HepaRegeniX GmbH (“HepaRegeniX”), a clinical-stage company advancing novel therapies to treat acute and chronic liver disease, announced that the first patient has been dosed in their Phase Ib clinical trial of its lead candidate HRX-215. The trial is evaluating the safety and efficacy of HRX-215, an orally available small-molecule inhibitor of MKK4, in patients undergoing partial liver resection due to liver metastases deriving from colorectal cancer. HXR-215 is designed to treat advanced-stage liver disease by increasing the regenerative capacity of hepatocytes. An initial data readout is planned for the second half of 2025.

“We aim to address a critical unmet need in patients with advanced liver disease who are often considered inoperable due to the limited regenerative capacity of the remaining liver after partial resection,” said Linda Greenbaum, Chief Medical Officer at HepaRegeniX. “HRX-215 may offer a new therapeutic option by promoting hepatocyte regeneration, thereby increasing the safety and feasibility of liver resections in patients who have insufficient predicted postoperative liver mass and/or reduced liver function associated with fatty liver (steatosis) or liver scarring (fibrosis).”

“Dosing the first patient in this trial marks an important milestone for HepaRegeniX as we advance HRX-215 into the next stage of clinical development,” said Elias Papatheodorou, Chief Executive Officer at HepaRegeniX. “Together with our recently completed €21.5 million Series C financing round, we are well-positioned to advance HRX-215 through clinical development and ultimately improve outcomes for patients facing limited treatment options.”

The randomized, double-blinded Phase Ib/IIa trial (NCT06638502), conducted in the United States, will evaluate the safety and efficacy of HRX-215 in 85 patients with liver metastases originating from colorectal cancer. Participants will be divided into three cohorts: (1) active treatment arm for patients requiring minor liver resection ( 30%), (2) active treatment arm including patients requiring major liver resection (50 – 72%), and (3) active treatment and a placebo comparator arms for patients requiring major liver resection.

The study builds on preclinical and clinical data published in Cell in March 2024, which demonstrated the potential of HRX-215 to significantly boost liver regeneration and prevent post-hepatectomy liver failure (PHLF) in animal models and which demonstrated acceptable safety profile and pharmacokinetics in a Phase I trial in healthy participants. The compound showed favorable safety and tolerability, with no drug-related adverse events observed.