Press Release

First-in-human data shared at The Liver Meeting® 2022 supported a favorable safety and tolerability profile for INT-787 in healthy adults

Company announces severe alcohol-associated hepatitis (sAH), a disease with no approved therapies, as its lead indication for INT-787

Company initiates Phase 2a FRESH study in patients with sAH

MORRISTOWN, N.J., Nov. 07, 2022 (GLOBE NEWSWIRE) --  Intercept Pharmaceuticals, Inc. (Nasdaq: ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced plans to focus development of its next-generation FXR agonist, INT-787, in severe alcohol-associated hepatitis (sAH). Alcohol-related liver disease is currently the leading indication for liver transplant listing in the U.S., with a marked increase in patients with sAH needing liver transplantation. Currently, there are no medicines with an approved indication to treat sAH.

Initial data from Intercept’s ongoing Phase 1 trial of INT-787 in healthy subjects was shared at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C., and supported a favorable safety and tolerability profile for INT-787 in healthy male and female adults. The company has also initiated the FRESH (FXR Effect on Severe Alcohol-Associated Hepatitis) study, a Phase 2a trial evaluating the safety, tolerability, efficacy and pharmacokinetics of INT-787 in subjects with sAH.

“As we begin our Phase 2a trial in patients with sAH, we are encouraged by the efficacy demonstrated in pre-clinical assessments, and the safety and tolerability in our single and multiple-ascending dose, first-in-human studies,” said M. Michelle Berrey, M.D., M.P.H., President of Research & Development and Chief Medical Officer of Intercept. “INT-787 is 16-fold more water-soluble than obeticholic acid, and in preclinical liver disease models modulates a significantly greater number of genes relative to OCA within the liver and intestine. This and other characteristics provide an opportunity to explore the potential for INT-787 in diseases which involve the gut as well as the liver such as sAH. By building on our decades of research in bile acids and FXR agonism, we hope to expand our pipeline to deliver effective treatments for the growing number of patients in the U.S. with chronic liver diseases.”

In a Phase 1, double-blind, placebo-controlled, single-ascending dose (SAD) and multiple-ascending dose (MAD) study, subjects were randomized to receive INT-787 or placebo (6:2 allocation) in each dose cohort. As of September 2022, 122 subjects had been randomized and dosed. Safety and tolerability were assessed based on adverse events, laboratory assessments, electrocardiograms (ECGs), vital signs, and physical examinations.

Results showed INT-787 was generally well tolerated in healthy subjects. No serious adverse events were reported. The majority of treatment-emergent adverse events were mild, and no treatment-limiting adverse events were identified. Mild pruritus was reported in 2 of 122 subjects and was not associated with dose. INT-787 showed rapid absorption with peak plasma concentration at 2 hours post-dose, and exposure increased in a dose-dependent manner. The half-life of total INT-787 ranged from 20 to 43 hours in cohorts with robust exposure. Renal excretion of conjugated INT-787 was observed in urine PK. The apparent steady state for total INT-787 concentration was reached by day 7 in the MAD study.

The Phase 1 study is ongoing and is expected to complete in Q1 2023.

The Phase 2a FRESH study is a randomized, double-blind, dose-escalation study that is expected to enroll approximately 50 patients with sAH across multiple clinical sites in the U.S., UK and France. The study aims to demonstrate and provide rationale for the selection of optimal dose(s) of INT-787 in the target patient population. INT-787 will be evaluated for safety and tolerability prior to dose escalation. Overall early efficacy, based on the Lille score at Day 7 compared to placebo, will be assessed for each dose cohort, as well as change in MELD score and mortality.

About Severe Alcohol-Associated Hepatitis (sAH)
Alcohol-related liver disease (ALD) as a cause of chronic liver disease is on the rise in the U.S. and is currently the leading indication for liver transplant listing overall in the U.S. Patients with severe alcohol-associated hepatitis (sAH) are now younger, with an increased representation of females compared to past decades, reflecting changing patterns of alcohol consumption in the U.S. Currently, there are no medicines with an approved indication to treat patients with sAH.

About Intercept
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, including primary biliary cholangitis (PBC), nonalcoholic steatohepatitis (NASH) and severe alcohol-associated hepatitis (sAH). For more information, please visit www.interceptpharma.com or connect with the Company on Twitter and LinkedIn.

Forward-Looking Statements
This press release contains forward-looking statements (“FLS”), including regarding our product pipeline, our clinical studies, and our research and development (“R&D”) plans. Important factors could cause actual results to differ materially from the FLS. For example, our clinical studies could be delayed, not reach enrollment targets, have methodological problems, or indicate that a studied drug is not effective, safe, or tolerable. As a result, our pipeline, studies, and R&D initiatives could be unsuccessful.

Contact

For more information about Intercept, please contact:

For investors:
Nareg Sagherian, Executive Director, Global Investor Relations
Investors@interceptpharma.com

For media:
Karen Preble, Executive Director, Global Corporate Communications
Media@interceptpharma.com

Source: Intercept Pharmaceuticals, Inc.