's been a lot of awareness about lipoprotein A likely being a causal risk factor for cardiovascular disease. There are ongoing trials across different companies for agents that reduce lipoprotein A by 80% to 90%.

And I think those are the drugs, the specific drugs. I think that degree of Lp(a) lowering will be required if we want to test the hypothesis that reducing Lp(a) independent of LDL improves outcomes. And we don't not have the answer to that yet, but that's something that I'm very excited in the future preventive cardiology because, again, that's a risk factor that's entirely genetic that can potentially be modified.

I don't think, again, you may be referring to the fact that the PCSK9 inhibitors lower Lp(a) by 20% or so. That is not -- that would definitely be an off-label use of a PCSK9 inhibitor for that reason. And the data so far, at least like the secondary analysis does not suggest that, that's a sufficient level of Lp(a) lowering. What I'll say happens in clinical practice is that Lp(a) is a clear risk-enhancing factor to drive lower LDL value. So if somebody has a high lipoprotein A, I'm going to be much more intensive with their LDL lowering.

Yes. I'm just as excited as I am scared about when the Lp(a) data comes out. I was part of those trials. I just -- let's wait and see as Fatima says, it's causal risk factor. Backing off what Fatima did say, PCSK9s do not affect hsCRP. Yes, we do know that bempedoic does reduce hsCRP, so does statins for that reason. So I'm -- all about inflammation, unfortunately, or fortunately, and I feel that inflammation is, I think, the crux of atherosclerosis progression. So I'd be excited to see what Lp(a) does, but it's not a slam dunk right now, far from it.

Your next question will come from Rick Miller with Cantor Fitzgerald.

Rick on for Kristen. Can you hear me okay?

Yes.

Yes, you mentioned -- to the doctors, you mentioned that at least some of your patients are on low-dose statin and either NEXLETOL or NEXLIZET. So how important could it be to have a fixed-dose triple combination versus just managing sort of multiple medications separately? And I'm asking, of course, because this is something that's sort of been talked about by Esperion and their partner.

That's a great question. And I've been a big fan of polypills forever. They just presented at the American Heart Association, a polypill for heart failure, in particular, in low-income settings to make things easy. It's good and bad. I think that it would make -- once you know a person can tolerate a specific combination, changing it to one pill sounds like a no-brainer, especially if that's even a lower dose that's currently available because I think you just need a little bit of statin.

I tell my patients a little bit of statin, probably you get the most benefit from even just 5 milligrams of rosuvastatin. Less incremental benefit and a lot more of the potential side effects when we go up to, for example, rosuvastatin 40. But the one downside to that is that it's important to isolate the effect of things. So you don't -- once you throw the statin in there and especially for a drug that's for statin-intolerant patients, there may be a little pushback from patients.

So I think that, that in practice may have to be tested in a different population, not necessarily a statin intolerant population or even just do 1 milligram, but like such a low dose statin that -- we still have a benefit, but not that would potentially cause side effects.

Yes, I agree. As we all know, the lowest dose of statin gives you 75% of your LDL lowering. So as Dr. Rodriguez has said, even rosuva 5 or 10 brings something to the table and increasing the statin thereafter just reduces your LDL by 6% each time you double up. So I agree, I'm all about combination therapy, Fatima. I do see your point about the side effects in that, but we are doing such an awful job capturing LDL reduction and getting to goal that whatever it takes at this point.

And I think as has been mentioned on this call, just like diabetes and hypertension, it's not going to be one therapy, maybe two or even three. So the great thing about bempedoic acid is its best friend is ezetimibe anyway. And then they can be best friends with statin. So it's going to be in the equation somewhere...

Yes, you're right, it's oral, but I'll say the other thing is that clinicians -- but I think this clinician inertia, like I read this [Technical Difficulty] my colleagues discuss -- some people even acknowledge LDL not a goal. Discuss the next visit. What's the discussion? It's going to not be a goal next visit too. Let's wait for another -- there's therapeutic inertia. So I think this off -- right at the beginning, your LDL is 150. The chance of getting it to where it needs to be to start with is very unlikely. Let's start the combination.

And again, we can predict this. We know that we saw that beautiful figure from the ESC guidelines. We know what medication can help us get to that desired LDL lowering. But that's not what is done in clinical practice. I think in clinical practice, people are very -- start something, then titrate and all those elements of needing to titrate and follow up are where we're losing people. We're losing opportunities to really increase lipid-lowering therapy.

If I could add, Dr. Patel and Dr. Rodriguez, we are currently developing a triple combination, and we're looking at a triple combination with both atorvastatin and rosuvastatin. And to your point, a low dose of a statin. And we've done the modeling, looking at low-dose statin plus NEXLIZET, and we see what the LDL efficacy can be.

It can be upwards to 70% reduction just with a low-dose statin. And to your point, it speaks also to having that flexibility of the suite of options where you have this triple combination, you can use NEXLETOL on its own, you can use NEXLIZET.

But I think also just going back to some of the remarks that you made earlier, gone are the days, and this is how ESC started, you may recall, of just using one therapy, as you mentioned earlier, to get to goal, you really have to look at how diabetes, hypertension has been managed. This is where lipid lowering is going. And I would say that we kind of saw that future coming and said, okay, how can we develop this polypill strategy. So we're really excited about it as we continue that development.

That's exciting, and that will serve the mantra of LDL reduction even better than what we have done thus far.

And patients do -- even though it's not true, do see it like as a failure to get an add-on drug. So when you put it in one pill, there's just like a psychology to that, this happens with hypertensive -- I think a lot of us -- I'll say, for antihypertensives prefer doing either low or medium doses of multiple drugs to kind of mitigate side effects.

Patients hate this. So like can you just double my existing drug because it's almost like a failure. But when you change it to a combination pill, number one, we know it increases adherence, but also it doesn't seem like an added burden to the patients where you do kind of pill counts [indiscernible] patients.

I'm always bartering with my patients where I said, listen, I'm going to give you bempedoic acid and in return, you're going to stop your ezetimibe, so I'm giving you NEXLIZET. So I'm changing one pill for another, and they love it. They truly do love it. I mean none of us on this call like to take pills if we don't have to, but the less number of pills are better.

And if you would give me something one in three, I'm more likely to take it than three separate pills. It's just a fact. And I think there's a perception about injections, too. I mean I don't think everyone is like, okay, yes, let me give -- take an injection medicine for the rest of my life for getting my LDL lower. I think people -- perception will be to take an oral agent first. GLP-1s are different. GLP-1s, as you said, Fatima, they give so many other effects, visual, psychosocial, whichever you want to call it. But when you're talking about cholesterol therapy, I'm not so sure.

And I would say this like anti-injections, anti -- anything that kind of gets deep in the cell sentiment is greater now than it was maybe historically, even though there's obviously exciting science in developing some of these therapies that are not just for LDL, but also for triglycerides and other factors in the atherosclerotic cascade, including lipoprotein A.

Fatima, I kind of want to ask you this question. The perception by the healthcare professionals, these days, we should fix diabetes, we should fix obesity, cholesterol is maybe not so important. But I recently learned that actually cholesterol management is probably the most important of the three factors treating the patients that we see in clinic.

Yes, there's a lot of data from the inter-heart study in terms of like the percent attributable risk for most particular myocardial infarctions. And LDL is the #1 risk factor that is modifiable, that is highly, highly modifiable that can explain a lot of that excess risk across populations. And to me, I mean, again, maybe biased but I think that it's so much easier to treat LDL cholesterol and to treat high blood pressure because high blood pressure, again, that's when you need a lot more patient feedback, a lot more visits, a lot -- it's more complicated.

I don't -- I think we had historically made cholesterol management very complicated, and we still have some residual pieces of that from the past with these LDL thresholds are too high with this perception that if your HDL is high, you're okay. And I see this in clinic all the time, somebody has been told your ratio is fine, don't worry about it. But now it's pretty simple. It's about -- all about LDL, the lower the better, the earlier the better and the longer the better.

Great. Okay. Well, that was our last question. So first of all, I just want to thank both Dr. Patel and Dr. Rodriguez. Thank you so much. We really appreciate your participation, the Q&A as well. LeAnne, thank you for your moderation and also being a very big contributor in setting up the symposium.

I think we're going to continue to do a series of sessions like this as we go into the New Year of 2026, but thank you so much. Before we close the session, I do want to mention, first of all, for those of you who have worn the uniform are wearing the uniform, past and present, thank you so much for the service to this great country.

So happy Veterans Day to all of you out there. And also, again, thank you for tuning in to our session on statin intolerance today. Again, more exciting things to come with Esperion, tune in next week, we'll be in London as we head to Jefferies, the Jefferies Conference, after that at the Piper Conference in New York City and look forward to continue to share more information about the organization and what we're doing. Thank you so much. Have a great afternoon and talk to everyone soon.

Hello, ladies and gentlemen, and thank you for standing by. Welcome to Esperion's Third Quarter 2025 Financial Results. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to Alina Venezia, Head of Investor Relations for Esperion Therapeutics. Please go ahead.

Thank you, operator. Good morning, and welcome to Esperion's Third Quarter 2025 Earnings Conference Call. With us on today's call are Sheldon Koenig, President and CEO; and Ben Halladay, CFO. Other members of the executive team will be available for Q&A following our prepared remarks. We issued a press release earlier this morning detailing the content of today's call. A copy can be found on the Investor page of our website, together with a copy of the presentation that we will also be referencing. I want to remind callers that the information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. I caution listeners that management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to the risks and uncertainties associated with the business.

These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and in our SEC filings. The content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 6, 2025. We undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call and webcast. As a reminder, this conference call and webcast are being recorded and archived. We will begin the call with prepared remarks and then open up the line for your questions.

I'll now turn the call over to Sheldon.

Thank you, Alina. Good morning, everyone, and thank you for joining us. Once again, we are very pleased to be reporting another strong quarter. Total revenue for the third quarter 2025 grew 69% year-over-year to $87.3 million. Looking at our strong U.S. performance, we saw nearly double-digit sequential quarterly prescription growth with U.S. net product revenue growing 31% year-over-year to $40.7 million. During the third quarter, we continued to lay the groundwork for the future by investing in enhanced patient access programs that are intended to drive prescription growth and revenue in the months and years ahead. While this impacted sequential growth this quarter, these were important onetime costs that we are confident will provide significant return on investment. That said, this was also our strongest third quarter of record, a particularly meaningful achievement given that this period has historically delivered more modest growth due to summer months and both patient and physician vacations.

This outstanding performance reflects the strength of our execution and the growing recognition of bempedoic acid as a differentiated treatment for patients, especially those who cannot tolerate statins. Our commercial strategy is resonating. Prescriber engagement is up. Patient access is expanding and our creative campaigns are winning industry recognition. In addition to our commercial momentum, we made important strategic progress this quarter. We finalized agreements with 4 generic manufacturers, including Dr. Reddy's, not to market generic versions of NEXLETOL and NEXLIZET prior to April 2040, which supports the long-term value for our blockbuster franchise. We also saw our bempedoic acid products included in the ESC/EAS guidelines, a significant validation of their clinical benefit and a strong signal for expanded use. We expect similar inclusion in U.S. guidelines in early 2026, further reinforcing our leadership in cardiovascular risk reduction in both primary and secondary prevention for patients who need alternatives to statins.

Turning to our progress in the U.S. market. During the third quarter, we outpaced the broader adjunct lipid-lowering market, delivering growth that exceeded all other non-statin products in the category, including branded products. This momentum reflects both the clinical relevance of our bempedoic acid products and the effectiveness of our winning commercial strategy. I want to take a moment to recognize the outstanding work of our commercial team. From sales and marketing to reimbursement and market access, their execution has been nothing short of exceptional, a textbook example of what commercial excellence looks like in our industry. Our continued growth is a direct result of making smart strategic choices, striking the right balance between in-person and digital engagement, investing in top-tier talent and high-impact programs and delivering bold award-winning marketing campaigns that resonate with our audience. Their dedication and agility have been instrumental in driving performance and positioning us for sustained growth.

In further support of these achievements, we are excited to welcome John Harlow to our team as Chief Commercial Officer effective November 17. John joins us with more than 2 decades of experience building and scaling commercial organizations across both large and emerging pharmaceutical companies. Most recently, he was Chief Commercial Officer at Melinta Therapeutics, where he led a team of 80 professionals across all commercial functions, where he nearly doubled revenue, delivering approximately 85% growth in 2024 from 2020. His proven ability to drive performance and inspire teams will be invaluable as we expand our reach, scale our operations and unlock the full potential of our portfolio. Turning now to our commercial progress. Last quarter, we launched several strategic marketing initiatives, including a targeted campaign aimed at patients who are statin intolerant, a population that represents a significant unmet need.

