Executive Summary / Key Takeaways

• Differentiated Oral Therapies Driving Growth: Esperion is demonstrating accelerating commercial momentum for NEXLETOL and NEXLIZET, its oral, once-daily, non-statin therapies, particularly among statin-intolerant patients and for primary prevention, a unique market position.
• First Operating Income Signals Profitability Path: The company achieved its first quarter of operating income from ongoing business in Q2 2025, reporting approximately $15 million, and projects sustainable profitability beginning in Q1 2026, supported by strong revenue growth and disciplined expense management.
• Expanding Global Footprint and Pipeline: Strategic international partnerships are yielding increasing royalty revenues and significant upcoming milestones, while a focused pipeline, including a triple combination product and a novel program for Primary Sclerosing Cholangitis (PSC), promises future growth.
• Strengthened Financial Position and IP: Recent financial restructuring and patent settlements extending NEXLETOL's U.S. exclusivity to 2040 have significantly de-risked the investment thesis and provided substantial operational flexibility.
• Competitive Edge in a Large Market: Esperion's ACLY inhibitor technology offers a compelling oral alternative with proven cardiovascular outcomes, differentiating it from injectable competitors and addressing a massive, underserved patient population.

The Dawn of a New Era: Esperion's Ascent in Cardiovascular Prevention

Esperion Therapeutics, Inc. (NASDAQ:ESPR) is carving out a distinct and increasingly vital niche in the vast landscape of cardiovascular disease (CVD) prevention. As a commercial-stage biopharmaceutical company, Esperion is dedicated to addressing the unmet needs of patients struggling with elevated low-density lipoprotein cholesterol (LDL-C), the primary driver of atherosclerotic cardiovascular disease (ASCVD). The company's journey, commencing operations in 2008, has culminated in a pivotal transformation, marked by recent regulatory successes, strategic financial restructuring, and a clear trajectory towards sustainable profitability.

At the heart of Esperion's strategy lies its proprietary ATP Citrate Lyase (ACLY) inhibitor technology, embodied in its flagship products, NEXLETOL (bempedoic acid) and NEXLIZET (bempedoic acid and ezetimibe). These oral, once-daily, non-statin medicines offer a differentiated mechanism of action, lowering LDL-C by reducing cholesterol biosynthesis and up-regulating LDL receptors. This technological advantage translates into tangible benefits for patients: NEXLETOL demonstrated an average 18% placebo-corrected LDL-C lowering in patients on statins, and a 20% reduction in statin-intolerant patients, crucially leading to a 13% lower risk of major adverse cardiovascular events (MACE) in the landmark CLEAR Outcomes trial. NEXLIZET, combining bempedoic acid with ezetimibe, achieved a mean LDL-C reduction of 38% compared to placebo when added to maximally tolerated statins. Beyond LDL-C, Esperion's therapies also showed a 22% reduction in hsCRP, a key marker of inflammation, and importantly, have no effect on glucose levels, offering a compelling profile for a broad patient demographic.

The market opportunity for Esperion's therapies is substantial. Cardiovascular disease remains the leading cause of death globally, affecting millions. A significant segment of this population, estimated at 70 million patients, is at risk and requires additional treatment options. Critically, statin intolerance, affecting approximately 30% of patients, represents a massive underserved population for whom Esperion's products are uniquely positioned. The company's expanded FDA labels, approved in March 2024, now include cardiovascular risk reduction and broader LDL-C lowering in both primary and secondary prevention patients, allowing for use alone or in combination with statins. This broadens the addressable market and solidifies Esperion's competitive moat.

U.S. Commercial Momentum and Competitive Edge

Esperion's U.S. commercial performance reflects the growing clinical adoption of NEXLETOL and NEXLIZET. In the second quarter of 2025, U.S. net product revenue surged to $40.3 million, marking a robust 42% year-over-year increase and a 15% sequential gain from Q1 2025. This growth was fueled by accelerating prescription volumes, with total retail prescription equivalents (TRPEs) increasing 10% from the first quarter of 2025, and the total prescriber base expanding to over 28,000 healthcare practitioners.

