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| About Pierre Beauparlant (Gemin X Pharmaceuticals Inc.) |
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Pierre Beauparlant, Ph.D. is Vice President, Research and Scientific Development at Gemin X Pharmaceuticals Inc. Dr. Beauparlant is leading drug discovery research at Gemin X Pharmaceuticals and is responsible for building and managing the company's intellectual property portfolio. Gemin X is developing small molecules that target specialized pathways for cancer, including key regulators in the genesis and progression of cancer. Prior to joining Gemin X, Dr. Beauparlant led product marketing efforts and contributed to the development of several therapies in the fields of immunology and neuroscience at Novartis Pharmaceuticals. Dr. Beauparlant holds a Ph.D. in microbiology and immunology from McGill University. He has published about 50 research papers and abstracts in the fields of molecular oncology and virology.
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Target Identification Permits Rational Development of the Prodrug GMX1777 for the Treatment of Melanoma
Pierre Beauparlant, GeminX Pharmaceuticals Inc.
GMX1777 is a prodrug of the cyanoguanidinopyridine GMX1778 and demonstrates strong anti-tumor activity in vitro and in vivo across a variety of human tumor cell lines and in xenograft models. To determine the primary mechanism of action of GMX1778, a combination of global metabolomics and targeted biochemical pathway profiling studies were undertaken to track intracellular physiological changes over time. Of the limited physiological changes in IM-9 cells observed after treatment with GMX1778 for 6 hours, there occurred a 60% decline of intracellular NAD+ levels, with a 91% decline noted at 13 hours. Further studies revealed that GMX1778 is a potent and specific inhibitor of nicotinamide phosphoribosyltransferase (NAMPRT), the rate limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). Because DNA damage repair pathways are extremely dependent on NAD+ levels, we tested a wide spectrum of DNA-damaging agents for synergistic cell killing in combination with GMX1778 in vitro. The DNA-alkylating agent, temozolomide, exhibited the greatest synergy with GMX1778 treatment. The clinical development of GMX1777 in combination with temozolomide is currently being explored for the treatment of melanoma patients. To this end pre-clinical development of a dosing schedule that would accommodate a combination treatment with temozolomide resulted in a dosing schedule of five daily 3 hour infusions of GMX1777. These results illustrate the impact that rational drug combinations utilizing targeted agents can have on the clinical development of novel cancer therapeutics.
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