Our research indicates that nearly 50% of individuals who begin statin therapy either discontinued treatment or had over a 6-month gap in therapy within 2 years. This gap leaves many patients vulnerable to cardiovascular events and presents a substantial market opportunity for NEXLETOL and NEXLIZET. To address this, we introduced our "Can’t take a statin? Make NEXLIZET happen!”" campaign. This initiative has already begun to elevate brand awareness among our key demographics with health care professionals reporting a significant increase in their prescription -- their perception of rating of NEXLETOL and NEXLIZET for statin-intolerant patients based on quantitative data. These findings further support the transition from awareness to use and the impact of our powerful marketing.

On September 22, we launched a pilot promotional ads on connected TV platforms such as Hulu and Disney+. Building on that momentum, we began airing branded commercials during Grey's Anatomy on Disney+ and Hulu starting October 10. These ads feature our award-winning lipid lurkers and are designed to spotlight the issue of statin intolerance while positioning NEXLETOL and NEXLIZET as compelling alternatives. We anticipate these commercials will generate approximately 18 million impressions, specifically targeting adults over the age of 50 who have a history of statin use, but have not been on therapy for at least a year. As of mid-October, we have already had greater than 6 million views of the full length of the commercial. We remain deeply committed to expanding the reach of these successful programs and are confident in their continued contribution to our growth trajectory. In addition to driving demand for our bempedoic acid products, we have made meaningful progress improving the access environment for patients and physicians alike.

In the third quarter, we achieved an 87% average approval rate for Medicare coverage with out-of-pocket costs of $29 for a 30-day supply compared to $64 for a 30-day supply in the first quarter of 2025. In the third quarter, we averaged an 86% approval rate for commercial coverage with an out-of-pocket cost of $36 for a 30-day supply compared to $55 for the first quarter of 2025. In addition, the benefits of these co-pay programs have improved patients fulfilling their prescriptions by 17%. These are meaningful cost reductions that underscore the growing payer confidence in our therapies and the fact that patient access for NEXLETOL and NEXLIZET has never been easier. Importantly, we added an enhanced coverage with 2 major Medicare providers beginning October 1. While this coverage required near-term investment, we believe it will drive volume into the future that will more than compensate for these onetime costs.

We now have greater than 90% of commercial lives and more than 80% of Medicare beneficiaries covered with all national commercial and Medicare payers covering all indications. This combined progress, including expanded payer coverage, reduced prior authorization barriers, enhanced reimbursement support resources and our balanced approach to direct and digital marketing resulted in a 9% increase in total retail prescription equivalents from Q2 2025 and a 7% increase in the number of health care professionals prescribing NEXLETOL and NEXLIZET, bringing our total prescriber base to more than 30,000 health care practitioners. This growth validates the rising confidence among clinicians and the expanding role our therapies are playing in addressing the unmet needs of statin-intolerant patients. The combined strength of our statin intolerance campaign, improving payer dynamics and the continued success of our Lipid Lurkers campaigns position us well for sustained momentum in the quarters ahead.

A very important advancement during the third quarter was the inclusion of bempedoic acid as a Class 1 Level A recommendation in the 2025 ESC/EAS guidelines. This endorsement by Europe's leading cardiovascular societies validates the clinical impact of our therapy for patients unable to tolerate statins and reinforces our commitment to expanding access to innovative lipid-lowering solutions. As I noted earlier, we believe this recognition will be reflected similarly in the forthcoming U.S. guidelines expected in Q1 2026. In preparation, we are laying the foundation to leverage this growth opportunity by increasing patient support programs, market access contract activation, engagement with integrated delivery networks and direct-to-consumer initiatives such as our connected TV campaign. Turning now to the progress we are making through our international partners around the world, where we continue to see significant growth in both geographic expansion and in-licensing product sales.

Let's start with Europe, where our partner, Daiichi Sankyo Europe continues to deliver robust revenue growth and expand market share for both NILEMDO and NUSTENDI. We expect the recent inclusion of ESC/EAS guidelines to support its expanded utilization across the 30 countries of the European Union, where Daiichi Sankyo Europe already has in excess of 600,000 patients who have been treated with our therapies in Europe. DSE also expanded their geographic reach with the launch of NILEMDO in Denmark, Sweden and Finland. Third quarter royalty revenue from DSE increased 21% sequentially to $16.4 million compared with the second quarter of 2025. In August 2025, DSE announced the development of oral triple combination liquid-lowering tablets with the Santorini study simulation showing improved LDL-C goal attainment aligned with the 2025 ESC/EAS guidelines.

We continue to make progress advancing multiple processes for the technology transfer for manufacturing of NILEMDO and NUSTENDI to DSE with expectations for DSE to ramp up beginning in early 2026, and with certain working capital benefits expected in 2025. In September, we are delighted to report that our Japanese partner, Otsuka Pharmaceutical, received marketing approval from the Japanese Ministry of Health, Labour and Welfare for NEXLETOL as a treatment for hypercholesterolemia and familial hypercholesterolemia. Most recently, Otsuka received favorable preliminary pricing approval from the National Health Insurance in Japan, which will trigger significant milestone payments from Otsuka upon final pricing approval. This favorable pricing is particularly encouraging as the Japanese market is the world's third largest cardiovascular prevention market, and the royalties on Japanese product sales will be a meaningful revenue contributor over time.

We are also expanding our international reach in a variety of other regional markets where cumulatively, we are building meaningful revenue streams through commercial partnerships. Our Canadian partner, HLS Therapeutics, has already filed new drug submissions to Health Canada for NEXLETOL and NEXLIZET and are on track for market approval by year-end 2025. Our partner in Israel, Neopharm Israel, also expects market approval of NEXLETOL and NEXLIZET by year-end 2025. CSL Seqirus, our partner in Australia and New Zealand, filed a marketing submission for NEXLETOL and NEXLIZET in July and expects to receive market approval in the fourth quarter of 2026. The progress with these international partnerships is expected to deliver a steady cadence of approvals and product launches over the coming months and year that will provide a growing royalty stream and a few potential milestone payments, all of which support our strategic focus to drive revenue growth and profitability.

Turning to our pipeline, where our strategy is to expand into high-need, high-value indications that highlight the broader potential of our novel ACLY biology beyond cardiovascular disease. Here, we were excited to nominate ESP-2001, our highly specific ACLY inhibitor as our first preclinical development candidate for the treatment of primary sclerosing cholangitis, or PSC. With this candidate selection, we will begin IND-enabling studies with a goal to file an IND with the FDA to initiate first-in-human clinical studies in 2026. PSC is a devastating condition with no approved treatment, and our preclinical data suggests ESP-2001 has the potential to meaningfully impact disease progression. We're proud to advance a candidate that reflects the capabilities of our next-generation ACLY inhibitor program and our commitment to addressing areas of high unmet need.

With that overview of the business, let me turn the call over to Ben for a detailed review of our financial progress during the third quarter.

Ben?

Thank you, Sheldon. Good morning, everyone, and thank you for joining us today. Our third quarter 2025 financial results can be found in the press release we issued this morning, and more detail will be included in our upcoming 10-Q. Second (sic) [ Third ] quarter 2025 total revenue was $87.3 million, an increase of 69%. U.S. net product revenue was $40.7 million compared to $31.1 million for the comparable period in 2024, an increase of 31%. Collaboration revenue was $46.7 million compared to $20.5 million for the comparable period in 2024, an increase of approximately 128%, driven by increases in royalty sales within our partner territories and product sales to our collaboration partners from our supply agreement. Turning to the rest of the P&L. For the second (sic) [ Third ] quarter of 2025, research and development expenses were $14.1 million compared to $10.4 million for the comparable period in 2024, an increase of 36%.

Selling, general and administrative expenses were $41.8 million compared to $40 million for the comparable period in 2024, an increase of 5%. The increase quarter-over-quarter was primarily related to the increased legal costs associated with the ANDA litigation and increased media costs. We are extremely pleased with our third quarter developments and are planning the business differently with a focus on laying the groundwork to significantly increase our sales and marketing efforts to accelerate our revenue growth as we prepare to introduce our Vision 2040. During the quarter, we made meaningful progress to extend our IP runway and now anticipate inclusion in the U.S. guideline recommendations in the first quarter of 2026, which provides substantial opportunity to solidify our position as a premier therapy and build on our blockbuster franchise.

In October, we closed on a $75 million follow-on equity offering, which provided net proceeds of approximately $72.6 million. This equity offering was not a result of any changes in our liquidity outlook, but rather a strategic decision to ensure the company is well capitalized in order to make the most of these developments. We are reiterating our full year 2025 operating expense guidance, which is expected to be approximately $215 million to $235 million, including $15 million in noncash expenses related to stock compensation.

With that, I will now turn the call back over to Sheldon for closing remarks.

Sheldon?

In closing, thank you, Ben. This was a quarter defined by strong execution, strategic progress and growing momentum across every facet of our business. From commercial performance and market access to international expansion and pipeline advancement, we are laying the groundwork for our future growth and delivering on our mission to transform cardiovascular preventative care for patients. We remain focused, energized and confident in our ability to drive sustained growth and long-term shareholder value. We look forward to a strong fourth quarter and to introduce our Vision 2040 in the new year. Thank you for your continued support and belief in our vision. We look forward to updating you on our progress in the quarters ahead.

Operator, we are now ready to open the call for questions.

[Operator Instructions] And our first question comes from Jessica Fye of JPMorgan.

This is on [indiscernible] for Jess. Just one question from us. What were the drivers behind the gross margins for this quarter? And how can we expect this to progress moving forward?

Yes. Thanks for the question. So the gross margin drivers were the same dynamic we've seen in previous quarters, right? We have low-margin tablet sales to our partners. And the margin that you see is really reiterates the importance of the tech transfer and moving that manufacturing off of our books, which we still expect to complete by the end of the year and early into next year. So going forward, I would expect the gross margins to get better over the course of 2026 and be much more in line with where you would expect a pharmaceutical company of this type to be.

And our next question comes from [ Dennis Ding ] of Jefferies.

This is Georgia Bank on for Dennis Ding. Can you comment a bit more on achieving sustainable profitability in Q1 of 2026? And should this include any incoming milestones?

So I'll start with the second half. We don't include milestones when we mention profitability. We -- I think last quarter mentioned a lot about sustainable ongoing profitability, and that's where our sort of mantra headset is. When we look at how we're tracking towards some of the statements you made before, candidly, we're tracking right in line with the forecast and outlook that we had used to make those statements. So we are still confident in achieving profitability. I think when you look at some of the expenses incurred in Q3, a lot of them were onetime or nonrecurring, which drove down some of that net income number. And again, we would not expect those to repeat next year, which may affected Q3, but does not affect our outlook on the company.

And our next question comes from Jason Zemansky of Bank of America.

On the progress. Just a question in terms of reimbursement per script. It looks like you said scripts were up 9% quarter-over-quarter, but U.S. revenues were fairly flat. Was there a onetime hit here? Sorry, if I missed it? And I guess, what does it mean moving forward in terms of reimbursement there?

Thank you, Jason. First of all, again, I want to emphasize and you picked it up, our reimbursement rate is -- first of all, is increasing, and it's really due to the strong coverage that we have in both commercial and the Medicare side of the business. There were onetime hits. We actually -- and we mentioned this in our prepared remarks, -- we really want to set that stage for future growth of the organization. And even thinking about the ANDA filing wins, et cetera, we've been talking about how we're planning to 2040 and hence, why we mentioned this Vision 2040, which we'll talk about more in the next couple of months and so forth. But the onetime hits where we actually made some investments with 2 of our larger Medicare plans to get more preferred access, which began on October 1, but we have to do some accounting to account for those adjustments starting in the third quarter. And we decided to do that for the benefit and the future of growth.

The other thing that we did is we also introduced a new e-voucher for our 90 count prescriptions. And what we saw there is when we initiated that program, we have seen less abandonment from patients. And basically, what it did is it provided equilibrium on the co-pay amount, whether it's a 30-day fill or a 90-day fill. And that was very important for us. So these were onetime commitments that we've made. And what's really interesting, I'll just put this out here right now. If you look at where we are in the fourth quarter on a like-for-like basis compared to this time last quarter, we're already seeing our gross sales increase by about 30%. So these things are already paying off for us, and we're happy we made these decisions for the future. Thank you.

And our next question comes from Kristen Kluska of Cantor Fitzgerald.

I know it's early days, so this isn't going to be reflected in the revenues. But now that the ESC guidelines have been changed for a little bit over 2 months, I'm curious if your partner has given any feedback about the level of incoming requests that they've gotten or how their reps dialogue has changed and the reception since that's occurred. And just trying to also understand again how this is going to really help give you a preview of what could come in the U.S. early next year.

