HepaRegeniX GmbH announced the publication of clinical and preclinical data on its first-in-class MKK4 inhibitor, HRX-215, in the journal Cell. The data demonstrate strongly enhanced liver regeneration and prevention of liver failure in preclinical models, along with safety and tolerability in a first-in-human trial. This news offers hope for improved outcomes in liver surgery and transplantation.
HRX-215: A Novel Approach to Liver Regeneration
HRX-215 is a small molecule inhibitor of Mitogen-Activated Protein (MAP) Kinase Kinase 4 (MKK4). The research, a collaboration between Tuebingen University Hospital, the Mayo Clinic in Rochester, and HepaRegeniX, suggests that inhibiting MKK4 unlocks the regenerative capacity of hepatocytes, even in severely diseased livers.
Dr. Wolfgang Albrecht, COO of HepaRegeniX, stated, "The positive results in terms of safety and tolerability confirm our intention to soon offer a drug that has the potential to revolutionize the treatment of severe liver diseases. The data pave the way for further Phase II studies evaluating the efficacy of HRX-215 in humans."
Preclinical and Clinical Findings
Preclinical studies showed that HRX-215 treatment boosts liver regeneration after partial liver removal (hepatectomy) without affecting intact livers. Furthermore, HRX-215 protected hepatocytes from cell death in a model of acute liver injury. In a Phase I study, HRX-215 was well-tolerated at all doses, with no drug-related adverse events observed in healthy volunteers.
Potential Applications in Liver Surgery and Transplantation
Complete resection of liver tumors is the only curative approach for patients with liver metastases from colorectal cancer or primary liver tumors. However, post-hepatectomy liver failure (PHLF) is a lethal complication that limits surgical treatment when the remaining liver volume is insufficient. HRX-215 could potentially make more extensive liver resections possible by preventing PHLF.
Prof. Lars Zender, Medical Director at the University Hospital Tuebingen, highlighted the potential of HRX-215 to address organ shortages in liver transplantation: "Due to the rapid enhancement of liver regeneration mediated by HRX-215, we assume that HRX-215 treatment would enable the safe transplantation of small left liver lobes in normal size adults."
