Study aims to determine whether MKK4 inhibitor can promote liver regeneration in patients with compromised liver function.
German biotech HepaRegeniX has initiated a clinical trial of its liver regeneration drug in patients undergoing partial liver resection due to liver metastases from colorectal cancer. The trial is a key step in evaluating the compound’s safety and therapeutic potential in humans with compromised liver function.
The trial, a randomized, double-blinded Phase 1b/2a study, is enrolling 85 patients in the United States and will assess HRX-215 in three patient groups differentiated by the extent of liver resection required. The study aims to determine whether the drug can enhance liver regeneration sufficiently to expand surgical eligibility and reduce post-operative complications.
HepaRegeniX, which closed a €21.5 million financing round in April, said that an initial data readout from the current trial is expected in 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 HepaRegeniX CMO Linda Greenbaum. “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 or liver scarring.”
The company’s lead program, HRX-215, is an orally administered small molecule designed to promote liver regeneration by selectively inhibiting mitogen-activated protein kinase kinase 4 (MKK4), a key regulator of liver regeneration. HRX-215 was developed in collaboration with Professor Lars Zender’s team at the University Hospital of Tübingen, whose work demonstrated MKK4’s role in controlling the regenerative activity of hepatocytes. By inhibiting MKK4, the drug is designed to reactivate the liver’s natural regenerative mechanisms, allowing for more robust hepatocyte recovery in both healthy and diseased livers.
HRX-215’s mechanism of action is thought to have strong potential in patients whose remaining liver tissue may be insufficient in volume or function to support recovery following surgery. In such cases, post-operative liver failure is a major risk, often disqualifying patients from potentially curative procedures. According to HepaRegeniX, its preclinical studies have shown that HRX-215 accelerates liver regrowth and stabilizes hepatocytes, improving survival and liver function after high-risk resections in animal models, and also reversed fibrotic and steatotic damage in diseased livers without inducing uncontrolled cell growth.
Beyond its application in liver metastasis surgery, it is thought the compound may have broader implications, such as supporting patients undergoing living donor liver transplantation and those with alcohol-associated hepatitis. Its potential to improve graft viability might also expand the pool of eligible donors, addressing a longstanding bottleneck in transplantation.