Yes. Thank you, Kristen. So actually, I just spoke to the CEO of Daiichi Sankyo in Europe. And I was saying this on the call yesterday. I don't know if this is the most professional thing to say, but it's not often that he's very -- German and he said, we are over the moon. This is a very U.S. expression. We are over the moon by the excitement that we've seen with physicians, key opinion leaders, et cetera, related to the guidelines, and they see it as already being very, very meaningful. He actually showed me some of the early trends. And to your point, it is early in some of their leading countries where they continue to show these positive inflections and it's only going to get better because of the guidelines. The guidelines really came across as representing bempedoic acid as a foundational therapy. And as what we've mentioned before, the way the guidelines were presented at ESC, they specifically said they added bempedoic acid based on 2 items, and that is practice-changing and compelling data, which is a result of the CLEAR Outcomes study.

We think that's a great indicator for what we're going to see here in the U.S. for our guidelines. As a matter of fact, our U.S. representatives have an approved piece where they're educating physicians on the EU guidelines because maybe many U.S. physicians, especially cardiologists, they look at EU guidelines because they have a goal of 55 milligrams per deciliter for high-risk patients. So it's a great lead-in for us of when the U.S. guidelines come out, which we think is going to be early first quarter, and they're going to use the meeting at ACC as a training ground. So again, some of these onetime investments that we've made, that's why we made them to set us up for that longer sustained pathway of growth.

Okay. And then just as it comes to Otsuka and the opportunity in Japan, now that there's preliminary pricing, what's really the next step for them with the authorities there? And then what is your expectation on the timing of when this could occur?

Yes. So with Otsuka, we -- to your point, we received preliminary pricing and that preliminary pricing, I will know we are very, very happy with it. It's fantastic. It's a great outcome for us. The next steps for them is they're waiting for final pricing and then shortly after the final pricing is when they will launch. And that launch will come, I would say, just a few days after the final approved pricing. We would expect all of that to happen probably in the next 2 to 3 weeks, just pending sort of administrative paperwork on their end. And then from there, it's off to the races for them. As Sheldon mentioned, this is the third largest lipid market in the world. And it's really just this regulatory hurdle is the last step for them to start getting out there and selling this product.

I would just add, we're excited personally because Ben and I will be heading out to Tokyo later this year to celebrate with them and help them and observe the launch. So it's really exciting.

And our next question comes from Paul Choi of Goldman Sachs.

I want to maybe just ask on what you're seeing with regard to 340B utilization of NEXLETOL and NEXLIZET and how you're thinking about that dynamic potentially evolving in 2026? And my second question is just with regard to the pipeline and PSC. I know you guys are still working on IND filing, but just how do you think about the number of centers? And just if you had to sort of put some bookends around what enrollment timing might look like? Any clarity there would be helpful.

Thanks, Paul. Good to hear from you. So on the 340B side, honestly, it's a miniscule unnoticeable portion of the business. And so as far as the dynamics going forward is it would have a non-impact on our outlook or on our revenues. It's not a factor in how we operate.

Thanks, Ben. Paul, regarding PSC, first of all, again, we're super excited about announcing ESP-2001. Just a little color. We actually were at a patient support group that they have. PSC did a symposium in Denver, where we were the highlighted company to speak about this potential drug for patients who they just need something with such an unmet need. And we've talked many times about how our drug is very differentiated, et cetera. As it relates to the amount of centers that we will need, we're still in the planning phase for that. I can tell you right now, we're planning to meet with the FDA just to think about also what are the necessary endpoints, et cetera. So we're in that preliminary aspect. We just had a Board meeting. We went over that plan actually yesterday.

So we'll continue to update you and others where we are, but we're trying to move this as quickly as possible because there is such an unmet need. And again, with ESP-2001, we have a drug that not only treats symptoms, et cetera, but repairs injury. And I think that's what's so most important. If we can prolong or even eliminate the fact for a patient to receive a liver transplantation, that's transformational in this disease. So stay tuned, and we'll be giving more information as we continue to receive it ourselves.

And our next question comes from Serge Belanger of Needham.

First question regarding the prescriber base. I think you continue to expand it. It was up 7% this quarter. What's the split between specialists and primary care physicians? And as you keep adding, is that -- are those proportions changing towards one side or another? And then a couple of quick ones for Ben. Any updates on the DSE manufacturing process? And should we expect guidance for 2026?

Serge, thanks for the question. I'll answer your first, turn it over to Ben for the second. So it's pretty steady right now as it relates to the segmentation, if you will, of prescribers. It's 60%, 6-0, primary care and about 40% cardiologists with a very small sliver of endocrinologists. That's exactly where we would have expected it. Even if you go back to the old days and you look at Zetia, now ezetimibe as an analog, a program I managed for a number of years, it was 60% primary care physicians, 40% cardiologists. And again, that's where the real opportunity is with these primary care physicians. The one other thing I'll just say before I turn it over to Ben, what really resonates with primary care physicians as well is our messaging related to primary prevention. And this is something that they're very interested in. And it's combine that with our statin intolerance strategy, it's really been gaining traction, as we mentioned in our prepared remarks.

Yes. So on the tech transfer, it's progressing nicely. We expect that manufacturing to ramp up early next year. And I think I said earlier, I would expect gross margin to dramatically improve over the course of 2026 to be in line with where you'd expect a small molecule oral medication to be. That will -- it won't be an overnight flip, but I do think it will get better and better. We are starting to see some of the working capital benefits associated with it now and into next year. And so we're looking forward to the benefits of that tech transfer. On guidance, we haven't made formal decision or announced anything as of yet. I think we're still batting that around internally. So we'll see is the answer there.

And our next question comes from Joe Pantginis of H.C. Wainwright.

This is Sara on for Joe. Kind of just wanted to follow up a bit on the prescription momentum. You guys have been seeing consistently double-digit script growth. I just wanted to get some maybe granularity on what you're seeing in the field right now that kind of gives you the confidence that the momentum will continue into the new year, especially with that January deductible reset that's historically been a headwind.

Yes. Great. Thank you. So what we're hearing from the field and just to add some color, we actually do business reviews every Friday with all of our field managers. And I think the feedback that we hear the most that really gives us confidence is the fact that I've been doing in this business for 30-some years, and it's the first time that I'm never hearing that it's hard to get the drug. The reimbursement is just so pristine that it's not difficult to get the drug. The message is easy. Talking to a physician and talking to them about the fact that, hey, doctor, if you have a patient who can't take a statin or can only take a low dose of a statin, you have an option now, an oral therapy with NEXLIZET or NEXLETOL. And that's really what's given us confidence.

We also have these attribute trackers that we do. So we're able to do market research that also gives us qualitative feedback that points to why physicians will write more and will continue to write more. And Lisa, I don't know if you want to add anything else. But -- we have Lisa Schafer, who heads up our marketing group also here.

Yes. The other thing that I would add is just around the ESC guidelines. So that is something that the cardiologists are really receptive to with the Level 1A recommendation and that will continue into next year because the guidelines for the U.S. will come out. So we have a lot of great tailwinds coming into fourth quarter and definitely expect it to continue next year in 1Q.

I'm showing no further questions at this time. I'd like to turn it back to Sheldon Koenig for closing remarks.

We're all doing the slides today, folks. So in closing, this was a -- thank you. It was a quarter defined by strong execution, strategic progress and growing momentum across every facet of our business. From commercial performance and market access to international expansion and pipeline advancement, we are laying the groundwork for our future growth and delivering on our mission to transform cardiovascular prevention for patients.

I want to remind everyone that next week on November 11 at 2:00 p.m. Eastern Time, we'll be hosting a virtual key opinion leader event on the role of bempedoic acid for the treatment of statin-intolerant patients that will feature discussion with a number of lipidology experts. We hope you can join us for that, what we expect will be an interesting and very informative event.

We're also looking forward to participating in a number of upcoming conferences, including Jefferies London and the Piper Sandler Healthcare Conferences, where we hope to have the opportunity to connect with many of you then. In the meantime, if you have any questions or would like to have a call with the team, just reach out to our Head of Investor Relations, Alina Venezia, and have a great day. Thank you so much.

This concludes today's conference call. Thank you for participating, and you may now disconnect.

Okay. Good morning, everybody. I'm Kristen Kluska, one of the biotech analyst at Cantor. Thank you so much to the Esperion Therapeutics team for being here today. We have Sheldon Koenig, the CEO; and Ben Halladay, the CFO. Thanks again for being here.

Thanks for having us.

Good to be here. Thank you.

Yes, our first conference together. Cool. So maybe to start, can you just provide a very high-level overview, and then we'll get into some of the specifics.

Yes, we'll do. First of all, again, thank you for having us at the conference. And on behalf of all the employees, we're happy to be here and have the chance to chat, and thanks for all the attendees.

Look, at Esperion, our mission is to essentially commercialize life-saving medications, which we're doing with NEXLIZET and NEXLETOL. We're also developing life-saving medications, what we think will be life-saving medications. We held an R&D Day back in April 24. You attended, and we have some interesting compounds. But right now, the focus is on commercializing NEXLIZET and NEXLETOL in the United States. You probably saw from our quarter 2 results, we have significant momentum, showing double-digit growth in all metrics. And we might get into this later, but we had a terrific European Society of Cardiology and the guidelines. So just really excited about the future and where we're heading.

That was a very exciting way to kick off a holiday weekend in the U.S. So thank you to our partners in Europe for that. So before we touch into some of the drugs, I think it's really important to talk a little bit about patient background. I think sometimes this is overlooked, right, but it's a critical part of the story. So when we think about these patients, how are physicians monitoring cardiovascular measures in the real world? And how do they then determine whether or not a patient is responding to a lipid-lowering therapy?

Yes. And I'll give you the -- really the real-world answer, not the academic answer, if you will. The real-world answer is there's a lot of, what I would call, fire and forget strategy with patients. Patient will go, get a lipid panel, will show elevated cholesterol and the physician will say, "I need to put you on the statin," and they put them on the statin. And they may or may not follow up. This is more in the primary care setting.

I think cardiologists do more follow-up, but for primary care physicians, they really don't. And I think what you heard in ESC because I'll put this now, and I think where the world is going, it's about how do you treat stronger, faster, no longer can you get to goal on one product. A statin is not going to do it. So now it's about combination therapy, similar to where we've been with hypertension and diabetes for years.

So a patient may come back after they get their lipid panel and they might need some additional LDL lowering. Doctor may add ezetimibe, may not, may say, let's wait another 6 months. And I think, personally, and that's why cardiovascular disease is the #1 killer not only in the world -- obviously, not only in the United States, but in the world, is because it's just somewhat laissez faire of treatment. And that's really unfortunate because you do have to treat fast, and that's the new emphasis.

I know one of the ways companies report data is by this whole notion of LDL-C lowering in percent. But how do we account for the fact that patients are obviously coming in with different baseline measures and levels of degree severity? Will the threshold of what really matters in the goals change depending on where they start off?

I think, look, we're -- what's happening right now is patients are coming in. As I mentioned earlier, they're coming in with elevated LDL. There's this notion of they're X percent away from goal. They're not at goal. You may recall in the United States back in -- I think it was 2016 with the revision of the AHA guidelines, they got rid of goals. That caused a lot of confusion in the United States.

And what you saw is physicians, especially cardiologists look to Europe for what is a goal, and that became the 55 milligrams per deciliter. And I think you're going to see that's going to be more and more is how do I get more aggressive with patients, especially at high risk to get them to these lower goals of LDL.

I went to a seminar at ESC. LDL cholesterol is what causes heart attacks and strokes. It's the buildup of that plaque. And there's other drugs out there to address CV risk, et cetera. All of them working together are trying to provide more protection for a patient, but you really have to get these physicians to realize they've got to get their patients to goal.

Okay. It's okay. So statins have been a great drug for several patients, but a lot of them don't tolerate it or they may not be responding. At what point are they going to their physician and saying, "Look, this isn't working for me. I need a new option." And how often is just changing statin actually solving the problem?

Yes. So usually, what happens is they present with some type of muscle ache or pain. And Ben and I are actually just talking today, not to violate HIPAA, but you may mind tell your story about rosuvastatin.

Yes, I'm on rosuvastatin and I've recently started feeling muscle pains, and I'm on the lowest dose of rosuvastatin 10 milligrams. And so Sheldon and I were talking earlier today, is this statin intolerance essentially?

And the same thing happened to me when I was originally put on atorvastatin. I'm a big runner or at least used to be, and I get this leg pain. And then my doctor would say, "Well, let's try you on a different statin at a lower dose." And that did help. But because it was just a low-dose statin, I couldn't get to goal. I think, as you know, I take NEXLIZET. And my cholesterol is a 40 milligram per deciliter. So I'm really excited about that.

But I think the point is that patients will come to their physicians and say, "I cannot take a statin." And I think what happens there is then they consider, well, I could try another statin or I can also just maybe even use a drug like NEXLIZET, which we're seeing a lot of momentum with that.

