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SLAS2020 Short Courses

Phenotypic Screening: Why, When and How

Phenotypic screening is experiencing a renaissance in the pharmaceutical industry based on its successful track record in delivering first-in-class medicines stemming from novel biology. Although phenotypic screening may appear to be similar to target-based screening, there are some fundamental differences between the two approaches. 

This course will deliver  theoretical and practical framework for the use of phenotypic drug discovery by (1) providing a broad context of the drug discovery process, (2) comparing and contrasting molecular target-driven and empirical phenotypic drug discovery strategies, (3) providing guidelines on why and when to utilize an empirical phenotypic drug discovery approach and (4) providing practical information to prosecute phenotypic programs more effectively. 

Attendees will participate in an active dialogue with instructors and other participants on course topics. Phenotypic Screening: Why, When and How is not a typical “how to” course, since no clear cut “one size fits all” strategy exists for an endeavor as complex as drug discovery.

Who Should Attend

  • Academic scientists considering or using phenotypic screens to discover novel biology and molecular probes.
  • Industry scientists considering or using phenotypic screens to discover novel targets and clinical candidates.
  • Commercial providers of reagents, instruments and services used in phenotypic screening.

Course Benefits

Attendees will leave this course with:

  • A high-level overview of the drug discovery and development process.
  • An overview of Pharma productivity with potential technical reasons for poor productivity.
  • An understanding of the pros and cons associated with hypothesis driven and empirical drug discovery.
  • Practical knowledge of key concepts and strategies in phenotypic screening supported by case studies and literature references to bring back to their organizations.

Course Topics

Morning Session:

  • Overview of pharma R&D productivity
  • Overview of the drug discovery and development process: Unmet medical need to registration
  • Relating R&D poor productivity to drug discovery strategies
  • Target-based & phenotypic drug discovery strategies: first in class & best in class
  • Choosing a screening strategy: multi-dimensional risk management

Afternoon Session:

  • Not all phenotypic assays are created equal: what are the characteristics of the best assays?
  • Which libraries should be screened and why? Small molecule and/or genetic screening?
  • What are key considerations and strategies for phenotypic screening hit triage and validation?
  • What are key considerations and strategies for target/mechanism identification and validation?
  • What are key considerations and strategies for phenotypic program progression?

Instructors

Fabien Vincent, Ph.D.

Fabien Vincent, Ph.D.
Pfizer

Fabien Vincent, Ph.D., is an Associate Research Fellow in the Hit Discovery and Lead Profiling Group at Pfizer. His laboratory provides molecular pharmacology support for the small molecule project portfolios of the Immunology and Inflammation research unit and the Centers for Therapeutic Innovation. This work includes designing hit identification strategies and screening funnels, developing assays for high-throughput screening as well as additional assays to elucidate the structure activity relationship of active compounds to understand their mechanism of action and facilitate translation to pre-clinical models. His main research interests are centered on improving the translation of discovery research to patients and specifically include phenotypic screening and atypical molecular mechanisms of action.

Vincent received a Diplôme d’Ingénieur in organic chemistry from CPE Lyon (France) before conducting graduate research in the fields of chemical biology and enzymology in the laboratory of Professor Harold Kohn at the University of Houston. He later became a post-doctoral fellow in chemical biology at the Genomics Institute of the Novartis Research Foundation in San Diego. He entered the field of drug discovery as both a drug discovery research project leader and molecular pharmacology-biochemistry group leader.

Vincent recently led a team of Pfizer scientists in an analysis of how best to approach phenotypic screening, and specifically how to design the optimal phenotypic assays, those which can best predict compounds and mechanisms that will be effective in patients (Sci. Trans. Med., 2015, 7, 293ps15). 

He was also a co-organizer of the 2019 Keystone Symposium “Phenotypic Drug Discovery: Recent Advances and Insights from Chemical and Systems Biology” surveying progress and advances in the field of phenotypic drug discovery.

David C. Swinney, Ph.D.

David C. Swinney
DCSwinney consulting

David Swinney, Ph.D., has a long interest to identify ways to reduce attrition in drug discovery. He has made contributions towards this goal through better understanding of how drugs work to provide effective, safe, therapeutically useful actions, and how these medicines and their respective mechanisms are discovered. Swinney believes that a better understanding of how medicines work will inform strategies to identify more effective and safer medicines, leading to an increase chance of success and thereby increasing productivity by reducing attrition. His analysis of how medicines were discovered concluded that the empiricism of phenotypic assays was important to the successful discovery of many first in class medicines. This work was published in Nature Reviews Drug Discovery in 2011 and contributed to the renaissance of phenotypic drug discovery.

He currently works as an independent consultant helping clients address specific issues in drug discovery, enzymology and quantitative pharmacology.  Swinney was founder and CEO at the Institute for Rare and Neglected Diseases Drug Discovery, aka iRND3, and Director at Roche Palo Alto. He has over 25 years of drug discovery experience leading efforts to identify promising strategies, leads, clinical candidates. At iRND3, he acquired funding to create a portfolio of early stage programs with leads that addressed neglected tropical diseases and cancer. Swinney has a Ph.D. in medicinal chemistry from the University of Washington —Seattle.

Jonathan Lee, Ph.D.

Jonathan Lee, Ph.D.
PDD4Patients LLC

Jonathan Lee, Ph.D., is a retired Senior Research Advisor with over 25 years of pharmaceutical industry experience.  His pharmaceutical experience includes portfolio/research management in conjunction with the evaluation, development and deployment of new technologies for drug discovery. His research emphasized the use of complex, physiologically-relevant cellular systems for target validation, lead generation, SAR support and biomarker discovery. He was an early adopter of modern empirical drug discovery approaches and was foundational in initiating Eli Lilly’s PD2 Initiative (currently OIDD), a collaborative open innovation venture where compounds from academic and biotech institutes are tested in Lilly’s Phenotypic Assay Platform without charge or commercial obligation.  Lee has fostered the international phenotypic drug discovery (PDD) community by initiating and managing the on-line PDD Special Interest group and serving as co-editor on three special issues focused on PDD through publications (11), invited lectures (17), teaching (SLAS since 2016) and by developing and co-organizing the first Keystone Symposium in this field, “Modern Phenotypic Drug: Defining the Path Forward

Jonathan is semi-retired but works as an independent consultant at PDD4Patients LLC which provides consulting services focusing on PDD to collaborators from startups, biotechs, academia and instrument companies.


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