The company's commercial execution is highly targeted and effective. Its "Can't take a statin? Make NEXLIZET happen" tagline and "lipid lurkers" consumer campaign are resonating, driving significant brand awareness and patient engagement. In Q2 2025 alone, the consumer statin intolerance website garnered over 650,000 visits, with 600,000 click-throughs to the physician site. Digital outreach is a powerful lever, accounting for 23% of total prescriptions and 38% of new writer prescriptions. An expanded U.S. field reimbursement manager team has also been instrumental, educating over 1,100 prescribers and boosting prior authorization approval rates to over 80%, with some major payers like CVS (CVS) and Aetna seeing approval rates as high as 93-94%.

Esperion's market access has significantly improved, with over 192 million lives now aligned to the new label. Crucially, step-edit criteria through ezetimibe have been removed in both commercial and Medicare contracts, simplifying the prescribing process. This enhanced access, combined with the recent inclusion of bempedoic acid in the 2025 ACC-AHA Multi-Society Guidelines for acute coronary syndrome (ACS) with Level 1A and 2A recommendations, further validates the products' clinical value and strengthens physician confidence. Esperion stands out as the only oral, non-statin therapy with both primary and secondary prevention indications, a key differentiator against competitors like Amgen (AMGN) (Repatha) and Regeneron (REGN) (Praluent), whose PCSK9 inhibitors are injectables and do not hold the same primary prevention indication. While larger players like AstraZeneca (AZN) and Pfizer (PFE) dominate the statin market, Esperion offers a crucial alternative for the significant statin-intolerant population.

Global Expansion and a Robust Pipeline for Future Growth

Beyond its U.S. commercial success, Esperion is strategically expanding its global footprint through a network of robust partnerships. Collaboration revenue, excluding a one-time milestone in Q2 2024, grew an impressive 105% year-over-year in Q2 2025. Daiichi Sankyo Europe (DSE), Esperion's partner in Europe, continues to drive strong sales of NILEMDO and NUSTENDI, contributing $13.6 million in royalty revenue in Q2 2025, a 30% sequential increase. DSE has now treated over 500,000 patients in Europe, a significant milestone that underscores the global market potential and reinforces confidence in building a similarly sized market in the U.S. The ongoing technology transfer for manufacturing to DSE is also expected to yield substantial reductions in future Cost of Goods Sold (COGS) and working capital costs for Esperion.

The Japanese market, the world's third-largest for cardiovascular prevention, represents a significant near-term catalyst. Otsuka Pharmaceutical (4578)'s New Drug Application (NDA) for bempedoic acid is on track for approval and National Health Insurance (NHI) pricing in the second half of 2025. This achievement is expected to trigger milestone payments of up to $120 million for Esperion. Further international expansion includes new license and distribution agreements with HLS Therapeutics (HLS) for Canada (expected approval Q4 2025), Neopharm Israel (expected approval H1 2026), and CSL Seqirus for Australia/New Zealand (marketing application filed July 2025, expected approval H2 2026). These partnerships are poised to deliver a consistent cadence of approvals, product launches, and growing royalty streams, supporting Esperion's long-term revenue growth.

Esperion's strategic vision extends to a focused pipeline leveraging its ACLY biology expertise. The company is developing a triple combination product (bempedoic acid, ezetimibe, and a statin) for the U.S. market, targeting commercialization in 2027. This therapy is anticipated to achieve LDL-C lowering in excess of 60%, positioning it as a potentially highly effective oral option that could rival existing injectables and emerging oral therapies. The regulatory path is expected to involve bioequivalence and stability studies, not a lengthy cardiovascular outcomes trial (CVOT), making it a more efficient development pathway. This triple combination is a critical life cycle management strategy, aimed at extending Esperion's patent position and offering physicians a comprehensive suite of oral options.

Beyond cardiovascular applications, Esperion is advancing a novel program targeting Primary Sclerosing Cholangitis (PSC), a rare, progressive liver disease with no approved therapies and an estimated $1 billion annual market opportunity. This high-need, high-value indication highlights the broader potential of ACLY biology. IND-enabling studies are underway, with first-in-human studies potentially initiating in the second half of 2026. This pipeline diversification, coupled with ongoing business development efforts to in-license or acquire synergistic cardiometabolic assets, underscores Esperion's commitment to long-term growth and innovation.