I think one thing to keep in mind is LDL-C is an asymptomatic disease, right? You don't feel bad when your cholesterol is high. But for 30% of the U.S. population or the global population, by taking something and addressing your LDL-C, you're turning that asymptomatic into a symptomatic disease through muscle pains or myalgia or a lot of the different side effects of statins. And that's where I think there's a real opportunity for additional therapies to come in and help get those people to goal.

Yes. It's interesting, right, when you have a condition where technically, you feel fine, but all of a sudden, you're getting on a medicine and you don't feel fine. And even though you understand the importance of your heart health, it's a change for you, right?

Exactly.

Okay. So -- and then I guess, just help us understand, though, like at what point do physicians say, "Okay, look, we tried you on another statin. We tried messing with the dosage. Now, it's really time for me to maybe offer a new drug that has a different mechanism of action for you."

It happens pretty quickly, and we're seeing that now. We pivoted to a strategy to really establish this beachhead of going after statin-intolerant patients. That's 2 types of patients. Patients who one can't take a statin at all, and there's a lot of them. We know the NLA put out a paper in February, said 30% of patients can't take a statin at all. And then there's those patients who can only take a low-dose statin.

And what's interesting, again, just to go back to the ESC guidelines and even our own data that we've shown is that with a low-dose statin and the SANTORINI study showed this as well by Daiichi Sankyo, a low-dose statin plus NEXLIZET gets close to 75% of patients to goal. So that's the beauty about NEXLIZET and NEXLETOL. You can use it with a statin or without a statin. And I think that's really important. And physicians have really picked up on that.

Okay. And then to the point earlier, part of this is like a lot of education because you're telling the patients they're at high risk. But again, they don't necessarily feel the aspects of their disease every day. So what does it take for -- like do you -- is it your understanding that these patients actually take that feedback quite seriously and they will do whatever it takes, if it means protecting their heart health, avoiding events?

If patients are educated appropriately, they will, especially if they have family history. It's something that motivates them. I'll just put in a quick commercial. We have a commercial that's going to be starting in about 20 days on connected TV directed to consumers. We're excited about it. So especially any of you Grey's Anatomy fans, they'll be running the new season, and we're -- that is going to also motivate consumers.

Okay. I am admittedly a Grey's Anatomy fan. So I look forward to seeing the commercials along with the, I don't know, 10-plus million people that are also still sticking with it after 20 seasons like me. So one source of pushback has been that statins are generic. So how does this play into the whole reimbursement dynamic?

Yes, it hasn't been an issue. Statins are always considered the cornerstone of therapy. If you look at our coverage, we have 92% favorable commercial coverage. If you look at Medicare, we're at 75%, again, preferred favorable coverage. So the co-pay is affordable. There's actually a really interesting paper that just came out in circulation about a month ago. I'm not sure if we sent it to you, but I will. But it basically shows what drives consumer preferences. And what drives is price and also convenience of dosing and hopefully an oral. We meet all of that criteria. So not only do we have this great reimbursement environment, we're oral, so you don't need to inject and it's easy. It's once a day with or without food.

Okay. So let's shift to some of the market initiatives now. Maybe just what's been your high-level strategy? You mentioned on your last earnings, this was a big inflection point in our view, at least so what's kind of been leading to that traction?

Yes. I think what's been leading to it is, again, we've been really out there messaging to physicians, similar to the questions that you asked is that we know you've got patients in your waiting room who can't take a statin who are not at goal because they can only take a partial dose of a statin. Why wouldn't you add NEXLIZET to them? You have 38% additional LDL efficacy. And that has really resonated with physicians.

The other thing is, as you know, from the CLEAR Outcomes study, we have a very unique indication from a primary prevention perspective. We're the only ones who've studied a drug like this in statin-intolerant patients. So it's a message that we can own, and that's really resonating with physicians. And what we're seeing is they're saying, "Hey, if this is the efficacy I get without a statin, what would it be if I added a statin?" And so we're seeing more of that as well as we move across our segmentation.

Okay. So we often talk about the U.S. opportunity, but I think my entire coverage universe, maybe even, you've been very smart to leverage successful partnerships in regions where they already have expertise. And you've been very clear, like let the experts in those territories, they will have the best chance of getting our drug out there. So just before we jump into all of those, obviously, each country is a different size, but just like from a prevalence standpoint, is it similar to the U.S.? Are there regions where it's lower, higher?

Yes. So I think kind of going from top of list down to bottom, Europe, they've demonstrated a fantastic traction for this drug. The guidelines only reinforce that. I think I've had people tell me this will now just sell itself in Europe. That's been the biggest. We think, honestly, there's a good chance this could be 1:1 U.S. to Europe and a $1 billion product in both markets.

I think after that, Japan is by far the biggest market. We think that's 1/3, and it's a close 1/3 to Europe. So there's a lot of opportunity. We know that statin intolerance is very prevalent in the Japanese population. You also tend to see more super responses than that. And the trial that Otsuka did to bridge that clearly define that.

After that, we also have partnerships in Canada, Australia, Israel. And I think those are -- they're smaller markets, but I think there's still a lot of opportunity there. And they've made -- we recently had some very good progress on the regulatory process there moving those forward. And it's all incremental, right, especially in Canada. It's a very tough reimbursement market in Canada to get any sort of favorable access there. But what they've managed to do has just been incredible. And I think we will have a very good outcome from those launches that will put meaningful top line for this company.

On that note, do you mind sharing what these new guidelines are? I'm not sure if everybody is aware as it's, quite frankly, hot off the press.

Yes, sure. So we actually received a Class Ia recommendation, which is really the best you can get. And I think what was important is that bempedoic acid was the only new therapy that actually received its own section in the guidelines. And the focus was really on, again, how do you strike fast, strike quickly. I think what was important about the guidelines and during the review of bempedoic acid itself during the guidelines, I was there live, was the fact that these changes were made based upon data that was practice-changing and essentially life-saving. That's really important. And it's something that, as you know, we mentioned in our press release.

It essentially demonstrates that bempedoic acid is a foundational therapy in treating patients. Again, as I said earlier, one drug doesn't get you to goal. And in every combination they showed, it was with bempedoic acid first. And then if you needed more to add more. But again, I'll say it again, the SANTORINI study showed that patients who are on a statin, are on bempedoic acid, 75% of them achieve goal. So there is room for other drugs, but for the majority of purposes, bempedoic acid is your partner of choice.

Okay. And then when we think about all these other geographies where you have existing partnerships, I know all of them are structured differently in terms of milestones and royalties, but what is the collective TAM or opportunity? And how is this going to keep the engine going for the U.S.?

Yes. I mean I think -- like I said before, I think Europe is definitely a $1 billion opportunity. I think from a TAM perspective, we -- 30% of the population is statin intolerant. And we think that there is a lot of opportunity to address that globally. We think that's consistent across all markets. The royalty streams are pretty consistent between each of the agreements, and that's just incremental top line to us addressing that 30% statin intolerance. So it's a pretty significant tailwind for the company that we expect over the years.

Overall, I think just from a collective TAM perspective, again, in the U.S., it's $70 million. Europe looks a lot like the U.S. This is one of the largest markets, one of the largest therapeutic markets in the world, no question about that.

Cool. So you're also working on a triple oral combination, which may have -- even more competitive to what we're seeing out there. How do you already, though, have a strong sense of what the combined LDL-C reduction could look like?

Yes. We've actually modeled that. And we actually conducted a study, and we looked at the use of atorvastatin 10 milligrams with bempedoic acid plus ezetimibe, and we showed anywhere between 65% and 72% LDL reduction. Again, I would direct you to the ESC guidelines where they've done their own modeling, and they're showing 65% plus LDL lowering in using a triple combination. We are doing a triple combination in both rosuvastatin and atorvastatin, so physicians will have a choice.

And I'm going to brag for the company in Daiichi Sankyo. We have the strategic foresight to see that combination therapy was going to be the future of therapy in cardiovascular medicine. When it came to lipids at ESC, that was the focus, combination therapies. So now not only do you have this powerful LDL-lowering drug, but it's a one pill, it's convenient. It just makes perfect sense. And so we're ahead of the game, and I'm excited about it. I will say we already have names for these drugs. We're not releasing them yet, but stay tuned because they're really good ones.

Does it start with an N?

No, it doesn't.

We can go through the alphabet if you want to try and guess that.

Let's see, we got [indiscernible]. So if this ultimately does become approved, how is it going to change the treatment paradigm, including a good way to be competitive with your other 2 existing therapies?

I think, one, it gives physicians flexibility. But regardless of if you're using the triple combo or if you want to be old-fashioned and use whatever combination you want, use drugs individually, et cetera, it's all about getting patients to goal faster. That's the theme here. How do I get patients to goal quicker? I think everyone thinks of atherosclerosis is this kind of, "Oh, I can live with it for years, I don't have to worry about it." That's not true, not to scare anybody, but plaque could break off right now and you can have a stroke or a heart attack. There's no such thing as it's going to take its time. It's a disease that, unfortunately, because it's quiet, you think you have time, but you may not. And that's why you have to treat aggressively. That's what triple combo or any combination therapy with our drug will allow you to do.

Okay. So on the competitive side, why don't you believe investors should be super hyper focused about this? And one would think even if they are successful, you're not competing over 10,000 patients worldwide, there should be plenty of room for others, right?

Yes, there's definitely room for others. Again, unfortunately, this is a disease that's the #1 killer in the world. We've got statins. We have PCSK9. We have bempedoic acid, you have bile sequestrants, cholestyramine, all drugs. We have all these drugs, right? And the fact is, again, it's a combination of the use. I would argue, of course, you would use NEXLIZET first is what the guideline showed in Europe, and we'll see what the U.S. will show.

But these other drugs, they're not in the market yet. When somebody asks me how you compete against a Merck or CETP, I would say, well, what do their labels look like because we have an outcome study. And we have to wait and see where these drugs end up. And in the meantime, we're available now, soon almost across the entire world, so.

Yes. Sorry, I should have asked you before these guidelines that come out, how do physicians actually react to them, abide by them? Like how important are they?

They're super important. So especially with cardiologists. Cardiologists really focus on the guidelines and what you find, at least in the United States. In Europe, they're very important. Everyone looks at them. In the U.S., it's usually really looked at by cardiologists and then through advocacy and talking to primary care physicians, the message gets carried through. But if you look at Entresto back in 2016, when they finally were allowed to be put into the guidelines, they were to be used as the primary anti-platelet after hospital discharge, the drug really took off, but it wasn't until then.

We've been able to show this momentum and all the payer coverage I talked to you about before we even have guidelines. So now with these guidelines, it's just really a reinforcement, if not even more of a catalyst to say, I should be using this more. Again, depending upon what the U.S. guidelines will say, but we feel, as we felt with ESC that we will be prominent in the U.S. guidelines.

Do we have a sense of when the U.S. guidelines might come out? And just historically, do we tend to see similarities? Do they kind of leverage off of each other depending on which one gets updated first?

They used to. Back in 2014 or 2016 when the changes were, they diverted away, as I mentioned earlier, with no goals. I think what you'll see now is there'll be more of an alignment because there is such controversy over the last time the guidelines were done. So late-breaking news, we think the guidelines will be available early first quarter before ACC. And the reason for that is that ACC, that meeting will be used as a training ground for the new guidelines. So that's the latest information that we have. That's new, and we'll be following that.

Cool. You heard it here first.

Yes, yes, yes, that's right.

So you did have an R&D Day this year, and we learned about the next indication that you're looking at, primary sclerosing cholangitis, or PSC for short. Unfortunately, it has been an area where we haven't seen much success. So what are the key things we can learn from others that have tried and failed? And what is it about this target that may make sense?

Yes. I'm not the expert in the science, but I think the way that it's been described to me and from what I've seen that Steve Pinkosky has been working on this is we have kind of found this intersection between cell metabolism and fibrosis, where we can not only go after the injury, but we can also provide healing itself. And no other compound that's been developed or being developed has been able to show that. And this is really due to ACLY biology. This is what really makes this pathway unique. And that's why we feel so, I would say, confident that we're going to have success. We hope to be in the clinic next year. That's our goal. And we're excited about this. And stay tuned. We'll be providing more of an update as we get into early next year as well where we are.

Is there a sense of when in the disease course, it might be best to try to treat these patients?

I think from what I understand about the disease, it's somewhat late -- it's almost a late presenting disease because it's not easy to diagnose. So I think it's right at diagnosis you'd want to start this type of therapy.

Yes. No, at your R&D Day, you had a mother kind of walking us through her son's experience and how he was diagnosed.

Right. And also often because this drug or this disease leads to transplantation, the sooner you can do something to maybe either delay that or not have that at all, I think, would be important.

So what's the current financial situation of the company? And anything else we should really be taking away today about Esperion?

