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Ncardia

1 Order Completed
Cologne, DE

About Ncardia

Founded: 2000 Type: Privately Held Size: 11-50 employees

Ncardia with the merger of Axiogenesis and Pluriomics is an international leader in the development and commercialization of in vitro models of healthy and diseased cell types and tissue. Ncardia's technologies greatly improve the speed and confidence in discovering new therapies, and reduce attrition of... Show more »

Ncardia with the merger of Axiogenesis and Pluriomics is an international leader in the development and commercialization of in vitro models of healthy and diseased cell types and tissue. Ncardia's technologies greatly improve the speed and confidence in discovering new therapies, and reduce attrition of failed compound getting better medicine to patients faster.

Combining decades of human iPSC stem cell technology experience under our belts, Ncardia uses stem cells to revolutionize the fields of drug discovery & development and life sciences research. Ncardia develops and commercializes stem cell-derived, in vitro differentiated cardiomyocytes, neurons and other cell types, as well as drug development assays and disease models, to help researchers discover cures.

Ncardia's flagship offerings are the Cor.4U® and Pluricyte human cardiomyocyte products, derived from induced pluripotent stem (iPS) cells, which are used in applications from single cell analysis to high-throughput screening (HTS) of pharmaceutical compounds.

Axiogenesis' innovative and proprietary cell types and assays accelerate and improve drug candidate selection, lower costs and thus increase overall drug development efficiency.

Selected Publications

  • Franz D, Olsen HL, Klink O, Gimsa J. Automated and manual patch clamp data of human induced pluripotent stem cell-derived dopaminergic neurons. Sci Data. 2017 Apr 25;4:170056. doi: 10.1038/sdata.2017.56.
  • Zhao L, Zhang B. Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes. Sci Rep. 2017 Mar 16;7:44735. doi: 10.1038/srep44735.
  • Blinova K, Stohlman J, Vicente J, Chan D, Johannesen L, Hortigon-Vinagre MP, Zamora V, Smith G, Crumb WJ, Pang L, Lyn-Cook B, Ross J, Brock M, Chvatal S, Millard D, Galeotti L, Stockbridge N, Strauss DG. Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias. Toxicol Sci. 2017 Jan;155(1):234-247. doi: 10.1093/toxsci/kfw200.
  • Goßmann M, Frotscher R, Linder P, Neumann S, Bayer R, Epple M, Staat M, Artmann AT, Artmann GM. Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells. Cell Physiol Biochem. 2016;38(3):1182-98. doi: 10.1159/000443124.
  • Frotscher R, Muanghong D, Dursun G, Goßmann M, Temiz-Artmann A, Staat M. Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue. J Biomech. 2016 Aug 16;49(12):2428-35. doi: 10.1016/j.jbiomech.2016.01.039.
  • Becker N, Stoelzle S, Göpel S, Guinot D, Mumm P, Haarmann C, Malan D, Bohlen H, Kossolov E, Kettenhofen R, George M, Fertig N, Brüggemann A. Minimized cell usage for stem cell-derived and primary cells on an automated patch clamp system. J Pharmacol Toxicol Methods. 2013 Jul-Aug;68(1):82-7. doi: 10.1016/j.vascn.2013.03.009.
  • Abassi YA, Xi B, Li N, Ouyang W, Seiler A, Watzele M, Kettenhofen R, Bohlen H, Ehlich A, Kolossov E, Wang X, Xu X. Dynamic monitoring of beating periodicity of stem cell-derived cardiomyocytes as a predictive tool for preclinical safety assessment. Br J Pharmacol. 2012 Mar;165(5):1424-41. doi: 10.1111/j.1476-5381.2011.01623.x.
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Our Services (17)


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Real-Time Cytotoxicity Assay

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IncuCyte S3

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DART Studies

Developmental and Reproductive Toxicology Studies
Price on request

µEST - In vitro Embryotoxicity Screening

The µ[email protected] test system utilises the ability of mouse embryonic stem cells (ES cells) to differentiate in vitro into various tissues of all three germ layers. Supposing that exposure of ES cells to embryotoxic and teratogenic compounds during this process interferes with correct... Show more »

µEST - In vitro Embryotoxicity Screening

The µ[email protected] test system utilises the ability of mouse embryonic stem cells (ES cells) to differentiate in vitro into various tissues of all three germ layers. Supposing that exposure of ES cells to embryotoxic and teratogenic compounds during this process interferes with correct differentiation, the resulting amount of a given tissue, e.g. cardiac tissue, will be a marker for developmental toxicity. To distinguish a specific embryotoxic effect from a plain cytotoxic effect, results of the µ[email protected] are compared to results from a standard cytotoxicity assay (XTT test).

