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Conference Documentation: ADMET

The poor success rate in developing a new drug from discovery to market is a major problem faced by the pharmaceutical industry today.
The goal of early ADME is to determine whether a candidate drug forms reactive metabolites as early as possible and mitigate attrition rates.
Reactive drug metabolites are known to be one of the factors behind unexpected drug-induced toxicity and therefore their identification early in the drug discovery process is of big importance.

Furthermore, cardiovascular toxicity is often to blame, accounting for approximately 27% of drug failures due to toxicity in the preclinical phase:
The overall attrition rate due to cardiovascular events in clinical development is 21%, indicating that several cardiovascular effects occur in Phase II and III clinical trials which are not detected in the preclinical studies or earlier clinical trials. Thus, the conference will feature a dedicated session on toxicity and highlight emerging technology to aid better prediction.

ADME parameters obtained from in vitro and in vivo models, which aid in the prediction of drug behaviors in patients, are important for the decision to advance, hold or terminate a drug candidate. However, incomplete ADME studies or misinterpretation of ADME data may cause failures in drug development. ADME studies are conducted with in vitro, in vivo or in silico models.

In vitro models generate many ADME parameters, including apparent permeability, metabolic stability, protein binding, blood-to-plasma partitioning, drug–drug interaction potentials (e.g., inhibition and induction of cytochrome P450 (CYP) and transporters), cell proliferation and cytotoxicity, and hERG inhibition. In vivo models of animals and healthy human subjects provide information such as drug oral bioavailability, exposures, distribution, clearance, and duration of exposure for a drug and its metabolites.

Finally, in silico models predict drug behaviors based on physicochemical properties of drug candidates in combination with crystal structures of a protein (an enzyme or a transporter) and database of ADME properties generated in laboratories. With the numerous models available, proper experimental model selection is essential for ADME property optimization.


Day 1
8:30
Registration & Coffee
9:00
Chair's Opening Remarks
Araz Raoof, Head Scientific Affairs & Analysis, Janssen Pharmaceutica
9:10
OPENING ADDRESS: How is ADMET Tackling Key Challenges of Drug Development?
Araz Raoof, Head Scientific Affairs & Analysis, Janssen Pharmaceutica
9:50
In Silico DMPK: A Bridging Position
Fabio Brocatelli, Scientist, Genentech, Inc.
10:30
Morning Coffee
11:00
Transporter Knockout Cell Lines in Preclincal Toxicology Assays and Services
Alessandro Spedito, European Market Sales Development Specialist , Sigma Aldrich Co Ltd
11:40
ADME evaluation and PK prediction for peptidomimetic NCEs
Contance Höfer, CDO, Priaxon AG
12:20
Networking Lunch
13:30
KEYNOTE ADDRESS: Opportunities for modelling of kidney disease and general toxicology studies.
Jamie Davies, Professor of Experimental Anatomy, University Of Edinburgh
14:10
Transational PK/PD modeling for efficacy and safety
Thierry Lave, Head DMPK and TOX Project Leaders and Modeling & Simulation, F. Hoffmann-La Roche
14:50
PK/PD modelling to validate drug targets and toxicity
Peter Littlewood, Director DMPK, Vertex Pharmaceuticals
15:30
Afternoon Tea
16:00
Exploratory ADME in preclinical and clinical studies to guide and accelerate clinical development
Mario Monshouwer, Senior Director Drug Metabolism Pharmacokinetics & Bioanalysis, Johnson & Johnson
16:40
Application of PK/PD Modelling in ADMET
Laurent Salphati, Senior Scientist, Genentech
17:20
Complementary use of high-throughput ADMET screening and In Silico modelling systems to strengthen non-animal alternatives
Mark Wenlock, Research Scientist, AstraZeneca
18:00
Panel Discussion
Araz Raoof, Head Scientific Affairs & Analysis, Janssen Pharmaceutica
18:00
Panel Discussion
Laurent Salphati, Senior Scientist, Genentech
18:00
Panel Discussion
Contance Höfer, CDO, Priaxon AG
18:00
Panel Discussion
Jamie Davies, Professor of Experimental Anatomy, University Of Edinburgh
18:20
Chair’s Closing Remarks and Close of Day One
Day 2
8:30
Registration & Coffee
9:00
Chair's Opening Remarks
Ian D. Wilson, Professor of Drug Metabolism and Molecular Toxicology, Imperial College London
9:10
OPENING ADDRESS: Future perspectives of ADMET evaluations and the current paradigm shifts in toxicology
Ian D. Wilson, Professor of Drug Metabolism and Molecular Toxicology, Imperial College London
9:50
Assessing transporter-mediated drug-drug interactions
Guy Webber, Scientific Manager for In Vitro and Discovery Services ,
10:30
Morning Coffee
11:00
Metabolic Drug-Drug Interactions due to CYP Enzyme Inactivation (Time-Dependent Inhibition)
Stephen Fowler, ADME Group Leader, In Vitro ADME, F. Hoffmann-La Roche
11:40
Toxicology pathways – Evidence-based mechanistic modelling
Nick Plant, Reader in Molecular Toxicology, University Of Surrey
12:20
Networking Lunch
13:30
Predicting human drug-Induced hepatotoxicity
Gerry Kenna, Director, FRAME
14:10
New strategies to reduce drug induced cardiovascular toxicity
Peter K Hoffmann, Global Preclinical Expert for Cardiovascular Safety, Novartis Institutes for BioMedical Reseach
14:50
Afternoon Tea
15:20
In vitro models and technologies for detecting Cardiotoxicity
Peter Clements, Director of Pathology, GSK
16:00
Which in vitro models, technologies and strategies to detect Hepatotoxicity and Cardiotoxicity at early stages of drug development?
Frank Atienzar, Associate Director In Silico in Vitro Toxicology, UCB BioPharma SPRL
16:40
Chair’s Closing Remarks and Close of Day Two

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