Esperion Unveils Promising Research Supporting Lead Development Candidates for Primary Sclerosing Cholangitis (PSC) at R&D Day 2025

Rhea-AI Summary

Esperion (NASDAQ: ESPR) announced new research for treating Primary Sclerosing Cholangitis (PSC), a rare liver disease, at their R&D Day 2025. The company unveiled lead candidates, including ESP-1336, which are novel allosteric inhibitors of ATP citrate lyase (ACLY) targeting hepatic inflammation and fibrosis.

The preclinical data shows promising results in reducing liver injury, inflammation, and fibrosis across multiple PSC-relevant models. The company's research utilized multi-omics and phenome-wide association studies to identify ACLY mechanisms linked to bile duct injury and PSC progression.

The market opportunity is estimated at over $1 billion annually, with approximately 76,000 diagnosed PSC patients across the U.S. and Europe as of 2024. The program may be eligible for Orphan Drug and Fast Track designations from the FDA.

Positive

• Novel PSC treatment targeting $1B+ market opportunity
• Promising preclinical data showing reduction in liver injury and inflammation
• Potential for Orphan Drug and Fast Track designations
• Large addressable market with 76,000 diagnosed patients in US/Europe
• Expansion beyond current product portfolio (NEXLETOL/NEXLIZET)

Negative

• Still in early preclinical stage, far from market approval
• No proven therapies currently exist for PSC, indicating high development risk
• Will require significant R&D investment for clinical trials

Insights

Biotech Industry Analyst

Esperion's expansion into PSC treatment shows promising strategic diversification with billion-dollar market potential despite being in early preclinical stages.

Esperion's strategic expansion into Primary Sclerosing Cholangitis (PSC) represents a significant diversification beyond their established cardiovascular franchise. By leveraging their expertise in ATP citrate lyase (ACLY) inhibition, they're targeting a rare liver disease with no approved therapies that can slow or halt progression - a classic "high unmet need" opportunity. The market potential is substantial, with Esperion citing $1 billion annual opportunity and approximately 76,000 diagnosed PSC patients across the US and Europe.

What's particularly noteworthy is that these next-generation ACLY inhibitors, including lead candidate ESP-1336, were developed in-house. This demonstrates Esperion's internal R&D capabilities extend beyond their marketed products NEXLETOL and NEXLIZET. The preclinical data package appears robust, showing efficacy in human liver microtissues and multiple disease models with consistent reductions in liver injury, inflammation, and fibrosis.

The potential for Orphan Drug and Fast Track designations could provide regulatory advantages and accelerated pathways to market. However, investors should recognize this program remains in preclinical stages, representing a long-term strategic investment rather than a near-term revenue driver. The scientific approach appears well-validated, with the involvement of prominent medical experts lending credibility to their research direction.

Hepatology Specialist

Esperion's novel ACLY inhibitors target critical metabolic pathways in PSC with compelling preclinical evidence of reduced liver injury and fibrosis.

Esperion's research into allosteric ACLY inhibitors for PSC addresses a significant unmet medical need in hepatology. PSC is a rare and progressive liver disease characterized by inflammation and scarring of the bile ducts that currently lacks any approved disease-modifying therapies. The scientific rationale is particularly compelling - ACLY occupies a central position in metabolic regulation, and by modulating acetyl-CoA levels in hepatobiliary cells, these inhibitors could disrupt multiple disease-driving pathways simultaneously.

The preclinical evidence presented demonstrates a sophisticated research approach. Using multi-omics analysis and phenome-wide association studies, Esperion has identified specific ACLY mechanisms linked to the triad of bile duct injury, inflammation, and fibrosis - the key pathological features driving PSC progression. Their lead candidates have shown consistent efficacy across multiple preclinical models, including human liver microtissues and both chemically and surgically induced liver injury models.

What distinguishes this approach is the focus on allosteric inhibition, which typically offers improved selectivity compared to active-site inhibitors. This suggests potential for a better safety profile - crucial for a chronic liver disease requiring long-term treatment. The endorsement from Dr. David Cohen, Chief of Gastroenterology at Brigham and Women's Hospital, adds significant credibility to this approach, noting that modulating acetyl-CoA levels could offer a "potentially transformative approach to treatment."

– Expands Development Portfolio with Introduction of a Novel Program Targeting PSC –

– Confirms Highly Specific Allosteric ACLY Inhibitor Shown to Reduce Liver Injury, Inflammation and Fibrosis Across Multiple PSC-Relevant Pre-Clinical Models –

– Demonstrates Internal R&D Capabilities with Wholly Owned, Next-Generation Candidates Targeting Liver and Kidney Disease –

– Esperion to Webcast R&D Day Event Today at 9:00 a.m. ET –

ANN ARBOR, Mich., April 24, 2025 (GLOBE NEWSWIRE) -- Esperion (NASDAQ: ESPR) today announced that the Company plans to highlight new research supporting its lead development candidates for the treatment of primary sclerosing cholangitis (PSC), a rare and progressive liver disease, today at 9:00 a.m. ET in New York City. A live webcast of the event will also be available. These candidates are novel allosteric inhibitors of ATP citrate lyase (ACLY), a key metabolic enzyme with emerging relevance in hepatic inflammation and fibrosis.

“We are leveraging our deep expertise in ACLY biology to expand our portfolio beyond NEXLETOL^® (bempedoic acid)/NEXLIZET^® (bempedoic acid and ezetimibe) and to address the urgent needs of patients living with PSC,” said Sheldon Koenig, Chief Executive Officer at Esperion. “Our lead candidates, including ESP-1336, are promising, potential first-in-class allosteric ACLY inhibitors, well-characterized with significant preclinical data, and represent a natural extension of our metabolic franchise. PSC is a rare and progressive liver disease with no approved therapies proven to slow or halt its progression. Our next-generation ACLY inhibitor discovery program was purpose-built to improve potency, selectivity, and guide indication and patient population selection through data-driven innovation.”

