Company to commence clinical trials of MKK4 inhibitor shown to induce liver regeneration ‘even in severely diseased livers.’
German biotech HepaRegenix has successfully secured €15 million in a Series C funding round to advance the clinical development of its regenerative liver therapy program. The company’s lead candidate, HRX-215, is designed to inhibit Mitogen-Activated Protein (MAP) Kinase Kinase 4 (MKK4), which is thought to be a crucial regulator of liver regeneration.
Having already completed a Phase 1 trial, HepaRegenix says the new funding will support a Phase 1b clinical trial of HRX-215 in the United States and an international multicenter Phase 2a clinical trial. The company also announced the transition of Elias Papatheodorou from Chairman to CEO, and the appointment of former Novartis exec Dr Linda Greenbaum, who joins as Chief Medical Officer.
“We are thrilled to secure this significant financing, which underscores the confidence our investors have in our science and our capabilities to bring effective treatments to patients suffering from liver diseases,” said Papatheodorou.
HepaRegenix’s approach is built on the research of Prof. Lars Zender and his team at the University Hospital Tübingen, Germany, who identified MKK4 as a key player in liver regeneration. The researchers demonstrated that MKK4 suppression can induce hepatocyte regeneration even in severely diseased livers, underpinning the company’s development of HRX-215 and other small molecule inhibitors.
By suppressing MKK4, HRX-215 aims to unlock the regenerative potential of hepatocytes, offering a promising treatment for both acute and chronic liver diseases. According to HepaRegenix, the treatment holds potential for patients with liver metastases or primary liver tumors, as well as potentially reducing waiting lists for liver transplants.
“MKK4 is a key regulator of liver regeneration, and MKK4 inhibition has been shown to induce liver regeneration after a partial hepatectomy,” said Greenbaum, HepaRegenix’s new CMO. “With this mode of action, HRX-215 has an immense potential to improve outcomes for patients who are currently not able to undergo potentially curative surgical resections due to liver tumors, and other patient groups affected by liver failure.”
Preclinical studies conducted by HepaRegenix showed promising results in various animal models, notably a reduction in hepatic steatosis and liver damage in a murine model of nonalcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC), with significant growth suppression of the carcinoma.
Further studies have shown that inhibiting MKK4 enhances hepatocyte proliferation in both mice and pigs, increases overall hepatocyte robustness, reduces alcohol-induced steatosis and chronic NASH, and decreases liver lipids without affecting body or liver weight. These results support the potential of HRX-215 as a breakthrough therapy in liver regeneration.
The funding round was led by Vesalius Biocapital IV with participation from Novo Holdings, Boehringer Ingelheim Venture Fund, and High-Tech Gründerfonds. Fabienne Roussel from Vesalius also joins the Board of Directors.
“There is an immense need for a treatment that can induce liver regeneration in patients suffering from liver damage, liver tumors, as well as in transplant settings,” said Roussel. “HRX-215 has potential to help these patients and make a meaningful impact on their lives.”