Yes. So I think the current financial situation is great, to be honest. I'm trying to come up with a better word to say it, but it's great. We've done a lot of work over the last 2 years correcting the capital structure of this company. That demonstrated trajectory has really continued to improve the financial profile of where -- not only where we're going, but also where we are. Q2, we announced we had positive operating income for the first time from ongoing operations. So not necessarily driven by large milestone or a onetime event. But just the things that we do every single day drove positive operating income.

And we've gone on record that Q1 2026, we believe, will be our first fully profitable quarter. Candidly, I don't think anyone believed us until Q2. And that now lets people draw a direct line from Q2 to Q1. But we've decreased the debt profile. We are -- we have ample cash. We've shown strong U.S. growth that has continued quarter over, quarter over quarter, and we don't see that changing anytime soon, to be honest, up until loss of exclusivity, to be honest. So yes, it's good.

And if I may ask a question, can you provide clarity around the Otsuka milestones?

Yes. No. So the other -- thank you, Sheldon, I was supposed to mention that earlier. So the other thing to keep in mind, as I said, we have ample cash now, but we also have large milestones with our Japanese partner, Otsuka, and those are tied to the regulatory process in Japan. And to be very clear, they are tied to both approval and pricing. We had a preliminary approval from the health authority last week. That's not the official approval, but it's one of those things that I don't think there's ever been a breakup between the 2 ever. So it's kind of a tentative approval. Pricing can't happen until that full official approval happens, but it usually happens shortly after. We've already had some of those pricing discussions, but we need both of those to achieve those milestones. But we're confident that those events will happen in the near future.

I think what we saw Friday was not that we ever thought that there was any risk, but just a derisking to the approval. So a very important milestone.

Wow, you had a great Friday.

Yes, it's been great.

Cool. Awesome. Well, thank you so much for being here. Really appreciate it. We're excited to see what you have in the next few months ahead.

Awesome. Thank you so much. Really appreciate it.

Hello, ladies and gentlemen, and thank you for standing by, and welcome to Esperion's Second Quarter 2025 financial results. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to Alina Venezia, Head of Investor Relations for Esperion Therapeutics. Please go ahead.

Thank you, operator. Good morning, and welcome to Esperion's Second Quarter 2025 Earnings Conference Call. With us on today's call are Sheldon Koenig, President and CEO; and Ben Halladay, CFO. Other members of the executive team will be available for Q&A following our prepared remarks. We issued a press release earlier this morning detailing the content of today's call. A copy can be found on the Investor page of our website together with a copy of the presentation that we will also be referencing. I want to remind callers that the information discussed on today's call is covered under the safe harbor provisions of the Private Securities Litigation Reform Act.

I caution listeners that management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to the risks and uncertainties associated with the business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and in our SEC filings. The content of this conference call contains time-sensitive information that is only accurate as of the date of this live broadcast, August 5, 2025.

We undertake no obligation to revise or update any forward-looking statements in the conference call and webcast. As a reminder, this conference call and webcast are being recorded and archived. We will begin the call with prepared remarks and then open the line for your questions.

I'll now turn the call over to you, Sheldon.

Thank you, Alina. Good morning, everyone, and thank you for joining us. We're thrilled to report a standout second quarter that delivered double-digit sequential growth, more than 42% year-over-year gains in U.S. net product sales and our first quarter of operating income from ongoing business. These results reflect accelerating clinical adoption of NEXLETOL and NEXLIZET fueled by our sharpened commercial execution, strong payer alignment and our ongoing targeted promotional strategy that's resonating with the statin-intolerant community. Total revenue for the second quarter 2025 grew 12% year-over-year to $82.4 million.

Looking at our strong U.S. performance, where we saw a return to sequential double-digit quarterly prescription and revenue growth, U.S. net product revenue grew 42% year-over-year to $40.3 million and grew 15% sequentially from the first quarter of 2025. Given our strong performance, we achieved operating income from ongoing business of approximately $15 million, giving us confidence that with continued global growth, we expect to transition to sustainable profitability beginning in the first quarter of 2026.

As we shared on our last call, the endorsement of NEXLETOL and NEXLIZET from leading cardiovascular professional societies was a powerful validation of our science, and it's already translated into action. Later this month, we look forward to the European Society of Cardiology, updating their lipid management guidelines at the Society's Annual Meeting, where we expect to be included in these updates.

Turning to the progress we made on a number of our core marketing initiatives, including our campaign to reach patients who are statin intolerant, our tagline, Can't take a statin? Make NEXLIZET happen was well received, and this catchy phrase supported increased brand awareness among our target audience. In fact, during the second quarter alone, we had more than 650,000 visits to our new consumer statin intolerance website and more than 600,000 click-throughs to our physician site underscoring the impact of this successful campaign. We are implementing the right balance of in-person and digital outreach and are pleased to report that 23% or nearly 1/4 of our prescriptions were written by physicians with only digital touch points.

In addition of prescriptions coming from new writers, 38% were driven by digital-only touch points. This highlights the importance of our digital omnichannel programs and underscores the impact they can continue to have. We remain committed to building on these successful programs and are confident in their continued contribution to our growth.

Our expanded U.S. field reimbursement manager support team made great strides in supporting our growing prescriber base by educating over 1,100 target prescribers on NEXLETOL and NEXLIZET favorable reimbursement landscape. This was evident by an increase in all targeted prescriber approval rates to over 80%. Combined with further expanded payer coverage, reductions in prior authorization requirements, increased reimbursement support resources and our appropriate balance of direct and digital marketing efforts, we believe we have significantly improved the access environment for patients and physicians alike, which resulted in a 10% increase in total retail prescription equivalents from this first quarter of 2025 and increase our total prescriber base to more than 28,000 health care practitioners.

This momentum validates the growing confidence among clinicians and the expanding role of our therapies in addressing the unmet needs of statin-intolerant patients. Our consumer marketing program featuring the lipid lurkers tackles a challenge of high cholesterol, a silent but serious threat by transforming it into mischievous characters that demand attention, which may be quietly lurking without their knowledge. Rather than relying on fear tactics, the lurkers personify LDL-cholesterol's hidden dangers making the risk tangible and manageable without intimidation. This fresh compelling approach reshapes how patients perceive and address their cardiovascular risk.

By blending engagement with patient empowerment, the campaign stood out in a crowded market, driving awareness and action for proactive cholesterol management with NEXLETOL and NEXLIZET, the next step after statins. This campaign has won the prestigious Med Ad News Best Consumer Digital campaign and is nominated for several more awards this year.

Moving forward, we plan to launch a consumer television ad later in the year that will stream on connected TV, such as Hulu and NBC Sports. These branded ads are expected to broaden awareness of statin intolerance and will feature our award-winning lipid lurkers. The combined strength of the statin intolerance and lipid lurkers campaign, coupled with improving payer dynamics support our continued growth now and into the future.

Speaking of future growth, we remain committed to Esperion's continued growth in cardiovascular risk reduction with our plans to develop a triple combination product. This therapy has the potential to be the most effective oral LDL-cholesterol lowering option and to rival both existing injectables and emerging oral therapies. Development remains on track. In addition, our business development efforts are progressing nicely as we evaluate a number of potential opportunities to in-license or acquire synergistic products to leverage our existing commercial infrastructure. We look forward to updating you on progress here as it unfolds.

Additionally, we reached important settlement agreements with 3 NEXLETOL -- 3 generic manufacturers have agreed not to market a generic version of NEXLETOL in the United States prior to 2040. We continue to identify opportunities to strengthen our intellectual property position and look forward to updating you on our progress.

Turning to our pipeline, where our strategy is to expand into high-need, high-value indications that highlight the broader potential of our novel ACLY biology, we continue to make progress advancing IND-enabling studies to support our recently introduced program targeting primary sclerosing cholangitis, known as PSC. PSC is a rare progressive liver disease with no approved therapies and represents a major unmet need with an estimated $1 billion annual market opportunity. We look forward to completing these studies and to filing an IND and potentially initiating first-in-human studies in the second half of 2026.

Throughout the second quarter, we and our international partners continue to make tremendous progress across a number of key geographies. Our European partner, Daiichi Sankyo Europe, continues to expand their reach of NILEMDO and NUSTENDI to benefit patients at the risk of cardiovascular disease who cannot manage their LDL cholesterol levels.

Our royalty revenue from DSE increased 30% from the first quarter of 2025 to $13.6 million in the second quarter of 2025. We are also thrilled to report that DSE has surpassed the 500,000 patient mark for patients who have been treated with our therapies in Europe. 0.5 million patients, this is a meaningful milestone that reinforces confidence in our ability to build a similarly sized market in the U.S.

Throughout the first half of the year, we continue to advance multiple processes for the technology transfer for manufacturing of NILEMDO and NUSTENDI to DSE with the various working capital benefits expected in 2025. Our Japanese partner, Otsuka Pharmaceuticals, submitted for approval of our bempedoic acid products in Japan for LDL-cholesterol lowering and remain on track for approval and national health insurance pricing in the second half of 2025. Upon this achievement, we expect to receive milestone payments of up to $120 million.

The Japanese market is the world's third largest cardiovascular prevention market, and we believe the royalties on Japanese product sales will be a major revenue contributor over time. Building on our global progress, we expanded our international reach through our commercial partnership with HLS Therapeutics, giving them the exclusive rights to commercialize NEXLETOL and NEXLIZET in Canada. Our previously filed new drug submissions to Health Canada are on track for review, and we continue to expect market approval in the fourth quarter of 2025.

Our partner in Israel, Neopharm Israel remains on track for market approval of NEXLETOL and NEXLIZET in the first half of 2026. And CSL Seqirus, our partner in Australia and New Zealand filed a marketing application in Australia for NEXLETOL and NEXLIZET in July 2025 and expects market approval in Q4 2026. The progress with these international partnerships is expected to deliver a consistent cadence of approvals and product launches over the coming months and year that will also provide a growing royalty stream and milestone payment, all of which support our strategic focus to drive revenue growth and profitability.

With that overview of the business, let me turn the call over to Ben for a detailed review of our financial progress during the second quarter. Ben?

Thank you, Sheldon. Good morning, everyone, and thank you for joining us. I'm extremely excited and proud to share our financial results today. Our second quarter 2025 financial results can be found in the press release we issued this morning and more detail will be included in our upcoming 10-Q. As you've heard Sheldon discuss, we had an exceptional second quarter, highlighted by our first of operating income from ongoing business in the company's history, which sets us up nicely and supports our plans to transition to sustainable profitability starting in the first quarter of 2026.

We are proud of the progress we've made and it underscores our long-held assertion that incremental growth when compounded and expanded will drop to the bottom line. Over time, this gives us considerable leverage as we move forward with confidence.

Turning now to the financial results. Second quarter 2025 total revenue was $82.4 million, up 12% from the comparable period in 2024. Note, this impressive growth was achieved even when compared to second quarter 2024, during which we received a $25 million onetime milestone payment, further highlighting the strength of our underlying business. U.S. net product revenue was $40.3 million compared to $28.3 million for the comparable period in 2024, an increase of approximately 42%.

Sequential quarterly net revenue growth was 15%. Collaboration revenue was $42.1 million compared to $45.5 million for the comparable period in 2024, a decrease of approximately 7%, driven by the settlement agreement milestone with DSE received in the 3 months ended June 30, 2024, offset partially by increases in royalty sales with our partner territories and product sales to our collaboration partners from our supply agreements. Excluding the settlement agreement milestone, collaboration revenue grew 105% from the comparable period.

Turning to the rest of the P&L. For the second quarter 2025, research and development expenses were $7.2 million compared to $11.5 million for the comparable period of 2024, a decrease of 37%. Selling, general and administrative expenses were $39.5 million compared to $44.2 million for the comparable period in 2024, a decrease of 11%. The decrease quarter-over-quarter was primarily related to decreased media and marketing costs. We are reiterating our full year 2025 operating expense guidance, which is expected to be approximately $215 million to $235 million, including $15 million in noncash expenses related to stock compensation.

We are on our way to transitioning to sustainable profitability starting in first quarter of 2026, and our operating income from ongoing business in the second quarter validates those expectations. We ended the quarter with cash and cash equivalents of $86.1 million, which combined with our excellent operational results and continued global growth well positions us to create value and achieve our goals.

With that, I will now turn the call back over to Sheldon for closing remarks. Sheldon?

Thank you, Ben. As you've heard today, we have yet again delivered strong results and are executing with precision and building meaningful momentum across every dimension of our business from commercial performance and clinical adoption to global expansion and pipeline innovation. We are not just growing, we are transforming the landscape of cardiovascular disease prevention for underserved patients. With NEXLETOL and NEXLIZET, we are delivering real-world impact. And with every new prescriber, every new patient reach and every new market entered, we are advancing our mission to reduce cardiovascular risk on a global scale.

