21 October 2021

Oncode Institute supports new preclinical collaboration between HepaRegeniX and the NKI

Goal is to explore the potential of its 2nd MKK4 inhibitor HRX-0233 for use in cancer combination therapy

Elize Brolsma

Elize Brolsma

Elize is part of Oncode’s communication team. She has over 10 years of experience in the com-munication industry, both for commercial and non-profit organisations. After obtaining her bache-lor and master degree in communication at Utrecht University, Elize worked as a communication professional at a research institute, PR agency, law firm and internet company. She has a strong focus on external communications and Public Relations. At Oncode - together with her colleagues - Elize produces the monthly newsletters for Oncode Investigators & Researchers and the Oncode digital magazine. She publishes content for the Oncode website and is responsible for all social media channels. She enjoys discussing science with researchers and support them in their outreach.
  • HRX-0233 is a new MKK4 inhibitor and the 2nd drug candidate from the company´s small molecule-based drug discovery platform
  • HRX-0223 is being investigated for the treatment of tumors with mutated KRAS gene, a common oncogenic driver in combination with other treatments
  • KRAS mutations are associated with poor prognosis

HepaRegeniX GmbH, a clinical stage company developing novel therapies for the treatment of acute and chronic liver diseases, announced a collaboration with the Netherlands Cancer Institute (NKI) to investigate HepaRegeniX’ new drug candidate HRX-0233 in preclinical in vivo models with Kirsten rat sarcoma virus (KRAS) mutant tumors. Under the partnership, NKI will conduct the preclinical research to find the most promising combinations of the small molecule inhibitor of Mitogen-Activated Protein (MAP) Kinase Kinase 4 (MKK4) with other inhibitors of the MAP kinase pathway. Preliminary data obtained by Prof. Bernards’ group at the NKI have shown promising results in cell culture experiments.[1] Oncode’s Valorization Team supported the contract negotiations.

“It is exciting to see our second MKK4 inhibitor candidate now entering the late preclinical development phase with the aim to learn more about the additional therapeutic potential of our new drug candidate HRX-0233 for patients with KRAS gene mutated cancers,” said Dr. Michael Lutz, CEO of HepaRegeniX. “Prof. Bernards and his group at the NKI are experts in cancer research, especially when it comes to uncovering synthetic lethal drug combinations, where the specific gene mutation and a drug efficiently kill the cancer cells.”

“HepaRegeniX has successfully discovered and developed drug candidates for the novel molecular target MKK4. Its inhibitor HRX-0233 shows promising initial results in synergy with other kinase-inhibitors in KRAS mutant tumors in vitro,” added Prof. René Bernards, Researcher of NKI and principal investigator at the Oncode Institute. “We are looking forward to the outcome and see a high value for this new small molecule in fighting KRAS mutant tumors.”

The mutation of the KRAS gene is present in 90 % of pancreatic, 40 % of lung, and 50 % of colorectal cancers and one of the most common oncogenic drivers. KRAS mutant tumors have a very poor response to current therapies[2].

[1] Xue Z, Vis DJ, Bruna A, Sustic T, van Wageningen S, Batra AS, Rueda OM, Bosdriesz E, Caldas C, Wessels LFA, Bernards R. MAP3K1 and MAP2K4 mutations are associated with sensitivity to MEK inhibitors in multiple cancer models. Cell Res. 2018;28(7):719-29

[2] Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Côté JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P (April 2006). "KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer". Cancer Research. 66 (8): 3992–5.

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