The mechanistic principle of the test was described by Spielmann et al. in 1997 and validated by the ECVAM Scientific Advisory Committee (ESAC) in 2001. The µ[email protected] test system was stated equivalent to the validated EST by ECVAM, and gained acceptance as "suitable for REACH" by ECVAM in 2008.

Predictivity of µ[email protected] (70 compounds tested within the ECVAM validation studies):

Specificity 87%
Sensitivity 88%
Negative predictive value 81%
Positive predictive value 91%
Accuracy 87%

***Cells
-Embryonic stem cells bearing a read-out system for cardiac differentiation
***Species
-Mouse
***Reporter
-TAQ GFP or SEAP
***Service Content
-Comparative investigation of embryotoxicity and/or teratogenicity and cytotoxcity of test compounds on differentiating mouse ESC.
***Delivery
-A study protocol will be sent to initiate the study. Results are sent as draft and final study report.
***Timeline
-Experiment time: 4 weeks per compound, Draft report: within 8 weeks

ADVANTAGES µEST® EMBRYOTOXICITY SCREENING

-Early identification of compounds that are embryotoxic or teratogenic.
-Fully in-vitro system eliminates animal testing.
-Highly sensitive, only a minute amount of compound (< 50 mg) required for testing.
-Elegant technique uses GFP or SEAP as reporter.
-Time and cost-effective for a more efficient and economical use of human and financial resources.

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Lonza µEST Mouse Cardiovascular Congenital disorders µEST screening Drug Discovery Toxicology Somatic Mutations Germline Mutations embryotoxicity toxicity Show 11 more tags Show less

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In vitro Cardiotoxicity Screening

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CardioFlux - Calcium-Flux functional analysis

Our Cardio.Flux Service provides high-throughput (HT) cardiac safety assessment by monitoring Ca2+ transients in healthy* cardiomyocytes. Direct, acute drug effects on both electrophysiology and contractility of cardiomyocytes can be detected with the HT Cardio.Flux Service and... Show more »

CardioFlux - Calcium-Flux functional analysis

Our Cardio.Flux Service provides high-throughput (HT) cardiac safety assessment by monitoring Ca2+ transients in healthy* cardiomyocytes. Direct, acute drug effects on both electrophysiology and contractility of cardiomyocytes can be detected with the HT Cardio.Flux Service and will help expedite decision making at early stages of preclinical drug development.

This service is based on executing fluorescent based assays that measure changes in intracellular calcium handling using the FLIPR® Tetra system (Molecular Devices). Since calcium is the interdependent regulator between cardiomyocyte electrophysiology and contraction, compounds affecting ion channels can (in)directly affect intracellular calcium transients. The analysis of fluorescent intracellular calcium transients is excellent for identifying acute compound effects on cardiomyocyte electrophysiology and contractility at high-throughput. We offer this service in collaboration with Pivot Park Screening Centre (PPSC), allowing ultra HT (uHT) screenings using automation and miniaturization.

Cell type- iPSC derived cardiomyocytes
Species- Human
Service type- Calcium-flux functional analysis
Format- 96 Well plate
Assay window- 30 Minute compound exposure
Compound concentrations*- 0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)
Positive controls- L-type Ca2+ channel blocker: Nitrendipine 100 nM
hERG blocker: Dofetilide 30 nM
Vehicle control- 0.1% DMSO
End-points- Peak frequency (beat rate), peak amplitude, peak width diameter and proarrhythmic events
Timelines- 3 Weeks (for up to 9 compounds)
Delivery- A study protocol will be sent to initiate the study. Results are sent as draft and final study report.

Cardio.Plex - Multi-parametric analysis

Ncardia’s Cardio.Plex Services provides a multiparametric analysis to investigate potential cardiotoxicity of test compounds over a relatively long time span. A combination of functional and structural toxicity analysis in fully functional and validated hiPSC-derived cardiomyocytes after compound treatment forms the basis of this service.

As complex mechanisms underlie drug-induced toxicity, some compound effects will only become evident after longer incubation times. Therefore, this service includes an analysis up to 48 hours after incubation. Efficient cardiac safety assessment should ideally include both, analysis of structural and functional toxicity of compounds. With Cardio.Plex, the functional toxicity will be analyzed by a combination of electrophysiology and impedance monitoring of hiPSC-derived cardiomyocytes. The structural toxicity is defined by the detection of Troponin I release after compound addition. Troponin I is a clinically relevant and established diagnostic marker for myocardial damage.