Looking ahead, we are energized by the opportunities in front of us. Our international partnerships are poised to unlock new revenue streams, and our pipeline is expanding into high-value areas of unmet need with the potential to shape the future of care. When you combine all these factors with diligent expense management, we are on the path to sustainable profitability beginning in the first quarter of 2026 and remain deeply committed to creating long-term value for our shareholders, our partners and most importantly, for the patients we serve. Thank you for your continued support and belief in our vision. We look forward to updating you on our continued progress next quarter.

At this time, we are ready for questions.

[Operator Instructions] That comes from Serge Belanger with Needham.

Congrats on the progress this quarter. A couple of quick questions on NEXLETOL and NEXLIZET. Can you remind us how many remaining prior auths are relative to the TAM for the product? And I think you mentioned you had over 80% approval rate for these prior auths. So is that a number you expect to continue improving on?

And secondly, for Ben, I think you mentioned you expect some of the working capital benefits from the tech transfer to DSE to start occurring later this year. Just curious what that will look like on the balance sheet when it starts coming together?

Great. BJ?

Yes. Serge, as far as the approval rates, as Sheldon had mentioned, in less than 60 days with the new field reimbursement team, they've hit 1,100 targets in those 60 days, and we're showing rates well over 80%. We have certain pacesetter regions that are even higher than 80%. But as you know, with our approval rates, like CVS, where we had our prior authorizations removed, we've hit an all-time high there at -- hitting 93% approval rates there, Aetna 94%. And overall, we're well over 80%, but we have the certain key places where we've negotiated those prior authorizations really and improve that UM criteria. We're at 92 million live updated -- or 192 million, excuse me, aligned to our new label, and we continue to just see these approvals increasing day after day.

Thanks, Serge. This is Ben. Thanks for the question. On the working capital side, this is just in line with what we've been emphasizing on the importance from the tech transfer, right? We have a long time -- long production time line with our product. And so as DSE takes over, we will start to ramp down inventory production on our side, which we expect to happen towards the second half of this year. So I would -- inventory will come down as we start working through that backlog, and they will start ramping up in 2026.

Our next question is from Kristen Kluska with Cantor Fitzgerald.

Congrats on a strong quarter. So if I look at the graph on Slide 10, where you talk about the growth. Can you -- it looks like the jump from April to May was probably the largest numerical gain in the 2.5 years. So if you can -- I know you talked about several growth levers, but what in particular really like stood out during that transition time?

Thanks, Kristen. I think really for us, it's really been our strategy. We've talked a lot today about going after statin-intolerant patients and really establishing this beachhead, which has really continued to drive growth and create a significant amount of awareness. I think what you've heard today also is our plans as we move forward. You heard our tagline Can't take a statin? Make NEXLIZET happen. We've got representatives out there that are promoting that. We have a lot of material that shows that asking the question, can you take a statin? So to me, I think that's what's really continuing to continue to drive the growth. I also have Lisa Schafer, who is our Head of Marketing in the U.S., also provide some comments.

Yes, absolutely. And we see the strong growth both from Medicare, which was Medicare and commercial, which was really great and also with primary care physicians and cardiologists. So it really was just sustained growth quarter-over-quarter, but the out-of-pocket expense for Medicare patients has really improved in the second quarter as they reach that deductible. So that really will be tailwinds for the rest of the year as well.

Okay. So with the growth of the new prescribers that are coming on board, is the #1 selling point essentially that they have an option for these statin-intolerant patients? I guess, what would you rank maybe as the #2 and #3 selling points than primary prevention, secondary or anything else in particular that's really standing out as the other 2 selling points.

Yes, absolutely. So the fact that NEXLETOL and NEXLIZET are the only products indicated for reducing CV events in primary prevention is a very strong selling point. In addition, the only products that had the CV risk reduction, as you mentioned, in statin-intolerant patients, no other product now or in the future is studying that population for CV risk reduction. So those are really the strongest points that we have.

Sheldon, anything to add to that?

[Operator Instructions] And it comes from Dennis Ding with Jefferies.

This is Georgia on for Dennis. Two questions from us. The first is, how do you view consensus U.S. revenue for the year, which is around $170 million and the underlying script growth required to get there? When will you consider giving revenue guidance? And then our second question is, can you remind us on the cadence of milestone payments from Otsuka? And are there very simple thresholds that need to be met and the contract language is very clear? And then can you reiterate that there won't be any confusion like we saw from Daiichi a few years ago?

Thanks for the question. I'll take those in 2 parts. So on the consensus side, yes, I think you can see that we're tracking nicely and in line. I think this was a good quarter in terms of beating consensus and we're tracking well ahead of where we would want to be for that. On the milestone side, I'll reiterate, we have milestones in the second half with the Japanese regulatory process, which is up to $120 million in milestone payments. We expect those to come like I said, in the second half of the year, we're confident we're going to achieve that full amount based on the contract language. There are tiers and thresholds associated with it, but looking and knowing what those are. I think we are in good shape to maximize the potential for those milestones.

Okay. And on the underlying script growth required to get there for the consensus, which is around $170 million?

We're not. I mean, we -- Georgia, we haven't really disclosed what we're doing. It falls in line with guidance. We haven't really given the financial guidance. We're not giving script guidance. But I think what's important is to show and something we've talked about before is that we will continue to demonstrate double-digit script growth, which we've done again this quarter with over 10% script growth, and we're confident that, that momentum will continue.

Our next question is from Jessica Fye with JPMorgan.

I have several questions this morning, mostly about the model and then kind of a bigger picture question. First, can you talk about the gross margin trend we should expect in the back half of the year and into '26? I guess I had thought it would kind of start to materialize, but maybe not. So just curious kind of how to think about the back half and then next year and frankly, ultimately, where you land. How should we think about gross to net over the rest of this year?

And then it looks like R&D, particularly after this quarter is tracking below the 2025 R&D guidance. Should we expect a significant ramp-up in R&D in the back half to kind of get you into that range? So those are the model questions. And then the last one is just basically I want to ask you to kind of make the case here that NEXLETOL will remain competitive in the non-statin LDL space with additional oral mechanisms coming to market.

Thanks, Jess. I will handle the very exciting model questions first and then turn it over to Sheldon for the competitor side. So looking at the model, I think kind of going in order of what you asked about on the gross margin side, the true benefits from the tech transfer will kick in, I think, early next year. This quarter was a good gross margin. I think it was largely in part due to the revenue mix as well as some of the underlying movement of materials that we had. But I think it's indicative of what we can expect once the tech transfer kicks in place and the beneficial margins we would see there.

On gross to net, I think we're in steady state at this point. We've seen 2 quarters of what post IRA gross to net would look like and the lack of the Medicare coverage gap. And frankly, it's been a huge tailwind for us over the course of this year. So we will not see that kind of compounding factor of gross to net worsening over the course of the year. And we will keep seeing the steady favorable gross to net, which you've seen so far in Q1 and Q2.

On the R&D side, Q2 was light, but I think that's mostly just a timing thing. We have our pediatric trial, which is beginning to ramp up. And you'll see in the second half. I would not use the word significant ramp-up. R&D still remains pretty minimal in the grand scope of our spend, but you will see an increase compared to Q2 as that pediatric trial starts to ramp up in the second half of the year.

Great. Thanks, Ben. Jeff, let me address your question as it relates to NEXLETOL and NEXLIZET being competitive into the future, and I'll segment this in 2 ways. We do these live now and actually our computers were updating while I was actually reading the script. So I want to reiterate one part of it. And that is from an IP perspective, we've already mentioned that we've had three of the ANDA filers settle to 2040. And that's important because, as you know, our baseline projections were always June of 2031, and we started to actually plan beyond that. So we're very confident, as we stated before, about our patent. And so from a future perspective, that's going to allow us to continue to grow these products for a number of years. That's one aspect.

But the second aspect is more about what do we have today. We're on the market today. We are the only product that study statin-intolerant patients. We are the only product that also has, as Lisa mentioned, an indication in primary prevention. No other future product is actually doing an outcome study, whether that be oral PCSK9 or CETP inhibition in primary prevention. Let's also not forget there have been 4 CETP inhibitors that have failed previously and it remains to be seen what happens with the CETP that's in development.

So we're very confident based upon where we stand, really a summary of what we did today from a reimbursement perspective, how we've been able to drive growth, physicians becoming more aware of this product. So very bright future ahead. And I've always said when this product becomes generic, it's going to be the most utilized generic product ever in lipid lowering. Our mission is to make that goal now.

Our next question comes from Jason Zemansky with Bank of America.

I guess, Sheldon, maybe for you, at a high level, we appreciate it's still early days in the launch, and we're certainly not overlooking the progress to date, but you've talked about the potential of bempedoic acid reaching blockbuster status and sort of comparing where we are, we're curious what gets you there? And when should we expect the inflection to occur, particularly given the potential of competitive oral non-statin agents entering and additional potential headwinds, including reductions in Medicare, Medicaid spend and so forth.

Yes. So first of all, it kind of goes back to Slide 10 of the presentation. We've seen an inflection. This is a big market. This is a TAM of 70 million patients. This isn't like an orphan rare, as you know, oncology product, where you see this hockey stick take off. It's something that -- a market that will continue to grow, and you'll continue to see the growth in our product. We're very happy in where we stand. The fact that we've been able to provide double-digit growth in basically every single metric that you look at. we think that, to your point, early in the launch, we've got a long way to go. We're just starting, and we're seeing tremendous gains.

As we mentioned today, Europe is a great bellwether as well as we continue to maximize our label from the CLEAR Outcome study. As you know, Jason, we haven't given guidance of when we'll be at certain points. But I think you can see by our ongoing successful quarters we're going to get there. As it relates to future competition, as I mentioned previously, we really need to see what the outcomes data shows for these products, and they're a long way off. So I would actually ask you to ask them how they think that will look versus us in the future. Thank you.

[Operator Instructions] We have a question from Joe Pantginis with H.C. Wainwright.

I have 2, please. So first, on the back end, with regard to PSC and your plans, what would you consider any, if any, rate-limiting steps that might potentially impact your second half of 2016 guidance?

I mean we don't really anticipate any, to be honest. Everything associated with our PSC program is baked in and incorporated into our expense guidance. And we've always reiterated, this is a relatively cheap program to move forward through the IND process, which we expect to continue in the second half of the year.

So that's from an expense front, also, like, say, from the scientific or preclinical study part components?

No, no, no, nothing this year.

Okay. Got it. And my second question, I will admit is somewhat rhetorical, but I would love your thoughts. So when you look at just the U.S. you talked about currently having about 28,000 health care providers prescribing the drug. Looking at your various marketing campaigns, the new ones coming up, the digital campaigns and what have you, what would you say would be the key inflection areas that would take you more quickly from 28,000 HCPs to say, 50,000 versus, say, 28,000 to 29,000?

Yes. Well, look, I mean, I think to your point, Joe, we've been showing this growth every quarter as it relates to physicians increasing prescribing I think what it's allowed us to do is also analyze what are the tactics getting us there. We talked about this TV ad and connected television. This is not a big DTC campaign. But this is something as more folks look at their phone or their tablet or their iPad. These are consumers and they're watching, whether that be Hulu or NBC Sports, as we mentioned, there will be others, consumers being driven to the physician also is very helpful. A matter of fact, we've done market research that has shown that every time a consumer has asked for this drug, they've gotten it. So this tactic of Can't take a statin? Make NEXLIZET happen. That's one that's driving physician growth. The consumer activation will also drive growth.

And what we're also seeing is that physicians who use this drug in patients who can't take a statin, whether they can't take a statin at all or they can only take a low dose of a statin, they say, well, if it works this well without even taking the statin, what would it be like if they were taking the statin. So we're seeing more adoption than that add-on therapy also. So -- and again, primary prevention is a big driver. So all of those levers are going to continue our growth. And again, I would remind folks that primary prevention is a lever, we own that airspace. Nobody now or in the future will have that type of indication.

No, perfect. I love the thoughts. I appreciate that. And again, it's just the growing strong blocking and tackling that you guys are doing.

And this concludes our Q&A session. I will turn it back to management for final comments.

Thank you, operator, and thank you all again for your time and attention this morning. We are looking forward to participating in a number of September conferences and hope to have the opportunity to connect with many of you then. In the meantime, if you have any questions or would like to have a call with the team, just reach out to our Head of Investor Relations, Alina Venezia, and have a great day and a great week. Take care.

And this concludes our conference. Thank you all for participating, and you may all disconnect.

Okay. Good morning, everyone. We'll continue with the next session, which is Esperion Therapeutics. I'm Paul Choi, and I cover the biotech sector here at the firm. It's our pleasure to have Sheldon here with us once again this year to talk about Esperion and commercial prospects as well as the recent pipeline updates that they talked about at their analyst event.

And so maybe just to kick it off, Sheldon, for those who may be unfamiliar with Esperion, even though it's actually a company that's been around for a while and in a couple of different iterations. Can you maybe just give us a little bit of background on the company?

