FEB 23, 2017 12:00 PM PST

Novel Precision medicines that exploit Proximity

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  • President and Chief Executive Officer Centrose
      Currently, Dr James Prudent serves as the Chief Executive Officer and Chairman of the Board at CENTROSE, a biotechnology company focused on developing precision therapies for diseases with high unmet need. While exploring interesting natural products, Dr. Prudent and his colleagues discovered that the "all powerful" Na,K-ATPase was interacting with multiple proteins at the cell surface. The biology of the various interacting proteins indicated an evolutionary pattern of energy regulation coupled to growth, motility, and survival. This discovery led to the invention of EDC Technology which allows for the unprecedented precise delivery of drugs. Currently the company has discovered multiple EDCs for cancer and autoimmune disease. Prior to CENTROSE, Dr. Prudent served as Chief Science Officer and Board Member at EraGen Biosciences (now Luminex) where he invented GENE-CODE and MULTI-CODE, technologies that incorporate an expanded genetic code into real-time and multiplexed diagnostic assays. Before EraGen, Dr. Prudent invented Invader Technology while at Third Wave (now Hologic). Invader is complimentary to PCR but does not amplify DNA; making Invader more accurate and easier to use. Today, Invader is being used by Hologic and Exact Sciences in their diagnostic products. Prior to Third Wave, Dr. Prudent received his Ph.D. in Chemistry at the UC - Berkeley under the direction of Professor Peter G. Schultz and his B.S. in Bacteriology and Medical Microbiology at the University of Wisconsin - Madison. He has over 100 publications, patents and patent applications. He is a recipient of the Frost and Sullivan Product of the Year Award and Biotechnology Industry Organization Innovation Award.


    Cell growth and regulation involve vast networks of interacting DNAs, RNAs, proteins, lipids and sugars. Through a fundamental strategy of life, these interactions push multiple cellular processes by increasing local concentrations of key molecules. Now scientists can exploit these interactions with a new type of precision therapy called the Extracellular Drug Conjugate (EDC).

    EDCs are a new type of ADC that use proximity to activate the drug’s potential. In the case of EDCs, a drugs activity is increased by over 1000-fold if both targets (antibody and drug) are within angstroms apart (i.e. they interact).   This talk will discuss how EDCs can exhibit low to mid-picomolar potencies, and with signal to noise ratios of > 1,000:1; both of which are dependent on the expression and interaction of two proteins.

    Specifically, this talk will focus on proteins that interact with the human Na,K-ATPase (NKA). An active plasma membrane ion pump, the NKA is required for life. Without it, the cell cannot maintain a proper ion potential and the cells dies by a natural death process known as necrosis. You will learn about; 1) how a small naturally occurring steroid can be delivered to specific cell types and how this delivery can affect cell growth and cytokine production, 2) how this knowledge can be exploited in precision medicine, and 3) how a blockbuster antibody medicine can be constructed to kill B-cells while having no effect on other blood cells. This talk will therefore describe a new level of therapeutic precision that depends on protein-protein proximity and not simply the expression of a single protein.

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