Screening Strategies in
ADME-Tox

Hayley Atkinson PhD Principal Scientist, Transporters & Permeability Cyprotex Discovery Ltd

Presentation Title

Regulatory Drug-Drug Interaction Studies - Design and Interpretation

Abstract

Understanding the potential for drug-drug interactions (DDI) is an important part of the drug development process. In this presentation, we will cover the key in vitro assays required for regulatory enzyme and transporter-based interactions, including planning and design of the studies, an overview of the methodology and how the data are interpreted to understand potential DDI risk. The presentation will touch on the new draft ICH M12 guidance for harmonisation of regulatory DDI studies.

Biography

Hayley Atkinson is a Principal Scientist in the permeability and drug transporter team at Cyprotex, UK where she acts as deputy scientific lead for drug transporter studies. Her research interests include prediction of transporter mediated drug-drug interactions with improved in vitro assays. Prior to joining Cyprotex in 2013, Hayley received her PhD from the University of Liverpool under Prof. Munir Pirmohamed where she conducted research on anti-epileptic drug transporters at the blood-brain barrier in the context of drug resistance.

Uprenda Dahal PhD Senior Principal Scientist Amgen

Presentation Title

Small Molecule ADME Assay Strategies with Examples

Abstract

Pharma industries generally use tiered approach for ADME data generation. Simpler discovery stage single point high throughput assays are performed in early stage to improve ADME properties via SAR as well as to filter out poor performing compounds to avoid drug liabilities; the definitive assays are performed in the later stage of the programs to define IVIVC and drug-drug interaction while mechanistic studies are performed routinely to understand/address the ADME challenges. In this presentation, small molecule ADME strategies will be discussed in high level. Examples will be presented to illustrate small molecule ADME strategies.

Biography

Upendra Dahal is a Senior Principal Scientist at Amgen. Apart from supervising junior scientists, and developing strategies for small molecule ADME screening to accelerate pipeline, Upendra’s current role involves representing Pharmacokinetics and Drug Metabolism (PKDM) in multi-disciplinary project teams from discovery to development stages, designing in vitro and in vivo studies to characterize/understand PKDM properties of the project compounds, and providing recommendations to teams to design better compounds to avoid metabolic and DDI liabilities. Upendra routinely analyzes and interprets in vitro and in vivo study data and proposes next steps/studies to understand PKDM related challenges and to mitigate risks. He routinely prepares documents for regulatory filing. Before joining Amgen Upendra worked at Celgene and Pfizer. Upendra has a diverse research interest and has demonstrated a good track record of peer reviewed publications in diverse research areas.

Chris Strock PhD VP US ADMET Operations Cyprotex Discovery Ltd

Presentation Title

Derisking Early: An Overview of In Vitro Toxicology Assays

Abstract

The drive to develop human cell-based models as alternatives to animal testing has gathered pace over the past few years. As models and analytical techniques become more sophisticated, these tools are now becoming more widely used and applied in drug discovery to de-risk early and prevent late stage failure. In this presentation, an overview of early in vitro toxicology assays will be provided along with an insight into new technologies such as 3D cell-based models, MEA and transcriptomics and how these advances have improved safety prediction.

Presentation Title

Tiered ADME-Tox Screening Strategies – Standard and Bespoke Approaches

Abstract

Common strategies for ADME-Tox screening within the pharmaceutical industry will be discussed. Based on our experience at Cyprotex, we will present a proposed standard tiered screening approach for compound triage and decision making during drug discovery and development. We will also provide examples of where this standard approach needs to be adapted based on project-specific requirements.

Biography

Chris Strock received his BS in Chemistry from Gannon University in Erie, PA. He worked as an organic chemist for DuPont Ag for a few years before getting his PhD in Biochemistry and Molecular Biology from the University of Maryland, Baltimore where he determined the calcium binding sites on the SR Calcium. Following his PhD, Chris was a Postdoctoral Fellow and Research Associate in the Oncology Department at Johns Hopkins University School of Medicine under Barry Nelkin, PhD where he identified CDK5, a protein important in migration of cells in neural development, as an essential molecule for metastasis in numerous cancer models. He then joined Cellumen where he developed his expertise in High Content Screening technology. While there, Chris specialized in assay development and was responsible for the design and development of High Content HTS Protein: Protein Interaction biosensor assays. He also worked in the HCS toxicology group, developing and optimizing assays for the in vitro toxicology assay, CellCiphr®.

After Cyprotex acquired Cellumen, Chris joined Cyprotex US in Watertown, MA where he has brought his expertise for the last 10 years in the area of HCS assay development, electrophysiology and toxicology. He is the co- chairman of the HesI NeuTox Group for prediction of Seizures using Microelectrode Array. He currently is the Watertown Site Head and the VP of US ADMET Operations and has more than 30 peer reviewed publications.

Michael Campognone Senior Director Evotec

Presentation Title

The Transition from Discovery to Development

Abstract

Often the transition between discovery and development can be challenging especially if separate departments are responsible for the individual areas. In this presentation, we will discuss how to navigate through this transition with consideration of careful study design and planning, analysis of data gaps and how to achieve efficiency gains. The presentation will build on Evotec’s own experience with case studies to demonstrate the optimal path through this process.

Biography

Michael joined Aptuit in 2015 (acquired by Evotec) and re-joined Evotec in 2018 as Senior Director of Business Development where he develops strategic biotech and pharma partnerships to advance partner assets through preclinical and clinical development. Throughout his 16 year career, Michael has supported dozens of preclinical leads and candidates through to clinical development via contract research and technical consultancy.