The Cardio.Plex Service will offer the most extensive evaluation of cardiotoxicity available to reduce the risk of missing any cardiotoxic effect of candidate drugs.

Cell type- iPSC derived cardiomyocytes
Species- Human
Service type- Electrophysiology and impedance functional analysis + Troponin I release analysis
Format- 96 Wells
Time points- Electrophysiology temporal study (0, 6, 12, 24 and 48 hours after compound addition)
Troponin I release (0, 8, 24, 32 and 48 hours after compound addition)
Compound concentrations*- 0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)
Positive controls- L-type Ca2+ channel blocker: Nifedipine 100 nM
hERG channel blocker: Dofetilide 30 nM
Nav 1.5 and hERG channel blocker: Mexiletine 30 µM
Ponatinib 10 µM (as positive control for Troponin I release)
Vehicle control- 0.1% DMSO
Readouts

  1. Electrophysiology: beat rate, beat rate CoV, field potential duration (FPD), depolarization peak amplitude, proarrhythmic events
  2. Contractility: impedance amplitude and peak width
  3. Troponin I release
    Timelines- 5 Weeks (for up to 9 compounds)
    Delivery- A study protocol will be agreed upon before study initiation. Results will be presented in graphs in a final study report.

Cardio.Effect - Impedance Functional Analysis

Ncardia’s Cardio.Effect Service provides you an economic cardiac safety analysis of drug candidates over a relatively long time frame (up to 48 hours). This service is ideal for screening larger numbers of compounds.

CardioEffect is based on impedance technology to provide a homogenous and standardized assay system for in vitro detection of compound effects on cell beating. This includes changes of spike amplitude, beating frequency, induction of arrhythmia, and beating arrest. In addition to phenotypic assessment of contractile motion, this assay provides a surrogate measure of cytotoxicity via the “Cell Index”.

CardioEffect provides an ideal tool to assess cardiomyocyte function, and safety pharmacology/ toxicity effects of drug candidates on human cardiomyocytes in a label-free, real time assay. Understanding cardiotoxic liabilities of compounds in early stages of drug development establishes confidence to move lead compounds towards pre-clinical and clinical development.

Cell type- iPSC derived cardiomyocytes
Species- Human
Service type- Impedance functional analysis
Format- 96 Well plate
Assay window- Cardiotoxicity temporal study (0, 12, 24 and 48 h after compound addition)
Compound concentration*- 0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)
Positive controls- L-type Ca2+ channel blocker: Nifedipine 100 nM
Myosin heavy chain inhibitor: Blebbistatin 0.4 µM
Vehicle (negative) control- 0.1% DMSO
Readouts

  1. Impedance amplitude and peak width; beating frequency, induction of arrhythmia and beating arrest, phenotypic assessment of contractile motion, this assay provides a surrogate measure of cytotoxicity via the “Cell Index”
    Timelines- 3 Weeks (for up to 9 compounds)
    Delivery- A study protocol will be agreed before study initiation. Analysis of raw data results will be presented in graphs in a final study report.

Cardio.Acute- CiPA like MEA Functional Analysis

Ncardia’s in-house Cardio.Acute Services provides an acute cardiac safety profile of test compounds based on the electrophysiology of fully functional and validated human cardiomyocytes.

Investigating the electrical activity of hiPSC-CMs’ acute response to drugs is part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative.* CiPA aims to replace current methods that evaluate proarrhythmic risk with assessments that are more clinically predictive and will improve effective drug development.

Ncardia is an official partner of the CiPA initiative and its Cor.4U® and Pluricyte® Cardiomyocytes are currently being used by different (non-)core partners. Our cardiomyocytes in combination with microelectrode array (MEA) platforms provide a highly relevant and predictive in vitro assay platform to study the cardiac safety profile of compounds during drug development.

Cell type- iPSC-derived cardiomyocytes
Species- Human
Service type- CiPA-like MEA functional analysis
Format- Up to 96 wells
Assay window- 30 Minute compound exposure
Compound concentrations*- 0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)
Positive controls- hERG channel blocker: Dofetilide 30 nM
Nav 1.5 and hERG channel blocker: Mexiletine 30 µM
Vehicle control- 0.1% DMSO
End-points- Beat rate, beat rate CoV, field potential duration (FPD), depolarization peak amplitude and proarrhythmic events
Timelines- 3 Weeks (for up to 9 compounds)
Delivery- A study protocol will be sent to initiate the study. Results are sent as draft and final study report.

Cardio.Long - Electrophysiology and Impedance Analysis

Ncardia’s long-term service provides you with a cardiac safety profile of your test compounds over a relatively long time frame. A combination of electrophysiology and impedance monitoring of fully functional and validated hiPSC-derived cardiomyocytes after compound treatment, followed by a thorough analysis by our electrophysiology and impedance experts forms the basis of this service.

As complex mechanisms underlie drug-induced arrhythmia, we provide this service to study acute to long-term (30 minutes – 48 hours) compound-effects on the electrophysiological behavior of cardiomyocytes. For instance, the drug pentamidine delays the terminal repolarization in the human heart. This is not established by acutely blocking cardiac inward rectifier currents, but by chronically reducing surface expression of the cardiac hERG potassium channel (Dennis, Wan and Ficker, 2007). Hence, the effect only becomes evident after longer incubation times. This example emphasizes the need for long-term cardiotoxic analysis in order to decrease the risk of missing cardiotoxic effects by acute measurements only.

Cell type- iPSC derived cardiomyocytes
Species- Human
Service type- Electrophysiology & impedance functional analysis
Format- 96 Wells
Time points- Cardiotoxic safety temporal study (0, 6, 12, 24 and 48 hours after compound addition)
Compound concentrations*- 0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)
Positive controls- L-type Ca2+ channel blocker: Nifedipine 100 nM
hERG channel blocker: Dofetilide 30 nM
Nav 1.5 and hERG channel blocker: Mexiletine 30 µM
Vehicle control- 0.1% DMSO
Readouts

  1. Electrophysiology: beat rate, beat rate CoV, field potential duration (FPD), depolarization peak amplitude, proarrhythmic events
  2. Impedance: amplitude and peak width
    Timelines- 5 Weeks (for up to 9 compounds)
    Delivery- A study protocol will be agreed upon before study initiation. Results of the study will be presented in graphs in a final study report.

Cardio.Force - Biomechanical analysis

The Cardio.Force Service offers a non-invasive in vitro assay to measure true contractility of human cardiac myocytes with exceptional accuracy under physiological mechanical boundary conditions. The standard assay service is based on Ncardia’s proprietary Cor.4CE® system, and uses monolayers of Cor.4U® human cardiomyocytes. In a customized assay format also vCor.4U® or co-cultures of the cardiomyocytes with hiPSC-derived FibroCor.4U® cardiac fibroblasts can be applied.

The combination of Cor.4U® with the Cor.4CE® system is the first in vitro assay setup to measure true contractile force of iPSC-derived cardiomyocytes in a system compatible with medium throughput. The system provides an ideal tool to assess pharmacological, safety pharmacological and toxicological effects of drug candidates on human cardiomyocytes.

Cell type- iPSC-derived Cor.4U® cardiomyocytes
Species- Human
Service type- Biomechanical analysis
Format- 8 wells (on 24 well plate)
Time points- 5-15 minutes after compound incubation
Compound concentrations*- 0.001 µM – 10 µM (in 5 logarithmic steps) in medium + 0.1 %DMSO
Positive control- Isoprenaline 0.001 µM – 0.1 µM; Verapamil 0.1 µM – 1 µM (in duplicates)
Vehicle control- 0.1% DMSO (in duplicates)
End-points- Highest dose - (optional washout)
Timelines- 7 weeks for up to 5 compounds (in quadruplicates)
Delivery- A study protocol will be agreed before study initiation. Results will be presented in a final study report.

Cardio.Tox - Structural Toxicity analysis

Efficient assessment of cardiotoxicity for drug candidates should ideally include both the structural and functional aspects of cardiac cell biology. Our Cardio.Tox Troponin I Service offers expert structural cardiotoxicity analysis of compounds.

This service is based on the detection of Troponin I release by hiPSC-derived cardiomyocytes. Troponin I is an established diagnostic marker for cardiovascular diseases. It is released into the circulation after cardiomyocyte damage induced by myocardial infarct or treatment with cardiotoxic drugs.

Due to the non-destructive nature of this assay, it can easily be combined with functional assays for a more comprehensive assessment for predicting cardiotoxicity.

