21st Annual International Conference on Drug-Drug Interactions. Zach Mitts Northwest Account Manager

Transcription

1 21st Annual International Conference on Drug-Drug Interactions Zach Mitts Northwest Account Manager

2 How memorable can a 5-minute presentation be?

3 COMPANY HISTORY From the work of our Founder, Dr. Andrew Parkinson Pre-1994 Academic Laboratory: Dr. Parkinson Biotech Incubator: University of Kansas Privately owned and operated CRO In vitro ADME: Lenexa, KS Global CRO Family Full Service ADME: Sekisui Medical Division, Daiichi pure chemical To the Global Partnership with Sekisui Medical Division, Ltd Present Expanded sq ft facility Headquarters Sekisui XenoTech, LLC, Kansas City, KS Joint Venture Launched Japan Distribution Agreement Europe Distribution Agreement 1st Mass Spec Aquired by Sekisui Medical Division CryoStax Patent 20 Year Celebration Singapore Distribution Non-clinical Bioanalysis Human Lysosomes Launched China Distribution Hepatosure Launch Korean Radiolabeling Services Distributorship XenoTech BioBank Launched BT:PBMC and Co-Culture Patent Jul-94 Jul-95 Jul-96 Jul-97 Jul-98 Jul-99 Jul-00 Jul-01 Jul-02 Jul-03 Jul-04 Jul-05 Jul-06 Jul-07 Jul-08 Jul-09 Jul-10 Jul-11 Jul-12 Jul-13 Jul-14 Jul-15 Jul-16 Drug Transporter Distributor Hepatochem Global Distribution XenoTech Entity Established Sole Ownership Korea Distribution High Res MS Capabilities Africa Distribution Exclusive NA Distributor of JCRB Cell-Lines New Headquarters Facility SMD assumes Japan Distribution Hepatotox Services Launched 1st Tecan Liquid Handler India Distribution Internal Launch of Drug Transport CYPEX Distributor Services New 45,000 sq ft Headquarters Kansas SMD ADME Tox Distributor City, KS

4 Sekisui-XenoTech Products Overview XenoTech is a provider of key reagents and test systems for in vitro drug metabolism studies Hepatocytes Subcellular Fractions Other ADME Products Human Individual or pooled CryostaX- Single freeze pool Fresh or Cryopreserved Numerous pre-clinical species (mouse, rat, dog, monkey, etc.) Qualyst certified 160+ catalog products Microsomes, S9, Cytosol Human Xtreme pool of 200 Hepatic and extrahepatic (intestine, kidney, lung, etc.) Custom Products JCRB cell bank 1,100 cell lines Multiple reagents Genotyped hepatocytes and subcellular fractions Lysosomes/tritosomes Kupffer cells BioBank

5 Customizable, single-freeze pooled hepatocytes (n = 2 to 20) Customizable, PLATEABLE single-freeze pooled hepatocytes (n = 2 to 20) A patented, novel and convenient approach to pooled human hepatocytes

6 Sekisui XenoTech Services -Kansas lab -Tokai Japan lab

7 Our Ultimate Client(s) XenoTech s ultimate clients are the regulatory agencies: US FDA (2017 Draft Guidance for Industry Drug Interactions) Japan PMDA, European Medicines Agency (EMA 2012 Guidance Drug Interactions) Regulatory Interests Evaluate the victim and perpetrator potential of new drug candidates Victims Drugs whose clearance or elimination is determined primarily by a single route (enzyme, transporter, renal or biliary excretion) Perpetrators Factors that influence exposure to a victim drug by altering routes of clearance or elimination (polymorphisms, inhibitors, inducers) Evaluation of Victim Potential Reaction phenotyping for enzymes (CYP, UGT, AO, etc.) Transporter phenotyping (uptake and efflux) Plasma protein binding Evaluation of Perpetrator Potential Enzyme inhibition (CYPs, UGT, etc.) Transporter Inhibition CYP and transporter induction

8 In Vitro ADME-DMPK Service Capabilities Kansas Lab Drug Metabolism Metabolic stability and species comparison Metabolite characterization/id Reaction phenotyping (CYP & UGT) Customized services Enzyme Inhibition Evaluate potential for direct and metabolism-dependent inhibition (MDI or TDI) Mechanistic studies (direct or MDI) Non-CYP enzymes (e.g., UGT, MAO, AO) XT Consulting Department Expert data review and study consultation Bioanalytical Non-GLP Bioanalysis GLP and non-glp in vitro study support Enzyme Induction In vitro studies in cultured hepatocytes (human and animal) Ex vivo studies in animals Toxicity & mechanistic studies Transporters FDA and EMA required transporters In vitro studies in mono-layer cell lines for uptake Bi-directional assay for efflux transporters Membrane-based vesicles and ATPase assays Discovery and Late-Preclinical Support Medium-throughput ADME screening studies (Discovery Plus ) Definitive ADME and DDI studies to support design and necessity of clinical studies

9 Drug Development Solutions Business Tokai, Japan Lab Sekisui XenoTech Administrative Support Radio-compound Synthesis 14 C, 3 H, 125 I, 35 S Custom synthesis and purification Unstable chemicals/intermediates On site in vivo/in vitro testing In vitro pharmacology Radio-receptor assays Second messenger pathways Kinase activation, etc. On- and off-target receptor activation Bioanalytical GLP and Non-GLP Bioanalysis Small molecules and biotherapeutics Biomarker analysis In vivo ADME Studies PK screening, Bioavailability, Various Species Mass Balance and Metabolite Profiling Distribution Studies (QWBA) Imaging MS (TOF), Chimeric mice Transporters (> 40) Mono-layer cell lines for uptake Bi-directional assay for efflux transporters Membrane-based vesicles and ATPase assays Oocytes, SNPs, double-transfectants, KO mice Discovery and Late-Preclinical Support Medium-throughput in vitro and in vivo ADME screening studies Definitive ADME studies to support IND submission and mechanistic studies

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