Yes, great. Well, first of all, thanks, Paul. Really appreciate the invitation of the Goldman Sachs meeting and a lot better weather than we had last year with the rain, so this is great.

As it relates to Esperion, Esperion has been an organization that's been around really since 2008, but when we really came on the map was probably in 2020 when the drugs both NEXLETOL and NEXLIZET were launched. Since then, we've had some I would say, really great achievements. We've had the launch of the CLEAR Outcomes study, which is a 14,000 patient outcome study. It was presented at ACC in 2023. We had a new label that came out in 2024. We'll talk more about that specifically.

We also -- on April 24 of this year, we had an R&D Day where we actually introduced an asset, ESP-1336. This is for primary sclerosing cholangitis, a very severe liver disease. It's an orphan disease. We're excited about this. And what I say about Esperion is we're one of the few small to midsize cap organizations that is not only commercializing a drug, but we also have a very interesting pipeline and a quick commercial will be at Bio next week in Boston. We have a very full dance card, which we're excited about that as well.

Okay. Great. Maybe let's start with the commercial side of things and you referenced the risk reduction label changed last year. And so now that it's been a little bit of time. Can you maybe tell us what has resonated the most with prescribers, either at the cardiology specialty side or in the general practitioner suite and in terms of uptick. And maybe on the flip side of that, what are sort of the resistance points about adopting NEXLETOL and NEXLIZET?

Yes, sure. I think, first of all, we are the only non-statin that has primary prevention. When you look at drugs today and even drugs that potentially could come out in the future, we own the airspace in primary prevention. And that is something that's really resonated with primary care physicians and also cardiologists.

First quarter, we had a really good quarter in the first quarter. We actually demonstrated growth in the flat market. And I can tell you in the second quarter through May, we're feeling really good about where we are. We've seen this acceleration and we see that continuing. So what's resonated as primary prevention, but the other thing is the statin intolerance message. So we've been really establishing a beachhead in statin intolerance.

The NLA came out in about mid-February and said up to 30% of patients cannot take a statin or do not want to take a statin. We actually did a small test. We went to physicians across the country who are not writing the drug, and we went to them simply with that message. Doctor, I know you have patients who cannot take a statin. And we've seen an adoption of nonprescribers. These are people who have never written the drug at an all-time high. So it's pretty amazing to see after 5 years, with a new drug being out there that new physicians are writing the drug. So we're getting breadth.

And of course, we're continuing to get depth from those who do write the drug. Why is it? Because they do have patients that do not want to take a statin or they can only take a small dose of a statin. So we're really establishing that beachhead every week. We're seeing an increase of the amount of new physicians and I think we're going to continue to see that. And then we'll continue to move across our segments. And again, for those patients who can take a statin, but cannot take a therapeutic dose, add NEXLIZET or NEXLETOL.

Maybe just for clarification, people may be familiar with ACC or AHA, but what is the NLA? Yes, who may not be in the lipidology don't...

Sure. So the NLA is the National Lipid Association. They worked very closely with the AHA and ACC. Many of their board members and directors are all members of the AHA and ACC. Recently had a meeting, I want to say it was in Miami, I missed it 2 weeks ago.

Okay. Great. And they also issued guidelines similar to ACC and AHA.

They absolutely do.

Okay. Great. Maybe one thing to help us think about Esperion is just think about both reimbursement on the commercial side as well as the Medicare/Medicaid side and cardiology and lipid reduction is obviously a very large field statins are generic, but you talked a little bit about the impact of the Medicare Part D redesign on your franchise. Can you maybe just remind us what was that sort of net impact to the degree you can quantify it? And then how does that -- how do these Medicare design changes potentially affect your outlook over the near and intermediate term?

Sure. Absolutely. And I think just to give a little detail before that because going back to your last question of what were some of the speed bumps, et cetera, as it relates to adoption. It was really these lengthy prior authorizations and step edits. Keep in mind, before CLEAR Outcomes study, we had a TAM of about 10 million. Post outcomes, we had a TAM of 70 million. And we knew once we have the outcome study, we could go to commercial providers and Medicare providers and readdress some of these prior authorizations and burdensome step at it.

If we just focus on Medicare alone where we have about 72% adoption by Medicare plans, what we've seen in some of these plans, they've eliminated the prior authorization. It's gone. And there's no step at it. In the remainder of plans, it's a very simple prior authorization of has this patient actually tried the statin, and all it takes is a physician to do an electronic look back of 6 months to see if they've done -- if they've been on the statin. They don't have to put together a binder or a lot of evidence, et cetera.

By the way, we have 193 million lives covered in that 72% Medicare coverage, which is all preferred. So we are not disadvantaged to anyone. As it relates to the IRA effects, so typically, as you know, the donut hole was later in the year in the third or fourth quarter. This year, there was a lot of confusion with patients and Medicare providers. It was $2,000. And what you had this year in the first quarter were patients wondering if they're even going to have Medicare because there's a lot of rhetoric from DC. And there's a lot that didn't understand their out-of-pocket costs.

What we see now in the second quarter most patients have gone through this $2,000 donut hole, and we're seeing 0 co-pay for many patients. At the very least, they might have to pay $30 or $35 and we didn't see $30 or $35 co-pays in Medicare patients until September, typically. We're seeing it now. So we see a nice tailwind here as it relates to Medicare and reimbursement from a Medicare perspective.

About a 3- to 6-month pull forward roughly speaking, all of these?

Yes.

And just as a reminder, the $2,000 you referenced is not specific to NEXLETOL and NEXLIZET. It's across all Medicare drugs, correct?

It's across all Medicare drugs. And what you see patients do typically is for nonsymptomatic drugs like for what we do, they really prioritize their symptomatic drugs first. So things for pain, also after taking a drug like an anti-platelet, et cetera, diabetes drugs, they'll prioritize those first, that gets them through the donut hole, and then that lessens their out-of-pocket expense for drugs like NEXLIZET and NEXLETOL.

Okay. Great. And then just you talked a little bit about the pull forward here of the lower out-of-pocket cost for patients here. I guess, does that, in your mind, open up or make it more easier, I guess, for patients to get on drug? And just does that accelerate uptake, I guess, in the back half of the year?

It definitely makes it a lot easier for a patient to get the drug. They don't have to think about getting through that donut hole. They don't have to think about paying a lot of money. It also helps with the messaging that we give to our physicians. They can see it. So we, again, view it as a tailwind for us.

Okay. Great. You recently announced an expansion of your sales field force. How much of that was sort of principle by the -- or driven by the label change versus last year versus what you've now seen, I guess, in terms of the impact from the Medicare redesign here? And when do you expect sort of the payoff from the sales force expansion to start happening? And I guess, show intangible ways and be accretive to your revenue?

Sure. So last year, in January, we extended our sales force by about 72 additional people, which gave us a total of 155 sales folks across the country. We also have 5 medical science liaisons as well as strategically placed.

What we also did is we expanded most recently, we went from 6 field reimbursement managers to 15. Why did we do that? We have 15 regions across the country, we dedicated 1 field reimbursement manager to each region. What do they do? They're actually not employees of Esperion. It's actually a company we use, but we actually manage them. And these are highly specialized individuals. They understand many of them are nurses or have worked in doctors' offices. They understand prior authorizations, step edits, et cetera. They basically act as sharpshooters for representatives to call into an office that's having a problem getting the drug approved.

We rolled that out on April 2 of this year. And I can tell you we're already seeing the dividends pay off. Now much of this is qualitative because I get feedback from the field on almost a daily basis, including pictures, which I got last week of representatives and field reimbursement managers working together, getting to an office. But I can see even in the trends for this quarter that there's something different that's happening, and we think it's a result of these field reimbursement managers.

Now we have to be careful how we measure them from a compliance perspective, et cetera. How we measure them is number of approvals. And I can tell you, our approval rates in both commercial and Medicare were in the low 70s, we're in the high 70s to low 80s right now. And I view that as a result of them being out there.

Okay. So you've already seen since April, roughly low double-digit improvement versus where you were baselining prior to that?

Correct.

Okay. Interesting. And then in terms of I guess, using that on the forward here, is that sort of going to be your standard practice here for this external reimbursement or prior authorization specialty team. And just is that something you want to build on further at this point? Or just kind of see how it goes, I guess for the next year?

Yes. I think what we want to do is we know going from 6 to 15 made sense because 6 couldn't cover the whole country. So we definitely think the investment of 15 is the right investment. I don't see adding any more. And I think there's actually a time, too, just from an expense savings perspective that we can back off once we have physicians really understanding across the country, how easy it is to actually get the drug. And I will say it's -- this is the easiest it's been. That was always the issues years ago, but now it's gotten a lot easier. And I think that for the next -- at least for this year, we'll keep the 15 and maybe even further.

Okay, great. You talked a little bit about your performance and gaining share in the first quarter in what was otherwise a flat market. First quarter is always a little bit tricky because of the turnover of the calendar and so forth. But I guess, just -- we've seen a few new products enter the market such as yours in 2020. What had been the Medicines Company? Now Novartis is also in the market and there also some clinical stage assets.

But I guess, in my mind, this is probably 1 of the more exciting times in sort of the cardiology field, lipid lowering field that we've seen in many, many years. And so as you think about the landscape, probably mindful of competing agents coming down the line. And so maybe one of the targets I want to address here briefly is LPA, just maybe share your high-level thoughts on LPA as a target. And then as you think about the various clinical stage assets that are out there, how does their potential competitive positioning look versus Esperion's portfolio?

Yes. And I'll try to make this quick because this is something I can speak about for an hour. I'm very passionate about this. And having been in this field since really the early 2000s. I've seen a lot of drugs and worked on a lot of drugs and looked at many of these targets. Lp(a), I think, is very interesting. We really need to see, I think, what the HORIZON study shows. That's the Novartis study, as you are aware, we are supposed to see those results this year. We won't see them until 2026 at some point because they just didn't have enough events is what we've been told publicly.

Lp(a) is not an identified or recognized biomarker by the FDA. So it's very difficult to really understand what will Lp(a) show us, and is it for just a certain type of patient. I mean if you look at the HORIZON data, it's not really the same cardiovascular type of patient is what we have in our Outcomes study. So it really remains to be seen.

If I look at the ODYSSEY and FOURIER study, the PCSK9 studies, if you looked at their LDL reduction, you could go to the CTT analysis and predict what the residual risk reduction was, which was 15%. Both of those drugs reduce Lp(a) and one could say it had no further effect over and beyond what was shown in ODYSSEY and FOURIER. So that's really the only surrogate that we can look at.

I'll be selfish and say for NEXLIZET and NEXLETOL, we reduced hsCRP by 22%. And if you go back to 2017, Novartis did a study specifically looking at lowering hsCRP and showed a 15% reduction in MACE-driven events. 27% of that was in heart attacks alone. So hsCRP as a recognized biomarker is something that we do. And obviously, if combined with the statin, they also do. So Lp(a) remains to be seen, and we'll just have to wait and see what the data shows.

As it relates to competition, obviously, we have a fifth generation CETP coming out, 4 previously have failed. And again, we really won't know the results. With the exception of the fact, we did see some results presented at EAS. And just high level, I think what no one is talking about is in the supplement you did see an increase in blood pressure of OV versus placebo. And you also saw the TANDEM, I believe it was the TANDEM study where you had to readjust or change hypertensive medications. We know that's something that's out these products before. But again, we have to wait and see.

And then lastly, CETP inhibition, we saw some news today that Merck has finished some of their Phase III data. We'll wait and see what that says at AHA. But I think the oral PCSK9. I think the issue there is you have to fast 8 hours, take the drug then wait 30 minutes and I don't know about you, but when I wake up, the more I'm hungry and I'm want to eat. So I think that's going to be commercially very difficult.

But look, I mean focusing on our drug, as I said before, I like this concept of the airspace that we own. We own primary prevention, and we also own the fact that you can take our drug with or without a statin.

Okay. Great. I'll talk a little bit about your partnerships, both in Europe and as well as in Japan. And your partner Otsuka there is in the midst of the regulatory process for an LDL-lowering indication there. Can you maybe tell us, first, what is the rough timeline based on what you and your partner have discussed for launching there? And just sort of what is the lipid lowering or cholesterol market opportunity in Japan? And is it mostly genericized? And just maybe help us understand sizing up that opportunity for you and your partner.

So Otsuka based in Japan, is commercializing the drug in Japan has been filed. They have close to 700 people dedicated to this product. You think about Esperion, we have 305 people in the United States. We've been in the launch meeting. We were in Tokyo in December and met with them. They're super excited. We think that will happen sometime in the fourth quarter. Unlike the United States, there's no PDUFA for Japan. So we think it will be in the fourth quarter.

