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This meeting took place in 2016
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Modern Phenotypic Drug Discovery: Defining the Path Forward (D1)
Organizer(s) Jonathan A. Lee, Ellen L. Berg and Eugene C. Butcher
April 2—6, 2016
Big Sky Resort • Big Sky, MT USA
Discounted Abstract Deadline: Dec 2, 2015
Abstract Deadline: Jan 5, 2016
Scholarship Deadline: Dec 2, 2015
Discounted Registration Deadline: Feb 2, 2016
Sponsored by Abide Therapeutics Inc., Janssen R&D: Pharmaceutical Companies of Johnson & Johnson, Merck & Co., Inc., Pfizer Inc., Takeda Pharmaceutical Company Limited and Vertex Pharmaceuticals Incorporated
Summary of Meeting:
Innovation and productivity in pharmaceutical drug discovery have been below expectations. Surprisingly, more first-in-class small molecule drugs approved by the FDA (1999-2008) were identified by functional approaches reminiscent of pre-genomics pharmacology (phenotypic drug discovery) than by contemporary molecular targeted strategies. This observation, and the unexpected difficulties of target validation, have diminished the impact of the “genomics revolution” and are arguably associated with the decline in innovation and productivity of pharmaceutical research. As a result, pharmaceutical researchers have begun to reevaluate the “Molecular Mindset” which has dominated our collective drug-hunting culture, and explore modern approaches to phenotypic screening. However, there is currently no single scientific forum where scientists from pharma, biotech, academia and instrument/service providers can meet and discuss strategies/issues related to phenotypic drug discovery (PDD). In part, this is because PDD encompasses multiple therapeutic areas and involves diverse disciplines including drug discovery, chemistry, cell biology, stem cell biology, systems biology, genomics, bioengineering and informatics. This Keystone Symposia meeting uniquely provides this interdisciplinary environment and is a particularly attractive venue given the increasing role of academia in drug discovery research. The conference will be a forum for the global PDD research community in which scientists from diverse institutions and scientific disciplines can meet to share/discuss/debate topics related to advantages/disadvantages of PDD and how PDD can complement targeted approaches. Significantly, the conference will provide a much needed forum for the growing interest in PDD, and can conceivably become the cornerstone of the global scientific movement for the reintroduction of functional biology/physiology-driven pharmaceutical research.
View Scholarships/Awards
Innovation and productivity in pharmaceutical drug discovery have been below expectations. Surprisingly, more first-in-class small molecule drugs approved by the FDA (1999-2008) were identified by functional approaches reminiscent of pre-genomics pharmacology (phenotypic drug discovery) than by contemporary molecular targeted strategies. This observation, and the unexpected difficulties of target validation, have diminished the impact of the “genomics revolution” and are arguably associated with the decline in innovation and productivity of pharmaceutical research. As a result, pharmaceutical researchers have begun to reevaluate the “Molecular Mindset” which has dominated our collective drug-hunting culture, and explore modern approaches to phenotypic screening. However, there is currently no single scientific forum where scientists from pharma, biotech, academia and instrument/service providers can meet and discuss strategies/issues related to phenotypic drug discovery (PDD). In part, this is because PDD encompasses multiple therapeutic areas and involves diverse disciplines including drug discovery, chemistry, cell biology, stem cell biology, systems biology, genomics, bioengineering and informatics. This Keystone Symposia meeting uniquely provides this interdisciplinary environment and is a particularly attractive venue given the increasing role of academia in drug discovery research. The conference will be a forum for the global PDD research community in which scientists from diverse institutions and scientific disciplines can meet to share/discuss/debate topics related to advantages/disadvantages of PDD and how PDD can complement targeted approaches. Significantly, the conference will provide a much needed forum for the growing interest in PDD, and can conceivably become the cornerstone of the global scientific movement for the reintroduction of functional biology/physiology-driven pharmaceutical research.
View Scholarships/Awards
No registration fees are used to fund entertainment or alcohol at this conference
The meeting will begin on Saturday, April 2 with registration from 16:00 to 20:00 and a welcome mixer from 18:00 to 20:00. Conference events conclude on Wednesday, April 6 with a closing plenary session from 17:00 to 19:00, followed by a social hour and entertainment. We recommend return travel on Thursday, April 7 in order to fully experience the meeting.
