Marseille, France, July 30, 2015 -Genoscience Pharma, a company focused on discovering and developing small molecules to treat cancer by targeting cancer stem cells, today announces that it will present data on its most promising candidate at The Liver Meeting® 2015: November 13 – 17, San Francisco, California

The details for the data presentations at AASLD are as follows. 

 Poster Presentation 

Title : Preclinical characterization of a novel first in class GNS561: autophagy inhibitor therapeutic candidate for treatment of hepatocellular carcinoma

Publication Number: 394 
Session Date and Time: November 14, 2015 from 2:00 PM to 7:30 PM 
Session: Clinical: Hepatocellular Carcinoma and Cholangiocarcinoma 
Room: Poster Hall


Background: In spite of successful approval and wide application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. Fortunately, there have been renewed and continued interests and active research in developing other molecularly targeted agents in HCC during the past few years. While there is early evidence of antitumor activity of several agents in phase I/II studies, phase III efforts with a few targeted agents have failed, highlighting the challenges in new drug development in HCC. For this reason, development of innovative drugs with original mechanism of action could improve treatment of HCC patients

Material and methods: We screened a library of autophagy inhibitor compounds and identified a new drug GNS561 as compound that kills tumor cells in a panel of HCC cell lines and primary tumor. Drug tolerance and plasma and liver pharmacokinetic were evaluated after single and repeated dosing in mice and rat.

Results: GNS561 demonstrates autophagy inhibition and apoptosis induction activities related to lysosome disruption. GNS 561 shows potent anti-proliferation activity when assayed against a panel of human tumor cell lines, notably against HCC cell lines (Mean EC50 2µM). In addition GNS561 demonstrates potent activity against a panel of HCC patient tumors even in those with sorafenib resistance (Mean EC50 3µM vs 11µM for sorafenib). GNS561 is highly selectively trapped in the liver, via uptake hepatocyte transporters. Plasma and liver PK in mice and rats after single and repeated doses confirm this selectivity (exposure ratio liver/plasma about 20 in mice) with a good oral bioavailability. Tolerance of single and repeated doses is excellent in both rats and mice

Conclusions: Our results provide a rationale for testing autophagy flux disruption as a novel therapeutic strategy for HCC. GNS561 is a liver selective drug which offers great promise for HCC treatment of non-responder or nontolerant patients to sorafenib. This compound is selected as a drug candidate for future investigation in HCC clinical trials.



Hepatocellular carcinoma (HCC), Resistance, Cancer, Lysosome, Autophagy, Liver





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