We have up to $130 million in milestones that will be paid to us. And I mentioned this about a week ago, but it's a good time to fit it in. Even without the milestones, we believe in 1Q 2026 will be profitable. That's a big statement for us considering where we were last year. So I just want to get that quick commercial in. But Otsuka, super excited about it, very excited. It's the third largest lipid lowering market. And many of those patients also cannot take a statin. I think the best analogy is ezetimibe, a drug I manage for 4 years, and that was a big market for us at Merck and it will be a big market for us also here at Esperion.

Okay. Great. And then just maybe related to that, your top line -- or sorry, your milestones are triggered by the approval and then presumably down the road sales and sales milestones.

It's actually based upon the language that we have in the U.S. label, which, as you know, based upon outcomes, which is in the U.S. label. The larger portion of the milestones is based upon the pricing that they can actually achieve from the Ministry of Japan. And we feel very confident that, that price will be on the higher tier based upon what we know.

Great. beyond the milestones, I guess, as you think about your international market opportunities with both Otsuka in Japan and DSE in Europe, just -- maybe in broad strokes, as you think about next-generation lipid-lowering therapy development there, how does that adoption curve in your mind, look, maybe on a 5- to 10-year view?

I think it simply said, it just continues to go up. And even looking at current lipid-lowering drugs that are on the market. You continue to see a growth of these drugs. Again, first quarter was flat for a number of reasons. But overall, if you look at 3 to 5 years, this is one of the largest markets in the world, lipid-lowering therapy. We talked about the TAM of 70 million patients. We've talked about the fact this is the #1 killer in the world, more so than cancer.

And there's so many patients in need and there's so much more science. I mean even the work that we're doing with our life cycle management and the development of a triple combination, I think we might get into our IP later. I think the sky is the limit as far as growth for these products. And we've always said that we believe we have an asset that's $1 billion plus in the United States, and we firmly believe that.

Okay. Maybe just since you brought on IP, you guys have been in a series of -- with some generic filers. There are a few outstanding, however, maybe just can you remind us what have you settled? And what are the terms on those settlements? And then for the ones with whom you remain in litigation, just sort of what sort of the next milestones or events we should look for might there be?

Yes. So we thought we really weren't going to have much insight into what was happening with the IP until the ANDA litigation began in 2027. And then we had one of the filers actually settle, as you mentioned, for April of 2040. Then the second filer came along and asked to settle, which was also around April of 2040 remains to be seen. What happens to others, we'll just have to watch. But we've always planned for a baseline of our patent expiry to be 2031 in June.

And I can sit here today and say, we're actually thinking now beyond 2031. Anything beyond 2031 would be a real big deal for us, but it simply for so many reasons. And we're starting to think about what that planning would look like. So we continue to watch and wait. We're ready for the litigation. So out of the 9, 2 have settled, again, we'll see if there's more but we've always believed in the strength of our patents. This drug is difficult to make. It's dangerous to make. And we know how to do it, others don't. So -- and I think that's what people are focusing on and seeing.

Just sort of the know-how of...

Exactly.

How to not more than just a small molecule.

That's correct.

Okay. Great. I want to shift gears maybe a little bit and talk about your R&D Day where you talked about PSC as an indication here that you're going to pursue as sort of your first expansion beyond lipid-lowering and cardiology. Can you maybe at a high level, walk us through how does CETP translate here into a liver disease -- sorry...

PSC.

PSC, excuse me. And just sort of what the basic high-level biology here that justifies picking this as your first non-cardiology indication?

Sure. So one thing about ACLY biology is that it has very broad use is what we're finding. We introduced our liver program, as we've mentioned in April. We also have a very extensive kidney program which you'll hear about more next year, but that can range anywhere from CKD, the polycystic kidney disease, et cetera. We'll talk about that more.

We picked PSC because we believe with ACLY biology, you can actually see with the cell type that there's an effect on the liver bile ducts, there's effect on fibrosis, there's an effect on inflammation and there's an effect on healing the injury. And I am not as bright as Steve Pinkosky, you saw him present this data, and he is off the chart smart. But as he always says, we have found kind of this intersection between cell metabolism and fibrosis.

And just talking about PSC. This is a very -- as you saw, this is a very terrible disease. It's an orphan disease. We were able to see a patient testimony who needed 2 liver transplants. The woman who runs the PSC coalition, her son has PSC, is a teenager. This disease leads to transplantation. We believe we have a drug that can potentially maybe cure the disease, postpone having a transplantation, et cetera, early, but we're also looking for ways to expedite the timeline, the timeline that you saw presented on April 24. So more to come on that. But it just really demonstrates how unique ACLY biology is.

And I can tell you, and just coming back to the commercial I did earlier for Bio folks that reached out to us that we're talking to in bio were very interested in that presentation and the science surrounding ACLY biology. I said we've had this effect on liver kidney. We think we might have an oncology effect, but we're not experts there. We would need help there. There are several papers that were written on ACLY biology and geoblastoma, but that's very early. But liver and kidney look good, and people want to understand more about it. And that was also one of the reasons of doing that R&D Day as well.

Great. Maybe just to keep on the thread here of PSC in terms of how hepatologists look at the disease and currently treat or manage it, what are sort of the options there? Obviously, if a patient has severe disease that progresses to transplantation is sort of the rescue but just sort of in between diagnosis and maybe getting to transplantation how are these patients manage?

Yes. Well, there's not a lot right now to manage it. And there are -- I think a lot of this is experimental use of different drugs. There's also a mechanical way, which is very painful, very time consuming of actually going in and performing surgery and cleaning out the bile ducts. That seems to have a temporary fix.

We heard 1 patient that was presented that's had to go through that 3 times. This drug also has comes with a lot of itching and plaque psoriasis, et cetera, so you've got to use drugs to control that. And it's not like a simple itch. We heard that you can itch from the top of your throat all the way down to your feet, et cetera. So there's just a lot of nasty side effects where you have to use a lot of different drugs. But I don't think anything right now really kind of stops that march towards liver transplantation. And that brings me back again to ACLY biology gets you to look at the fibrosis that causes it do something around the injury, do something around the inflammation. We think that probably has something to do with hsCRP. And so those are the important elements that have been missing before to treat the disease.

Right. One question that's come up is there are obviously -- there's a commercial stage NASH drug as well as some clinical stage NASH drugs as well out there. And they target fibrosis, which is one of the key symptoms in PSC. How does that NASH ecosystem landscape potentially affect you guys? Is that completely -- is it adjacent? Or is it overlapping at all?

I think it's -- I think there is adjacent and overlapping maybe. I think there's definitely a partnership there. because you're dealing with so many different liver-related diseases. And right now, I think everyone is still waiting to see -- obviously, you have the Madrigal drug out there that seems to be doing well, that's focused on MASH.

I think it's something that can be used by physicians, our drug, should it come out, along with drugs like maybe that Madrigal has and others. So it's something over and beyond MASH. MASH was an option that we thought about, but we actually felt that is an area that is a bit crowded right now and this was an area that was very specific to us that if you look at the regulatory timeline as well, it would be quicker to actually get to the market, and there's a need for it.

Okay. And maybe since you just announced it at your R&D Day, just sort of broad strokes, when do you guys start in the clinic, what are rough timelines for the development program here in PSC and what's the aspiration in terms of the timeline potentially to get to the market?

Yes. So the timeline that we put out there was sometime in the early 2030s. We would like to do something before that. What I can say is that we are exploring ways to do that. We do have a meeting that will be set up with the FDA where we'll discuss that. It remains to be seen if we would have to do an Outcomes study, our understanding right now is that we wouldn't, and I think that is something also that could bring speed to the market.

Again, there's a real need for the drug. I think right now, it's just a race to do everything that we need to do to get to clinic. And I would say stay tuned. We're going to update everyone more as we get to the latter half of third quarter.

Okay. Great. Maybe turning to other aspects of the pipeline. In the past, you had talked about developing a statin ezetimibe combination with bempedoic acid, primarily for your European partner, DSE, but now you're talking more about development here for -- more recently talking about development for the domestic market.

Can you maybe just walk us through what has been the sort of change in your thought process? This was probably mostly going to be a partnered asset but now you're thinking about doing this in-house and just sort of what was the logic or thought process there?

Yes. The biggest change was the fact that we didn't have to do a clinical study. We only need a bioequivalent study in the United States, and we're able to use the bioequivalent study that's actually being conducted by Daiichi Sankyo to do that. That was really it because we knew physicians were interested in it. There's always been this talk of polypill strategy. I think in the United States, there's been a failure in the past of combining drugs both across therapeutic areas. [indiscernible] was an example, Merck tried to do it with ZOCOR and JANUVIA, it just didn't mix.

But physicians are ready to use a polypill where it addresses the same therapeutic area, in this case, LDL lowering. And the formulation is unique because it's with a low-dose statin, again, keen in on the fact that patients really can't tolerate higher doses of statin, and it's a play on convenience. So now you have 3 pills that you can just take in one. It also gives the flexibility of a physician to say, I might just want to use NEXLETOL, I might just want to use NEXLIZET or I can now use a triple combination. I think the beauty of it is it could be the -- potentially the most efficacious LDL lowering drug on the market in 1 pill. And we're excited about it. We actually have a lipid advisory board meeting coming up end of June. These are all the high-level lipid folks in the United States. We'll be talking about this.

And we are also going to think about is there some clinical information that potentially we could put into the label if we did a small study, so we'll keep everyone an update on that as well.

Okay. Do you feel like just on that last point, a small clinical studies required here, just so you can actually show LDL data on label for this package here versus just bioequivalents and just sort of do you feel like that's a necessary step in your clinical development?

It's not a necessary step. It's more of a life cycle management consideration. It would give a little more data for somebody to speak about. Remember, there was some data that was done in Phase II that looked at the addition of atorvastatin plus ezetimibe plus bempedoic acid, which showed almost a 70%, 70 percent LDL lowering. You can't use that in promotion, but if you could do a small study, then it gives you something to talk about, but it's not necessary at all.

Okay. Just as you think about what, at least in my mind, is a relatively low clinical development -- clinical risk development program here. And do you think downstream to the commercial stage, how do you think about positioning this fixed-dose triple combination versus your current portfolio? What is the messaging there versus your current portfolio?

Yes. It's really for those patients who are already taking a statin and it allows the doctor to say, "Wow, I've already have experience with NEXLIZET, I have experience with NEXLETOL, hey, it might be easier for you Johnny to take this triple combination" would you rather do that? The pill size really isn't any bigger. We've seen some mockups of it. So to me, it's just a continuation of the franchise.

There are some physicians out there that just don't want to use combination therapies. We still have many physicians that like using ezetimibe with NEXLETOL and the statin. We don't really understand the behavior behind that. But I go back to about 3 years ago, we did behavioral research, and this is like the overall view. Physicians today are just very apathetic about treatment. They felt that all they could do was use a statin and it could use ezetimibe. And this is even with injectable PCSK9s out there, especially primary care physicians, and this is all we could do.

And honestly, they just felt bad about that. They couldn't do more for their patients. We've changed that with NEXLIZET. By the way, our new tagline with physicians. So they remember sometimes is that can't take a statin, make NEXLIZET happen. And that really resonates. Now we've given them this kind of power to do more and to do something different that triple combination also helps them do that for the patient and make it easier for them.

Okay. Would there be any potentially new IP associated with the fixed dose combination here? Beyond the sort of 2040s that we had talked about with earlier in your litigation...

Not in the United States. But in Europe, we think there is, and that's something we're still researching.

Okay. Great. We're coming up on time here, and so maybe Sheldon to close it out, you've started talking about your next stage pipeline beyond cardiology as well as developing this triple combination. But as you sort of think about other next steps for Esperion here, how does BD figure in that potentially? Because you talked about transitioning to profitability as early as the first quarter of next year, you can start to build cash and so forth potentially down the road. How do you think about BD maybe?

Yes. So our #1 focus is really growing the franchise of NEXLIZET and NEXLETOL. I've said this many times, we have been involved and have conducted a landscape analysis of products that are out there, specifically in the cardiometabolic area. So looking at obesity, high blood pressure, heart failure, even diabetes. And there's many companies out there that have some interesting products. They have either filed the drug. They're waiting for approval. They're about to file, nothing in the clinic. We don't want to take risk and do that.

The -- I would say, silver lining in the macro environment that we have today that cost $80 million to $100 million of stand up a sales force like we have and have all the other support areas. We have the infrastructure. So what we've already talked -- what we've always talked about is how do we leverage our infrastructure. We don't have to go out and buy anything. How do we leverage our infrastructure and say, "Hey, company x, we can market and sell this drug for you. And let's talk about what that deal would look like if we do that". So we're doing that. We're having those conversations. We're not in any rush. We want to make sure it's the right drug. And we feel good about where we are in the stage, and we'll continue to update folks on our progress there.

Okay. Great. We just hit time. So my thanks to Sheldon, thank you Esperion for joining us.

Thank you so much, Paul. Thank you.