SATURDAY, APRIL 2
SUNDAY, APRIL 3
MONDAY, APRIL 4
TUESDAY, APRIL 5
WEDNESDAY, APRIL 6
THURSDAY, APRIL 7
Conference Program Print | View meeting in 12 hr (am/pm) time
The meeting will begin on Saturday, April 2 with registration from 16:00 to 20:00 and a welcome mixer from 18:00 to 20:00. Conference events conclude on Wednesday, April 6 with a closing plenary session from 17:00 to 19:00, followed by a social hour and entertainment. We recommend return travel on Thursday, April 7 in order to fully experience the meeting.
SATURDAY, APRIL 2
18:00—20:00
Welcome Mixer
No registration fees are used to fund alcohol served at this function.
08:00—08:30
Welcoming Remarks
*
Jonathan A. Lee,
PDD4Patients LLC, USA
*
Ellen L. Berg,
Eurofins DiscoverX, USA
*
Eugene C. Butcher,
Stanford University, USA
08:30—09:30
Keynote Address
*
Eugene C. Butcher,
Stanford University, USA
David C. Swinney,
iRND3, Institute for Rare and Neglected Diseases, USA
The Value of Phenotypic Assays to Drug Discovery: Historical Perspective
The Value of Phenotypic Assays to Drug Discovery: Historical Perspective
09:30—11:00
Why Revisit PDD?
*
Eugene C. Butcher,
Stanford University, USA
John Moffat,
Genentech, Inc., USA
Phenotypic and Targeted Drug Discovery Are Complimentary Strategies
Phenotypic and Targeted Drug Discovery Are Complimentary Strategies
Bernard H. Munos,
FasterCures, USA
Pharma Research Productivity: A New Perspective on Phenotypic vs. Target-Based Screening
Pharma Research Productivity: A New Perspective on Phenotypic vs. Target-Based Screening
17:00—19:00
PDD: Recent Clinical Successes
*
Ellen L. Berg,
Eurofins DiscoverX, USA
Nicholas A. Meanwell,
Bristol-Myers Squibb, USA
Phenotypic Screening for Antiviral Agents
Phenotypic Screening for Antiviral Agents
Rebecca M. Pruss,
Windhover Biomed, France
Maintenance of Motor Function in Spinal Muscular Atrophy by Olesoxime: A Recent Clinical Success for Phenotypic Drug Discovery
Maintenance of Motor Function in Spinal Muscular Atrophy by Olesoxime: A Recent Clinical Success for Phenotypic Drug Discovery
Jon Tinsley,
Summit Therapeutics, UK
Modulators of Utrophin Production for the Treatment of Duchenne Muscular Dystrophy
Modulators of Utrophin Production for the Treatment of Duchenne Muscular Dystrophy
Veronica Soloveva,
Merck, USA
Short Talk: Identification and Characterization of the Antiviral Activity of GS-5734 using Phenotypic Approaches
Short Talk: Identification and Characterization of the Antiviral Activity of GS-5734 using Phenotypic Approaches
19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.
