Pipeline
Our pipeline features innovative therapies in development to address liver regeneration and treatment resistance in oncology.
MKK4 inhibition for liver regeneration
HepaRegeniX is developing innovative therapeutics based on a novel molecular target and molecule. The inhibition of MKK4 has therapeutic potential to unlock and accelerate both functional and volumetric liver regeneration after extended liver resection or transplantation of small liver grafts from healthy, living donors to patients in need of a new liver.
Results of preclinical studies suggest a therapeutic potential of MKK4 inhibition in acute-on-chronic liver failure such as severe alcohol-associated hepatitis.
MKK4-inhibition in oncology
KRAS is one of the most frequently mutated oncogenes and associated with the most common and lethal cancer types, such as colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer. While targeted KRAS inhibitors have shown some benefit, overall survival remains limited due to resistance mechanisms, including feedback activation of the MKK4 pathway. Preclinical data suggest that MKK4-inhibition could restore sensitivity to KRAS inhibitors and enhance efficacy when used in combination.
HRX-215
Our lead candidate, HRX-215, is a first-in-class, orally available small molecule inhibitor of MKK4 (Mitogen-Activated Protein (MAP) Kinase Kinase 4) designed for use in liver regeneration. HRX-215 showed outstanding results in preclinical animal models by reducing post-surgical liver failure and dramatically improving survival in pigs requiring 85% liver resection, a well-established hepatectomy animal model that is typically lethal. In a Phase Ia clinical trial in healthy participants, HRX-215 demonstrated favorable safety and tolerability profiles and excellent pharmokinetics. Our clinical development strategy is planned through Phase IIa with clinical trials in major liver resections and living donor liver transplantation. HRX-215 has further potential in patients with chronic liver disease and severe alcohol-associated hepatitis.3 (click to see publication)
HRX-233
HRX-233 is an additional small molecule inhibitor of MKK4 with distinct pharmacokinetic properties being developed as combination therapy for KRAS-driven cancers.5(click to see publication) Currently, the response of certain KRAS inhibitors in cancer treatment is limited by compensatory signaling mechanisms that reduce their efficacy. Our preclinical mouse studies show that combining HRX-233 with KRAS inhibitors leads to more sustained tumor suppression in NSCLC and CRC models compared to monotherapy. By targeting adaptive resistance, HRX-233 has the potential to enhance the therapeutic impact of KRAS inhbitors and improve treatment outcomes in KRAS-mutant cancers.