Cell type- iPSC-derived cardiomyocytes
Species- Human
Service type- Structural toxicity based on biomarker detection
Format- 96 Wells (Up to 384 wells possible)
Time points- (8, 24, 32, 48 and 64 hours after compound addition)
Compound concentration*- 0.1, 1, 10 µM in medium + 0.1% DMSO
Positive control- Ponatinib 10 µM
Vehicle control- 0.1% DMSO
End-points- Released Troponin I detection
Timelines- 3 Weeks for up to 9 compounds (in triplicates)
Delivery- A study protocol will be agreed before study initiation. Results will be presented in graphs in a study report.

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Axion Maestro XCELLigence ACEA XCELLigence Hamamatsu FDSS Nanion CardioExcyte Microelectrode Array ACEA Nanion Human calcium dye transient transfection Xpress.4U GCAMP6 ChR2 Channel Rhodopsin Lipidsome mRNA Cardiovascular Cardiomyopathy Arrhythmia Transient expression MEA Impedance calcium imaging calcium dye calcium transient Drug Discovery Toxicology hERG Nav1.5 Ion Channel calcium efflux calcium Hamamatsu CardioExcyte Show 35 more tags Show less

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Custom Cell-Based Assay Development

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Cardiovascular Drug Efficacy Services

Current drug development strategies are very expensive and lead to high drug attrition rates. One major reason for low success rates is the lack of predictive preclinical models for efficacy (and safety) testing. At Ncardia we combine our cardiovascular knowledge with expertise on... Show more »

Cardiovascular Drug Efficacy Services

Current drug development strategies are very expensive and lead to high drug attrition rates. One major reason for low success rates is the lack of predictive preclinical models for efficacy (and safety) testing. At Ncardia we combine our cardiovascular knowledge with expertise on hiPSC-derived cardiomyocyte manufacturing to offer you predictive and translational in vitro disease models, and assays for efficacy screening at any throughput.

Disease modeling

Preclinical efficacy studies are commonly conducted by utilizing animal models, and primary cells or immortalized cell lines. However, all these models have shortcomings, which can negatively impact the predictivity of such studies.
With the discovery of human induced pluripotent stem cell (hiPSC) technologies, we can now generate virtually any human cell type from hiPSCs. This makes the technology an ideal tool for efficacy screening studies which require human cell-based models that exhibit the disease phenotype.

At NCardia, we are specialized in the generation of hiPSC-derived cardiomyocytes. Our proprietary differentiation protocol of Pluricyte® Cardiomyocytes is serum-free and easily scalable, providing a relatively mature cardiomyocyte model without genetic modifications, with high predictivity in cardiac toxicity and efficacy assays. Based on this proprietary technology, high quality (diseased) cardiomyocytes can be generated from any individual with any genetic, ethnic or disease background. Alternatively, our healthy hiPSC-derived cardiomyocytes can be modified through addition of cytokines, hormones, chemicals or other ligands to the culture medium, or by the use of genetic technologies. In combination with specialized assay development experience, we can generate highly relevant “disease in a dish” models for efficacy studies. For more detailed and mechanistic investigations (for improved translation to in vivo, for instance), more complex in vitro techniques like 3D cultures, co-cultures with other cell types, and/or mimicking a physiologically relevant environment of the cells can be applied to create “organ-on-a-chip” models. Just let us know which features you need in the model and we can discuss the possibilities.

Benefits

Why you should work with us for our drug efficacy studies:
Cardiovascular expertise - make use of our knowledge
Results you can trust - guaranteed by the reproducible and translatable production of hiPSC-derived cells
Save time and money - make use of our state-of-the-art technologies and equipment
Customized approach - our goal is to meet your objectives

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Axion Maestro Hamamatsu FDSS Nanion CardioExcyte Human Mouse CNS/Neurology Pain Cardiovascular Neurodegenerative diseases Neuropathy Cardiomyopathy calcium imaging Drug Discovery Environmental samples calming effect Cytotoxicity biomarker Client-specified hERG Nav1.5 Cav1.2 Ion Channel calcium efflux calcium embryotoxicity toxicity drug safety Axiogenesis Cor.4CE Show 28 more tags Show less

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Toxicology

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Specialized Cell-Based Assays

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Drug Discovery & Development

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Drug Discovery & Development Services

Drug Discovery & Development Services

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In vitro Toxicity Testing

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Action Potential Duration Assay

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Cytotoxicity Assays

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Cytotoxicity Assays Services

Cytotoxicity Assays Services

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Electrophysiology

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Project Management

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Angiogenesis & Endothelial Cell Assays

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Assay Development

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Cell-Based Assays

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Biology

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Pharmacology & Toxicology

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Roman Bucerius

Director BD & Sales Europe bei Ncardia
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Christopher Fleming

Senior Scientist, Product Support

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