08:00—11:00
Challenges to Modern PDD/Lessons Learned
*
Jonathan A. Lee,
PDD4Patients LLC, USA
Neil O. Carragher,
University of Edinburgh, Scotland
Accelerating PDD through Integrating MOA Profiling with Agile Chemical Design: Shifting the Bottlenecks from Target Deconvolution to Disease Relevance
Accelerating PDD through Integrating MOA Profiling with Agile Chemical Design: Shifting the Bottlenecks from Target Deconvolution to Disease Relevance
Ellen L. Berg,
Eurofins DiscoverX, USA
Phenotypic Chemical Biology for Predicting Efficacy and Safety
Phenotypic Chemical Biology for Predicting Efficacy and Safety
Fabien Vincent,
Pfizer Inc., USA
Lessons Learned in Phenotypic Screening
Lessons Learned in Phenotypic Screening
Michael R. Jackson,
SBP Medical Discovery Institute, USA
Phenotypic Screening of Patient Derived Cells: Balancing Throughput with Relevance
Phenotypic Screening of Patient Derived Cells: Balancing Throughput with Relevance
Bridget Wagner,
Broad Institute, USA
Short Talk: Small-Molecule Stimulation of Human Beta-Cell Proliferation
Short Talk: Small-Molecule Stimulation of Human Beta-Cell Proliferation
11:00—12:00
Panel 1: PDD Trends and Roadblocks
*
David C. Swinney,
iRND3, Institute for Rare and Neglected Diseases, USA
Ellen L. Berg,
Eurofins DiscoverX, USA
Jonathan A. Lee,
PDD4Patients LLC, USA
Bernard H. Munos,
FasterCures, USA
Fabien Vincent,
Pfizer Inc., USA
Neil O. Carragher,
University of Edinburgh, Scotland
Michael R. Jackson,
SBP Medical Discovery Institute, USA
17:00—19:00
New Biological Models
Eugen Dhimolea,
Dana Farber Cancer Institute, Harvard Medical School, USA
Engineering 3-D in vitro Tumor Models of Antineoplastic Drug Resistance
Engineering 3-D in vitro Tumor Models of Antineoplastic Drug Resistance
Salman Khetani,
University of Illinois at Chicago, USA
Microengineered Human Liver Models for Drug Screening and Disease Modeling
Microengineered Human Liver Models for Drug Screening and Disease Modeling
Sandy Hinckley,
Sanford Burnham Prebys Medical Discovery Institute, USA
Short Talk: Phenotypic Screening of Neuronal Networks using High-throughput Multielectrode Arrays
Short Talk: Phenotypic Screening of Neuronal Networks using High-throughput Multielectrode Arrays
Deborah Greene Nguyen,
Organovo, USA
Short Talk: Bioprinted Three-dimensional (3D) Human Tissues for Toxicology and Disease Modeling
Short Talk: Bioprinted Three-dimensional (3D) Human Tissues for Toxicology and Disease Modeling
David Gerber,
Galenea Corp., USA
Short Talk: Targeting Synaptic Function for CNS Drug Discovery
Short Talk: Targeting Synaptic Function for CNS Drug Discovery
19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.
08:00—11:00
Translational PDD: Physiologically Relevant Models
*
Fabien Vincent,
Pfizer Inc., USA
Andrew Reaume,
Melior Discovery, Inc., USA
Case Studies and Overall Learnings from 10 Years of Phenotypic Screening with a Broad-Based Panel of In Vivo Models
Case Studies and Overall Learnings from 10 Years of Phenotypic Screening with a Broad-Based Panel of In Vivo Models
Mark Mercola,
Stanford University, USA
Functional and Chemical Genomics to Decipher Heart Failure Mechanisms
Functional and Chemical Genomics to Decipher Heart Failure Mechanisms
Tom Large,
Blue Oak Pharmaceuticals, USA
Discovery of Novel Psychiatric Drugs using a Target-agnostic, Systems Neurobiology Strategy
Discovery of Novel Psychiatric Drugs using a Target-agnostic, Systems Neurobiology Strategy
Jason Ptacek,
Ionpath, Inc, USA
Short Talk: Phenotypic Human Primary Cell Based Tumor Microenvironment Models for Evaluation of Drug Combinations for Immune Oncology
Short Talk: Phenotypic Human Primary Cell Based Tumor Microenvironment Models for Evaluation of Drug Combinations for Immune Oncology
David A. Mann,
Cellular Dynamics International Inc., USA
Short Talk: Relevant Phenotypic Drug Discovery: Innate, Induced and Engineered Human iPSC Models
Short Talk: Relevant Phenotypic Drug Discovery: Innate, Induced and Engineered Human iPSC Models
Denise V. Barrault,
University of Edinburgh, UK
Short Talk
Short Talk
11:00—11:30
NIH Common Fund Program
Aaron Pawlyk,
Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA
In Search of Phenotypes to Illuminate the Druggable Genome
In Search of Phenotypes to Illuminate the Druggable Genome
17:00—19:00
Biologically Relevant Chemical Diversity
*
Paul Clemons,
Broad Institute of Harvard and MIT, USA
Chemical Diversity Expressed through Small-Molecule Performance: Diverse Readouts, Phenotypes and Genetic Determinants
Chemical Diversity Expressed through Small-Molecule Performance: Diverse Readouts, Phenotypes and Genetic Determinants
Herbert Waldmann,
Max Planck Institute for Molecular Physiology, Germany
Natural Product Inspired Compound Collections: Evolutionary Principle, Chemical Synthesis, Phenotypic Screening and Target Identification
Natural Product Inspired Compound Collections: Evolutionary Principle, Chemical Synthesis, Phenotypic Screening and Target Identification
Nicole E. Bodycombe,
Pfizer, USA
Compound Subsets in Phenotypic Screening
Compound Subsets in Phenotypic Screening
Andrea Galmozzi,
The Scripps Research Institute, USA
Short Talk: Phenotypic Screening of Fully Functionalized Fragment-Based Chemical Probes Reveals PGRMC2 As A New Regulator of Adipocyte Physiology of Therapeutic Potential for Obesity-Linked Diabetes
Short Talk: Phenotypic Screening of Fully Functionalized Fragment-Based Chemical Probes Reveals PGRMC2 As A New Regulator of Adipocyte Physiology of Therapeutic Potential for Obesity-Linked Diabetes
19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.