Financial Health and the Path to Sustainable Profitability

Esperion's financial narrative is shifting from a history of operating losses to a clear path towards profitability. In Q2 2025, the company achieved its first quarter of operating income from ongoing business, reporting approximately $15 million. This milestone provides management with confidence in its projection to transition to sustainable profitability beginning in the first quarter of 2026. This outlook is supported by accelerating revenue growth and disciplined expense management.

The company's full-year 2025 operating expense guidance remains between $215 million and $235 million, including $15 million in non-cash stock compensation. Research and development expenses, while lower in Q2 2025, are expected to see a slight ramp-up in the second half of the year due to the pediatric trial, though remaining a minimal portion of overall spend. Selling, general, and administrative expenses have also seen decreases, reflecting efficient allocation of marketing resources.

Esperion's liquidity position is robust, with cash and cash equivalents totaling $86.1 million as of June 30, 2025. This is further bolstered by strategic financial restructuring undertaken in 2024. The company monetized a portion of its European royalties through a $304.7 million royalty purchase agreement with OMERS Life Sciences, which also enabled the early termination of a previous revenue interest facility. Additionally, Esperion secured a $150 million secured term loan and issued new $100 million convertible notes, primarily to repay $210.1 million of its 2025 convertible debt. These moves have significantly strengthened the balance sheet and provided operational flexibility.

The remaining 2025 convertible notes amount to $54.9 million, due in November 2025. Management anticipates that current cash, expected future product sales, and upcoming collaboration milestones, particularly the up to $120 million from Otsuka in H2 2025, will ensure a stronger cash position by year-end 2025 and fund operations for the foreseeable future. The gross-to-net dynamics are also expected to stabilize post-IRA, allowing revenue growth to more closely align with prescription growth.

Risks and Forward Outlook

While Esperion's trajectory is positive, investors should be aware of certain risks. The company identified a material weakness in its internal control over financial reporting related to inventory accounting in Q2 2025, which required a corrected earnings release. Management is actively implementing remediation plans, but failure to fully address this could impact financial reporting accuracy and investor confidence. Furthermore, while patent settlements have extended NEXLETOL's U.S. exclusivity to 2040, ongoing ANDA litigation for NEXLIZET continues.

Regulatory and pricing pressures, particularly from federal legislation like the Inflation Reduction Act (IRA) and the One Big Beautiful Bill Act (OBBB Act), could influence future revenue, though the OBBB Act's changes to orphan drug exemptions are favorable. Macroeconomic and geopolitical uncertainties also pose potential headwinds. Despite these, Esperion's management remains confident in its ability to achieve sustainable profitability by Q1 2026, driven by continued double-digit script growth, expanding global partnerships, and a promising pipeline.

Conclusion

Esperion Therapeutics stands at a pivotal juncture, transforming from a development-focused entity into a commercially vibrant and soon-to-be profitable biopharmaceutical company. Its core investment thesis is rooted in the unique positioning and proven efficacy of its oral ACLY inhibitor therapies, NEXLETOL and NEXLIZET, which address a massive, underserved patient population, particularly those with statin intolerance and a need for primary cardiovascular risk reduction. The company's strategic execution in the U.S. market, coupled with a rapidly expanding global footprint through high-value partnerships, is translating into tangible revenue growth and a clear path to sustainable profitability.

The robust financial restructuring of 2024 and the extension of NEXLETOL's patent exclusivity to 2040 provide a strong foundation and significant de-risking for long-term value creation. With a focused pipeline aimed at developing a triple combination product and exploring novel indications like PSC, Esperion is leveraging its technological leadership to secure future growth drivers. As the company approaches its projected profitability in Q1 2026 and anticipates substantial international milestones, Esperion presents a compelling opportunity for discerning investors seeking exposure to a differentiated player in the critical cardiovascular prevention market.