“ACLY is a promising target in hepatic disease, given its central role in metabolic regulation,” said David E. Cohen MD, PhD, Chief, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital. “By modulating acetyl-coenzyme A (acetyl-CoA) levels in multiple hepatobiliary cell types, these inhibitors may disrupt key disease-driving pathways in PSC, offering a potentially transformative approach to treatment.”

R&D Day Guest Speakers

• Christos S. Mantzoros, MD, DSc, PhD, h.c. mult., Professor of Medicine Harvard Medical School
• David E. Cohen, MD, PhD, Chief, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital
• Mary Pressley Vyas, Vice President, Strategic Initiatives, PSC Partners
  

R&D Day Highlights

• Target validation underpins Esperion’s next-generation ACLY inhibition discovery program in liver diseases.
  
  
  • Selected PSC as the lead indication for next-generation ACLY inhibition discovery program.
    
  • Utilized multi-omics, phenome-wide association studies, and preclinical disease modeling to uncover novel ACLY pathways and disease links beyond cardiovascular disease.
  • Identified ACLY mechanisms linked to bile duct injury, inflammation, and fibrosis – key drivers of PSC progression.
    
    
• Progressing a differentiated ACLY inhibitor program with strong preclinical data.
  
  
  • Discovered lead candidates through high-throughput and structure-based screening, optimized for PSC-specific biology.
    
  • Observed efficacy in human liver microtissues, and chemically and surgery induced liver injury models.
  • Showed consistent reductions in liver injury, inflammation, and fibrosis across multiple preclinical models.
    
    
• PSC represents a large unmet medical need with no approved therapies and significant market potential.
  
  
  • Potential eligibility for Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration.
  • Estimated >$1 billion annual market opportunity.
  • Estimated prevalence of approximately 76,000 diagnosed PSC patients across the U.S. and Europe as of 2024.

Webcast Information
A live webcast of the R&D event will be available and those who intend to join virtually can register for the webcast on the Investor section of the Esperion website. The archived replay will be available approximately two hours after completion of the event and will be archived on the Company's website for approximately 90 days.

A copy of the R&D Day presentation can be found here.

About Primary Sclerosing Cholangitis
Primary Sclerosing Cholangitis (PSC) is a rare, progressive, cholestatic, immune‐mediated disease of the bile ducts. Bile ducts carry the digestive liquid bile from the liver to the small intestine. In PSC, inflammation and injury cause scarring, stricturing, and concentric, obliterative fibrosis within the bile ducts. These processes make the bile ducts hard and narrow leading to biliary cirrhosis, portal hypertension, and eventually hepatic failure in a majority of patients.

The pathogenesis of PSC remains unknown and there is no proven medical or interventional therapy to halt the progression of disease. A liver transplant is the only known long-term treatment option for PSC, however up to 30% of patients who receive a liver transplant for PSC experience recurrence.

About Esperion Therapeutics
Esperion Therapeutics, Inc. is a commercial stage biopharmaceutical company focused on bringing new medicines to market that address unmet needs of patients and healthcare professionals. The Company developed and is commercializing the only U.S. Food and Drug Administration (FDA) approved oral, once-daily, non-statin medicines for patients who are at risk for cardiovascular disease and are struggling with elevated low density lipoprotein cholesterol (LDL-C). These medications are supported by the nearly 14,000 patient CLEAR Cardiovascular Outcomes Trial. Esperion continues to build on its success with its next generation program which is focused on developing ATP citrate lyase inhibitors (ACLYi). New insights into the structure and function of ACLYi fully enables rational drug design and the opportunity to develop highly potent and specific inhibitors with allosteric mechanisms.

Esperion continues to evolve into a leading global biopharmaceutical company through commercial execution, international partnerships and collaborations and advancement of its pre-clinical pipeline. For more information, visit esperion.com and follow Esperion on LinkedIn and X.

Forward-Looking Statements
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding marketing strategy and commercialization plans, current and planned operational expenses, future operations, commercial products, clinical development, including the timing, designs and plans for the CLEAR Outcomes study and its results, plans for potential future product candidates, financial condition and outlook, including expected cash runway, and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions. Any express or implied statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Esperion’s actual results to differ significantly from those projected, including, without limitation, the net sales, profitability, and growth of Esperion’s commercial products, clinical activities and results, supply chain, commercial development and launch plans, the outcomes and anticipated benefits of legal proceedings and settlements, and the risks detailed in Esperion’s filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Esperion disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

Esperion Contact Information:
Investors:
Alina Venezia
investorrelations@esperion.com
(734) 887-3903

Media:
Tiffany Aldrich
corporateteam@esperion.com
(616) 443-8438

FAQ

What is the market potential for Esperion's PSC treatment program?

The PSC treatment program has an estimated annual market opportunity exceeding $1 billion, with approximately 76,000 diagnosed patients across the U.S. and Europe as of 2024.

How does Esperion's ESP-1336 work in treating PSC?

ESP-1336 works as an allosteric inhibitor of ATP citrate lyase (ACLY), targeting hepatic inflammation and fibrosis by modulating acetyl-coenzyme A levels in hepatobiliary cells.

What are the key findings from Esperion's preclinical studies for PSC treatment?

The preclinical studies showed consistent reductions in liver injury, inflammation, and fibrosis across multiple models, including human liver microtissues and chemically induced liver injury models.

What regulatory advantages could Esperion's PSC treatment receive?

The treatment may be eligible for both Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration.