Onxeo Announces First Outcomes of Livatag® Preclinical Plan

  • Livatag® Nanoformulation Leads to Increased Exposure and Preferential Affinity for Liver, Supporting Current Relive Phase III Study Rationale
  • Demonstrates Enhanced Effect in Combination with Immunotherapy

 Paris (France), Copenhagen (Denmark) – Onxeo S.A. (Euronext Paris, Nasdaq Copenhagen: ONXEO), an innovative company specializing in the development of orphan oncology therapeutics, today announced data from 2 in vivo studies of the Livatag® preclinical plan confirming that the nanoparticle formulation meets the pharmacological requirements for a hepatocellular carcinoma (HCC) treatment and, furthermore, that the combination of Livatag® with immunotherapy produces an enhanced efficacy effect, validating Onxeo’s comprehensive strategy to explore further potential indications for its key product candidate.

The studies were performed in an orthotopic (implantation of tumor cells into the liver of mice) HCC model in immune-competent mice. Orthotopic models are considered relevant to the clinical situation and a good predictor of drug efficacy. Results demonstrate that Livatag® (doxorubicin TransdrugTM) generates a 12-fold increase in exposure in the tumor tissue within the liver compared to free doxorubicin, without increasing the drug’s exposure in the heart or other vital organs. These findings complete, and go beyond, data from a mechanistic study of Livatag® previously reported at the 2016 American Association for Cancer Research (AACR) Annual Meeting that revealed that the distribution of Livatag® nanoparticles in healthy liver was approximately six times higher compared to free doxorubicin, which indicate that Livatag® nanoparticles have a preferential affinity for and are able to target the liver and more particularly, the liver tumor tissue.

As part of this program, Onxeo has also been exploring the potential of Livatag® when administered with emerging immuno-oncology agents of various classes, such as promising PD-1 and CTLA-4 checkpoint inhibitors currently in development. A current study demonstrates that Livatag® produces an enhanced effect in tumor response (reduction in tumor volume) when given in combination with immuno-oncology agents in the orthotopic HCC model. Specifically, Livatag® co-administration with antibodies is associated with a positive increase in circulating T-cell populations, which is consistent with the observed reduction in tumor volume.

Graham Dixon, PhD, Chief Scientific Officer at Onxeo, commented, “These preclinical findings are important because they reinforce our previous research showing that Livatag® Transdrug™ technology dramatically improves the drug’s exposure in liver cancer tissue, demonstrating high affinity for the liver, without increasing exposure in other organs. These data validate the interest of Livatag® as a potential new therapeutic option for HCC treatment. Besides, we are pleased to share the first data demonstrating an enhanced anti-cancer response generated by Livatag® in combination with immuno-oncology agents in murine HCC models. Results from this study will enable us to extend the value of one of our lead assets and add to the growing value of Onxeo’s pipeline. In addition to sharing results from the Phase III ReLive trial next year, we look forward to continued evaluation of Livatag® in combination with immunotherapy agents and delivering a plan to advance Livatag® in the clinic in additional indications.”

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