Esperion Therapeutics has nominated ESP-2001, a highly-specific allosteric ATP citrate lyase (ACLY) inhibitor, as its preclinical development candidate for treating primary sclerosing cholangitis (PSC), marking the company's expansion beyond cardiovascular disease into rare liver disorders. The company announced plans to begin Investigational New Drug (IND)-enabling studies with a goal to file an IND with the U.S. Food and Drug Administration in 2026.
Addressing Critical Unmet Medical Need
PSC represents a significant area of unmet medical need, affecting approximately 76,000 diagnosed patients across the U.S. and Europe with no FDA-approved therapies currently available. The rare, progressive, cholestatic, immune-mediated disease of the bile ducts is characterized by chronic inflammation and scarring that can lead to cirrhosis, liver failure, transplant, and death.
"PSC is a devastating condition with no approved treatments, and our preclinical data suggest ESP-2001 has the potential to meaningfully impact disease progression through multiple mechanisms," said Sheldon Koenig, President and Chief Executive Officer of Esperion.
Promising Preclinical Results
ESP-2001 was discovered leveraging Esperion's expertise in ACLY therapy and utilizing Evotec's integrated drug discovery platform. The compound was identified through integration of high-throughput, virtual, and structure-based screening approaches and subsequently optimized for novel ACLY-dependent activities associated with PSC pathogenesis.
In multiple preclinical models, ESP-2001 consistently reduced markers of liver and bile duct injury, inflammation, and fibrosis. The drug is designed to target the liver and bile duct injury, inflammation, and fibrosis associated with PSC and related diseases.
Significant Market Opportunity
ESP-2001 represents a potential blockbuster market opportunity of over $1 billion annually, given the lack of approved treatment options for the estimated 76,000 diagnosed PSC patients. Esperion retains exclusive global development and commercialization rights for this wholly owned asset.
The compound has potential eligibility for Orphan Drug and Fast Track designations from the U.S. FDA and PRIME designation from the European Medicines Agency, which could accelerate its development timeline.
Disease Background and Current Treatment Landscape
Primary sclerosing cholangitis affects the bile ducts that carry digestive liquid bile from the liver to the small intestine. In PSC, inflammation and injury cause scarring, structuring, and concentric, obliterative fibrosis within the bile ducts, making them hard and narrow. This leads to biliary cirrhosis, portal hypertension, and eventually hepatic failure in a majority of patients.
The disease also increases the risk of various carcinomas and is frequently associated with inflammatory bowel disease, particularly ulcerative colitis. The cause of PSC remains unknown, and there is no proven medical or interventional therapy to halt disease progression. A liver transplant is currently the only known long-term treatment option, though up to 30% of patients who receive a liver transplant for PSC experience recurrence.
Strategic Partnership and Development Platform
Esperion is continuing its partnership with Evotec to leverage their INDiGO platform, an integrated, clinical-enabling solution designed to derisk and accelerate the development of small molecule drug candidates from candidate nomination to IND submission.
"The nomination of ESP-2001 marks a pivotal moment in Esperion's evolution as we expand our therapeutic focus beyond cardiovascular disease," Koenig noted. "We are 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."