08:00—09:00
Keynote Address
*
John Moffat,
Genentech, Inc., USA
Enrique Saez,
The Scripps Research Institute, USA
Chemical Proteomic Strategies to Advance Phenotypic Screening
Chemical Proteomic Strategies to Advance Phenotypic Screening
09:00—11:30
Target/MOA Identification/Deconvolution
*
John Moffat,
Genentech, Inc., USA
Monica Schenone,
Pfizer Inc., USA
Target Identification and Mechanism of Action in Drug Discovery
Target Identification and Mechanism of Action in Drug Discovery
Jeremy Jenkins,
Novartis Institutes for BioMedical Research, USA
Systems Approaches to Elucidating Compound-Effect Pathways
Systems Approaches to Elucidating Compound-Effect Pathways
Andreas Bender,
University of Cambridge, UK
Towards Understanding Phenotypic Readouts - Utilizing Multiple Types of Chemical and Biological Data to Rationalize Compound Action
Towards Understanding Phenotypic Readouts - Utilizing Multiple Types of Chemical and Biological Data to Rationalize Compound Action
Vladimir Chupakhin,
Janssen Pharmaceuticals, Belgium
Short Talk: The New Approaches for a Computational Target Deconvolution of the Phenotypic Hits
Short Talk: The New Approaches for a Computational Target Deconvolution of the Phenotypic Hits
Susanne Swalley,
Biogen, USA
Short Talk: Phenotypic Drug Discovery in SMA: Parallel Efforts in Preclinical Development and Target Identification
Short Talk: Phenotypic Drug Discovery in SMA: Parallel Efforts in Preclinical Development and Target Identification
11:30—12:30
Panel 2: Identification of Molecular Targets and Biological "Mechanisms of Action": How Much is Enough?
*
Eugene C. Butcher,
Stanford University, USA
Susanne Swalley,
Biogen, USA
Tom Large,
Blue Oak Pharmaceuticals, USA
Marco Prunotto,
F. Hoffmann-La Roche Ltd., Switzerland
Nicholas A. Meanwell,
Bristol-Myers Squibb, USA
Rebecca M. Pruss,
Windhover Biomed, France
17:00—19:00
Network Biology: New Technologies and Informatics
Andrea Califano,
Columbia University, USA
Systematic Elucidation of Druggable Dependencies in Human Malignancies: A New Take on Precision Medicine
Systematic Elucidation of Druggable Dependencies in Human Malignancies: A New Take on Precision Medicine
Anne E. Carpenter,
Broad Institute of Harvard and MIT, USA
Increasing the Content of High-Content Phenotypic Assays: Targeting Diseases and Characterizing Compounds via Cell Painting and Image-Based Profiling
Increasing the Content of High-Content Phenotypic Assays: Targeting Diseases and Characterizing Compounds via Cell Painting and Image-Based Profiling
*
Marco Prunotto,
F. Hoffmann-La Roche Ltd., Switzerland
Short Talk: Application of Molecular Phenotype to Phenotypic Drug Discovery: Results of a PoC Study
Short Talk: Application of Molecular Phenotype to Phenotypic Drug Discovery: Results of a PoC Study
19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.
20:00—23:00
Entertainment
Entertainment is not subsidized by conference registration fees nor any U.S. federal government grants. Funding for this expense is provided by other revenue sources.
*Session Chair †Invited, not yet responded.
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